POL Scientific / JBM / Volume 11 / Issue 3 / DOI: 10.14440/jbm.2024.0037
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RESEARCH ARTICLE

Extraordinary variance in meta-analysis of venom toxicity of 160 most lethal ophidians and guidelines for estimating human lethal dose range

Brian P. Hanley1* ,  Gustavo Gross2
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1 Butterfly Sciences PO Box 2363, Davis, CA 95617, USA
2 University of Texas Rio Grande Valley School of Medicine, 1201 West University Drive, ITT 1.210, Edinburg, TX 78539, USA
JBM 2024 , 11(3), e99010029; https://doi.org/10.14440/jbm.2024.0037
Submitted: 22 July 2024 | Revised: 16 August 2024 | Accepted: 5 September 2024 | Published: 24 October 2024
© 2024 by the Journal of Biological Methods published by POL Scientific. Licensee POL Scientific, USA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Background: This is the first meta-analysis to characterize intra-ophidian-species variation in whole venom. Being the largest possible meta-analysis at this time, it encompasses all known records of animal lethality studies over the past 100 years. These results were not artifacts of resistant test-animal species and showed orders of magnitude beyond the 1.6 logs (40-fold change) range of lethal dose documented in the literature between amphibians, lizards, and mice. Methods: A total of 1003 lethal dose study results for 160 of the most lethal venomous ophidian species in the world were analyzed. Results: LDLo was not different from LD50 across studies, indicating the true range of toxicity is probably larger. The belief that, for the route of inoculation, IC < IV < IP < IM < SC was well supported (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 was 2.96 logs (917-fold change, N = 20). Within mouse species, for multiple routes of inoculation, the widest LD range was 3.6 logs (4,150-fold change, N = 20). The strongest correlation for the range of lethal dose results was the number of studies (R2 = 0.56), followed by the number of test-animal species (R2 = 0.55) and then the number of routes of inoculation (R2 = 0.43). Conclusion: Scientists working with humans should use combined LDLo and LD50 meta-datasets for all data and calculate mean, median, minimum, range, and standard deviation as shown in the supplement spreadsheet, and the equations we provide. Standard deviation multiples may provide the desired safety for experimenters. For estimating the LD50 range and minimum lethal dose for species with little data, we recommend curating a meta-dataset of related snakes, and computational research to strengthen this estimation.

Keywords
Venom toxicity
LD50
LDLo
Venom meta-analysis
Venom lethality
Funding
No grants supported this work.
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Conflict of interest
The authors declare no competing interests.
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Journal of Biological Methods, Electronic ISSN: 2326-9901 Print ISSN: TBA, Published by POL Scientific
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