Induction of Gastrointestinal Tract Nuclear Anomalies in B6C3F1 Mice by 3-Chloro-4-(Dichloromethyl)-5-Hydroxy-2(5H)-Furanone and 3,4-(Dichloro)-5-Hydroxy-2(5H)-Furanone, Mutagenic Byproducts of Chlorine Disinfection

摘要

Two chlorinated hydroxylated furanones, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and 3,4-(dichloro)-5-hydroxy-2(5H)-furanone (MA), potent bacterial mutagens and by-products of chlorine disinfection, induce nuclear anomalies in the gastrointestinal tract of B6C3F1 mice. In this bioassay the two chlorohydroxyfuranones were approximately comparable to the epichlorohydrin (EPI), a known rodent gastrointestinal tract carcinogen but were much less potent than methylnitrosourea (MNU). The duodenum was the most sensitive tissue responding by both increased numbers of nuclear anomalies per mouse and increased incidence of animals presenting the aberrations 24 hours after a single oral dose of 0.38 and 0.46 mmol/kg of MX and MA respectively. The proximal colon responded to MX but not MA and neither compound produced increased nuclear anomalies in the forestomach. Although this is the first study demonstrating that chlorohydroxyfuranones are capable of inducing genotoxicity in vivo it is clear that their potency in the gastrointestinal tract nuclear anomalies assay is not comensurate with their extreme mutagenicity in Salmonella.