Enabling novel paradigms: a biological questions-based approach to human chemical hazard and drug safety assessment.

Autor:	Berridge BR; Division of Translational Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA., Bucher JR; Retired (Division of Translational Toxicology, NIEHS), Hillsborough, North Carolina 27278, USA., Sistare F; Chapel Hill, North Carolina 27517, USA., Stevens JL; Paradox Found Consulting Services, Apex, North Carolina 27523, USA., Chappell GA; ICF, Reston, Virginia 20190, USA., Clemons M; ICF, Reston, Virginia 20190, USA., Snow S; ICF, Reston, Virginia 20190, USA., Wignall J; ICF, Reston, Virginia 20190, USA., Shipkowski KA; Division of Translational Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Jazyk:	angličtina
Zdroj:	Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2024 Feb 28; Vol. 198 (1), pp. 4-13.
DOI:	10.1093/toxsci/kfad124
Abstrakt:	Throughput needs, costs of time and resources, and concerns about the use of animals in hazard and safety assessment studies are fueling a growing interest in adopting new approach methodologies for use in product development and risk assessment. However, current efforts to define "next-generation risk assessment" vary considerably across commercial and regulatory sectors, and an a priori definition of the biological scope of data needed to assess hazards is generally lacking. We propose that the absence of clearly defined questions that can be answered during hazard assessment is the primary barrier to the generation of a paradigm flexible enough to be used across varying product development and approval decision contexts. Herein, we propose a biological questions-based approach (BQBA) for hazard and safety assessment to facilitate fit-for-purpose method selection and more efficient evidence-based decision-making. The key pillars of this novel approach are bioavailability, bioactivity, adversity, and susceptibility. This BQBA is compared with current hazard approaches and is applied in scenarios of varying pathobiological understanding and/or regulatory testing requirements. To further define the paradigm and key questions that allow better prediction and characterization of human health hazard, a multidisciplinary collaboration among stakeholder groups should be initiated. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology.)
Databáze:	MEDLINE
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