Environmental occurrence, exposure, toxicity, and transformation of benzothiazoles: A review

Benzothiazoles (BTs) are a class of aromatic heterocyclic compounds consisting of a benzene ring fused with a 1,3-thiazole ring. They have been widely used as vulcanization accelerators, fungicides, corrosion inhibitors, herbicides, anti-cancer drugs, etc., leading to their ubiquitous presence in various environmental media. Numerous studies have demonstrated that BTs exhibit multiple toxic effects. In this review, we systematically summarized research findings on the environmental occurrence, exposure, toxicity, and transformation of BTs. Benzothiazole (BTH) and 2-hydroxy-benzothiazole (2-OH-BTH) are the predominant BTs, with the highest detection frequencies and concentrations in environmental media and human biological samples. In some special cases, inhalation is estimated to be the primary exposure pathway, compared with ingestion and dermal contact. BTs have been reported to possess multiple toxic effects, including neurotoxicity, developmental and reproductive toxicity, endocrine-disrupting effects, and immunotoxicity. By integrating network toxicology analysis and reported experimental results, we highlighted that the aryl hydrocarbon receptor could be the key toxic target of BTs. BTs can further transform into diverse derivatives in wastewater treatment systems and the natural environment, with BTH and 2-OH-BTH being the main transformation products. The TP-Transformer model predicted that some BT-derived pharmaceuticals can be transformed into 2-amino-benzothiazole (2-ABTH), indicating that they are potential sources of environmental pollution. The predicted toxicity of most transformation products was reduced, while chlorinated derivatives exhibited increased toxic potential. Finally, we proposed BT-derived pharmaceuticals as a potential neglected source of BTs, and more attention should be given to the precise identification of transformation products and understanding the toxic mechanisms.