Toxicity Assessment of Mixed Exposure of Nine Perfluoroalkyl Substances at Concentrations Relevant to Daily Intake

Overview

Journal Toxics

Date 2024 Jan 22

PMID 38251008

Authors

Kazuki Takeda

Taki Saito

Sakura Sasaki

Akifumi Eguchi

Makoto Sugiyama

Saeka Eto

Kio Suzuki

Ryo Kamata

Affiliations

Soon will be listed here.

Abstract

Per- and poly-fluoroalkyl substances (PFAS) exhibit high persistence in the environment and accumulate within the human body, warranting a thorough assessment of their toxicity. In this study, we exposed mice (male C57BL/6J mice aged 8 weeks) to a composite of nine PFAS, encompassing both long-chain PFAS (e.g., perfluorooctanoic acid and perfluorooctanesulfonic acid) and short-chain PFAS (e.g., perfluorobutanoic acid and perfluorobutanesulfonic acid). The exposure concentrations of PFAS were equivalent to the estimated daily human intake in the composition reported (1 µg/L (sum of the nine compounds), representing the maximum reported exposure concentration). Histological examination revealed hepatocyte vacuolization and irregular hepatocyte cord arrangement, indicating that exposure to low levels of the PFAS mixture causes morphological changes in liver tissues. Transcriptome analysis revealed that PFAS exposure mainly altered a group of genes related to metabolism and chemical carcinogenesis. Machine learning analysis of the liver metabolome showed a typical concentration-independent alteration upon PFAS exposure, with the annotation of substances such as glutathione and 5-aminovaleric acid. This study demonstrates that daily exposure to PFAS leads to morphological changes in liver tissues and alters the expression of metabolism- and cancer-related genes as well as phospholipid metabolism.

Citing Articles

Closing the Gaps in Understanding PFAS Toxicology and Metabolism.

MacMillan D, Wetmore B, Dasgupta S, Baldwin W Toxics. 2025; 13(1.

PMID: 39853019 PMC: 11769177. DOI: 10.3390/toxics13010019.

Exploring Toxicity of Per- and Polyfluoroalkyl Substances (PFAS) Mixture Through ADMET and Toxicogenomic In Silico Analysis: Molecular Insights.

Baralic K, Petkovski T, Piletic N, Maric D, Djordjevic A, Antonijevic B Int J Mol Sci. 2024; 25(22).

PMID: 39596398 PMC: 11594668. DOI: 10.3390/ijms252212333.

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