Ethchlorvynol: potential of metabolites for adverse effects in man

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.