In vitro human skin permeation of benzene in gasoline: Effects of concentration, multiple dosing and skin preparation.

In vitro human skin benzene permeation was measured from gasoline formulations with benzene concentrations ranging from 0.8 to 10 vol% and from neat benzene. Steady-state fluxes (JSS), permeability coefficients (kp) and lag times (tlag) were calculated from infinite dose exposures. Permeation of benzene from small gasoline doses administered over a two-day period was also studied. The thermodynamic activity of benzene in gasoline at 30 °C was determined and the solution is near-ideal over the range from 0.8 to 100 vol%. JSS through human epidermal membranes were linear (R2=0.92) with concentration over the range from 0.8 to 10 vol%. JSS (μg/cm2/h) from gasoline (0.8 vol% benzene=6.99 mg/ml) through epidermis and full-thickness skin were 9.37±1.41 and 1.82±0.44, respectively. Neat benzene JSS was 566±138. Less than 0.25% of the total applied benzene mass from finite doses (10 μl/cm2) of gasoline was detected in receptor cells, and a small reduction of barrier function was observed from six total doses administered over 2 days. Application of these results to dermal exposure assessment examples demonstrates a range of systemic benzene uptakes that can be expected from occupational and consumer dermal exposures to gasoline, depending on the type and extent of exposure.