Alcohols: Ethanol and Methanol

Abstract

Ethanol is a human teratogen with a long history, and experimental studies of its teratogenicity extend back to the turn of the century (Feré 1895; Stockard 1910; Pearl 1916). Methanol is also a well-known human toxicant, producing ocular toxicity and death following acute exposure by a number of routes(Tephly and McMartin 1984; Kavet and Nauss 1990),but human developmental toxicity has not been reported. Methanol has recently been identified as a rodent teratogen in studies undertaken because of the potential for occupational exposures or increased use of this alcohol in vehicle fuels (Nelson et al. 1985; Rogers et al. 1993; Bolon et al. 1993). This chapter describes the dysmorphogenic effects of prenatal exposure to ethanol in humans and experimental animals and reviews the literature germane to understanding the pathogenesis and underlying mechanisms of ethanol- and methanol-induced birth defects. These alcohols have common pathways of metabolism which must be considered when evaluating putative mechanisms by which these alcohols might produce dysmorphogenesis following maternal exposure; aspects of the pharmacokinetics of ethanol and methanol relevant to evaluating animal models and mechanisms of action are presented. In this analysis, we also discuss in vitro approaches, principally whole embryo culture, which have been important in elucidating the developmental toxicity of ethanol, methanol, and their metabolites, as well as for furthering our understanding of mechanisms of action.