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. However, 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 developing 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%, respectively. Both compounds caused deformations and lethality in a dose-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 excessive flexion or extension of one or more toes. No histopathological alterations or differences in bone formation were seen in the limbs or toes of any chicks from any group; however, extensive cranial hemorrhage occurred in all nicotine sulfate-treated chicks. There was a statistically significant (P < or = 0.01) decrease in movement in coniine and nicotine sulfate treated chicks as determined by ultrasound. Control chicks were in motion an average of 33.67% of the time, while 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 coniine-induced arthrogryposis. Data from this model support a mechanism involving nicotinic receptor blockade with subsequent decreased fetal movement.
Forsyth
C S
CS
Interdisciplinary Toxicology Program, Oregon State University, Corvallis 97331.
Frank
A A
AA
Watrous
B J
BJ
Bohn
A A
AA
D000470:Alkaloids / Q000633:toxicity*; D000818:Animals; D001176:Arthrogryposis / Q000139:chemically induced; D002543:Cerebral Hemorrhage / Q000139:chemically induced; D002642:Chick Embryo; D009538:Nicotine / Q000633:toxicity; D010880:Piperidines; D013723:Teratogens / Q000633:toxicity*
D000470:Alkaloids; D010880:Piperidines; D013723:Teratogens; D009538:Nicotine; C007112:coniine