Initial uptake kinetics in human skin exposed to dilute aqueous trichloroethylene in vitro

In vitro uptake of 14C-labeled trichloroethylene (TCE) from dilute (approximately 5-ppb) aqueous solutions into human surgical skin was measured using accelerator mass spectrometry (AMS). We analyzed 105 breast-tissue samples obtained from three subjects, representing 27 separate exposure experiments conducted at approximately 20 degrees C for 0, 1, 5, 15, 30, or 60 min. The AMS data obtained positively correlate with (p approximately 0) and vary significantly nonlinearly with (p = 0.0094) exposure duration. These data are inconsistent (p approximately 0) with predictions made for TCE by a proposed U.S. Environmental Protection Agency (USEPA) dermal-exposure model, even when uncertainties in its recommended parameter values for TCE are considered, but are consistent (p = 0.17) with a 1-compartment model for exposed skin-surface tissue governed in vitro by a maximum effective permeability of K*p = 0.28 cm h-1 (+/- 7.0%) and a first-order rate constant of k1 = 1.2 h-1 (+/- 16%). The apparent compartment depth is estimated to be approximately 40-100 microns, i.e., to comprise much or all of the epidermis. In contrast, the USEPA model implies only negligible TCE penetration beyond SC during a 1-h exposure. The K*p estimate based on the 1-compartment model fit is consistent with estimates for TCE based on in vivo studies, which supports the hypothesis that the USEPA model underpredicts short-term dermal uptake of TCE from water. It is shown that for humans, this fit also implies that normalized total uptake of TCE from water by short-term dermal contact in vivo is predicted to be fK*p, where f is approximately 80% for longer normothermic exposures and approximately 95% during a brief hot shower or bath. This study illustrates the power of AMS to facilitate analyses of contaminant biodistribution and uptake kinetics at very low environmental concentrations.