Practical guidance to evaluate in vitro dermal absorption studies for pesticide registration: An industry perspective
Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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Practical guidance to evaluate in vitro dermal absorption studies for pesticide registration : An industry perspective. / Kluxen, Felix M; Felkers, Edgars; Jensen, Signe M; Domoradzki, JeanneY; Lorez, Christine; Fisher, Philip; Wiemann, Christiane.
I: Regulatory Toxicology and Pharmacology, Bind 142, 105432, 2023.Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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TY - JOUR
T1 - Practical guidance to evaluate in vitro dermal absorption studies for pesticide registration
T2 - An industry perspective
AU - Kluxen, Felix M
AU - Felkers, Edgars
AU - Jensen, Signe M
AU - Domoradzki, JeanneY
AU - Lorez, Christine
AU - Fisher, Philip
AU - Wiemann, Christiane
N1 - Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2023
Y1 - 2023
N2 - While there are some regulatory assessment criteria available on how to generally evaluate dermal absorption (DA) studies for risk assessment purposes, practical guidance and examples are lacking. The current manuscript highlights the challenges in interpretating data from in vitro assays and proposes holistic data-based assessment strategies from an industry perspective. Inflexible decision criteria may be inadequate for real data and may lead to irrelevant DA estimates. We recommend the use of mean values for reasonably conservative DA estimates from in vitro studies. In cases where additional conservatism is needed, e.g., due to non-robust data and acute exposure scenarios, the upper 95% confidence interval of the mean may be appropriate. It is critical to review the data for potential outliers and we provide some example cases and strategies to identify aberrant responses. Some regional regulatory authorities require the evaluation of stratum corneum (SC) residue, but here, as a very simple pro-rata approach, we propose to review whether the predicted post 24-h absorption flux exceeds the predicted elimination flux by desquamation because otherwise it is not possible for the SC residue to contribute to systemic dose. Overall, the adjustment of DA estimates due to mass balance (normalization) is not recommended.
AB - While there are some regulatory assessment criteria available on how to generally evaluate dermal absorption (DA) studies for risk assessment purposes, practical guidance and examples are lacking. The current manuscript highlights the challenges in interpretating data from in vitro assays and proposes holistic data-based assessment strategies from an industry perspective. Inflexible decision criteria may be inadequate for real data and may lead to irrelevant DA estimates. We recommend the use of mean values for reasonably conservative DA estimates from in vitro studies. In cases where additional conservatism is needed, e.g., due to non-robust data and acute exposure scenarios, the upper 95% confidence interval of the mean may be appropriate. It is critical to review the data for potential outliers and we provide some example cases and strategies to identify aberrant responses. Some regional regulatory authorities require the evaluation of stratum corneum (SC) residue, but here, as a very simple pro-rata approach, we propose to review whether the predicted post 24-h absorption flux exceeds the predicted elimination flux by desquamation because otherwise it is not possible for the SC residue to contribute to systemic dose. Overall, the adjustment of DA estimates due to mass balance (normalization) is not recommended.
U2 - 10.1016/j.yrtph.2023.105432
DO - 10.1016/j.yrtph.2023.105432
M3 - Review
C2 - 37302560
VL - 142
JO - Regulatory Toxicology and Pharmacology
JF - Regulatory Toxicology and Pharmacology
SN - 0273-2300
M1 - 105432
ER -
ID: 356955722