PT - JOURNAL ARTICLE AU - J P Horwitz AU - W Brukwinski AU - J Treisman AU - D Andrzejewski AU - E B Hills AU - H L Chung AU - C Y Wang TI - Ethchlorvynol: potential of metabolites for adverse effects in man. DP - 1980 Mar 01 TA - Drug Metabolism and Disposition PG - 77--83 VI - 8 IP - 2 4099 - http://dmd.aspetjournals.org/content/8/2/77.short 4100 - http://dmd.aspetjournals.org/content/8/2/77.full SO - Drug Metab Dispos1980 Mar 01; 8 AB - Identification of low levels of a metabolite of unaltered skeletal structure, 1-chloro-3-ethynylpent-1-en-3,4-diol (VII), detected in biological specimens of both nonfatal and fatal poisonings with DL-1-chloro-3-ethylpent-1-en-4-yn-3-ol (ethchlorvynol, la), has been achieved by high-resolution GC/MS. Corroborative evidence for the assigned structure (VII) was provided by synthesis, the design of which included as a central objective, concurrent access to 1-chloro-3-ethynyl-3,4-epoxy-1-pentene (VI), the putative direct precursor of VII. The diastereomeric epoxide mixture (VI) is mutagenic toward Escherichia coli WP2 try-hcr-, a UV-deficient repair strain. By contrast, neither Ia, VI, nor VII proved to be mutagenic toward Salmonella typhimurium (TA98, TA100, TA1535, and TA1539) with or without a liver postmitochondrial fraction. However, the epoxides (VI) proved cytotoxic to, for example, TA100, which apparently overlies its potency as a mutagen. The cytotoxicity of VI was also apparent in an in vitro culture system.