Accession Number : ADA322413

Title :   Estimation of Dermal Permeability Coefficients for Dibromomethane and Bromochloromethane Pharmacokinetic Approach.

Descriptive Note : Final rept. Dec 92-Feb 95,

Corporate Author : ARMSTRONG LAB BROOKS AFB TX OCCUPATIONAL AND ENVIRONMENTAL HEALTH DIRECTORATE

Personal Author(s) : Jepson, G. W.

PDF Url : ADA322413

Report Date : DEC 1995

Pagination or Media Count : 183

Abstract : An understanding of dermal permeability of organic chemicals is important where occupational and environmental chemical exposures to humans are likely. It is equally important in the selection of therapeutic agents for and in the design of transdermal drug delivery systems. A great deal of in vitro work has been done to describe the involved transport processes, but very little research attention has been paid to systemic involvements and the overall pharmacokinetics of the relevant uptake and distribution processes. In this work, a physiologically based pharmacokinetic modeling approach is presented which describes chemical concentrations in rat blood following dermal exposures to two halogenated hydrocarbons, dibromomethane and bromochloromethane. These chemicals were dermally administered to live rats using and exposure cell with an area of 3.14/sq cm. Each rat was surgically fitted with a jugular cannula and a dermal exposure cell 24 hours prior to the chemical exposure. Water, corn oil, and mineral oil were used a vehicles. Blood concentrations of the test substances were measured and physiologically based model was used to quantitatively describe their distribution, metabolism, and elimination. An experimentally good mass balance in conjunction with the model allowed permeability coefficients to be estimated for given chemical exposures. These were normalized to actual partitioning into the skin and used to calculate normalized permeability coefficients. The normalized permeability coefficients were then used within the model to predict chemical concentrations in blood that resulted from independent chemical exposures. The model was modified for use in an open dermal exposure and model simulations were generated to predict chemical blood concentrations for a range of exposures and physiological conditions.

Descriptors :   *PHARMACOKINETICS, *DRUGS, *CHEMOTHERAPEUTIC AGENTS, TEST AND EVALUATION, SIMULATION, PERMEABILITY, ENVIRONMENTS, RATS, DISTRIBUTION, HUMANS, CHEMICALS, WATER, CELLS, MASS, METABOLISM, IN VITRO ANALYSIS, TRANSPORT PROPERTIES, COEFFICIENTS, PHYSIOLOGICAL EFFECTS, BALANCE, EXPOSURE(PHYSIOLOGY), OILS, HALOGENATED HYDROCARBONS, MINERAL OILS, SKIN(ANATOMY), CONCENTRATION(CHEMISTRY), BLOOD, CORN, OCCUPATIONAL DISEASES.

Subject Categories : Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE