Compendium of the most significant studies with reference to properties, intake, effects.

Herman A, Aerts O, Jacobs MC, Scheers C, Gilissen L, Goossens A, Baeck M. Evolution of methylisothiazolinone sensitization: A Belgian multicentric study from 2014 to 2019. Contact Dermatitis. 2021 Dec;85(6):643-649. doi: 10.1111/cod.13956.

Abstract. In the 2010s an epidemic of allergic contact dermatitis to methylisothiazolinone (MI) occurred in Europe. European authorities banned the use of methylisothiazolinone in leave-on cosmetics in 2017 and limited its use in rinse-off products in 2018.

Castelli R, Scalvini L, Vacondio F, Lodola A, Anselmi M, Vezzosi S, Carmi C, Bassi M, Ferlenghi F, Rivara S, Møller IR, Rand KD, Daglian J, Wei D, Dotsey EY, Ahmed F, Jung KM, Stella N, Singh S, Mor M, Piomelli D. Benzisothiazolinone Derivatives as Potent Allosteric Monoacylglycerol Lipase Inhibitors That Functionally Mimic Sulfenylation of Regulatory Cysteines. J Med Chem. 2020 Feb 13;63(3):1261-1280. doi: 10.1021/acs.jmedchem.9b01679.

Abstract.  We describe a set of benzisothiazolinone derivatives that are potent inhibitors of monoacylglycerol lipase, the primary degrading enzyme for the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG).

King N, Latheef F, Wilkinson M. Trends in preservative allergy: Benzisothiazolinone emerges from the pack. Contact Dermatitis. 2021 Dec;85(6):637-642. doi: 10.1111/cod.13968.

Abstract. Our data show a significant increase in the prevalence of contact allergy to BIT over the last 6 years, probably as a consequence of increased use in household products. 

Varga Z, Nicol E, Bouchonnet S. Photodegradation of benzisothiazolinone: Identification and biological activity of degradation products. Chemosphere. 2020 Feb;240:124862. doi: 10.1016/j.chemosphere.2019.124862. 

Abstract. Compared with experimental data, the calculated oral rat LD50 values were found to be the most relevant and thus used for toxicity estimation. The photoproducts including a phenolic or a sulfino group or both functions were found potentially more toxic than benzisothiazolinone.

Kwak S, Choi YS, Na HG, Bae CH, Song SY, Kim HG, Kim YD. Benzisothiazolinone upregulates the MUC5AC expression via ERK1/2, p38, and NF-κB pathways in airway epithelial cells. Toxicol Res (Camb). 2019 Jul 16;8(5):704-710. doi: 10.1039/c9tx00135b.

Abstract. Mucus plays an important role in protecting the respiratory tract from irritants. However, mucus hypersecretion is a major indicator of airway diseases. 1,2-Benzisothiazolin-3-one, as a microbicide, induces asthmatic inflammation. 

Eckhardt T, Goddard R, Lehmann C, Richter A, Sahile HA, Liu R, Tiwari R, Oliver AG, Miller MJ, Seidel RW, Imming P. Crystallographic evidence for unintended benzisothiazolinone 1-oxide formation from benzothiazinones through oxidation. Acta Crystallogr C Struct Chem. 2020 Sep 1;76(Pt 9):907-913. doi: 10.1107/S2053229620010931.

Abstract. 1,3-Benzothiazin-4-ones are a promising new class of drugs with activity against Mycobacterium tuberculosis, which have already reached clinical trials.

Garcia-Hidalgo E, Schneider D, von Goetz N, Delmaar C, Siegrist M, Hungerbühler K. Aggregate consumer exposure to isothiazolinones via household care and personal care products: Probabilistic modelling and benzisothiazolinone risk assessment. Environ Int. 2018 Sep;118:245-256. doi: 10.1016/j.envint.2018.05.047.

Abstract. A Quantitative Risk Assessment for BIT using Sensitization Assessment Factors (SAFs) indicates that around 1% of the Swiss population is at risk to be sensitized by benzisothiazolinone in cosmetics and household chemicals. For isothiazolinones in general the presented higher-tier modelling approach suggests that household cleaners are currently more important sources of exposure than cosmetics.