Dermal Uptake of 18 Dilute Aqueous Chemicals: In Vivo Disappearance-Method Measures Greatly Exceed In Vitro-Based Predictions

作者：Bogen Kenneth T^*

来源：Risk Analysis, 2013, 33(7): 1334-1352.

DOI：10.1111/j.1539-6924.2012.01901.x

• Absorption
• contaminants
• dead
• living
• models
• percutaneous
• regulations
• skin
• uncertainty
• water

Average rates of total dermal uptake (K-up) 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 (K-p) through skin into receptor solution. Widely used (PCR-vitro) methods estimate K-up by applying diffusion theory to increase K-p predictions made by a physico-chemical regression (PCR) model that was fit to a large set of K-p measures. Here, K-up 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 K-up. 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 K-up 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 K-up 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.

• 出版日期2013-7