Study on 2-Methyl-4-Isothiazoline-3-one

2-Methyl-4-Isothiazoline-3-one, sometimes erroneously called methylisothiazoline, it is a kind of white to yellow powder with Molecular Formula:C4H5NOS and Molecular Weight:115.15, a powerful biocide and preservative within the group of isothiazolinones, used in personal care products. The CAS Registry Number is 2682-20-4 .

2-Methyl-4-Isothiazoline-3-one is cosmetic preservative. Its main uses are leave-on products, namely hand and body lotions and moisturisers (including facial moisturisers), sun tanning lotions and some rinse-off products like shampoos (mostly zinc pyrithione based anti-dandruff shampoos), surfactants and conditioners.

2-Methyl-4-Isothiazoline-3-one(CAS NO:2682-20-4) is commonly used in products in conjunction with methylchloroisothiazolinone, a mixture sold under the registered trade name Kathon CG. A common indication of sensitivity to Kathon CG is allergic contact dermatitis. Sensitization to this family of preservatives was observed as early as the late 1980s. Due to increased use of isothiazolinone-based preservatives in recent years, an increase in reported incidences of contact allergy to this product have been reported, and in 2013 it was dubbed the 2013 Contact Allergen of the Year.

2-Methyl-4-Isothiazoline-3-one in sterile deionised water has been tested in procaryotic cells for genemutation in several tester strains. The results of the bacterial gene study demonstrated the absence of mutagenic effects in bacteria at the gene level.

Some studies have shown 2-Methyl-4-Isothiazoline-3-one to be allergenic and cytotoxic, and this has led to some concern over its use. In 2002, there was an in vitro study of the neurotoxicity of this compound in the department of Neurobiology at the University of Pittsburgh. In that study, it was shown that a short exposure to concentrations of 2-Methyl-4-Isothiazoline-3-one of 30-100 micromolar were lethal to mature neurons in tissue culture, but not to other brain cells, such as astrocytes . 

2-Methyl-4-Isothiazoline-3-one and its closely related analog, chloromethylisothiazolinone or CMIT, affect the ability of young or developing neurons to grow processes in tissue culture. The specific protein affected by 2-Methyl-4-Isothiazoline-3-one is called focal adhesion kinase, or FAK. Normal FAK function is required for the growth of axons and dendrites. 

FAK has to be modified by a process called phosphorylation to perform its function, so phosphates are added to FAK’s amino acid chain. It inhibits the tyrosine phosphorylation of FAK by another kinase called Src, preventing the growth of axons and dendrites, at least in culture. These findings were published in the Journal of Pharmacology and Experimental Therapeutics.

 The toxic actions of 2-Methyl-4-Isothiazoline-3-one on developing neurons occurs at much lower concentrations than those inducing lethal injury. 2-Methyl-4-Isothiazoline-3-one is even more potent, working at concentrations as low as 0.1 micromolar. One micromolar is approximately 0.115 parts per million.

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