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APPLICATION OF THE EXPOSURE DOSE ESTIMATING MODEL (ERDEM) TO ASSESSMENT OF DERMAL EXPOSURE IN THE RAT TO MALATHION
Citation:
Evans, M V., F W. Power, C C. Dary, R. TORNERO-VELEZ, AND J. Blancato. APPLICATION OF THE EXPOSURE DOSE ESTIMATING MODEL (ERDEM) TO ASSESSMENT OF DERMAL EXPOSURE IN THE RAT TO MALATHION. Presented at Society of Toxicology, Baltimore, MD, March 21-25, 2004.
Description:
APPLICATION OF THE EXPOSURE DOSE ESTIMATING MODEL (ERDEM) TO ASSESSMENT OF DERMAL EXPOSURE IN THE RAT TO MALATHION.
Evans, M.V1., Power, F.W2., Dary, C.C2., Tornero-Velez, R2., and Blancato, J.N2.
1 NHEERL, US EPA, ORD, ETD, RTP, NC; 2 NERL, US EPA, ORD, EDRB, LV, NV
Renewed interest in the study of dermal exposure to malathion has emerged as a consequence of the prescriptive use of this organophosphorus (OP) insecticide as a pediculicide. The present PBPK/PD model in ERDEM was expanded to include metabolic descriptions needed to link exposure scenarios involving use patterns of malathion with potential health effects. This model allows for the estimation of malathion and malaoxon concentrations in the following organs: skin, fat, kidneys, brain, liver, rapidly perfused, and slowly perfused organs. Physiological values were obtained from the literature. Partition coefficients for parent and metabolites were calculated using tissue-composition based equations. An oral gavage study combining time course metabolite data at different doses was used to calibrate the complex metabolic scheme described in the model. An acceptable fit was obtained for all the metabolite data by adjusting the metabolic parameters in the model. Computer predicted values for malaoxon concentration were then related to acetylcholinesterase (AChE) levels. A preliminary estimate for the maximum velocity (Vmax) of malaoxon activation was 3x10-5 mg/hr-kg, with an affinity constant (Km) of 8x10-3 mg/liter. The AChE equations described aging,as well as regeneration of AChE. The rat PBPK model was used to extrapolate to humans to predict AChE inhibition in children of different ages exposed dermally to malathion when treating head lice. (This work has been funded by the United States Environmental Protection Agency. It has been subjected to Agency review and approved for publication).