The toxic factor in white snakeroot: identity, analysis and prevention.

White snakeroot (Eupatorium rugosum Houtt) has been known to cause trembles in animals and milk sickness in humans since the American Revolution. It still continues to poison animals. Horses and goats are particularly sensitive to white snakeroot poisoning. Resurgence of livestock production on small farm units, and utilization of fresh raw milk may result in milk sickness; if the animals have white snakeroot exposure. The goat is the only animal with good toxicity threshold data. In other animals and humans the toxicity thresholds of white snakeroot are not known, and that until responsible toxic principles are identified and their fate in animals and milk studied, such an assessment will not be possible. The toxic component(s) in white snakeroot has not been identified. The mechanism of action of the toxin in animals or humans remains unknown. However, metabolic studies in chicks initially suggest that a specific metabolic enzyme may be the target of the toxic principle. Components of white snakeroot that are toxic after microsomal activation have been isolated. Cytochrome P-450 is responsible for this activation. Activation in vitro can be totally inhibited by the cytochrome P-450 specific autocatalytic inhibitor, 1-aminobenzotriazole. In view of the importance of white snakeroot in the history of the United States and the ongoing problems today, it would be most unfortunate if studies were not pursued expeditiously to identify the toxicant(s) responsible, and to understand the mechanism(s) of action and toxicity thresholds.