Comparative Developmental Toxicity of Acetylenic Alcohols on Embryos and Larvae of Xenopus laevis

Abstract

Xenopus laevis embryos and larvae were tested to assess the relative toxicity and teratogenicity of a series of 14 acetylenic alcohols. Tertiary propargylic alcohols and alkene-ols were expected to act as simple narcotics and not be teratogenic. However, primary and secondary propargylic and homopropargylic alcohols might be metabolically activated, by alcohol dehydrogenase, to become teratogenic. Mid-to-late blastula stage embryos were exposed to graded concentrations of each alcohol for 96 h. Embryo malformation (EmEC50) and lethality (EmLC50) endpoints were determined for each alcohol, and the Mortality/Malformation Index (MMI) was calculated as a measure of relative teratogenic potential. Additionally, untreated, healthy-appearing 5-day-old tadpoles were exposed to each alcohol for 96 h, and the tadpole lethality endpoint (Td5LC50) was determined. The ratio of the embryo LC50 to tadpole LC50 (E/T) was calculated as a measure of alcohol reactivity. The primary propargylic alcohols had teratogenic potential, producing head, eye, gut, and skeletal malformations and MMI values > 3.0. All other alcohols caused only edema and improper gut coiling. The E/T ratios indicated that primary and secondary propargylic and homopropargylic alcohols were reactive, whereas tertiary propargylic alcohols and alkene-ols were not. In addition, quantitative structure-activity relationships (QSARs) were explored, and comparisons of tadpole and fathead minnow lethality data indicated that toxicity in one system can be used to predict toxicity in the other.