Risk Assessment of 5-Chloro-2-Methylisothiazol-3(2H)-One/2-Methylisothiazol-3(2H)-One (CMIT/MIT) Used as a Preservative in Cosmetics

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/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 µg/cm 2 /day for all representative cosmetics and 0.00584 µg/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.

Effect of Application Amounts on In Vitro Dermal Absorption Test Using Caffeine and Testosterone

“…The dermal absorption rate is crucial for the risk assessment of cosmetics majorly absorbed through the skin [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ] Several factors affect dermal absorption, such as donor characteristics, including gender [ 9 ], disease [ 10 ], age [ 11 ], race [ 12 ], vehicle [ 13 ], test substances (physicochemical properties, particle size) [ 14 , 15 ], skin condition [ 16 ], hydration [ 17 ], pH [ 18 ], stress [ 19 ], and physical or chemical damage [ 20 ], etc.…”

Anti-Pigmentary Natural Compounds and Their Mode of Action

“…Since melanogenesis is complex and a variety of factors and pathways are involved, further research on the whitening activity of natural compounds is needed. Furthermore, although the whitening activity of these natural compounds has been well established in vitro, it is difficult to ensure efficacy in humans, since there are many confounding factors for manifesting whitening effects in human skin [63,64]. Thus, further investigation of these natural compounds' whitening activity in vivo, in artificial skin models, or in clinical trials would be required to apply them to whitening cosmetics [65].…”

Isothiazolinones as Novel Candidate Insecticides for the Control of Hemipteran Insects

“…While isothiazolinones, such as Kathon have been reported to cause skin sensitization in humans and may induce apoptosis in human keratinocytes [ 35 ]. A review of case studies indicates that they are safe to human when the concentration is below 15 mg/L [ 18 ]. When plants were sprayed with isothiazolinones at the concentrations used in our experiments (up to 150 mg/L), the plants did not suffer any appreciable sign of toxicity (data not shown).…”

“…Isothiazolinones are a class of broad spectrum microbicides that have been widely used to control the growth of microorganisms such as bacteria, fungi and yeast in cooling water systems and cosmetics, among others [ 18 ]. However, whether they can be used as insecticides for the control of agricultural pests, remains unexplored.…”