Practical guidance to evaluate in vitro dermal absorption studies for pesticide registration: An industry perspective.
Data assessment
Dermal absorption
Dermal penetration
Non-dietary risk assessment
Outliers
Journal
Regulatory toxicology and pharmacology : RTP
ISSN: 1096-0295
Titre abrégé: Regul Toxicol Pharmacol
Pays: Netherlands
ID NLM: 8214983
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
received:
13
02
2023
revised:
05
06
2023
accepted:
08
06
2023
medline:
17
7
2023
pubmed:
12
6
2023
entrez:
11
6
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37302560
pii: S0273-2300(23)00100-9
doi: 10.1016/j.yrtph.2023.105432
pii:
doi:
Substances chimiques
Pesticides
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
105432Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SMJ has no conflicts of interest to declare. FMK, EF, JYD, CL, PF and CW are members of CropLife Europe expert groups and are employed by commercial companies with a financial interest in the subject matter. CropLife Europe finances the publication fees of the current manuscript.