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Dermal Uptake of 18 Dilute Aqueous Chemicals: In Vivo Disappearance‐Method Measures Greatly Exceed In Vitro ‐Based Predictions
Author(s) -
Bogen Kenneth T.
Publication year - 2013
Publication title -
risk analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.972
H-Index - 130
eISSN - 1539-6924
pISSN - 0272-4332
DOI - 10.1111/j.1539-6924.2012.01901.x
Subject(s) - in vivo , in vitro , aqueous solution , chemistry , biophysics , environmental chemistry , biochemistry , biology , organic chemistry , microbiology and biotechnology
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.