Salmonella and mammalian-cell mutagenicity of 3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone

3-Chloro-4-(chloromethyl)5-hydroxy-2(5H)-furanone (CMCF), a chlorine disinfection by-product in drinking water, was mutagenic in the Salmonella/his (Ames) assay for both base-pair substitution strains (TA1535, TA100 TA102) and frameshift strains (TA97, TA98) with the highest mutagenic response observed in strain TA100 (1292 revertants/μg). The presence in TA100 of pKM101 plasmid, which enhances error-phone DNA repair, greatly increased susceptibility of CMCF mutagenicity relative to the isogenic strain TA1535 lacking pKM101. In the Chinese hamster ovary (CHO) cell hprt (6-thioguanine resistance) locus assay, the mutagenicity of CMCF (1.04 mutants/10⁶ clonable cells per μg/ml) was barely detectable because of the low mutagenicity/cytotoxicity ratio. From the present experiments it appears that CMCF acts in a manner similar to that of another drinking water mutagen, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX). However, CMFC appears to be a less potent mutagen in vitro than MX