Systemic uptake and clearance of chloroform by hairless rats following dermal exposure: II. Absorption of the neat solvent.

Abstract

Blood concentrations of chloroform were monitored after exposing small areas (approximately 5.5 cm2) of the backs of hairless rats to liberal excesses of the solvent for either 1, 3, or 8 min. The amounts absorbed were quantified by comparing areas-under-the-curves (AUCs) of blood concentration versus time plots to the AUC obtained on infusing an aqueous chloroform solution of known concentration for 30 min (positive control). Chloroform penetrated the dermal barrier rapidly, the skin's horny layer and the deeper skin tissues acting as reservoirs for chloroform only for short durations. Evaporative and physiological clearance from these reservoirs was rapid once the chloroform was removed from the surface. Pressure of the template used to confine the exposure affected uptake. For blood levels, the time to reach the maximum blood concentration increased with increased exposure duration. Amounts absorbed also depended on exposure duration. Blood level profiles indicated systemic uptake of chloroform following a 3-min exposure was about 1.3-fold higher than for a 1-min exposure (not significant), while the 8-min exposure produced an AUC roughly 3.8-fold higher than found at 3 min (p = 0.026). Chloroform is rapidly cleared from rat blood (terminal elimination rate constant = 0.009/min). Calculations indicated that its absorption from these area-limited exposures far exceeds that which would be absorbed had the chloroform been presented to the skin as a saturated aqueous solution.