IN-VITRO AND IN-VIVO PERCUTANEOUS-ABSORPTION OF C-14 CHLOROFORM IN HUMANS

Chloroform has been found in potable water and there is concern that s ignificant dermal absorption may arise from daily bathing and other ac tivities. The present study examines percutaneous absorption of C-14-c hloroform in vivo using human volunteers and in vitro using fresh, exc ised human skin in a flow-through diffusion cell system. Fifty microli tre doses of either 1000 mu g ml(-1) chloroform in distilled water, (1 6.1 mu g cm(-2)) or 5000 mu g ml(-1) of chloroform in ethanol, (80.6 m u g cm(-1)) were applied to the forearm of volunteers with exhaled air and urine being collected for analysis. Single doses of either 0.4 mu g ml(-1) chloroform in distilled water (low dose, 0.62 mu g cm(-2), 1 .0 ml dosed) or 900 mu g ml(-1) chloroform in distilled water (high do se, 70.3 mu g cm(-2), 50 mu l dosed) were applied to discs of the exci sed abdominal skin placed in flow-through diffusion cells and perfused with Hepes buffered Hank's balanced 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 maximu m pulmonary excretion occurred between 15 min and 2 h after dosing. Th e 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 demonstra te that a significant amount of the dissolved chloroform penetrates th rough 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.