Identifying Human Specific Adverse Outcome Pathways of Per- and Polyfluoroalkyl Substances Using Liver-Chimeric Humanized Mice.

ABSTRACT:

Background

Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants with myriad adverse effects. While perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are the most common contaminants, levels of replacement PFAS, such as perfluoro-2-methyl-3-oxahexanoic acid (GenX), are increasing. In rodents, PFOA, PFOS, and GenX have several adverse effects on the liver, including nonalcoholic fatty liver disease.

Objective

We aimed to determine human-relevant mechanisms of PFAS induced adverse hepatic effects using FRG liver-chimeric humanized mice with livers repopulated with functional human hepatocytes.

Methods

Male humanized mice were treated with 0.067 mg/L of PFOA, 0.145 mg/L of PFOS, or 1 mg/L of GenX in drinking water for 28 days.

SUBMITTER: Robarts DR 

PROVIDER: S-EPMC9915685 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature