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Dose-additivity modeling for acute and repeated exposure to a mixture of N-methycarbamate Pesticides
Citation:
Mwanza, J. C., R. C. Hertzberg, L. Haber, M. Kohrman-Vincent, R. Li, R. Pan, R. Lyles, J. E. SIMMONS, AND D. W. HERR. Dose-additivity modeling for acute and repeated exposure to a mixture of N-methycarbamate Pesticides. Presented at International Toxicology of Mixtures Conference, Washington, DC, October 21 - 23, 2011.
Impact/Purpose:
Few data exist for modeling physiological changes after exposure to N-methylcarbamates. Therefore, we examined the effects of acute exposure (0-75 mg/kg) to a 1:1.45 mixture of propoxur:carbaryl for brain (central) and erythrocyte (peripheral) measures of ChE activity, and the duration of the Photic After Discharge (PhAD) as a measure of central physiological function in rats.
Description:
The toxicity of N-methylcarbamate pesticides is attributed to the reversible inhibition of cholinesterase (ChE) enzymes in the central and peripheral nervous system. The inhibition of ChE following a single exposure to this class of pesticides has been modeled using a dose-addition model. However, few data exist for modeling physiological changes after exposure to N-methylcarbamates. Therefore, we examined the effects of acute exposure (0-75 mg/kg) to a 1:1.45 mixture of propoxur:carbaryl for brain (central) and erythrocyte (peripheral) measures of ChE activity, and the duration of the Photic After Discharge (PhAD) as a measure o fcentral physiological function in rats. We then examined if the dose-additive model derived from acute treatment could be used to predict the responses following 14 days of treatment (0-45 mg/kg/day) with the carbamate mixture. Acute exposure to the mixture resulted in less than dose-additive results at middle dosages for brain ChE activity, greater than additive response at high dosages for erythrocyte ChE activity, and a dose-additive response for the PhAD duration. Compared with acute treatment, repeated treatment with the mixture resulted in similar responses for brain ChE activity and the PhAD duration, with less inhibition of erythrocyte ChE activity at middle dosages. This repeated treatment with the carbamate mixture resulted in less than dose-additive responses at middle dosages for brain and erythrocyte ChE activity, and dose-additive responses for the PhAD duration. These results show that conclusions regarding dose-additivity can vary depending on the endpoint quantified and the specific dosage. However, the acute dose-additive model predicted most of the responses and, in this data set, could be applied to predict effects after repeated exposures for these N-methylcarbamates with reversible effects. This is an abstract ofa presentation and does not reflect EPA policy.