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Predictive Organophosphorus (Op) Pesticide Qsars and PBPK/Pd Models for Risk Assessment of Susceptible Sub-Populations

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Abstract: Successful use of the Exposure Related Dose Estimating Model (ERDEM) in risk assessment of susceptible human sub-populations, e.g., infants and children, requires input of quality experimental data. In the clear absence of quality data, PBPK models can be developed and possibly enhanced through the judicious use of predictive Quantitative Structure Activity Relationships (QSAR). A thorough review of the available physicochemical and biological data revealed substantial data gaps and variances among experimental protocols. Published OP rat liver P450 microsomal Vmax, Km values on oxon formation were reviewed and compared with current studies with human liver microsomal P450 CYPs. Information on the inhibition of B-esterases (kis) by oxons, hydrolysis of the oxons (Vmax, Km) by plasma and liver A-esterases were reviewed along with conjugation reactions involving leaving groups. Deficiencies were evident for certain PBPK model parameters related to percutaneous absorption, i.e., Kp (cm/h), and tissue/blood partition coefficients and metabolic parameter such as Vmax and Km). From an understanding of the limitations of the available data, a predictive scenario-based PBPK/PD model was generated for 31 OP insecticides of interest to EPA from provisional QSAR estimates. New research is needed to obtain the necessary data for continued model construction and validation.

This work has been funded (wholly) or (in part) by the United States Environmental Protection Agency under Interagency Assistance Agreement (DW 47944301) to GSA. It has been subjected to Agency review and approved for publication.

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Citation:Dary, C. C., J. B. Knaak, F. W. Power, C. B. Thompson, and J. N. Blancato. Predictive Organophosphorus (Op) Pesticide Qsars and PBPK/Pd Models for Risk Assessment of Susceptible Sub-Populations. Presented at Society of Toxicology, Las Vegas, NV, September 26-27, 2002.
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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: 09/26/2002
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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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