Characterization of Potential Adverse Outcome Pathways Related to Metabolic Outcomes and Exposure to Per- and Polyfluoroalkyl Substances Using Artificial Intelligence
Abstract
:1. Introduction
2. Materials and Methods
2.1. Application of the AOP-helpFinder
2.1.1. Development of the Dictionaries of Stressors and Events to Be Screened
2.1.2. Automatic Screening of the Literature Using the AOP-helpFinder Tool—Multistep Procedure
3. Results
3.1. Linking PFAS to Adverse Effects
3.1.1. Collected Data from In Vivo Studies Using the AOP-helpFinder
3.1.2. Collected Data from In Vitro Studies Using the AOP-helpFinder
3.1.3. Collected Data from Epidemiological Studies Using the AOP-helpFinder
3.2. Linking PFAS to AOPs
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Study Type (Number of Publ. Associated with Event) | Organism or Organism From Which Cells Were Originally Derived | Frequency (%) | Main Event Identified (Number of Publ. Associated with Event) | Substances Associated with Event |
---|---|---|---|---|
In vivo (114) | Rat | 40 | Hepatotoxicity (16) | PFCAs (C8-C12), PFOS |
Decreased cholesterol (8) | PFDA, PFOS | |||
PPARα activation (6) | PFOA, PFOS | |||
Mouse | 53 | Hepatotoxicity (13) | PFOA, PFOS, 6:2 FTSA, 6:2 FTCA, 6:2 Cl-PFESA, HFPO-TA, PFO2HxA, PFO3OA, PFO4DA | |
PPARα activation (13) | PFCAs (C8-C10), PFHxS, PFOS | |||
Decreased body weight (7) | PFCAs (C8-C10), PFOS | |||
Others, e.g., hamster, guinea pig, monkey, zebrafish, carp | 7 | Hepatotoxicity, decreased body weight | PFOA, PFOS, PFDoDA |
Study Type (Number of Publ. Associated with Event) | Organism or Organism From Which Cells Were Originally Derived | Frequency (%) | Main Event Identified (Number of Publ. Associated with Event) | Substances Associated with Event |
---|---|---|---|---|
In vitro (75) | Rat | 20 | Increased ROS (6) | PFOA, PFOS, 8:2 FTOH, PFOSA, PFDoDA |
Cell death (3) | 8:2 FTOH, PFOS, PFOA, PFOSA | |||
Activation of AhR (1) | PFCAs (C8-C12), PFHxS, PFOS | |||
Mouse | 17 | PPARα activation (4) | PFCAs (C5-C9, C11-C12), PFHxS, PFOS | |
Increased ROS (4) | PFOA, PFDA, PFOS | |||
Human | 60 | Increased ROS (12) | PFCAs (C8-C11), PFHxS, PFOS | |
Hepatotoxicity (11) | PFOA, PFOS | |||
PPARα activity (3) | PFOA, PFOS, PFOSA | |||
Others, e.g., baikal seal, hamster | 4 | Increased ROS, PPARα activity | PFOA, PFOS, PFAAs (C4-C12) |
Event | Identified Publications via AOP-helpFinder | Identified Associations with PFAS (Number of Publ.) | No Associations Found (Number of Publ.) | |
---|---|---|---|---|
Hypertension | Total number of publications: | 20 | ||
Years: | 2012–2020 | |||
Addressed hypertension or preeclampsia: | 15 | PFBA (1), PFOA (9), PFNA (4), PFDA (1), PFHxS (2), PFHpS (1), PFOS (3), br-PFOS (2), PFDS (1), MeFOSAA (1), total 12-PFAS (1), | PFOA (3), PFNA (1), PFHxS (2), PFOS (4), EtFOSAA (1) | |
Did not address hypertension: | 5 | e.g., higher uric acid levels | ||
Overweight and obesity | Total number of publications: | 15 | ||
Years: | 1996–2019 | |||
Addressed overweight or obesity: | 7 | PFOA (3), PFNA (2), PFOS (1) | PFOA (1), PFNA (1), PFHxS (1), PFOS (2), PFOSA (1) | |
Did not address overweight or obesity: | 8 | e.g., lower birth weight, elevated LDL or TC, study participants were obese in general | ||
Insulin resistance | Total number of publications: | 11 | ||
Years: | 2010–2019 | |||
Addressed insulin resistance: | 11 | ↓ HOMA-IR↓: PFHxS (4), PFOS (1), PFOA (1), PFNA (2), PFDA (1), PFAA4 (1) ↑ HOMA-IR↑: PFHxS (1), PFOS (2), PFOA (1), PFDoDA (1) GDM: PFHxS (1), PFHpA (1), PFOA (1), PFNA (2), PFDoDA (1) | PFOA (2), PFNA (2), PFHxS (1), PFOS (2), | |
Did not address insulin resistance: | 0 | |||
Type 2 diabetes mellitus | Total number of publications: | 4 | ||
Years: | 2018–2020 | |||
Addressed insulin resistance: | 4 | PFOS (1), PFOA (2) | PFOS (1) | |
Did not address insulin resistance: |
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Kaiser, A.-M.; Zare Jeddi, M.; Uhl, M.; Jornod, F.; Fernandez, M.F.; Audouze, K. Characterization of Potential Adverse Outcome Pathways Related to Metabolic Outcomes and Exposure to Per- and Polyfluoroalkyl Substances Using Artificial Intelligence. Toxics 2022, 10, 449. https://doi.org/10.3390/toxics10080449
Kaiser A-M, Zare Jeddi M, Uhl M, Jornod F, Fernandez MF, Audouze K. Characterization of Potential Adverse Outcome Pathways Related to Metabolic Outcomes and Exposure to Per- and Polyfluoroalkyl Substances Using Artificial Intelligence. Toxics. 2022; 10(8):449. https://doi.org/10.3390/toxics10080449
Chicago/Turabian StyleKaiser, Andreas-Marius, Maryam Zare Jeddi, Maria Uhl, Florence Jornod, Mariana F. Fernandez, and Karine Audouze. 2022. "Characterization of Potential Adverse Outcome Pathways Related to Metabolic Outcomes and Exposure to Per- and Polyfluoroalkyl Substances Using Artificial Intelligence" Toxics 10, no. 8: 449. https://doi.org/10.3390/toxics10080449