Journal
ENVIRONMENT INTERNATIONAL
Volume 170, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.envint.2022.107642
Keywords
Behavior; Development; Perfluoroalkyl; PFAS; Transcriptomic; Zebrafish
Categories
Funding
- National Institute for Occupational Safety and Health through the Pilot Research Project Training Program of the University of Cincinnati Education and Research Center Grant [T42OH008432]
- Illinois Occupational and Environmental Health and Safety Education and Research Center at the University of Illinois at Chicago [T42OH008672]
- National Institutes of Health, National Institute of Environmental Health Sciences [ES031646]
- Purdue Research Foundation Research Grant
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This study compared the toxicity of three different chain length per-fluoroalkyl acids on developing zebrafish, finding that they induced different behavioral, morphological, and molecular pathway alterations. The results support the predictive value of transcriptome approach in predicting adverse health outcomes associated with per-fluoroalkyl acid exposure.
Perfluoroalkyl substances (PFAS) are a class of synthetic chemicals that are persistent in the environment. Due to adverse health outcomes associated with longer chain PFAS, shorter chain chemicals were used as replacements, but developmental toxicity assessments of the shorter chain chemicals are limited. Toxicity of three per-fluoroalkyl acids (PFAAs) [perfluorooctanoic acid (PFOA), composed of 8 carbon (C8), perfluorohexanoic acid (PFHxA, C6), and perfluorobutanoic acid (PFBA, C4)] was compared in developing zebrafish (Danio rerio). LC50s at 120 h post fertilization (hpf) assessed potency of each PFAA by exposing developing zebrafish (1-120 hpf) to range of concentrations. Zebrafish were then exposed to sublethal concentrations (0.4-4000 ppb, mu g/L) throughout embryogenesis (1-72 hpf). Effects of the embryonic exposure on locomotor activities was completed with the visual motor response test at 120 hpf. At 72 hpf, morphological changes (total body length, head length, head width) and transcriptome profiles to compare altered molecular and disease pathways were determined. The LC50 ranking followed trend as expected based on chain length. PFOA caused hyperactivity and PFBA hypoactivity, while PFHxA did not change behavior. PFOA, PFHxA, and PFBA caused morphological and tran-scriptomic alterations that were unique for each chemical and were concentration-dependent indicating different toxicity mechanisms. Cancer was a top disease for PFOA and FXR/RXR activation was a top canonical pathway for PFBA. Furthermore, comparison of altered biological and molecular pathways in zebrafish exposed to PFOA matched findings reported in prior epidemiological studies and other animal models, supporting the predictive value of the transcriptome approach and for predicting adverse health outcomes associated with PFHxA or PFBA exposure.
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