Dermal uptake of 18 dilute aqueous chemicals: in vivo disappearance-method measures greatly exceed in vitro-based predictions.
Average rates of total dermal uptake (Kup ) from short-term (e.g., bathing) contact with dilute aqueous organic chemicals (DAOCs) are typically estimated from steady-state in vitro diffusion-cell measures of chemical permeability (Kp ) through skin into receptor solution. Widely used ("PCR-vitro") methods estimate Kup by applying diffusion theory to increase Kp predictions made by a physico-chemical regression (PCR) model that was fit to a large set of Kp measures. Here, Kup predictions for 18 DAOCs made by three PCR-vitro models (EPA, NIOSH, and MH) were compared to previous in vivo measures obtained by methods unlikely to underestimate Kup . A new PCR model fit to all 18 measures is accurate to within approximately threefold (r = 0.91, p < 10(-5) ), but the PCR-vitro predictions (r > 0.63) all tend to underestimate the Kup measures by mean factors (UF, and p value for testing UF = 1) of 10 (EPA, p < 10(-6) ), 11 (NIOSH, p < 10(-8) ), and 6.2 (MH, p = 0.018). For all three PCR-vitro models, log(UF) correlates negatively with molecular weight (r(2) = 0.31 to 0.84, p = 0.017 to < 10(-6) ) but not with log(vapor pressure) as an additional predictor (p > 0.05), so vapor pressure appears not to explain the significant in vivo/PCR-vitro discrepancy. Until this discrepancy is explained, careful in vivo measures of Kup should be obtained for more chemicals, the expanded in vivo database should be compared to in vitro-based predictions, and in vivo data should be considered in assessing aqueous dermal exposure and its uncertainty.
Exponent, Inc., 475 14th Street, Suite 400, Oakland, CA 94612, USA. kbogen@exponent.com
Kenneth T
KT
Bogen
D000818:Animals; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption