Physiologically based pharmacokinetic modeling of the temperature-dependent dermal absorption of chloroform by humans following bath water exposures

The kinetics of chloroform in the exhaled breath of human volunteers expose d 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 degrees 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 kin etics. At 40 degrees C, no differences were observed between males and fema les. Therefore, Kps were determined (similar to 0.06 cm/hr) at a skin blood how rate of 18% of the cardiac output. At 30 and 35 degrees C, males exhal ed more chloroform than females, resulting in lower effective Kps calculate d 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 m u g for males and 11.5 and 39.9 mu g for females exposed at 35 and 40 degre es C, respectively. At 30 degrees C, only 2/5 males and 1/5 females had det ectable concentrations of chloroform in their exhaled breath. For perspecti ve, the total intake of chloroform would have ranged from 79-194 mu g if th e volunteers had consumed 2 liters of water orally at the concentrations us ed in this study. Thus, the relative contribution of dermal uptake of chlor oform to the total body burdens associated with bathing for 30 min and drin king 2 liters of water (ignoring contributions from inhalation exposures) w as predicted to range from 1 to 28%, depending on the temperature of the ba th.