Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Risk Assessment of 5-Chloro-2-Methylisothiazol-3(2H)-One/2-Methylisothiazol-3(2H)-One (CMIT/MIT) Used as a Preservative in Cosmetics

  • Kim, Min Kook (Division of Toxicology, College of Pharmacy, Sungkyunkwan University) ;
  • Kim, Kyu-Bong (College of Pharmacy, Dankook University) ;
  • Lee, Joo Young (College of Pharmacy, The Catholic University of Korea) ;
  • Kwack, Seung Jun (College of Natural Science, Changwon National University) ;
  • Kwon, Yong Chan (Division of Toxicology, College of Pharmacy, Sungkyunkwan University) ;
  • Kang, Ji Soo (Division of Toxicology, College of Pharmacy, Sungkyunkwan University) ;
  • Kim, Hyung Sik (Division of Toxicology, College of Pharmacy, Sungkyunkwan University) ;
  • Lee, Byung-Mu (Division of Toxicology, College of Pharmacy, Sungkyunkwan University)
  • Received : 2019.02.12
  • Accepted : 2019.03.05
  • Published : 2019.04.15
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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 $1.25{\mu}g/cm^2/day$ 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 $0.77512{\mu}g/cm^2/day$ for all representative cosmetics and $0.00584{\mu}g/cm^2/day$ 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

References

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