Development of a reference and proficiency chemical list for human steatosis endpoints in vitro

Frontiers in Endocrinology

Endocrinology

Barbara Kubickova¹  Miriam N. Jacobs¹ 

[1] Radiation, Chemical and Environmental Hazards (RCE), Department of Toxicology, UK Health Security Agency (UKHSA), Harwell Science and Innovation Campus, Chilton, United Kingdom;

关键词: HepaRG;    human hazard;    lipid accumulation;    triglyceride;    drug-induced liver injury;    validation;    alternative method;    new approach methodology;   

DOI  :  10.3389/fendo.2023.1126880

 received in 2022-12-18, accepted in 2023-03-17,  发布年份 2023

来源: Frontiers

【 摘 要 】

The most prevalent liver disease in humans is non-alcoholic fatty liver disease, characterised by excessive hepatic fat accumulation, or steatosis. The western diet and a sedentary lifestyle are considered to be major influences, but chemical exposure may also play a role. Suspected environmental chemicals of concern include pesticides, plasticizers, metals, and perfluorinated compounds. Here we present a detailed literature analysis of chemicals that may (or may not) be implicated in lipid accumulation in the liver, to provide a basis for developing and optimizing human steatosis-relevant in vitro test methods. Independently collated and reviewed reference and proficiency chemicals are needed to assist in the test method development where an assay is intended to ultimately be taken forward for OECD Test Guideline development purposes. The selection criteria and considerations required for acceptance of proficiency chemical selection for OECD Test Guideline development. (i.e., structural diversity, range of activity including negatives, relevant chemical sectors, global restrictions, etc.) is described herein. Of 160 chemicals initially screened for inclusion, 36 were prioritized for detailed review. Based on the selection criteria and a weight-of-evidence basis, 18 chemicals (9 steatosis inducers, 9 negatives), including some environmental chemicals of concern, were ranked as high priority chemicals to assist in vitro human steatosis test method optimisation and proficiency testing, and inform potential subsequent test method (pre-)validation.

【 授权许可】

Unknown   
Copyright © 2023 Kubickova and Jacobs

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