Application of AOPs to assist regulatory assessment of chemical risks - Case studies, needs and recommendations

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Authors

BAJARD ÉP.ESNER Lola Murielle ADAMOVSKÝ Ondřej AUDOUZE Karine BAKEN Kirsten BAROUKI Robert BELTMAN Joost B. BERONIUS Anna BONEFELD-JORGENSEN Eva Cecilie CANO-SANCHO German DE BAAT Milo L. DI TILLIO Filippo FERNANDEZ Mariana F. FITZGERALD Rex E. GUNDACKER Claudia HERNANDEZ Antonio F. HILSCHEROVÁ Klára KARAKITSIOS Spyros KUCHOVSKÁ Eliška LONG Manhai LUIJTEN Mirjam MAJID Sanah MARX-STOELTING Philip MUSTIELES Vicente NEGI Chander Kant SARIGIANNIS Dimosthenis SCHOLZ Stefan SOVADINOVÁ Iva STIERUM Rob TANABE Shihori TOLLEFSEN Knut Erik VAN DEN BRAND Annick D. VOGS Carolina WIELSOE Maria WITTWEHR Clemens BLÁHA Luděk

Year of publication 2023
Type Article in Periodical
Magazine / Source Environmental Research
MU Faculty or unit

Faculty of Science

Citation
Web https://www.sciencedirect.com/science/article/pii/S0013935122019776?via%3Dihub
Doi http://dx.doi.org/10.1016/j.envres.2022.114650
Keywords Adverse outcome pathways; Mechanistic toxicology; Hazard assessment; Regulatory risk assessment; Biomarkers of effect; New approach methodologies
Attached files
Description While human regulatory risk assessment (RA) still largely relies on animal studies, new approach methodologies (NAMs) based on in vitro, in silico or non-mammalian alternative models are increasingly used to evaluate chemical hazards. Moreover, human epidemiological studies with biomarkers of effect (BoE) also play an invaluable role in identifying health effects associated with chemical exposures. To move towards the next generation risk assessment (NGRA), it is therefore crucial to establish bridges between NAMs and standard approaches, and to establish processes for increasing mechanistically-based biological plausibility in human studies. The Adverse Outcome Pathway (AOP) framework constitutes an important tool to address these needs but, despite a significant increase in knowledge and awareness, the use of AOPs in chemical RA remains limited. The objective of this paper is to address issues related to using AOPs in a regulatory context from various perspectives as it was discussed in a workshop organized within the European Union partnerships HBM4EU and PARC in spring 2022. The paper presents examples where the AOP framework has been proven useful for the human RA process, particularly in hazard prioritization and characterization, in integrated approaches to testing and assessment (IATA), and in the identification and validation of BoE in epidemiological studies. Nevertheless, several limitations were identified that hinder the optimal usability and acceptance of AOPs by the regulatory community including the lack of quantitative information on response-response relationships and of efficient ways to map chemical data (exposure and toxicity) onto AOPs. The paper summarizes suggestions, ongoing initiatives and third-party tools that may help to overcome these obstacles and thus assure better implementation of AOPs in the NGRA.
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