Dermal Uptake of 18 Dilute Aqueous Chemicals: In Vivo Disappearance‐Method Measures Greatly Exceed In Vitro‐Based Predictions. Issue 7 (10th October 2012)

• Record Type: Journal Article
• Authors: Bogen, Kenneth T.
• Is Part Of: Risk analysis. Volume 33:Issue 7(2013)
• Page Start: 1334
• Page End: 1352
• Publication Date: 2012-10-10
• Subjects: Technology -- Risk assessment -- Periodicals; 658.403
• DOI: 10.1111/j.1539-6924.2012.01901.x
• Languages: English
• ISSNs: 0272-4332

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Average rates of total dermal uptake (<italic>K</italic><sub>up</sub>) from short‐term (e.g., bathing) contact with dilute aqueous organic chemicals (DAOCs) are typically estimated from steady‐state <italic>in vitro</italic> diffusion‐cell measures of chemical permeability (<italic>K</italic><sub>p</sub>) through skin into receptor solution. Widely used ("PCR‐<italic>vitro</italic>") methods estimate <italic>K</italic><sub>up</sub> by applying diffusion theory to increase <italic>K</italic><sub>p</sub> predictions made by a physico‐chemical regression (PCR) model that was fit to a large set of <italic>K</italic><sub>p</sub> measures. Here, <italic>K</italic><sub>up</sub> predictions for 18 DAOCs made by three PCR‐<italic>vitro</italic> models (EPA, NIOSH, and MH) were compared to previous <italic>in vivo</italic> measures obtained by methods unlikely to underestimate <italic>K</italic><sub>up</sub>. A new PCR model fit to all 18 measures is accurate to within approximately threefold (<italic>r</italic> = 0.91, <italic>p</italic> < 10<sup>−5</sup>), but the PCR‐<italic>vitro</italic> predictions (<italic>r</italic> > 0.63) all tend to underestimate the <italic>K</italic><sub>up</sub> measures by mean factors (UF, and <italic>p</italic> value for testing UF = 1) of 10 (EPA, <italic>p</italic> < 10<sup>−6</sup>), 11 (NIOSH, <italic>p</italic> < 10<sup>−8</sup>), and 6.2 (MH, <italic>p</italic> = 0.018). For all three PCR‐<italic>vitro</italic> models, log(UF) correlates negatively with molecular weight (<italic>r</italic><sup>2</sup> = 0.31 to 0.84, <italic>p</italic> = 0.017 to < 10<sup>−6</sup>) but not with log(vapor pressure) as an additional predictor (<italic>p</italic> > 0.05), so vapor pressure appears not to explain the significant <italic>in vivo</italic>/PCR‐<italic>vitro</italic> discrepancy. Until this discrepancy is explained, careful <italic>in vivo</italic> measures of <italic>K</italic><sub>up</sub> should be obtained for more chemicals, the expanded <italic>in vivo</italic> database should be compared to <italic>in vitro‐</italic>based predictions, and <italic>in vivo</italic> data should be considered in assessing aqueous dermal exposure and its uncertainty.</p> </abstract>