Development of a network of carcinogenicity adverse outcome pathways and its employment as an evidence framework for safety assessment

Cayley, Alex; Foster, R.; Hill, Emma M.; Kane, Steven; Kocks, Grace; Myden, Alun; Newman, Daniel A.; Stalford, S. A.; Vessey, Jonathan D.; Zarei, Reza; Oliveira, Antonio Anax F De

doi:10.14573/altex.2201311

Cited by 7 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…org/ chemi calsa fety/ riskasses sment/ oecd-qsar-toolb ox. htm accessed 15/03/2024) and (Cayley et al 2023), respectively). Similarly, comparative analyses of the more recent biomarker databases can support the development of additional regulatory tools and their application for carcinogenicity in Module A, existing information, as shown for example by (Oku et al 2022).…”

Section: Forward Lookmentioning

confidence: 99%

A modular strategy for the testing and assessment of non-genotoxic carcinogens

Louekari,

Jacobs

2024

Arch Toxicol

View full text Add to dashboard Cite

A modular strategy is described for the testing and assessment (MoSt) of non-genotoxic carcinogenicity (NGTxC) that is suitable for regulatory applications. It utilizes and builds upon work conducted by the OECD expert group on NGTxC. The approach integrates relevant test methods from the molecular- to cellular- and further to tissue level, many of which have been recently reviewed. Six progressive modules are included in the strategy. Advice is provided for the iterative selection of the next appropriate test method within each step of the strategy. Assessment is completed by a weight of evidence conclusion, which integrates the different streams of modular information. The assessment method gives higher weight to findings that are mechanistically linked with biological relevance to carcinogenesis. With a focus on EU-REACH, and pending upon successful test method validation and acceptance, this will also enable the MoSt for NGTxC to be applied for regulatory purposes across different regulatory jurisdictions.

show abstract

Section: Forward Lookmentioning

confidence: 99%

A modular strategy for the testing and assessment of non-genotoxic carcinogens

Louekari,

Jacobs

2024

Arch Toxicol

View full text Add to dashboard Cite

show abstract

“…Networks of AOPs incorporating known mechanisms leading to an adverse outcome may be required in order to successfully utilise AOPs in IATAs. Progress to this end has been made for specific endpoints such as thyroid hormone disruption (within the ecotoxicity domain) ( Knapen et al, 2020 ), and a recently published network of (mammalian-relevant) AOPs for carcinogenicity ( Cayley et al, 2022 ). In silico models can form part of an IATA ( OECD, 2020 ), and therefore mapping relevant in silico models to AOPs could increase their use in an IATA and also introduce a predictive entry point to potentially relevant AOPs.…”

Section: Introductionmentioning

confidence: 99%