Intravenous dose-lethality study of American pit viper venoms in mice using standardized methods

Abstract

An intravenous dose-lethality study of 14 clinically important North and South American pit viper venoms was carried out in mice using standardized, rigorous protocols developed to meet international (WHO) guidelines and US government (FDA) regulations for the development of new treatment products. The study was undertaken in order to establish baseline LD 50 values for the ongoing testing of a new crotalid antivenin F AB prepared from sheep immunoglobulin (IgG). The venoms (lyophilized and pooled from juvenile and adult snakes of both sexes) were taken from 10 rattlesnake (nine Crotalus and one Sistrurus) species, two Agkistrodon species, and two Bothrops species. The dose-response data were subjected to probit analysis. Median lethal dose (LD 50 ) values and their 95% confidence limits (CL) were calculated and statistical comparisons between the median potencies were made. The intravenous LD 50 s (and 95% CL) ranged from a low of 0.13 (0.10–0.15) mg kg –1 for Crotalus durissus terrificus , to a high of 6.32 (5.76–6.94) mg kg –1 for Crotalus horridus horridus . Significant positive rank-order correlations were also found for comparisons between the present LD 5O s and published LD 5O s for intravenous, intraperitoneal, and subcutaneous administration.