Final Report of the Safety Assessment of Methylisothiazolinone

@article{Burnett2010FinalRO,
  title={Final Report of the Safety Assessment of Methylisothiazolinone},
  author={Christina L. Burnett and Wilma Fowler Bergfeld and Donald V. Belsito and Curtis D. Klaassen and James G. Marks and Ronald C. Shank and Thomas J. Slaga and Paul W. Snyder and F. Alan Andersen},
  journal={International Journal of Toxicology},
  year={2010},
  volume={29},
  pages={187S - 213S}
}
Methylisothiazolinone (MIT) is a heterocyclic organic compound used as a preservative in cosmetics and personal care products in concentrations up to 0.01%. MIT is a colorless, clear liquid with a mild odor that is completely soluble in water; mostly soluble in acetonitrile, methanol, and hexane; and slightly soluble in xylene. Consistent with its solubility, dermal penetration is low. The Cosmetic Ingredient Review Expert Panel noted the in vitro evidence of neurotoxicity but concluded that… 

Figures and Tables from this paper

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TLDR
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Methylisothiazolinone contact allergy: a review

TLDR
Repeated exposure to MI showed that many patients allergic to MI reacted to 50 ppm which is half the maximum permitted concentration of MI in cosmetics, which could be the first sign of an epidemic of MI contact allergy.

Analytical method development of methylisothiazolinone, a preservative, in rat plasma using LC-MS/MS.

Outbreak of methylisothiazolinone allergy targeting those aged ≥40 years

TLDR
The first cases of allergic contact dermatitis caused by MI through cosmetic exposure were reported in 2010, and in that year MI was incorporated into the cosmetic/face patch test series, representing a 27-fold increase in the permitted concentration of MI.

Ex vivo human skin permeation of methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI)

TLDR
Overall results show that MI in formulations or in aqueous standard solutions quickly permeated the skin with time lags less than 15 min while MCI was much slower (>3.5 h); this confirms that MCI reacts readily with skin and may induce local irritation.

Amended Safety Assessment of Methylisothiazolinone as Used in Cosmetics

TLDR
The Cosmetic Ingredient Review Expert Panel concluded that MI is safe for use in rinse-off cosmetic products at concentrations up to 100 ppm and safe in leave-on cosmetic products when they are formulated to be nonsensitizing, which may be determined based on a quantitative risk assessment.

Methylisothiazolinone: dermal and respiratory immune responses in mice.

[Isothiazolinones as causal factors of contact allergy epidemics in the 20th and 21st centuries].

TLDR
To counteract the increasing problem of contact allergy epidemic to MI, the recommendations have been developed, suggesting the ban on the use of MI in "leave-on" cosmetics and maximum concentration of 15 ppm in "rinse-off" products.

Contact Dermatitis Caused by Preservatives

TLDR
The most important classes of preservatives physicians are most likely to encounter in their daily practice are reviewed, specifically isothiazolinones, formaldehyde and formaldehyde-releasers, iodopropynyl butylcarbamate, methyldibromoglutaronitrile, and parabens.
...

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