Title: Risk science in the 21st century: a data-driven framework for incorporating new technologies into chemical safety assessment
Authors: Russell S. Thomas; Ricky Cheung; Margit Westphal; Daniel Krewski; Melvin E. Andersen
Addresses: National Center for Computational Toxicology, US Environmental Protection Agency, USA ' Public Health Agency of Canada, 785 Carling Avenue, Ottawa, Ontario K1A 0K9, Canada ' McLaughlin Centre for Population Health Risk Assessment, Institute of Population Health, University of Ottawa, 1 Stewart St., Ottawa, Ontario, K1N 6N5, Canada ' McLaughlin Centre for Population Health Risk Assessment, Institute of Population Health, University of Ottawa, 850 Peter Morand, Ottawa, Ontario, K1G 3Z7, Canada; Department of Epidemiology and Community Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5, Canada; Risk Sciences International, 55 Metcalfe Street, Suite 700, Ottawa, ON K1P 6L5, Canada ' ScitoVation, Research Triangle Park, North Carolina, USA
Abstract: One of the major challenges in chemical safety assessment is prioritisation of the large number of chemicals in commerce. Over the past five years, a new tiered approach to chemical safety assessment that uses margin of exposure (MOE) as the metric for determining the level of testing required, identifies chemicals of greatest concern. This paper evaluates the role of new technologies and novel tools in improving different steps of chemical risk assessment processes such as high throughput screening (HTS) in vitro assay platforms, high content biological omics assays, molecular biomarkers, quantitative structure activity relationship (QSAR) modelling, in vitro to in vivo extrapolation (IVIVE) and physiologically-based pharmacokinetic (PBPK) modelling. Other technologies such as functional genomics, bioinformatics, and computational biology can expedite the analysis. This new approach could potentially be used to prioritise and categorise chemicals on the domestic substance list (DSL) under the Canadian Environmental Protection Act (CEPA).
Keywords: risk assessment; chemical safety assessment; margin of exposure; MOE; tiered approach; predictive toxicology; risk science; safe chemicals; new technologies; high throughput screening; HTS; in vitro assay platforms; biological omics assays; molecular biomarkers; quantitative structure activity relationship; QSAR modelling; in vitro to in vivo extrapolation; IVIVE; physiologically-based pharmacokinetics; PBPK modelling; functional genomics; bioinformatics; computational biology.
DOI: 10.1504/IJRAM.2017.082560
International Journal of Risk Assessment and Management, 2017 Vol.20 No.1/2/3, pp.88 - 108
Received: 18 Jan 2016
Accepted: 19 Jan 2016
Published online: 01 Mar 2017 *