Final Report of the Safety Assessment of Methylisothiazolinone

@article{Burnett2010FinalRO,
  title={Final Report of the Safety Assessment of Methylisothiazolinone},
  author={Christina L. Burnett and W. Bergfeld and D. Belsito and C. Klaassen and J. Marks and R. C. Shank and T. Slaga and P. Snyder and F. A. 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… Expand
Amended Safety Assessment of Methylisothiazolinone as Used in Cosmetics
TLDR
Methylisothiazolinone is safe for use in rinse-off cosmetic products at concentrations up to 100 ppm (ie, 0.01%) and safe in leave-on cosmetic products when they are formulated to be nonsensitizing, which may be determined based on a quantitative risk assessment or similar methodology. Expand
Methylisothiazolinone
TLDR
The background and reasons for adding MI to the routine screening patch testing series are reviewed, including the importance of a very relevant preservative allergen that, to date, has managed to stay under the radar in the United States. Expand
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. Expand
Analytical method development of methylisothiazolinone, a preservative, in rat plasma using LC-MS/MS.
TLDR
An analytical method that was useful in detecting the profile of MI in the plasma using an LC-MS/MS-coupled multiple reaction monitoring (MRM) technique and determined half-life, and area under the curve (AUC) of MI using a non-compartment model are developed. Expand
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. Expand
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. Expand
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. Expand
Methylisothiazolinone: dermal and respiratory immune responses in mice.
TLDR
It is indicated that MI can be classified as a strong dermal sensitizer and irritant, but not an asthmogen after initial dermal sensitization, followed by an airway challenge, which is indicative for acute sensory irritation. Expand
[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. Expand
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. Expand
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References

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Contact dermatitis from methylisothiazolinone in a paint factory
TLDR
The data show that MI holds a potential for eliciting and propably inducing contact allergy in humans, and whether this preservative is safe to use in cosmetics where billions of consumers are exposed needs a care full monitoring. Expand
Biocides: Characterization of the Allergenic Hazard of Methylisothiazolinone
Biocides used in many every day products often are able to act as haptens and so may cause allergic reactions in the skin. In addition, where exposure of the respiratory tract may occur, they shouldExpand
Mutagenicity of cosmetic products containing Kathon®
TLDR
The mutagenic evaluation of Kathon® 886 resulted in a dose response similar to that seen with some cosmetic products but at a 1,000‐fold lower concentration, and activity was also reduced by the addition of S‐9 mix, which reduced activity both with and without cofactors present. Expand
Chemical reactivity of some isothiazolone biocides.
TLDR
NMR spectral studies indicated that for CMIT the mercaptoacrylamide form is capable of tautomerization to a highly reactive thio-acyl chloride, which is suggested to account for much of this enhanced antimicrobial activity. Expand
Cross‐reactivity between methylchloroisothiazolinone/methylisothiazolinone, methylisothiazolinone, and other isothiazolinones in workers at a plant producing binders for paints and glues
TLDR
Patch testing is pursued in a group of individuals to see the potential cross-reaction pattern between MCI and MI and also 2 potentiallyCross-reacting isothiazolinones, namely octylisothiazolone (OIT) and 4,5-dichloro-2-n-octyl-4-isoth Diazolin-3-one ( dichlorinated OIT). Expand
Methylisothiazolinone, A Neurotoxic Biocide, Disrupts the Association of Src Family Tyrosine Kinases with Focal Adhesion Kinase in Developing Cortical Neurons
TLDR
It is suggested that a disruption of FAK-SFK complexes due to SFK inhibition leads to FAK dysfunction, with detrimental effects to immature neurons, and prolonged exposure to low levels of MIT and related compounds may have damaging consequences to the developing nervous system. Expand
In Vitro Neurotoxicity of Methylisothiazolinone, a Commonly Used Industrial and Household Biocide, Proceeds via a Zinc and Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase-Dependent Pathway
TLDR
A brief exposure to methylisothiazolinone is shown to be highly toxic to cultured neurons but not to glia, and the toxic actions of this biocide are zinc dependent and require the activation of p44/42 extracellular signal-regulated kinase (ERK) via a 12-lipoxygenase-mediated pathway. Expand
Bovine corneal opacity and permeability test: an in vitro assay of ocular irritancy.
TLDR
The bovine corneal opacity and permeability assay allows investigation of two important components of eye irritation, in a one-day experiment, using an ocular tissue, and represents a useful approach to assess ocular irritation at least for the authors' needs. Expand
Occupational contact allergy and dermatitis from methylisothiazolinone after contact with wallcovering glue and after a chemical burn from a biocide.
TLDR
Two cases are reported in which skin exposure to a newly launched biocide containing 2-methyl-4-isothiazolin-3-one (MI) and 1,2-benzisoth Diazolin- 3-one led to sensitization to Ml, which in the second case was preceded by a chemical burn. Expand
Contact allergy to the active ingredients of Kathon CG in the guinea pig.
TLDR
Preservative Kathon CG (K-CG) is a commercial preparation, consisting of the two active ingredients (a.i.) and 5-chloro-2-methyl-4-isothiazolin-3-one and also of other components, demonstrated to be a strong sensitizer and 243-K- CG a weak sensitizers. Expand
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