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Venom variability
Venom composition is not static. Even within a single individual, it will vary in quantity and relative proportions of components over time. Greater variability in components is seen between individuals of a species, greater still between species. Further, venom continues to evolve, sometimes rapidly, so there may be wide variations in venom composition and toxicity within a single species, over its geographic range. This is especially true for widely distributed species and may cause problems in antivenom effectiveness. Thus venom variability in nature can be observed at the following levels:

  • Interfamily
  • Intergenus
  • Interspecies
  • Intersubspecies
  • Intraspecific
  • Geographical
  • Interindividual
    • Seasonal
    • Diet/habit variability
    • Age-dependent variability
    • Sexual variability

There are a number of factors affecting studies of venom activity and potency, which may be the result of or cause artefactual venom variability. As many predictions of venom activity and possible clinical effects are based on venom studies, it is important to understand these potential sources of variability in either the venom or the results of venom research.

Choice of Venom for Research

Pooled venom

This may introduce many variabilities, because each pooled batch of venom will contain venom from different specimens, compounding both intra-individual and intra-specific variability. However, pooled venom may be best for determining the potential range of activities within a species.

Individual venoms

This more costly method removes intra-specific variability, but not intra-individual variability.

Method of venom collection

This can be critical, as some organisms produce many venom components, but eject them sequentially, rather than as a uniform mixture. This may apply particularly to Cnidarians (jellyfish etc) and their stinging cells. It is probably less important in snakes. However, the immediate fate of the venom after collection may be important, particularly in relation to environmental conditions that might denature certain components.

Sample storage

This is clearly important. Exposure to heat may cause damage to certain toxins. Prolonged storage in liquid form may damage others.

Toxicity & Lethality Studies

There are many potential variables in such research that may affect comparability and interpretation of results. The choice of test animal may be crucial, because each species may respond differently. The choice of route is also critical.

The standard test of toxicity is the LD50 (lethal dose 50%), that dose of the test substance which, on average, will kill 50% of the test animal by the specified route. Mice are most commonly used. As the test is potentially distressing for the test animals, alternatives are being actively developed. However, the LD50 remains the most universal standard for determining and comparing toxicity of venoms.

The Australian funnel web spider, Atrax robustus, is a good example of this variability. Males are more toxic than females. The venom has low toxicity in most laboratory animals, yet is lethal in humans. Thus standard LD50 testing in mice would show the venom to be weak. If this were used to guide clinical responses to potential envenoming, then it would be very eroneous. A less extreme example occurs in snakes, also from Australia. The rough scaled snake, Tropidechis carinatus has a much less potent venom than the tiger snake, Notechis scutatus, on LD50 testing in mice. Yet clinically, the two venoms are virtually identical in the type and severity of effects on envenomed humans.

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