Dermal absorption study OECD TG 428 mass balance recommendations based on the EFSA database

Kluxen, Felix M.; Grégoire, Sébastien; Schepky, Andreas; Hewitt, N.; Klarić, Martina; Domoradzki, Jeanne; Felkers, Edgars; Fernandes, João Miguel; Fisher, P.; McEuen, Steven F.; Parr-Dobrzanski, R.; Wiemann, Christiane

doi:10.1016/j.yrtph.2019.104475

Cited by 8 publications

(2 citation statements)

References 21 publications

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“…Mean human in vitro data from the EFSA dermal absorption database (EFSA DA DB) were selected based on the criteria presented in Kluxen et al ( 2019 ); further “Wax block” and “Pasta bait” formulation types were excluded. Mean human in vitro data using studies with multiple concentrations and mean rat in vitro and in vivo data and corresponding human in vitro data were collected from CLE member companies in a Microsoft Excel (Redmond, USA) sheet.…”

Section: Methodsmentioning

confidence: 99%

A new conceptional model for deriving average dermal absorption estimates from studies with multiple tested concentrations for non-dietary risk assessment of pesticides

Kluxen¹,

Felkers²,

McEuen

et al. 2022

Arch Toxicol

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Dermal absorption values are used to translate external dermal exposure into potential systemic exposure for non-dietary risk assessment of pesticides. While the Environmental Protection Agency of the United States of America (US EPA) derives a common dermal absorption factor for active substances covering all related products, the European Food Safety Authority (EFSA) requests specific product-based estimates for individual concentrations covering the intended use rates. The latter poses challenges, because it disconnects exposure dose from applied dose in absorption studies, which may not be suitable in scenarios where concentration is not relevant. We analyzed the EFSA dermal absorption database, collected 33 human in vitro studies from CropLife Europe (CLE) companies, where ≥3 in-use dilution concentrations were tested, and 15 dermal absorption triple pack datasets. This shows that absolute dermal absorption correlates with absolute applied dose on a decadic logarithm-scale, which is concordant with the toxicological axiom that risk is driven by exposure dose. This method is radically different from the current European approach focused on concentrations and offers new insights into the relationship of internal and external exposure doses when utilizing data from in vitro studies. A single average dermal absorption value can be simply derived from studies with multiple tested concentrations, by calculating the y-intercept of a linear model on a decadic logarithm scale while assuming a slope of 1. This simplifies risk assessment and frees resources to explore exposure refinements. It also serves as a basis to harmonize dermal absorption estimation globally for use in exposure-driven risk assessments.

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Section: Methodsmentioning

confidence: 99%

A new conceptional model for deriving average dermal absorption estimates from studies with multiple tested concentrations for non-dietary risk assessment of pesticides

Kluxen¹,

Felkers²,

McEuen

et al. 2022

Arch Toxicol

Self Cite

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show abstract

“…Investigating the reference chemical testosterone, Heylings et al [ 27 ] demonstrated that a mass balance of 99% could be achieved for testosterone using a radio-labelled substance and conducting the experiments according to a highly standardised protocol in agreement with OECD TG 428 [ 4 ]. While these results referred to one substance only (testosterone) and are based on an in-house database of in vitro dermal absorption studies on the pesticides of a single laboratory [ 28 ], Kluxen et al [ 29 ] described the EFSA recovery criterion as not realistic based on the interpretation of statistical analysis of the EFSA dataset [ 3 ] on in vitro dermal absorption studies of pesticides, explaining these findings, e.g., with low laboratory standards. In the EU, EFSA requirements [ 3 ] have to be met for pesticides in dermal absorption studies performed according to OECD 428.…”

Section: Resultsmentioning

confidence: 99%

In Vitro Human Dermal Absorption Studies on Pesticides in Complex Mixtures: Investigation of Guidance Criteria and Possible Impact Parameters

Pieper,

Engel,

Wend

et al. 2024

Toxics

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Pesticides must not pose unacceptable risks to human health, so risk assessments are conducted before products are authorised. Dermal exposure is often the main route of intake, so estimating realistic and trustworthy dermal absorption values is crucial for risk assessment. Although there are agreed test guidelines for in vitro dermal absorption studies, not every product is tested due to cost reasons. The present dataset consists of 945 individual in vitro experiments on the dermal absorption of human skin with 179 active substances of pesticides in 353 different mixtures, including concentrates and dilutions. The dataset was evaluated to identify the possible impacts of experimental conditions and physico-chemical properties on dermal absorption. The dataset was also analysed to assess the appropriateness of the pro rata correction for untested dilutions, and the set concentration cut-off to decide on the dilution status for choosing a default value on dermal absorption. The study found that the implementation of specific guidelines improved the harmonisation of study conduct, with support for approaches such as pro rata correction and default values. Further analysis of the specific co-formulants may identify influencing factors that may be more important than the experimental variables.

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Comparative study of the percutaneous permeation and bioaccumulation of a cyclic siloxane using frozen-thawed and nonfrozen ex vivo human skin

Mojsiewicz‐Pieńkowska

Krenczkowska

Bazar

et al. 2022

Toxicology in Vitro

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Dermal absorption study OECD TG 428 mass balance recommendations based on the EFSA database

Cited by 8 publications

References 21 publications

A new conceptional model for deriving average dermal absorption estimates from studies with multiple tested concentrations for non-dietary risk assessment of pesticides

A new conceptional model for deriving average dermal absorption estimates from studies with multiple tested concentrations for non-dietary risk assessment of pesticides

In Vitro Human Dermal Absorption Studies on Pesticides in Complex Mixtures: Investigation of Guidance Criteria and Possible Impact Parameters

Comparative study of the percutaneous permeation and bioaccumulation of a cyclic siloxane using frozen-thawed and nonfrozen ex vivo human skin

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