Carbaryl, Carbofuran, and Methomyl - National Marine Fisheries ...

exposures. The analysis is predicated on the toxic potencies of the three insecticides added
together to predict the resulting cumulative effect to AChE activity and mortality.
Mixture toxicity is typically described by three general responses: antagonistic, additive, or
synergistic. Antagonism and synergism are where the toxic response is not predicted by the
individual potencies of the pesticides found in the mixture. Antagonistic effects of a mixture
lead to less than expected toxicity on the organismal endpoint. Mechanistically, the pesticides
are likely interacting with one another to reduce the toxic potency of individual pesticides.
Synergistic effects of a mixture lead to a greater than expected effect on the organismal endpoint
and the pesticides within the mixture enhance the toxicity of one another. The third general type
of mixture toxicity and the one most frequently reported is additivity (known also as doseaddition
or concentration-addition). This type of response is defined by adding the individual
potencies of pesticides together to predict the effect on the biological endpoint. Additivity has
been demonstrated for many pesticide classes as well as other organic compounds such as PAHs,
PCBs, and dioxins.
Additive toxicity of chemicals that share a mode or mechanism of toxic action is well established
in the scientific literature, and as a result has been informing regulatory decisions for more than a
decade. In 1996, the National Academy of Sciences recommended a dose-additive approach to
assessing risks to human infants and children from pesticide exposure. EPA currently assesses
human risk of pesticide mixtures for pesticides that share a common mechanism of toxic action
e.g., N-methyl carbamates [such as carbaryl, carbofuran, methomyl], organophosphorus
insecticides, chloroacetanilide and triazine herbicides, as mandated by FQPA. The analysis EPA
conducts is predicated on additive toxicity and applies dose-addition to set tolerance limits of
pesticide residues on food. For example, the toxic potencies of the N-methyl carbamates are
added together to determine pesticide tolerance limits for edible crops. Although additive
toxicity is evaluated when determining risk to humans, EPA OPP has yet to apply a similar
approach to address cumulative toxicity of pesticides that share a common mode or mechanism
of action in the evaluation of terrestrial and aquatic species. That said, the use of dose-addition
for mixtures containing acetylcholinesterase-inhibiting pesticides is well established and has
been extended to protection of aquatic life (Belden, Gilliom et al. 2007).
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