CIR Supplement Manuscript

International Journal of Toxicology

2023, Vol. 42(Supplement 3) 32S–36S
EDTA and Salts © The Author(s) 2023
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DOI: 10.1177/10915818231204270
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Priya Cherian*, Wilma F. Bergfeld**, Donald V. Belsito**,

Curtis D. Klaassen**, Daniel C. Liebler***, James G. Marks***,
Ronald C. Shank***, Thomas J. Slaga**, Paul W. Snyder**,
Monice Fiume†, and Bart Heldreth‡

Abstract
The Expert Panel for Cosmetic Ingredient Safety reviewed newly available studies since their original assessment in 1998, along
with updated information regarding product types and concentrations of use and confirmed that EDTA and certain salts are safe
as cosmetic ingredients in the practices of use and concentration as described in this report.

Keywords
safety, cosmetics, EDTA, Calcium Disodium EDTA, Diammonium EDTA, Dipotassium EDTA, HEDTA, TEA-EDTA,
Tetrasodium EDTA, Tripotassium EDTA, Trisodium EDTA, Trisodium HEDTA

The Expert Panel for Cosmetic Ingredient Safety first pub- these ingredients are reported to be used in 25 and 1 for-
lished a final report on the Safety Assessment of EDTA and mulation, respectively. In 1998, the maximum concentrations
Salts in 1998.1 The Expert Panel concluded that EDTA, of use were reported for EDTA (2% in hair products; rinse-off)
Calcium Disodium EDTA, Diammonium EDTA, Dipotassium and Trisodium EDTA (2% in bath soaps and detergents; rinse-
EDTA, triethanolamine (TEA)-EDTA, Tetrasodium EDTA, off).1 According to 2019 concentration of use data, the in-
Tripotassium EDTA, Trisodium EDTA, hydroxyethyl ethyl- gredient with the highest maximum concentration of use is
enediamine triacetic acid (HEDTA), and Trisodium HEDTA Disodium EDTA, which is used at 3% in “other hair coloring
are safe as used in cosmetic formulations as described in that preparations.”11 This ingredient was previously reported to be
report. Because it has been at least 15 years since the report used at a maximum of 1% in bath products. Disodium EDTA
was published, in accord with Cosmetic Ingredient Review is also reported to have the highest concentration of use in
Procedures, an updated search was performed, and the Expert leave-on products (.85%; hair color sprays) and in products
Panel considered whether the safety assessment of EDTA and which would come in contact with the skin (.6%; skin
the related salts should be reopened. Data identified in the cleansing). All other in-use ingredients are reported to be used
published literature2-9 that have become available since the at 2% or less.
original report was issued support the original conclusion. The Although a substantial increase in frequency of use was
Expert Panel also considered updated information regarding reported, the lack of evidence of genotoxic and clinical effects
product types and ingredient use frequencies as reported in the continues to support the safety of this ingredient group.
US Food and Drug Administration (FDA) Voluntary Cosmetic According to the Expert Panel, EDTA and its salts did not pose
Registration Program (VCRP) database,10 and the maximum a toxicological risk as used in cosmetics; and therefore, the
use concentrations provided by the Personal Care Products original conclusion was reaffirmed.
Council.11 The Expert Panel determined to not reopen this
safety assessment and reaffirmed the original conclusion that
EDTA and salts of EDTA are safe as cosmetic ingredients in
*Cosmetic Ingredient Review Senior Scientific Analyst/Writer
the present practices of use and concentration, as given in
**Expert Panel for Cosmetic Ingredient Safety Member
Table 1. ***Expert Panel for Cosmetic Ingredient Safety Former Member
According to VCRP data from 2019, Disodium and Tet- †
Cosmetic Ingredient Review Senior Director
‡
rasodium EDTA are reported to be used in 12,509 and 7691 Cosmetic Ingredient Review Executive Director
formulations, respectively, while in 1998 they were reported to
Corresponding Author:
be used in 1165 and 1285 formulations.1,10 In addition, in Bart Heldreth, Executive Director, Cosmetic Ingredient Review, 1620 L
1998, Calcium Disodium EDTA and Tripotassium EDTA Street, NW, Suite 1200, Washington, DC 20036, USA.
were not reported to be in use. According to 2019 VCRP data, Email: [email protected]
Table 1. Current and Historical Frequency and Concentration of Use of EDTA and Salts According to Duration and Exposure.

# of Uses Max Conc of Use (%) # of Uses Max Conc of Use (%)

Calcium Disodium EDTA Dipotassium EDTA

Cherian et al.

201910 19981 201911 1998, 19991 201910 19981 201911 1998, 19991

Totals* 25 NR .000098–.025 NR 17 21 .054 .05–.09

Duration of use
Leave-on 1 NR .025 NR 7 16 NR .09
Rinse-off 24 NR .000098–.00059 NR 10 5 .054 .09
Diluted for (Bath) Use NR NR NR NR NR NR NR NR
Exposure type
Eye area 1 NR NR NR 8 1 NR NR
Incidental ingestion 22 NR .000098–.00059 NR NR NR NR NR
Incidental inhalation-spray 2a NR .000098a NR 5c 9a; 6c NR .09
Incidental inhalation-powder NR NR NR NR 5c NR NR NR
Dermal contact 2 NR .025 NR 17 21 .054 .05–.09
Deodorant (underarm) NR NR .025 NR NR NR NR NR
Hair – non-coloring NR NR NR NR NR NR NR NR
Hair-coloring 1 NR NR NR NR NR NR NR
Nail NR NR NR NR NR NR NR NR
Mucous membrane 22 NR .000098–.00059 NR NR NR NR NR
Baby products NR NR NR NR NR NR NR NR

Disodium EDTA EDTA

10 1 11 1 10 1
2019 1998 2019 1998, 1999 2019 1998 201911 1998, 19991

Totals* 12509 1165 .00002–3 .001–1 1011 923 .000004–2 .02–2

Duration of use
Leave-on 8455 590 .000075–.85 .001–0.6 210 85 .0000055–0.1 .03–0.5
Rinse-off 3931 498 .00002–3 .005–0.8 794 835 .000004–2 .02–2
Diluted for (bath) use 123 77 .05 .1–1 7 3 .025 NR
Exposure type
Eye area 755 33 .05–.33 .1–0.6 28 5 .0001–.05 .03–.05
Incidental ingestion 39 NR .00033–0.1 .05–0.1 25 NR NR NR
Incidental inhalation- 150; 3986a; 33; 271a; .0001–.85; .00075–.12a; .05–.2; .02–0.5a; 2; 58a; 52c 2; 38a; .0000055–.0005; .05–0.1a;
spray 2292c 125c .1–0.2c .05–0.6c 15c .0033–0.1a .03–0.5c
b c
Incidental inhalation- 50; 11b; 2292c 13; 1b; 125c .1; .00045–.35b; .1–0.2c .02–.05; .05–0.6c 3; 2 ; 52 2; 15c .00001–0.1b .1; .03–0.5c
powder
Dermal contact 9988 783 .000075–0.6 .01 - 1 284 122 .000004–0.1 .03–0.5

(continued)
33S
Table 1. (continued) 34S
Disodium EDTA EDTA

201910 19981 201911 1998, 19991 201910 19981 201911 1998, 19991

Totals* 12509 1165 .00002–3 .001–1 1011 923 .000004–2 .02–2

Deodorant (underarm) 57a 2a NR 0.2a 26a 3a NR .1–0.5a

Hair – non-coloring 1664 303 .00002–.95 .005–0.8 175 72 .0000055–.22 .05–0.3
Hair-coloring 631 76 .016–3 .05–0.4 506 725 .000055–2 .02–2
Nail 20 1 NR .001–.02 11 3 NR NR
Mucous membrane 1377 130 .000075–.25 .05–1 111 19 .02–.052 .05–0.3
Baby products 45 5 .2–.35 NR 4 NR NR .03

HEDTA Tetrasodium EDTA

201910 19981 201911 1998, 19991 201910 19981 201911 1998, 19991

Totals* 1 1 NR NR 7691 1285 .000002–1.9 .004–1.3

Duration of use
Leave-on 1 NR NR NR 3230 355 .002–0.5 .005–0.5
Rinse-off NR 1 NR NR 4391 825 .000002–1.9 .004–1.3
Diluted for (bath) use NR NR NR NR 70 105 NR .01–0.1
Exposure type
Eye area NR NR NR NR 571 24 .002–0.1 .004–0.5
Incidental ingestion NR NR NR NR 6 1 .08 .009–.02
Incidental inhalation-spray NR NR NR NR 54; 1327a; 665c 11; 106a; 87c .043–.15; .02–.26a; .078c .04–.08; .04–0.2a; .04–0.3c
Incidental inhalation-powder NR NR NR NR 102; 9b; 665c 1; 1a; 87c .048; .02–.26b; .078c .04; 0.1a; .04–0.3c
Dermal contact NR NR NR NR 5630 634 .004–.56 .004–0.5
Deodorant (underarm) NR NR NR NR 47a 9a .016–0.5 .04–0.3a
Hair – non-coloring 1 1 NR NR 1047 414 .000002–.75 .02–1.3
Hair-coloring NR NR NR NR 918 225 .01–1.9 .3–0.4
Nail NR NR NR NR 7 4 .05 0.2
Mucous membrane NR NR NR NR 2277 265 .024–.56 .009–0.5
Baby products NR NR NR NR 50 14 .19–0.2 .05–0.3

Tripotassium EDTA Trisodium EDTA

10 1 11 1 10 1
2019 1998 2019 1998, 1999 2019 1998 201911 1998, 19991

Totals* 1 1 .01 NR 507 616 .000000045–.35 .00001–2

Duration of use
Leave-on NR NR .01 NR 368 479 .0000045–.24 .00001–0.5
Rinse-off 1 1 NR NR 137 130 .000000045–.35 .03–2
Diluted for (bath) use NR NR NR NR 2 7 NR .01–0.4
International Journal of Toxicology 42(Supplement 3)

(continued)
Table 1. (continued)

Tripotassium EDTA Trisodium EDTA

201910 19981 201911 1998, 19991 201910 19981 201911 1998, 19991
Cherian et al.

Totals* 1 1 .01 NR 507 616 .000000045–.35 .00001–2

Exposure type
Eye area NR 1 NR NR 137 128 .0005–0.2 0.3
Incidental ingestion NR NR NR NR NR 4 0.2 NR
Incidental inhalation-spray NR NR NR NR 5; 76a; 82c 11; 117a; 65c .05; .0000045a .00001–.01; .01–0.5a; .02–0.2c
Incidental inhalation-powder NR NR NR NR 8; 82c 11; 65c .1; .002–.24c .07–.2; .021–0.2c
Dermal contact 1 1 .01 NR 415 531 .0005–.24 .00001–2
Deodorant (underarm) NR NR NR NR NR 1a NR 0.2a
Hair – non-coloring NR NR NR NR 5 29 .000000045–.0000045 .01–0.4
Hair-coloring NR NR NR NR 28 18 .35 .1–0.5
Nail NR NR NR NR 2 10 NR .1–0.2
Mucous membrane NR NR NR NR 52 27 0.2 .01–2
Baby products NR NR NR NR 1 1 NR NR

Trisodium HEDTA

201910 19981 201911 1998, 19991

Totals* 124 159 .000017–0.3 .1–0.7

Duration of use
Leave-on 24 13 .004–0.1 .1–0.3
Rinse-off 97 144 .02–0.3 .1–0.7
Diluted for (bath) use 3 2 .000017 NR
Exposure type
Eye area 3 1 NR NR
Incidental ingestion NR NR NR NR
Incidental inhalation-spray 5a; 2c 3a .004a .1–0.3a; 0.1c
Incidental inhalation-powder 2c NR .021–0.1b 0.1c
Dermal contact 92 35 .000017–0.1 .1–0.5
Deodorant (underarm) NR 6a NR .1–0.3a
Hair – non-coloring 32 23 .004–.13 .1–0.7
Hair-coloring NR 98 .11–0.3 0.1
Nail NR 2 NR NR
Mucous membrane 62 22 .000017–.084 .2–0.5
Baby products NR NR NR NR
a
It is possible these products are sprays, but it is not specified whether the reported uses are sprays.
b
It is possible these products are powders, but it is not specified whether the reported uses are powders.
c
Not specified whether a spray or a powder, but it is possible the use can be as a spray or a powder; therefore, the information is captured in both categories.
35S

NR, No reported use.

36S International Journal of Toxicology 42(Supplement 3)

Author’s Note 3. Whittaker P, Seifried H, San R, Clarke J, Dunkel V. Genotoxicity

of iron chelators in L5178Y mouse lymphoma cells. Environ
Unpublished sources cited in this report are available from the Di-
Mol Mutagen. 2001;38:347-356.
rector, Cosmetic Ingredient Review, 1620 L Street, NW, Suite 1200,
4. NIH U.S. National Library of Medicine. CCRIS: Ethyl-
Washington, DC 20036, USA.
enediaminetetraacetic acid. 2000.
5. Marins J, Sassone L, Fidel S, Ribeiro D. In Vitro genotoxicity
Author Contributions
and cytotoxicity in murine fibroblasts exposed to EDTA,
The articles in this supplement were sponsored by the Cosmetic NaOCl, MTAD, and citric acid. Braz Dent J. 2012;23(5):
Ingredient Review. 527-533.
6. Juzeniene A, Juzenas P, Iani V, Moan J. Topical applications of
Declaration of Conflicting Interest iron chelators in photosensitization. Photochem Photobiol Sci.
The author(s) declared the following potential conflicts of interest 2007;6:1268-1274.
with respect to the research, authorship, and/or publication of this 7. Laborde-Castérot H, Villa A, Rosenberg N, Dupont P, Lee H,
article: The articles in this supplement were sponsored by the Garnier R. Occupational rhinitis and asthma due to EDTA-
Cosmetic Ingredient Review. Containing detergents or disinfectants. Am J Ind Med. 2012;
55:677-682.
Funding
8. Sánchez-Pedreño P, Garcı́a-Bravo B, Frı́as-Iniesta J. Contact
The author(s) disclosed receipt of the following financial support for allergy to tetrasodium EDTA in a sunscreen. Cont Derm. 2009;
the research, authorship, and/or publication of this article: The articles 61:125-126.
in this supplement were sponsored by the Cosmetic Ingredient Re- 9. Kimura M, Kawada A. Contact dermatitis due to trisodium
view. The Cosmetic Ingredient Review is financially supported by the ethylenediaminetetra-acetic acid (EDTA) in a cosmetic lotion.
Personal Care Products Council. Cont Der. 1999;40:341.
10. US Food and Drug Administration (FDA) Center for Food
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