Risk Assessment of 5-Chloro-2-Methylisothiazol-3(2H)-One/2-Methylisothiazol-3(2H)-One (CMIT/MIT) Used as a Preservative in Cosmetics
Toxicol. Res. 2019;35:103−117
Published online April 15, 2019;  https://doi.org/10.5487/TR.2019.35.2.103
© 2019 Korean Society of Toxicology.

Min Kook Kim1, Kyu-Bong Kim2, Joo Young Lee3, Seung Jun Kwack4, Yong Chan Kwon1, Ji Soo Kang1, Hyung Sik Kim1 and Byung-Mu Lee1

1Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Suwon, Korea
2College of Pharmacy, Dankook University, Cheonan, Korea
3College of Pharmacy, The Catholic University of Korea, Bucheon, Korea
4College of Natural Science, Changwon National University, Changwon, Korea
Byung-Mu Lee, Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Seobu-ro 2066, Suwon, Gyeonggi-do 16419, Korea
E-mail: bmlee@skku.edu
Received: February 12, 2019; Revised: March 4, 2019; Accepted: March 5, 2019
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
The mixture of 5-chloro-2-methylisothiazol-3(2H)-one (CMIT) and 2-methylisothiazol-3(2H)-one (MIT), CMIT/MIT, is a preservative in cosmetics. CMIT/MIT is a highly effective preservative; however, it is also a commonly known skin sensitizer. Therefore, in the present study, a risk assessment for safety management of CMIT/MIT was conducted on products containing 0.0015% of CMIT/MIT, which is the maximum MIT level allowed in current products. The no observed adverse effect level (NOAEL) for CMIT/MIT was 2.8 mg/kg bw/day obtained from a two-generation reproductive toxicity test, and the skin sensitization toxicity standard value for CMIT/MIT, or the no expected sensitization induction level (NESIL), was 1.25 μg/cm2/day in humans. According to a calculation of body exposure to cosmetics use, the systemic exposure dosage (SED) was calculated as 0.00423 mg/kg bw/day when leave-on and rinse-off products were considered. Additionally, the consumer exposure level (CEL) amounted to 0.77512 μg/cm2/day for all representative cosmetics and 0.00584 μg/cm2/day for rinse-off products only. As a result, the non-cancer margin of safety (MOS) was calculated as 633, and CMIT/MIT was determined to be safe when all representative cosmetics were evaluated. In addition, the skin sensitization acceptable exposure level (AEL)/CEL was calculated as 0.00538 for all representative cosmetics and 2.14225 for rinse-off products; thus, CMIT/MIT was considered a skin sensitizer when all representative cosmetics were evaluated. Current regulations indicate that CMIT/MIT can only be used at concentrations 0.0015% or less and is prohibited from use in other cosmetics products. According to the results of this risk assessment, the CMIT/MIT regulatory values currently used in cosmetics are evaluated as appropriate.
Keywords : Risk assessment, CMIT/MIT, Preservative, Cosmetics, Skin sensitization, Margin of safety


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