Systemic Uptake and Clearance of Chloroform by Hairless Rats Following DermalExposure: I. Brief Exposure to Aqueous Solutions

摘要

The systemic uptake of chloroform from dilute aqueous solutions into livehairless rats under conditions simulating dermal environmental exposure was studied. Whole blood was sampled during a 30-minute immersion of an animal within water containing a known concentration of chloroform and then for 5.5 hours following its removal from the bath. The amount of chloroform systemically absorbed was determined by comparing the AUCs of the blood concentration versus time plots from dermal exposure to that obtained after IV infusion (for a period of 30 minutes) of an aqueous solution containing a known amount of chloroform (positive control). Although dermal data implied 2-compartment disposition characteristics, IV infusion data fit best to a 3-compartment disposition. Linear pharmacokinetics was observed both by IV administration and percutaneous absorption at the dose levels studied. Our findings suggest that about 10.2 mg of chloroform was systemically absorbed after dermal exposure of a rat to an aqueous solution of 0.44 mg/ml. This amount is substantially higher than the predictions of risk models put forth by other investigators. Reasonable agreement existed between a past estimate of uptake based on depletion of bath level of chloroform and the actual uptake measured in these experiments. The estimated onset of systemic entry seen here is entirely consistent with our estimate of how long it takes to establish the diffusion gradient across the stratum corneum based on tape stripping.