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A DOSE-RESPONSE STUDY OF THE TOXICITY OF A MIXTURE OF 7N-METHYL CARBAMATE PESTICIDES IN ADULT, MALE RATS.
Citation:
PADILLA, S. J., WOODROW SETZER, R. S. MARSHALL, D. L. HUNTER, P. PHILLIPS, KATHY L. MCDANIEL, V. C. MOSER, AND A. LOWIT. A DOSE-RESPONSE STUDY OF THE TOXICITY OF A MIXTURE OF 7N-METHYL CARBAMATE PESTICIDES IN ADULT, MALE RATS. . Presented at Society of Toxicology, San Diego, CA, March 05 - 09, 2006.
Description:
There is scarce knowledge regarding the toxicity of pesticide mixtures, especially mixtures of the anticholinesterase N-methyl carbamates. A mixture study was conducted using 7 N-methyl carbamates (carbaryl, carbofuran, formetanate HCl, methiocarb, methomyl, oxamyl, and propoxur). The proportion of the carbamates in the mixture was based on relative potency factors: they were combined in an equipotent manner using the individual-chemical BMD10 values (calculated from the individual dose-response curves) as the point of comparison. The composition of the mixture was 41.6% carbaryl, 1.5% carbofuran, 1.6% formetanate HCl, 19.6% methiocarb, 5.1% methomyl, 1.5% oxamyl, and 29.1% propoxur. The mixture study consisted of 13 dosage groups with 10 male, Long-Evans rats (90 days old) in each group. Carbamates were given in two vehicles: either corn oil (carbaryl, carbofuran, methiocarb and propoxur) or water (formetanate, oxamyl, and methomyl). Every animal received both vehicles, one dose immediately after the other. Five different dosage levels of the mixture were given, predicted to produce <5%, 10%, 25%, 45% or 60% brain cholinesterase inhibition, and also each carbamate was given alone at a previously tested dosage to confirm the original dose-response data. Motor activity evaluations were conducted starting at 15 minutes after dosing, and brain tissue was taken at 40 minutes for measurement of cholinesterase activity using a radiometric assay. Comparison of the predicted and experimental brain cholinesterase data indicated that the dose-additive model predicted the degree of cholinesterase inhibition within the 95% confidence limits at each dose. These data suggest that the acute toxicity of a mixture of N-methyl carbamate pesticides behaves in a dose-additive manner, as is the default assumption for a group of chemicals with the same mechanism of toxicity. This is an abstract of a proposed presentation and does not reflect Agency policy.