The challenge of using read-across within the EU REACH regulatory framework; how much uncertainty is too much? Dipropylene glycol methyl ether acetate, an exemplary case study

Ball, Nicholas; Bartels, Michael; Budinsky, Robert A.; Klapacz, Joanna; Hays, Sean M.; Kirman, Christopher R.; Patlewicz, Grace

doi:10.1016/j.yrtph.2013.12.007

Cited by 50 publications

(28 citation statements)

References 29 publications

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“…the outcomes of the 2010 dossiers submitted to the eCHA are only now becoming apparent; additionally only about 5% of these dossiers will be subject to a formal technical compliance evaluation. that said, for cases where read-across has been accepted or denied (see Ball et al, 2014), a number of questions have been raised. Is there a higher burden of proof depending on the presence or absence of adversity?…”

Section: Boxmentioning

confidence: 99%

“…this assumes that the experimental data is of sufficient sensitivity in the first place. This type of uncertainty appeared to be a factor in the case of Ball et al (2014) where there was no significant adversity for the analogues and endpoints under consideration. The specific endpoint under consideration also appears to be an issue.…”

Section: Boxmentioning

confidence: 99%

“…The specific endpoint under consideration also appears to be an issue. In Ball et al (2014), the read-across was accepted for a 90-day study but the same underlying rationale was not accepted for the developmental toxicity endpoint.…”

Section: Boxmentioning

confidence: 99%

“…BASF has been developing a database (MetaMap ® tox) in which metabolomics and toxicity data are evaluated in combination (van Ravenzwaay, 2007). the database contains data for more than 500 chemicals (from 28-day read-across is in development (Patlewicz et al, in prep), elements of which were communicated at QSAR 2014 (Aptula et al, 2014) and at the 9 th World Congress on Alternatives and Animal Use in the life Sciences (Ball et al, 2014). Neither the eCHA RAAF or the Blackburn and Stuard (2014) frameworks discuss how to resolve read-across uncertainties (aside from using default assessment factors), and understanding how to practically exploit other tools such as the tox-21c approaches to address uncertainty is a major priority.…”

Section: Negative Read-acrossmentioning

confidence: 99%

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Read-across approaches - misconceptions, promises and challenges ahead

Patlewicz

2014

ALTEX

Self Cite

108

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Summary Read-across is a data gap filling technique used within category and analogue approaches. It has been utilized as an alternative approach to address information requirements under various past and present regulatory programs such as the OECD High Production Volume Programme as well as the EU's Registration, Evaluation, Authorisation and restriction of CHemicals (REACH) regulation. Although read-across raises a number of expectations, many misconceptions still remain around what it truly represents; how to address its associated justification in a robust and scientifically credible manner; what challenges/issues exist in terms of its application and acceptance; and what future efforts are needed to resolve them. In terms of future enhancements, read-across is likely to embrace more biologicallyorientated approaches consistent with the Toxicity in the 21 st Century vision (Tox-21c). This Food forThought article, which is notably not a consensus report, aims to discuss a number of these aspects and, in doing so, to raise awareness of the ongoing efforts and activities to enhance read-across. It also intends to set the agenda for a CAAT read-across initiative in 2014CAAT read-across initiative in -2015 to facilitate the proper use of this technique.

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Section: Boxmentioning

confidence: 99%

Section: Boxmentioning

confidence: 99%

Section: Boxmentioning

confidence: 99%

Section: Negative Read-acrossmentioning

confidence: 99%

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Read-across approaches - misconceptions, promises and challenges ahead

Patlewicz

2014

ALTEX

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108

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“…For that reason, uncer-549 tainties need to be identified and appraised 550 Ball et al, 2014;Blackburn and Stuard, 2014; Patlewicz et al, 551 2014). However, the concept and definition of uncertainty has been 552 described as ambiguous; it tends to incorporate a variety of553 methodologies with the aim of meeting different goals (Péry 554 et al, 2013).…”

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confidence: 99%

A strategy for structuring and reporting a read-across prediction of toxicity

Schultz

Amcoff

Berggren

et al. 2015

Regulatory Toxicology and Pharmacology

1,235

130

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Category formation, grouping and read across methods are broadly applicable in toxicological assessments and may be used to fill data gaps for chemical safety assessment and regulatory decisions. In order to facilitate a transparent and systematic approach to aid regulatory acceptance, a strategy to evaluate chemical category membership, to support the use of read-across predictions that may be used to fill data gaps for regulatory decisions is proposed. There are two major aspects of any read-across exercise, namely assessing similarity and uncertainty. While there can be an over-arching rationale for grouping organic substances based on molecular structure and chemical properties, these similarities alone are generally not sufficient to justify a read-across prediction. Further scientific justification is normally required to justify the chemical grouping, typically including considerations of bioavailability, metabolism and biological/mechanistic plausibility. Sources of uncertainty include a variety of elements which are typically divided into two main issues: the uncertainty associated firstly with the similarity justification and secondly the completeness of the read-across argument. This article focuses on chronic toxicity, whilst acknowledging the approaches are applicable to all endpoints. Templates, developed from work to prepare for the application of new toxicological data to read-across assessment, are presented. These templates act as proposals to assist in assessing similarity in the context of chemistry, toxicokinetics and toxicodynamics as well as to guide the systematic characterisation of uncertainty both in the context of the similarity rationale, the read across data and overall approach and conclusion. Lastly, a workflow for reporting a read-across prediction is suggested.

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Lehren aus dem Gruppieren von Chemikalien zur Bewertung der Risiken für die Gesundheit des Menschen

Wohlleben

Mehling²,

Landsiedel

2023

Angewandte Chemie

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Analog zum Periodensystem, das Elemente nach ihrer Ähnlichkeit der Strukturen und chemischen Eigenschaften gruppiert, kann die Gefahr chemischer Stoffe in Gruppen mit ähnlichen Strukturen und ähnlichen toxikologischen Eigenschaften bewertet werden. Im Folgenden werden Fallbeispiele zu Gruppierungsstrategien vorgestellt, welche die Bewertungen von Gefahr, Exposition und Risiko für die menschliche Gesundheit unterstützen. Sowohl unter EU-REACh als auch im US-TSCA New Chemicals Programm ist in der Regel die strukturelle Ähnlichkeit die Grundlage für eine Gruppierungt. Allerdings ist dieses Kriterium nicht immer angemessen und ausreichend. Auf der Grundlage der gewonnenen Erkenntnisse leiten wir zehn Grundsätze für die Gruppierung ab, darunter: die transparente Darstellung des Zwecks der Gruppierung, die Definition der Kriterien für eine Gruppierung und die Grenzen der Gruppen, eine dieEinbeziehung oder der Ausschluss eines Stoffs in oder aus einer Gruppe aufgrund toxikologischer Eigenschaften und eine Begründung der Zuordnung durch robuste Daten aus angemessenen Methoden. Diese Grundsätze gelten sowohl für eine erste Gruppierung zur Priorisierung weiterer Maßnahmen als auch für die endgültige Gruppierung zur Gewinnung von Daten für die Risikobewertung. Beides kann ein effektives Risikomanagement forcieren.

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The challenge of using read-across within the EU REACH regulatory framework; how much uncertainty is too much? Dipropylene glycol methyl ether acetate, an exemplary case study

Cited by 50 publications

References 29 publications

Read-across approaches - misconceptions, promises and challenges ahead

Read-across approaches - misconceptions, promises and challenges ahead

A strategy for structuring and reporting a read-across prediction of toxicity

Lehren aus dem Gruppieren von Chemikalien zur Bewertung der Risiken für die Gesundheit des Menschen

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