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Impact of Chemical Proportions on the Acute Neurotoxicity of a Mixture of Seven Carbamates in Rats
Citation:
MOSER, V. C., S. J. PADILLA, J. E. SIMMONS, L. Haber, AND R. C. Hertzberg. Impact of Chemical Proportions on the Acute Neurotoxicity of a Mixture of Seven Carbamates in Rats. Presented at Internaitonal Toxicology of Mixtures Conference, Washington, DC, October 21 - 23, 2011.
Impact/Purpose:
We evaluated behavioral (motor activity) and ChE-inhibitory (brain, RBC) effects of a seven-carbamate mixture at the time of peak acute effects in adult Long-Evans male rats. The mixture consisted of: carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl, and propoxur.
Description:
Environmental exposures generally involve multiple chemicals and pathways, and statistical methodologies now exist to evaluate interactions among any number of chemicals in defined mixtures. N-methyl carbamate pesticides are presumed to act through a common mode of action, that is, inhibition of acetylcholinesterase (ChE) at cholinergic nerve terminals. We used a dose-additivity model to test experimentally the default assumptions of additivity. The best fitting models were used for the single-chemical dose-response data and used to develop a combined prediction model, which was then compared to the experimental mixture data. We evaluated behavioral (motor activity) and ChE-inhibitory (brain, RBC) effects of a seven-carbamate mixture at the time of peak acute effects in adult Long-Evans male rats. The mixture consisted of: carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl, and propoxur. In a relative potency (RPF) mixture, proportions of each carbamate within the mixture were set at equitoxic component doses: carbaryl was present at the highest proportion and oxamyl and carbofuran the lowest. A different composition was developed based on the tonnage of each carbamate sold in California in 2005. This California environmental (CE) mixture had more methomyl than carbaryl, and propoxur was in the smallest proportion. The experimental data showed that the RPF mixture did not deviate from dose-additivity for RBC ChE and motor activity, and brain ChE showed greater-than-additive (synergistic) response but only at a middle dose. On the other hand, the CE mixture showed greater-than-additive responses on all three endpoints and at the middle to high doses for each. Thus, the mixing ratio of these chemicals clearly influenced their interactive properties. These approaches for studying pesticide mixtures improve evaluations of potential toxicity under varying experimental conditions that may mimic human exposures. This is an abstract of a proposed presentation and does not reflect US EPA policy.