Assessment of in vitro human dermal absorption studies on pesticides to determine default values, opportunities for read-across and influence of dilution on absorption

Aggarwal, Manoj; Battalora, Michael; Fisher, P.; Hüser, A.; Parr-Dobrzanski, R.; Soufi, Masoud Dehghani; Mostert, Volker; Strupp, Christian; Whalley, Paul; Wiemann, Christiane; Billington, Richard

doi:10.1016/j.yrtph.2014.01.012

Cited by 25 publications

(29 citation statements)

References 18 publications

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“…ECPA pooled data from 295 Good Laboratory Practice (GLP) and OECD 428-compliant in vitro human dermal absorption studies (Aggarwal et al, 2014 and2015). A dataset was created covering physicochemical properties for 152 agrochemical active substances (a.s.), 19 formulation types, tested at different concentrations to provide 762 records 3 in total.…”

Section: Ecpa Dataset/manuscriptsmentioning

confidence: 99%

“…The statistical analysis carried out by ECPA (Aggarwal et al, 2014(Aggarwal et al, , 2015 proceeded sequentially. The first step of this analysis attempted to relate dermal absorption to the physical form (solid/liquid).…”

Section: Ecpa Manuscriptsmentioning

confidence: 99%

“…The so-called Linear Model is the standard technique to analyse the effect of the variation of a set of variables on a response variable. This should be used here using all potential explanatory variables (a.s. properties including MW and logPow, concentration, formulation type) jointly (in contrast with one at a time as by Aggarwal et al 2014Aggarwal et al , 2015 in combination with variable selection techniques to identify the main causes of variation in dermal absorption values.…”

Section: Figure 1: Dermal Absorption (%) For Liquid Concentrates By Fmentioning

confidence: 99%

“…In particular, ECPA referred to a manuscript submitted to a scientific journal for publication where several amendments to the EFSA Guidance on dermal absorption were proposed (Aggarwal et al, 2014).…”

mentioning

confidence: 99%

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Assessment of new scientific studies on human in vitro dermal absorption

2015

EFS2

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This EFSA scientific report describes the results from the evaluation of new human in vitro studies on dermal absorption made available by European Crop Protection Association (ECPA) and the German public organisation Bundesinstitut für Risikobewertung (BfR) and their possible impact on the guidance on dermal absorption (EFSA, 2012). A quality check was performed in order to verify if new studies were conducted according to the current regulatory standards and to identify potential deviations from EFSA guidance on dermal absorption. In addition, a plausibility check to validate the correctness of data entry in the datasets from sources (study reports) was undertaken applying a two tiers (I and II) validation protocol. Although a number of deviations from the EFSA guidance on dermal absorption have been identified, the outcome of the evaluation indicates that the new studies comply with the current regulatory standards. EFSA recommendations to address the variability within studies and to improve the consistency of interpretation have not been applied routinely. In addition the datasets as provided to EFSA are not completed, lacking individual data or other information addressing variability. However, the overall conclusion regarding the scientific quality of the provided datasets is that they are consistent and solid and include a relevant number of in vitro dermal adsorption studies with human skin. The new data provide sufficient information for the revision of the current guidance or the development a new guidance on dermal absorption. For the exploitation of the new datasets, in the revision of the current guidance or the development of a new guidance on dermal absorption, it is recommended to add the missing information, to compile a comprehensive dataset and to analyse dermal absorption data applying a model-based statistical protocol.

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Section: Ecpa Dataset/manuscriptsmentioning

confidence: 99%

Section: Ecpa Manuscriptsmentioning

confidence: 99%

Section: Figure 1: Dermal Absorption (%) For Liquid Concentrates By Fmentioning

confidence: 99%

mentioning

confidence: 99%

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Assessment of new scientific studies on human in vitro dermal absorption

2015

EFS2

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“…In particular, ECPA referred to a manuscript submitted to a scientific journal for publication in which several amendments to the EFSA PPR Panel guidance on dermal absorption were proposed (Aggarwal et al, 2014).…”

Section: Background As Provided By Efsamentioning

confidence: 99%

Guidance on Dermal Absorption

2012

EFSA Journal

191

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The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. AbstractThis guidance on the assessment of dermal absorption has been developed to assist notifiers, users of test facilities and Member State authorities on critical aspects related to the setting of dermal absorption values to be used in risk assessments of active substances in Plant Protection Products (PPPs). It is based on the 'scientific opinion on the science behind the revision of the guidance document on dermal absorption' issued in 2011 by the EFSA Panel on Plant Protection Products and their Residues (PPR). The guidance refers to the EFSA PPR opinion in many instances. In addition, the first version of this guidance, issued in 2012 by the EFSA PPR Panel, has been revised in 2017 on the basis of new available data on human in vitro dermal absorption for PPPs and wherever clarifications were needed. Basic details of experimental design, available in the respective test guidelines and accompanying guidance for the conduct of studies, have not been addressed but recommendations specific to performing and interpreting dermal absorption studies with PPPs are given. Issues discussed include a brief description of the skin and its properties affecting dermal absorption. To facilitate use of the guidance, flow charts are included. Guidance is also provided, for example, when there are no data on dermal absorption for the product under evaluation. Elements for a tiered approach are presented including use of default values, data on closely related products, in vitro studies with human skin (regarded to provide the best estimate), data from experimental animals (rats) in vitro and in vivo, and the so called 'triple pack' approach. Various elements of study design and reporting that reduce experimental variation and aid consistent interpretation are presented. A proposal for reporting data for assessment reports is also provided. The issue of nanoparticles in PPPs is not addressed. Data from volunteer studies have not been discussed since their use is not allowed in EU for risk assessment of PPPs.

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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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Assessment of in vitro human dermal absorption studies on pesticides to determine default values, opportunities for read-across and influence of dilution on absorption

Cited by 25 publications

References 18 publications

Assessment of new scientific studies on human in vitro dermal absorption

Assessment of new scientific studies on human in vitro dermal absorption

Guidance on Dermal Absorption

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

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