Comparison of dermal uptake data for pharmacokinetic model development in rats.
Gies-RA; Hinderliter-PM; Woodstock-AD; Thrall-KD
Toxicologist 2006 Mar; 90(1):121-122
Percutaneous absorption is an occupationally important route of exposure for solvents and other chemicals. Prior dermal studies have shown that while dermal exposures can be a significant contributor to total absorbed dose, predictive methods do not generally provide an accurate estimate of percutaneous absorption. With the goal of providing data suitable for pharmacokinetic model development, dermal exposures to both lipophilic and hydrophilic chemicals were conducted in F344 rats. Uptake was measured via exhaled breath to allow detection of rapid concentration changes. Exposures were conducted by placing a set amount of test compound, either neat or in an aqueous formulation, into a sealed chamber secured to the back of the rat for approximately three hours and placing the animal in a gas uptake chamber. To test sample chamber integrity, the animal was placed back into the gas uptake chamber for 30 minutes after sacrifice. Exposures were conducted for acetone, ethyl benzene, styrene, methyl ethyl ketone (MEK) and methyl n-butyl ketone (MnBK). Exposures were run with neat test material, in aqueous vehicle, or both neat and aqueous depending on solubility. All exposures were repeated at least three times and experiments with leaking test chambers were discarded. The concentration of acetone peaked at approximately 10-20 minutes while styrene and ethylbenzene were still increasing at the end of the three hour exposures. This data will allow the addition of a dermal exposure route to existing pharmacokinetic models for acetone, ethyl benzene, styrene and MEK. Additional exposures (oral, intraperitoneal and gas uptake) were conducted as the basis for constructing a model for MnBK.
Laboratory-animals; Animals; Animal-studies; Solvents; Exposure-levels; Exposure-chambers; Exposure-assessment
Disease and Injury: Allergic and Irritant Dermatitis
The Toxicologist. Society of Toxicology 45th Annual Meeting and ToxExpo, March 5-9, 2006, San Diego, California
Battelle Memorial Institute, Richland, Washington