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USE OF PBPK/PD MODELS AND FOLIAR TRANSFER COEFFICIENTS IN ASSESSING REENTRY INTO PESTICIDE TREATED CITRUS AND TURF
Citation:
Knaak, J. B., C C. Dary, G. T. Patterson, AND J N. Blancato. USE OF PBPK/PD MODELS AND FOLIAR TRANSFER COEFFICIENTS IN ASSESSING REENTRY INTO PESTICIDE TREATED CITRUS AND TURF. Presented at Annual Meeting of Society of Toxicology, Philadelphia, PA, March 19-23, 2000.
Impact/Purpose:
Research will be conducted to develop and apply integrated microenvironmental, and physiologically-based pharmacokinetic (PBPK) exposure-dose models and methods (that account for all media, routes, pathways and endpoints). Specific efforts will focus on the following areas:
1) Develop the Exposure Related Dose Estimating Model (ERDEM) System.
Includes: Updating the subsystems and compartments of the ERDEM models with those features needed for modeling chemicals of interest to risk assessors;
Designing and implementing the graphical user interface for added features.
Refining the exposure interface to handle various sources of exposure information;
Providing tools for post processing as well as for uncertainty and variability analyses;
Research on numerical and symbolic mathematical/statistical solution methods and computational algorithms/software for deterministic and stochastic systems analysis.
2) Apply ERDEM and other quantitative models to understand pharmacokinetics (PK) and significantly reduce the uncertainty in the dosimetry of specific compounds of regulatory interest.
Examples of the applications are:
exposure of children to pesticides
study design
route-to-route extrapolation
species extrapolation
experimental data analysis
relationship between parametric uncertainty and the distribution of model results
validity of scaling methods within species
validity of scaling methods from one species to another species
reduction of uncertainty factors for risk assessment
Description:
Physiologically based pharmacokinetic and pharmacodynamic (PBpK/PD) models describing the fate of dermally applied "C-ring labeled ethyl parathion and isofenphos and inhibition of H-esterases (acetyleholin-, butyrylcholine-and carboxyl-) by oxons in the rat were used in conjunction with foliar transfer coeffcients to assess reentry levels/intervals into treated citrus (parathion) and turf (isofenphos) to harvest fruit ox for recreational use, respectively. Michaelis-Menten kinetics were used to describe the desulfuration of parathion and isofenphos to their oxons and hydrolysis of parent chemicals and oxons. Bimolecular rate constants, ki (pM'1 hr'1) were used to describe inhibition. Rates for enzyme synthesis, reactivation and aging were considered. A foliar transfer coefficient (slope of the regression line relating exposure in pg/h and foliar dislodgeable residue in ug/cm2, (twosided leaf residue) of 104 cm2/h was used in both models. According to the PBPK/PD models, -3% of the parathion and isofenphos foliar residues transferred to human skin were dermally absorbed over an 8 hr wok day in citrus or 2 hz on turf. Exposure to foliar residues of 0.09 ug/cm2 (two-sided leaf residue) of parathion on citrus and 0.6 p,g/cmz (two-sided leaf residue) of isofenphas on turf resulted in no red blood cell cholinesterase inhibition. On the basis of ChE NOELS of 0.05 mg/kg/day for parathion and isofenphos in chronic studies, margin of exposures (MOEs) of 16 and 10, respectively, were calculated.
The U.S. Environmental protection Agency (EPA), through its Office of Research and Development, participated in this research and approved this abstract as a basis for an oral presentation. The actual presentation has not been peer reviewed by the EPA.