Evaluation of the dermal absorption of methyl ethyl ketone in F344 rats using real-time breath analysis and PBPK modeling.
Toxicologist 2002 Mar; 66(1-S):167
Methyl ethyl ketone (MEK) is an industrial solvent found as a component of a variety of paints and coatings. Dermal exposure to MEK can result from the occupational or household use of paints and other commercial products. To understand the significance of these exposures, the dermal bioavailability of MEK was assessed in F344 male rats using a combination of real-time exhaled breath analysis and physiologically based pharmacokinetic (PBPK) modeling. Animals were exposed to MEK at a 5 mg/ml aqueous concentration using a 2.5-cm diameter occluded glass patch system attached to a clipper-shaved area on the back of the rat. Immediately following exposure the animal was placed in a glass off-gassing chamber and exhaled breath was monitored as chamber concentration in real time using an ion trap mass spectrometer (MS/MS). This real-time methodology was able to discern the uptake, peak concentration and clearance phases associated with the dermal exposure. For example, the exhaled breath profile clearly demonstrated the rapid absorption of MEK, with peak chamber concentrations ranging from 20 to 25 ppm observed within 30-60 minutes from the start of exposure. The PBPK model describing the exposure and off-gassing system was used to estimate a single dermal permeability coefficient to describe all the sets of exhaled breath data from n=6 animals. These rat studies using aqueous MEK will form the basis for comparing the dermal bioavailability of MEK in various paint products and may ultimately aid in understanding human health risk under a variety of exposure scenarios.
Paints; Coatings; Dermatology; Animal-studies; Laboratory-animals; Solvents; Skin-absorption; Skin-exposure
Disease and Injury: Allergic and Irritant Dermatitis
The Toxicologist. Society of Toxicology 41st Annual Meeting and ToxExpo, March 17-21, 2002, Nashville, Tennessee
Battelle Memorial Institute, Richland, Washington