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.
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Abbreviations
- BIT:
-
1,2-Benzisothiazolin-3-one
- CEL:
-
Consumer exposure level
- CIR:
-
Cosmetic Ingredient Review
- cMEM:
-
Complete minimum essential medium
- CMIT:
-
5-Chloro-2-methylisothiazol-3(2H)-one
- EC3:
-
Effective concentration of chemical required to induce in the LLNA, a three-fold increase in lymph node cell proliferation compared with vehicle control values
- EU:
-
European Union
- HRIPT:
-
Human Repeat Insult Patch Testing
- IP:
-
Intraperitoneal
- IV:
-
Intravenous
- IVS:
-
In vitro score
- LD:
-
Lethal dose
- LLNA:
-
Local lymph node assay
- LOAEL:
-
Lowest observed adverse effect level
- MIT:
-
2-methylisothiazol-3(2H)-one
- NOAEL:
-
No observed adverse effect level
- NOEL:
-
No observed effect level
- RD:
-
Respiratory rate decrease
- RIVM:
-
National Institute for Public Health and the Environment
- SAF:
-
Sensitisation assessment factors
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Kim, M.K., Kim, KB., Lee, J.Y. et al. 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. 35, 103–117 (2019). https://doi.org/10.5487/TR.2019.35.2.103
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DOI: https://doi.org/10.5487/TR.2019.35.2.103