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A PBPK Model of Pyrethroid Pesticides for Application in Risk Assessment

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Abstract: Pyrethroids are among the most potent and effective insecticides available, and are applied singly or in combination in agricultural and indoor insect control. The Food Quality Protection Act (FQPA) of 1996 requires the US EPA to consider the cumulative (multi-chemical) effects of exposure to pesticides having a 'common mechanism of toxicity'. For the risk assessment of pyrethroids, estimation of the extent of exposure and detailed knowledge of their kinetics is of prime importance. Towards this end, we have developed a physiologically-based pharmacokinetic (PBPK) model for evaluating dose resulting from residential and dietary exposures in humans. The application of PBPK models in risk assessment offers key benefits including: prediction of target dose, dose extrapolation in cases of non-linearity, and route of exposure extrapolation. In this project, studies examining the pharmacokinetics of permethrin and deltamethrin in rodents were used to derive the basic model structure. The model included skin, fat, liver, brain, and lumped tissue compartments. Physiological values were obtained from the literature. Tissue-blood partition coefficients were based on Log[Kow] and tissue composition. The model provides a systematic and quantitative framework for considering the impact of aggregate exposure routes (dermal, oral, inhalation). Human urinary excretion studies and computational methods were employed to derive parameters relevant to humans. The low coefficients of dermal permeability (Kp) of these highly lipophillic pesticides (Log[Kow]: 4.5-7) and their low volatility (Vapor Pressure: 10 -11 - 10 -7 mm Hg) suggest that the oral routes (dietary and oral non-dietary) and inhalation (aerosol) have greatest influence on target tissue dose. These preliminary findings will aid in shaping the development of a cumulative risk model of pyrethroids.

The opinions expressed in this manuscript are those of the author and do not reflect opinions or policy of the Environmental Protection Agency. Mention of trade names or commercial products does not constitute an endorsement or recommendation for use.
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Citation:Tornero-Velez, R., C. C. Dary, M. Dellarco, and J. Blancato. A PBPK Model of Pyrethroid Pesticides for Application in Risk Assessment. Presented at Exposure Assessment in a Changing Environment, Utrecht, The Netherlands, June 16-18, 2004.
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Contact: Liz Hope - (919) 541-2785 or hope.elizabeth@epa.gov
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Division: Human Exposure & Atmospheric Sciences Division
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Branch: Exposure & Dose Research Branch
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Product Type: Abstrct/Oral
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Presented: 06/17/2004
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Related Entries:
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Bullet Item Models and Modeling Methods for Assessing Human Exposure and Dose to Toxic Chemicals and Pollutants
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Last Updated on Monday, October 22, 2007
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