Integration of Animal, Population, and Toxicogenomic Evidence on the Hematotoxic and Immunosuppressive Effects of Environmental Exposure to PFAS Mixtures in Adolescents
Abstract
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are emerging contaminants widely found in drinking water and food, potentially entering the human body through these sources. To investigate these effects, we simulated PFAS exposure doses in animal models, ranging from general population to occupational levels, and analyzed blood and spleen samples. Epidemiological studies linked PFAS exposure to immunosuppression and hematotoxicity, while toxicogenomic analyses validated the underlying biological mechanisms. PFAS exposure caused immunotoxic effects, including altered blood parameters and lymphocyte edema. Cellular abnormalities such as decreased cytoplasmic density, incomplete rough endoplasmic reticulum, chromatin condensation, lymphocyte nuclear shrinkage, and reduced mitochondrial cristae were observed. Epidemiological evidence revealed a dose-response relationship between mixed PFAS exposure and hematologic indices such as hematocrit (HCT), hemoglobin (HGB), platelet count (PLT), platelet-to-lymphocyte ratio (PLR), white blood cell count (WBC), monocyte percentage, and platelet large cell ratio (PLCR), with perfluorooctanoic acid (PFOA) playing a dominant role. Toxicogenomic analysis identified genes associated with platelets, anemia, and leukocyte function, linked to inflammation, Th17 cell differentiation, apoptosis, lipid metabolism, atherosclerosis, and JAK-STAT signaling. This study provides novel insights into the hematotoxicity and immunosuppressive effects of mixed PFAS exposure, emphasizing the need for PFAS substitution, removal, and policies addressing mixed exposures to protect public health.
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Epidemiological analyses demonstrate dose-response relationships between mixed PFAS exposures-and PFOA in particular-and alterations in hematologic indices (hematocrit, hemoglobin, platelets, WBC count, inflammatory markers).
“Epidemiological analyses demonstrate dose–response relationships between mixed PFAS exposures—and PFOA in particular—and alterations in hematologic indices, including hematocrit, hemoglobin, platelets, WBC count, and inflammatory markers, implicating pathways like JAK-STAT, apoptosis, Th17 differentiation, and atherosclerosis [74].”
From Exposure to Per- and Polyfluoroalkyl Substances (PFASs) in Healthcare: Environmental and Clinical Insights (2025) · cites this paper as [74]
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- Authors
- Du, X., Xu, X., Dong, X.-X., Liang, X., Wu, Y., Du, Z., Pan, C.-W., Liang, G., Li, Y.-Z., Zheng, Y.-J., Qin, Y., Qian, K., Xu, J., Hong, X., Li, D.-L., & Zheng, W.
- Affiliations
- Fudan University (CN)
- Fujian Medical University (CN)
- Soochow University (CN)
- Shanghai Municipal Center For Disease Control Prevention (CN)
- Yunnan University (CN)
- Department of Ophthalmology
- University of Shanghai for Science and Technology (CN)
- Corresponding author
- Hong, Xinyu
- Li, Dan-Lin
- Zheng, Weiwei
- Venue
- Environmental Science & Technology
- Publisher
- American Chemical Society (ACS)
- Published
- 2025-05-23
- Volume
- 59
- Issue
- 22
- Pages
- 10841-10853
- ISSN
- 0013-936X (ISSN-L)
- 1520-5851
- OpenAlex
- W4410629773
- Cited by
- 24
- References
- 59
- Citations by year
- 2026: 18 · 2025: 6
- FWCI
- 7.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Environmental Science & Technology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Shanghai Municipality (21 ZR1438400)
- Shanghai Municipal Health Commission
- National Natural Science Foundation of China (2024YFA1802700, 81202165, 81773379, 82122058)
- Family Foundation of the Three-Year Public Health Action Plan of Shanghai (GWV-1.1, GWV-10.1-XK11, GWVI-11.1-39, GWVI-11.1-41, GWVI-4)
- Project of Shanghai Huangpu District health Commission (HLM202109)
- Young Talents (2017YQ023)
- Shanghai Jiading District Key Medical Specialty Project (ZK2024B05)
- General Program (202040186)
- Public Health Discipline Construction of Pudong New Area Health System (PWGw2020-04)
- Shanghai Jiading District High-Quality Development Key Discipline of Environmental Health (GWGZLXK-2023-03)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Physical Sciences › Environmental Science › Water Science and Technology › Fluoride Effects and Removal
- Keywords
- per- and polyfluoroalkyl substances, PFAS mixtures, hematologic toxicity, immunosuppression, adolescents, perfluorooctanoic acid, toxicogenomics, lymphocyte abnormalities, platelet function, hematological parameters, platelet-to-lymphocyte ratio, JAK/STAT signaling, Th17 cell differentiation, apoptosis, lipid metabolism, atherosclerosis, inflammation, drinking water contamination, occupational exposure, dose-response relationship
- MeSH terms
- Adolescent, Animals, Environmental Exposure, Environmental Pollutants, Fluorocarbons, Humans, Toxicogenetics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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