EPA HQ OPP 2012 0167 0116 - Content

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION
MEMORANDUM
Date: 12/21/2017
SUBJECT: Cypermethrin, Zeta-cypermethrin, and Alpha-cypermethrin. Draft Human

Health Risk Assessment for Registration Review
PC Code: 109702; 129064, and 209600 DP Barcode: 0425964

Decision No.: 501315 Registration Nos.: See Appendix D
Petition No.: NA Regulatory Action: Reg Review ORA
Risk Assessment Type: Single Chemical Case No.:
Aggregate
TXR No.: 0057630 CAS No.: 52315-07-8; 67375-30-8
MRID No.: 446852-01, and 451115-01 40 CFR: §180.418
FROM: Margarita Collantes, M.S., Biologist _ �t1ff'��{Z_u04?�

Douglas Dotson, Ph.D., Chemist 1�d
Krystle Yozzo, Ph.D., Biologist � /J--tA._ ',f-..._ � ,_fr
Risk Assessment Branch II
And
Seyed Tadayon, Chemid�

Risk Assessment Branch III
'15,...__ (oy
Health Effects Division (7509P)
THROUGH: Christina Swartz, Branch Chief

Risk Assessment Branch II
Health Effects Division (HED, 7509P)
Donna Davis, HED Risk Assessment Review Committee �a.

Thomas Moriarty, BED Risk Assessment Review Commi�l'-- fin,.
TO: Susan Bartow, Chemical Review Manager
Kevin Costello, Branch Chief
Risk Management and Implementation Branch IV
Pesticide Re-Evaluation Division (7508P)
Page 1 of 138
The Pesticide Reevaluation Division (PRD) requested that the Health Effects Division (HED)
conduct a draft risk assessment (DRA) for the insecticides, cypermethrin, zeta-cypermethrin, and
alpha-cypermethrin.
This document contains HED’s DRA to support registration review. It incorporates updated
endpoints for risk assessment as well as the most recent data and assumptions for conducting
dietary, residential, occupational, and aggregate exposure assessments. Some occupational
scenarios had risks of concern that could be mitigated through use of additional personal
protective equipment (PPE), such as gloves, engineering controls or a respirator. Risk estimates
of concern were identified for the following residential scenarios:
 Residential handlers using an alpha-cypermethrin microencapsulated concentrate in

livestock housing, applied with a mechanically pressurized handwand:
 Residential post-application exposure from cypermethrin dermal, and combined dermal
and incidental oral exposures for children 1 to <2 years following broadcast applications
to lawns using a wettable powder formulation;
 Residential post-application exposure from zeta-cypermethrin, combined dermal and
incidental oral exposures for children 1 to <2 years old from contact with pets treated
with pet collars;
 Residential post-application exposure from alpha-cypermethrin incidental oral, and
combined dermal and incidental oral exposures, for children 1 to <2 years resulting from
indoor perimeter and spot treatments using course stream spray on carpets and hard
surfaces as well as pin stream spray on carpets; and
 Residential post-application exposure from alpha-cypermethrin combined dermal and
incidental oral exposures for children 1 to <2 years resulting from broadcast application
to turf.
Page 2 of 138
Contents
1.0 Executive Summary ............................................................................................................. 5
2.0 HED Conclusions .............................................................................................................. 12
2.1 Data Deficiencies........................................................................................................ 12
2.2 Tolerance Considerations ........................................................................................... 12
2.2.1 Enforcement Analytical Method ................................................................................ 12
2.2.2 International Harmonization ....................................................................................... 13
2.2.3 Recommended Tolerances ...................................................................................... 13
3.0 Introduction ........................................................................................................................ 17
3.1 Chemical Identity ....................................................................................................... 17
3.3 Pesticide Use Pattern .................................................................................................. 20
3.4 Anticipated Exposure Pathways ................................................................................. 20
3.5 Consideration of Environmental Justice ..................................................................... 20
4.0 Hazard Characterization and Dose-Response Assessment ................................................ 21
4.1 Toxicology Studies Available for Analysis ................................................................ 22
4.3.1 Pyrethroid Pharmacokinetic (PK) and Pharmacodynamic (PD) Profile .................... 25
4.3.2 Pharmacokinetics (PK) ............................................................................................... 26
4.3.3 Pharmacodynamics (PD) ............................................................................................ 27
4.4 Safety factor for Infants and Children (FQPA Safety Factor) .................................... 31
4.4.1 Completeness of the Toxicology Database ................................................................ 31
4.4.2 Evidence of Neurotoxicity .......................................................................................... 31
4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ............. 32
4.4.4 Residual Uncertainty in the Exposure Database......................................................... 33
4.5 Toxicity Endpoint and Point of Departure Selections ................................................ 33
4.5.1 Dose-Response and Hazard Assessment .................................................................... 33
4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment ........... 36
4.5.3 Cancer Classification and Risk Assessment Recommendation .................................. 37
4.6 Endocrine Disruptor Screening Program .................................................................... 41
5.0 Dietary Exposure and Risk Assessment ............................................................................ 42
5.1 Metabolite/Degradate Residue Profile........................................................................ 42
5.1.1 Summary of Plant and Animal Metabolism Studies .................................................. 42
5.1.2 Summary of Environmental Degradation ................................................................... 42
5.1.3 Comparison of Metabolic Pathways ........................................................................... 43
5.1.4 Residues of Concern Summary and Rationale ........................................................... 43
5.2 Food Residue Profile .................................................................................................. 44
5.3 Water Residue Profile ................................................................................................. 44
5.4 Dietary Risk Assessment ............................................................................................ 45
5.4.1 Description of Residue Data Used in Dietary Assessment......................................... 45
5.4.2 Percent Crop Treated Used in Dietary Assessment .................................................... 47
5.4.3 Acute and Chronic Dietary Assessments.................................................................... 47
6.0 Residential Exposure and Risk Estimates .......................................................................... 48
6.1 Residential Handler Exposure/Risk Estimates.................................................................... 49
6.2 Residential Post-application Exposure/Risk Estimates ...................................................... 57
7.0 Aggregate Exposure/Risk Characterization ....................................................................... 72
7.1 Acute Aggregate Risk................................................................................................. 72
7.2 Short-Term Aggregate Risk Estimates ....................................................................... 72
8.0 Non-Occupational Spray Drift Exposure and Risk Estimates ............................................ 76
Page 3 of 138
9.0 Non-Occupational Bystander Post-Application Inhalation Exposure and Risk Estimates . 78
10.0 Cumulative Exposure/Risk Characterization ..................................................................... 79
11.1 Occupational Hander Exposure/Risk Estimates ......................................................... 80
11.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates ............................. 94
11.2.2 Occupational Post-application Dermal Exposure/Risk Estimates ................................. 95
12.0 Public Health and Pesticide Epidemiology Data ............................................................... 96
13.0 References .......................................................................................................................... 99
Appendices.................................................................................................................................. 100
Appendix A. Toxicology Profile and Executive Summaries ................................................ 100
A.1 Toxicology Data Requirements ................................................................................ 100
A.2. Toxicity Profile Tables................................................................................................... 101
Appendix B. Physical/Chemical Properties ............................................................................... 109
Appendix C. International Residue Limit Status Sheet ............................................................. 111
Appendix D. Summary of Use Directions ................................................................................. 118
Appendix E. Review of Human Research ................................................................................. 135
Appendix F: Aggregate Risk Calculations ................................................................................ 136
Page 4 of 138
1.0 Executive Summary
Cypermethrins are classified as type II pyrethroids, and, like other pyrethroids, cause
neurotoxicity from interaction with sodium channels leading to clinical signs of neurotoxicity.
The pyrethroid insecticide, cypermethrin, is a racemic mixture of eight isomers (each with
percentages of 11-14%). Zeta- and alpha-cypermethrin are enrichments of the more
insecticidally-potent isomers (e.g., alpha-S and cis-2-R isomers). While cypermethrin, zeta-
cypermethrin, and alpha-cypermethrin are separate active ingredients (ais) with distinct end-use
products, they are included together in this risk assessment because of the close similarity of
their uses, toxicity, and chemical characteristics. In this document, the term “cypermethrins” is
used when referring to cypermethrin, alpha-cypermethrin and zeta-cypermethrin together,
whereas cypermethrin, alpha-cypermethrin and zeta-cypermethrin are used when referring to the
specific end-use products.
Cypermethrins are registered for use on a wide variety of agricultural food/feed crops, livestock,
and sod farms; recreational sites (i.e., golf courses, athletic fields); indoor
residential/commercial/industrial sites/structural/perimeter and lawn uses; gardens and trees; as
well as a mosquito adulticide, termiticide, and pet uses. The mosquito adulticide use may be
applied by commercial and residential handlers and is not required to be applied by federal, state,
tribal or local government officials responsible for public health and adult mosquito control.
Humans could be exposed to the cypermethrin(s) residues from consuming food treated for
agricultural pest management purposes. Agricultural applications can result in cypermethrins
reaching surface and ground water, both of which can serve as sources of drinking water.
Furthermore, there is potential for occupational and residential handlers to be exposed via the
dermal and inhalation routes of exposure while mixing/loading the pesticide, and during
application. There is also the potential for post-application exposure to occupational workers
entering treated fields and to non-occupational bystanders who may be exposed to spray drift
from occupational applications. Adults and children can also be exposed in residential settings by
contacting treated residential turf, indoor and outdoor environments, as well as treated pets via
inhalation, dermal, and incidental oral (children only) routes of exposure.
Hazard
Type II pyrethroids, such as the cypermethrins, contain an alpha-cyano moiety, and in rats
produce a syndrome that includes pawing, burrowing, salivation, hypothermia, and coarse
tremors leading to choreoathetosis. The adverse outcome pathway (AOP) shared by pyrethroids
involves the ability to interact with voltage-gated sodium channels (VGSCs) in the central and
peripheral nervous system, leading to changes in neuron firing and, ultimately, neurotoxicity.
The toxicology database for the cypermethrins is largely complete with respect to guideline
toxicity studies; while each of the ais does not have a complete database, studies have been
bridged across the 3 chemicals and together are considered to be adequate to support human
health risk assessment. When evaluated together, the toxicity database for cypermethrin, zeta-
cypermethrin, and alpha-cypermethrin can be used to characterize the overall suite of effects
associated with cypermethrin exposure, including potential developmental and reproductive
toxicity, immunotoxicity, and neurotoxicity. Acceptable developmental toxicity studies in rats
and rabbits, reproduction studies in rats, neurotoxicity studies (ACN, SCN, and DNT) in rats,
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and immunotoxicity studies in rats are available. While the database is considered to be
complete with respect to the guideline toxicity studies, EPA lacks additional data to address the
potential for juvenile sensitivity to all pyrethroids, including the cypermethrins. research efforts
are underway to address juvenile sensitivity for the pyrethroids including cypermethrins.
The cypermethrins have been evaluated for a variety of toxic effects in experimental studies.
The cypermethrins affect the nervous system, and neurotoxicity is the most sensitive effect
observed throughout the toxicology database. Effects (clinical signs of neurotoxicity) were seen
for all three compounds across species, sexes, and routes of administration. The endpoints and
points of departure (PODs) selected for risk assessment are based on neurotoxicity and are
protective of all toxic effects observed in the database. Literature studies indicate a possibility of
increased postnatal sensitivity in juvenile rats to the neurotoxic effects of pyrethroid
insecticides. In light of the literature studies, and pending receipt of additional information to
better characterize potential sensitivity of the young, an additional 3X Food Quality Protection
Act (FQPA) Safety Factor (SF) (as estimated by pharmacokinetic (PK) modeling) has been
applied to risk assessments for infants and children < 6 years old.
There was no evidence of increased quantitative or qualitative susceptibility in the available rat
and rabbit developmental toxicity studies and rat two-generation reproductive studies with the
cypermethrins. A developmental neurotoxicity (DNT) study with zeta-cypermethrin indicated
increased sensitivity in the offspring, based on body weight changes in pups in the absence of
treatment-related effects in maternal animals at the highest dose tested. However, there is a clear
NOAEL for effects seen in pups and the doses and endpoints selected for risk assessment are
protective of the susceptibility.
For pyrethroid chemicals, the pharmacokinetics indicate that the onset of neurotoxicity is rapid,
with the time to peak effect for neurobehavioral effects occurring within hours. This is followed
by rapid metabolism and elimination that does not result in accumulation. For the cypermethrins,
the points of departure (PODs) for clinical signs after single or repeated exposure are comparable
across durations of exposure; thus, neurotoxicity does not seem to progress with increased
exposure. Therefore, repeated dosing is essentially a series of acute exposures. As there is no
apparent increase in hazard from repeated/chronic exposures to cypermethrins, the acute
exposure assessment is protective of chronic exposures. The totality of the information suggests
that only single day risk assessments need to be conducted for cypermethrins.
Cypermethrin is classified as a Group C “Possible human carcinogen”, based on an increased

incidence of benign lung adenomas and adenomas plus carcinomas combined in females in a
mouse carcinogenicity study. No tumors were seen in cypermethrin cancer studies in rats or in a
cancer study in mice with alpha-cypermethrin. The agency has determined that quantification of
cancer risk using a non-linear approach (i.e., RfD) will adequately account for all chronic
toxicity, including carcinogenicity, that could result from exposure to the cypermethrins.
Endpoints and Uncertainty Factors

The dose and endpoint for dermal, incidental oral, and acute dietary risk assessments were
selected from the Wolansky et al. (2006) acute oral study in rats, and for inhalation risk
assessments from an inhalation toxicity study, with cypermethrin. While the toxicology studies
have been bridged across the 3 active ingredients, the acute neurotoxicity studies indicate an
Page 6 of 138
apparent 5X increased toxicity for alpha-cypermethrin relative to cypermethrin. Adjustments
were made to the alpha-cypermethrin PODs for oral/dermal assessments and Human Equivalent
Concentrations/Doses (HEC/HEDs) for inhalation assessments to account for the increased
toxicity of alpha-cypermethrin in comparison to cypermethrin. Lastly, consistent with other
pyrethroids in this class, the acute dosing studies generally result in lower NOAELs compared to
longer-term dietary administration studies, and the neurotoxic effects do not increase over
repeated administration. Therefore, the non-cancer endpoints are protective for acute and repeat
exposures, and an endpoint for chronic dietary risk assessment was not selected.
Dermal toxicity studies are available for both cypermethrin and zeta-cypermethrin, and no
systemic effects were observed in the studies. Furthermore, based on what is known about
pyrethroids (and the cypermethrins) there is no concern for developmental toxicity. Therefore, an
adult dermal endpoint was not selected for cypermethrin or zeta-cypermethrin. However, due to
concern for increased toxicity of alpha-cypermethrin, HED conducted a dermal assessment using
the Wolansky study POD and chemical specific dermal absorption information; this approach is
considered to be conservative for alpha-cypermethrin. Furthermore, due to increased quantitative
susceptibility noted in the zeta-cypermethrin DNT study and the decreased ability of children to
detoxify pyrethroids (Anand et al. 2006; de Zwart et al. 2008; Yang et al. 2009) a dermal risk
assessment was conducted for all of the cypermethrins for children <6 years old to protect for
potential offspring effects. The dose and endpoint for dermal risk assessment were selected from
the Wolansky et al. (2006) acute oral study. Since the PODs and endpoints are based on
cypermethrin data and there is concern for increased toxicity after exposure to alpha-
cypermethrin, a 5X potency factor was applied to the alpha-cypermethrin NOAEL.
For inhalation risk assessments, an inhalation toxicity study in rats was chosen and human
equivalent concentrations (HECs) were calculated and used for risk assessment. For inhalation
risk assessments, the interspecies uncertainty factor was reduced from 10X to 3X because the
HEC calculation accounts for pharmacokinetic (not pharmacodynamic) interspecies differences
between animals and humans. Since the PODs and endpoints are based on cypermethrin data,
and there is concern for increased toxicity after exposure to alpha-cypermethrin, a 5X potency
factor was applied to the HECs/HEDs used in alpha-cypermethrin risk assessments.
The LOCs for occupational and residential risks are based on the various uncertainty and safety
factors retained or applied for specific routes of exposure. For assessing residential exposure
(incidental oral, dermal, and inhalation), the 10X FQPA SF was reduced to 3X for children < 6
years old, based on the increased quantitative susceptibility seen in studies on pyrethroid PK
and the increased quantitative juvenile susceptibility observed in high dose studies in the
literature. For adults and children 6 ≥ years, the traditional factors were applied (10X
intraspecies and 10X interspecies) but there was sufficient data to remove the 10X FQPA factor
for dermal exposures. For inhalation exposure for all index life stages, the standard interspecies
uncertainty factor was reduced from 10X to 3X (due to the HEC calculation accounting for
pharmacokinetic (not pharmacodynamic) interspecies differences); the intraspecies uncertainty
factor remains at 10X.
Residue Chemistry
Adequate residue chemistry data are available for supporting the established tolerances and for
evaluating dietary exposure and risk associated with residues of cypermethrins in or on food
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commodities. The submitted studies include those related to analytical methods, metabolism in
plants and livestock, storage stability, residue levels in plants and livestock, and residue levels in
rotational crops.
For all three cypermethrins, HED has concluded the residue of concern for risk assessment and
tolerance enforcement is the parent compound. Cypermethrin contains the same isomers as
alpha-cypermethrin and zeta-cypermethrin, and the analytical method does not distinguish
between the isomers. As a result, analysis for cypermethrin will detect the total residues of all
three isomers.
Dietary Exposure and Risk Assessment

HED conducted an acute aggregate dietary (food and drinking water) exposure assessment using
the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database
(DEEM-FCID) Version 3.16. This software uses 2003-2008 food consumption data from the
U.S. Department of Agriculture’s (USDA’s) National Health and Nutrition Examination Survey,
What We Eat in America, (NHANES/WWEIA). The acute assessment is a refined probabilistic
assessment based on a combination of tolerance level residues for many commodities and
Pesticide Data Program (PDP) monitoring data for the commodities that make the most
significant contribution to dietary exposure. Estimates of the maximum percent crop treated
were used for the same commodities for which PDP data were used and for one commodity for
which the tolerance was used. Although tolerance level residues were used for most
commodities, these commodities are not highly consumed ones. Refining the residue estimates
for these commodities would not have a significant effect on exposure and risk estimates. In
most cases conservative default processing factors were used. For drinking water, HED used the
peak surface water estimated drinking water concentration (EDWC) of 3.77 ppb. As a class of
chemicals, the pyrethroids have low solubility in water and a high affinity to bind to soils. Given
these physical/chemical properties, it is unlikely that oral exposure from drinking water will be a
major pathway of exposure.
The U.S. population and all population subgroups have exposure and risk estimates that are not
of concern. At the 99.9th percentile of exposure, the risk estimate for the general U.S. population
is 29% of the acute population adjusted dose (aPAD). The population subgroup with the highest
risk estimate is Children 3-5 years old, which uses 92% of the aPAD. The acute dietary risk
assessment incorporated the 5X toxicity factor for alpha-cypermethrin by multiplying the
residues of alpha-cypermethrin used in the analysis by a factor of 5, and then comparing the
exposure to the Wolansky (unadjusted) POD; this approach allowed HED to make full use of the
monitoring data, which don’t distinguish between the isomers, and to allow for inclusion of all 3
isomers in one acute dietary exposure analysis.
In order to assess short-term aggregate risk to cypermethrins, the average dietary (food and
drinking water) exposure was calculated. The chronic dietary exposure assessment is a highly
refined assessment based on PDP monitoring data for most commodities. HED made the
assumption of 100% crop treated for all commodities with agricultural uses. As a result, percent
crop treated estimates were not used to calculate the anticipated residues used for agricultural
commodities. Tolerance level residues were used for a limited number of commodities;
however, these commodities are not highly consumed ones and, therefore, they make a negligible
contribution to the dietary risk. As with the acute assessment, conservative default processing
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factors were generally used for processed commodities. The cypermethrins have food handling
establishment (FHE) uses that were accounted for in the chronic dietary exposure assessment.
For these uses, HED used a residue value of one-half the tolerance. For drinking water, HED
used the annual average surface water EDWC of 0.066 ppb. The chronic exposure estimates
were incorporated into the aggregate human health risk assessment.
Residential Handler Exposure and Risk Assessment

Cypermethrins are currently registered for use on turf grass (including golf courses, residential
lawns, athletic fields), recreational sites (i.e., golf courses, athletic fields); indoor
residential/commercial/industrial sites/structural/perimeter; gardens and trees; as well as a
mosquito adulticide, termiticide, and pet uses. Existing residential uses were re-assessed to
reflect updates to HED’s 2012 Residential SOP as well as updated application rates and
scenarios. In accordance with current guidance, only those product labels without specific
clothing and/or PPE requirements have been assessed for residential handler exposure.
Since no adult dermal endpoint of concern was selected for cypermethrin and zeta-cypermethrin,
only inhalation risks were calculated. All representative residential handler inhalation risk
estimates resulted in margins of exposure (MOEs) greater than the LOC and are not of concern
(i.e., inhalation MOEs are > 30).
An aggregate risk index (ARI) was calculated for alpha-cypermethrin since the LOCs for dermal
exposure (100) and inhalation exposure (30) are different. All of the residential handler risk
estimates for alpha-cypermethrin are not of concern (i.e., the ARI is > the LOC of 1) with one
exception:
 Residential handlers using a microencapsulated concentrate in livestock housing applied
using a mechanically pressurized handwand had a dermal MOE of 62 and an ARI of 0.61
which are of concern. However, since exposure estimates for microencapsulated
formulations are based on surrogate unit exposure data for liquid formulations, the
calculated MOEs and ARI are conservative.
Residential Post-application Exposure and Risk Assessment
All cypermethrin and zeta-cypermethrin representative indoor and outdoor children’s dermal,
incidental oral and combined post-application scenarios resulted in MOEs greater than the LOC
of 300 and are not of concern with two exceptions:
 cypermethrin dermal and combined dermal and incidental oral exposures for children 1 to
<2 years old resulted in risk estimates of concern from broadcast applications to lawns
using wettable powder formulation (MOE = 94), and
 zeta-cypermethrin combined dermal and incidental oral exposures for children 1 to <2
years old resulted in risk estimates of concern from contact with pets treated with pet
collars (i.e., LOC =300; with MOEs ranging from 1.9 to 190).
All alpha-cypermethrin representative indoor and outdoor post-application

scenarios for adults and children are not of concern (i.e., MOEs ≥300) with the following
exceptions:
 Children 1 to <2 years old incidental oral (MOE = 270), and combined dermal and
incidental oral exposures resulting from indoor perimeter and spot treatments (MOEs
Page 9 of 138
ranging from 140 to 260) using course spray on carpets and hard surfaces as well as pin
stream spray on carpets; and
 Children 1 to <2 years old combined dermal and incidental oral exposures resulting from
broadcast applications to lawns using a liquid formulation (MOE = 270).
Chemical-specific turf transferrable residue (TTR) and dislodgeable foliar residue (DFR) data
were available for cypermethrin and have been incorporated into the post-application assessment.
Chemical specific DFR data were only used for alpha-cypermethrin as it was the only active
ingredient which had registered uses for gardens and trees.
Spray Drift Exposure Assessment

A quantitative spray drift assessment for liquid formulations of cypermethrin and zeta-
cypermethrin is not required because the maximum application rate to a crop/target site
multiplied by the adjustment factor for drift of 0.26 is less than the maximum direct spray
residential turf application rate for any cypermethrins product. However, since there were risks
of concern from the direct turf use for the wettable powder formulation of cypermethrin, and the
liquid formulation for alpha-cypermethrin a spray drift assessment was performed for the indirect
exposures from registered agricultural uses. Results indicate that there are no risk estimates of
concern associated with drift. Adult dermal MOEs range from 8,200 to 15,000 for alpha-
cypermethrin. The combined (dermal + incidental oral) MOEs for children (1 < 2 years) range
from 5,300 to 9,000 for cypermethrin and from 4,100 to 7,400 for alpha-cypermethrin.
Aggregate Exposure and Risk Assessment

The acute aggregate risk estimates are equivalent to the corresponding dietary (food plus water)
risk estimates, which are not of concern. The short-term aggregate risk assessment is based on
background dietary exposure from food and drinking water and potential residential exposure for
adults and children older than 6 years of age (dermal and inhalation) or children less than 6 years
of age (dermal, inhalation and incidental oral). Certain indoor, lawn and pet exposure scenarios
did result in risk estimates below their respective LOCs and are of concern. These exposure
scenarios have not been quantitatively combined with background exposure from food and water
since this would result in risks of concern. Of the remaining representative residential exposure
scenarios, HED selected only the most conservative, or worst case, residential adult and
children’s scenarios to be included in the aggregate estimates, based on the lowest overall MOEs
(i.e., highest exposure estimates) that are above the LOC. There are no aggregate risk estimates
of concern resulting from the use of these worst-case representative residential scenarios in the
assessment.
Occupational Handler Exposure and Risk Estimates

Cypermethrins are currently registered for use on a wide variety of agricultural food/feed crops,
livestock, sod farms, and mosquito and termiticide control uses. All cypermethrin and zeta-
cypermethrin handler scenarios resulted in risk estimates greater than the LOC (inhalation LOC
= 30) with baseline attire (i.e., long sleeve shirt, pants, shoes and socks, no respirator), and
engineering controls for aerial applications and are not of concern with two exceptions:
 Mixing/loading/applying liquid formulations of cypermethrin with a mechanically
pressurized handgun to structural sites for control of termites (MOE = 28). Use of a
respirator with protection factor (PF) of 5 results in an inhalation MOE of 140; and
Page 10 of 138
 Mixing/loading/applying liquid formulations of use of zeta-cypermethrin with handheld
fogging equipment to structural and industrial sites (MOE = 9.9). Use of a respirator
with protection factor (PF) of 5 results in an inhalation MOE of 49, which is not of
concern.
An aggregate risk index (ARI) approach was used for alpha-cypermethrin since the LOCs for
dermal exposure (100) and inhalation exposure (30) are different. Occupational handler
scenarios for alpha-cypermethrin are not of concern (ARI ≥ 1) with baseline attire and PPE (i.e.,
gloves and no respirator) with three exceptions:
 Mixing/loading truck mounted fogger for mosquito vector control resulted in an ARI of
0.61 with baseline attire (i.e., no gloves or respirator) and is of concern. The use of gloves
results in an ARI of 3.5, which is not of concern;
 Applying alpha-cypermethrin using truck mounted fogger resulted in an ARI of 0.074
with baseline attire (i.e., no gloves or respirator) and is of concern. Use of engineering
controls results in an ARI of 8.9, which is not of concern;
 Mixing/loading and applying alpha-cypermethrin with a manually pressurized handwand
to turf, poultry/livestock housing, foundations and perimeters resulted in risk estimates of
concern when using baseline attire and no respirator (ARIs = 0.2, 0.2, and 0.35
respectively). The use of gloves results in ARIs above the LOC (31, 33 and 55,
respectively); and
 Mixing/loading/applying alpha-cypermethrin with a mechanically pressurized handgun to
poultry/livestock housing, structures to control termites and typical field crops resulted in
risk estimates of concern when using baseline attire and no gloves or respirator (ARIs =
0.36, 0.9, and 0.54, respectively). The use of a PF5 respirator for applications to poultry
housing, and gloves for applications to structures and field crops, results in ARIs above
the LOC of 1 (1.1, 1.7. and 1.6 respectively).
Occupational Post-application Exposure and Risk

Although there is potential for dermal post-application exposure, an adult dermal endpoint was
not selected for cypermethrin and zeta-cypermethrin, and a quantitative dermal post-application
exposure assessment was not performed. However, a dermal endpoint was selected for alpha-
cypermethrin and a quantitative post-application assessment was performed. There are no
occupational post-application risk estimates of concern associated with alpha-cypermethrin. All
post-application exposure scenarios resulted in dermal risk estimates greater than the LOC
(dermal LOC = 100) on the day of application and are not of concern. For the foliar uses of
alpha-cypermethrin, chemical-specific dislodgeable foliar residue (DFR) data are available and
were used.
Although a quantitative occupational post-application inhalation exposure assessment was not

performed, an inhalation exposure assessment was performed for all cypermethrin, zeta-
cypermethrin and alpha-cypermethrin occupational/commercial handlers which resulted in no
risks of concern. Handler exposure resulting from application of pesticides outdoors is likely to
result in higher exposure than from post-application activities. Therefore, it is expected that
these handler inhalation exposure estimates would be protective of most occupational post-
application inhalation scenarios.
Page 11 of 138
Considerations of Environmental Justice
Potential areas of environmental justice concerns were considered in this human health risk
assessment to the extent possible.
Human Studies Review

This risk assessment relies in part on data from studies in which adult human subjects were
intentionally exposed to a pesticide or other chemical. These data, which include studies from
PHED 1.1; the AHETF database; Outdoor Residential Exposure Task Force (ORETF) database;
the Residential SOPs (Treated, Lawns/Turf, Indoor Environments, and Pets); and other registrant
submitted exposure monitoring studies (MRID 451115-01, and 446852-01) are (1) subject to
ethics review pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with
applicable ethics requirements. For certain studies, the ethics review may have included review
by the Human Studies Review Board. Descriptions of data sources, as well as guidance on their
use, can be found at the Agency website1.
2.0 HED Conclusions
2.1 Data Deficiencies
There are no data deficiencies associated with the toxicology, residue chemistry, or exposure
databases for cypermethrins.
2.2 Tolerance Considerations
Adequate data have been submitted to support the established tolerances for residues of
cypermethrins in or on food commodities. There are no outstanding data with respect to
tolerances.
2.2.1 Enforcement Analytical Method
Adequate tolerance-enforcement methods are available in PAM Volume II for determining

residues of cypermethrin, zeta-cypermethrin and alpha-cypermethrin in plant (Method I) and
livestock (Method II) commodities. Both methods are gas chromatographic methods with
electron-capture detection (GC/ECD), and have undergone successful Agency petition method
validations (PMVs). Method I has a limit of detection (LOD) of 0.01 ppm, and Method II has
LODs of 0.005 ppm in milk, and 0.01 ppm in livestock tissues. These methods are not
stereospecific; thus no distinction is made between residues of cypermethrin (all 8
stereoisomers), zeta-cypermethrin (enriched in 4 isomers) and alpha-cypermethrin (2 isomers).
The January 1994 FDA PESTDATA database (PAM Volume I) indicates that residues of
cypermethrin are completely recovered (>80%) using multi-residue method Sections 302 (Luke),
303 (Mills, Onley and Gaither) and 304 (Mills fatty food).
1
http://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/occupational-pesticide-handler-exposure-data
and http://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/occupational-pesticide-post-application-
exposure
Page 12 of 138
2.2.2 International Harmonization
For the cypermethrins, there are numerous commodities that have both U.S. tolerances and
Codex MRLs. Appendix C contains tables of the commodities with U.S. tolerances and the
Codex, Canadian, and Mexican MRLs for those commodities. When there are both U.S.
tolerances and Codex MRLs for the same commodity, the MRLs are generally not harmonized.
The U.S. tolerances are usually higher than the Codex MRLs. In these cases, harmonization
might not be feasible because the tolerances are based on residue trials that resulted in residues
that necessitated the higher residue limit. In a limited number of cases, however, the U.S.
tolerances are lower than the Codex MRLs. These MRLs could potentially be harmonized
because, in most cases, there isn’t a significant difference between the U.S. tolerance and the
Codex MRL. For all three of the cypermethrins, there is a tolerance of 0.2 ppm for the meat of
cattle, goat, horse, and sheep, and a Codex MRL of 2 ppm. There is also a U.S. tolerance of 0.05
ppm for hog meat for all three cypermethrins and a Codex MRL of 2 ppm. The U.S. tolerances
for these livestock commodities could potentially be raised to 2 ppm. The cypermethrins all
have a tolerance of 0.05 ppm for both the fat and meat of poultry, while there is a Codex MRL of
0.1 ppm for these commodities. The U.S. tolerance could potentially be raised to 0.1 ppm.
There are six plant commodities for which alpha- and zeta-cypermethrin have tolerances that are
lower than the Codex MRLs. These commodities are sugar beet roots, field corn grain, popcorn
grain, rice grain, soybean seed, and wheat grain. These MRLs could potentially be harmonized.
Zeta-cypermethrin alone is registered for use on stone fruit, peanuts, and wheat straw. Alpha-
cypermethrin alone is registered for use on alfalfa hay. The MRLs for these commodities could
potentially be harmonized as well. At this time HED is not formally recommending for these
tolerance changes pending input from stakeholders during the comment period for the Draft Risk
Assessment.
Canada’s Pest Management Regulatory Agency (PMRA) has also established MRLs for the
cypermethrins. In almost all cases, the Canadian MRLs are lower than the U.S. tolerances. The
Canadian MRLs for the citrus fruit crop group and the dried beans subgroup (6B) are higher than
the U.S. tolerances. However, the Codex MRLs for these commodities are lower than the U.S.
tolerances. As a result, HED does not recommend that the tolerances be harmonized with the
Canadian MRLs. Mexico has established MRLs for almost all of the same commodities that
have U.S. tolerances. Mexico adopts the U.S. tolerances or Codex MRLs for its export purposes.
For the cypermethrins, in almost all cases, Mexico adopted the U.S. tolerance.
2.2.3 Recommended Tolerances
Tolerances for the cypermethrins are listed in 40CFR §180.418. This CFR entry is divided into
three sections. Section 180.418(a)(1) is for residues resulting from agricultural applications of
cypermethrin, §180.418(a)(2) is for residues resulting from agricultural applications and FHE
uses of zeta-cypermethrin, and §180.418(a)(3) is for residues resulting from agricultural
applications and FHE uses of zeta-cypermethrin.
The residue of concern for tolerance enforcement is total cypermethrin. The tolerance
expressions for zeta-cypermethrin and alpha-cypermethrin include both coverage and
compliance statements. As a result, these statements are adequate and do not require revision.
However, the tolerance expression for cypermethrin needs to be updated to address both
Page 13 of 138
coverage and compliance as delineated in HED’s Interim Guidance on Tolerance Expressions
(S. Knizner; 27 May 2009).
The tolerance expression for cypermethrin in 40CFR §180.418(a)(1) should be revised to state:
“Tolerances are established for residues of cypermethrin, including its metabolites and
degradates, in or on the commodities in the table below. Compliance with the tolerance levels
specified below is to be determined by measuring only cypermethrin, (S)-cyano(3-
phenoxyphenyl)methyl (±)-cis-trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane
carboxylate, in or on the commodity.”
The cypermethrins are registered on commodities that are part of crop groups or subgroups. In
the case of alpha-cypermethrin, some of the crop group tolerances were established for the
updated groups. As a result, these groups do not need to be updated. However, tolerances were
also established for one group and one subgroup that have not been updated (the leafy vegetable
group, Crop group 4, and the head and stem Brassica subgroup, Subgroup 5A). Cypermethrin is
registered on the two Brassica leafy greens subgroups (subgroups 5A and 5B), which have not
been updated. Finally, zeta-cypermethrin is registered for use on several crop groups and
subgroups that have not been updated: Berry group, 13; Brassica, head and stem, subgroup 5A;
Brassica, leafy greens, subgroup 5B; Fruit, citrus, group 10, Fruit, pome, group 11; Fruit, stone,
group 12; Nut, tree, group 14; and Vegetable, fruiting, group 8. Groups 8, 10, 11, 12, 13, and 14
can be updated to their respective groups 8-10, 10-10, 11-10, 12-12, 13-07, and 14-12 because
the current and updated groups have the same representative commodities. The tolerances for
the updated groups should be the same as those for the current groups. Because of changes in
the representative commodities for the leafy vegetable groups and subgroups and the
establishment of the new group, Stalk, Stem, and Leaf Petiole Vegetable Group (22), the leafy
vegetable group (Vegetable Leafy, Except Brassica, Group 4), the Brassica, Head and Stem,
Subgroup 5A, and the Brassica, Leafy Greens Subgroup 5B, cannot be directly updated to the
new and updated groups and subgroups. Instead, they should be replaced with the following
groups and subgroups.
Cypermethrin: A tolerance of 14 ppm should be established for the Brassica leafy greens
subgroup 4-16B. A tolerance of 2.0 ppm should be established for the Brassica head and stem
subgroup, 5-16, and a tolerance of 2.0 ppm should be established for kohlrabi.
Zeta-Cypermethrin: A tolerance of 14 ppm should be established for the Leafy vegetable group,
4-16; a tolerance of 2.0 ppm should be established for Brassica, head and stem vegetable group,
5-16; and a tolerance of 10 ppm should be established for the Leaf petiole vegetable subgroup,
22B.
Alpha-Cypermethrin: A tolerance of 10 ppm should be established for the Leafy greens

subgroup, 4-16A; a tolerance of 2.0 ppm should be established for Brassica, head and stem
vegetable group, 5-16; and a tolerance of 10 ppm should be established for the Leaf petiole
vegetable subgroup, 22B.
When the tolerances for the updated crop groups and subgroups are established, the tolerances
for the previous crop groups should be canceled.
Page 14 of 138
Recommendations for Changes to Individual Tolerances
HED is recommending that a small number of individual tolerances be deleted or changed. For
zeta-cypermethrin, there is a tolerance of 2.0 ppm for cabbage. This tolerance should be deleted
because HED is recommending in favor of a tolerance of 2.0 ppm for the Brassica head and stem
vegetable group (Group 5-16), which includes cabbage. Zeta-cypermethrin also has a tolerance
of 0.05 ppm for pecan. This tolerance should be deleted because HED is recommending in favor
of a tolerance of 0.05 ppm for tree nut crop group (14-12) which includes pecan.
The 40CFR listing for alpha-cypermethrin gives a tolerance of 10 ppm for the citrus fruit crop
group (10-10). This tolerance should be changed to 0.35 ppm in the 40CFR listing. HED
recommended in favor of the 0.35 ppm tolerance in a human health risk assessment prepared for
alpha-cypermethrin in 2012 (D376098, K. Middleton, et al., 9/11/2012).
The analytical enforcement method for the cypermethrins does not distinguish between the
isomers. For this reason, the tolerances for the three cypermethrins should be consistent from
one to the other. A tolerance of 6.0 ppm is established for cypermethrin in or on green onions,
whereas a tolerance of 3.0 ppm is established for both zeta- and alpha-cypermethrin. The 3.0
ppm tolerance should be raised to 6.0 ppm. A tolerance of 30 ppm is established for zeta-
cypermethrin in or on alfalfa hay, whereas a tolerance of 15 ppm is established for alpha-
cypermethrin. The 15 ppm tolerance should be raised to 30 ppm. A tolerance of 4.0 ppm is
established for cypermethrin in or on head lettuce, whereas HED is recommending in favor of a
tolerance of 10 ppm for zeta- and alpha-cypermethrin in or on the Leafy vegetable group (Group
4-16). The cypermethrin 4.0 ppm tolerance should be raised to 10 ppm. Finally, a tolerance of
0.1 ppm is established for cypermethrin and zeta-cypermethrin in hog fat, whereas a tolerance of
1.0 ppm is established for alpha-cypermethrin. The 0.1 ppm tolerances should be raised to 1.0
ppm.
The tolerance recommendations discussed above are summarized in the tables below.
TABLE 2.2.a. Tolerance Summary for Cypermethrin (40CFR §180.418)(a)(1).

Tolerances to be Established or Canceled
Commodity Current Recommended Comments; Correct Commodity Definition
Tolerance (ppm) Tolerance
(ppm)
Brassica, head and stem, group None 2.0 Updated crop group tolerance
5-16
Brassica, leafy greens, subgroup None 14 Updated crop group tolerance
4-16B
Kohlrabi None 2.0 Now in subgroup 22A (no subgroup tolerance)
Brassica, head and stem, None None Cancel
subgroup 5A
Brassica, leafy greens, subgroup None None Cancel
5B
Hog, fat 0.1 1.0 Raise to be consistent with alpha-cypermethrin
tolerance
Lettuce, head 4.0 14 Raise to be consistent with zeta-cypermethrin crop
group 4-16 tolerance
Page 15 of 138
TABLE 2.2.b. Tolerance Summary for zeta-Cypermethrin (40CFR §180.418)(a)(2).
(ppm)
Vegetable, leafy, group 4-16 None 14 Updated crop group tolerance
5-16
Stalk, stem, and leaf petiole None 10 Updated crop group tolerance
vegetable, subgroup 22B
Brassica, head and stem, 2.00 None Cancel
subgroup 5A
Brassica, leafy greens, subgroup 14.00 None Cancel
5B
Vegetable, leafy, except 10.00 None Cancel
Brassica, group 4
Berry and small fruit, group 13- None 0.8 Updated crop group tolerance
07
Berries group 13 0.8 None Cancel
Fruit, citrus, group 10-10 None 0.35 Updated crop group tolerance
Fruit, citrus, group 10 0.35 None Cancel
Fruit, pome, group 11-10 None 2 Updated crop group tolerance
Fruit, pome, group 11 2 None Cancel
Fruit, stone, group 12-12 None 1 Updated crop group tolerance
Fruit, stone, group 12 1 None Cancel
Nut, tree, group 14-12 None 0.05 Updated crop group tolerance
Nut, tree, group 14 0.05 None Cancel
Vegetable, fruiting, group 8-10 None 0.2 Updated crop group tolerance
Vegetable, fruiting, group 8 0.2 None Cancel
Onion, green 3.0 6.0 Raise to be consistent with cypermethrin tolerance
Cabbage 2.0 None Cancel: Cabbage is a member of group 5-16, so
the individual tolerance is not necessary
Hog, fat 0.1 1.0 Raise to be consistent with alpha-cypermethrin
tolerance
Okra 0.2 None Cancel: Okra is a member of group 8-10, so the
individual tolerance is not necessary
Pistachio 0.05 None Cancel: Pistachio is a member of group 14-12, so
the individual tolerance is not necessary
Pecan 0.05 None Cancel: Pecan is a member of group 14-12, so the
individual tolerance is not necessary
Turnip, greens 14 None Cancel: Turnip greens are a member of group 4-
16, so the individual tolerance is not necessary
TABLE 2.2.c. Tolerance Summary for alpha-Cypermethrin (40CFR §180.418)(a)(3).

(ppm)
Leafy greens, subgroup 4-16A None 14 Updated crop group tolerance
5-16
Stalk, stem, and leaf petiole None 10 Updated crop group tolerance
vegetable, subgroup 22B
Page 16 of 138
TABLE 2.2.c. Tolerance Summary for alpha-Cypermethrin (40CFR §180.418)(a)(3).
(ppm)
Brassica, head and stem, 2.00 None Cancel
subgroup 5A
Vegetable, leafy, except 10.00 None Cancel
Brassica, group 4
Onion, green 3.0 6.0 Raise to be consistent with cypermethrin tolerance
Alfalfa, hay 15 30 Raise to be consistent with zeta-cypermethrin
tolerance
Fruit, citrus, group 10-10 10 0.35 Decrease: HED originally recommended in favor
of a tolerance of 0.35 ppm
2.3 Label Recommendations
No specific label recommendations are being made; however, HED has identified some risk
estimates of concern for occupational handlers. Some of these risk estimates are not of concern
with the addition of PPE beyond what is currently on labels, such as respirators and engineering
controls and should be considered as potential options for mitigating any risks identified in this
assessment. Additionally, label information (e.g., concentration of liquid formulation), and
application rates (listed as product applied per area, as well as dilutions of the product to be
applied) should be clearly specified for all use sites on all registered labels.
While no specific label recommendations are being made, HED notes that there are risk
estimates of concern for residential handlers applying microencapsulated products. Furthermore,
HED identified combined dermal and incidental oral risk estimates of concern for children (1 to
< 2 yrs. old) resulting from contact with treated pet collars, indoor surfaces, and lawns/turf.
This risk assessment relies on a 2015 study by the Agricultural Handler Exposure Task Force
(AHETF) that measured dermal and inhalation exposure for workers who mixed and loaded
water-soluble packet pesticide products. Commensurate with the behaviors and practices
represented by this data, labels for products formulated in water-soluble packaging should
incorporate the Agency’s revised instructions for proper mixing and loading of water-soluble
packets. This revised language is aimed at ensuring that water-soluble packets are allowed to
dissolve in water via mechanical agitation as intended and prevent them from being ruptured by
streams of water or other means.
3.0 Introduction
3.1 Chemical Identity
The nomenclature for cypermethrin, zeta-cypermethrin and alpha-cypermethrin is presented in

Tables 3.1a, b, and c below.
Page 17 of 138
TABLE 3.1.a: Cypermethrin Nomenclature.
Compound chemical
structure
Common name Cypermethrin

Empirical formula C22H19Cl2NO3
Molecular weight 416.3 g/mole
IUPAC name (RS)-α-cyano-3-phenoxybenzyl (1RS,3RS;1RS,3SR)-3-(2,2-dichlorovinyl)-2,2-
dimethylcyclopropanecarboxylate
or
(RS)-α-cyano-3-phenoxybenzyl (1RS)-cis-trans-3-(2,2-dichlorovinyl)-2,2-
CAS name cyano(3-phenoxyphenyl)methyl 3-(2,2-dichloroethenyl)-2,2-

CAS registry number 52315-07-8
End-use product (EP) Numerous
Table 3.1.b: Zeta-Cypermethrin Nomenclature.

Compound
Cl
O
O
Cl H
O
N
Common name Zeta-cypermethrin

Company experimental name FMC 56701
IUPAC name (S)-α-cyano-3-phenoxybenzyl (1R)-cis-trans-3-(2,2-dichlorovinyl)-2,2-
or
(S)-α-cyano-3-phenoxybenzyl (1RS, 3RS, 1SR, 3SR)-3-(2,2-dichlorovinyl)-2,2-
CAS name (S)-cyano(3-phenoxyphenyl)methyl (±)-cis-trans-3-(2,2-dichloroethenyl)-2,2-
Page 18 of 138
Table 3.1.b: Zeta-Cypermethrin Nomenclature.
End-use product (EP) 1.5 lb ai/gal EC (Fury® or Mustang® 1.5 EC Insecticide; USEPA Reg. No. 279-3125)
1.5 lb ai/gal EW (Mustang® 1.5 EW Insecticide; USEPA Reg. No. 279-3126)
0.4 lb ai/gal ZetaGard LBT Insecticide Dust; File Symbol 39039-EN
TABLE 3.1.c: Alpha-cypermethrin Nomenclature.

Compound chemical
structure
Common name Alpha-cypermethrin

Company experimental name BAS 310 I or AC 900049
Empirical formula C22H19Cl2NO3
Molecular weight 416.3 g/mole
IUPAC name A racemic mixture comprised of:
(R)-α-cyano-3-phenoxybenzyl (1S,3S)-3-(2,2-dichlorovinyl)-2,2-
and
(S)-α-cyano-3-phenoxybenzyl (1R,3R)-3-(2,2-dichlorovinyl)-2,2-
or (synonymously)
(R)-α-cyano-3-phenoxybenzyl (1S)-cis-3-(2,2-dichlorovinyl)-2,2-
and
(S)-α-cyano-3-phenoxybenzyl (1R)-cis-3-(2,2-dichlorovinyl)-2,2-
CAS name (R)-cyano(3-phenoxyphenyl)methyl (1S,3S)-rel-3-(2,2-dichloroethenyl)-2,2-
End-use product (EP) BAS 310 40 I EC insecticide (EPA File Symbol 7969-EOI), 10.9% ai (w/w), 0.83
lb ai/gal.
3.2 Physical/Chemical Characteristics
The cypermethrins have high octanol/water partition coefficients and low water solubility
values. The log Koc values are 5.5 or higher, and the water solubilities are 45 ppb or lower. The
compounds also have low vapor pressure, which decreases their ability to volatilize. The vapor
pressure values are 3 x 10-9 or lower, at 20-25°C.

The physicochemical properties are summarized in Appendix B.
Page 19 of 138
3.3 Pesticide Use Pattern
Cypermethrins end-use products are registered for use on a wide variety of agricultural food/feed
crops, livestock, sod farms; recreational (i.e. golf courses, athletic fields); indoor and outdoor
residential/commercial/industrial sites/structures and lawns; gardens and trees; as well as
mosquito adulticide, termiticide, and pet uses. They are formulated as a wide variety of end use
products (i.e., liquid concentrates, micro-encapsulated, granules, water dispersible granules,
wettable powders, water soluble packages, read-to-use aerosols, foggers, impregnated wipes, ear
tags and cattle strips, pet spot-on and collars). Cypermethrin end-use products contain 0.03% to
40% of the active ingredient, zeta-cypermethrin end-use products contain 0.05% to 18.1% of the
active ingredient while alpha -cypermethrin end-use products contain 0.05% to 10.9% of the
active ingredient. Agricultural end-use products may be applied using ground, chemigation,
aerial equipment and handheld equipment. Industrial, commercial and residential end-use
products are applied using a variety of hand held equipment (i.e., backpack, low pressure
handwands, handgun, injectors, trigger spray bottles, aerosol sprays, push and rotary type
spreaders and foggers). Mixers, loaders, applicators and other handlers must wear baseline
clothing (long-sleeved shirt, long pants, socks, and shoes) and personal protective equipment
(PPE) ranging from use of chemical resistant gloves to the addition of coveralls; chemical
resistant footwear, headgear and apron; eyewear; and respiratory protection devices when
working in non-ventilated space or applying termiticide by rodding or slab injections.
A summary of the representative registered agricultural and commercial end-use products and
use sites with the highest application rates or percent active ingredient (ai) is provided in
Appendix D for the agricultural uses, non-agricultural, and residential uses of cypermethrins.
3.4 Anticipated Exposure Pathways
Humans could be exposed to cypermethrin residues from consuming food treated for agricultural
pest management purposes. Agricultural applications can result in cypermethrins reaching
surface and ground water, both of which can serve as sources of drinking water. However,
because of the low water solubility of the chemical and its affinity to bind to soil organic matter,
drinking water concentrations will be very low. Furthermore, there is potential for occupational
and residential handlers to be exposed via the dermal and inhalation routes of exposure while
mixing/loading the pesticide, and during application. There is also the potential for post-
application exposure to occupational workers entering treated fields and to non-occupational
bystanders who may be exposed to spray drift from occupational applications. Adults and
children can also be exposed in residential settings by contacting treated residential turf, indoor
and outdoor environments, as well as treated pets via inhalation, dermal, and incidental oral
(children only) routes of exposure. All of the relevant exposure pathways have been included in
this risk assessment.
3.5 Consideration of Environmental Justice
Potential areas of environmental justice concerns, to the extent possible, were considered in this
human health risk assessment, in accordance with U.S. Executive Order 12898, “Federal Actions
to Address Environmental Justice in Minority Populations and Low-Income Populations,”
Page 20 of 138
(http://www.archives.gov/federal-register/executive-orders/pdf/12898.pdf). As a part of every
pesticide risk assessment, OPP considers a large variety of consumer subgroups according to
well-established procedures. In line with OPP policy, HED estimates risks to population
subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water
consumption, and activities in and around the home that involve pesticide use in a residential
setting. Extensive data on food consumption patterns are compiled by the U.S. Department of
Agriculture under the National Health and Nutrition Examination Survey, What We Eat in
America, (NHANES/WWEIA). These food consumption patterns are used in pesticide risk
assessments for all registered food uses of a pesticide. These data are analyzed and categorized
by subgroups based on age and ethnic group. Additionally, OPP is able to assess dietary
exposure to smaller, specialized subgroups, and exposure assessments are performed when
conditions or circumstances warrant. Whenever appropriate, non-dietary exposures are also
evaluated based on home use of pesticide products which includes calculating associated risks
for adult applicators and for children, youths, and adults entering or playing in previously treated
areas. Further considerations are currently in development, as OPP has committed resources and
expertise to the development of specialized software and models that consider exposure to
bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific
subgroups.
4.0 Hazard Characterization and Dose-Response Assessment
Cypermethrin, zeta-cypermethrin, and alpha-cypermethrin (the cypermethrins) are members of

the pyrethroid class of chemicals. Pyrethroids have historically been classified into two groups,
Type I and Type II, based upon chemical structure and toxicological effect. Type I pyrethroids,
which lack an alpha-cyano moiety, induce in rats a syndrome consisting of aggressive sparring,
altered sensitivity to external stimuli, hyperthermia, and fine tremors progressing to whole-body
tremors and prostration (T-syndrome). Type II pyrethroids, which contain an alpha-cyano
moiety, in rats produce a syndrome that includes pawing, burrowing, salivation, hypothermia,
and coarse tremors leading to choreoathetosis (CS-syndrome) (Verschoyle and Aldridge 1980;
Lawrence and Casida 1982). Cypermethrin, zeta-cypermethrin, and alpha-cypermethrin are Type
II pyrethroids and the biochemical responses and resulting clinical signs of neurotoxicity are
consistent with those of Type II pyrethroids. The adverse outcome pathway (AOP, based on the
Bradford-Hill criteria) shared by pyrethroids involves the ability to interact with voltage-gated
sodium channels (VGSCs) in the central and peripheral nervous systems, leading to changes in
neuron firing and, ultimately, neurotoxicity (Figure 4.0).
Target Altered In Vivo

VGSC
Tissue Neuronal Clinical
Alterations
Dose Excitability Signs
Figure 4.0. Adverse outcome pathway for pyrethroids.
Although cypermethrin, zeta-cypermethrin and alpha-cypermethrin are separate active

ingredients with different end-use products, they are included together in the hazard evaluation
based on the following considerations:
Page 21 of 138
 All three cypermethrins are structurally similar (type II-α-cyano pyrethroids) and share a
common mode of action (interaction with voltage gated sodium channels). The main
target tissue for all three chemicals is the central and peripheral nervous system.
 The qualitative nature of the toxicological effects (i.e., neurotoxicity) for the
cypermethrins is similar following oral and inhalation routes of exposure. For
cypermethrin, zeta-cypermethrin, and alpha-cypermethrin, the toxic effects observed are
relatively consistent across the database.
 The toxicology database for the cypermethrins is largely complete. When evaluated
together, the toxicity database for cypermethrin, zeta-cypermethrin, and alpha-
cypermethrin can be used to characterize the overall suite of effects associated with
cypermethrin exposure, including potential developmental and reproductive toxicity,
immunotoxicity, and neurotoxicity.
4.1 Toxicology Studies Available for Analysis
The database of experimental toxicology studies available for the cypermethrins provides a
robust characterization of the hazard potential for children 6 years old and older as well as for
adults. However, there are ongoing efforts to develop data (see Section 4.4) to inform the
potential sensitivity of infants and young children to pyrethroids as a class. Despite the missing
studies and the ongoing scientific efforts, HED has chosen points of departure and uncertainty
factors in this risk assessment that are protective of the effects associated with exposure to the
cypermethrins. In addition, numerous studies from the scientific literature have also been
conducted over several decades that describe the pharmacodynamic and pharmacokinetic profile
of the pyrethroids in general. This scientific literature has been reviewed by several groups
(Soderlund et al. 2002; Shafer et al. 2005; Wolansky and Harrill 2008). The data from the
following studies were used to evaluate the hazard potential of the cypermethrins:
 Wolansky Acute Oral Rat Study (cypermethrin)

 WIL Laboratory Acute Oral Rat Study (cypermethrin)
 McDaniel Acute Oral Rat Neurobehavioral Study (cypermethrin)
 21 Day Dermal Studies in the Rat and Rabbit (cypermethrin and zeta-cypermethrin)
 Dermal Penetration Study in the Rat (alpha-cypermethrin)
 21-Day Inhalation Study (cypermethrin)
 90 Day Rat Studies (cypermethrin, alpha- and zeta-cypermethrin)
 90 Day Dog Studies (cypermethrin and alpha-cypermethrin)
 Chronic Dog Studies (cypermethrin and alpha-cypermethrin)
 Chronic/Cancer Mouse Studies (cypermethrin and alpha-cypermethrin)
 Chronic/Cancer Rat Study (cypermethrin)
 Developmental Studies in the Rat and Rabbit (cypermethrin, alpha- and zeta-
cypermethrin)
 Reproduction Studies in the Rat (cypermethrin and zeta-cypermethrin)
 Acute Neurotoxicity (ACN) Studies in the Rat (cypermethrin, alpha- and zeta-
cypermethrin)
 Subchronic Neurotoxicity (SCN) Studies in the Rat (cypermethrin and zeta-
Page 22 of 138
cypermethrin)
 Developmental Neurotoxicity (DNT) Study in the Rat (zeta-cypermethrin)
 Metabolism Studies in the Rat and Human (cypermethrin and alpha-cypermethrin)
4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)
Cypermethrin, is a racemic mixture of eight isomers. Zeta- and alpha-cypermethrin are

enrichments of the more insecticidally-potent isomers (e.g., alpha-S and cis-2-R isomers).
Metabolism data available for cypermethrin and alpha-cypermethrin in the rat show rapid
absorption and clearance, similar to other pyrethroids. After oral exposure to the cis- and trans-
isomers of cypermethrin separately, and cypermethrin (i.e., equimolar mixture of the cis- and
trans-isomers), >70% of the radiolabel was excreted within 24 hours, with >53% in the urine and
<20% in the feces in males. However, in females, the cis isomer was excreted equally in urine
and feces, approximately 35% of the administered dose (AD) via each route. Less than 1% of
the AD was expired in the air. The fat tissue retained the most radiolabeled material after dosing
with the cis and trans isomers, with little reduction from day 1 to day 8. The liver was also a
target organ, however, concentrations rapidly decreased after dosing on day 1. Oral exposure to
alpha-cypermethrin, resulted in total recovery of 94-95% administered dose in the excretion and
tissue. Approximately half of the dose was absorbed, and the dose was quickly eliminated.
Absorption, based on radioactivity found in the urine, cage wash, and tissues, was at least
53-55% AD (biliary excretion was not evaluated). Most of the dose was excreted within 24
hours (>76% AD). After 4 days, slightly more of the dose was excreted in the urine (50-53%
AD) than in the feces (38-43% AD). Radioactive residues in the cage wash, tissues, and the
residual carcass accounted for <2% AD each.
4.3. Summary of Toxicological Effects
The cypermethrins (cypermethrin, zeta-cypermethrin, and alpha-cypermethrin) have been

evaluated for a variety of toxic effects in experimental toxicity studies. The cypermethrins affect
the nervous system, and neurotoxicity is the most sensitive effect observed throughout the
toxicology database. In fact, tremors, gait abnormalities, limb conditions, ataxia and
hypersensitivity were observed across species, sexes, durations, and routes of administration.
Additionally, body weight changes were routinely observed and mortality was seen in a few
studies in rats and dogs. There are a number of acute neurotoxicity studies available for
cypermethrin with clinical signs noted within 4-6 hours of oral dosing during the time to peak
effect. As noted previously, these include a guideline ACN study, the WIL study, the Wolansky
study, and a special acute oral neurobehavioral study (McDaniel and Moser 1993). For zeta-
cypermethrin and alpha-cypermethrin, acute neurotoxicity data are limited to guideline ACN
studies. When comparing the results of the guideline ACN for all three chemicals, the clinical
signs observed for alpha-cypermethrin and zeta-cypermethrin occur at doses that are 5-fold and
3-fold, respectively, lower than those causing toxicity for cypermethrin. Additionally, slight
nerve degeneration was seen in the guideline ACN study with alpha-cypermethrin, but not with
cypermethrin or zeta-cypermethrin. The nerve degeneration with alpha-cypermethrin was
observed at doses higher than where clinical signs were seen. Decreased body weight, body
weight gain, and food consumption were observed for all three isomers in the chronic, 90-day rat
toxicity studies with the effects occurring at lower doses for alpha-cypermethrin than for
cypermethrin or zeta-cypermethrin. Tremors were observed in the 90-day dog studies for both
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cypermethrin and alpha-cypermethrin, with the effects occurring at lower doses for alpha-
cypermethrin than for cypermethrin. Alpha-cypermethrin was also more toxic than cypermethrin
in chronic feeding studies in dogs.
Dermal toxicity studies are available for zeta-cypermethrin (rat) and cypermethrin (rabbit). No
systemic effects were observed in the rat dermal study with zeta-cypermethrin at doses up to the
limit dose. In the rabbit dermal study with cypermethrin, systemic effects were observed (focal
necrosis of the liver, decreased testicular weights and decreased body weight in females).
However, these observations in the rabbit were not considered appropriate for use in risk
assessment since they were seen in abraded animals only, which does not accurately represent
anticipated exposure and results in compromised test conditions and results. Additionally,
abrasion of the skin would alter the permeability of the skin, and as a result, the effects are not
considered relevant for risk assessment. No systemic toxicity was seen in non-abraded animals in
the rabbit dermal toxicity study.
In the previous risk assessment, a dermal penetration value of 2.5% was calculated by comparing
the maternal LOAEL of 25 mg/kg/day from the zeta-cypermethrin developmental study in rats
and the NOAEL of 1000 mg/kg/day (limit dose) from the zeta-cypermethrin 21-day dermal study
in rats. Since that risk assessment, the alpha-cypermethrin registrant submitted an in vivo dermal
absorption study in rats for alpha-cypermethrin (MRID 47944084). The newly submitted dermal
absorption study is considered more robust for risk assessment (compared to use of the
calculated dermal absorption factor, or DAF); this study was used to refine the dermal absorption
value. A portion of the administered dose (0.76-0.78%) remained in the skin at the application
site and surrounding skin at 120 hours post-application, with the low dose providing a
conservative estimate of dermal absorption factor (DAF) of 13.4%.
There was no evidence of increased quantitative or qualitative susceptibility in the available

developmental toxicity or reproduction studies for the cypermethrins. In the rat developmental
toxicity studies with cypermethrin and zeta-cypermethrin, there was no evidence of
developmental toxicity up to the highest doses tested. In the rat developmental toxicity study
with alpha-cypermethrin, decreased fetal body weight was seen. Maternal effects observed with
all three cypermethrins included a number of clinical signs.
In the rabbit developmental toxicity studies with cypermethrin and alpha-cypermethrin, there
was no evidence of developmental toxicity up to the highest dose tested. Maternal effects seen
in rabbits included decreased body weight gain, anorexia, abdomino-genital staining, decreased
feces, and red or pink material in the pan (cypermethrin) and body weight loss and decreased
food consumption (alpha-cypermethrin). A developmental rabbit study is not available for zeta-
cypermethrin.
In the rat reproduction study with cypermethrin, effects were limited to decreased body weight
gain in adult and offspring animals at the highest dose tested. In the rat reproduction study with
zeta-cypermethrin, limited clinical signs and decreased body weight gain were observed in adults
and decreased body weight gain was seen in pups at the same dose; more pronounced clinical
signs and mortality were observed in maternal and offspring animals at higher doses. A rat
reproduction study is not available for alpha-cypermethrin. Quantitative susceptibility was seen
in the rat DNT study, conducted on zeta-cypermethrin. In the DNT study, decreased pup weight
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was observed in the absence of treatment related maternal toxicity. DNT data are not available
for cypermethrin or alpha cypermethrin.
Male reproductive effects were identified for cypermethrin in literature studies (Li et al. 2013;
Hu et al. 2013) and were reviewed as a part of the Endocrine Disruptor Screening Program
(EDSP) screening for cypermethrin. However, the effects were observed at doses higher (1.7 to
4X) than the doses currently used for risk assessment. Therefore, the current risk assessment is
considered protective of potential male reproductive effects.
There was no evidence of immunotoxicity in the toxicology database or in a rat immunotoxicity

study with alpha-cypermethrin.
Cypermethrin is classified as a Group C “Possible human carcinogen”, based on an increased

incidence of benign lung adenomas and adenomas plus carcinomas combined in females in a
mouse carcinogenicity study (TXR# 0055252, J. Quest, 2/17/1988). No tumors were observed in
cypermethrin cancer studies in rats or in cancer studies in mice with alpha-cypermethrin. There
is no genotoxicity concern for the cypermethrins.
Acute lethality studies with the cypermethrins indicate moderate acute toxicity via the oral route
(Toxicity Categories II and III) and low toxicity via the dermal and inhalation routes (Toxicity
Categories III and IV). Additionally, mild irritation was seen in primary eye and skin irritation
studies but no dermal sensitization was observed.
4.3.1 Pyrethroid Pharmacokinetic (PK) and Pharmacodynamic (PD) Profile
OPP is making best use of the extensive scientific knowledge about the AOP for pyrethroids in
the risk assessments for this class of pesticides. In this way, information on a subset of
pyrethroids can be used to help interpret and understand the toxicological profile for other
members of the class. In that regard, a group of pesticide registrants and product formulators
known as the Council for the Advancement of Pyrethroid Human Risk Assessment (CAPHRA)
is collecting metabolism and tissue dosimetry data from rats and human tissues across different
life stages. The CAPHRA initially presented its experimental data and proposed path forward to
the SAP on May19th 2015 (USEPA 2015). Based on the comments from the SAP, the CAPHRA
continued to pursue its research efforts and gather additional data. Currently, data from
CAPHRA to develop PBPK models for deltamethrin and permethrin have been submitted to the
agency and are scheduled to be reviewed by the SAP in 2018.
In addition to the efforts of the CAPHRA, the extensive body of scientific literature on the
pyrethroids provides insight into the contributions of PK and PD to the general toxicity profile of
this class of chemicals. This information also provides valuable insight into the potential age-
related differences in toxicity for the pyrethroids. This scientific literature has been reviewed by
several groups (Soderlund et al. 2002; Shafer et al. 2005; Wolansky and Harrill 2008) and the
following sections of the risk assessment discuss the specific issues related to pyrethroid PK,
pyrethroid PD, and age-related differences in pyrethroid toxicity. Furthermore, the agency will
be updating its literature review for pyrethroids as described below prior to completion of the
revised risk assessments.
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In recent years, the National Academies’ National Research Council (NRC) has encouraged the
agency to move towards systematic review processes to enhance the transparency of scientific
literature reviews that support chemical-specific risk assessments to inform regulatory decision
making (NRC 2011, 2014). The NRC defines systematic review as “a scientific investigation
that focuses on a specific question and uses explicit, pre-specified scientific methods to identify,
select, assess, and summarize the findings of similar but separate studies” (NRC 2014).
According to the NRC, systematic reviews “have several common elements: transparent and
explicitly documented methods, consistent and critical evaluation of all relevant literature,
application of a standardized approach for grading the strength of evidence, and clear and
consistent summative language.” EPA’s Office of Chemical Safety and Pollution Prevention is
currently developing systematic review policies and procedures, and is working to develop a
systematic review for the pyrethroids.
4.3.2 Pharmacokinetics (PK)
PK can be defined as what the body does to the chemical; in this case, how pyrethroids are
distributed and eliminated following exposure. Specific to pyrethroids, PK refers to the
process(es) that determine(s) the concentration of the pyrethroids reaching sodium channels.
The underlying PK of pyrethroids is an important determination of their toxicity because the
concentration of pyrethroid at the sodium channel relates to the extent of toxicity; greater
pyrethroid concentration translates as increased neurotoxicity. Physiological processes that
significantly contribute to the PK include metabolism, protein binding, and partitioning.
Carboxylesterases and cytochrome P450 enzymes are the two major enzyme families responsible
for the metabolism of pyrethroids. It is the ontogeny of these enzymes that accounts for the age-
related sensitivity observed after pyrethroid exposures, as described below in more detail. In
terms of partitioning, pyrethroids tend to distribute into fat. However, pyrethroid residues in
fatty tissue are not available to interact with the voltage-gated sodium channels (VGSCs) in vital
tissues and, therefore, do not contribute to overall toxicity.
Age-dependent PK differences have been identified for several pyrethroids; that is, there are
differences in the ability of adults and juveniles to metabolize pyrethroids. The enzymes that
metabolize and detoxify pyrethroids are present in rats and humans at birth (Koukouritaki et al.
2004; Yang et al. 2009). As a result, both juveniles and adults are able to tolerate low doses of
pyrethroids when the internal dose, or the amount of pyrethroid at the sodium channel, is low.
However, the expression, and therefore activity, of these enzymes increases with age, conveying
in adults a greater capacity than juveniles to detoxify pyrethroids (Anand et al. 2006; de Zwart et
al. 2008; Yang et al. 2009). For example, the rate of in vitro metabolism of deltamethrin by
plasma carboxylesterases, plus hepatic carboxylesterases and cytochrome P450s (microsomes) is
at least 6 times as high for post-natal day (PND) 90 rats as for PND 10 rats (Anand et al. 2006).
In humans, expression of hepatic carboxylesterases is significantly lower in infants <3 weeks old
but then increase to near adult levels (Hines et al. 2016). Similar information is also available
for the major human P450s involved in pyrethroid metabolism (CYP2C8, CYP2C19, and
CYP3A4). CYP2C19 levels are approximately 80% of adult values from >5 months to 10 years,
CYP3A4 reaches near adult levels by 1-2 years, and CYP2C8 levels are comparable to adult
levels after 6 months of age (Koukouritaki et al. 2004; Stevens et al. 2003; Song et al. 2015). As
a consequence, higher internal doses (i.e., those associated with high doses in experimental
toxicology studies) overwhelm the clearance mechanisms in juveniles, but because adults have
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greater enzyme activity, they are able to tolerate higher doses prior to the onset of toxicity. As a
matter of perspective, the anticipated exposures from typical dietary or residential activities are
not expected to overwhelm the premature metabolic systems in juveniles.
To better understand the role of PK and reduce uncertainty associated with extrapolating across
species (i.e., rat to human) and life stages, the agency developed PBPK models designed to
predict pyrethroid concentration in tissues following in vivo exposure. The agency has
determined that the important PK properties relevant to the metabolism and distribution of
pyrethroids in the body are sufficiently similar for members of this class such that using a
‘generic’ or family model structure for this class is scientifically appropriate. In other words,
because of the similarities in the PK profiles of pyrethroids, a single model structure is able to
predict the tissue dose based on the PK of every member of the class. The family modeling
approach was primarily developed based on PBPK modeling performed with deltamethrin and
was presented to, and supported by, the Federal Insecticide, Fungicide, and Rodenticide
Scientific Advisory Panel (FIFRA SAP) (USEPA 2007).
The initial deltamethrin PBPK model presented to the SAP was developed in the adult male
Sprague Dawley (SD) rat (Mirfazaelian et al. 2006). The deltamethrin PBPK model was further
refined based on oral bioavailability and disposition studies in rats and included estimates for
target tissue concentrations in humans (Godin et al. 2010). The initial PBPK model was also
extended by accounting for age-dependent changes in physiological and biochemical parameters
(Tornero-Velez et al. 2010) to address juvenile sensitivity in rats. This model predicts that,
compared to adult rats (i.e., 90-days old), equivalent brain concentrations of deltamethrin would
be achieved with a 3.8X fold lower oral dose in 10-day old rats and 2.5X lower dose in 21-day
old rats. For example, the internal dose from an administered dose of 1 mg/kg in the adult is
equivalent to the internal dose from an administered dose of 0.26 mg/kg (≈1 mg/kg÷3.8 mg/kg)
in the 10-day old rat and to an administered dose of 0.4 mg/kg (≈1 mg/kg÷2.5 mg/kg) in the 21-
day old rat. As a result, the agency concludes that juvenile rats are three times as sensitive as
adult rats with respect to pyrethroid PK. At this time, the agency considers that the differences
in the PK profile observed in the rat are relevant to humans. Therefore, for food use pyrethroids,
the PK contribution to the FQPA SF is 3X for children less than 6 years old and 1X for children
6 years of age or older and for adults. Further information regarding the decision to retain the
FQPA SF and the choice of age groups it applies to can be found in the Re-Evaluation of the
FQPA Safety Factor of Pyrethroid Pesticides memo (D381210, E. Scollon, 6/27/2011).
4.3.3 Pharmacodynamics (PD)
PD can be defined as the changes that chemicals cause to the body, in this case, how pyrethroids
interact with the sodium channels. Substantial evidence from in vitro and in vivo studies support
the AOP illustrated in Figure 4.3 and the disruption of sodium channels by pyrethroids as an
early key event (Lund and Narahashi 1982; Salgado et al. 1989; Song and Narahashi 1996;
Tabarean and Narahashi 1998; Soderlund et al. 2002).
There are several studies that provide specific information for cypermethrin. Choi and
Soderlund (2006) examined interactions of several pyrethroids, including cypermethrin, with
mammalian VGSCs expressed in Xenopus oocytes (i.e., frog oocytes). With respect to altered
neuronal excitability, Type I pyrethroids cause slight prolongations of the sodium current tails
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(e.g. ~20 ms), often resulting in long trains of action potentials. In contrast, Type II pyrethroids
significantly prolong sodium current tails (e.g., 200 ms to minutes) typically resulting in
increased resting membrane potential and ultimately causing depolarization dependent action
potential block. Cypermethrin behaved in a manner consistent with type II pyrethroids by
producing prolonged tail currents that activated more slowly and did not detectably inactivate
during a 40 ms depolarization. Additionally, Cao et. al. (2011a) measured sodium (Na) influx in
primary cultures of mammalian (mouse) neurons and demonstrated that cypermethrin caused
increases in Na influx in this model; this confirms the ability of cypermethrin to interact with
VGSC in intact mammalian neurons. An additional study by Cao et. al. (2011b) demonstrated
that the interaction of cypermethrin with VGSC caused changes in neuronal excitability that
resulted in calcium influx into intact mouse neurons. As this effect of cypermethrin was entirely
blocked by the VGSC blocker tetrodotoxin, it provides evidence that the changes in sodium
channel function lead to changes in neuronal excitability, as illustrated in Figure 4.3.
Figure 4.3 Resting modification of rat Nav1.8 sodium channels by cypermethrin expressed in Xenopus oocytes.
Channel current vs time traces from individual representative oocytes in the absence or presence (*) of 100 µM
cypermethrin were obtained during and after 40-ms depolarizations from 100 mV to 10 mV. Calibration bars: 20 ms
for the x-axis and 500 nAmp on the y-axis. Data extracted from Figure 3 in Choi and Soderlund (2006).
HED would prefer to use an early key event in the AOP for pyrethroids in selection of points of
departure, such as sodium channel modification. However, in vivo techniques used to detect
VGSC alteration and altered neuronal excitability are not practical for use in risk assessment at
this time, and approaches for extrapolating in vitro findings to in vivo measures are not yet
developed. As such, the Agency is focusing its efforts for all pyrethroids in hazard
characterization and identification on the apical endpoint (i.e., changes in neurobehavior in
laboratory animals). Neurotoxicity resulting from pyrethroids is generally characterized by
tremors, hyper- or hypothermia, heightened response to stimuli, salivation, reduced locomotor
activity, or convulsions (Soderlund et al. 2002; Wolansky and Harrill 2008; Weiner et al. 2009).
In addition, results from a study by Wolansky et al. (2006) indicated that motor activity is a
sensitive and robust measure of neurotoxicity for this class of compounds. The changes in motor
activity observed were not specific to either of the syndromes described for pyrethroids and were
observed with both Type I and Type II pyrethroids.
In contrast to the age-related PK differences identified in the 2011 analysis, PD contributions to

pyrethroid toxicity are not age-dependent, even though there are several variations of sodium
channels, called isoforms, which are differentially expressed by tissue and age. Because of the
nature of the interaction of pyrethroids with sodium channels, it is difficult to obtain dynamic
information in vivo. To date, a readily useable biomarker of in vivo pyrethroid interaction with
sodium channels has not been identified, making it impractical to determine the isoform
combinations that are present and being acted upon by pyrethroids. Therefore, much of the
information available to the agency to characterize the PD relationship between pyrethroids and
sodium channels has been derived from in vitro studies using frog oocytes or neuronal cells
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cultured in defined media. These in vitro techniques do not provide a direct quantitative measure
of in vivo pyrethroid activity. However, these techniques consistently and qualitatively
demonstrate that sodium channel isoforms expressed in juveniles are not more sensitive to
pyrethroid perturbation compared to isoforms expressed in adults and that,
pharmacodynamically, the rat is a conservative model for humans. For example, Meacham et al.
(2008), expressed adult and juvenile isoforms of rat sodium channels in frog oocytes and
compared their sensitivity following exposure to deltamethrin. The isoforms had comparable
responses at environmentally relevant concentrations (<500 nM) of deltamethrin, suggesting a
lack of PD difference between juveniles and adults at low exposure levels. In addition, in a
direct comparison of a homologous rat and human VGSC isoform NaV1.3, the rat isoform was 4-
fold more sensitive than the equivalent human sodium channel to the pyrethroid tefluthrin (Tan
and Soderlund 2009). This observation suggests that the rat is a highly-sensitive model, and
extrapolations from the rat would be protective of human health. The occurrence and ontogeny
of VGSCs in humans is not as well characterized compared to those of the rat. However, based
on the comparable function and distribution of sodium channels between the species, the rat is an
appropriate surrogate for the evaluation of human PD (Goldin et al. 2000; Goldin 2002). As a
result, the agency concludes that juvenile rats are not more sensitive than adults with respect to
pyrethroid pharmacodynamics based on sodium channel data. Therefore, the PD contribution to
the FQPA factor will be 1X.
4.3.4 Critical Duration of Exposure
One of the key elements in risk assessment is the appropriate integration of temporality between
the exposure and hazard assessments. For the cypermethrins, neurotoxicity is the most sensitive
endpoint, with effects observed within 4-6 hours of oral dosing. This is consistent with the
toxicity profiles for other pyrethroids, with a time to peak effect for neurobehavioral effects
ranging from 4 to 8 hours; (Wolansky and Harrill 2008; Weiner et al. 2009; Scollon et al. 2011).
In addition, the combination of rapid absorption, metabolism, and elimination observed for the
cypermethrins, precludes accumulation and increased potency following repeated dosing.
Therefore, for most pyrethroids, the acute toxicity studies (with bolus dosing) typically result in
neurotoxicity at lower doses. In general, rat dietary studies on pyrethroids tend to have higher
NOAELs/LOAELs because, as rats feed continuously, pyrethroids are metabolized and excreted
from the system relatively quickly, and the overall systemic concentration in the rat remains low.
In contrast, bolus/gavage dosing results in greater maximal plasma concentrations immediately
after dosing. For the cypermethrins, the NOAELs and LOAELs for clinical signs after single or
repeated exposure are comparable; thus, neurotoxicity does not seem to progress with duration of
exposure (Table 4.3.4). The endpoint and POD from the Wolansky study with cypermethrin was
selected for oral and dermal risk assessments; a route-specific study with cypermethrin was used
for inhalation exposure. Lower PODs were determined for dog studies with cypermethrin and
alpha-cypermethrin. However, when the NOAELs of the Wolansky study and the dog studies are
adjusted to human equivalent doses (HEDs) using ¾ body weight scaling, the resulting doses are
comparable (Table 4.3.4).
Although the Wolansky study and inhalation study with cypermethrin are considered the most
appropriate for risk assessment, the available acute neurotoxicity studies indicate that toxicity for
alpha-cypermethrin and zeta-cypermethrin occur at doses that are 5-fold and 3-fold, respectively,
lower than those causing toxicity for cypermethrin. A 3X factor was not used quantitatively in
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the risk assessment to address the increased toxicity for zeta-cypermethrin because the PODs
from the Wolansky study and the zeta-cypermethrin DNT are considered the same (7.16 mg/kg
and 7.4 mg/kg/day, respectively), and therefore, the cypermethrin POD is protective of the
potential increased toxicity and the increased sensitivity observed in the zeta-cypermethrin DNT
study. For alpha-cypermethrin, the increased toxicity was accounted for by dividing the PODs
by a 5X potency factor. This approach is protective of all toxic effects observed in the database.
BASF provided a rationale supporting bridging of toxicity data for cypermethrin, zeta-
cypermethrin and alpha-cypermethrin in order to reduce the 5X potency factor associated with
alpha-cypermethrin. However, the additional information and weight-of-evidence consideration
provided by BASF did not adequately address uncertainties for HED to recommend removal of
the 5X potency factor for alpha-cypermethrin (D441671, K. Yozzo, 9/13/2017).
Table 4.3.4. Points of Departure for neurological effects observed in toxicology studies with Cypermethrin,
Zeta-cypermethrin, and Alpha-cypermethrin.
Study Duration Study findings
Cypermethrin Zeta-cypermethrin Alpha- Allometric
cypermethrin Scaling for HED
ComparisonC
(mg/kg/day) NOAEL LOAEL NOAEL LOAEL NOAEL LOAEL NOAEL LOAEL
Wolansky Acute, BMDL1SD1 BMD = BMDL1SD BMD = BMDL1SD BMD = 2.08 3.25
single = 11.20 = N/A = N/A
exposure 7.16 N/A N/A
Acute Acute, 30 100 10 50 4 20 N/A N/A
neurotoxicity single
exposure
Acute Acute, ND 20 N/A N/A N/A N/A N/A N/A
neurotoxicity single
McDaniel and exposure
Moser, 1993
Subchronic 90 days 31 77 5/31 26.3/55.6 N/A N/A N/A N/A
neurotoxicity (M/F)
≠ ≠ ≠ ≠
Subchronic 90 days 9.3 29.6 N/A N/A
Rat
Developmental 10 days 17.5 35 12.5 25 9 15 N/A N/A
Rat
≠ ≠
Developmental 10 days 100 450 N/A N/A N/A N/A
Rabbit
Sub-chronic 90 days 24.6 37.0 N/A N/A 2.25 6.75 *1.38 *4.15
dog
≠ ≠
Reproductive 120 days 7 27 N/A N/A N/A N/A
toxicity
≠ ≠
Chronic dog 1 year 6/5.7 20.4/18.1 N/A N/A +3.50 +12.50
(feeding) (M/F)
Chronic dog 1 year 5 15 N/A N/A N/A N/A 3.07 9.22
(capsule)
1BMD
1SD is the central estimate of the dose that results in decreased motor activity compared to control animals based upon a 1
standard deviation using Benchmark Dose Analysis. BMDL1SD is the 95% lower confidence limit of the central estimate. Data
located in Wolansky (2006), MRID 47885701. ≠ No neurotoxic clinical signs observed in the study. * alpha-cypermethrin. +
cypermethrin. C Human Equivalent Doses calculated based on allometric scaling: Scaling Factor 0.75; Default weights: rat = 0.5
kg, dog = 10 kg, Human = 70 kg; NOAELH=NOAELD (BWD/BWH)^1-0.75; Sample and Arenal, 1999. N/A. not applicable. ND,
not determined.
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4.4 Safety factor for Infants and Children (FQPA Safety Factor)2
No evidence of increased quantitative or qualitative susceptibility was noted in the

developmental or reproduction studies for the cypermethrins. However, body weight changes
were seen in pups in the DNT study with zeta-cypermethrin in the absence of treatment-related
effects in maternal animals, suggesting quantitative susceptibility. The degree of concern for the
observed susceptibility is low because there is a clear NOAEL from the study, and because the
same magnitude of body weight loss was observed in dams and pups, although it was not
considered adverse in the dams. The POD from the Wolansky study is lower than the POD from
the DNT study, and therefore the risk assessment is protective of the observed susceptibility.
After reviewing the extensive body of peer-reviewed literature on pyrethroids, the agency has no
residual uncertainties regarding age-related sensitivity for women of child bearing age as well as
for all adult populations and children ≥6 years of age, based on the absence of pre-natal
sensitivity observed in 76 guideline studies for 24 pyrethroids and the scientific literature.
Additionally, no evidence of increased quantitative or qualitative susceptibility was seen in the
pyrethroid scientific literature related to PD. The agency is retaining a 3X FQPA uncertainty
factor to protect for exposures of children <6 years of age based on the increased quantitative
susceptibility seen in studies on pyrethroid PKs and the increased quantitative juvenile
susceptibility observed in high dose studies in the literature. There is no residual uncertainty in
the exposure database because adequate residue data are available to assess dietary exposure. In
addition, many conservative assumptions were made in the dietary exposure assessment.
Residential scenarios were assessed using maximum application rates and chemical-specific data
such as turf transferable residue (TTR) data and dislodgeable foliar residue (DFR) data. As a
result, exposure will not be underestimated.
4.4.1 Completeness of the Toxicology Database
The toxicology database for the cypermethrins is largely complete. When evaluated together, the
toxicity database for cypermethrin, zeta-cypermethrin, and alpha-cypermethrin can be used to
characterize the overall suite of effects associated with cypermethrin exposure, including
potential developmental and reproductive toxicity, immunotoxicity, and neurotoxicity.
Acceptable developmental toxicity studies in rats and rabbits, reproduction studies in rats,
neurotoxicity studies (ACN, SCN, and DNT) in rats, and immunotoxicity studies in rats are
available. While the database is considered to be complete with respect to the guideline toxicity
studies, EPA lacks additional data to address the potential for juvenile sensitivity to all
pyrethroids, including the cypermethrins. As noted previously, additional research efforts are
underway to address juvenile sensitivity for the pyrethroids including cypermethrins.
4.4.2 Evidence of Neurotoxicity
Like other pyrethroids, the cypermethrins cause neurotoxicity by interacting with sodium
channels, leading to clinical signs of neurotoxicity. These effects are well characterized and
2
HED’s standard toxicological, exposure, and risk assessment approaches are consistent with the requirements of
EPA’s children’s environmental health policy (https://www.epa.gov/children/epas-policy-evaluating-risk-children).
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adequately assessed by the available guideline and non-guideline studies. There are no residual
uncertainties with regard to evidence of neurotoxicity for the cypermethrins.
4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal
No evidence of increased qualitative or quantitative susceptibility was noted in the

developmental toxicity or reproduction studies for the cypermethrins. However, quantitative
susceptibility was seen in the rat developmental neurotoxicity (DNT) study with zeta-
cypermethrin with an increased sensitivity in the offspring based on body weight changes in pups
(5-10%) in the absence of treatment-related effects in maternal animals. Although there was a 5-
8% decrease in maternal body weight in this study, a body weight decrease of <10% is generally
not considered adverse in adults, as this is considered to be within the range of variability
because the magnitude of body weight per se is typically small (as an example, a 3gram decrease
in body weight from a 338 g rat), and adults are no longer in the growth/development phase. In
contrast, the offspring are at a stage of growth and development and are therefore expected to be
gaining rather than losing weight. Thus, a smaller % decrease in body weight is considered
adverse in the young relative to adults. In the case of zeta-cypermethrin, the decrease in body
weight of the young is comparable to adults; however, it was considered adverse in the young
but not in the adults. This disparity in interpretation leads to an apparent increase in sensitivity in
the young; however, concern is reduced since the magnitude of body weight decrements was
similar in adult and young animals. The results from the DNT study are very similar to results
observed in the reproduction studies where body weight changes (decreased BW gain) were seen
in maternal and offspring animals at doses similar to those in the DNT study, with no indication
of increased susceptibility. Therefore, there is no residual concern for effects observed in the
study and a clear developmental NOAEL and LOAEL were identified.
High-dose studies in the scientific literature also indicate that younger animals are more
susceptible to the toxicity of pyrethroids. For example, Sheets et al. (1994) found increased
brain deltamethrin levels in young rats (PND 11 and 21) relative to adult rats (PND 72). These
age-related differences in toxicity are principally due to age-dependent PK. The activity of
enzymes associated with the metabolism of pyrethroids increases with age (Anand et al. 2006).
However, in context, normal dietary or residential exposures of juveniles are not expected to
overwhelm their ability to metabolize pyrethroids. In support, at a dose of 4.0 mg/kg
deltamethrin (near the Wolansky study LOAEL value of 3.0 mg/kg for deltamethrin), the
change in the acoustic startle response was similar between adult and young rats (Sheets et al.
1994). In addition, EPA’s Office of Research and Development (ORD) recently developed an
age-dependent PBPK model for deltamethrin (Tornero-Velez et al. 2010) that predicts a 3–fold
increase of pyrethroid in neuronal tissue in younger animals compared to adults. There are
several studies (in vitro and in vivo) that indicate that PD contributions to pyrethroid toxicity are
not age-dependent. Examination of specific VGSCs has demonstrated that there is a lack of
increased sensitivity in either juvenile specific isoforms (Meacham et al. 2008) or in human
isoforms compared to rat variants (Tan and Soderlund 2009).
After reviewing the extensive body of peer-reviewed literature on pyrethroids, the agency has no
residual uncertainties regarding age-related sensitivity for women of child bearing age as well as
for all adult populations and children ≥6 years of age, based on the absence of pre-natal
sensitivity observed in 76 guideline studies for 24 pyrethroids and the scientific literature.
Page 32 of 138
Additionally, no evidence of increased quantitative or qualitative susceptibility was seen in the
pyrethroid scientific literature related to PD. The agency is retaining a 3X FQPA Safety Factor
to protect for exposures of children <6 years of age based on the increased quantitative
susceptibility seen in studies on pyrethroid PK and the increased quantitative juvenile
susceptibility observed in high dose studies in the literature. Further information regarding the
decision to retain the FQPA Safety Factor and the choice of age groups it applies to can be found
in section 4.5.1.
4.4.4 Residual Uncertainty in the Exposure Database
There are no residual uncertainties with regard to exposure. The dietary exposure assessments
are based on high-end health protective residue levels (that account for parent and metabolites of
concern), processing factors, and percent crop treated assumptions. Furthermore, conservative,
upper-bound assumptions were used to determine exposure through drinking water and
residential sources, such that these exposures have not been underestimated.
4.5 Toxicity Endpoint and Point of Departure Selections
4.5.1 Dose-Response and Hazard Assessment
Based on the registered use pattern for the cypermethrins, dietary, dermal, inhalation, and
incidental oral exposure are expected.
The selected endpoints for the cypermethrins are based on clinical signs of neurotoxicity that are
consistent with type II pyrethroids. Consistent with other pyrethroids in this class, the acute
dosing studies generally result in lower NOAELs compared to longer-term dietary administration
studies. In addition, the neurotoxic effects do not increase over repeated administration;
therefore, the non-cancer endpoints are protective both for acute (single dose) and repeat
exposures. The guideline experimental toxicology studies available for cypermethrin, zeta-
cypermethrin, and alpha-cypermethrin are generally high quality and were considered in the
POD selection process and in the weight of the evidence evaluation. In addition to the typical
guideline studies, data from two special studies (Wolansky study on motor activity and the WIL
FOB study evaluating neurobehavioral outcomes) are available for cypermethrin (Nemec 2006;
Wolansky et al. 2006). Wolansky et al. (2006) measured motor activity at the time of peak effect
after exposure to 11 pyrethroids, including cypermethrin. Dose-response relationships were
determined using 6-11 doses per pyrethroid (6 doses used for cypermethrin) and 3-18 rats per
dose group (8 animals/group used for cypermethrin), minimizing variability and increasing the
confidence in the benchmark dose (BMD) estimates determined from this study. Moreover, each
pyrethroid was evaluated by the same scientist thus decreasing some of the variability associated
with neurobehavioral measures. In the WIL study, 17 pyrethroids have been evaluated using a
specially designed (FOB) study focused on the outcomes associated with pyrethroid toxicity
syndromes. The cypermethrin data from the WIL study were not used as part of the POD
selection since the Wolansky study was considered more appropriate based on study design.
Observations of tremors, gait abnormalities, limb conditions, and hypersensitivity were

prominent findings in the guideline experimental toxicology studies and were considered in the
point of departure (POD) determination. However, guideline studies typically have only three
Page 33 of 138
treatment groups and often do not evaluate clinical signs at the time of peak effect. Moreover,
scoring metrics for behavioral parameters vary widely among guideline studies. Given the
multiple strengths associated with the design of the Wolansky et. al. (2006) study and the
resulting well-defined dose-response curve, it was determined that the study provided the most
robust data set for extrapolating risk from the cypermethrins. It should be noted that Wolansky
data are only available for the racemic mixture of these chemicals (i.e., cypermethrin), not for
zeta-cypermethrin and alpha-cypermethrin.
A BMD analysis has been conducted by the agency for all the pyrethroids included in the
Wolansky study (MRID 47885701). Overall, due to the large number of doses and high quality
measurements, the BMD analysis yielded high confidence results. In performing BMD analysis,
a benchmark response (BMR) must be selected. As a general approach, it is preferred to use a
combination of biological and statistical factors in the BMR selection. In the case of motor
activity data, there is no specific level of change established by the scientific community as being
considered adverse. Therefore, OPP has elected to use one standard deviation (1SD) from the
control group as suggested for continuous endpoints in the agency’s draft BMD guidance
(USEPA 2000) as the BMR. OPP has estimated both the BMD1SD and the BMDL1SD (where the
BMDL1SD is the lower 95% confidence limit of the BMD1SD).
For oral risk assessments for the cypermethrins, HED used the endpoint and dose from the
Wolansky study; the route and duration of exposure are considered appropriate, and the endpoint
and dose are protective for all neurotoxic effects observed in the cypermethrins toxicity data.
Since the PODs and endpoints are based on cypermethrin data and there is concern for increased
toxicity after exposure to alpha-cypermethrin, a 5X potency factor was applied to the oral POD
used for the alpha-cypermethrin risk assessments. Although there was no systemic toxicity
observed in dermal studies, HED conducted dermal risk assessments for children exposed to the
cypermethrins following use of the actives in residential environments in order to be protective
of the susceptibility observed in the DNT study. Due to the apparent 5X increase in toxicity with
alpha-cypermethrin relative to cypermethrin, dermal risk assessments were conducted for both
adults and children exposed to alpha-cypermethrin. The endpoint and dose from the oral
Wolansky study were used to assess dermal exposure, along with chemical-specific dermal
absorption data. For inhalation assessments, the Health Effects Division relied on the
cypermethrin route-specific inhalation study in rats, and calculated human equivalent
concentrations/doses (HECs/HEDs). The details are provided as follows.
Combined Acute Dietary Risk Assessment for Alpha-cypermethrin, Cypermethrin, and

Zeta-cypermethrin
Acute Dietary: Alpha-cypermethrin, Cypermethrin, and Zeta-cypermethrin (all populations)

As mentioned above, current analytical methods for tolerance enforcement are not stereospecific
and the qualitative nature of the toxicological effects (i.e., neurotoxicity) for the cypermethrins is
similar following oral and inhalation routes of exposure; thus, no distinction is made between
residues of cypermethrin, zeta-cypermethrin, and alpha-cypermethrin in foods. As a result,
dietary assessments included all of the cypermethrins; however, the different toxicities of
cypermethrin/zeta-cypermethrin and alpha-cypermethrin were accounted as discussed above.
For acute dietary risk assessment, HED selected the POD and endpoint from the acute oral
(Wolansky) study with cypermethrin in rats. The BMDL1SD value of 7.16 mg/kg is based on
Page 34 of 138
decreased locomotor activity at the BMD1SD value of 11.20 mg/kg. Since the PODs and
endpoints are based on cypermethrin data and there is concern for increased toxicity after
exposure to alpha-cypermethrin, a 5X potency factor was applied to the POD used for the alpha-
cypermethrin risk assessments. Therefore, the revised BMDL1SD for alpha-cypermethrin risk
assessment is 1.4 mg/kg/day. [HED notes that for the purpose of conducting the dietary
exposure modeling, the 5X potency factor was accounted for by adjusting the residue data, rather
than using the lower POD; more information is provided Section 5.4.1].
Chronic Dietary: Alpha-cypermethrin, Cypermethrin, and Zeta-cypermethrin (all populations)

There is no increase in hazard from repeat exposures to the cypermethrins; therefore, a chronic
dietary POD was not selected. The acute endpoint is protective of potential effects from repeat
dosing.
Occupational and Residential Exposure Assessments for Cypermethrin/Zeta-cypermethrin

and Alpha-cypermethrin.
Separate occupational and residential exposure assessments were conducted for the 3 active
ingredients, based on their respective use patterns/labels. The PODs for alpha-cypermethrin were
different than for cypermethrin/zeta-cypermethrin due to the use of the 5X factor.
Incidental Oral (Short-term)

The acute oral (Wolansky) study with cypermethrin in rats was selected to evaluate short-term
incidental oral exposure based on the endpoint of decreased locomotor activity observed at the
BMD1SD value of 11.20 mg/kg (POD = 7.16 mg/kg for cypermethrin/zeta-cypermethrin and 1.4
mg/kg/day for alpha-cypermethrin). This study is appropriate for the route (oral) and duration of
exposure and is protective of all offspring effects in the reproduction and developmental studies.
The PODs are applicable to all child (1 to < 2 years old) incidental oral exposure scenarios.
Dermal (Short-term)
The Wolansky study was selected for dermal risk assessment since the study provides the most
robust data and the POD is based on the effect of concern for the cypermethrins (neurotoxicity)
for adults and is protective of observed susceptibility in the DNT study with zeta-cypermethrin.
Similar to the incidental oral endpoint described above, the POD for cypermethrin and zeta-
cypermethrin, 7.16 mg/kg/day, is applicable for dermal post-application risk assessment for
children 1<2 yrs. old. Since the PODs and endpoints are based on cypermethrin data, and there is
concern for increased toxicity after exposure to alpha-cypermethrin, a 5X potency factor was
applied to the POD, and for alpha-cypermethrin, the POD of 1.4 mg/kg/day is applicable to all
populations (i.e., adults and children). A dermal absorption factor (DAF) of 13.4% (see Section
4.3) will be applied to convert oral doses to dermal equivalent doses to assess risk from dermal
exposure.
Inhalation (Short-term)
A route-specific 21-day rat inhalation study with cypermethrin was used to assess short-term
inhalation exposure were based on increased salivation observed at the LOAEL of 0.05 mg/L
(NOAEL = 0.01 mg/L). This dose and endpoint are appropriate since the effects were seen
following exposure via the route (inhalation) and duration (short-term) of concern. Additionally,
the effects seen in the inhalation study are consistent with the pyrethroid profile, are protective of
neurotoxicity, and human equivalent doses are protective of the oral POD. Since the PODs and
Page 35 of 138
endpoints are based on cypermethrin data, and there is concern for increased toxicity after
exposure to alpha-cypermethrin, a 5X potency factor was applied to the HECs/HEDs used in
alpha-cypermethrin risk assessments (Tables 4.5.4.2 and 4.5.5.5).
The methods and dosimetry equations described in EPA’s reference concentration (RfC)
guidance (1994) are suited for calculating HECs based on the inhalation toxicity point of
departure (NOAEL, LOAEL, or BMDL) for use in MOE calculations. The regional-deposited-
dose ratio (RDDR), which accounts for the particulate diameter (mass median aerodynamic
diameter [MMAD] and geometric standard deviation [g] of aerosols), can be used to estimate
the different dose fractions deposited along the respiratory tract. Thus, the RDDR is used to
adjust an observed inhalation particulate exposure of an animal to the predicted inhalation
exposure for a human. For the subchronic inhalation study a RDDR of 3.1 was estimated.
Uncertainty Factors/Level of Concern (LOCs) for Risk Assessment
For acute dietary exposure, an uncertainty factor of 100X was applied for adults and children ≥ 6
years old, based on the 10X interspecies and 10X intraspecies factors. For acute dietary
exposure for children <6 years old, an uncertainty factor of 300X was applied (10X interspecies,
10X intraspecies, and 3X FQPA factor). The FQPA uncertainty factor was reduced from 10X to
3X for all applicable oral (including dietary and incidental oral) exposure scenarios to protect for
exposures of children <6 years of age based on the increased quantitative susceptibility seen in
studies on pyrethroid PK and the increased quantitative juvenile susceptibility observed in high
dose studies.
The LOCs for occupational and residential risks are based on the various uncertainty and safety
factors retained or applied for specific routes of exposure (Table 4.5.1). As in the dietary
assessment, the 10X FQPA SF was reduced to 3X for children under 6 years old based on the
increased quantitative susceptibility for assessing residential exposure (oral, dermal, and
inhalation). For adults and children 6 years and older, the traditional factors were applied (10X
intraspecies and 10X interspecies) for oral and dermal exposures. For inhalation exposure, the
standard interspecies uncertainty factor was reduced from 10X to 3X (due to the HEC calculation
accounting for pharmacokinetic (not pharmacodynamic) interspecies differences); the
intraspecies uncertainty factor remains at 10X. The LOCs are summarized in Table 4.5.1.
Table 4.5.1. Occupational and Residential LOCs for MOEs

Route LOC
Occupational Dermal Exposure 100X
Occupational Inhalation Exposure 30X
Residential Incidental Oral Exposure < 6 years old: 300X
≥ 6 years old: 100X
Residential Dermal Exposure
< 6 years old: 300X
≥ 6 years old: 30X
Residential Inhalation Exposure
< 6 years old: 100X
4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment
For the cypermethrins, oral, dermal, and inhalation exposures can be combined for all durations
since the oral and dermal endpoints are based on the same toxicological effects (clinical signs
related to neurotoxicity), and the effects seen in the inhalation study (increased salivation) are
consistent with the pyrethroid profile and the endpoint is protective of the neurotoxicity observed
Page 36 of 138
in the oral studies.
4.5.3 Cancer Classification and Risk Assessment Recommendation
Cypermethrin is classified under the 1986 Agency Cancer Guidelines as a Group C “Possible
human carcinogen”, based on an increased incidence of benign lung adenomas and adenomas
plus carcinomas combined in females in a mouse carcinogenicity study on cypermethrin (TXR#
0055252, J. Quest, 2/17/1988). The presence of common benign tumors (lung adenomas), in one
sex (females) of one species (mice), together with the lack of mutagenic activity, was not
considered strong enough evidence of carcinogenicity to warrant a quantitative estimation of
human risk. Taking into account all of this information, the agency has determined that
quantification of risk using a non-linear approach (i.e., aPAD or aRfD) will adequately account
for all chronic toxicity, including carcinogenicity, that could result from exposure to the
cypermethrins. While the agency would typically use a cPAD to protect for cancer concerns, use
of the aPAD is considered protective because increasing toxicity with increasing duration of
exposure is not demonstrated for the cypermethrins. The NOAEL in the mouse cancer study is
57 mg/kg/day and tumors were seen at 229 mg/kg/day. The acute point of departure (POD) of
7.16 mg/kg/day selected for risk assessment is 32 fold lower than the dose that induced lung
tumors in mice. Only the mouse study with cypermethrin resulted in tumor formation: no
evidence of carcinogenicity was observed in cancer studies in rats with cypermethrin or mice
with alpha-cypermethrin.
4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk
Assessment (Note: There are separate endpoint tables for alpha-cypermethrin and
cypermethrin/zeta-cypermethrin).
Cypermethrin/Zeta-cypermethrin
Table 4.5.4.1: Summary of Toxicological Doses and Endpoints for Cypermethrin/Zeta-cypermethrin for Use
in Dietary, Non-Occupational, and Occupational Human Health Risk Assessments (PODs and endpoints based
on cypermethrin toxicology data)
Uncertainty/
Exposure/ Point of RfD, PAD, Level of Concern Study and Toxicological
FQPA Safety
Scenario Departure for Risk Assessment Effects
Factors
Acute Dietary Wolansky
BMDL1SD = UFA = 10x
(children ≥ 6 aRfD = 0.0716 mg/kg/day
7.16 mg/kg UFH =10x BMD = 11.20 mg/kg based
years old and aPAD= 0.0716 mg/kg/day
FQPA SF = 1x on motor activity
adults)
Acute Dietary BMDL = UFA = 10x Wolansky
1SD aRfD = 0.0716 mg/kg/day
(children <6 7.16 mg/kg UFH =10x BMD = 11.20 mg/kg based
aPAD= 0.024 mg/kg/day
years old) FQPA SF = 3x on motor activity
Incidental Wolansky
BMDL1SD = UFA = 10x
Oral Short- Residential LOC for MOE =
7.16 mg/kg UFH =10x BMD = 11.20 mg/kg based
Term (1-30 300
FQPA SF = 3x on motor activity
days)
Page 37 of 138
Table 4.5.4.1: Summary of Toxicological Doses and Endpoints for Cypermethrin/Zeta-cypermethrin for Use
in Dietary, Non-Occupational, and Occupational Human Health Risk Assessments (PODs and endpoints based
on cypermethrin toxicology data)
Uncertainty/
FQPA Safety
Factors
Short-term
Dermal
(1 to 30 days) N/A N/A N/A N/A
(children ≥ 6
years old and
adults)
Short-term
UFA = 10x Wolansky
Dermal BMDL1SD = UFH =10x Residential LOC for MOE =
(1 to 30 days) 7.16 mg/kg BMD = 11.20 mg/kg based
FQPA SF = 3x 300
(children < 6 on motor activity
DAF = 13.4%
years old)
Short-term NOAEL = 0.01
Inhalation mg/L UFA = 3x 21-day inhalation study in
Residential LOC for MOE = the rat.
(1 to 30 days) (See HEC UFH =10x
100 LOAEL = 0.05 mg/L based
(children < 6 calculations, FQPA SF = 3x
years old) on increased salivation.
Table 4.5.4.6)
Short-term
NOAEL = 0.01 Residential LOC for MOE =
Inhalation 21-day inhalation study in
mg/L UFA = 3x 30
(1 to 30 days) the rat.
(See HEC UFH =10x
(children ≥ 6 LOAEL = 0.05 mg/L based
calculations, FQPA SF = 1x Occupational LOC for MOE =
years old and on increased salivation.
Table 4.5.4.2) 30
adults)
Cancer (oral, Classification: Group C “Possible human carcinogen based on lung adenomas in female mice. No
dermal, Q1* has been derived. A non-linear approach is recommended for cancer assessment.
inhalation)
Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to mark
the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no
observed adverse effect level. LOAEL = lowest observed adverse effect level. BMD = benchmark dose. BMDL = benchmark
dose (lower limit of a 95% confidence interval). UF = uncertainty factor. UFA = extrapolation from animal to human
(interspecies). UFH = potential variation in sensitivity among members of the human population (intraspecies). FQPA SF =
FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of
exposure. LOC = level of concern. N/A = not applicable. HEC = human equivalent concentration; HED = human equivalent
dose.
Table 4.5.4.2 Summary of HEC/HED values for Cypermethrin/Zeta-cypermethrin

Toxicity Duration *HED (mg/kg/day)
*HEC
Population Scenario Adjustment
Daily Weekly mg/L mg/m3
Occupational Handler 0.75 1 0.023 23.250 2.20
Handler N/A N/A 0.031 31.0 0.73
Outdoor post-
N/A N/A 0.031 31.0 0.84
application
Residential
Indoor post-
NA 0.71 0.022 22.14 0.52
application
Bystander 0.25 0.71 0.006 5.536 --
HEC =human-equivalent concentration; HED =human-equivalent dose.
HEC =rat NOAEL*(daily duration adjustment) *weekly daily duration adjustment *RDDR*
HED = HEC x human specific conversion factor x activity factor for the exposure scenario x daily duration
Note: The inhalation HECs/HED have been calculated based on the 2016 revised methodology.
Page 38 of 138
Alpha-cypermethrin
Table 4.5.4.3 Summary of Toxicological Doses and Endpoints for Alpha-Cypermethrin for Use in Dietary and
Non-Occupational Human Health Risk Assessments (PODs and endpoints based on cypermethrin toxicology
data)
Uncertainty/
FQPA Safety
Factors
Acute Dietary BMDL1SD = Wolansky BMD = 11.20
7.16 mg/kg UFA = 10x
(children ≥ 6 aRfD = 0.014 mg/kg/day mg/kg based on motor
*7.16/5 = UFH =10x
years old and aPAD = 0.014 mg/kg/day activity
FQPA SF = 1x
adults) 1.4 mg/kg/day
BMDL1SD = UFA = 10x Wolansky
Acute Dietary 7.16 mg/kg
UFH =10x aRfD = 0.014 mg/kg/day BMD = 11.20 mg/kg
(children < 6 *7.16/5 = FQPA SF = 3x aPAD = 0.005 mg/kg/day based on motor activity
years old)
1.4 mg/kg/day
Incidental BMDL1SD = UFA = 10x Wolansky
Oral Short- 7.16 mg/kg UFH =10x BMD = 11.20 mg/kg
*7.16/5 = Residential LOC for MOE = 300
Term (1-30 FQPA SF = 3x based on motor activity
days) 1.4 mg/kg/day
Short-term
Dermal BMDL1SD = UFA = 10x
7.16 mg/kg Wolansky
(1 to 30 days) UFH =10x
*7.16/5 = Residential LOC for MOE = 100 BMD = 11.20 mg/kg
(children ≥ 6 FQPA SF = 1x
based on motor activity
years old and 1.4 mg/kg/day DAF = 13.4%
adults)
Short-term BMDL1SD = UFA = 10x Wolansky
Dermal 7.16 mg/kg UFH =10x
(1 to 30 days) *7.16/5 = Residential LOC for MOE = 300 BMD = 11.20 mg/kg
FQPA SF = 3x
(children < 6 based on motor activity
1.4 mg/kg/day DAF = 13.4%
years old)
Short-term NOAEL = 0.01 21-day inhalation study in
Inhalation mg/L UFA = 3x the rat.
(1 to 30 days) (See HEC UFH = 10x Residential LOC for MOE = 100 LOAEL = 0.05 mg/L
(children < 6 calculations, FQPA SF = 3x based on increased
years old) Table 4.5.4.5) salivation.
Short-term
NOAEL = 0.01 21-day inhalation study in
Inhalation
mg/L UFA = 3x the rat.
(1 to 30 days)
(See HEC UFH =10x Residential LOC for MOE = 30 LOAEL = 0.05 mg/L
(children ≥ 6
calculations, FQPA SF = 1x based on increased
years old and
adults) Table 4.5.4.5) salivation.
Cancer (oral, Classification: Group C “Possible human carcinogen” based on benign lung adenomas in female
dermal, mice. No Q1* has been derived. A non-linear approach is recommended for cancer assessment.
inhalation)
observed adverse effect level. LOAEL = lowest observed adverse effect level. BMD = benchmark dose. BMDL = benchmark
dose (lower limit of a 95% confidence interval). UF = uncertainty factor. UFA = extrapolation from animal to human
(interspecies). UFH = potential variation in sensitivity among members of the human population (intraspecies). FQPA SF =
FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of
exposure. LOC = level of concern. N/A = not applicable. HEC = human equivalent concentration; HED = human equivalent
dose. * The PODs and endpoints are based on cypermethrin data; however, increased toxicity (5X) was seen in toxicity studies
Page 39 of 138
with alpha-cypermethrin. Therefore, to protect for the increased toxicity observed in toxicity studies with alpha-cypermethrin, a
potency factor was applied (BMDL1SD = 7.16 mg/kg/ 5 = 1.4 mg/kg/day).
Table 4.5.4.4 Summary of Toxicological Doses and Endpoints for Alpha-Cypermethrin for Use in
Occupational Human Health Risk Assessments (PODs and endpoints based on cypermethrin toxicology
data)
Exposure/ Point of Uncertainty Level of Concern for Study and Toxicological
Scenario Departure Factors Risk Assessment Effects
BMDL1SD =
Short- term 7.16 mg/kg UFA= 10x Wolansky
Occupational LOC for
dermal (1 day to UFH=10x BMD = 11.20 mg/kg
MOE = 100
6 months) *7.16/5= DAF = 13.4% based on motor activity
1.4 mg/kg/day
NOAEL = 0.01
mg/L 21-day inhalation study in
Short-term the rat.
(See HEC UFA= 3x Occupational LOC for
Inhalation (1 day LOAEL = 0.05 mg/L
calculations, UFH=10x MOE = 30
to 6 months) based on increased
Table 4.5.4.5)
salivation.
Cancer (oral, Classification: Group C “Possible human carcinogen” based on benign lung adenomas in
dermal, female mice. No Q1* has been derived. A non-linear approach is recommended for cancer
inhalation) assessment.
observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation
from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population
(intraspecies). MOE = margin of exposure. LOC = level of concern. N/A = not applicable. HEC = human equivalent
concentration; HED = human equivalent dose. * The PODs and endpoints are based on cypermethrin data; however, increased
toxicity (5X) was seen in toxicity studies with alpha-cypermethrin. Therefore, to protect for the increased toxicity observed in
toxicity studies with alpha-cypermethrin, a potency factor was applied.
Table 4.5.4.5 Summary of HEC/HED values for Alpha-cypermethrin

Toxicity Duration
*HEC *HED (mg/kg/day)
Population Scenario Adjustment
Daily Weekly mg/L mg/m3
Occupational Handler 0.75 1 0.023 23.250 2.20/5= 0.44
Handler N/A N/A 0.031 31.0 0.73/5 = 0.15
Outdoor post-
N/A N/A 0.031 31.0 0.84/5= 0.17
application
Residential Indoor post-
N/A 0.71 0.022 22.14 0.52/5= 0.10
application
5.536/5=
Bystander 0.25 0.71 0.006 N/A
1.11
HEC =human-equivalent concentration; HED =human-equivalent dose.
HEC =rat NOAEL*(daily duration adjustment)*weekly daily duration adjustment *RDDR*
HED = HEC x human specific conversion factor x activity factor for the exposure scenario x daily duration
Note: The inhalation HECs/HED have been calculated based on the 2016 revised spreadsheets.
* The PODs and endpoints are based on cypermethrin data; however, increased toxicity (5X) was seen in toxicity studies with
alpha-cypermethrin. Therefore, to protect for the increased toxicity observed in toxicity studies with alpha-cypermethrin, a
potency factor was applied.
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4.6 Endocrine Disruptor Screening Program
As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse
outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and
chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental,
reproductive, and general or systemic toxicity. These studies include endpoints which may be
susceptible to endocrine influence, including effects on endocrine target organ histopathology,
organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss,
and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and
chronic studies that assess growth, developmental and reproductive effects in different
taxonomic groups. As part of its reregistration decision for cypermethrins, EPA reviewed these
data and selected the most sensitive endpoints for relevant risk assessment scenarios from the
existing hazard database. However, as required by FFDCA section 408(p), cypermethrins are
subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).
EPA has developed the EDSP to determine whether certain substances (including pesticide
active and other ingredients) may have an effect in humans or wildlife similar to an effect
produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator
may designate.” The EDSP employs a two-tiered approach to making the statutorily required
determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a
chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal
systems. Chemicals that go through Tier 1 screening and are found to have the potential to
interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA
will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2
testing is designed to identify any adverse endocrine-related effects caused by the substance, and
establish a dose-response relationship between the dose and the E, A, or T effect.
Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October
2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals,
which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals
identified for EDSP screening was published on June 14, 20133 and includes some pesticides
scheduled for registration review and chemicals found in water. Neither of these lists should be
construed as a list of known or likely endocrine disruptors.
Cypermethrin is on List 1 for which EPA has received all of the required Tier 1 assay data. The
Agency has reviewed all of the assay data received for the appropriate List 1 chemicals and the
conclusions of those reviews are available in the chemical-specific public dockets (see EPA-HQ-
OPP-2012-0167) for cypermethrin. For further information on the status of the EDSP, the
policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1
screening battery, please visit our website.4
3
See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of
chemicals.
4
http://www.epa.gov/endo/
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5.0 Dietary Exposure and Risk Assessment
5.1 Metabolite/Degradate Residue Profile
5.1.1 Summary of Plant and Animal Metabolism Studies

HED MARC Determination of Residues of Concern (D269584, Y. Donovan, 11/3/2000)
The nature of residues of the cypermethrins is adequately understood in plants, rotational crops,
livestock commodities, surface water, and groundwater based on information provided on
cypermethrin and zeta-cypermethrin. In addition, metabolism studies for alpha-cypermethrin in
cabbage, wheat, lactating cow, and laying hen provide further confirmation of the conclusions
drawn from cypermethrin and zeta-cypermethrin data (W. Drew, D378683, 9/7/2012).
In plants, the major route of cypermethrin metabolism is via hydrolysis of the ester linkage and
subsequent ring hydroxylation of some components. Ester hydrolysis yielded DCV acid and the
unstable phenoxybenzyl cyanohydrin or its hydroxylated metabolite, which rapidly break down
to the m-phenoxybenzaldehyde product. The aldehyde metabolites are further oxidized or
reduced to the corresponding acids (mPB acids) or alcohols (m-PB alcohol) and their hydroxyl
products. Metabolites were found almost entirely in a conjugated form. Studies in sheep and
cows have shown that cypermethrin is rapidly absorbed, distributed to a variety of organs and
tissues, metabolized, and rapidly excreted from the body. There are no major differences in the
absorption, distribution, retention or excretion between the species. Differences, where they do
occur, are related to the rate rather than the nature of the metabolites formed, and the conjugation
reactions. Cypermethrin, both the cis and trans isomers, and zeta-cypermethrin are primarily
metabolized by cleavage of the ester bond. The metabolites PBA and cyclopropane carboxylic
acid (CPA) are mainly excreted as conjugates. The type of conjugate differs in a number of
animal species dosed with cypermethrin. Minor quantities of hydroxylated PBA (conjugated)
may also be found.
5.1.2 Summary of Environmental Degradation

I. Maher, D378901/D385246, 2/22/2011
Based on similarities in the chemical properties and toxicological endpoints, environmental fate
and ecotoxicity data are bridged between racemic cypermethrin and the enriched isomeric
mixtures (i.e., alpha-cypermethrin and zeta-cypermethrin). As a class of chemicals, the
pyrethroids have low solubility in water and a high affinity to bind to soils. Given these
physical/chemical properties, it is unlikely that oral exposure from drinking water will be a major
pathway of exposure. There is a complete environmental fate database for zeta-cypermethrin.
Zeta-cypermethrin is expected to have little mobility in soil surfaces (Koc ≥ 20,800 L/kg) and
leaching into groundwater is not expected to be an important transport process. Volatilization is
not expected to be an important transport process either, since zeta-cypermethrin has a relatively
low vapor pressure and Henry's Law constant (refer to Appendix B). Zeta-cypermethrin is
moderately persistent in the environment and degrades through a combination of biotic and
abiotic mechanisms. Zeta-cypermethrin is relatively stable to hydrolysis at acidic and neutral pH
levels, but degrades in a few days under alkaline conditions (pH 9, half-life of ~2 days). Zeta-
cypermethrin is relatively light stable, but still undergoes photolysis in water, with half-lives of
about a month or more in distilled water. The rate of photolysis appears to be enhanced in
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natural waters (which contain photosensitizing agents like humic and fulvic acids), where the
accelerated degradation results in half-lives of a few days. Zeta-cypermethrin photo-degrades on
soil with dark control corrected half-lives of ~128 days. Under both aerobic and anaerobic soil
conditions, zeta-cypermethrin biodegrades relatively slowly in soils, with half-lives on the order
of about 2 months. In contrast, under aerobic and anaerobic aquatic metabolism conditions, the
degradation rate is enhanced, with half-lives of around 9 to 17 days. If released to water, zeta-
cypermethrin partitions to sediment and may degrade slowly. Major degradates observed in
laboratory studies result from cleavage at the ester moiety of zeta-cypermethrin, which formed 3-
(2,2-dichloro-ethenyl)-2,2-dimethylcyclopropanecarboxylic acid (DCVA) and 3-
phenoxybenzaldehyde. The latter is further oxidized to 3-phenoxybenzoic acid (3-PBA).
Another product observed in the soil photolysis study only was cyperamide.
5.1.3 Comparison of Metabolic Pathways
The metabolism of zeta-cypermethrin is similar to that of cypermethrin, based on a comparison

of the metabolic profiles from studies with zeta-cypermethrin and cypermethrin. A wide range
of studies in mice, rats, dogs, sheep, cows and humans has shown that cypermethrin is rapidly
absorbed, distributed to a variety of organs and tissues, metabolized, and rapidly excreted from
the body (WHO; 1989). There are no major differences in the absorption, distribution, retention
or excretion between the species. Differences, where they do occur, are related to the rate rather
than the nature of the metabolites formed, and the conjugation reactions.
Cypermethrin, both the cis and trans isomers, and zeta-cypermethrin are primarily metabolized
by cleavage of the ester bond. The metabolites PBA and cyclopropane carboxylic acid (CPA)
are mainly excreted as conjugates. The type of conjugate differs in a number of animal species
dosed with cypermethrin, but humans and rats have the same pathway. Minor quantities of
hydroxylated PBA (conjugated) may also be found.
The metabolites identified in the plant metabolism studies are either found as metabolites in the
animal studies, or are intermediaries in the metabolic pathways elucidated in animals; therefore,
there are no residues of concern in plant studies, nor are there any unique metabolic pathways in
the plant, that are not represented in the rat metabolism study.
5.1.4 Residues of Concern Summary and Rationale
Based on the available data, HED has concluded that for all three active ingredients, the parent
compound is the only residue of concern for both tolerance enforcement and risk assessment in
plants, livestock commodities, and drinking water. The tolerance enforcement methods for plant
and animal commodities do not distinguish between zeta-cypermethrin, alpha-cypermethrin, and
cypermethrin. These conclusions are summarized in Table 5.1.4.
Table 5.1.4 Residue Definitions for the Cypermethrins

Matrix Risk Assessment Tolerance Expression
Plants Primary Crop Cypermethrin Cypermethrin
Rotational Crop Cypermethrin Cypermethrin
Livestock Ruminant Cypermethrin Cypermethrin
Poultry Cypermethrin Cypermethrin
Drinking Water Cypermethrin Not Applicable
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5.2 Food Residue Profile
Adequate residue data are available for the purpose of evaluating the registered uses of the
cypermethrins that could potentially result in dietary exposure. These uses include agricultural
uses on crops and the uses in food and feed handling establishments. The residue chemistry
database consists of adequate plant metabolism, animal metabolism, field trial, storage stability,
rotational crop, and analytical method studies. There are no outstanding residue chemistry
studies.
The monitoring data demonstrate that cypermethrin residues are low or non-detectable in most
commodities. Residues are sometimes found in leafy vegetables, peaches, cucurbits, fruiting
vegetables, some berries, and cereal grain forage, straw, and stover. In all other monitored
commodities, however, almost all samples had non-detectable residues. In processing studies,
residues generally concentrated in oils and were reduced in juices. These observations are
consistent with what would be expected from pyrethroids, which generally have high octanol
water partition coefficients and low water solubility values. Residues also concentrate in dried
commodities.
5.3 Water Residue Profile

I. Maher, D378901/D385246, 2/22/2011
In general, cypermethrin is applied at a maximum seasonal use rate (0.6 lb. ai/A for most uses)
4X that of zeta-cypermethrin (0.15 lb. ai/A for most uses). As a class of chemicals, the
pyrethroids have low solubility in water and a high affinity to bind to soils. Given these
physical/chemical properties, it is unlikely that oral exposure from drinking water will be a major
pathway of exposure.
The Environmental Fate and Effects Division (EFED) provided estimated residues of zeta-
cypermethrin in drinking water from the use of zeta-cypermethrin and cypermethrin on cotton.
The cotton use results in the highest estimated drinking water concentrations (EDWCs) for all
assessed use scenarios, including those associated with the petitions currently under review. The
EDWCs used in this dietary assessment are summarized in Table 5.3. The surface water
EDWCs were generated using the FQPA Index Reservoir Screening Tool (FIRST) Model and
the ground water estimates are from the Screening Concentration In GROund Water (SCI-GroW)
Model. The models and their descriptions are available at the USEPA internet site:
http://www.epa.gov/oppefed1/models/water/.
No monitoring data are currently available to further characterize potential drinking water
exposure. In the dietary risk assessment conducted to support the DRA for registration review,
HED incorporated the surface water EDWCs directly into the dietary model, since surface water
estimates were higher than those provided for ground water. In the acute assessment, an EDWC
of 3.77 ppb was used. In the chronic assessment, an EDWC of 0.066 ppb was used.
The use of the surface water values in the dietary assessment is therefore protective of potential
exposure through ground water sources of drinking water.
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Table 5.3. Tier I Analysis - EDWCs in surface water and ground water for cypermethrin and zeta-
cypermethrin.
Drinking Water Source Maximum Use Pattern Exposure EDWC (ppb)
Surface water Cotton Peak (acute) 3.77
Annual average (chronic) 0.066
Ground water Cotton Peak & annual average 0.0036
5.4 Dietary Risk Assessment
HED conducted acute and chronic dietary (food and drinking water) exposure assessments using
the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database
(DEEM-FCID) Version 3.16. This software uses 2003-2008 food consumption data from the
U.S. Department of Agriculture’s (USDA’s) National Health and Nutrition Examination Survey,
What We Eat in America, (NHANES/WWEIA).
A chronic dietary risk assessment is not required for the cypermethrins because repeated
exposure does not result in a POD lower than that resulting from acute exposure. Therefore, the
acute dietary risk assessment is protective of chronic dietary risk. However, HED performed a
chronic dietary exposure assessment for use in the aggregate assessment, since there are
residential exposures for the cypermethrins that will need to be aggregated with background
exposure from dietary sources. In the aggregate human health risk assessment, the average or
chronic exposure estimates will be combined with the appropriate residential exposure estimates
and compared to the chemical-specific PODs for the three different cypermethrins.
5.4.1 Description of Residue Data Used in Dietary Assessment
Acute Assessment:
The acute dietary exposure assessment is a refined probabilistic assessment based on tolerance
level residues for most commodities and PDP monitoring data for the commodities that make the
most significant contribution to dietary risk. Estimates of the maximum percent crop treated were
used for the same commodities for which PDP data were used and for one commodity for which
the tolerance was used. Although tolerance level residues were used for most commodities,
these commodities are not highly consumed ones. Refining the residue estimates for these
commodities would not have a significant effect on exposure and risk estimates. Conservative
default processing factors were used for the processed commodities for which they were
available, except for three cases: (1) when tolerances were set for processed commodities
because processing studies showed concentration to a level where the tolerance for the raw
agricultural commodity was not adequate, (2) when empirical processing factors were available,
and (3) where monitoring data were used directly for processed commodities.
To account for the apparent increased toxicity of alpha-cypermethrin relative to cypermethrin,

HED applied a 5x toxicity factor to the alpha-cypermethrin acute dietary POD. The labels
specify that the application rates of alpha-cypermethrin must be lower than that of cypermethrin
and zeta-cypermethrin. In this assessment, the increased toxicity of alpha-cypermethrin was
actually accounted for by multiplying the residues of alpha-cypermethrin by a factor of 5. It was
not applied when tolerance level residues were used because of the lower application rates of
alpha-cypermethrin. This 5X factor was applied when HED used PDP data as the residue values.
By adjusting the alpha-cypermethrin residue values instead of the POD, HED was able to include
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all 3 isomers in the acute dietary analysis, and then compare the exposure values to the POD for
cypermethrin.
Of the three isomeric mixtures, zeta-cypermethrin has the greatest number of tolerances. HED
used residue distribution files (RDFs) containing distributions of monitoring data values for the
commodities that made the greatest contribution to dietary risk. In cases where one of these
commodities is registered for use on zeta-cypermethrin as well as on alpha-cypermethrin, three
RDFs were used for the same commodity. One RDF contained the unadjusted monitoring data
values and was used for zeta-cypermethrin and possibly cypermethrin (if a tolerance for the
commodity has been established for cypermethrin). The second RDF contained the same residue
values multiplied by a factor of 5 to account for the increased toxicity of alpha-cypermethrin.
The third RDF contained only zeros. The maximum percent crop treated estimates were used to
direct the software to select residue values or zeros from the three RDFs the appropriate
percentage of time (i.e., the percent crop treated).
While the assessment was refined to the extent possible using PDP data, it is still considered to
be conservative due the inherent assumption that the higher monitoring values could be a result
of use of alpha-cypermethrin, whereas alpha-cypermethrin residues would be expected to be
much lower due to the lower application rates. Furthermore, tolerance level residues were used
for numerous commodities, along with default processing factors in some instances.
Chronic Assessment:
The chronic dietary exposure assessment is a highly refined assessment based on PDP
monitoring data for most commodities. HED made the assumption that 100% of all commodities
with tolerances would be treated by incorporating ½ LOD values for all non-detects when
monitoring data were used (i.e., rather than assuming the residue could be zero). Tolerance level
residues were used for a limited number of commodities; however, these commodities are not
highly consumed ones and, therefore, they make a negligible contribution to dietary exposure.
Refining the residue estimates for these commodities would have an insignificant effect on
exposure estimates. As with the acute assessment, conservative default processing factors were
used for the processed commodities for which they were available, with the exception of the
cases discussed above. The cypermethrins have food handling establishment (FHE) uses that
need to be accounted for in the chronic dietary exposure assessment. For these uses, HED used a
refined residue value of one-half the tolerance (since the FHE tolerances of 0.05 ppm were based
on the limit of quantitation, or LOQ), in accordance with current guidance (ChemSAC Database,
Policy Issues Addressed (Updated 2/27/98), 2_POLICY.TBL.doc). BEAD provided an estimate
of the probability that a food item a person consumes contains residues as a result of treatment in
an FHE at some point with any pesticide. It is not specific to the cypermethrins. This estimate
of 4.65% is equivalent to a percent crop treated estimate. In the chronic assessment, this value
was used for the same commodities as the ones with the FHE residue value (0.025 ppm). In
cases where the total anticipated residue from the FHE use exceeded the total anticipated residue
from the agricultural use, the FHE anticipated residue was used. The total anticipated residue
from the FHE use is 0.001163 ppm (0.025 ppm x 0.0465). If an agricultural commodity had a
lower total anticipated residue value, then the FHE anticipated residue was used. For example, if
a commodity had a tolerance of 0.01 ppm and a percent crop treated estimate of 1%, its total
anticipated residue would be 0.0001 ppm. In this case, the FHE total anticipated residue value is
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higher and would have been substituted for the agricultural use anticipated residue and percent
crop treated estimate.
5.4.2 Percent Crop Treated Used in Dietary Assessment
Acute Assessment:
Cypermethrin
The following maximum percent crop treated estimates (J. Alsadek, 2/8/2017) were used in the
acute dietary risk assessment for the following crops that are currently registered for
cypermethrin: lettuce, head: 5%; lettuce, leaf: 5%; broccoli: 10%; cabbage: 10%; cauliflower:
10%.
Zeta-Cypermethrin
The following maximum percent crop treated estimates (A. Shah, 10/6/2016) were used in the
acute dietary risk assessment for the following crops that are currently registered for zeta-
cypermethrin: lettuce, head: 75%; lettuce, leaf: 75%; spinach: 55%; celery: 60%; broccoli:
30%; cabbage: 45%; cauliflower: 25%; bean, green: 20%; tomato, puree: 20%; orange, juice:
55%; grapefruit, juice: 65%; peach: 10%; grape: 5%; rice: 15%; sugarcane: 2.5%.
Alpha-Cypermethrin
The following maximum percent crop treated estimates (J. Alsadek, 9/29/2016) were used in the
acute dietary risk assessment for the following crops that are currently registered for
cypermethrin: lettuce, head: 20%; lettuce, leaf: 20%; spinach: 2.5%; celery: 2.5%; broccoli:
2.5%; cabbage: 2.5%; cauliflower: 2.5%; bean, green: 2.5%; tomato, puree: 2.5%; orange, juice:
2.5%; grapefruit, juice: 2.5%; rice: 85%.
Chronic Assessment:
In the chronic assessment, HED made the conservative assumption of 100% crop treated for all
commodities with established tolerances. However, percent CT was effectively incorporated
into the assessment through the use of monitoring data for some commodities, which reflect the
percent CT for commodities in commerce. For the FHE uses, BEAD provided an estimate of the
probability that a food item a person consumes contains residues as a result of treatment in an
FHE at some point with any pesticide. It is not specific to the cypermethrins. This estimate is
4.65%. In the chronic assessment, HED used this value for all commodities that do not have
established tolerances. HED also used this value when the total anticipated residue for a
commodity was higher for the FHE use than it was for the agricultural use.
5.4.3 Acute and Chronic Dietary Assessments
Results of Acute Dietary (Food and Drinking Water) Exposure and Risk Assessment:
HED is concerned when dietary risk estimates exceed 100% of the PAD. The acute dietary risk
of the general U.S. population to residues of the cypermethrins is estimated to be 29% of the
aPAD. The population subgroup with the highest estimated dietary risk is Children 3-5, which
uses 92% of the aPAD. The acute dietary risk estimates of the general population and all
population subgroups are not of concern. The estimated exposure of the U.S. population and all
regulated subgroups is given in the Table 5.4.3.
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Results of Chronic Dietary (Food and Drinking Water) Exposure Assessment:
The chronic dietary exposure of the general U.S. population to residues of the cypermethrins is
estimated to be 0.00027 mg/kg/day. The population subgroup with the highest estimated dietary
exposure is Children 1-2, which has an exposure estimate of 0.00071 mg/kg/day. The estimated
exposure of the U.S. population and all regulated subgroups is given in the Table 5.4.3.
Contribution of Residues in Drinking Water

The EDWCs are conservative estimates of residues in drinking water; however, they are low
because the cypermethrins have high octanol/water partition coefficients and low water solubility
values. HED performed critical commodity contribution analyses to determine the contribution
of residues in drinking water to acute and chronic dietary exposure. For the acute assessment,
HED performed this analysis for the general U.S. population and the population subgroup with
the highest dietary risk estimate, Children 3-5. For the chronic assessment, HED performed this
analysis for the general U.S. population and the population subgroup with the highest dietary
exposure estimate, Children 1-2. In both acute assessments, residues in drinking water
contributed less than 0.1% of the dietary exposure. In the chronic assessment for the general
U.S. population, residues in drinking water contributed approximately 12% (0.00003 mg/kg/day)
of the dietary exposure, and for the subgroup Children 1-2, residues in drinking water
contributed approximately 6% (0.00004 mg/kg/day) of the dietary exposure.
Results of Cancer Dietary Exposure and Risk Assessment:

HED classified cypermethrin as a “possible human carcinogen” and determined that a non-linear
approach should be used for cancer assessment. As the acute dietary exposure estimates are not
of concern, cancer risk is not of concern.
Table 4. Summary of Dietary (Food and Drinking Water) Exposure and Risk for the
Cypermethrins.
Acute Dietary
Chronic Dietary Cancer
(99.9th Percentile)
Population Subgroup Dietary Dietary Dietary
Exposure % aPAD1 Exposure % cPAD Exposure Risk
(mg/kg/day) (mg/kg/day) (mg/kg/day)
General U.S. Population 0.020630 29 0.000260
All Infants (<1 year old) 0.022154 92 0.000670
Children 1-2 years old* 0.021491 90 0.000710
Children 3-5 years old* 0.022196 92 0.000544
Children 6-12 years old 0.012560 18 0.000294 NA NA NA
Youth 13-19 years old 0.019003 27 0.000181
Adults 20-49 years old 0.025012 35 0.000220
Adults 50-99 years old 0.017582 25 0.000231
Females 13-49 years old 0.017749 25 0.000213
1
The aPAD is 0.0716 mg/kg/day
*The population subgroups with the highest exposure estimates.
6.0 Residential Exposure and Risk Estimates
HED has assessed residential handler and post-application exposures for existing residential
indoor and outdoor uses with the highest application rates or percent ais which are protective of
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all other application rates. Existing residential uses were re-assessed to reflect updates to HED’s
2012 Residential SOPs5 along with a revision to the inhalation POD for children ≤ 6 years of age
(D359207, M. Collantes, 7/24/2009; and D406746, M. Crowley, 12/4/2012). These exposures
have been further updated herein to reflect updated application rates and scenarios. Chemical-
specific turf transferrable residue (TTR) and dislodgeable foliar residue (DFR) data are available
for cypermethrin and have been incorporated into the post-application assessment. Chemical-
specific DFR data were only used for alpha-cypermethrin as it was the only active ingredient
registered for use on residential gardens and trees. Only those product labels without specific
clothing and/or PPE requirements have been assessed for residential handler exposure.
6.1 Residential Handler Exposure/Risk Estimates
HED uses the term “handlers” to describe those individuals who are involved in the pesticide
application process. HED believes that there are distinct tasks related to applications and that
exposures can vary depending on the specifics of each task. Residential handlers are addressed
somewhat differently by HED as homeowners are assumed to complete all elements of an
application without use of any protective equipment.
There are registered cypermethrin product labels with residential use sites (e.g., lawns, indoor
environments, garden and trees and pets such as horses and dogs) that do not require specific
clothing (i.e., long sleeve shirt/long pants) and/or personal protective equipment (PPE), and these
labels have been considered in the residential handler assessment for cypermethrins. A summary
of the representative registered residential handler and use scenarios with the highest application
rates or percent ai is provided in Appendix D Table D.2.
The quantitative exposure assessment developed for residential handlers is based on the
following scenarios:
Cypermethrin
 Mixing/Loading/Applying liquid concentrate formulation to indoor surfaces,
Garden/Trees and Lawns/Turf using manually-pressurized handwand sprayer
 Mixing/Loading/Applying liquid concentrate formulation to indoor surfaces,
Garden/Trees and Lawns/Turf using trigger pump sprayer
 Mixing/Loading/Applying liquid concentrate formulation to Garden/Trees, and
Lawns/Turf using hose-end sprayer
 Mixing/Loading/Applying liquid concentrate formulation to Garden/Trees, and
lawns/Turf using backpack sprayer
 Mixing/Loading/Applying wettable powders in water-soluble packaging formulation to
indoor surfaces, Garden/Trees and Lawns/Turf using manually-pressurized handwand
sprayer
indoor surfaces, Garden/Trees and Lawns/Turf using hose-end sprayer
indoor surfaces, Garden/Trees and Lawns/Turf using backpack sprayer
5
Available: http://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-procedures-
residential-pesticide
Page 49 of 138
indoor surfaces, Garden/Trees and Lawns/Turf using sprinkler can
 Mixing/Loading/Applying liquid concentrate formulation to horses using sponge or wipe
 Mixing/Loading/Applying liquid concentrate formulation to horses using Trigger spray
bottle
 Apply ready-to-use indoor/outdoor surface (including bed bug treatment) direct product
using aerosol spray
 Apply ready-to-use indoor/outdoor surface direct product using trigger spray bottle
Zeta- Cypermethrin
 Mixing/Loading/Applying liquid concentrate formulation to indoor surfaces, home
gardens/trees, residential lawns, home perimeter and horses using manually-pressurized
handwand sprayer
 Mixing/Loading/Applying liquid concentrate formulation to home gardens/trees,
residential lawns, and home perimeter using hose-end sprayer
 Mix/load/Apply liquid concentrate formulation to horses using trigger spray
 Load and applying granular formulation to residential lawn, home perimeter, ornamentals
and flower gardens using rotary spreader
 Applying pet collar (99/1 liquid/dust formulation)
 Applying pet collar (50/50 liquid/dust formulation) and
 Applying pet collar (1/99 liquid/dust formulation)
Alpha -Cypermethrin
 Mixing/Loading/Applying microencapsulated formulation to residential lawns,
gardens/trees, home perimeter, shrubbery and vegetation around stagnant pools, ponds
and areas where mosquitoes may rest, and livestock and poultry housing using manually-
pressurized handwand sprayer
gardens/trees, ornamentals, home perimeter, shrubbery and vegetation around stagnant
pools, ponds and areas where mosquitoes may rest, and livestock and poultry housing
using hose-end sprayer and
gardens/trees, ornamentals, home perimeter, shrubbery and vegetation around stagnant
pools, ponds and areas where mosquitoes may rest, and livestock and poultry housing
using backpack sprayer
 Applying ready-to-use formulation to indoor surfaces using an aerosol can
Total Release Fogger:

A quantitative assessment was not required for handling of the total release fogger product since
the labels state that the room/house must be vacated immediately by the user once fogging is
initiated.
Liquid Spot-on for Horses

A quantitative inhalation handler assessment was not required for cypermethrin spot-on end use
products for horses since inhalation exposure is anticipated to be negligible.
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Dog Collar Formulation Assumption:
As described in the recent 2016 tetrachlorvinphos (TCVP) risk assessment (W. Britton,
D436833, 12/21/2016), due to the uncertainty associated with whether pet collars are liquid
and/or dust formulated products, residential handler exposures for pet collar applications are
assessed assuming pet collars could be liquid and solid (dust) formulations concurrently with
varying ratios of liquid/dust (e.g., 99/1, 50/50, and 1/99 liquid/dust). When assessing pet collars
as a liquid formulation, surrogate unit exposures (UEs) for spot-on products are used (per the
2012 Residential SOPs), which assume negligible inhalation exposure for handlers. In order to
assess pet collars as a dust formulation, shaker can surrogate UE data are used (Treated Pet SOP,
Table 8-1) which include the potential for inhalation exposures. This assessment approach
reflects an update to the 2012 assessment of zeta-cypermethrin pet collar application.
Combining Exposures/Risk Estimates:

Since no adult dermal endpoint was selected for adults for cypermethrin and zeta-cypermethrin,
only inhalation risks were calculated and no routes of exposure were combined. However, an
aggregate risk index (ARI) approach was used for alpha-cypermethrin since the LOCs for dermal
exposure (100) and inhalation exposure (30) are different. The target ARI is 1; therefore, ARIs
of less than 1 are risk estimates of concern. The aggregate risk index (ARI) was calculated as
follows.
Aggregate Risk Index (ARI) = 1÷ [(Dermal LOC ÷ Dermal MOE) + (Inhalation LOC ÷
Inhalation MOE)]
Summary of Residential Handler Non-Cancer Exposure and Risk Estimates

All residential handler risk estimates for the cypermethrins are not of concern (i.e., inhalation
MOEs are > 30, dermal MOEs are > 100, or ARI is > 1) with one exception:
 residential handlers applying alpha-cypermethrin as a microencapsulated concentrate in

livestock housing using a manually pressurized handwand resulted in a dermal MOE of
62 and an ARI of 0.61 which is of concern.
However, unit exposure values and estimates for the microencapsulated formulated end-use
product used to assess handler exposure resulting from treating livestock housing are based on
surrogate unit exposure values for liquid formulations. Pesticides are encapsulated to be released
over time, allowing farmers to apply the pesticides less often rather than requiring very highly
concentrated and perhaps toxic initial applications followed by repeated applications to protect
those that might be exposed to the chemicals.6 Therefore, use of surrogate liquid unit exposure
values for microencapsulated formulations may result in conservative exposure risk estimates.
For residential handlers, exposures from application to turf were not combined with exposures
from treating gardens/trees because concurrent use of separate pesticide products that contain the
same active ingredient to treat the same or different pests does not typically occur. Therefore,
although the same products allow treatment of gardens/trees and turf, these exposures were not
combined for residential handlers.
The residential handler exposure and risk estimates are summarized in Table 6.1
6
http://www.microteklabs.com/technical-overview.html
Page 51 of 138
Table 6.1. Residential Handler Non-Cancer Exposure and Risk Estimates for Cypermethrin.
Formulation Equipment Inhalation Maximum Area Treated or Inhalation
Use Site Unit Exposure Application Amount Handled
Dose MOE
(mg/lb ai) Rate1 Daily2
(mg/kg/day)3 LOC = 304
Mixer/Loader/Applicator
Cypermethrin ME 0.2 RTU Reg No. 100-1303
Liquid Concentrate
Manually-pressurized 0.016
Indoor Spot 1.1 0.5 gals 0.000079 9,300
Handwand lb ai/gal
Crack & Crevice
Liquid Concentrate Manually-pressurized
0.018 0.002 lb ai/gal 5 gallons 0.0000023 320,000
Lawns/Turf Handwand
Hose-end Sprayer 0.022 0.44 lb ai/A 0.5 acres 0.000061 12,000
Manually-pressurized 0.00001 lb
0.018 1200 ft2 0.0000027 270,000
Handwand ai/ft2
Liquid Concentrate Hose-end Sprayer 0.0014 0.002 lb ai/gal 11 gallons 0.00000039 1,900,000
Garden/Trees
0.00001 lb
Backpack 0.14 1200 ft2 0.000021 35,000
ai/ft2
Bonide Cyper WSP 40% ai Reg. No. 4-482
Indoor
Perimeter/Spot/
(course
application); Manually-pressurized
1.1 0.017 lb ai/gal 0.5 gallons 0.00012 6,200
Perimeter /Spot/ Handwand
(pinstream
application); Crack
and Crevice
Lawn Hose-end Sprayer 0.034 0.44 lb ai/A 0.5 acres 0.000094 7,800
Manually-pressurized 0.017 lb ai/gal 5 gallons 0.00019 38,000
0.018
Handwand 0.01 lb ai/ft2 1200 ft2 0.0027 270
0.017 lb ai/gal 11 gallons 0.0008 9,200
Hose-end Sprayer 0.034
Outdoor 0.01 lb ai/ ft2 1200 ft2 0.0051 140
/Perimeter/Spot/
Crack & Crevice Backpack 0.018 0.017 lb ai/gal 5 gallons 0.00019 38,000
Gardens/Trees
Backpack 0.018 0.01 lb ai/ ft2 1200 ft2 0.0027 270
0.017 lb ai/gal 5 gallons 0.000036 20,000
Sprinkler can 0.034
0.01 lb ai/ ft2 1200 ft2 0.0051 140
Raid Ant & Roach 26 0.1% ai Reg. No. 4822-596
Ready-to-Use
Indoor Use Only
Broadcast Surface 0.001 lb ai/16 1 can 0.000038 19,000
Direct Spray, Aerosol can 3
oz. can
Insect Repellent
Perimeter/ Spot/ 0.5 can 0.000019 39,000
MGK 29811 0.05% ai Reg. No. 1021-2604
Indoor/Outdoor
0.00052
Spot/ Crack &
Aerosol can 3 lb ai/16 oz. 0.5 can 0.00001 75,000
Crevice and Bed
can
Bug
Chemsico Insecticide Ready-to-Use Reg. No. 9688-134
Indoor Crack & 0.021 lb 1 Bottle
Crevice, perimeter, Trigger spray bottle 0.061 0.000016 46,000
ai/bottle (broadcast
Page 52 of 138
Table 6.1. Residential Handler Non-Cancer Exposure and Risk Estimates for Cypermethrin.
Formulation Equipment Inhalation Maximum Area Treated or Inhalation
Use Site Unit Exposure Application Amount Handled
Dose MOE
(mg/lb ai) Rate1 Daily2
(mg/kg/day)3 LOC = 304
foundation treatment)
0.5 bottle (spot
0.000008 91,000
treatment)
Outdoor perimeter,
foundation 2 Bottles 0.000032 23,000
Farnam Crash Wipe-On Insecticide Repellent 0.15% ai Reg. No 270-253

Horses 0.0004 lb ai/pet
Sponge/Wipe/Roll On 0.21 2 horses 0.0000021 350,000
(4 oz./horse)
Farnam Crash II Fly Spray 0.6% ai Reg. No. 270-376
Horses 0.00016 lb
ai/bottle
RTU Trigger Spray 3.3 (12 ml/horse) 2 horses 0.000013 55,000
0.00016
lb ai/horse
1. Based on registered application rates summarized in Appendix D, Table D.2. Application rates presented as lbs ai/1000ft2 in Appendix
C, Table C.1 were recalculated to lbs ai/ft2 to better reflect calculations for area treated (i.e., lbs ai/1000ft2 ÷ 1000 = lbs ai/ft2).
2. Based on HED’s 2012 Residential SOPs (http://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-
procedures-residential-pesticide).
3. Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled
(A/day or gallons/day) ÷ Body Weight (80 kg).
4. Inhalation MOE = Inhalation POD (0.73 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
Table 6.1.2. Residential Handler Non-Cancer Exposure and Risk Estimates for Zeta -Cypermethrin
Formulation Equipment Inhalation Unit Maximum Area Treated Inhalation
Use Site Exposure Application or Amount Dose MOE
(mg/lb ai) Rate1 Handled (mg/kg/day)3 LOC = 304
Daily2
F6570 EW Master Insecticide 0.35% EPA Reg 279-3347
Lawns/Turf Manually-pressurized
0.018 0.0035 lb ai/gal 5 gallons 0.0000039 190,000
Handwand
Hose-end Sprayer 0.022 0.15 lb ai/A 0.5 acres 0.000021 35,000
Backpack 0.14 0.0035 lb ai/gal 5 gallons 0.000031 24,000

Garden/Trees, Manually-pressurized 0.0000034 lb
0.018 1200 ft2 0.00000092 800,000
And Home Handwand ai/ft2
Vegetable Hose-end Sprayer 0.0014 0.0035 lb ai/gal 11 gallons 0.00000067 1,100,000
Garden Backpack 0.14 0.0035 lb ai/gal 5 gallons 0.000031 24,000
Indoor Spot Manually-pressurized
and Crack & 1.1 0.0035 lb ai/gal 0.5 gallons 0.000024 30,000
Handwand
Crevice
Evercide 28511 0.75% ai Reg. No. 1021-1859
Liquid
Concentrate Manually-pressurized 0.018 0.0022 lb ai/ft2 1200 ft2 0.00059 1,200
Barrier Handwand
Liquid 0.00625 lb ai/gal
Concentrate Trigger Spray 3.3 2 horses 0.00052 1,400
(12.8 oz./gal)
Horses
Loader/Applicator
F0570 OTC Granular Insecticide 0.344% ai Reg. No. 279-3297
Push-type rotary Spreader 0.0026 0.15 lb ai/A 0.5 acres 0.0000024 300,000
Page 53 of 138
Table 6.1.2. Residential Handler Non-Cancer Exposure and Risk Estimates for Zeta -Cypermethrin
Formulation Equipment Inhalation Unit Maximum Area Treated Inhalation
Use Site Exposure Application or Amount Dose MOE
(mg/lb ai) Rate1 Handled (mg/kg/day)3 LOC = 304
Daily2
Granular 0.0000034 lb
Belly grinder 0.039 1200 ft2 0.000002 370,000
Lawns/Turf ai/ft2
0.0000034 lb
Hand dispersal 0.38 100 ft2 0.000019 38,000
ai/ft2
Granular 0.0000034 lb
Push-type rotary Spreader 0.0026 1200 ft2 0.00000013 5,500,000
Garden/Trees ai/ft2
0.0000034 lb
Spoon 0.087 1200 ft2 0.0000044 160,000
ai/ft2
0.0000034 lb
Hand dispersal 0.38 1200 ft2 0.000019 38,000
ai/ft2
Apply
YT-1601 Dog Tag 10% ai Reg. No. 39039-14
Dog Tag 99/1 0.0018 0.0000013 530,000
liquid/dust 18
Dog Tag (Surrogate unit
50/50 exposure for dust 0.002 2 animals/day 0.00039 1,800
RTU
liquid/dust using shaker
Dog Tag 1/99 can)
0.0018 0.00091 800
liquid/dust
2
1. Based on registered application rates summarized in Appendix D, Table D.2. Application rates presented as lbs ai/1000ft in Appendix
C, Table C.2 were recalculated to lbs ai/ft2 to better reflect calculations for area treated (i.e., lbs ai/1000ft2 ÷ 1000 = lbs ai/ft2).
2. Based on HED’s 2012 Residential SOPs (http://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-
procedures-residential-pesticide).
3. Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled
(A/day or gallons/day) ÷ Body Weight (80 kg).
4. Inhalation MOE = Inhalation POD (0.73 mg/kg/day) ÷ Inhalation Dose (mg/kg/day). LOC =30
Page 54 of 138
Table 6.1.3. Residential Handler Non-Cancer Exposure and Risk Estimates for Alpha-Cypermethrin.
Formulation Equipment Level of Concern Dermal Inhalation Maximum Area Treated Dermal Inhalation Total
Use Site Unit Unit Application Rate1 or Amount Dose MOE4 Dose MOE6 ARI7
Exposure Exposure Handled (mg/kg/day)3 (mg/kg/day)5
(mg/lb ai) (mg/lb ai) Daily2
Fedona CS (TC-305) 3% a.i. (0.25 lb ai/gal) Reg. No. 499-570
Microencapsulated Manually 0.004 lb ai/gal
Indoor spot, bed bug, pressurized 69 1.1 0.5 gallons 0.0002 6,100 0.000028 5,500 45
crack and crevice, hand wand (-0.05%)
Microencapsulated Hose -end 0.085 lb ai/A

13.4 0.022 0.5 A 0.0010 1,500 0.000012 13,000 14
Lawns/Turf sprayer (1 oz./100ft2)
Manually 0.00013
pressurized 63 0.018 5 gallons 0.000071 20,000 0.00000015 1,000,000 200
hand wand lb ai/gal
Microencapsulated
Garden/Ornamentals/ Back pack 0.00013
130 0.14 5 gallons 0.00014 9,900 0.0000011 130,000 97
Trees lb ai/gal
Hose -end 0.00013 13,000,00
Dermal (100) 58 0.0014 5 gallons 0.000063 22,000 0.000000011 220
sprayer lb ai/gal 0
Inhalation (30)
Manually 0.43 lb ai/A
Microencapsulated pressurized 63 0.018 0.5 A 0.022 62 0.000048 3,100 0.61
(5 oz./1000ft2)
Livestock Housing hand wand
(darkling beetle) 0.0000097
Backpack 130 0.14 5 gallons 0.0025 550 0.00002 7,400 5.4
lb ai/ft2
Hose-end
13.4 0.022 0.00022 6,200 0.0000028 55,000 60
Sprayer
Microencapsulated Diluted Rate -
Backpack 130 0.14 0.02 lb ai/A 0.0022 640 0.000018 8,600 6.3
Mosquito Vector 0.5 A
Control Manually (0.25 lb ai/gal)
pressurized 63 0.018 0.0011 1,300 0.0000023 67,000 13
hand wand
TC-327 0.05% a.i. Reg. No. 499-569
0.00052
Ready to Use Aerosol Dermal (100) 1 can
0.11 3 lb ai/can 0.00000004 29000000 0.0000098 15,000 510
Indoor Environment Can Inhalation (30) (16 oz.)
1 Based on registered application rates summarized in Appendix D, Table D.2.
2 Based on HED’s 2012 Residential SOPs (http://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-procedures-residential-pesticide).
3 Dermal Dose = Dermal Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A/day or gallons/day) × DAF (13.4 %) ÷ Body Weight (80 kg).
4 Dermal MOE = Dermal POD (1.4 mg/kg/day) ÷ Dermal Dose (mg/kg/day).
5 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A/day or gallons/day) ÷ Body Weight (80 kg).
Page 55 of 138
6 Inhalation MOE = Inhalation POD (0.15 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
7 Aggregate Risk Index (ARI) = 1÷ [(Dermal LOC ÷ Dermal MOE) + (Inhalation LOC ÷ Inhalation MOE)]
Page 56 of 138
6.2 Residential Post-application Exposure/Risk Estimates
There is the potential for post-application exposure for individuals exposed as a result of being in
an environment that has been previously treated with cypermethrins.
No systemic effects were seen in the dermal cypermethrin study; therefore, no dermal post-
application exposure assessment was conducted for adults or children > 6 years of age for
cypermethrin and zeta-cypermethrin. However, due to increased quantitative susceptibility noted
in the zeta- cypermethrin developmental neurotoxicity (DNT) study, dermal post-application
exposure assessments were conducted for children < 6 years to protect for potential offspring
effects. Furthermore, due to the additional concern for potential increased of alpha-
cypermethrin, dermal post-application exposure assessments were conducted for adults and
children. Inhalation exposures are assessed for adults and children from the alpha-cypermethrin
mosquito control use. Incidental oral exposures were assessed for children 1 to < 2 for all
cypermethrins.
The quantitative exposure/risk assessment for residential post-application exposures is based on

the following scenarios:
Cypermethrin scenarios reflected in Table 6.2.3:

 Children 1 to < 2 years old dermal post-application exposures from contact with
cypermethrin residues deposited on treated turf (high contact lawn activities);
 Children 1 to < 2 years old incidental oral (i.e. hand-to-mouth, object-to-mouth, soil
ingestion, granular ingestion) post-application exposures from contact with cypermethrin
residues deposited on treated turf (high contact lawn activities);
cypermethrin residues deposited on indoor surfaces;
 Children 1 to < 2 years old incidental oral (i.e. hand-to-mouth, object-to-mouth) post-
application exposures from contact with residues deposited on indoor surfaces.
Zeta-cypermethrin scenarios reflected in Tables 6.2.4 and 6.2.5:

 Children 1 to < 2 years old dermal post-application exposures from contact with residues
deposited on treated turf (high contact lawn activities);
ingestion, granular ingestion) post-application exposures from contact with residues
deposited on indoor surfaces;
 dermal post-application exposures from contact with residues deposited on dogs treated
with pet collars;
 Children 1 to < 2 years old incidental oral (i.e. hand-to-mouth, object-to-mouth,) post-
application exposures from contact with residues deposited on dogs treated with pet
collars
Page 57 of 138
Alpha-cypermethrin scenarios reflected in Tables 6.2.6 through 6.2.9:
 Adult dermal post-application exposures from contact with alpha-cypermethrin residues
deposited on treated turf (high contact lawn activities and mowing) gardens and trees;
 Adult dermal post-application exposures from contact with residues deposited on treated
turf resulting from vector mosquito control using truck mounted fogger;
 Adult inhalation post-application exposures resulting from alpha-cypermethrin vector
mosquito control using truck mounted fogger;
 Adult dermal post-application exposures from contact with residues deposited on indoor
surfaces;
residues deposited on treated turf (high contact lawn activities, mowing, and golfing),
gardens and trees;
residues deposited on treated turf (high contact lawn activities, mowing, and golfing),
gardens and trees;
 Children 1 to < 2 years old dermal post-application exposures from contact with alpha-
cypermethrin residues deposited on treated turf from vector mosquito control using truck
mounted fogger;
 Children 1 to < 2 years old incidental oral post-application exposures from contact with
alpha-cypermethrin residues deposited on treated turf from vector mosquito control using
truck mounted fogger;
ingestion, granular ingestion) post-application exposures from contact with residues
deposited on indoor surfaces;
Available Residue Data
Turf Transferable Residues (TTR):

Wettable powder and emulsifiable concentrate TTR Study: MRID 45111501:
Post-application exposures from treated turf were assessed using 0-day residue data from a turf
transferable residue study conducted with wettable powder and emulsifiable concentrate
cypermethrin products. The chemical-specific turf transferable residue (TTR) data collected with
the Modified California Roller Method are available for cypermethrin, underwent secondary
review by HED7, and were determined to be acceptable for use in risk assessment. Corrected
TTR values have been reassessed to incorporate current regression modeling into this assessment
resulting in a day-0 TTR of 0.026 µg/cm2 at the study application rate of 0.44 lbs. ai/acre for
emulsifiable concentrate and 0.085 µg/cm2 at the study application rate of 4.59 lbs. ai/acre for
Page 58 of 138
wettable powder. The TTR Day-0 transferable residues were adjusted to reflect the current
maximum application rate (0.44 lb. ai/acre) for use of cypermethrins on turf. See Table 6.2.1 for
a summary of results from the TTR data.
Table 6.2.1. Key Results from TTR study (MRID 451115-01)

Study Adjusted Day
Study Day 0 Day 0
Application 0 Trans.
Site Trans. Residue (%)
Rate Residue1
(µg/cm2) Transferability
(lbs. ai/acre) (µg/cm2)
Emulsifiable Concentrate
California 0.026 0.39 0.44 0.026
Missouri 0.007 0.15 0.44 0.007
Pennsylvania 0.025 0.47 0.44 0.025
Wettable Powder
California 0.616 1.1 4.59 0.06
Missouri 0.355 0.64 4.59 0.034
Pennsylvania 0.891 1.16 4.59 0.085
1. Adjusted Day 0 Transferable Residue = Day 0 Transferable Residue x (max label application rate (0.44 lbs ai/A) /
study application rate (4.59 lb ai/A for wettable powder and 0.44 lbs ai/A for emulsifiable concentrate))
Dislodgeable Foliar Residue (DFR) – (MRID No. 44685201) - Alpha-cypermethrin

A DFR study is available for use in estimating post-application risks to alpha-cypermethrin
resulting from contact with gardens and trees. In this study, foliar dislodgeable residues were
measured from mustard greens treated with 6 applications of alpha-cypermethrin at a rate of 0.1
lb ai/acre per application. DFR measurements were conducted at the following intervals: just
prior to each application, just after each application (after the spray had dried), on Days 1, 2, and
4 after the first and second applications, and on Days 1, 2, 4, 7, 10, 14, 21, 28, and 35 after the
sixth (final) application. HED has concluded that the DFR values from this study are the best
available data for assessing dermal post-application exposure from contact with foliage treated
with alpha-cypermethrin, and has used these DFR data in the post-application exposure and risk
assessment. A summary of the DFR study is presented in Table 6.2.2.
Table 6.2.2. Summary of DFR Residues and Regression Analysis Results for Alpha-Cypermethrin
Statistic
Mustard Greens MRID #446852-01
Application Rate (lb ai/A) 0.1
Measured Average Day 0 Residue (µg/cm2) 0.3051
Predicted Day 0 Residue (µg/cm2) 0.259
Adjusted Day 0 Transferable Residue1 (µg/cm2) 0.065
Slope -0.117
Half-Life (days) 5.9
2
R 0.76
1. Adjusted Day 0 Transferable Residue = Day 0 Transferable Residue x (max label application rate (0.025 lb
ai/A) / study application rate (0.1 lbs ai/A)
Page 59 of 138
Wide Area Mosquito Control Using Ground-based Truck-Mounted-Foggers -Alpha-
cypermethrin only
The post-application exposure potential from mosquito adulticide applications has been
considered for ground based truck foggers. No chemical-specific exposure data have been
submitted to support the alpha-cypermethrin mosquito adulticide use. Therefore, to assess the
potential for dermal and hand-to-mouth exposure from this use, the algorithms and inputs
presented in the 2012 Residential SOPs, Lawns/Turf section were used, coupled with chemical
specific cypermethrin TTR data. The cypermethrin TTR (0.026 µg/cm2) data for liquid
formulations were adjusted to reflect the single maximum application rates (0.02 lb. ai/A) for use
of cypermethrin on turf for mosquito control. The deposition of cypermethrin from mosquito
applications is not based on the application rate alone, but also includes use of empirical data to
determine how much pesticide is deposited downwind on residential lawns as a result of
mosquito adulticide treatments at the maximum single application rates. The TTR data are then
used to determine the fraction of the total residue deposited following the mosquitocide
application which can result in exposures to impacted individuals.
In an analysis from 2013 (C. Peck, D407817, 3/28/2013), the Environmental Fate and Effects
Division (EFED) reviewed eight published studies on ground ultralight volume (ULV)
application in which deposition was measured. The studies varied in collection media (i.e., grass
clippings and coupons), distance from application or spray head (ranging from 8 meters to 500
meters), and chemical measured (i.e., fenthion, malathion, naled, and permethrin). After
considering the available data, HED has determined that an off-target deposition rate of 8.7
percent of the application rate may be used to evaluate ground-based ULV applications (i.e., 8.7
percent of the target application rate deposits on turf). This value is the 90 percent upper
confidence limit on the mean and is slightly higher than the mean values from all the data points
observed in the studies (7.1%, n= 94). The adjusted application rate was then used to define
TTR levels by scaling the available cypermethrin TTR data as appropriate. The adjusted TTR
(0.026 µg/cm2 x 0.02 lb ai/A/0.44 lb ai/A = 0.0011 µg/cm2), was further adjusted to account for
the revised deposition rate of 8.7 % or 0.087 (0.087 x 0.0011 µg/cm2 = 0.0001 µg/cm2).
Inhalation exposures are estimated using a recently developed Well Mixed Box (WMB) Model
approach based on the Residential SOPs for outdoor foggers.
Pyrethroid Post-Application Indoor Fraction of Residue Available for Transfer (Fai):

Chemical-specific data provided by the Non-Dietary Exposure Task Force (NDETF) were used
for the fraction of residue available for transfer (Selim, 2004a; Selim, 2003b; Selim, 2003c;
Selim, 2000; Selim, 2002b; Selim, 2002c). The NDETF studies examined the transferability of
residues from bare hand-presses on carpets and hard surfaces for deltamethrin, permethrin, and
pyrethrins. For carpets, the fraction transferred was 0.048, 0.02 and 0.01 for pyrethrins,
permethrin and deltamethrin, respectively. For hard surfaces, the fraction transferred was 0.04,
0.03, and 0.05 for pyrethrins, permethrin, and deltamethrin, respectively. Since the values were
so similar across the three chemicals, the average fraction transferred was used for all the
8
The value currently reported in the Residential SOPs for fraction transferred from carpets for pyrethrin is 0.03, but
this has been identified as a typo, and should be 0.04. This error will be corrected in the next revision to the
Residential SOPs.
Page 60 of 138
pyrethroids in the cumulative assessment: 0.02 for carpets and 0.04 for hard surfaces. These
same transfer fractions were used to assess cypermethrins.
Pyrethroid Indoor Dermal Deposited Residue Values (DepR) for Purpose of Calculating
Incidental Oral Exposure:
For the estimated deposited residue values following an indoor broadcast, perimeter/spot/bedbug,
and crack and crevice application of a pyrethroid, HED’s policy is to use the collective
pyrethroid data rather than individual chemical-specific data from SOPs. The following
information was used in the cypermethrins dermal post-application exposure algorithms to
calculate exposure following perimeter/spot, crack and crevice surface directed indoor
application:
 Perimeter/Spot/Bedbug applications (Coarse):

o Use a default deposited residue value of 2.6 µg/cm2 with no adjustment for
percent ai. This value is a combination of the pyrethroid data from Keenan (2007)
and esfenvalerate data from Selim (2008) for all pyrethroids.
 Perimeter/Spot/Bedbug applications (Pinstream):
percent ai. This value is a combination of the pyrethroid data from Keenan (2007)
and the ORD Test house date (D390098) for all pyrethroids
 Crack and crevice applications:
percent ai. This value is a combination of the pyrethroid data from Keenan
(2007), the esfenvalerate data from Selim (2008) and the ORD Test house date
(D390098) for all pyrethroids
Pyrethroid Indoor Surface Directed Post-application Inhalation Exposure:

HED has received and reviewed an Office of Research and Development (ORD) exposure study
that was performed in the U.S. EPA’s Indoor Air Quality (IAQ) Research House (C. Smith,
D390098, 9/15/2011). This study simulated crack and crevice applications of four pesticides:
two emulsifiable concentrate products applied via a handheld sprayer (permethrin and
cypermethrin), one aerosol can product (propoxur), and one gel bait product (fipronil). The
application pattern used in this study is considered a reasonable representation of an indoor crack
and crevice application but also can represent other indoor applications such as perimeter (coarse
and pinstream) as well as surface directed broadcast uses due to the nature of the applications
(applications were made to floor-to-ceiling paneling on three walls of an interior room). Air
concentrations of all four chemicals were collected using stationary air samplers suspended 75
cm above the floor in the room of application (the living room) and two other rooms in the test
house (the den and master bedroom). Air samples were collected during the application and 1,
1.5, 2, 2.5, 3, 7, 14, 21, 28, and 35 days after application. Permethrin and cypermethrin air
concentrations were not found in any measurable quantities in any room in the research house.
The NDETF has performed an analysis of all the pyrethroid surface deposition and hand press
exposure data that they produced. This analysis shows the exposure data for one pyrethroid can
generally be used to represent the entire chemical class. Based on this NDETF analysis and the
generally low vapor pressure of pyrethroids, HED believes it is appropriate to use the air
Page 61 of 138
concentration data from the ORD study as a surrogate for pyrethroids when they are applied as
surface-directed applications indoors. HED does not have concerns for pyrethroids in general for
the post-application inhalation exposure scenario given that all air concentration values were
below the limit of quantitation in the ORD study.
Dermal and Incidental Oral Post-application Exposure Resulting from Contact with Dog
Collars:
Because there is uncertainty whether pet collars are liquid and/or dust formulated products, HED
assumes that the active ingredient present in pet collars could be transferred in either form (liquid
or dust) from the collar to the pet’s fur and result in the potential for post-application exposures
from contact with the treated pet. As a result, residential post-application dermal and incidental
oral exposures were evaluated assuming both liquid and solid (dust) formulations are present
concurrently at varying ratios (e.g., 99/1, 50/50, and 1/99 liquid/dust). Post-application
inhalation exposure is anticipated to be negligible.
This approach uses the same methodologies described in the 2012 Residential SOPs for
assessment of post-application exposure assessment for pet collar usage. However, whereas the
2012 Residential SOPs recommend that pet collars be assessed as a liquid formulation, the
present approach assesses pet collar exposures as both a liquid and solid form. Transfer
coefficients specific to each formulation were used in the assessment. The individual dust and
liquid formulation post-application risks were estimated, and then another step was included in
the assessment where the liquid and dust risks were averaged assuming 99/1, 50/50, and 1/99
ratios.
In conjunction with this evaluation approach, the agency intends to request and review additional
information relating to all registered pet collar products as they undergo registration review, as
well as any proposed new pet collar uses. This evaluation will continue until the agency is
satisfied that, based on the design and operation of pet collar products, a final formulation type
decision can be made along with recommendations for human health risk assessment of
exposures to pet collar-treated pets.
Post-application Exposure Resulting from Contact with Treated Horses:

Currently, there are no methodologies in place to assess post-application exposures to treated
horses. HED is currently updating the 2012 Residential SOPs. Those updates may have an
impact on the need for post-application assessments for treated horses in the future.
Post-application Inhalation Exposure Resulting From Fogger Applications:

Post-application inhalation exposure following use of indoor foggers is expected to be negligible
since most fogger product labels typically state a period of no-entry following application
(usually up to 4 hours), as well as a ventilation period before occupants can return. HED does
not have concerns for post-application inhalation exposure resulting from indoor fogger
applications of cypermethrins.
Page 62 of 138
Combining Exposure and Risk Estimates
Since adult (alpha-cypermethrin only) and child dermal and incidental oral exposure routes for
share a common toxicological endpoint, risk estimates have been combined for those routes
using the following formula:
Total MOE = Point of Departure (mg/kg/day) / Combined Dermal (mg/kg/day) + Incidental
Oral (mg/kg/day)
Although the inhalation exposure route shares a common toxicological endpoint, the post-
application inhalation exposure resulting from sprays which have settled (volatilization) on lawn,
indoor environments and pet collar use is anticipated to be negligible and therefore was not
combined with dermal and incidental oral exposure with one exception. The alpha-cypermethrin
post-application inhalation exposure resulting from mosquito vector control applications is not
considered to be negligible, and therefore is combined with dermal and incidental oral exposure
(for children only) using an aggregate risk index (ARI) approach since the LOCs for inhalation
exposure (adult = 30; child = 100) are different from the dermal exposure (adult = 100; and child
= 300) and incidental oral exposure (LOC = 300). The target ARI is 1; therefore, ARIs of less
than 1 are risk estimates of concern. The aggregate risk index (ARI) was calculated as follows.
Inhalation MOE)]
The incidental oral scenarios (i.e., hand-to-mouth and object-to-mouth) should be considered
inter-related and it is likely that they occur interspersed amongst each other across time.
Combining these scenarios with the dermal exposure scenario would be overly-conservative
because of the conservative nature of each individual assessment. Therefore, the post-
application exposure scenarios that were combined for children 1 to < 2 years old are the dermal
and hand-to-mouth scenarios. This combination should be considered a protective estimate of
children’s exposure.
Summary of Residential Post-application Non-Cancer Exposure and Risk Estimates

All the representative indoor and outdoor children’s dermal, incidental oral and combined post-
application scenarios resulting from exposures to cypermethrin and zeta-cypermethrin resulted in
MOEs greater than the LOC of 300 and are not of concern, with two exceptions:
 All children 1 to <2 years old combined dermal and incidental oral exposures resulting
from broadcast applications of cypermethrin to lawns using wettable powder formulation
(MOE = 94), and
 zeta-cypermethrin combined dermal and incidental oral exposures for children 1 to <2
years old resulting from contact of pets treated with pet collars are of concern (i.e., LOC
= 300 with MOEs ranging from 1.9 to 190).
All alpha-cypermethrin representative indoor and outdoor post-application scenarios for

adults and children are not of concern (i.e., MOEs ≥300) with the following exceptions:
 All children 1 to <2 years old incidental oral (MOE = 270), and combined dermal and
incidental oral exposures resulting from indoor perimeter and spot treatments (MOEs
ranging from 140 to 260), and
Page 63 of 138
 All children 1 to <2 years old combined dermal and incidental oral exposures resulting
from broadcast applications to turf (MOE = 270).
A summary of the registered residential post-application exposure and risk estimates for the
cypermethrins indoor and outdoor environments and pet uses is provided in Tables 6.2.3 through
6.2.9.
Page 64 of 138
Table 6.2.3 Children (1 < 2 years) Residential Post-application Non-cancer Exposure and Risk Estimates for Cypermethrin
MOEs2
Post-application Exposure Scenario Combined Routes
(Dermal LOC = 300)
Dose Combined
Formulation (Incidental Oral
(mg/kg/day)1 (X indicates included MOEs3
Use Site Route of Exposure LOC = 300)
in Combined MOE)
Dermal: Carpet 0.0046 1,600 X
Dermal - Mattress 0.0058 1,200 X 460*
Hand-to-mouth: Carpet 0.0051 1,400 X
Indoor- Object-to-Mouth - Carpet 0.002 3,500 NA
Perimeter/Spot/ Dermal: Hard surface 0.0046 1,600 X
Bedbug (Coarse) Hand-to-mouth: 1,100
0.0026 2,800 X
Hard surface
Object-to-Mouth –
0.001 5,300 NA
Hard Surface
1,300
Object-to-Mouth - Carpet 0.001 6,100 NA
Indoor
Dermal: Hard surface 0.0026 2,700 X
Perimeter/Spot/
Hand-to-mouth: 1,800
(Pin Stream) 0.0015 4,900 X
Hard surface
Liquid Object-to-Mouth
0.001 9,100 NA
Hard Surface
5,000
Object-to-Mouth - Carpet 0.0003 23,000 NA
Indoor Crack and Dermal: Hard surface 0.0007 10,000 X
crevice Hand-to-mouth: 6,700
0.00039 18,000 X
Hard surface
Object-to-Mouth
0.0002 34,000 NA
Hard Surface
Dermal 0.023 310 X
310
Hand-to-mouth 0.0035 2,000 X
High Contact Object-to-Mouth 0.0001 66,000
Lawn Activities NA NA
Soil Ingestion 0.000015 480,000
Wettable
Dermal 0.076 94 X 94
Powder
Page 65 of 138
Table 6.2.3 Children (1 < 2 years) Residential Post-application Non-cancer Exposure and Risk Estimates for Cypermethrin
MOEs2
(Dermal LOC = 300)
Dose Combined
Formulation (Incidental Oral
Use Site Route of Exposure LOC = 300)
in Combined MOE)
Hand-to-mouth 0.011 610 X

Object-to-Mouth 0.00035 20,000
NA NA
Soil Ingestion 0.000015 480,000
1. Dose (mg/kg/day) algorithms provided in 2012 Residential SOPs (https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-procedures-residential-pesticide) as well as
Appendix A.
2. MOE = POD ((7.16 mg/kg/day) ÷ Dose (mg/kg/day). Bolded risk estimates are of concern.
3. Combined MOE = 1 ÷ (1/dermal MOE) + (1/incidental oral MOE)]. where applicable.
3*. Combined MOE = 1 ÷ [(1/dermal carpet MOE) + (1/dermal mattress MOE) + (1/incidental oral MOE)].

Table 6.2.4 Children (1 < 2 years) Residential Post-application Non-cancer Exposure and Risk Estimates for Zeta-Cypermethrin
MOEs2
(Dermal LOC = 300)
Dose Combined
Formulation (Incidental Oral LOC =
Use Site Route of Exposure 300)
in Combined MOE)
770
Indoor- Hand-to-mouth: Carpet 0.0051 1,400 X
Perimeter/ Object to Mouth - Carpet 0.002 3,500 NA
Spot/Bedbug Dermal: Hard surface 0.0046 1,600 X
(Coarse) Hand-to-mouth: 1,000
0.0026 2,800 X
Not for Use Hard surface
On Mattress Object to Mouth –
0.001 5,300 NA
Hard Surface
Liquid Dermal: Carpet 0.0026 2,700 X
1,300
Indoor Object to Mouth - Carpet 0.001 6,100 NA
Perimeter/ Dermal: Hard surface 0.0026 2,700 X
Spot/Bedbug Hand-to-mouth: 1,800
(Pin Stream) 0.0015 4,900 X
Hard surface
Object to Mouth –
0.001 9,100 NA
Hard Surface
Dermal: Carpet 0.0007 10,000 X 5,000
Page 66 of 138
Table 6.2.4 Children (1 < 2 years) Residential Post-application Non-cancer Exposure and Risk Estimates for Zeta-Cypermethrin
MOEs2
(Dermal LOC = 300)
Dose Combined
Formulation (Incidental Oral LOC =
Use Site Route of Exposure 300)
in Combined MOE)
Object to Mouth - Carpet 0.0003 23,000 NA
Dermal: Hard surface 0.0007 10,000 X
Indoor Crack
Hand-to-mouth: 6,700
and crevice 0.00039 18,000 X
Hard surface
Object to Mouth –
0.0002 34,000 NA
Hard Surface
Dermal 0.0079 900 X
900
Liquid
Object-to-Mouth 0.00003 220,000
High Contact NA NA
Soil Ingestion 0.000005 1,400,000
Lawn
Dermal 0.0087 820 X
Activities 450
Solid Object-to-Mouth 0.00004 190,000
Soil Ingestion 0.000005 1,400,000 NA NA
Granular Ingestion 0.1 75
Appendix A.
2. MOE = POD (7.16 mg/kg/day) ÷ Dose (mg/kg/day) .Bolded risk estimates are of concern.
3. Combined MOE = ((7.16 mg/kg/day) ÷ Dermal Dose (mg/kg/day) + Incidental Oral Dose (mg/kg/day) or 1 ÷ [(1/dermal MOE) + (1/incidental oral MOE)], where applicable.
Page 67 of 138
Pet Collar:
Post-application assessments for the pet collars were performed assuming pet collars could be
either liquid or solid (dust) formulations, assuming 99/1, 50/50, and 1/99 liquid/dust ratios. All
children 1 to <2 years old incidental oral exposures to pets treated with pet collars are of concern
(i.e., MOEs <300). Table 5.2.5 provides a summary of the combined dermal and hand-to-mouth
exposure and risk estimates resulting from the pet collar formulations.
6.2.5 Residential Post-Application Incidental Oral Exposure Estimates from Zeta Cypermethrin Pet Collar Tag
using 99/1, 50/50 and 1/99 Ratios of Liquid/Solid Formulations for children (1-2 yrs.).
Combined
Maximum Liquid Dose
Route of Solid Dose MOEs1
Lifestage Use Site Application (mg/kg/day)
Exposure Pet Size (mg/kg/day) (LOC =
Rate
300)
99% Liquid/1% Solid
0.0009
small 0.048 2.08 100
YT-1601 Dog Tag lb ai/pet
10% ai Reg. No. Dermal & 0.0013
Child 39039-14 medium 0.031 1.34 160
HTM lb ai/pet
0.0018
large 0.026 1.13 190
lb ai/pet
50% Liquid/50% Solid
0.0009
small 0.048 2.08 6.7
10% ai Reg. No. 0.0013
Child 39039-14 Dermal & medium 0.031 1.34 10
lb ai/pet
HTM
0.0018
large 0.026 1.13 12
lb ai/pet
1% Liquid/99% Solid
0.0009
small 0.089 3.83 1.9
10% ai Reg. No. Dermal & 0.0013
Child 39039-14 medium 0.031 1.34 5.4
HTM lb ai/pet
0.0018
large 0.026 1.13 6.4
lb ai/pet
1. Combined MOE = Liquid Dose (mg/kg/day) + Solid Dose (mg/kg/day)
Episodic Granular Ingestion:

The zeta-cypermethrin incidental granular ingestion estimate resulted in a MOE of 75 which is
below the LOC. The default granular ingestion rate of 0.3 grams/day was adjusted to 0.045
grams/day (1/10 of the product) to reflect the amount of product applied on a per area basis (1
lb/1000ft2) as explained in the Residential SOP for Turf and Lawns. The reduction in ingestion
rate resulted in an estimated dose of 0.0143 mg/kg/day and a MOE of 100 which is below the
LOC for incidental ingestion of granules. However, ingestion of granules is considered an
episodic (or acute) event and not a routine behavior for children. Since HED does not believe
that this would occur on a regular basis, the scenario is considered to be an episodic poisoning
event rather than a short-term exposure typically assessed in HED’s human health risk
assessments. Furthermore, the registered label instructs the user to thoroughly water treated
Page 68 of 138
areas after application so that both granules and lawns are moistened to ensure granules dissolve
properly.
Table 6.2.6. Adult Residential Post-application Non-cancer Exposure and Risk Estimates for Alpha-cypermethrin
MOEs2
Dose Dermal LOC = 100
Formulation Use Site Route of Exposure ARI3
(mg/kg/day)1 Inhalation LOC = 30
Liquid Indoor- Dermal: Carpet 0.005 300

(micro- Perimeter/Spot/Bedbug Dermal: Hard surface 0.002 590
encapsulated) (Coarse) Not for Use On
Mattress
Indoor Dermal: Carpet 0.003 510
Perimeter/Spot/Bedbug Dermal: Hard surface 0.001 1,000
(Pin Stream) Not for Use
On Mattress
Indoor Crack and crevice Dermal: Carpet 0.001 1,900 NA
Dermal: Hard surface 0.0004 3,800
High Contact Lawn Dermal 0.0022 620
Activities
Gardens Dermal 0.0004 3,500
Trees Dermal 0.00004 38,000
Indoor Plants Dermal 0.000005 290,000
Mowing Turf Dermal 0.0000462 30,000
Golfing Dermal 0.000178 7,800
Mosquito Vector Control Dermal 0.0004 200,000 270
Truck Mounted Fogger Inhalation 0.0038 8,000
1. Dose (mg/kg/day) algorithms provided in 2012 Residential SOPs (https://www.epa.gov/pesticide-science-and-assessing-
pesticide-risks/standard-operating-procedures-residential-pesticide) as well as Appendix A.
2. MOE = POD (1.4 mg/kg/day) ÷ Dose (mg/kg/day). Bolded risk estimates are of concern.
3. ARI = 1/((100/200,000) + (30/8,000))
4. DFR = 0.259 (MRID 44685201). Adjusted DFR for application rate = 0.259 x (0.025 label rate/0.1 study rate) = 0.065
Table 6.2.7. Children (11<16 years) Residential Post-application Non-cancer Exposure and Risk Estimates for
Alpha-cypermethrin
Formulation Post-application Exposure Scenario Dose (mg/kg/day)1 MOEs2
Use Site Route of Exposure (Dermal LOC = 100)
Micro- Mowing Turf Dermal 0.000053 26,000
encapsulated Golfing Dermal 0.0002 6,700
Table 6.2.8. Children (6<11 years) Residential Post-application Non-cancer Exposure and Risk Estimates
for Alpha-cypermethrin
Formulation Post-application Exposure Scenario Dose (mg/kg/day)1 MOEs2
Use Site Route of Exposure (Dermal LOC = 100)
Liquid Gardens 0.0003 5,100
(micro- Trees 0.00003 56,000
Dermal
encapsulated) Indoor Plants 0.000003 430,000
Golfing 0.00024 5,700
Page 69 of 138
Table 6.2.9. Children (1 < 2 years) Residential Post-application Non-cancer Exposure and Risk Estimates for Alpha-cypermethrin
MOEs2
(Dermal LOC = 300)
Combined
Dose (Inhalation LOC = 100)
Formulation (X indicates MOEs3
(mg/kg/day)1 (Incidental Oral LOC =
Use Site Route of Exposure included in Or ARI4
300)
Combined MOE)
Mosquito Vector Dermal 0.0006 120,000 X
Control Truck Inhalation 0.0038 8,000 X 55 (ARI)
Mounted Fogger Hand-to-Mouth 0.000012 99,000 X
Dermal: Carpet 0.005 310 X
140 (MOE)
Hand-to-mouth: Carpet 0.005 270 X
Indoor-
Object-to-Mouth: Carpet 0.002 690 NA
Perimeter/Spot/Bed
Dermal: Hard surface 0.005 310 X
bug (Coarse)
Hand-to-mouth: 200 (MOE)
Not for Use On 0.003 550 X
Hard surface
Mattress
Object-to-Mouth:
0.001 1000 NA
Hard Surface
Dermal: Carpet 0.003 530 X
260 (MOE)
Hand-to-mouth: Carpet 0.003 480 X
Indoor
Perimeter/Spot/Bed
Dermal: Hard surface 0.003 530 X
Micro- bug (Pin Stream)
Hand-to-mouth: 350 (MOE)
encapsulated Not for Use On 0.001 950 X
Hard surface
Liquid Mattress
Object-to-Mouth:
0.001 1800 NA
Hard Surface
Dermal: Carpet 0.001 2,000 X 1,000
Hand-to-mouth: Carpet 0.001 1,800 X (MOE)
Indoor Crack and Dermal: Hard surface 0.001 2,000 X
1,300
crevice Hand-to-mouth:
0.0004 3,600 X (MOE)
Hard surface
Object-to-Mouth:
0.0002 6700 NA
Hard Surface
Dermal 0.0044 310 X
High Contact Lawn 270 (MOE)
Activities
Object-to-Mouth 0.00011 13,000 NA
Page 70 of 138
Appendix A.
2. MOE = POD (mg/kg/day) ÷ Dose (mg/kg/day). Bolded risk estimates are of concern.
3. Combined MOE = 1 ÷ [(1/dermal MOE) + (1/incidental oral MOE)], where applicable.
4. ARI (for mosquito use) = 1/((300/120,000) + (100/8,000) + (300/99,000))
Page 71 of 138
7.0 Aggregate Exposure/Risk Characterization
In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposure and
risk estimates from three major sources: food, drinking water, and residential exposures. In an
aggregate assessment, exposures from relevant sources are added together and compared to
quantitative estimates of hazard (e.g., a NOAEL or PAD), or the risk estimates themselves can
be aggregated. When aggregating exposures and risks from various sources, HED considers
both the route and duration of exposure.
7.1 Acute Aggregate Risk
Acute aggregate risk from exposure to the cypermethrins results from exposure to residues in
food and drinking water alone. The acute dietary exposure analysis included both food and
drinking water; therefore, acute aggregate risk estimates are equivalent to the acute dietary risk
estimates, as discussed in Section 5.4.3, above. Acute aggregate risk estimates are not of
concern for the general U.S. population or any population subgroup.
7.2 Short-Term Aggregate Risk Estimates
Short-term aggregate risk assessments are needed for adults and children exposed in residential
settings and through food and water; these assessments include exposure through the dermal and
inhalation route for adults, and from dermal, inhalation and incidental oral exposure for children.
Since the PODs and endpoints are based on cypermethrin data and there is concern for potential
increased toxicity of alpha-cypermethrin, a 5X potency factor was applied to the PODs and the
HECs/HEDs used for the alpha-cypermethrin risk assessments. Therefore, separate aggregate
exposure assessments were conducted for alpha-cypermethrin and cypermethrin/zeta-
cypermethrin. No additional factors were added to cypermethrin/zeta-cypermethrin risk
assessments since the PODs and endpoints selected were adequately protective.
As identified in the residential post-application section 6.2, certain exposure scenarios resulted in
risk estimates below their respective LOCs and are of concern. These exposure scenarios have
not been included quantitatively in the aggregate assessment since additional background
exposure from food and water would only increase the risk estimates. Of the remaining
residential exposure scenarios, HED selected only the most conservative, or worst case,
residential adult and children’s scenarios to be included in the aggregate estimates, based on the
lowest overall MOE (i.e., highest exposure and risk estimates).
The worst case cypermethrin/zeta-cypermethrin residential exposure for adults that is not of
concern resulted from applying cypermethrin with a sprinkler can to home gardens. The adult
oral LOC is equal to 100, while the inhalation LOC is equal to 30. Therefore, the ARI approach
was used to calculate aggregate exposure and risk for adults. An ARI ≥ 1 is not of concern. The
adult aggregate risk estimate is an ARI of 4.6 and is not of concern. The worst-case residential
exposures for children 1 to <2 years old that were not of concern resulted from post-application
exposure to treated lawns following use of broadcast application of cypermethrin. For children
(1to <2 years) the oral, dermal and incidental oral LOC is 300. Post-application inhalation
exposure resulting from treated lawns is anticipated to be negligible. The short-term aggregate
Page 72 of 138
risk estimated is an MOE of 300 for children 1 to <2 years old, and is not of concern. A
summary of the cypermethrin/zeta-cypermethrin aggregate assessments is provided in Table
7.2.1.
The worst case alpha-cypermethrin residential exposure for adults resulted from applying a
micro-encapsulated formulation to poultry/livestock housing using a backpack sprayer. The adult
dermal and oral LOC is 100, while the inhalation LOC is 30. Therefore, the ARI approach was
used to calculate aggregate exposure for adults. An ARI ≥ 1 is not of concern. The adult
aggregate assessment resulted in an ARI of 5 which is not of concern. The worst case residential
exposure for children 11 to <16 years old resulted from post-application dermal exposure from
golfing on treated turf. The worst case residential exposure for children 6 to <11 years old
resulted from post-application dermal exposure to treated gardens. The worst-case residential
exposure for children 1 to <2 years old resulted from post-application exposure to indoor hard
surfaces following perimeter and crack and crevice applications. Although the oral, dermal and
incidental oral LOCs for children are different from the inhalation LOC, the respective
residential scenarios included in the aggregate assessment result in negligible inhalation
exposure. Therefore, MOEs for the short-term aggregate risk assessment were calculated (and
included only oral, dermal and background dietary exposure). Aggregate risk estimates for
children 11-16 yrs., children 6-11 yrs., and children 1to < 2 yrs. resulted in MOEs of 3,600,
2,400 and 330, respectively, and are not of concern. The alpha-cypermethrin short-term
aggregate risk estimates are given in Table 7.2.2.
Equations used to determine the aggregate MOEs are given in Appendix F.
Page 73 of 138
Table 7.2.1: Short-Term Aggregate Risk Calculations for Cypermethrin and Zeta-cypermethrin
Aggregate Aggregate
Chronic Incidental Incidental Dermal Dermal
LOC for Inhalation Inhalation MOE ARI
Index Dietary Oral Oral Oral Residential Residential
Aggregate Residential Residential (food, water, (food, water,
Lifestage Exposure1 MOE1 Residential Residential Exposure2 MOE2
Risk Exposure2 MOE2 and and
(mg/kg/day) Exposure2 MOE2 (mg/kg/day)
residential)3 residential)4
Adult
Inhalation 0.0051
(59 -99 0.000231 31,000 NA NA NA NA 140 NA 4.6
LOC = 30
yrs.)
Children Dermal &
1 – 2 yrs. Incidental
Oral LOC =
300 0.000710 10,600 0.0035 2,000 0.02 310 NA NA 300 NA
Inhalation
LOC = 100
1. Dietary Exposure = See Table 5.4.3; Oral MOE = NOAEL (7.16 mg/kg/day)/Chronic Dietary Exposure (0.000237 or 0.000742 mg/kg/day)
2. Residential Exposure = Dermal, Inhalation and incidental oral exposures from for adults and children 1-2 yrs. see Tables 6.1. and 6.2.3.
3. Total Aggregate MOE = Short-term oral NOAEL (7.16 mg/kg/day)/(Child Dietary Exposure (mg/kg/day) + Incidental Oral Exposure (mg/kg/day) + Dermal
Exposure (mg/kg/day)). Values rounded to 2 significant figures.
4. Total Aggregate ARI = 1/(Adult Dietary LOC (100)/Adult Oral MOE) + (Inhalation LOC (30)/Inhalation MOE)
Page 74 of 138
Table 7.2.2: Short-Term Aggregate Risk Calculations for Alpha-cypermethrin
Aggregate Aggregate
Chronic Incidental Incidental Dermal Dermal
LOC for Inhalation Inhalation MOE ARI
Index Dietary Oral Oral Residential Residential
Aggregate Oral MOE1 Residential Residential (food, water, (food, water,
Lifestage Exposure1 Residential Residential Exposure2 MOE2
Risk Exposure2 MOE2 and and
(mg/kg/day) Exposure2 MOE2 (mg/kg/day)
residential)3 residential)4
Adult 0.00002
0.000231 6,000 0.00255 550 7400 NA 5
(59 -99 yrs.)
Children
11-16 yrs.
Residential; 0.000181
Dermal 7,700 0.0002 6,700 3,600 NA
Children
LOC =
13-19 yrs. 100 NA NA
Dietary
Inhalation
Children LOC = 30
6-11 yrs.
Residential; NA NA
0.000294 4,800 0.0003 5,100 2,400 NA
Children
6-12 yrs.
Dietary
Children Dermal
1 – 2 yrs. LOC =
300
0.000710 2,000 0.001 950 0.003 530 330 NA
Inhalation
LOC =
100
1. Dietary Exposure = See Table 5.4.3; Oral MOE = NOAEL (1.4 mg/kg/day)/Chronic Dietary Exposure (mg/kg/day)
2. Residential Exposure = Dermal, Inhalation and incidental oral exposures from for adults and children 1-2 yrs. see Tables 6.1. and 6.2.3.
3. Total Aggregate MOE = Short-term oral NOAEL (1.4 mg/kg/day)/(Dietary Exposure (mg/kg/day) + Residential Exposure (mg/kg/day)). Values rounded to 2
significant figures.
4. Total Aggregate ARI = 1/(Dietary LOC/Dietary MOE) + (Residential LOC/Residential MOE)
Page 75 of 138
8.0 Non-Occupational Spray Drift Exposure and Risk Estimates
Off-target movement of pesticides can occur via many types of pathways and it is governed by a
variety of factors. Sprays that are released and do not deposit in the application area end up off-
target and can lead to exposures to those it may directly contact. They can also deposit on
surfaces where contact with residues can eventually lead to indirect exposures (e.g., children
playing on lawns where residues have deposited next to treated fields). The potential risk
estimates from these residues can be calculated using drift modeling coupled with methods
employed for residential risk assessments for turf products.
The approach to be used for quantitatively incorporating spray drift into risk assessment is based
on a premise of compliant applications which, by definition, should not result in direct exposures
to individuals because of existing label language and other regulatory requirements intended to
prevent them. Direct exposures would include inhalation of the spray plume or being sprayed
directly. Rather, the exposures addressed here are thought to occur indirectly through contact
with impacted areas, such as residential lawns, when compliant applications are
conducted. Given this premise, exposures for children (1 to 2 years old) and adults who have
contact with turf where residues are assumed to have deposited via spray drift thus resulting in an
indirect exposure are the focus of this analysis analogous to how exposures to turf products are
considered in risk assessment.
Several cypermethrin, zeta-cypermethrin, and alpha cypermethrin products have existing labels
for use on turf; thus, it was considered whether the risk assessment for that use may be
considered protective of any type of exposure that would be associated with spray drift. It should
be noted that the registered residential uses on turf result in exposure greater than potential
exposure from spray drift; therefore, no new residential assessment needs to be completed. If the
maximum application rate on crops adjusted by the amount of drift expected is less than or equal
to existing turf application rates, the existing turf assessment is considered protective of spray
drift exposure.
The currently registered maximum single application rate of cypermethrin/zeta-cypermethrin and

alpha-cypermethrin for any crop/target site is ≤ 0.1 lb ai/A and 0.025 lb ai/A, respectively. The
highest degree of spray drift noted for any application method immediately adjacent to a treated
field (Tier 1 output from the aerial application using fine to medium spray quality) results in a
deposition fraction of 0.26 of the application rate. A quantitative spray drift assessment
for cypermethrin and zeta-cypermethrin is not required because the maximum application rate to
a crop/target site multiplied by the adjustment factor for drift of 0.26 is less than the maximum
direct spray residential turf application rate (0.44 lb ai/A for cypermethrin; 0.15 lb ai/A for zeta-
cypermethrin; and 0.085 lb ai/A for alpha-cypermethrin) for any cypermethrin, zeta-
cypermethrin, and alpha-cypermethrin products. The turf post-application MOEs have been
assessed for all cypermethrins, are based on the revised SOPs for Residential Exposure
Assessment (i.e., see above in Section 5.2), and are not of concern. However, since there were
risks of the concern from the direct turf use for the wettable powder formulation of cypermethrin
and liquid formulation for alpha-cypermethrin, a spray drift assessment was performed for
indirect exposures from registered agricultural uses.
Page 76 of 138
In order to evaluate the drift potential and associated risks for the wettable powder formulation
of cypermethrin, and liquid formulation for alpha-cypermethrin an approach based on drift
modeling coupled with techniques used to evaluate residential uses of pesticides was utilized.
Essentially, a residential turf assessment based on exposure to deposited residues has been
completed to address drift from the agricultural applications of cypermethrin. In the spray drift
scenario, the deposited residue value was determined based on the amount of spray drift that may
occur at varying distances from the edge of the treated field using the AgDrift (v2.1.1) model and
the Residential Exposure Assessment Standard Operating Procedures Addenda 1: Consideration
of Spray Drift Policy. Once the deposited residue values were determined, the remainder of the
spray drift assessment was based on the algorithms and input values specified in the recently
revised (2012) Standard Operating Procedures for Residential Risk Assessment (SOPs).
A screening approach was developed based on the use of the AgDrift model in situations where
specific label guidance that defines application parameters is not available.9,10 AgDrift is
appropriate for use only when applications are made by aircraft, airblast orchard sprayers, and
groundboom sprayers. When AgDrift was developed, a series of screening values (i.e., the Tier
1 option) were incorporated into the model and represent each equipment type and use under
varied conditions. The screening options specifically recommended in this methodology were
selected because they are plausible and represent a reasonable upper bound level of drift for
common application methods in agriculture. These screening options are consistent with how
spray drift is considered in a number of ecological risk assessments and in the process used to
develop drinking water concentrations used for risk assessment. In all cases, each scenario is to
be evaluated unless it is not plausible based on the anticipated use pattern (e.g., herbicides are
not typically applied to tree canopies) or specific label prohibitions (e.g., aerial applications are
not allowed). Section 6.1 provides the screening level drift related risk estimates.
In many cases, risks are of concern when the screening level estimates for spray drift are used as
the basis for the analysis. In order to account for this issue and to provide additional risk
management options additional spray drift deposition fractions were also considered. These drift
estimates represent plausible options for pesticide labels.
Summary of Non-occupational Spray Drift Exposure and Risk Estimates:

Exposures were considered for 50 feet wide lawns where the nearest side of the property was
directly adjoining the treated field (at field edge). Results are presented in Tables 8.1 (Adults)
and 8.2 (Children 1 < 2 years) and indicate that there are no risk estimates of concern. Adult
dermal MOEs range from 8,200 to 15,000 for alpha-cypermethrin. The combined (dermal +
incidental oral) MOEs for children (1 < 2 years) range from 5,300 to 9,000 for cypermethrin and
from 4,100 to 7,400 for alpha-cypermethrin.
9https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/models-pesticide-risk-assessment#AgDrift
10Note that for many cases the scenarios outlined in the screening approach represent actual use practice so risk assessors should
be aware and characterize these appropriately.
Page 77 of 138
Table 8.1. Adult Risk Estimates (MOEs) Related to Indirect Exposure to Spray Drift for the Dermal Route of Exposure.
MOEsb (Dermal LOC =
Crop/Rate Application Rate Estimated TTR 100)
Spray Type/ Nozzle Configuration
Group (lb ai/A) (ug/cm2)a
At Edge
Ornamentals, Typical and High Acreage Row Crops
Alpha-Cypermethrin
Aerial Fine to Medium 8,200
Groundboom High Boom Very fine to Fine 0.025 0.001 11,000
Airblast Sparse 15,000
a. Cypermethrin Estimated TTR (ug/cm2) = Application Rate (0.1 lb ai/A) * Fraction of Transferable ai (0.01) * Fraction of Residue
that dissipates in one day (0.1) * Conversion Factor (4.5E8) * Area unit Conversion Factor (2.7E-7) = 0.011 based on MRID 451115-
01. Adjusted TTR (ug/cm2) = (Application Rate (0.1 lb ia/A) *Study TTR ( 0.026 ug/cm2))/0.44 lb ai/a = 0.0059
b. Alpha-cypermethrin Estimated TTR (ug/cm2) = Application Rate (0.025 lb ai/A) * Fraction of Transferable ai (0.01) * Fraction of
Residue that dissipates in one day (0.1) * Conversion Factor (4.5E8) * Area unit Conversion Factor (2.7E-7) = 0.0027 based on MRID
451115-01 . Adjusted TTR (ug/cm2) = (Application Rate (0.025 lb ia/A) *Study TTR ( 0.026 ug/cm2))/0.44 lb ai/a = 0.0014
c. MOEs at various distances from field edge = dermal BMDL ([mg/kg/day) ÷ Dose (mg/kg/day), where the dermal dose is calculated
using the algorithms provided in the Turf Residential SOPs (http://www.epa.gov/pesticide-science-and-assessing-pesticide-
risks/standard-operating-procedures-residential-pesticide), and the TTR used in the calculations is the estimated TTR * drift fraction
of spray drift that deposits on lawns at various distances from the field edge (see Appendix A.1.7).
Table 8.2. Children (1 < 2 years) Risk Estimates (MOEs) Related to Indirect Exposure to Spray Drift for Combined Dermal and
Incidental Oral Routes of Exposure.
MOEsb (Dermal/Incidental
Crop/Rate Application Rate Estimated TTR Oral LOC = 300)
Spray Type/ Nozzle Configuration
Group (lb ai/A) (ug/cm2)a
At Edge
Ornamentals, Typical and High Acreage Row Crops
Cypermethrin
Alpha-Cypermethrin
m2
a. Cypermethrin Estimated TTR (ug/c ) = Application Rate (0.1 lb ai/A) * Fraction of Transferable ai (0.01) * Fraction of Residue
that dissipates in one day (0.1) * Conversion Factor (4.5E8) * Area unit Conversion Factor (2.7E-7) = 0.011 based on MRID 451115-
01. Adjusted TTR (ug/cm2) = (Application Rate (0.1 lb ia/A) *Study TTR ( 0.026 ug/cm2))/0.44 lb ai/a = 0.0059
b. Alpha-cypermethrin Estimated TTR (ug/cm2) = Application Rate (0.025 lb ai/A) * Fraction of Transferable ai (0.01) * Fraction of
Residue that dissipates in one day (0.1) * Conversion Factor (4.5E8) * Area unit Conversion Factor (2.7E-7) = 0.0027 based on MRID
451115-01 . Adjusted TTR (ug/cm2) = (Application Rate (0.025 lb ia/A) *Study TTR ( 0.026 ug/cm2))/0.44 lb ai/a = 0.0014
c. MOEs at various distances from field edge = dermal BMDL ([mg/kg/day) ÷ Dose (mg/kg/day), where the dermal dose is
calculated using the algorithms provided in the Turf Residential SOPs (http://www.epa.gov/pesticide-science-and-assessing-pesticide-
risks/standard-operating-
9.0 Non-Occupational Bystander Post-Application Inhalation Exposure and Risk Estimates
Volatilization of pesticides may be a source of post-application inhalation exposure to

individuals nearby pesticide applications. The agency sought expert advice and input on issues
related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act
Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on
March 2, 2010 (http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2009-0687-
0037). The agency has evaluated the SAP report and has developed a Volatilization Screening
Tool and a subsequent Volatilization Screening Analysis
(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219).
Page 78 of 138
During Registration Review, the agency will utilize this analysis to determine if data (i.e., flux
studies, additional route-specific inhalation toxicological studies) or further analysis is needed
for cypermethrins.
The Agency has also developed a preliminary bystander volatilization inhalation exposure
assessment for cypermethrins utilizing the currently available inhalation toxicity and air
monitoring data. The pesticide Air Monitoring Network (AMN) is the first multi‐year air
monitoring study conducted by DPR. DPR monitored a total of 37 chemicals which included
cypermethrin (i.e., 32 pesticides and 5 pesticide breakdown products) in three communities.
Pesticides monitored in the AMN study were selected based primarily on potential risk to human
health. http://www.cdpr.ca.gov/docs/emon/airinit/amn_2014_report_final.pdf
A total of 157 samples were collected for cypermethrin in 2014. The integrated ambient air
samples from 3 different locations throughout Salinas, Shafter and Ripon Counties were
collected. The sampling locations were chosen for their proximity to both known areas of
cypermethrin applications and human populations.
All reported results for the air concentration of cypermethrin were less than the established
method detection limit (MDL) of 4.7 ng/m3. Therefore, a quantitative risk assessment was not
conducted.
10.0 Cumulative Exposure/Risk Characterization
The Agency is required to consider the cumulative risks of chemicals sharing a common
mechanism of toxicity. The Agency has determined that the pyrethroids and pyrethrins share a
common mechanism of toxicity (http://www.regulations.gov; EPA-HQ-OPP-2008-0489-
0006). As explained in that document, the members of this group share the ability to interact
with voltage-gated sodium channels ultimately leading to neurotoxicity. In 2011, after
establishing a common mechanism grouping for the pyrethroids and pyrethrins, the Agency
conducted a cumulative risk assessment (CRA) which is available at http://www.regulations.gov;
EPA-HQ-OPP-2011-0746. In that document, the Agency concluded that cumulative exposures
to pyrethroids (based on pesticidal uses registered at the time the assessment was conducted) did
not present risks of concern. For information regarding EPA’s efforts to evaluate the risk of
exposure to this class of chemicals, refer to https://www.epa.gov/ingredients-used-pesticide-
products/pyrethrins-and-pyrethroids.
Since the 2011 CRA, for each new pyrethroid and pyrethrin use, the Agency has conducted a
screen to evaluate any potential impacts on the CRA prior to those uses being granted. Prior to a
final registration review decision for the cypermethrins, the Agency will determine whether the
2011 CRA needs to be updated based on the availability of any new hazard, use, or exposure
information that could potentially change the conclusions of or otherwise impact the 2011 CRA.
Page 79 of 138
11.0 Occupational Exposure/Risk Characterization
11.1 Occupational Hander Exposure/Risk Estimates
Based on the registered use patterns and current labeling, types of equipment and techniques that
can be used, occupational handler exposure is expected from the registered uses. The
quantitative exposure/risk assessment developed for occupational handlers is based on the
scenarios listed in Tables 11.1 -11.2.
Combining Exposures/Risk Estimates:

No dermal endpoint was selected for cypermethrin and zeta-cypermethrin; therefore, no handler
routes of exposure are combined. A total aggregate risk index (ARI) was calculated for alpha-
cypermethrin since the LOC values for dermal exposure (100) and inhalation exposure (30) are
different. The target ARI is 1; therefore, ARIs of less than 1 are risk estimates of concern. The
aggregate risk index (ARI) was calculated as follows.
Inhalation MOE)]
Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates

Occupational handler scenarios of cypermethrin and zeta-cypermethrin resulted in risk estimates
equal to or greater than the inhalation LOC (MOE ≥ 30) with baseline attire (i.e., no respirator),
and engineering controls for aerial applications with two exceptions:
 Mixing/loading/applying liquid formulations of cypermethrin with a mechanically
pressurized handgun to structural sites for control of termites (MOE = 28). Use of a
respirator with protection factor (PF) of 5 will result in an inhalation MOE of 140; and
 Mixing/loading/applying zeta-cypermethrin with handheld fogging equipment to
structural and industrial sites (MOE = 9.9). Use of a respirator with protection factor
(PF) of 5 will result in an inhalation MOE of 49. It should be noted that several
termiticide registered labels already require the use of respirator in non-ventilated areas;
other labels did not (i.e., Reg No. 70506-21).
Occupational handler scenarios for alpha-cypermethrin all resulted in risk estimates above the
level concern (ARI ≥ 1) with baseline attire (i.e., gloves and no respirator) and are not of
concern, with the following exceptions;
 Mixing/loading truck mounted fogger for mosquito vector control resulted in an ARI of
0.61 with baseline attire (i.e., no gloves or respirator) and is of concern. The use of gloves
would result in an ARI of 3.5, which is not of concern;
 Application of alpha-cypermethrin using truck mounted fogger for mosquito vector
control resulted in an ARI of 0.074 with baseline attire (i.e., no respirator) and is of
concern. Engineering controls are required to reach an ARI above the LOC (ARI = 8.9);
 Mixing/loading and applying alpha-cypermethrin with a manually pressurized handwand
to turf, poultry/livestock housings, foundation and perimeters resulted in risk estimates of
concern when using baseline attire and no respirator (ARIs = 0.2, 0.2, and 0.35
respectively). The use of gloves results in ARIs above the LOC (31, 33 and 55,
respectively); and
Page 80 of 138
 Mixing/loading and applying alpha-cypermethrin with a mechanically pressurized
handgun to poultry/livestock housings, structural termiticide use and typical field crops
resulted in risk estimates of concern when using baseline attire and no respirator (ARIs =
0.36, 0.9 and 0.54 respectively). The use of PF5 respirator and gloves for applications to
poultry housing, and gloves for structural termiticide applications and to field crops
would result in ARIs above the LOC (1.1, 1.7, and 1.6, respectively).
A summary of occupational handler risk estimates is provided in Tables 11.1, 11.2 and 11.3
below.
The Agency matches quantitative occupational exposure assessment with appropriate

characterization of exposure potential. While HED presents quantitative risk estimates for human
flaggers where appropriate, agricultural aviation has changed dramatically over the past two
decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of
their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily
from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide
applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent
(2012) NAAA survey. The Agency will continue to monitor all available information sources to
best assess and characterize the exposure potential for human flaggers in agricultural aerial
applications.
HED has no data to assess exposures to pilots using open cockpits. The only data available is for
exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the
engineering control (enclosed cockpits) and baseline attire (long-sleeve shirt, long pants, shoes,
and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls,
pilots are not required to wear protective gloves for the duration of the application. With this
level of protection, there are no risk estimates of concern for aerial applicators.
Water-soluble packaging is an engineering control designed to prevent direct contact between

users and the pesticide formulation in the packages, thereby reducing exposures. Users place the
packets into water which dissolves the packaging, releasing the formulation into the water
without exposure to significant dusts or liquid aerosols. The formulation within the packaging
then mixes with the water so it can be applied as a liquid spray.
This risk assessment relies on a 2015 study by the Agricultural Handler Exposure Task Force
(AHETF) that measured dermal and inhalation exposure for workers who mixed and loaded
water-soluble packet pesticide products. This data is considered the most reliable data for
conducting exposure and risk assessments for such products. During the initial stages of the
AHETF field study, the AHETF identified work practices that the Agency agreed were
inconsistent with the use of water-soluble packaging as an engineering control intended to reduce
exposures. For example, AHETF observed that some workers placed the packets in removable
baskets hanging from the open tank hatch and used streams of water from hoses or overhead
recirculation systems as agitation methods to break open and dissolve the packaging, resulting in
visible and substantial amounts of airborne powder and/or liquid aerosol where the mixer/loader
was working. Current labels, including those under consideration in this risk assessment, are
silent or unclear on the use of baskets in the hatch and methods of agitation.
Page 81 of 138
The AHETF, in consultation with the Agency, California’s Department of Pesticide Regulation
(CDPR) and the Canadian Pest Management Regulatory Agency (PMRA), drafted a set of best
practices for handling and adding water-soluble packets to spray tanks. The resulting AHETF
“mixing/loading water-soluble packet” dataset excludes monitoring results for activities
inconsistent with these practices. Commensurate with use of the new dataset, the Agency has
since formatted those best practices into label language to be included on all water-soluble
packet pesticide products. This revised language ensures that users know water-soluble packets
are intended to dissolve in water via mechanical agitation and not to rupture them via streams of
water or other means. In order to achieve the intended benefits from proper use of water-soluble
packaging, these best practices should be incorporated directly on product labels, conflicting
language should be removed from the same labels, and users should receive effective and timely
training on the new procedures.
Page 82 of 138
Table 11.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for the Registered Agricultural Uses of Cypermethrin
Exposure Scenario Crop or Target1 Maximum Inhalation Area Treated Inhalation Inhalation
Application Unit or Amount Dose MOE
Rate Exposure Handled (mg/kg/day) 4
(LOC = 30)5
3
Daily Acres
lb ai/A or lb (ug ai/lb)
or Gallons or
ai/gallon Baseline2
Animals
Mixer/Loader
Mixing/Loading Liquids for Aerial Application Orchards/Vineyards 350A 0.0000959 23,000
Field Crop, Typical 350A 0.0000959 23,000
Field Crop, High Acreage 1200A 0.000329 6,700
Mixing/Loading Liquid for Airblast application Orchards/Vineyards 40A 0.000011 200,000
Mixing/Loading Liquids for Chemigation Orchards/Vineyards
Application 0.1 lb ai/A 0.219
Field Crop, Typical 350A 0.0000959 23,000
Field Crop, High Acreage
Mixing/Loading Liquids for Groundboom Orchards/Vineyards 40A 0.000011 200,000
Application 0.0000219 100,000
Field Crop, Typical 80A
Applicator
Applying Sprays with Aerial Application Orchards/Vineyards 0.0049
350A 0.00000215 1,000,000
Equipment Field Crop, Typical (engineering
Field Crop, High Acreage control) 1200A 0.00000735 300,000
Applying Sprays with Airblast Application Orchards/Vineyards
0.1 lb ai/A 4.71 40A 0.000235 9,400
Equipment
Applying Sprays with Groundboom Application Orchards/Vineyards 40A 0.000017 130,000
Equipment Field Crop, Typical 0.34 80A 0.000034 65,000
Applying RTU (L) with sponge Application Animal (direct), livestock 0.00039 lb 8 Animals 0.00000811 270,000
208
Equipment ai/animal
Flagger
Flagging for Aerial Applications (Sprays) Orchard/Vineyard 0.1 lb ai/A 0.35 350A 0.000154 140,000
Mixing/Loading/Applying Liquid Formulations Landscaping, 0.0167 lb 69.1 40 gals 0.000578 3,800
with Backpack Sprayer trees/shrubs/bushes ai/gal
Page 83 of 138
(LOC = 30)5
3
Daily Acres
or Gallons or
ai/gallon Baseline2
Animals
Landscaping, turf (lawns,
athletic fields, parks, etc.)
Structural (termiticide) 0.08 lb ai/gal 30 0.0012 1,800
Animal (direct), livestock 0.0167 lb 30 0.00025 8,800
Foundations/perimeter ai/gal 2.58 0.0000215 100,000
Mixing/Loading/Applying Liquid Formulations Landscaping, 0.0167 lb 30 40 gals 0.00025 8,800
with a Manually Pressurized Handwand trees/shrubs/bushes ai/gal
Landscaping, turf (lawns,
Food handling establishment 1100 0.00919 240
Warehouse
Foundations/perimeter 30 0.00025 8,800
Mounds/nests
Residential Living Spaces 1100 0.00919 240
(homes, apartments)
Mixing/Loading/Applying Liquid Formulations Orchard/Vineyard 0.00033 lb 8.68 1000 gals 0.0000358 61,000
with a Mechanically Pressurized Handwand ai/gal
Landscaping, 0.0167 lb 8.68 0.00181 1,200
trees/shrubs/bushes ai/gal
Landscaping, turf (lawns, 0.44 lb ai/A 1.9 5A 0.0000523 42,000
Structural (termiticide) 0.08 lb ai/gal 79 1000 gals 0.079 28
15.8 0.0158 140
PF 5
Respirator
Warehouse 0.0168 lb 79 0.0165 130
ai/gal
Field crop, typical 0.03 lb ai/gal 8.68 0.00325 680
Page 84 of 138
(LOC = 30)5
3
Daily Acres
or Gallons or
ai/gallon Baseline2
Animals
Mixing/Loading/Applying Wettable Powder Landscaping, turf (lawns, 0.0165 lb 69.1 40 gals 0.00057 3,900
(WSP) Formulation with Backpack Sprayer athletic fields, parks, etc.) ai/gal
Foundations/perimeter 2.58 0.0000213 100,000
Mixing/Loading/Applying Wettable Powder Landscaping, turf (lawns, 0.0165 lb 30 0.000248 8,900
(WSP) Formulation with a Manually Pressurized athletic fields, parks, etc.) ai/gal
Handwand Food handling establishment 1100 0.00908 240
Warehouse
Foundations/perimeter 0.0165 lb 30 0.000248 240
ai/gal
Residential Living Spaces 0.0165 1100 40 gals 0.00908 240
(homes, apartments)
Mixing/Loading/Applying Wettable Powder Landscaping, turf (lawns, 0.44 lb ai/A 18 5A 0.000495 4,400
(WSP) Formulation with a Mechanically athletic fields, parks, etc.)
Pressurized Handwand Warehouse 0.0165 79 1000 gals 0.0163 130
Animal (direct), livestock
1 Assessment is based on maximum registered cypermethrin application rate for each scenario. Crops were grouped according to registered application rates and applicable
exposure scenarios to cover all registered use sites Field Crop, Typical (Head and Stem Brassica, Leafy Brassica Greens, Head Lettuce, Bulb Vegetables), Field Crop, High
Acreage (Cotton) and Orchards/Vineyards (Pecan).
2 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (11/2016); Level of mitigation: No Respirator
3 Exposure Science Advisory Council Policy #9.1.
4 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (acre or gal) × Area Treated or Amount Handled (A or
gal/day) ÷ BW (80 kg).
5 Inhalation MOE = Inhalation POD (2.2 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
Page 85 of 138
Table 11.2. Occupational Handler Non-Cancer Exposure and Risk Estimates for the Registered Agricultural Uses of Zeta-Cypermethrin
Exposure Scenario Crop or Target1 Maximum Inhalation Unit Area Treated or Inhalation Inhalation
Application Exposure Amount Handled Dose MOE
Rate (ug ai/lb) Daily3Acres or (mg/kg/day)4 (LOC = 30)5
Gallons
lb ai/A or lb Baseline2
ai/gallon
Mixer/Loader
Mixing/Loading Liquids for Orchards/Vineyards 350A 0.0000479 46,000
Aerial Application Field Crop, Typical 350A 0.0000479 46,000
Mixing/Loading Liquid for Orchards/Vineyards 0.00000548
40A 400,000
Airblast application
Mixing/Loading Liquids for Orchards/Vineyards 0.05 lb ai/A 0.219
Chemigation Application Field Crop, Typical 350A 0.0000479 46,000
Field Crop, High Acreage
Mixing/Loading Liquids for Orchards/Vineyards 40A 0.00000548 400,000
Groundboom Application 0.000011 200,000
Field Crop, Typical 80A
Mixing/Loading Granules for Greenhouse (ornamentals, roses, cut
Tractor-drawn Spreader flowers, container stock, vegetables) 0.5 lb ai/A 1.7 60A 0.000638 3,400
Application
Applicator
Applying Sprays with Aerial Orchards/Vineyards 0.0049
350A 0.00000107 2,100,000
Application Equipment Field Crop, Typical (engineering
Field Crop, High Acreage control) 1200A 0.00000368 600,000
Applying Sprays with Airblast Orchards/Vineyards
0.05 lb ai/A 4.71 40A 0.000118 19,000
Application Equipment
Applying Sprays with Orchards/Vineyards 40A 0.0000085 260,000
Groundboom Application Field Crop, Typical 0.34 80A 0.000017 130,000
Equipment Field Crop, High Acreage 200A 0.0000425 52,000
Applying Granules with Greenhouse (ornamentals, roses, cut
Tractor-drawn Spreader flowers, container stock, vegetables) 0.5 lb ai/A 1.2 60A 0.00045 4,900
Equipment
Flagger
Page 86 of 138
Gallons
ai/gallon
Flagging for Aerial Orchard/Vineyard 0.0000766
0.05 lb ai/A 0.35 350A 29,000
Applications (Sprays)
Mixing/Loading/Applying Landscaping, trees/shrubs/bushes) and
Liquid Formulations with 69.1 0.00173 1,300
right-of ways
Backpack Sprayer Greenhouse (ornamentals, roses, cut
140 0.0035 630
flowers, container stock, vegetables),
Landscaping, turf (lawns, athletic 0.0000645 34,000
2.58
fields, parks, etc.)
Structural (termiticide) 30 0.00075 2,900
Animal (direct), livestock 0.05 lb 30 0.00075 2,900
Foundations/perimeter 2.58 40 0.0000645 34,000
ai/Gal
Mixing/Loading/Applying Industrial/commercial (tires, rail
Liquid Formulations with yards, junk yards, etc.), 8916
0.223 9.9
Fogging Equipment Foundations/perimeter, Structural No Resp
(handheld, portable, and (e.g., bridges, shipyards, home decks,
stationary) foundations), Structural (termiticide),
Field-grown ornamental crops, 1783
0.446 49
Greenhouse (ornamentals, roses, cut PF5 Respirator
flowers, container stock, vegetables
Mixing/Loading/Applying Greenhouse (ornamentals, roses, cut
Liquid Formulations with a flowers, container stock, vegetables),
Manually Pressurized Landscaping, trees/shrubs/bushes,
Handwand plants/flowers, turf (lawns, athletic
fields, parks, etc.), 0.00075 2,900
30
Industrial/commercial (tires, rail 0.05 lb ai/gal 40 gals
yards, junk yards, etc.),
Poultry/livestock house/horse
barn/feed lot, Animal (direct),
livestock
Food handling establishment, 1100 0.0275 80
Page 87 of 138
Gallons
ai/gallon
Warehouse
Mixing/Loading/Applying Orchard/Vineyard, Field crop, typical 0.005 lb
Liquid Formulations with a 8.68 0.000543 4,100
ai/gal
Mechanically Pressurized 1000 gals
Greenhouse (ornamentals, roses, cut 0.075
Handwand 0.05 lb ai/gal 120 29
flowers, container stock, vegetables),
Landscaping, turf (lawns, athletic
0.5 lb ai/A 1.9 5A 0.0000594 37,000
Structural (termiticide), Warehouse, 79 0.0494 45
Industrial/commercial (tires, rail 0.05 lb ai/gal 1000 gals
8.68 0.00543 410
yards, junk yards, etc.)
Loading/Applying Granules Greenhouse (ornamentals, roses, cut
Formulations with Belly flowers, container stock, vegetables),
grinder spreader Landscaping, trees/shrubs/bushes,
Industrial/commercial (tires, rail 0.5 lb ai/A 62 1A 0.000388 5,700
yards, junk yards, etc.), Landscaping,
turf (lawns, athletic fields, parks, etc.)
Loading/Applying Granules Greenhouse (ornamentals, roses, cut
Formulations with Rotary flowers, container stock, vegetables),
Spreader Landscaping, trees/shrubs/bushes,
Industrial/commercial (tires, rail 0.5 lb ai/A 10 5A 0.000313 7,000
yards, junk yards, etc.), Landscaping,
turf (lawns, athletic fields, parks, etc.)
Loading/Applying Dust Airports/landing fields, bathroom
Formulations with shaker can premises/hard surfaces,
commercial/industrial lawns,
commercial/ industrial premises,
commercial storages/warehouses, 0.00000037
commercial transportation facilities- 17500 1000ft2 0.000081 260
lb ai/ft2
nonfeed/nonfood, eating
establishments, electrical
supplies/equipment, food processing
plant premises, greenhouse-empty,
Page 88 of 138
Gallons
ai/gallon
greenhouses-in use, hospitals/medical
institutions (human/veterinary),
hold/domestic dwellings, ornamental
and/or shade trees, ornamental
herbaceous plants/nonflowering
plants/woody shrubs and vines,
paths/patios, recreational areas,
recreation area lawns, solid waste
containers, residential lawns, sewage
systems.
1. Assessment is based on maximum registered Zeta cypermethrin application rate for each scenario. Crops were grouped according to registered application rates and
applicable exposure scenarios to cover all registered use sites Field Crop, Typical (Animal Feed, nongrass, Brassica, Head and Stem, Berry Group 13, Brassica, Leafy
Greens, Grass, animal feed, Artichoke, globe, Peanuts, Sugarcane, Vegetables, bulb, Vegetables, cucurbit, Vegetables, fruiting, Vegetables, leafy, Lettuce, Head,
Vegetables, Root and Tuber (except sugar beet)), Field Crop, High Acreage (Alfalfa, Barley, Buckwheat, Oats, Rye, Wheat, Corn, Field, Corn, Sweet, Cotton, Canola,
Rapeseed, Crambe, Flax, Rice, Sorghum and Millet, Soybeans, Sunflower, Beet, sugar) and Orchards/Vineyards (Fruit, Citrus, Fruit, Pome, Fruit, Stone, Fruit, tropical
(avocado), Nut, Tree).
2. Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (11/2016); Level of mitigation: No Respirator
3. Exposure Science Advisory Council Policy #9.1.
4. Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (acre or gal) × Area Treated or Amount Handled (A or
5. Inhalation MOE = Inhalation POD (2.2 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
Page 89 of 138
Table 11.3. Occupational Handler Non-Cancer Exposure and Risk Estimates for the Registered Agricultural Uses of Alpha-Cypermethrin
Dermal Inhalation
Unit Unit Area Treated
Maximum Exposure Exposure or Amount Inhalation
Application Rate Dermal MOE Inhalation MOE
1 (ug ai/lb) (ug ai/lb) Handled Dermal Dose
Exposure Scenario Crop or Target Dose ARI8
lb ai/A or Daily3 (mg/kg/day)6 (LOC = 100)7 (LOC = 30)5
(mg/kg/day)4
lb ai/gallon Baseline Unless Acres or
Otherwise Stated2 Gallons
Mixer/Loader
Orchards/Vineyards 350A 0.00323 430 0.000024 18,000 4.3
Mixing/Loading
Field Crop, Typical 350A 0.00323 430 0.000024 18,000 4.3
Liquids for Aerial
Application Field Crop, High
1200A 0.0111 130 0.0000821 5,400 1.3
Acreage
Mixing/Loading
Liquid for Airblast Orchards/Vineyards 40A 0.000369 3,800 0.00000274 160,000 38
application
Mixing/Loading Orchards/Vineyards 0.025 lb ai/A 220

Liquids for Field Crop, Typical
0.219 350A 0.00323 430 0.000024 18,000 4.3
Chemigation Field Crop, High
Application Acreage
Mixing/Loading Orchards/Vineyards 40A 0.000369 3,800 0.00000274 160,000 38

Liquids for Field Crop, Typical 80A 0.000737 1,900 0.00000548 80,000 19
Groundboom Field Crop, High
Application 200A 0.00184 760 0.0000138 32,000 7.5
Acreage
220 0.023 61 0.61
Mixing/Loading Vector Control (e.g.
Liquids for Truck mosquitocides), 0.25 lb ai/A 37.6 250 A
0.0039 360 0.00017 2600 3.5
Mounted Fogger terrestrial areas Baseline &
gloves
Applicator
Applying Sprays Orchards/Vineyards
0.0049 350A 0.0000305 46,000 0.000000536 820,000 450
with Aerial Field Crop, Typical
2.08 (engineerin
Equipment g control) 1200A 0.000105 13,000 0.00000184 240,000 130
Acreage 0.025 lb ai/A
Applying Sprays
with Airblast
Orchards/Vineyards 1770 4.71 40A 0.00296 470 0.0000589 7,500 4.6
Application
Equipment
Page 90 of 138
Dermal Inhalation
(mg/kg/day)4
Applying Sprays Orchards/Vineyards 40A 0.000132 11,000 0.00000425 100,000 110

with Groundboom Field Crop, Typical 80A 0.000263 5,300 0.0000085 52,000 51
78.6 0.34
Equipment 200A 0.000658 2,100 0.0000213 21,000 20
Acreage
0.074
1770 4.71 0.186 7.5 0.0037 120
Applying Sprays Vector Control (e.g.
with Truck Mounted mosquitocides), 0.25 lb ai/A 14.6 250 A
Sprayer terrestrial areas Engineerin 0.068 0.0015 920 0.000053 8,300 8.9
g Controls
Flagger
Flagging for Aerial 0.025
Applications Orchard/Vineyard 11 0.35 350A 0.000161 8,700 0.0000383 11,000 70
(Sprays) lb ai/A
Greenhouse
(ornamentals, roses,
cut flowers, 13,200 140 0.001 13,000 0.0000084 52,000 120
container stock,
vegetables) 0.00012
lb ai/gal
Nursery
Mixing/Loading/ (ornamentals,
Applying Liquid 5,8400 69.1 0.00047 3,000 0.00000415 110,000 30
vegetables, trees,
Formulations with container stock) 40 gals
Backpack Sprayer
Structural
0.004 lb ai/gal 0.000657 2,100 0.0000585 7,500 19
(termiticide)
2,510 30
Poultry/livestock
house/horse 0.0098 lb ai/gal 0.00163 860 0.000148 3,000 7.9
barn/feed lot
Foundations/
0.0059 lb ai/gal 8,260 2.58 0.00327 430 0.00000761 58,000 4.3
perimeter
Mixing/Loading/ Greenhouse 0.0008 1,700 0.0000018 240,000 17
Page 91 of 138
Dermal Inhalation
(mg/kg/day)4
Applying Liquid (ornamentals, roses,

Formulations with a cut flowers,
Manually container stock,
Pressurized vegetables) 0.00012
Handwand 100,000
Nursery lb ai/gal
(ornamentals,
30
vegetables, trees,
container stock),
Landscaping, turf 100,000 0.071 20 0.2

(lawns, athletic 0.085 lb ai/A 430 5 acres 0.00016 2,800
fields, parks, etc.) 0.0003 4,600 31
(Gloves)
Food Handler
Establishments;
0.004 lb ai/gal 29,000 1,100 0.0077 180 0.0022 200 1.4
Residential Living
Spaces
Poultry/livestock 100,000 0.065 21 0.21

house/horse 0.0098 lb ai/gal 40 gals 0.000145 3,000
430
barn/feed lot 0.00028 4900 33
(Gloves)
30
100,000 0.039 35 0.35
Foundations/
0.0059 lb ai/gal 430 0.000088 5,000
perimeter 0.00017 8300 55
(Gloves)
6050 0.025 55 0.54
Mixing/Loading/ Orchards/Vineyards 0.0025 lb ai/gal 2050 8.68 0.000271 1,600
0.00859 160 1.6
Applying Liquid (Gloves)
Formulations with a Greenhouse
Mechanically (ornamentals, roses, 1000 gals
Pressurized cut flowers, 0.00012 lb ai/gal 3500 120 0.0007 2,000 0.00018 2,400 16
Handwand container stock,
vegetables)
Poultry/livestock 0.0098 lb ai/gal 1800 79 0.0295 47 0.00968 45 0.36
Page 92 of 138
Dermal Inhalation
(mg/kg/day)4
house/horse 640 15.8 (PF5

barn/feed lot 0.0105 130 0.0019 230 1.1
(Gloves) Respirator)
Nursery
(ornamentals,
0.00012 lb ai/gal 6050 8.68 0.0012 1,100 0.000013 34,000 11
vegetables, trees,
container stock),
Landscaping, turf
(lawns, athletic 0.085 lb ai/A 1140 1.9 5A 0.000812 1,700 0.0000101 44,000 17
1800 0.0121 120 0.9
Structural
0.004 lb ai/gal 640 79 0.0039 110
(termiticide) 0.00429 330 1.7
(Gloves)
1000 gals
6050 0.025 55 0.54
Field crop, typical 0.0025 lb ai/gal 2050 8.688.68 0.000271 1,600
0.00859 160 1.6
(Gloves)
1 Assessment is based on maximum registered alpha cypermethrin application rate for each scenario. Crops were grouped according to registered application rates and
applicable exposure scenarios to cover all registered use sites.
2 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (11/2016); Level of mitigation:
3 Exposure Science Advisory Council Policy #9.1.
4 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (acre or gal) × Area Treated or Amount Handled (A or
5 Inhalation MOE = Inhalation NOAEL (0.44 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
6 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated (A/day) x DAF (13.4%) ÷ BW (80
kg).
7 Dermal MOE = Dermal POD (1.4 mg/kg/day) ÷ Dermal Dose (mg/kg/day).
8 Aggregate Risk Index = 1/{[1/(Dermal MOE/Dermal UF (100))] + [1/(Inhalation MOE/Inhalation UF(30))]} where an ARI greater than 1.
Page 93 of 138
11.2 Occupational Post-application Exposure/Risk Estimates
11.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates
Agricultural and Commercial Outdoor Uses:

There are multiple potential sources of post-application inhalation exposure to individuals
performing post-application activities in previously treated fields. These potential sources
include volatilization of pesticides and resuspension of dusts and/or particulates that contain
pesticides. The agency sought expert advice and input on issues related to volatilization of
pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel
(SAP) in December 2009, and received the SAP’s final report on March 2, 2010
(http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2009-0687-0037). The agency
has evaluated the SAP report and has developed a Volatilization Screening Tool and a
subsequent Volatilization Screening Analysis
(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). During Registration
Review, the agency will utilize this analysis to determine if data (i.e., flux studies, additional
route specific inhalation toxicity studies) or further analysis is required for cypermethrins.
In addition, the Agency is continuing to evaluate the available post-application inhalation

exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the
Agency will continue to identify the need for and, subsequently, the way to incorporate
occupational post-application inhalation exposure into the agency's risk assessments.
Although a quantitative occupational post-application inhalation exposure assessment was not

performed, an inhalation handler exposure assessment was performed for occupational/
commercial handlers. Handler exposure resulting from application of pesticides is likely to result
in higher than post-application exposure. Therefore, it is expected that these handler inhalation
exposure estimates would be protective of most occupational post-application inhalation
exposure scenarios (with the exception of indoor termiticide applications).
Furthermore, inhalation exposure during dusty mechanical activities such as shaking and
mechanical harvesting is another potential source of post-application inhalation
exposure. However, the airblast applicator scenario is believed to represent a reasonable worst
case surrogate estimate of post-application inhalation exposure during these dusty mechanical
harvesting activities. The non-cancer inhalation risk estimate for commercial airblast application
is not of concern (i.e., MOE > 30).
The Worker Protection Standard for Agricultural Pesticides contains requirements for protecting
workers from inhalation exposures during and after greenhouse applications through the use of
ventilation requirements. [40 CFR 170.110, (3) (Restrictions associated with pesticide
applications)]
Commercial applicators do not typically return to the treated areas after an indoor commercial
pesticide application (sites such as warehouses, food handling establishments, and hotels, etc.)
and thus an occupational post-application inhalation exposure assessment was not performed for
commercial applicators.
Page 94 of 138
11.2.2 Occupational Post-application Dermal Exposure/Risk Estimates
Occupational Post-application Dermal Exposure Data and Assumptions

Dislodgeable Foliar Residue (DFR) Data: As noted in the residential post-application section, a
DFR study is available for alpha-cypermethrin (MRID 44685201), and these data were used in
the occupational post-application assessment.
Occupational Post-application Non-Cancer Dermal Risk Estimates

Using the short-term dermal toxicity POD and data from the cypermethrin DFR study, the MOEs
for post-application activities range from 180 to 2,800. The MOEs are above the LOC of 100 on
the day of treatment (i.e., day 0) and consequently the risk is not of concern. A summary of the
post-application exposure and risk assessment for alpha-cypermethrin is presented in Table
11.2.2.
Table11.2.2. Occupational Post- application Non-Cancer Exposure and Risk Estimates for Alpha-
Cypermethrin
Transfer
DFR1 Dermal Dose
Crop/Crop Group Activities Coefficient 2 MOE3
(µg/cm ) (mg/kg/day)2
(cm2/hr.)
Short- & Intermediate-Term
Alfalfa Irrigation (hand set) 1900 0.002 850
Tree nuts Scouting 580 0.001 2,800
Cucurbit Vegetables Irrigation (hand set) 1900 0.001 2,800
Fruiting Vegetables Irrigation (hand set) 1900 0.001 2,800
Leafy Vegetables Hand Weeding 4200 0.004 380
Legume vegetables (succulent
Irrigation (hand set) 1900 0.001 2,800
or dried except soybeans)
Corn (all) Detasseling, Hand 8800 0.06 0.008 180
Citrus Fruits Harvesting, Hand 1400 0.001 1,200
Roots and Tuber Vegetables Irrigation 1900 0.002 850
Sorghum (grain) and millet Irrigation (hand set) 1900 0.001 2,800
Soybeans Irrigation (hand set) 1900 0.001 2,800
Wheat and triticale Irrigation (hand set) 1900 0.001 2,800
Rice Irrigation (hand set) 1900 0.001 2,800
Cotton Mechanical Harvesting, Tramper 5050 0.0034 410
1 Predicted day zero DFR from MRID 446852-01 of 0.259 µg/cm2 Adjusted DFR for application rate = 0.259 x (0.025 label
rate/0.1 study rate) = 0.06
2 Daily Dermal Dose = [DFR (µg/cm2) × Transfer Coefficient × 0.001 mg/µg × 8 hr./day × 13.4 % (DAF)  BW (80 kg).
3 MOE = POD (1.4 mg/kg/day) / Daily Dermal Dose.
Restricted Entry Interval

Cypermethrins are classified as low toxicity via the dermal or inhalation routes of exposure
(Toxicity Categories III and IV). Additionally, mild irritation was seen in primary eye and skin
irritation studies, but no dermal sensitization was observed. Short-term post-application risk
estimates were not a concern on day 0 (12 hours following application) for all post-application
activities associated with the foliar uses of alpha-cypermethrin. Under 40 CFR 156.208 (c) (2),
if product contains only one ai and it is classified as Toxicity Category III or IV for acute dermal,
eye irritation or/and primary skin irritation, the product shall be assigned a 12-hour REI.
Page 95 of 138
Therefore, the [156 subpart K] Worker Protection Statement interim REI of 12 hours is adequate
to protect agricultural workers from post-application exposures to the cypermethrins.
12.0 Public Health and Pesticide Epidemiology Data
In support of this draft human health risk assessment for registration review, HED prepared two
separate reports of the incidents associated with cypermethrins. While cypermethrin and zeta-
cypermethrin are separate active ingredients, each registered in separate end-use products, they
were assessed together in this incident assessment because of the close similarity of their uses,
toxicity, and chemical characteristics (D444168, S. Recore, and E. Evans, 11/28/2017). . A
separate incident report was prepared for alpha-cypermethrin (D444324, S. Recore, and E.
Evans, 11/28/2017) and is summarized below.
Cypermethrin and Zeta-cypermthrin:

Cypermethrin and zeta-cypermethrin incidents were previously reviewed on January 3, 2012 (S.
Recore, D396106). At that time, there were 605 incidents for cypermethrin and zeta-
cypermethrin reported to Main IDS and 4,342 incidents reported to Aggregate IDS. It was
concluded that because of the relatively high frequency of cypermethrins exposures, HED
determined it would further evaluate cypermethrin acute poisoning events reported in the
available pesticide incident surveillance databases.
For cypermethrin and zeta-cypermthrin, an updated Tier I analysis of a broad set of available
incident data sets were reviewed. Trend analyses and summaries (root cause analysis) with
respect to incidents was performed, as well as additional analysis on a product-specific (as
opposed to active ingredient) basis. This updated Tier I cypermethrins analysis includes human
observation data from the following sources: OPP’s Incident Data System (IDS) database,
NIOSH SENSOR-Pesticides, the Agency-sponsored National Pesticide Information Center
(NPIC), and California’s Pesticide Incident Surveillance Program (PISP).
The current IDS analysis for cypermethrin and zeta-cypermethrin, from January 1, 2011 to
December 8, 2015, found 771 cases in Main IDS and 5200 incidents in Aggregate IDS. In the
Main IDS from 2012 to today, there are 3 single active ingredient incidents (moderate severity)
and 1 multiple (minor severity reported to the database involving alpha-cypermethrin). In
Aggregate IDS from 2012 to today (11/13/17), there were no incidents reported to the database
for alpha-cypermethrin. A query of SENSOR-Pesticides from 1998-2012 identifies a total of 947
incidents involving cypermethrins. A query of SENSOR 1998-2014 finds no cases for alpha-
cypermethrin. From January 1, 2010 to December 31, 2015, 94 human incidents involving
cypermethrin were reported to NPIC, and 198 cases were reported to PISP between 2010 and
2013 that involve the active ingredient, cypermethrin.
HED found that the acute health effects reported for cypermethrin are consistent among the
databases queried. These health effects primarily include respiratory, neurological,
gastrointestinal and dermal effects. HED did not identify any aberrant effects outside of those
anticipated. These effects are generally mild/minor to moderate and resolve rapidly.
The IDS incident trend for cypermethrin, from 2006 to 2014, was reviewed. These incidents are
primarily residential cases. The cypermethrin incident trend appears to be increasing until 2012
Page 96 of 138
and then decreases slightly. In SENSOR-Pesticides, cypermethrins cases have trended upward
over the 15-year span reviewed, with 8 cases reported in 1998 and 76 cases reported in 2012.
The majority of the SENSOR cases are residential. These cases were made ill primarily when
applying a product (mainly foggers) or from being in close proximity to a residential application.
In California PISP, the majority of cypermethrin cases were residential. Eighteen out of 180
cypermethrin cases in PISP were agricultural. The occupational cases in SENSOR primarily
occurred in indoor work settings such as offices and retail establishments. Overall, very few
agricultural cases involving cypermethrin have been reported in the databases.
The available incident data from IDS, NPIC, California PISP, and SENSOR-Pesticides similarly
report that the majority of cypermethrin incident cases are residential. Further, these datasets
suggest that most of the reported residential cypermethrin incidents involve the use of indoor
foggers or indoor sprays. Based on the narratives associated with the incident reports, many of
these incidents occur due to accidental exposure during application and post-application of the
product.
The high number of reported incidents is likely related to the fact that pyrethroids are now
among the most commonly used pesticides in residential settings (Hudson, 2013). Pyrethroids
are much less acutely toxic to humans than many older chemicals including
organophosphates. EPA cancelled almost all indoor organophosphate uses and now the
pyrethroids have, in many cases, replaced them for residential insect control, with a variety of
pyrethroid products now widely available to consumers. The residential use of pyrethroids
increased from less than 1 million pounds used in 2001 to 2–4 million pounds used in 2007. Due
to this increase in the availability and usage of pyrethroid products, an increase in the numbers of
acute illnesses and injuries from pyrethroids is expected. Pyrethroid cases are the most
commonly reported incidents in both SENSOR and the American Association of Poison Control
Centers (AAPCC) (Roberts, 2013) and while the majority are low in severity, EPA continues to
monitor the pyrethroid incidents for trends in exposure illness scenarios, symptoms and
products.
Although there are a high number of cypermethrins incidents reported to IDS and SENSOR-
Pesticides, we note that there was only one death reported to IDS which was under investigation
for malicious intent and has no further details. NPIC, SENSOR and PISP had no deaths reported
associated with cypermethrin. The majority (87%) of these incidents were classified as low
severity. Low severity means that a person alleged or exhibited some symptoms, but they were
minimally traumatic, the symptoms resolved rapidly and usually involved skin, eye or respiratory
irritation. Further, these cypermethrins cases generally involved products containing multiple
active ingredients. Incidents involving multiple pesticides are considered to provide less certain
information about the potential effects of exposure from a particular pesticide.
Alpha-cypermethrin:
From January 1, 2012 to November 13, 2017, there were four incidents involving alpha-
cypermethrin reported to the Incident Data System (IDS). A query of SENSOR-Pesticides 1998-
2013 identified no cases involving alpha-cypermethrin.
Page 97 of 138
The Agricultural Health Study (AHS) is a federally-funded study that evaluates associations
between pesticide exposures and cancer and other health outcomes and represents a collaborative
effort between the US National Cancer Institute (NCI), National Institute of Environmental
Health Sciences (NIEHS), CDC’s National Institute of Occupational Safety and Health
(NIOSH), and the US EPA. Alpha-cypermethrin is not included in the AHS, and therefore this
study does not provide information for this report.
Based on the low frequency and severity of alpha-cypermethrin incidents reported to both IDS
and SENSOR-Pesticides, there does not appear to be a concern at this time. The Agency will
continue to monitor the incident data and if a concern is triggered, additional analysis will be
conducted.
Page 98 of 138
13.0 References
D443172, Cypermethrins: Acute and Chronic Aggregate Dietary (Food and Drinking Water)
Exposure and Risk Assessments for Registration Review, D. Dotson, 12/14/2017
D269584, HED MARC Determination of Residues of Concern, Y. Donovan, 11/3/2000)
D443900, Cypermethrin, Zeta-cypermethrin, and Alpha-cypermethrin Occupational and

Residential Registration Review Risk Assessment, S. Tadayon, and M. Collantes, 12/20/2017
D378901/D385246, Cypermethrins: Tier I Drinking Water Exposure Assessment to Support

Registration Review, I. Maher, 2/22/2011
D444168, Cypermethrin and Zeta-cypermethrin: Tier I Update Review of Human Incidents and
Epidemiology for Draft Risk Assessment, S. Recore and E. Evans, 11/28/2017
D444324, Alpha-cypermethrin: Tier I Update Review of Human Incidents and Epidemiology for
Draft Risk Assessment, S. Recore and E. Evans, 11/28/2017
TXR# 0055252; Evaluation of the Carcinogenic Potential of Cypermethrins, Quest, 2/17/1998
D443898, Cypermethrin: Review of Determination of Transferable Residues on Turf Treated

with cypermethrin (MRID No. 451115-01); S. Tadayon, 10/26/2017
D443899, Cypermethrin: Secondary Review of “Determination of Dislodgeable Foliar Residues

of Cypermethrin from Mustard Green Plants”, MRID# 446852-01, S. Tadayon, 10/17/2017
D381210, Re-evaluation of the FQPA Safety Factor for Pyrethroid Pesticides, E. Scollon,
06/27/2011
D394576, Pyrethroid Cumulative Risk Assessment, K. Whitby, 10/04/2011
Page 99 of 138
Appendices
Appendix A. Toxicology Profile and Executive Summaries
A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for food and non-food uses for cypermethrins are listed below. Use of the new
guideline numbers does not imply that the new (1998) guideline protocols were used.
Table A1. Toxicology Requirements for the Cypermethrins (Cypermethrin,

Zeta-Cypermethrin, and Alpha-cypermethrin)
Guideline Number and Toxicity Study Required Satisfied
870.1100 Acute Oral Toxicity ................................................. yes yes
870.1200 Acute Dermal Toxicity ............................................ yes yes
870.1300 Acute Inhalation Toxicity ........................................ yes yes
870.2400 Primary Eye Irritation .............................................. yes yes
870.2500 Primary Dermal Irritation ........................................ yes yes
870.2600 Dermal Sensitization................................................ yes yes
870.3100 Oral Sub-chronic (Rodent) ...................................... yes yes
870.3150 Oral Sub-chronic (Non-Rodent) .............................. yes yes
870.3200 21-Day Dermal ........................................................ yes yes
870.3250 90-Day Dermal ........................................................ no -
870.3465 90/28-Day Inhalation ............................................... yes yes
870.3700 Developmental Toxicity (Rodent) ........................... yes yes
870.3700 Developmental Toxicity (Non-rodent) .................... yes yes
870.3800 Reproduction ........................................................... yes yes
870.4100 Chronic Toxicity (Rodent)....................................... yes yes
870.4100 Chronic Toxicity (Non-rodent) ................................ yes yes
870.4200 Oncogenicity (Rat) .................................................. yes yes
870.4200 Oncogenicity (Mouse) ............................................. yes yes
870.4300 Chronic/Oncogenicity .............................................. yes yes
870.5265 Mutagenicity: Gene Mutation - bacterial ................. yes yes
870.5380 Mutagenicity: Cytogenetics ..................................... yes yes
870.5450 Mutagenicity: Dominant Lethal Assay .................... yes yes
870.5550 Mutagenicity: Other Genotoxic Effects ................... yes yes
870.6100 Acute Delayed Neurotoxicity (Hen) ........................ no -
870.6100 90-Day Neurotoxicity (Hen) .................................... no -
870.6200 Acute Neurotoxicity Screening Battery (Rat) .......... yes yes
870.6200 90 Day Neuro. Screening Battery (Rat) ................... yes yes
870.6300 Developmental Neurotoxicity .................................. yes yes
870.7485 General Metabolism ................................................ yes yes
870.7600 Dermal Penetration .................................................. yes yes
870.7800 yes yes
Immunotoxicity........................................................
.........
Page 100 of 138

A.2. Toxicity Profile Tables
Table A.2a Acute Toxicity of Cypermethrin, Zeta-Cypermethrin and Cypermethrin Technical
Guideline
No. Study Type MRIDs # Results Toxicity Category
LD50 (M): 134.4 mg/kg
Acute Oral – rat
870.1000 41776115 LD50 (F): 86.0 mg/kg II
Zeta-Cypermethrin
Clinical signs of neurotoxicity observed.
LD50 (M): 247 mg/kg
LD50 (F): 309 mg/kg females
Acute Oral – rat
870.1000 00056800 Deaths: 150 mg/kg, usually in first day. II
Cypermethrin
Clinical signs of neurotoxicity, gait
abnormalities; some persisting to 14 days.
Acute Oral – rat
870.1000 47944061 LD50 (F): > 2000 mg/kg bw III
Alpha-Cypermethrin
Acute Dermal – rat 00056800 LD50 > 4920 mg/kg/day. Clinical signs of
III
Cypermethrin neurotoxicity.
870.1100
rabbit – Cypermethrin 00056800 Abraded skin: LD50 > 2460 mg/kg.
Lacrimation, discharge from the eye and
III
"nervous and shaking".
Acute Dermal – rat LD50 > 2000 mg/kg bw
870.1100 47944062 III
Alpha-Cypermethrin Males, females combined
LC50 (M): not calculated- considered to
be less sensitive
Acute Inhalation – rat
870.1200 42395702 LC50 (F): 2.5 (1.6-3.4) mg/L. IV
Cypermethrin
Clinical signs of neurotoxicity; MMAD
ranged from 2.22 to 2.62 µm
Acute Inhalation – rat LC50 (M): > 2.79 mg/L
870.1200 47944063 III
Alpha-Cypermethrin LC50 (F): > 2.29 mg/L
Primary Eye Irritation –
Slight redness of conjunctivae, chemosis
870.2400 rabbit 00056800 III
& discharge. Persisted to day 7.
Cypermethrin
Primary Eye Irritation – Moderate conjunctival redness and slight
870.2400 rabbit 47944064 to moderate conjunctival chemosis. III
Alpha-cypermethrin Reversed by 72 hours
Primary Skin Irritation – Slight to mild erythema on intact &
870.2500 rabbit 00056800 abraded skin. Reversed by 48 hours. IV
Cypermethrin Primary Irritation Index: 0.71
Moderately irritating
Primary Skin Irritation –
Slight to marked erythema, moderate
870.2500 rabbit 47944065 III
edema, scaling to severe scaling.
Alpha-cypermethrin
Reversed by 7 days.
Not a sensitizer in Buehler assay.
Dermal Sensitization – 00056800
870.2600 Moderate sensitizer in Magnusson N/A
Cypermethrin 40377701
Kligman Maximization method.
870.2600 Dermal Sensitization – 47944066 Not a sensitizer N/A
Alpha-cypermethrin
Page 101 of 138

Table A.2.b Subchronic, Chronic, and Other Toxicity*
Guideline Study Type MRID No. (year)/ Results
No Classification /Doses
870.3100 90-Day oral toxicity-rat: MRID 00056802 & NOAEL = 7.5 mg/kg/day
cypermethrin 92027034 LOAEL = 75 mg/kg/day based on
(1980)/supplementary decreased body weight in both sexes
ppm = 0, 75, 150 or 1500
mg/kg/day = 0, 3.75, 7.5 or
75
870.3100 90-Day oral toxicity-rat: MRID 41776101 NOAEL = 13.8 (M), 16.3 (F) mg/kg/day
zeta- cypermethrin (1990)/Acceptable LOAEL = 28.2 mg/kg/day (M) based on
ppm = 0, 10, 50, 150, 250, decreased body wt, body wt gain and food
500 or 900 consumption; at 55.7 mg/kg/day, mortality
mg/kg/day = M: 0, 0.6, 2.7, as well as decreased RBC, WBC, HGB &
8.4, 13.8, 28.2 or 55.7 HCT plus increase in BUN.
F: 0, 0.6, 3.3, 9.6, 16.3, 32.2 mg/kg/day (F) based on decreased body
32.2 or 65.2 wt, body wt gain and food consumption as
well as interference with estrous cycle and
decreased glucose; mortality at 65.2
mg/kg/day.
870.3100 90-Day oral toxicity-rat: MRID 47944068 NOAEL = 9.3 mg/kg/day
alpha-cypermethrin (1982)/Acceptable LOAEL = 29.6 mg/kg/day based on reduced
ppm = 0, 20, 60, 180, or body weights, body weight gains (M),
540 decreased food consumption in both sexes,
mg/kg /day = M: 0, 1.02, and gait changes (M).
1.74, 9.3 or 29.6
F: 0, 1.2, 3.8, 11.3 or 35
870.3150 90-Day oral toxicity-dog: MRID 44527002 NOAEL = 24.6 (M), 34.3 (F) mg/kg/day
cypermethrin (1994)/Acceptable LOAEL = 37.0 (M), 45.2 (F) mg/kg/day
ppm = 0, 300, 600, 800 or based on tremors as well as decreased body
1100 wt and body wt gains in both sexes.
mg/kg /day = M: 0, 10.4,
20.7, 24.6 or 37.0
F: 0, 12.2, 25.4, 34.3 or
45.2
870.3150 90-Day oral toxicity-dog: MRID 00112929 NOAEL = 12.5 mg/kg/day
cypermethrin (1977)/Unacceptable LOAEL = 37.5 mg/kg/day based on clinical
ppm = 0, 5, 50, 500 or 1500 signs (whole body tremors, exaggerated gait,
mg/kg/day = 0, 0.125, 1.25, ataxia, incoordination, hyperaesthesia,
12.5 or 37.5 licking & chewing of paws; diarrhea,
anorexia) & decreased body wt.
870.3150 90-Day oral toxicity-dog: MRID 47944069 NOAEL = 2.25 mg/kg/day
alpha-cypermethrin (1984)/Acceptable LOAEL = 6.75 mg/kg/day based on clinical
ppm = 0, 30, 90 or 270 signs (tremors, gait abnormalities, ataxia,
mg/kg/day= 0, 0.75, 2.25 or agitation, head nodding, and lip licking).
6.75
870.3200 21-Day dermal toxicity-rat: MRID 45010401 NOAEL = systemic: 1000 mg/kg/day.
zeta- cypermethrin (1999)/Acceptable LOAEL = not determined
mg/kg/day = 0, 100, 500 or
1000
870.3200 21-Day dermal toxicity-rabbit: MRID 00090035 NOAEL = Systemic nonabraded animals:
cypermethrin (1981)/Acceptable 200 mg/kg/day (Highest Dose Tested)
mg/kg/day = 0, 2, 20 or 200
Page 102 of 138

LOAEL = Systemic nonabraded animals: not
determined
Dermal: 200 mg/kg/day based on signs of
dermal irritation.
870.3465 21-Day inhalation toxicity-rat: MRID 43507101 NOAEL = 0.01 mg/L
cypermethrin (1994)/Acceptable LOAEL = 0.05 mg/L based on increased
mg/L = 0, 0.01, 0.05 or salivation.
0.25 (nose only)
870.3700a Prenatal developmental-rat: MRID 00056804, Maternal NOAEL = 35 mg/kg/day
cypermethrin 92027039 & 92027601 LOAEL = 70 mg/kg/day based on splayed
(1978)/Acceptable limbs, spasms & hypersensitivity to noise &
mg/kg/day = 0, 17.5, 35 or convulsions.
70 Developmental NOAEL = 70 mg/kg/day
(Highest Dose Tested).
LOAEL = not determined.
Updated: previous maternal
NOAEL/LOAEL based on decreased
BWG only.
870.3700a Prenatal developmental-rat: MRID 41776102 Maternal NOAEL = 12.5 mg/kg/day
zeta- cypermethrin (1990)/Acceptable LOAEL = 25 mg/kg/day, based on ataxia,
mg/kg/day = 0, 5, 12.5, 25 urine-stained abdominal fur, fecal-stained
or 35 perineal fur, decreased food consumption &
decreased body wt gain.
Developmental NOAEL≥35 mg/kg/day
LOAEL = not determined
870.3700a Prenatal developmental-rat: MRID 47944073 Maternal NOAEL = 9 mg/kg/day
alpha- cypermethrin (1994)/Acceptable LOAEL = 15 mg/kg/day based on decreased
mg/kg/day = 0, 3, 9 or body wt gain and food consumption, and
18/15 increased incidence of clinical signs
(unsteady gait, piloerection, limb splay, and
hypersensitivity to sound and touch).
Developmental NOAEL = 9 mg/kg/day
LOAEL = 15 mg/kg/day based on decreased
fetal weights (4%).
870.3700b Prenatal developmental-rabbit MRID 43776301 & Maternal NOAEL = 100 mg/kg/day
(1994)/Acceptable decreased body wt gain; anorexia,
mg/kg/day = 0, 100, 450 or abdomino-genital staining, decreased feces
700 & red or pink material in the pan (few does).
At 700, anorexia, abdomino-genital staining,
decreased feces & red or pink material in the
pan were observed.
LOAEL = >700 mg/kg/day (Highest Dose
Tested)
870.3700b Prenatal developmental-rabbit: MRID 00056805 Maternal NOAEL = 30 mg/kg/day
cypermethrin (1978)/Unacceptable LOAEL = not determined
[dosed by capsule] Developmental NOAEL = 30 mg/kg/day
mg/kg/day = 0 (empty), 0 LOAEL = not determined
(corn oil), 3, 10 or 30
870.3700b Prenatal developmental-rabbit: MRID 47944072 Maternal NOAEL = 15 mg/kg/day
alpha-cypermethrin
Page 103 of 138

(1994)/Acceptable LOAEL = 30 mg/kg/day based on a slight
mg/kg/day = 0, 3, 15 or 30 body weight loss and decreased food
consumption.
Note: At 35 mg/kg/day (range finding
study), body weight loss and markedly
reduced food consumption were observed
throughout dosing.
(Highest Dose Tested).
LOAEL = not determined
870.3800 Reproduction and fertility effects-rat MRID 00112912, Parental/Offspring NOAEL = 7.5
cypermethrin 42068504 & 92027040 mg/kg/day
(1982)/Acceptable LOAEL = 50/37.5 mg/kg/day based on
ppm = 0, 50, 150, or clinical signs, decreased body wt gain in
1000/750 (to 750 after wk both sexes, and decreased mean litter weight
12 due to severe gain during lactation.
neurological signs)
mg/kg/day = 0, 2.5, 7.5 or
50/37.5 [2 litters/
generation]
870.3800 Reproduction and fertility effects-rat MRID 00090040 Parental/Systemic NOAEL = 5 mg/kg/day
cypermethrin (1979)/Unacceptable LOAEL = 25 mg/kg/day based on decreased
ppm = 0, 10, 100, or 500 body wt gain.
mg/kg/day = 0, 0.5, 5 or 25 Offspring NOAEL = 5 mg/kg/day
[2 litters/generation] LOAEL = 25 mg/kg/day based on decreased
body wt gain (lactation day 21).
(Unacceptable study: not updated based on

current practices, decreased body weight
gain observed in isolation is not considered
adverse)
870.3800 Reproduction and fertility effects-rat MRID 41968204 Parental/Systemic NOAEL = 7 mg/kg/day
zeta-cypermethrin (1991)/Acceptable LOAEL = 27 mg/kg/day based on decreased
ppm = 0, 7.5, 25, 100, 375 body wt gain (most noticeable during
or 750 lactation) hypersensitivity to sound, and
mg/kg/day = 0, 0.5, 1.8, 7, increased relative brain wts. M & F; at 45
27 or 45 mg/kg/day, some neurotoxic clinical signs in
[1 litter/generation] a few animals (some mortality).
Offspring NOAEL = 7 mg/kg/day
LOAEL = 27 mg/kg/day based on decreased
body wt gain during lactation; at 45
mg/kg/day, pup mortality.
870.4100b Chronic toxicity-dog (capsule) MRID 00112909, NOAEL = 5 mg/kg/day

cypermethrin 42068503 & 92027037 LOAEL = 15 mg/kg/day based on body
(1982)/Acceptable tremors, gait abnormalities, uncoordination,
mg/kg/day = 0, 1, 5 or 15 disorientation & hypersensitivity to noise
plus decrease in body weight.
Updated: previous NOAEL/LOAEL
based on gastrointestinal effects
Page 104 of 138

870.4100b Chronic toxicity-dog (feeding) MRID 44536801 NOAEL = 6 mg/kg/day (M), 5.7 mg/kg/day
cypermethrin (1995)/Acceptable (F)
ppm = 0, 100, 200, 600 or LOAEL =20.4 mg/kg/day (M), 18.1
1100 mg/kg/day (F) based on decreased body wt
mg/kg/day = M: 0, 2.9, 6.0, & wt gains and clinical signs (tremors,
20.4, 33.9 excessive salivation, irregular gait); at 33.9
F: 0, 3.3, 5.7, 18.1, 38.1 mg/kg/day, mortality.
870.4100b Chronic toxicity-dog (feeding) MRID 47944070 NOAEL = 4.11 mg/kg/day (M); 4.29
alpha-cypermethrin 1995)/Acceptable mg/kg/day (F)
ppm = 0, 60, 120 or 240 LOAEL = 7.9 mg/kg/day (M); 8.45
mg/kg/day = M: 0, 2.02, mg/kg/day (F)based on clinical signs (skin
4.11 or 7.90 reddening, hair loss, and tail irritation)
F: 0, 2.18, 4.29 or 8.45
870.4200a Chronic Toxicity/ Carcinogenicity-rat MRID 00112910 & NOAEL = 75 mg/kg/day
cypermethrin 92027041 LOAEL = not determined
(1982)/Acceptable Updated: previous NOAEL/LOAEL
ppm = 0 #1, 0 #2, 20, 150 based on decreased BWG only.
or 1500
mg/kg/day = 0, 0, 1, 7.5 or
75
870.4200b Carcinogenicity-mice MRID 00112911 & NOAEL = 57 mg/kg/day
(1982)/Acceptable hematological changes.
ppm = 0 (control #1), 0 At 229 mg/kg/day, benign alveologenic
(control #2), 100, 400 or neoplasms were also observed in females
1600 Updated: previous NOAEL/LOAEL
mg/kg/day = 0 (control #1), based on increased liver weights only with
0 (control #2), 14, 57 or no corresponding enzyme changes or
229 histopathology.
[M = 97 weeks; F = 101
weeks]
870.4200b Carcinogenicity-mice MRID 47944071 NOAEL = 10.6 mg/kg/day
alpha-cypermethrin 1999)/Acceptable LOAEL = 35.2 mg/kg/day (M) based on
ppm = 0, 30, 100, or 300 decreased body weight, body weight gains,
mg/kg/day = M: 0, 3.0, and clinical signs
10.6 or 35.2 Updated: previous NOAEL/LOAEL
F: 0, 3.5, 11.5 or 37.7 based on decreased body weights of <
10%, decreased food efficiency of < 4%,
and limited clinical signs (ungroomed,
skin encrustation, and urine staining).
No evidence of carcinogenicity
870.5100 Salmonella typhimurium & S. MRID 41968205 Weak mutagen effects noted at 10,000, 5000
cerevisiae reverse mutation assay (1992)/Acceptable and 3333 µg/plate in absence of metabolic
zeta-cypermethrin µg/plate = 0, 100, 333, activation in Salmonella strain TA100 in two
1000, 3333, 5000, 10000 studies. Strains TA98, TA1S3S, TA1537
and TA 1538 did not indicate mutagenic
effect in presence or absence of S-9
activation.
870.5100 Salmonella typhimurium & S. MRIDs 00090037, Negative up to doses of 2500 µg/plate.
cerevisiae reverse mutation assay 92027042, 92027062,
cypermethrin 00090036, 00126834
(1981)/Acceptable
Page 105 of 138

µg/plate = 4, 20, 100, 500,
2500
870.5300 In vitro cell gene mutation test MRID 41968206 Negative up to doses of 1000 µg/mL.
zeta-cypermethrin (1990)/Acceptable
µg/ml = 0, 1, 10, 25, 50,
100 (estimated limit of
solubility), 400, 700 and
1000
870.5380 in vivo cytogenetics MRIDs 0090038, No evidence of structural chromosomal
cypermethrin 92027043 aberrations in rat bone marrow at 20 or 40
(1980)/Acceptable mg/kg.
mg/kg = 0, 20, 40 mg/kg
870.5450 Dominant lethal assay in the rodent MRID 00090039 No evidence of dominant lethal activity in
cypermethrin (1980)/Acceptable CD-1 strain mice up to 10 mg/kg/day for
mg/kg/day = 0, 2.5, 5, 7.5, five consecutive days.
10 for 5 days
870.5550 Unscheduled DNA synthesis in MRID 41599801 No unscheduled DNA synthesis was
mammalian cells in culture (1990)/Acceptable observed at any dose level up to 200 mg/kg
cypermethrin mg/kg = 100, 200 in corn oil in Alpk:APfSD strain rats (males)
assessed 4 and 12 hours post dosing. 200
mg/kg dose was considered near the MTD.
870.5550 Unscheduled DNA synthesis in MRID 41968207 Negative up to doses of 4500 µg/mL
mammalian cells in culture (1989)/Acceptable
zeta-cypermethrin µg/ml = 0, 14, 45, 140, 450
1400 and 4500
870.6200a Acute neurotoxicity screening battery- MRID 43152001 NOAEL = 30 mg/kg/day
rat (1994)/Acceptable LOAEL = 100 mg/kg based primarily on
cypermethrin mg/kg = 0, 30, 100 or 200 ataxia and related conditions (staggered or
4, 0.6, 2, 4 ml/kg corn oil impaired gait, decreased activity, splayed
hindlimbs and limp conditions in addition to
decreased motor activity in males and
females.
rat (1998)/Acceptable LOAEL = 50 mg/kg/day based on clinical
zeta-cypermethrin mg/kg/day = 0, 10, 50 or signs (abdominogenital staining, oral
250 discharge, splayed hindlimbs, staggered gait
& tremors); FOB findings (abnormal mobile
posture, splayed hindlimbs, soiled fur &
unable to walk); at 250 mg/kg/day, more
severe findings.
rat: (1993)/Nonguideline (no LOAEL = 20 mg/kg/day based on clinical
alpha-cypermethrin positive control data) signs (gait abnormalities, prostration,
mg/kg/day = 0, 4, 20, or 40 thrashing, vocalization, piloerection,
0.67, 3.33, and 6.67 mL/kg unkempt appearance), FOB findings (limb
to achieve doses of 4, 20, abnormalities and increased reactivity), and
and 40 mg/kg, respectively. mortality. At 40 mg/kg/day, clinical
The control received 6.67 neurotoxic signs, FOB effects, mortality, and
mL/kg of corn oil. slight nerve degeneration.
870.6200b Subchronic neurotoxicity screening MRID 43152002 NOAEL = 31 mg/kg/day
battery-rat: 1993/Acceptable LOAEL = 77 mg/kg/day based on the
cypermethrin ppm = 0, 500, 1300 or 1700 following: males: decreased body weight
Page 106 of 138

mg/kg/day = M: 0, 31, 77 gain and increased landing foot splay;
or 102 females: ataxia, splayed hindlimbs, impaired
F: 0, 37, 95 or 121 gait and decreased feces as well as decreased
body weight gain.
870.6200b Subchronic neurotoxicity screening MRID 44962202 NOAEL = 5.0 mg/kg/day (M); 31.5
battery-rat: (1999)/Acceptable mg/kg/day (F)
zeta-cypermethrin ppm = 0, 75, 400 or 750 LOAEL = 26.3 mg/kg/day (M) based on
mg/kg/day = M: 0, 5.0, decreased motor activity, increased landing
26.3 or 47.2 foot splay, and decreased body weights,
F: 0, 5.9, 31.5 or 55.6 body weight gains, and food consumption;
55.6 mg/kg/day (F) based on decreased body
weights, body weight gains, and food
consumption.
870.6300. Developmental neurotoxicity-rat: MRID 46670402 Maternal: NOAEL= 17.3 mg/kg/day
zeta-cypermethrin (2005)/Acceptable/ Non- LOAEL= not determined
guideline. Offspring: NOAEL = 7.4 mg/kg/day
ppm = 0, 50, 125 or 300 LOAEL = 17.3 mg/kg/day based on
mg/kg/day = 0, 2.9, 7.4 or decreased body weight (5-10%)
17.3.
870.7485 Metabolism and pharmacokinetics-rat: MRID 41551102 -04 > 70% of the radiolabel was excreted within
cypermethrin (1977- 78)/Acceptable 24 hours, with >53% in the urine and <20%
0.61 mg/animal; 1.3 mg/kg; in the feces in males. However, in females,
1 mg/kg or less cis was excreted equally in urine and feces,
approximately 35% of the administered dose
(AD) via each route. Less than 1% of the
AD was expired in the air. Radiolabel was
retained in fatty tissues after dosing with the
cis and trans isomers, with little reduction
from day 1 to day 8.
870.7485 Metabolism and pharmacokinetics- MRID 43261603 Mean total DCVA excretion was 0.33% of
human (1992)/Acceptable the administered dose. However, considering
cypermethrin 31.03 mg that DCVA is further metabolized this value
would under estimate dermal absorption.
The sum of 3PBA and 4OH3PBA excretion
ranged from 0.85 to 1.77% (mean 1.23%).
Because cypermethrin is hydrolyzed to yield
equimolar quantities of DCVA and 3PBA
these values are not additive.
870.7485 Metabolism and pharmacokinetics-rat MRIDs 47944080; A single dose of 2 or 200 mg/kg of benzyl or
alpha-cypermethrin 47944081; 47944083 cyclopropyl labeled cypermethrin resulted in
(1982;1983;1980)/ total recovery of 94-95% administered dose
Acceptable/nonguideline in the excretion and tissue distribution
groups. Approximately half of the dose was
absorbed, and the dose was quickly
eliminated. Absorption, based on
radioactivity found in the urine, cage wash,
liver, skin, brain, gonads, adrenals, spleen,
lung, kidney, fat, muscle, and residual
carcass, was at least 53-55% AD (biliary
excretion was not evaluated). Most of the
dose was excreted within 24 hours (>76%
AD). After 4 days, slightly more of the dose
Page 107 of 138

was excreted in the urine (50-53% AD) than
in the feces (38-43% AD). Radioactive
residues in the cage wash, tissues, and the
residual carcass accounted for <2% AD
each.
870.7800 Immunotoxicity-rat MRID 48273201; NOAEL = 34 mg/kg/day
alpha-cypermethrin 48273202 LOAEL = not determined
(2010)/Acceptable
ppm = 0, 50, 150 or 450
mg/kg/day = 0, 4, 12 or 34
870.7600 Dermal penetration-rat MRID 47944084 The low dose (1.5 µg/cm2) provided the
alpha-cypermethrin (2006)/Acceptable most conservative estimate of total
absorption at 13% AD, and should be
considered for a dermal penetration factor in
risk assessment
Non- Metabolism and pharmacokinetics- MRID 47944082 Regardless of the dose or number of doses,
guideline human (1985)/Acceptable/ urinary excretion of free and conjugated
alpha-cypermethrin nonguideline cyclopropane carboxylic acid occurred
primarily within the first 24 hour period after
administration each day (30-75% AD). The
average excretion during this period
considering all subjects (and each day
following administration in the repeated
dose study) was 43% AD in the single study
and 49% AD in the repeated dose study.
Non- Acute Oral Toxicity in Rats – FOB MRID: N/A At ≥ 20 mg/kg/day, clinical signs observed
Guideline (McDaniel and Moser 1993.) (gait abnormalities (ataxia, tip toe walking,
cypermethrin limb dragging), decreased grip strength (4-
12%), and decreased motor activity
observed).
Non- Wolansky et. al. 47885701 BMDL1SD = 7.16
Guideline Acute Oral Toxicity in Rats - Motor (2006)/Acceptable BMD = 11.20
Activity
cypermethrin
Non- WIL Study 47050505 BMDL20 = 55.9
Guideline Acute Oral Toxicity in Rats – FOB (2006)/Acceptable BMD20 = 76.3
cypermethrin
*alpha-cypermethrin and zeta-cypermethrin are bridged to the database with cypermethrin. Therefore, studies for all three
chemicals are included.
Page 108 of 138

Appendix B. Physical/Chemical Properties
Table B.1. Physicochemical Properties of the Technical Grade Test Compound: Cypermethrin.
Parameter Value Reference
Melting point 80.5°C
pH Not Available
Density 1.23 g/mL at 25°C
Water solubility (25°C) 0.004 mg/L at 20°C
Solvent solubility miscible in acetone, acetonitrile, methylene
chloride, and toluene
Vapor pressure 1.4 x 10-9 mmHg at 20°C
Dissociation constant, pKa Not available
Octanol/water partition coefficient, 6.3
Log(KOW)
UV/visible absorption spectrum Not available
Table B.2. Physicochemical Properties of the Technical Grade Test Compound: Zeta-Cypermethrin.
Melting point 53-56°C MRID 46971402 1,
pH 4.5 (1% suspension) unless otherwise
noted.
Density 1.219 g/mL at 25°C
Water solubility (25°C) 45 ppb
Solvent solubility miscible in acetone, acetonitrile, methylene
chloride, and toluene
Vapor pressure 3 x 10-9 mm Hg at 20°C2
Dissociation constant, pKa Not available
Octanol/water partition coefficient, >6
Log(KOW)
UV/visible absorption spectrum Not available
1
Values as reported by the petitioner.
2
Cypermethrin: Phase 4 HED Risk Assessment for the Reregistration Eligibility Decision (RED). PC Code
109702; DP Barcode D293416. April 6, 2006.
Page 109 of 138

Table B.3 Physicochemical Properties of Technical Grade (95.4-99.0%) Alpha-Cypermethrin.
Melting point/range 81.4-83.7C FAO/WHO Evaluation Report
454/2005
pH Not available.
Density 1.33 g/cm3 47th Joint FAO/WHO Expert
Water solubility 2.06 µg/L (20°C)* Committee on Food Additives
Solvent solubility (21°C) Solvent Solubility (g/L) (JECFA 47) 1997
Acetone Miscible
Dichloromethane Miscible
Ethyl acetate 584
n-Hexane 6.5
Methanol 21.3
Toluene 596
2-Propanol 9.6
Vapor pressure 2.55 x 10-9 mm Hg (25C)
Dissociation constant, pKa Not available.
Octanol/water partition coefficient, 5.5 FAO/WHO Evaluation Report
Log(KOW) 454/2005
UV/visible absorption spectrum Not available.
* The water solubility of alpha-cypermethrin (98.0%), at 20°C in 0.01M buffers at pH values of approximately 4 to
9, ranges from 4.59 to 7.87 µg/L, as measured by the OECD and EEC microcolumn techniques. In distilled water
alone the solubility is slightly less (2.06 µg/L). The solubility is not strongly dependent on pH values within the
range of 4 to 9. It is likely that ionic strength differences account for differences in solubility between values in pure
water and in the buffer solutions.
Page 110 of 138

Appendix C. International Residue Limit Status Sheet
CYPERMETHRIN (11-17-2017)
Summary of US and International Tolerances and Maximum Residue Limits for Cypermethrin
US Canada Mexico1 Codex2
Residue Definition:
40 CFR 180.418(a)(1) cyano(3-phenoxy- cypermethrin (sum of
(S)-cyano(3-phenoxyphenyl)methyl (±)-cis-trans-3-(2,2- phenyl)methyl 3- isomers).
dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate (2,2-dichloro- The residue is fat soluble.
ethenyl)-2,2-
dimethylcyclo-
propanecarboxylate
Commodity Tolerance (ppm) / Maximum Residue Limit (mg/kg)
Commodity US Canada Mexico1 Codex
Brassica, head and stem, group 5-16 2.0 0.5 2.0 1
Brassica, leafy greens, subgroup 4-16B 14 0.1 (def)2 14 0.7
Cattle, fat 1.0 0.1 1 -
Cattle, meat 0.2 0.1 0.2 2
Cattle, meat byproducts 0.05 0.1 0.05 0.05
Cotton, gin byproducts 11.0 - - -
Cotton, undelinted seed 0.5 0.1 (def)2 0.5 0.1
Egg 0.05 0.03 0.05 0.01
Goat, fat 1.0 0.1 (def)2 1.0 -
Goat, meat 0.2 0.1 0.2 2
Goat, meat byproducts 0.05 0.1 0.05 0.05
Hog, fat 0.1 0.05 0.1 -
Hog, meat 0.05 0.05 0.05 2.0
Horse, fat 1.0 0.1 (def)2 1 -
Horse, meat 0.2 0.1 0.2 2
Horse, meat byproducts 0.05 0.1 0.05 0.05
Kohlrabi 2.0 0.1 (def)2 2 1
Lettuce, head 14 0.1 (def)2 4 0.7
Milk, fat (reflecting 0.10 in whole milk) 2.5 0.05 (milk) 2.5 0.05 (milk)
Onion, bulb 0.1 0.1 0.1 0.01
Onion, green 6.0 0.1 (def)2 6 -
Pecan 0.05 0.05 0.05 0.05
Poultry, fat 0.05 0.1 0.05 0.1
Poultry, meat 0.05 0.1 0.05 0.1
Sheep, fat 1.0 0.1 1 -
Sheep, meat 0.2 0.1 0.2 2
Sheep, meat byproducts 0.05 0.1 0.05 0.05
1
Mexico adopts US tolerances and/or Codex MRLs for its export purposes.
(def)2 = Canadian default MRL
cyano(3-phenoxyphenyl)methyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate
Page 111 of 138

Zeta-CYPERMETHRIN (11-17-2017)
Summary of US and International Tolerances and Maximum Residue Limits for Zeta-Cypermethrin
Residue Definition:
(S)-cyano(3-phenoxyphenyl)methyl (±)-cis-trans-3-(2,2- phenyl)methyl 3- isomers).
ethenyl)-2,2-
dimethylcyclo-
propanecarboxylate
Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)
Alfalfa, forage 15 - - -
Alfalfa, hay 30 - - 30 (fodder)
Alfalfa, seed 0.50 0.1 (def)2 0.5 -
Almond, hulls 6 0.1 (def)2 6 -
Animal feed, nongrass, group 18, forage 8 - - -
Animal feed, nongrass, group 18, hay 40 - - -
Artichoke, globe 0.60 0.1 0.6 0.1
Avocado 0.50 0.1 (def)2 0.5 -
Barley, grain 3.0 0.1 (def)2 3 2
Barley, hay 6.0 - - -
Barley, straw 20.0 - - -
Beet, sugar, roots 0.05 0.05 0.05 0.1
Beet, sugar, tops 0.20 0.1 (def)2 0.2 -
Berry group 13 0.8 0.1 (0.2 strawberry) 0.8 0.07 (strawberry)
Borage, seed 0.2 0.05 0.2 -
Brassica, head and stem, group 5-16 2.0 0.5 2 1
Buckwheat, grain 3.0 0.1 (def)2 3 0.3
Buckwheat, hay 6.0 - - -
Buckwheat, straw 20.0 - - -
Canistel 0.50 0.1 (def)2 0.5 -
Castor oil plant, refined oil 0.4 - - -
Castor oil plant, seed 0.2 0.1 (def)2 0.2 -
Cattle, fat 1.00 0.1 (def)2 1 -
Cattle meat 0.2 0.1 (def)2 0.2 2
Cattle, meat byproducts 0.05 0.1 (def)2 0.05 0.05
Chinese tallowtree, refined oil 0.4 - - -
Chinese tallowtree, seed 0.2 0.1 (def)2 0.2 -
Cilantro, leaves 10 0.1 (def)2 10 -
Citrus, dried pulp 1.8 - - -
Citrus, oil 4.0 - - -
Corn, field, forage 9.0 - - -
Corn, field, grain 0.05 0.05 0.5 0.3
Corn, field, stover 30 - - -
Corn, pop, grain 0.05 0.1 (def)2 0.5 0.3
Corn, pop, stover 30 - - -
Corn, sweet, forage 15.00 - - -
Corn, sweet, kernel plus cob with husks 0.5 0.05
0.05 0.05
removed
Corn, sweet, stover 15.00 - - -
Cotton, undelinted seed 0.5 0.1 0.5 0.1
Page 112 of 138

2
Crambe, seed 0.2 0.1 (def) 0.2 -
Cuphea, seed 0.2 0.05 0.2 -
Echium, seed 0.2 0.05 0.2 -
Egg 0.05 0.03 0.05 0.01
Euphorbia, refined oil 0.4 - - -
Euphorbia, seed 0.2 0.1 (def)2 0.2 -
Evening primrose, refined oil 0.4 - - -
Evening primrose, seed 0.2 0.1 (def)2 0.2 -
Flax, seed 0.2 0.05 0.2 0.1
Food/Feed handling establishments 0.05 - - -
Fruit, citrus, group 10-10 0.35 1 0.35 0.3 (0.5 grapefruit)
Fruit, pome, group 11-10 2 1 (apple), 2 (pear) 2 0.7 (apple and pear)
Fruit, stone, group 12-12 1 0.1 (def)2 1 2
Goat, fat 1.00 0.1 (def)2 1 -
Goat, meat 0.2 0.1 0.2 2
Goat, meat byproducts 0.05 0.1 0.05 0.05
Gold of pleasure, seed 0.2 0.05 0.2 -
Grain, aspirated fractions 10.0 - - -
Grape 2 0.5 2 0.2
Grass, forage, fodder, and hay, group 17, - -
10 -
forage
Grass, forage, fodder, and hay, group 17, - -
35 -
hay
Hare’s-ear mustard, seed 0.2 0.05 0.2 -
Hog, fat 1.0 0.05 0.1 -
Hog, meat 0.05 0.05 0.05 2
Horse, fat 1.00 0.1 (def)2 1 -
Horse, meat 0.2 0.1 0.2 2
Horse, meat byproducts 0.05 0.1 0.05 0.05
Jojoba, refined oil 0.4 - - -
Jojoba, seed 0.2 0.1 0.2 -
Lesquerella, seed 0.2 0.1 (def)2 0.2 -
Lunaria, seed 0.2 0.1 (def)2 0.2 -
Mango 0.70 0.1 (def)2 0.7 0.7
Meadowfoam, seed 0.2 0.1 (def)2 0.2 -
Milk fat (reflecting 0.10 in whole milk) 2.50 0.05 (milk) 2.5 0.05 (milk)
Milkweed, seed 0.2 0.05 0.2 -
Mustard, seed 0.2 0.05 0.2 0.1
Niger seed, refined oil 0.4 - - -
Niger seed, seed 0.2 0.1 (def)2 0.2 0.1
Nut, tree, group 14-12 0.05 0.05 0.05 0.05
Oat, grain 3.0 0.1 (def)2 3 2
Oat, hay 6.0 - - -
Oat, straw 20.0 - - -
Oil radish, seed 0.2 0.05 0.2 -
Okra 0.2 0.1 (def)2 0.2 0.5
Onion, bulb 0.10 0.1 (def)2 0.1 0.01
Onion, green 3.00 0.1 3 -
Papaya 0.50 0.1 0.5 0.5
Page 113 of 138

0.5 (cowpea) 0.05
0.05 (field pea)
Pea and bean, dried shelled, except soybean,
0.05 0.1 (def)2: (chickpea, 0.05
subgroup 6C
pigeon pea)
0.05 0.05 (broad & lima bean,

Pea and bean, succulent shelled, subgroup
0.1 0.5 cowpea, pigeon pea)
6B
0.7 (snap bean)
Peanut 0.05 0.05 0.05 0.1
Poppy, seed 0.2 0.05 0.2 0.1
Poultry, fat 0.05 0.1 0.05 0.1
Poultry, meat 0.05 0.1 0.05 0.1
Rapeseed 0.2 0.05 0.2 0.1
Rice, grain 1.50 0.1 1.5 2
Rice, hulls 6.00 - - -
Rice, wild, grain 1.5 0.1 (def)2 1.5 0.3
Rose hip, refined oil 0.4 - - -
Rose hip, seed 0.2 0.1 (def)2 0.2 -
Rye, grain 3.0 0.1 (def)2 3 2
Rye, hay 6.0 - - -
Rye, straw 20.0 - - -
Safflower, seed 0.2 0.1 (def)2 0.2 0.1
Sapodilla 0.50 0.1 (def)2 0.5 -
Sapote, black 0.50 0.1 (def)2 0.5 -
Sapote, mamey 0.50 0.1 (def)2 0.5 -
Sesame, seed 0.2 0.05 0.2 0.1
Sheep, fat 1.00 0.1 (def)2 1 -
Sheep, meat 0.2 0.1 0.2 2
Sheep, meat byproducts 0.05 0.1 0.05 0.05
Sorghum, grain, forage 0.1 - - -
Sorghum, grain, grain 0.5 0.1 (def)2 0.5 0.3
Sorghum, grain, stover 5.0 - - -
Soybean, seed 0.05 0.1 (def)2 0.5 0.7
Star apple 0.50 0.1 (def)2 0.5 -
Stokes aster, refined oil 0.4 - - -
Stokes aster, seed 0.2 0.1 (def)2 0.2 -
Sugarcane, cane 0.60 0.1 (def)2 0.6 0.2
Sunflower, refined oil 0.5 - - -
Sunflower, seed 0.2 0.1 0.2 0.1
Sweet rocket, seed 0.2 0.05 0.2 -
Tallowood, refined oil 0.4 - - -
Tallowood, seed 0.2 0.1 (def)2 0.2 -
Tea oil plant, refined oil 0.4 - - -
Tea oil plant, seed 0.2 0.1 (def)2 0.2 -
0.1 (def)2 0.2 0.07
Vegetable, cucurbit, group 9 0.2
(0.3 tomato)
0.2 0.2 (tomato), 0.1 (bell pepper)
0.1 (def)2
Vegetable, fruiting, group 8 0.2 2 (nonbell pepper)
(0.3 Tomato)
0.02 (eggplant)
Vegetable, leafy, except Brassica, group 4 14 0.1 (def)2 10 0.7
Vegetable, legume, edible podded, 0.5 0.05-0.7
0.5 0.5
subgroup 6A
Page 114 of 138

Vegetable, root and tuber, group 1, except 0.1 0.01
0.1 0.1
sugar beet
Vegetable, stalk, stem, and leaf petiole, 1: Celery 10 -
10
subgroup 22B 0.1 (def)2: Rhubarb
Vernonia, refined oil 0.4 - - -
Vernonia, seed 0.2 0.1 (def)2 0.2 -
Wheat, forage 3.0 - - -
Wheat, grain 0.2 0.1 (def)2 0.2 2
Wheat, hay 6.0 - - -
Wheat, straw 7.0 - 7 10
1
Page 115 of 138

Alpha-CYPERMETHRIN (11-17-2017)
Summary of US and International Tolerances and Maximum Residue Limits for Alpha-Cypermethrin
Residue Definition:
(R)-cyano(3-phenoxyphenyl)methyl (1S,3S)-rel-3-(2,2- phenyl)methyl 3- isomers).
ethenyl)-2,2-
dimethylcyclo-
propanecarboxylate
Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)
2
Alfalfa, hay 15 0.1 (def) 15 30
Beet, sugar, roots 0.05 0.1 (def)2 0.05 0.1
Beet, sugar, tops 0.20 0.1 (def)2 0.2 -
Brassica, head and stem, group 5-16 2.0 0.1 (def)2 2 1
Cattle, fat 1.0 0.1 (def)2 1 -
Cattle, meat 0.20 0.1 (def)2 0.2 2
Cattle meat byproducts 0.05 0.1 (def)2 0.05 0.05
Citrus, dried pulp 1.8 - - -
Citrus, oil 4.0 - - -
Corn, field, grain 0.05 0.1 (def)2 0.05 0.3
Corn, pop, grain 0.05 0.1 (def)2 0.05 0.3
Corn, sweet, kernel plus cob with husks 0.05 0.05
0.05 0.1 (def)2
removed
Cotton, undelinted seed 0.50 0.1 (def)2 0.2 0.1
Egg 0.05 0.1 (def)2 0.05 -
Food/Feed Handling Establishments 0.05 - - -
10 0.3 (orange, lemon, lime)
Fruit, citrus, group 10-10 10 0.1 (def)2
0.5 (grapefruit)
Goat, fat 1.0 0.1 (def)2 1 -
Goat, meat 0.20 0.1 (def)2 0.2 2
Goat, meat byproducts 0.05 0.1 (def)2 0.05 0.05
Hog, fat 1.0 0.1 (def)2 1 -
Hog, meat 0.05 0.1 (def)2 0.05 2
Horse, fat 1.0 0.1 (def)2 1 -
Horse, meat 0.20 0.1 (def)2 0.2 2
Horse, meat byproducts 0.05 0.1 (def)2 0.05 0.05
Milk, fat, reflecting 0.10 pm in whole milk 2.5 0.1 (def)2 (Milk) 2.5 0.05
Nut, tree, group 14-12 0.05 0.1 (def)2 0.05 0.05
Pea and bean, dried shelled, except soybean, 0.05 0.05 (chickpea, lentil)
0.05 0.1 (def)2
subgroup 6C 0.7 (guar)
Pea and bean, succulent shelled, subgroup 2 0.05 0.05
0.10 0.1 (def)
6B
Poultry, fat 0.05 0.1 (def)2 0.05 0.1
Poultry, meat 0.05 0.1 (def)2 0.05 0.1
Rice, grain 1.5 0.1 (def)2 1.5 2
Sheep, fat 1.0 0.1 (def)2 1 -
Sheep, meat 0.20 0.1 (def)2 0.2 2
Sheep, meat byproducts 0.05 0.1 (def)2 0.05 0.05
Sorghum, grain, grain 0.50 0.1 (def)2 0.5 0.3
Soybean, seed 0.05 0.1 (def)2 0.5 0.7
Vegetable, cucurbit, group 9 0.20 0.1 (def)2 0.2 0.07
Page 116 of 138

Summary of US and International Tolerances and Maximum Residue Limits for Alpha-Cypermethrin
0.2 0.2 (tomato), 0.1 (bell pepper)
Vegetable, fruiting, group 8-10 0.20 0.1 (def)2 2 (nonball pepper)
0.03 (eggplant)
Vegetable, leafy, group 4 10 0.1 (def)2 10 0.7
Vegetable, legume, edible podded, subgroup 2 0.05-0.7 0.5
0.50 0.1 (def)
6A
Vegetable, root and tuber, group 1, except 0.1 0.01
0.10 0.1 (def)2
sugar beet
Wheat grain 0.20 0.1 0.2 2
1
Page 117 of 138

Appendix D. Summary of Use Directions
Table D.1: Summary of Representative Registered Occupational/Commercial Products and Use Directions
Method of Application Use Site Product and Maximum Maximum Maximum Use Directions,
Formulation Application No. Seasonal Application Timing,
(Reg. No.) Rate1 Applications Application Type and Limitations
Rate
(lb ai/A)
Cypermethrin
Aerial, Ground Cotton Cyper G-AG 2.5 0.1 lb ai/A 10 0.4 lb ai/A Do not make applications
(groundboom and EC less than 5 days apart. Do
airblast) and 30.6% ai not graze or feed cotton for
Chemigation Insecticide Reg. forage. 12-hr REI.
No. 83222-7 PHI-14days
Head and Stem Brassica (2.5 lb ai/gal) 0.1 lb ai/A NS 0.6 lb ai/A Do not make applications
Leafy Brassica Greens Restricted Use 0.4 lb ai/A less than 7 days apart. 12-
Head Lettuce 0.6 lb ai/A hr REI.
Bulb Vegetables Battery 2.5 EC 0.1 lb ai/A 0.5 lb ai/A PHI – 1 to 21 days
Insecticide depending on the crop.
30.6% a.i. Pecans and bulb vegetables
Reg. No. also restrict grazing in
1381-188 treated areas or using cut
(2.5 lb ai/gal) treated crops/cover crops
Restricted Use for feed.
Ground (airblast) Pecans Ammo 2.5 EC 0.1 lb ai/A 0.5 lb ai/A

Equipment Insecticide
30.6% a.i.
Reg. No.
279-3027
(2.5 lb ai/gal)
Restricted Use
Page 118 of 138

Rate
(lb ai/A)
Trenching, rodding, sub- Buildings/Structures, Subterranean Cypermethrin 2.5 0.3% - 0.6% Reapply as NS Do not treat when raining.
slab injections, course (Pre-construction and post EC Termiticide/ emulsion Necessary Do not allow treatment to
fan spraying of soil construction soil treatment for Insecticide 30.6% concentrate runoff from target areas.
surfaces, crack and termite control) a.i. *0.0244 to Do not treat soil beneath
crevice void injections, Reg. No. 0.0488 structures that contain
Foam applications, spot 70506-21 lb ai/gal wells or cisterns.
treatment, course fan (2.5 lb ai/gal) **0.02 -
spray of wood Restricted Use 0.08 lb ai/gal
Demon Max 0.25 – 1.0
Insecticide 25.3% emulsion
a.i. Reg. No. concentrate
100-1218
(2 lb ai/gal EC)
Prevail FT
Termiticide 24.8
a.i. Reg No 279-
3082 (2 lb ai/gal
EC)
Manually Pressurized Indoor/ Outdoor Surface Direct Cypermethrin 2.5 Do not apply as a space
handwand Sprays for insect control EC Termiticide/ spray. Use only in well
Spot, Crack and Crevice Insecticide 30.6% *0.008 ventilated areas. Do not
a.i. lb ai/gal use concentrate or
Reg. No. (outdoor) – emulsion in fogging
70506-21 0.016 lb ai/gal equipment. Do not use in
(2.5 lb ai/gal) (indoor) warehouse or greenhouses
Restricted Use where raw agricultural
commodities or crops are
Demon Max grown or stored.
Insecticide 25.3%
a.i. Reg. No.
100-1218
(2 lb ai/gal EC)
Page 119 of 138

Rate
(lb ai/A)
Cyper-Active 2.14
EC
26% a.i.
Reg. No.
1021-2626
(2.14 lb ai/gal)
1 fl. oz.
Cynoff EC /1000ft2
Termiticide/ (cluster flies)
Insecticide 24.8%
a.i.
Reg. No.
279-3081
(2 lb ai/gal)
Lawns/Turf for Insect Control Cypermethrin 2.5 0.44 lb ai/A Do not water treated areas
EC Termiticide/ or to point of run-off or apply
Insecticide 30.6% lb ai/ 1000 ft2 when raining.
a.i. or
Reg. No. (0.00001 lb
70506-21 ai/ft2)
(2.5 lb ai/gal)
Restricted Use
Cyper-Active 2.14
EC
26% a.i.
Reg. No.
1021-2626
(2.14 lb ai/gal)
Crack and Crevice, Spot Indoor/ Outdoor Surfaces Cyper WSP 0.0086 - 0.017 Reapply as Reapply as Do not apply product to
Treatment using hand 40% a.i. lb ai/gal Necessary Necessary residential or institutional
areas, when occupants are
Page 120 of 138

Rate
(lb ai/A)
held equipment with Reg. No. 53883- (0.1 – 0.2% present in the immediate
coarse low pressure 340 concentration treated area.
of ai)
Demon WP
Broadcast application Lawns/Turf Insecticide in 0.44 lb ai/A Do not water treated areas
WSP 40% a.i. or to point of run-off or apply
Reg. No. 0.01 lb ai/ when raining.
100-1000 1000 ft2
Trenching, rodding, Outdoor perimeter barrier treatment Demon WP .67
wood injection – termites (pre and post construction) Insecticide in oz./1000ft2(4
(emulsion spray, foam) WSP 40% a.i. gal/10 ln ft./1
Reg. No. ft. deep)
100-1000
Broadcast application 0.93 lb ai/A
Wipe-on Roll-on Horses Farnam Crash! Apply 4 fl. oz. Using protective gloves or
Wipe-On over entire mitt apply 2-4 fl. oz. over
Insecticide/ body entire horses body
Repellent 0.00039 lb
0.15% ai ai/horse
Reg. No. 270-253
Zeta Cypermethrin
Aerial, Airblast, Alfalfa Liquid, Mustang 0.05 3 0.15 Foliar application, RTIs
Groundboom, and Animal Feed, nongrass Insecticide 0.05 3 0.15 are 3 to 21 days, and PHIs
Chemigation Artichoke, globe (EPA Reg # 279- 0.05 4 0.20 are 1-45 days depending
Barley, Buckwheat, Oats, Rye, 3126 0.05 5 0.25 on the crop. REI is 12 hrs.
Wheat
Beet, sugar 0.05 3 0.15
Berry Group 13 0.05 6 0.3
Brassica, Head and Stem 0.05 6 0.3
Brassica, Leafy Greens 0.05 6 0.3
Corn, Field 0.05 4 0.20
Corn, Sweet 0.05 3 0.15
Cotton 0.05 6 0.3
Page 121 of 138

Rate
(lb ai/A)
Canola, Rapeseed, Crambe, Flax 0.05 6 0.3
Legume Vegetables 0.05 6 0.3
Fruit, Citrus 0.05 4 0.20
Fruit, Pome 0.05 6 0.3
Fruit, Stone 0.05 6 0.3
Fruit, tropical (avocado) 0.05 6 0.3
Grass, animal feed 0.05 3 0.15
Nut, Tree 0.05 5 0.25
Peanuts 0.05 6 0.3
Rice 0.05 4 0.20
Sorghum and Millet 0.05 5 0.25
Soybeans 0.05 6 0.3
Sunflower 0.05 5 0.25
Vegetables, bulb 0.05 5 0.25
Vegetables, cucurbit 0.05 6 0.3
Vegetables, fruiting 0.05 6 0.3
Vegetables, leafy 0.05 6 0.3
Lettuce, Head 0.05 6 0.3
Vegetables, Root and Tuber (except 0.05 6 0.3
sugar beet)
Granule applicator Commercial/industrial lawns F6131 G 0.125 - 0.5 Reapply as 0.5 Do not make applications
premises, electrical Insecticide0.05% lb ai/A Necessary during rain.
supplies/equipment, greenhouse- ai Do not apply more than
empty, greenhouses-in use, Reg Nos. 0.25 lb ai/A on residential
household/domestic dwellings, 279-3342, sites. May be applied up to
industrial / construction areas 0.5 lb ai/A on non-
(outdoor), nonagricultural outdoor Ortho ZB FAK residential use sites.
buildings/structures, rights-of-way/, 0.05% ai 0.25 – 0.5
ornamentals, trees/ plants/shrubs and Reg. No. lb ai/A
vines/ recreational areas, athletic 279-2714
fields, parks and residential lawns.
Page 122 of 138

Rate
(lb ai/A)
Bulbous Duster Indoor residential, non-residential, Zeta-Cyp Dust 0.01- 0.016 lb Reapply as NS DO NOT apply this
Crack and crevice and Non Food/Feed areas of Food Insecticide ai/A or Necessary product directly to clothing
Handling Establishments, Outdoor 0.075% ai. or in food/feed areas of
surfaces, trees, shrubs, ornamentals, Reg No 279-3259 food handling
parks, athletic fields, parks and establishments, restaurants
lawns, sewers, ant mounds. or other areas where food
is commercially prepared
Telecommunication Conduits 0.67 g/cu ft. or processed.
RTI-7 days
Dust Bag or Direct Cattle, sheep, goats and horses Y-tex Python 2 oz /animal Reapply as NS RTI 3 days
application Dust Livestock Necessary
Insecticide,
0.075% Reg. No.
39039-9
Rotary Spreader Poultry Houses ZetaGard LBT 12.5 lb/ 500 Reapply as 50 lbs/ RTI 7 days. Do not apply
Insecticide, linear ft, 36" Necessary 20,000 ft2 with power dust equipment
0.375% Reg. No. band (1500 ft2) per 6 week
39039-20 0.41 lb ai/A period
Backpack sprayer or Animal Barns, indoor/outdoor hard Emulsifiable Reapply as NS Applying this product in
handheld equipment. surfaces, food/feed handling Concentrate 0.13 – 0.71 lb Necessary calm weather when rain is
establishments, home vegetable EVERCIDE ai /A not predicted for the next
gardens, ornamental trees/ground 28511 24 hours
cover/ plants/ shrubs and vines, solid 0.75% 0.00048 –
waste sites, residential lawns,parks, Reg Number 0.0125 lb
recreational and athletic fields, lawns 1021-1859 ai/gal
and turf
Indoor residential, non-residential, ZETA-CYP EW 0.05 – 1.14 Reapply as NS Do not apply this product
and Non Food/Feed areas of Food 17.1% lb ai/A Necessary to edible crops. Keep
Handling Establishments, Outdoor Reg Number. (0.1 - 0.4 fl people and pets off
surfaces, trees, shrubs, ornamentals, 279-3243 oz/1000 ft2) surfaces until dry.
parks, athletic fields, parks and
lawns, sewers, ant mounds 0.005 lb ai/gal
Page 123 of 138

Rate
(lb ai/A)
Hand Held equipment Spot and broadcast applications to Triple Crown Ornamentals -
(manually pressurized, golf course, sod farms, ornamentals, Golf Insecticide 0.000048 –
hose end sprayer) landscape, parks, athletic and 2.7% a.i. 0.00015
recreational fields Reg. No. lb ai/gal
279-3457
(0.25 lb ai/gal) turf –
0.0195 – 0.068
lb ai/A
Hand Animal treatment (ear tag) Animal 0.0042/animal 2 tags/animal NS
Python Y-TEX for cattle
Insecticide cattle
ear tags 10% ai
Reg. No. 39039-4
Dog Collar YT-1601 DOG 0.0009 NS Do not use on puppies less
TAG lb ai/pet (4g) than 6 months of age. For
Reg No. 0.0013 dogs weighing 56 pounds
39039-14 lb ai/pet (6g) or greater, use
0.0018 one .28 oz. (8 gram)
lb ai/pet (8g) medallion. This .28 oz. (8
gram) product may only be
used on dogs
weighing 56 pounds or
greater. May not be used
on dogs weighing 55
pounds or less.
Wipe or Spray Horses Evercide 28511 0.00625 Reapply as NS
0.75% ai lb ai/gal necessary
Reg No. (12.8 fl oz/gal)
1021-1859
Alpha Cypermethrin
Aerial, Ground Brassica Fastac EC 0.025 lbs ai/ A 3 0.075 lbs ai/ Foliar Application interval
(Groundboom, Airblast), Citrus fruits Insecticide, or 0.0025 lb is 4-14 days apart
A/season
and Chemigation Cucurbit vegetables Liquid, ai/gal depending on crop.
Fruiting vegetables 10.9% ai (11.4 fl ozs Minimum Spray Volume =
Page 124 of 138

Rate
(lb ai/A)
Leafy vegetables (0.83 lbs ai/gal) product/A/ 2-10 gal/A (aerial); 10-100
Legume vegetables (succulent or Reg. No. 7969- season) gal/A (ground) depending
dried except soybeans 298 on crop.
Root and tuber vegetables (except Leaves of root and tuber
sugar beet vegetables cannot be used
Sugar beets for food or feed.
PHI’s are 1-50 days
Tree nuts
depending on crop
Sorghum (grain) and millet
Soybeans
Aerial, Ground, Wheat and triticale Foliar Application
(Groundboom) Alfalfa intervals from 3-7 days,
and Chemigation but may vary depending on
Rice application rate and crop.
Wild Rice Minimum Spray Volume = 2
5 gal/A (aerial); 5-10 gal/A
(ground) depending on crop.
Ultra-low Volume (ULV)
spray application is
prohibited. PHI’s are 3-14
days depending on crop
Broadcast Corn (field) Foliar Application interval
Aerial, Ground Field Corn Grown for Seed is 3-5 days apart
(Groundboom) Popcorn depending on crop.
and Chemigation Sweet Corn Do not apply within 30
days of harvest for grain
and 60 for forage.
Do not apply within 3 days
of harvest of ears or forage
or livestock grazing.
Minimum Spray Volume =
2 gal/A (aerial); 10-20
gal/A (ground).
Page 125 of 138

Rate
(lb ai/A)
PHI’s are 3-60 days
depending on crop
Aerial, Ground Cotton Pre- and Post-emergence;
(Groundboom) Foliar; Broadcast
and Chemigation Application interval is 3-5
days depending on pests.
Do not graze or feed cotton
for forage.
Minimum Spray Volume =
1 gal/A (aerial); 5 gal/A
(ground). PHI is 14 days
depending on crop
Crack & Crevice (Void) Indoor/Outdoor – Commercial, TC-327 0.00054 lb NS Residual time using
treatment using injection Residential and Food Handling (Reg. No. 499- ai/can application rates is up to
tube or tip. Establishments 569) 90 days depending on
Ready-to-use pests. Reapply as
Spot application using pressurized liquid necessary, but no more
RTU container. (0.05% ai) than 2 times per week.
Perimeter application Applications must be at
using RTU container. least 3 days apart. Use
with the supplied actuator,
injection tubes/tip or other
BASF equipment.
Crack & Crevice (Void) TC-305 2 fl Residual time using
treatment using injection Reg. No. 499- oz/gal/1000 application rates range
tube or tip. 570), ft2 or 0.0039 lb from 30- 90 days
Microencapsulate ai/gal depending on pests.
Spot application using d liquid Reapply as necessary, but
injection tube or low concentrate 3.0% no more than 2 times per
pressure handheld ai week. Applications must
equipment. (0.25 lb ai/gal) be at least 3 days apart.
Apply with equipment
designed for void
applications.
Page 126 of 138

Rate
(lb ai/A)
Perimeter, 0.01 spot 0.0039-0.0059 Product is to be used as a
(spray) or general lb ai/gal residual/supplemental
surface application using (20 fl oz/10 treatment. Use higher
low pressure handheld gal) application rate to inhibit
equipment. wood-infesting insect sand
termite infestations in
exposed tubing, cracks or
cold joints (this is not a
substitute for other termite
treatments).
General surface
applications for FHE may
be used when the facility is
not in operation and
food/feed has been covered
or removed from the
application area.
Perimeter (spray) Lawns/Ornamentals TC-305 Ornamentals - Not for use in commercial
application using Microencapsulate 0.00013 lb greenhouses or nurseries.
backpack sprayer or d liquid ai/gal (6 fl To be used in golf courses,
handheld equipment. concentrate EPA oz/100 gals) hobby greenhouse, interior
Reg. No. 499- Turf – scapes, landscapes and
570) 0.085 lb ai/A lawns. Residual Time =
(3.0% ai) (1 fl 30-90 days depending on
(0.25 lb ai/gal) oz/1000ft2) pest.
Perimeter (spray) Livestock Housing TC-305 0.17 lb ai/A To be use in and on
application using Microencapsulate (2 fl oz/ 1000 outside surfaces of outer
backpack sprayer or d liquid ft2) or 0.0039 building. Treat a band of
handheld equipment. concentrate EPA lb ai/gal (2 fl 6-10 ft. around/adjacent to
Reg. No. oz/gal) to the building.
Poultry Houses 499-570 0.425 lb ai/A Residual time using
(3.0% ai) (5 fl oz/1000 application rates is up to
(0.25 lb ai/gal) ft2 ) or 0.0098 90 days depending on
lb ai/gal or
Page 127 of 138

Rate
(lb ai/A)
Truck Mounted Fogger Outdoor Mosquito 16fl oz/A or pests. Reapply as
Handheld and back 0.03 lb ai/A or necessary, but no more
sprayer 0.0003 lb ai than 2 times per week.
/gal (100 Applications must be at
gallons least 3 days apart.
dilution)
Impregnated Net Tobacco Warehouse Carifend Effective for up to 5 years
0.34 % a.i.
Reg No. 7969-367
1. Application rate based on registered labels
Page 128 of 138

Table D.2: Summary of Representative Registered Residential/Commercial Products and Use Directions
Method of Use Site Product and Maximum Maximum Maximum Use Directions, Application Timing,
Application Formulation Application No. Seasonal Type and Limitations
(Reg. No.) Rate1 Applications Application
Rate
(lb ai/A)
Cypermethrin
Handheld Indoor/ Outdoor Surfaces Bonide cyper NA NA Do not allow adults, children or pets
manually Perimeter, Spot, Crack and Crevice WSP Spot, C&C to enter the treated area or contact
pressurized Insecticide 0.0086 0.172 treated surfaces until sprays have
handwand 40% a.i. lb ai/A dried. Do not water treated area to
Reg. No. or point of run-off or apply when raining.
4-482 Barrier/ Use product indoors and outdoors as a
perimeter spot, crack and crevice application.
0.468 – 0.936 Do not use as space spray.
lb ai/A
Residential Lawns, Ornamental Cypermethrin 0.44 lb ai/A NA NA Do not use in greenhouses where
And/ or Shade Trees ME 0.21% Or 0.00001 lb plants are grown for food.
RTU ai/ft2
Reg No. Or 0.002 lb
100-1303 ai/gal
Concentrated Indoors Cyper-Active 1 (2 oz) can NA NA Do not use in green houses. Wait 2
Fogger E2 WB TRA treats 3200 ft3 hours after application, then open
0.824% a.i. windows, vents and doors for two
Reg. No. hours. If an odor is still detected,
1021-2763 additional ventilation is required. Do
not allow adults, children or pets to
Cyper-Active enter the treated area until vapors,
AS2 TRA mists and aerosols have dispersed and
0.824% a.i. treated area is thoroughly ventilated.
Reg. No. Do not used multiple canisters in a
1021-2764 room.
RTU Aerosol Indoor Use Only Raid Ant & 0.0010 NA Repeat Apply to surfaces only. Do not spray
Surface Direct Roach 26 lb ai/can every 4-6 up into air. Exit area immediately and
Spray 0.1% a.i. assumed can is weeks as remain outside the treated area until
Reg. No. 16 oz necessary sprays have dried.
4822-596
Page 129 of 138

Rate
(lb ai/A)
Trigger/ Pump Indoor/ Outdoor Chemsico C&C - 0.021 lb NA Up to 12 Do not water the treated area to point
Sprayer Insecticide ai/bottle months of of runoff. Do not make applications
Crack & Crevice, perimeter, RTU CG control during rain. People and pets should
foundation 0.2% ai Perimeter/ not be allowed in treated areas until
Reg. No. foundation – spray has dried.
9688-314 0.27 lb ai/A
(1.3 gal/350 ft2)
Aerosol Can Indoor/Outdoor MGK 29811 0.00052 NA NA Apply as needed.
Spot/Crack & Crevice and Bed RTU 0.05% ai lb ai/can
Bug Treatment Reg. No.
1021-2604
Wipe Horses Farnam Crash! 2 – 4 fl oz (60- NA NA Do not use on foals under 12 weeks
Wipe-On 120 ml) over old. Do not allow product to contact
Insecticide entire body animal’s eyes, nose, mouth or sores.
Repellent Repeat as necessary but no more than
0.15% a.i. 0.0004 once every 5-7 days.
Reg. No. lb ai/pet
270-253
RTU Trigger Farnam Crash! One day Apply one- NA For animal use only. Do not use on
Spray II Fly Spray application rate day dose no foals under 12 weeks old. Do not use
0.60% a.i. = 12 ml (48 more than on horses or foals intended for
Reg. No. secs) once daily. slaughter. Do not apply over cuts,
270-376 0.00016 wounds or irritated skin. Do not apply
lb ai/bottle For residual near eyes or mouth. Do not allow
Residual protection adults, children or pets to enter treated
protection apply residual area or contact treated surfaces until
application rate dosage every sprays have dried.
= 30-60 ml 3-4 days
(120-240 secs)
0.00071 lb
ai/animal
Spot on Cyper Horse RTU Applicator Apply once Reapply Do not apply product to foals less than
Spot on tube contains every 7 days every 8 days 3 months of age.
17.5% a.i. as needed
Page 130 of 138

Rate
(lb ai/A)
Reg, No. 0.00213 lb
53883-152 ai/animal
Assumed 0.187
fl oz used to
treat one horse
Zeta Cypermethrin
Handheld Outdoor Residential F6570 EW 0.15 lb ai/A 1 NS Repeat as needed, should not apply
manually Outdoor Residential, Institutional Master 0.15 lb ai/A or more than once every 7 days for
pressurized & Commercial Lawn Insecticide, 0.0035 lb ai/gal ornamentals
handwand 0.35%
Soil under firewood 0.51 lb ai/A or
EPA Reg. No.
0.0075 lb ai/gal
279-3347
Ant Mound Treatment 0.08/A (20
mounds)/A
Ornamentals 0.15 lb ai/A or
0.0035 lb ai/gal
Home Vegetable Gardens 0.15 lb ai/A or
Corn (Sweet corn) 0.0035 lb ai/gal NS NS Repeat as needed, Re-treatment is
or 0.0000034 ft2 recommended at least once per season
(3 months), outdoors. For long-lasting
residual control/action leave spray
undisturbed. The product will keep on
killing for up to 12 months* PHI
3days
Fruiting Vegetables (i.e. PHI 1 day
Tomatoes)
Berries crop Group PHI 3 days
Grapes PHI 1day
Legume Vegetables – succulent PHI 1day
Edible – Podded Beans, Succulent
Shelled Beans, and Dried Shelled
Beans
Cucurbit Vegetables PHI 1 day
Page 131 of 138

Rate
(lb ai/A)
Peanuts PHI 7 day
Brassica Vegetables PHI 1day
Root and Tuber Vegetables (except PHI 1 day
sugar beets)
Leafy Vegetables PHI 1 day
Pome Fruit (i.e. pears) PHI 14 days
Tree Nuts (i.e. Pecans) PHI 7 days
Sunflowers PHI 1day
Avocado, Black Sapote, Canistel, PHI 1day
Mamey Sapote, Mango, Papaya,
Sapodilla, Star Apple
Stone Fruit PHI 14 days
Residential Lawn NS
Pump Pressure Outdoor/Indoor Homes, Food Evercide Surface spray –
Sprayer or Handling Establishments, athletic 28511 0.0025 lb ai/gal
Watering Can fields, lawns, flowers, ornamentals, 0.75% ai (5.12 oz/gal)
trees, shrubs, home gardens; Reg. No. House plants,
barrier, horses 1021-1859 trees, shrubs –
0.00048 lb
ai/gal (1 oz/gal)
Home garden –
0.00048 –
0.00146 lb
ai/gal
Outdoor barrier
– 0.71 lb ai/A
(26.7 oz/800ft2)
Outdoor use -
0.128 lb ai/A
(16 oz/2650 ft2)
Horses – 0.0025
lb ai/gal
Page 132 of 138

Rate
(lb ai/A)
(12.8 oz/gal)
Granule Outdoor Residential, ornamentals, 0.344% F0570 0.15 lb ai/A NS NS Repeat application should be limited
Applicator flowers and lawns OTC Granular or 0.0000034 lb to not more than once per seven days.
Insecticide, ai/ft2
EPA Reg. No.
279-3297
Dog medallion Dogs 0.0009 lb ai/pet NS NS Do not use on puppies less than 6
YT-1601 Dog (4g) months of age.
Tag, 10% ai, 0.0013 lb ai/pet May not be used on dogs weighing
Reg. No. (6g) less than 14 pounds.
39039-14 0.0018 lb ai/pet
(8g)
Alpha Cypermethrin
Perimeter (spray) Lawns/Ornamentals/Tree/Garden Fedona CS Ornamentals - NS Not for use in commercial
application using 3.0 % ai 0.00012 lb greenhouses or nurseries. To be used
backpack sprayer Reg No ai/gal (6 fl in golf courses, hobby greenhouse,
or handheld 499-570 oz/100 gal) interiorscapes, landscapes and lawns.
equipment. 0.25 lb ai/gal Lawn/Turf - Residual Time = 30-90 days
0.085 lb ai/A or depending on pest.
0.0085 lb ai/gal
(1 fl oz/ 1000
ft2)
Livestock/Poultry Housing 0.085 lb ai/A To be use in and on outside surfaces
1.0 fl oz/1,000 of outer building. Treat a band of 6-10
ft2) or 0.0085 lb ft. around/adjacent to the building.
ai/gal Use higher application rate to control
0.44 lb ai/A darkling beetles only.
(5.0 fl oz/1,000
ft2 for darkling
beetles only).
Page 133 of 138

Rate
(lb ai/A)
Mosquito 0.02 lb ai/A Reapply as necessary but not more
than twice per week. Applications
must be at least 3 days apart.
Wood Destroying Insects 0.002 – 0.004
(termites) lb ai/gal (0.025
– 0..05%)
0.11 lb ai/A
(2 fl oz/1600
ft2)
Ready to Use PT Fendona 0.00052 Reapply as necessary but not more
pressurized (TC-327) lb ai/can than twice per week. Applications
insecticide Commercial, Industrial and Pressurized must be at least 3 days apart.
spot/crack and Residential Areas; Livestock and Insecticide (assuming can NA NA
crevice Poultry houses 0.05 % ai is 16 oz and
application Reg. No. density of
499-569 water)
1.Application rate based on registered labels
Page 134 of 138

Appendix E. Review of Human Research
This risk assessment relies in part on data from studies in which adult human subjects were
intentionally exposed to a pesticide or other chemical. These data are subject to ethics review
pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics
requirements. For certain studies, ethics review may have included review by the Human
Studies Review Board. Descriptions of data sources as well as guidance on their use can be
found at http://www.epa.gov/pesticides/science/handler-exposure-data.html and
http://www.epa.gov/pesticides/science/post-app-exposure-data.html.
Page 135 of 138

Appendix F: Aggregate Risk Calculations
The following equations were used to calculate the risk estimates provided in Tables 7.2.1 and
7.2.2 of the Short-Term Aggregate Risk Estimates Section
Cypermethrin/Zeta-cypermethrin
Short-term Aggregate Risk for Adults (Adults 50 -99 years)
For adults, the only oral exposure is the background dietary exposure from food and drinking
water which has an LOC of 100. This exposure is combined with inhalation exposure which has
an LOC of 30 and is thus aggregated using the 1/ARI approach.
Chronic Dietary Exposure = 0.000231 mg/kg/day;

Oral (Dietary) MOE = Oral NOAEL (7.16 mg/kg/day)/Chronic Dietary Exposure (0.000231
mg/kg/day) = 31,000
Residential Handler Inhalation Exposure = 0.0051 mg/kg/day

Residential Handler Inhalation MOE = 140
Total Aggregate ARI for the Adult Population =

1/(Oral LOC/ Oral MOE) + (Inhalation LOC/Inhalation MOE) = 1/(100/30,000 + 30/140) = 4.6
Short-term Aggregate Risk for Children 1-2 yrs. old

Inhalation exposure is anticipated to be negligible. The dermal and incidental oral (hand-to-
mouth) exposure for Children 1-2 yrs. old is added to the background dietary (oral) exposure to
arrive at the total aggregate exposure estimate.
Chronic Dietary Exposure = 0.000710 mg/kg/day

Dietary (Oral) MOE = Dietary (Oral) NOAEL (7.16 mg/kg/day)/Dietary Exposure (0.000710
mg/kg/day) = 10,600
Dermal post-application exposure = 0.023 mg/kg/day

Dermal post-application MOE from turf = 310
Incidental post-application exposure = 0.0035 mg/kg/day
Incidental Oral MOE from turf = 2,000
Aggregate MOE = NOAEL (7.16 mg/kg/day) ÷ (Dietary Exposure (mg/kg/day) + Residential

(Dermal + Incidental Oral) Exposure (mg/kg/day) = 300
Page 136 of 138

Alpha-cypermethrin
Short-term Aggregate Risk for Adults (Adults 50 -99 years)
For adults, the only oral exposure is the background dietary exposure from food and drinking
water which has an LOC of 100. This exposure is combined with inhalation exposure, which
had an LOC of 30 and thus an aggregate exposure estimate was calculated using the 1/ARI
approach.
Chronic Dietary Exposure = 0.00023 mg/kg/day;

Oral (Dietary) MOE = Oral NOAEL (1.4 mg/kg/day)/Chronic Dietary Exposure (0.000231
mg/kg/day) = 6,000
Residential Handler Inhalation Exposure = 0.00002 mg/kg/day

Residential Handler Inhalation MOE = 7,400
Residential Handler Dermal Exposure = 0.00255
Residential Handler MOE = 550
Total Aggregate ARI for the Adult Population =

1/[(Oral (Dietary) LOC/ Oral MOE) + (Inhalation LOC/Inhalation MOE) + (Dermal LOC/
Dermal MOE)] = 5
Short-term Aggregate Risk for Children 11-16 years old (Dietary Youth 13 – 19 yrs.)
The dermal exposure for Children 11-16 yrs. old is added to the background dietary exposure
(Youth 13 – 19 yrs.) to arrive at the total aggregate exposure estimate.

Dietary (oral) MOE = Oral NOAEL (1.4 mg/kg/day)/Chronic Dietary Exposure (0.000181
mg/kg/day) = 7,700
Residential Post-application Dermal Exposure = 0.0002 mg/kg/day

Residential post-application Dermal MOE =6,700
Total Aggregate MOE = NOAEL (1.4 mg/kg/day) ÷ [Dietary Exposure (0.000192 mg/kg/day) +
Dermal Exposure (0.0002 mg/kg/day] = 3,600
Short-term Aggregate Risk for Children 6-11 yrs. old (Dietary Children 6 – 12 yrs.)
The dermal exposure for Children 6-11 yrs. old is added to the background dietary exposure
(Dietary Children 6 – 12 yrs.) to arrive at the total aggregate exposure estimate.

Dietary (Oral) MOE = Oral NOAEL (1.4 mg/kg/day)/Chronic Dietary Exposure (0.000294
mg/kg/day) = 4,800

Residential Post-application Dermal MOE =5,100
Page 137 of 138

MOE = NOAEL (1.4 mg/kg/day) ÷ [Dietary Exposure (0.000294 mg/kg/day) + Dermal
Exposure (0.000338 mg/kg/day] = 2,400
Short-term Aggregate Risk for Children 1-2 yrs. old

The dermal and incidental oral (hand-to-mouth) exposure for Children 1-2 yrs. old is added to
the background dietary exposure to arrive at the total aggregate exposure estimate.

Dietary (Oral) MOE = Oral NOAEL (1.4 mg/kg/day)/Chronic Dietary Exposure (0.000710
mg/kg/day) = 2,000
Residential Post-application Incidental Oral Exposure = 0.001 mg/kg/day

Residential Post-application Incidental Oral MOE = 950
Residential Post-application Dermal MOE =530
MOE = NOAEL (1.4 mg/kg/day) ÷ [Dietary Exposure (0.000710 mg/kg/day) +Incidental Oral
Exposure (0.001 mg/kg/day + Dermal Exposure (0.003)] = 330
Page 138 of 138

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY

SUBJECT: Cypermethrin, Zeta-cypermethrin, and Alpha-cypermethrin. Draft Human

PC Code: 109702; 129064, and 209600 DP Barcode: 0425964

FROM: Margarita Collantes, M.S., Biologist _ �t1ff'��{Z_u04?�

Seyed Tadayon, Chemid�

THROUGH: Christina Swartz, Branch Chief

Donna Davis, HED Risk Assessment Review Committee �a.

 Residential handlers using an alpha-cypermethrin microencapsulated concentrate in

Cypermethrin is classified as a Group C “Possible human carcinogen”, based on an increased

Endpoints and Uncertainty Factors

Dietary Exposure and Risk Assessment

Residential Handler Exposure and Risk Assessment

All alpha-cypermethrin representative indoor and outdoor post-application

Spray Drift Exposure Assessment

Aggregate Exposure and Risk Assessment

Occupational Handler Exposure and Risk Estimates

Occupational Post-application Exposure and Risk

Although a quantitative occupational post-application inhalation exposure assessment was not

Human Studies Review

2.0 HED Conclusions

2.1 Data Deficiencies

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Adequate tolerance-enforcement methods are available in PAM Volume II for determining

2.2.3 Recommended Tolerances

Alpha-Cypermethrin: A tolerance of 10 ppm should be established for the Leafy greens

TABLE 2.2.a. Tolerance Summary for Cypermethrin (40CFR §180.418)(a)(1).

TABLE 2.2.c. Tolerance Summary for alpha-Cypermethrin (40CFR §180.418)(a)(3).

2.3 Label Recommendations

3.1 Chemical Identity

The nomenclature for cypermethrin, zeta-cypermethrin and alpha-cypermethrin is presented in

Common name Cypermethrin

CAS name cyano(3-phenoxyphenyl)methyl 3-(2,2-dichloroethenyl)-2,2-

Table 3.1.b: Zeta-Cypermethrin Nomenclature.

Common name Zeta-cypermethrin

TABLE 3.1.c: Alpha-cypermethrin Nomenclature.

Common name Alpha-cypermethrin

3.2 Physical/Chemical Characteristics

3.4 Anticipated Exposure Pathways

3.5 Consideration of Environmental Justice

4.0 Hazard Characterization and Dose-Response Assessment

Cypermethrin, zeta-cypermethrin, and alpha-cypermethrin (the cypermethrins) are members of

Target Altered In Vivo

Figure 4.0. Adverse outcome pathway for pyrethroids.

Although cypermethrin, zeta-cypermethrin and alpha-cypermethrin are separate active

4.1 Toxicology Studies Available for Analysis

 Wolansky Acute Oral Rat Study (cypermethrin)

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)

Cypermethrin, is a racemic mixture of eight isomers. Zeta- and alpha-cypermethrin are

4.3. Summary of Toxicological Effects

The cypermethrins (cypermethrin, zeta-cypermethrin, and alpha-cypermethrin) have been

There was no evidence of increased quantitative or qualitative susceptibility in the available

There was no evidence of immunotoxicity in the toxicology database or in a rat immunotoxicity

Cypermethrin is classified as a Group C “Possible human carcinogen”, based on an increased

In contrast to the age-related PK differences identified in the 2011 analysis, PD contributions to

4.3.4 Critical Duration of Exposure

No evidence of increased quantitative or qualitative susceptibility was noted in the