EFFECT OF CONIINE ON THE DEVELOPING CHICK-EMBRYO

Coniine, an alkaloid from Conium maculatum (poison hemlock), has been shown to be teratogenic in livestock. The major teratogenic outcome is arthrogryposis, presumably due to nicotinic receptor blockade. Howeve r, coniine has failed to produce arthrogryposis in rats or mice and is only weakly teratogenic in rabbits. The purpose of this study was to evaluate and compare the effects of coniine and nicotine in the develo ping chick. Concentrations of coniine and nicotine sulfate were 0.015% , 0.03%, 0.075%, 0.15%, 0.75%, 1.5%, 3%, and 6% and 1%, 5%, and 10%, r espectively. Both compounds caused deformations and lethality in a dos e-dependent manner. All concentrations of nicotine sulfate caused some lethality but a no effect level for coniine lethality was 0.75%. The deformations caused by both coniine and nicotine sulfate were excessiv e flexion or extension of one or more toes. No histopathological alter ations or differences in bone formation were seen in the limbs or toes of any chicks from any group; however, extensive cranial hemorrhage o ccurred in all nicotine sulfate-treated chicks. There was a statistica lly significant (P less than or equal to 0.01) decrease in movement in coniine and nicotine sulfate treated chicks as determined by ultrasou nd. Control chicks were in motion an average of 33.67% of the time, wh ile coniine-treated chicks were only moving 8.95% of a 5-min interval, and no movement was observed for nicotine sulfate treated chicks. In summary, the chick embryo provides a reliable and simple experimental animal model of conine-induced arthrogryposis. Data from this model su pport a mechanism involving nicotinic receptor blockade with subsequen t decreased fetal movement. (C) 1994 Wiley-Liss, Inc.