Chloroform has been found in potable water and there is concern that significant dermal absorption may arise from daily bathing and other activities. The present study examines percutaneous absorption of 14C-chloroform in vivo using human volunteers and in vitro using fresh, excised human skin in a flow-through diffusion cell sys tem. Fifty microlitre doses of either 1000 μg ml-1 chloro form in distilled water, (16.1 μg cm-2) or 5000 μg ml-1 of chloroform in ethanol, (80.6 μg cm-1) were applied to the forearm of volunteers with exhaled air and urine being collected for analysis. Single doses of either 0.4 μg ml-1 chloroform in distilled water (low dose, 0.62 μg cm-2, 1.0 ml dosed) or 900 μg ml-1 chloroform in distilled water (high dose, 70.3 μg cm -2, 50 μl dosed) were applied to discs of the excised abdominal skin placed in flow-through dif fusion cells and perfused with Hepes buffered Hank's bal anced salt solution, with a wash at 4 h. In vivo absorption was 7.8 ± 1.4% (water as vehicle) and 1.6 ± 0.3% (ethanol as vehicle). Of the dose absorbed in vivo, more than 95% was excreted via the lungs (over 88% of which was CO2), and the maximum pulmonary excretion occurred between 15 min and 2 h after dosing. The percentage of dose absorbed in vitro (skin + perfusate) was 5.6 ± 2.7% (low dose) and 7.1 ± 1.4% (high dose). The above data demon strate that a significant amount of the dissolved chloro form penetrates through the human skin, and that a higher percentage of the applied dose was absorbed using water as vehicle. In addition, the in vitro method offers a good estimate for in vivo data.
Assessment of Vehicle Volatility and Deposition Layer Thickness in Skin Penetration Models