Toxicological Sciences 53, 13-23 (2000)
Copyright © 2000 by the Society of Toxicology
Physiologically Based Pharmacokinetic Modeling of the Temperature-Dependent Dermal Absorption of Chloroform by Humans following Bath Water Exposures
* Battelle Memorial Institute, Pacific Northwest Division, Chemical Dosimetry, Post Office Box 999, P7-59, 902 Battelle Boulevard, Richland, Washington 99352;
Battelle Memorial Institute, Atmospheric Science and Applied Technology, Columbus, Ohio 43201;
Office of Research and Development, U.S. Environmental Protection Agency, Reston, Virginia 20192
The kinetics of chloroform in the exhaled breath of human volunteers exposed skin-only via bath water (concentrations < 100 ppb) were analyzed using a physiologically based pharmacokinetic (PBPK) model. Significant increases in exhaled chloroform (and thus bioavailability) were observed as exposure temperatures were increased from 30 to 40°C. The blood flows to the skin and effective skin permeability coefficients (Kp) were both varied to reflect the temperature-dependent changes in physiology and exhalation kinetics. At 40°C, no differences were observed between males and females. Therefore, Kps were determined (~0.06 cm/hr) at a skin blood flow rate of 18% of the cardiac output. At 30 and 35°C, males exhaled more chloroform than females, resulting in lower effective Kps calculated for females. At these lower temperatures, the blood flow to the skin was also reduced. Total amounts of chloroform absorbed averaged 41.9 and 43.6 µg for males and 11.5 and 39.9 µg for females exposed at 35 and 40°C, respectively. At 30°C, only 2/5 males and 1/5 females had detectable concentrations of chloroform in their exhaled breath. For perspective, the total intake of chloroform would have ranged from 79–194 µg if the volunteers had consumed 2 liters of water orally at the concentrations used in this study. Thus, the relative contribution of dermal uptake of chloroform to the total body burdens associated with bathing for 30 min and drinking 2 liters of water (ignoring contributions from inhalation exposures) was predicted to range from 1 to 28%, depending on the temperature of the bath.
Key Words: chloroform; PBPK modeling; dermal bioavailability; temperature dependence; human.
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