Enzyme Mediated Chloroform Biotransformation and Quantitative Cancer Risk Analysis of Trihalomethanes Exposure in South East Asia

Abstract

Adverse effects of chloroform exposure on human health have raised concern over the practice of chlorine-based disinfection method. Chloroform is the most prominent species of trihalomethanes (THMs), which are formed due to the reaction between chlorine and aromatic fractions of natural organic matter in water distribution system. In developing countries of South East Asia, chloroform has been estimated in the range of 85–97 % of total THMs in drinking water. The United States Environmental Protection Agency (USEPA) has categorized chloroform in the probable (B2) carcinogen group, but epidemiological studies have suggested its striking correlation with carcinogenicity. This chlorinated disinfection by-product elicits non-genotoxic–cytotoxic mode of the mechanistic approach towards hepatic and renal carcinogenesis. DNA hypomethylation is one of its significant consequences which facilitate cell proliferation on the molecular level. Evidences have validated the crucial role of cytochrome P450 (CYP2E1) enzyme in chloroform-induced cytolethality. The magnitude of chloroform exposure, routes of administration, and gender specifications influence the extent of the cellular damage. Chloroform exposure takes place through multi-pathways such as inhalation, ingestion, and dermal contact which eventually get biotransformed to induce tumorigenesis at susceptible sites. THM-mediated cancer risk has exceeded the USEPA reference value by 10–100 times in few South East Asian countries but the reference limit has been surpassed by 899 times in India. The review concludes with discussion towards perspective on reconsideration over prevailing disinfection techniques.