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narrative_review·biomedical research, preclinical research, research methods·PMC10109535

A pragmatic framework for the application of new approach methodologies in one health toxicological risk assessment

Toxicological Sciences · 6 authors, 6 centres

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TL;DR

The central result is a proposed standardized process to apply NAMs while accounting for complexities and uncertainties.

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It argues that traditional animal studies are slow, expensive, have ethical limitations, and may not fully translate to human health outcomes due to interspecies differences.

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narrative_review

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biomedical research

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AI pipeline

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ORIGINAL PAPER

PMC10109535

A pragmatic framework for the application of new approach methodologies in one health toxicological risk assessment

Toxicological Sciences

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ABSTRACT

Abstract Globally, industries and regulatory authorities are faced with an urgent need to assess the potential adverse effects of chemicals more efficiently by embracing new approach methodologies (NAMs). NAMs include cell and tissue methods ( in vitro ), structure-based/toxicokinetic models ( in silico ), methods that assess toxicant interactions with biological macromolecules ( in chemico ), and alternative models. Increasing knowledge on chemical toxicokinetics (what the body does with chemicals) and toxicodynamics (what the chemicals do with the body) obtained from in silico and in vitro systems continues to provide opportunities for modernizing chemical risk assessments. However, directly leveraging in vitro and in silico data for derivation of human health-based reference values has not received regulatory acceptance due to uncertainties in extrapolating NAM results to human populations, including metabolism, complex biological pathways, multiple exposures, interindividual susceptibility and vulnerable populations. The objective of this article is to provide a standardized pragmatic framework that applies integrated approaches with a focus on quantitative in vitro to in vivo extrapolation (QIVIVE) to extrapolate in vitro cellular exposures to human equivalent doses from which human reference values can be derived. The proposed framework intends to systematically account for the complexities in extrapolation and data interpretation to support sound human health safety decisions in diverse industrial sectors (food systems, cosmetics, industrial chemicals, pharmaceuticals etc.). Case studies of chemical entities, using new and existing data, are presented to demonstrate the utility of the proposed framework while highlighting potential sources of human population bias and uncertainty, and the importance of Good Method and Reporting Practices. Keywords: new approach methodologies (NAMs), risk assessment, framework, metabolism, uncertainty, in vitro

CITATION EXPORT

Kelly A Magurany, Xiaoqing Chang, Rebecca Clewell et al.. A pragmatic framework for the application of new approach methodologies in one health toxicological risk assessment. Toxicological Sciences. (2023). https://doi.org/10.1093/toxsci/kfad012

AUTHORS

6 · 6 CENTRES

Kelly A Magurany, Xiaoqing Chang, Rebecca Clewell, Sandra Coecke, Esther Haugabrooks, Sue Marty

1 NSF International, Ann Arbor, Michigan 48105, USA
2 Inotiv-RTP, Morrisville, North Carolina 27560, USA
3 21st Century Tox Consulting, Chapel Hill, North Carolina 27517, USA
4 European Commission Joint Research Centre, Ispra, Italy
5 Coca-Cola Company (formerly Physicians Committee for Responsible Medicine), Atlanta, Georgia 30313, USA
6 The Dow Chemical Company, Midland, Michigan 48667, USA