Evaluation of mutagenic and carcinogenic properties of brominated and chlorinated acetonitriles: by-products of chlorination.
The present study was undertaken to determine if chlorinated and brominated acetonitriles formed during the chlorination of drinking water possess mutagenic and/or carcinogenic properties. Chloroacetonitrile (CAN), dichloroacetonitrile (DCAN), trichloroacetonitrile (TCAN), bromochloroacetonitrile (BCAN), and dibromoacetonitrile (DBAN) were tested for their ability (1) to produce point mutations in the Salmonella/microsome assay, (2) to induce sister chromatid exchanges (SCE) in Chinese hamster ovary (CHO) cells in vitro, (3) to produce micronuclei in polychromatic erythrocytes in CD-1 mice, and (4) to act as tumor initiators in the skin of Sencar mice. DCAN and BCAN were found to be direct-acting mutagens in Salmonella. All five haloacetonitriles induced SCE in CHO cells in vitro. This activity paralleled the extent of chlorine substitution and was further enhanced in the dihaloacetonitrile series when bromine was substituted for chlorine. None of the haloacetonitriles showed evidence of activity in the mouse micronucleus assay. DBAN, BCAN, and CAN initiated tumors in the mouse skin with topical applications followed by a 20-week promotion schedule of 12-O tetradecanoylphorbol-13-acetate applications (p less than 0.02). These data indicate that the haloacetonitriles do display mutagenic and carcinogenic properties in some test systems and the hazard associated with their occurrence in drinking water and production within the gastrointestinal tract require further evaluation.
D000097:Acetonitriles / Q000008:administration & dosage / Q000633:toxicity*; D000287:Administration, Topical; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced; D002713:Chlorine; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D010212:Papilloma / Q000139:chemically induced; D012475:Salmonella / Q000187:drug effects / Q000235:genetics; D012854:Sister Chromatid Exchange / Q000187:drug effects; D012878:Skin Neoplasms / Q000139:chemically induced*; D014873:Water Pollutants / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D014881:Water Supply
D000097:Acetonitriles; D014873:Water Pollutants; D014874:Water Pollutants, Chemical; D002713:Chlorine; C032159:acetonitrile