Methylchloroisothiazolinone / methylisothiazolinone: epidemiological retrospective study.
Lorente-Lavirgen AI, Almeida C, Bernabeu J, Valero V, Lorente R.
Eur Ann Allergy Clin Immunol. 2019 May 15;51(3):131-134. doi: 10.23822/EurAnnACI.1764-1489.92.

"Slime": A trending cause of isothiazolinone contact allergy in children.
Salman A, Demir G, Apti O.
Contact Dermatitis. 2019 Jun;80(6):409-411. doi: 10.1111/cod.13237. Epub 2019 Mar 15.

Contact allergy to methylchloroisothiazolinone/methylisothiazolinone in north-eastern Italy: a temporal trend from 1996 to 2016.
Dusefante A, Mauro M, Belloni Fortina A, Corradin MT, Larese Filon F.
J Eur Acad Dermatol Venereol. 2019 May;33(5):912-917. doi: 10.1111/jdv.15453.

Allergic contact dermatitis caused by glitter glue used as make-up containing methylchloroisothiazolinone.
Vincenzi C, Ravaioli GM, Lambertini M, Guicciardi F, Piraccini BM, Bardazzi F, La Placa M.
Contact Dermatitis. 2019 Feb;80(2):128-130. doi: 10.1111/cod.13139. Epub 2018 Nov 8.

Mixture Toxicity of Methylisothiazolinone and Propylene Glycol at a Maximum Concentration for Personal Care Products.
Park J, Lee H, Park K.
Toxicol Res. 2018 Oct;34(4):355-361. doi: 10.5487/TR.2018.34.4.355.

Occupational allergic contact dermatitis caused by Acticide MV, a brand name for the mixture methylchloroisothiazolinone/methylisothiazolinone.
Santiago L, Gonçalo M.
Contact Dermatitis. 2018 Jul;79(1):46-47. doi: 10.1111/cod.12984. Epub 2018 Mar 23.

An Italian multicentre study on methylchloroisothiazolinone/methylisothiazolinone contact sensitivity: understanding the structure-activity relationship.
Stingeni L, Bianchi L, Foti C, Romita P, Rigano L, Hansel K; MCI/MI SIDAPA network.
Contact Dermatitis. 2018 Apr;78(4):297-299. doi: 10.1111/cod.12935.

The Role of Cleaning Products in Epidemic Allergic Contact Dermatitis to Methylchloroisothiazolinone/Methylisothiazolinone.
Marrero-Alemán G, Saavedra Santana P, Liuti F, Hernández N, López-Jiménez E, Borrego L.
Dermatitis. 2018 Mar/Apr;29(2):77-80. doi: 10.1097/DER.0000000000000352.

Occupational facial contact dermatitis caused by methylchloroisothiazolinone/methylisothiazolinone in a stainless steel aerosol spray.
Todberg T, Opstrup MS, Johansen JD, Hald M.
Contact Dermatitis. 2017 Sep;77(3):173-174. doi: 10.1111/cod.12773.

Ex vivo human skin permeation of methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI).
Berthet A, Spring P, Vernez D, Plateel G, Hopf NB.
Arch Toxicol. 2017 Nov;91(11):3529-3542. doi: 10.1007/s00204-017-1978-x.

Multicenter Patch Testing With Methylisothiazolinone and Methylchloroisothiazolinone/Methylisothiazolinone Within the International Contact Dermatitis Research Group.
Isaksson M, Ale I, Andersen KE, Elsner P, Goh CL, Goossens A, Jerajani H, Matsunaga K, McFadden J, Bruze M.
Dermatitis. 2017 May/Jun;28(3):210-214. doi: 10.1097/DER.0000000000000272.

Allergenic Ingredients in Facial Wet Wipes.
Aschenbeck KA, Warshaw EM.
Dermatitis. 2017 Nov/Dec;28(6):353-359. doi: 10.1097/DER.0000000000000268.

Allergic contact dermatitis caused by methylchloroisothiazolinone/methylisothiazolinone in a medical device.
Schliemann S, Isaksson M, Persson C, Bruze M, Tittelbach J, Elsner P.
Contact Dermatitis. 2016 Nov;75(5):312-314. doi: 10.1111/cod.12610.

Four cases of allergic contact dermatitis caused by methylchloroisothiazolinone/methylisothiazolinone in ironing water.
Atkar R, Todd P.
Contact Dermatitis. 2016 Nov;75(5):316-317. doi: 10.1111/cod.12552.

Methylchloroisothiazolinone is a chemical compound, a chlorinated isothiazolinone, 4-isothiazolin-3-one. It is one of the most widespread chemical preservative components used in cosmetic products.

The name describes the structure of the molecule:

• Methyl indicates the presence of a methyl group, a functional group consisting of one carbon atom bonded to three hydrogen atoms.
• chloro refers to the presence of chlorine in the compound, an element that contributes to the antimicrobial properties of the preservative.
• isothiazolinone indicates that the compound belongs to the class of isothiazolinones, a family of preservatives known for their effectiveness against a wide range of microorganisms, including bacteria, fungi, and yeasts.

Raw Materials and Their Functions

• Isothiazolinone Compounds. The base compounds used in the synthesis of methylchloroisothiazolinone. These compounds act as antimicrobial agents.
• Chlorine. Used to chlorinate isothiazolinone, enhancing its preservative properties.
• Industrial Chemical Synthesis of Methylchloroisothiazolinone
• Synthesis. The process begins with the synthesis of isothiazolinone compounds, followed by their chlorination to form methylchloroisothiazolinone.
• Reaction Control. The synthesis and chlorination reaction is monitored to ensure it occurs correctly and the final product has the desired antimicrobial properties.
• Purification. After synthesis, methylchloroisothiazolinone is purified to remove impurities and by-products.
• Quality Control. The purified methylchloroisothiazolinone undergoes quality checks to ensure it meets the required standards. After quality control, it is packaged for use as a preservative in cosmetic and personal care products.

Form and Color

 Methylchloroisothiazolinone is typically a liquid. This compound is usually colorless or very light in color.

What it is used for and where

Methylchloroisothiazolinone is a chemical compound used as a preservative in various products, including cosmetics, skincare products, and household cleaning products and  is used as a preservative for its ability to prevent the growth of microorganisms in products. However, it is also known for its potential to cause allergic reactions in some people, which is why its use is regulated in many countries.

Cosmetics

It is a restricted ingredient as  V/39 a Relevant Item in the Annexes of the European Cosmetics Regulation 1223/2009. Substance or ingredient reported: Mixture of 5-Chloro-2-methyl-isothiazol-3(2H)-one and 2-Methylisothiazol-3(2H)-one with magnesium chloride and magnesium nitrate.

Product Type, body parts    Rinse-off: Maximum concentration in ready for use preparation    0.0015% (of a mixture in the ratio 3:1 of 5-Chloro-2-methyl-isothiazol-3(2H)-one and 2-Methylisothiazol-3(2H)-one

Preservative. Any product containing organic, inorganic compounds, water, needs to be preserved from microbial contamination. Preservatives act against the development of harmful microorganisms and against oxidation of the product.

It is found in:

• soaps
• detergents
• creams
• shampoo
• glitter glue as make-up
• aerosol spray deodorants
• medical devices
• ironing water

Methylchloroisothiazolinone exercises function:

• preservative
• antioxidant
• fungicidal

Safety

This ingredient is effective in preventing the growth of bacteria, mold, and yeast, thereby helping to extend the shelf life of products. However, it is important to note that it can cause allergic reactions in some individuals, and its use is regulated in many countries.

However, its action caused an increase in cases of awareness in recent years with a widespread of dermatitis (1).

Methylchloroisothiazolinone studies

• Molecular Formula: C₄H₄ClNOS
• Molecular Weight: 149.592 g/mol
• UNII: DEL7T5QRPN
• CAS: 26172-55-4   137662-59-0  137086-87-4
• EC Number: 247-500-7

Synonyms:

• 5-Chloro-2-methyl-4-isothiazolin-3-one
• 3(2H)-Isothiazolone, 5-chloro-2-methyl-
• 5-chloro-2-methylisothiazol-3(2h)-one
• 5-Chloro-2-methyl-2H-isothiazol-3-one
• Chloromethylisothiazolinone
• 2,3-Dihydro-2-methyl-3-oxo-5-chloroisothiazole
• 5-Chloro-2-methyl-4-isothiazolin-3-one (CMI)
• 4-ISOTHIAZOLIN-3-ONE, 5-CHLORO-2-METHYL-
• 5-chloro-2-methyl-1,2-thiazol-3-one
• 5-chloro-n-methylisothiazolin-3-one
• N-Methyl-5-chloroisothiazolin-3-one
• Chloromethylisothiazolone
• 5-chloro-2-methyl-2h-isothiazolin-3-one
• 5-chloro-2-methyl-3(2H)-isothiazolinone
• 2-Methyl-5-chloroisothiazolin-3-one
• 5-chloro-2-methyl-isothiazol-3-one
• 2-Methyl-5-chloro-3-isothiazolone
• 5-Chloro-2-methyl-3-isothiazolone
• 5-chloro-2-methylisothiazolin-3-one
• 5-Chloro-2-methyl-isothiazol-3(2H)-one
• 5-chloro-N-methylisothiazolone
• 5-Chloro-2-methyl-3(2H)-isothiazolone
• 5-Chloro-2-methyl-4-isothiazolin-3-one solution
• 5-Chloride-2-Methyl-4-Isothiazoline-3-Ketone
• N-Methyl-5-chloroisothiazolone (5-Chloro-2-methyl-4-isothiazolin-3-one)
• CMIT
• Kathon CG 5243
• Bioace
• Kathon IXE
• CHEBI:53621

References________________________________________________________________________

(1) Contact allergy to methylchloroisothiazolinone/methylisothiazolinone in north-eastern Italy: a temporal trend from 1996 to 2016. Dusefante A, Mauro M, Belloni Fortina A, Corradin MT, Larese Filon F.  J Eur Acad Dermatol Venereol. 2019 May;33(5):912-917. doi: 10.1111/jdv.15453.

(2) Lichenoid contact dermatitis secondary to methylisothiazolinone (MI).
Raymond J, Konya J, Bakis-Petsoglou S.
JAAD Case Rep. 2016 Oct 6;2(5):380-383.