Estimation of volatile organic compound exposure concentrations and time to reach a specific dermal absorption using physiologically based pharmacokinetic modeling

A procedure was proposed to estimate dermal exposures based on a physiologically based pharmacokinetic (PBPK) model developed in rats. The study examined vapor concentrations ranging from 500 to 10,000 ppm for dibromomethane and 2,500 to 40,000 ppm for bromochloromethane. These concentrations were reconstructed based on chemical blood levels measured in 4 hr, with errors varying from 0.0% to 52.0%. The PBPK approach adequately predicted the blood concentrations and helped simulate contaminant transport through the stratum corneum and distribution in the body compartments. The proposed technique made it possible to estimate the skin absorption time (SAT) obtained from acute inhalation toxicity data. An inverse relationship exists between the SAT and exposure concentration. The method can be helpful in toxicology and risk assessment of hazardous volatile organic compounds.