Accession Number : ADA308303
Title : The Utility of Partition Coefficients in Dermal Model Development for Rat and Guinea Pig.
Descriptive Note : Interim rept. Dec 93-Dec 94,
Corporate Author : ARMSTRONG LAB WRIGHT-PATTERSON AFB OH TOXICOLOGY DIV
Personal Author(s) : Garrity, B. L. ; Jepson, G. W. ; McDougal, J. N.
PDF Url : ADA308303
Report Date : FEB 1995
Pagination or Media Count : 18
Abstract : The ability to extrapolate usable dermal penetration data from one species to another is fundamental to specific applications in risk assessment. The goal of this work is to quantitatively explain the movement of chemicals across the dermal barrier in differing species. The chemical absorbed during the exposure in amount per time per area (mg/hr/cm(2)) is defined as the flux of the chemical. In order to estimate the total amount of chemical absorbed during the exposure, a physiologically-based pharmacokinetic (PBPK) model can be used if appropriate physiological and kinetic parameters are known. A primary data requirement of PBPK models is the partition coefficients for the chemical in blood and each of the tissue groups that display distinct kinetic behavior. In this study, blood, muscle, liver, and fat harvested from male Fischer 344 rats and male Hartley guinea pigs were exposed to four test chemicals. Using a vial equilibration method, the tissue:air partition coefficient was determined for Chloropentafluorobenzene (CPFB), 1,2-Dichlorobenzene (DCB), 1-Iodoheptafluoropropane (C(3)F(7)I) and Perfluorohexyl Iodide (C(6)F(13)I). The tissue:air partition coefficients generated in this study covered a four order magnitude range and were incorporated into PBPK models that were used for describing species differences in organic chemical absorption through the dermal barrier.
Descriptors : *CHEMICALS, *COEFFICIENTS, *PHARMACOKINETICS, REQUIREMENTS, RISK, DATA MANAGEMENT, RATS, PARAMETERS, TEST EQUIPMENT, ESTIMATES, PENETRATION, ORGANIC MATERIALS, VOLATILITY, ANIMALS, PHYSIOLOGY, FIRE FIGHTING, KINETICS, ABSORPTION, LIVER, HALOGENATED HYDROCARBONS, SKIN(ANATOMY), BLOOD, AIRCRAFT FIRE CONTROL SYSTEMS, TOXICOLOGY, BEHAVIORAL SCIENCES, FIRE EXTINGUISHERS, PHYTOTOXICITY, GUINEA PIGS, ORGANIC CHEMISTRY, AIR POLLUTION EFFECTS(ANIMALS).
Subject Categories : Pharmacology
Distribution Statement : APPROVED FOR PUBLIC RELEASE