Meta-analysis of venom toxicity of 167 most lethal ophidian species provides a basis for estimating human lethal doses
Abstract Background: This is the first meta-analysis to characterize intra-ophidian-species variation in whole venom. The largest possible meta-analysis possible at this time, it encompasses all known records of animal lethality studies over the past 100 years. These results are not artifacts of resistant test-animal-species, and show orders of magnitude beyond the 1.6 logs (40 fold change) range of lethal dose documented in literature between amphibians, lizards and mice. Methods: 1198 lethal dose study results for 167 of the most lethal venomous ophidian species in the world are analyzed. Results: LDLo does not differentiate from LD50 across studies, indicating the true range of toxicity is probably larger. The belief that for route of inoculation, IC<IV<IP<IM<SC has good support (R2 = 0.90). However, 5% of ICs were the highest dose, and 7% of SC inoculations were the lowest dose. Within the mouse test species, for one route of inoculation, the widest LD range is 3 logs (1000 fold change, N = 14). Within mouse, for multiple routes of inoculation, the widest LD range is 3.6 logs (4,150 fold change), N = 20, SC/IM. The strongest correlate for range of lethal dose results is the number of studies (R2 = 0.56); followed by the number of test-animal-species (R2 = 0.55); then by the number of routes of inoculation (R2 = 0.43). Conclusions: Scientists working with humans should use combined LDLo and LD50 meta-datasets for all data and calculate: mean, median, minimum, range, and standard deviations. Standard deviation multiples will provide desired coverage. For estimating LD50 range and minimum lethal dose for species with little data, I recommend curating a meta-dataset of related snakes, and computational research to strengthen this.