Bio: Prof. Dr. Paul Carmichael has worked in the Safety & Environmental Assurance Centre (SEAC) of Unilever in the UK since 2004, where he is responsible for the development and implementation of novel non-animal-based approaches for assuring human and environmental health; that is to say, how can consumer and environmental safety be assured without using and harming animals? He has over forty years’ experience in toxicology and cancer research, largely in the academic arena, and prior to Unilever, he was a Senior Lecturer at Imperial College London in the Faculty of Medicine, where he taught pharmacology and toxicology and conducted research into advances in toxicology. A graduate of Surrey University with a B.Sc. in Biochemistry/Toxicology and a Ph.D. from King’s College London, he was a postdoctoral scientist at the Institute of Cancer Research (Royal Marsden Hospital) for seven years, exploring mechanisms of chemical genotoxicity and carcinogenicity. He currently has close academic links with Peking and Shenyang Medical Universities in China (Schools of Public Health) and is a past Assistant Professor of Pathology and Laboratory Medicine at Brown University in the USA. He has been an Endowed Professor at Wageningen University, Division of Toxicology in the Netherlands, since March 2020. His passion is the advancement of new safety assessment approaches using the inspiration of ‘Toxicity Testing in the 21st Century’ – this can be termed ‘next generation risk assessments’ or NGRA.

Abstract: The integration of New Approach Methodologies (NAMs) and Next Generation Risk Assessment (NGRA) is particularly challenging for complex toxicological endpoints such as repeated dose systemic toxicity, as a variety of mechanisms can lead to observed toxicological effects. Therefore, a one-to-one replacement of the sub-chronic and chronic repeated animal tests is not a viable strategy. Instead, a promising approach is to derive surrogate points of departure for systemic toxicity from an in vitro battery that is designed to provide bioactivity measures that are not linked to specific hazards but is protective of human health. In vitro batteries may comprise a variety of technologies including high-throughput transcriptomics (HTTr), high-throughput phenotypic profiling (HTPP; cell painting), in vitro pharmacology profiling (IPP), and reporter-gene based assays and cellular stress panels (CSP). The presentation will discuss the outcome of an evaluation of a systemic toolbox in the context of a Tier 1 risk assessment of consumer products. The toolbox comprises physiologically based kinetic (PBK) models to predict internal exposures, and bioactivity NAMs designed to give broad coverage across many different toxicity modes of action (HTTr, IPP, CSP). The output of the toolbox is the calculation of a bio-activity: exposure ratio (analogous to a margin of internal exposure), which can be used to inform decision-making. In this work we have expanded upon an initial pilot study of 10 chemicals with an additional 38 chemicals and 70 consumer exposure scenarios. We found that, for the majority of these (>90%), the NAM-based workflow is protective of human health, enabling us to make animal-free safety decisions for systemic toxicity and preventing unnecessary animal use.