Degitz SJ et al. (2024), Evaluating potential developmental toxicity of ...

XB-ART-60639

J Appl Toxicol 2024 Mar 26; doi: 10.1002/jat.4599.

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Evaluating potential developmental toxicity of perfluoroalkyl and polyfluoroalkyl substances in Xenopus laevis embryos and larvae.

Degitz SJ , Degoey PP , Haselman JT , Olker JH , Stacy EH , Blanksma C , Meyer S , Mattingly KZ , Blackwell B , Opseth AS , Hornung MW .

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As part of the US Environmental Protection Agency's perfluoroalkyl and polyfluoroalkyl substances (PFAS) Action Plan, the agency is committed to increasing our understanding of the potential ecological effects of PFAS. The objective of these studies was to examine the developmental toxicity of PFAS using the laboratory model amphibian species Xenopus laevis. We had two primary aims: (1) to understand the developmental toxicity of a structurally diverse set of PFAS compounds in developing embryos and (2) to characterize the potential impacts of perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), and hexafluoropropylene oxide-dimer acid (HFPO-DA a.k.a. GenX), on growth and thyroid hormone-controlled metamorphosis. We employed a combination of static renewal and flow-through exposure designs. Embryos were exposed to 17 structurally diverse PFAS starting at the midblastula stage through the completion of organogenesis (96 h). To investigate impacts on PFOS, PFOA, PFHxS, and HFPO-DA on development and metamorphosis, larvae were exposed from premetamorphosis (Nieuwkoop Faber stage 51 or 54) through pro metamorphosis. Of the PFAS tested in embryos, only 1H,1H,10H,10H-perfluorodecane-1,10-diol (FC10-diol) and perfluorohexanesulfonamide (FHxSA) exposure resulted in clear concentration-dependent developmental toxicity. For both of these PFAS, a significant increase in mortality was observed at 2.5 and 5 mg/L. For FC10-diol, 100% of the surviving embryos were malformed at 1.25 and 2.5 mg/L, while for FHxSA, a significant increase in malformations (100%) was observed at 2.5 and 5 mg/L. Developmental stage achieved was the most sensitive endpoint with significant effects observed at 1.25 and 0.625 mg/L for FC10-diol and FHxSA, respectively. In larval studies, we observed impacts on growth following exposure to PFHxS and PFOS at concentrations of 100 and 2.5 mg/L, respectively, while no impacts were observed in larvae when exposed to PFOA and HFPO-DA at concentration of 100 mg/L. Further, we did not observe impacts on thyroid endpoints in exposed larvae. These experiments have broadened our understanding of the impact of PFAS on anuran development.

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Species referenced: Xenopus tropicalis Xenopus laevis
Genes referenced: pfas
GO keywords: larval development [+]

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	Supplemental Figure S1. PFOA verification of chemical concentration. Solid line indicates the mean measured test concentration (2.1 mg/L). Test concentrations were confirmed for all treatment tanks weekly throughout the study.
	Supplemental Figure S2. PFHxS chemical verification. Solid line indicates the mean measured test concentration (2.08 mg/L). Test concentrations were confirmed for all treatment tanks weekly throughout the study.
	Supplemental Figure S3. HFPO-DA chemical verification. Solid line indicates the mean measured test concentration (2.26 mg/L). Test concentrations were confirmed for all treatment tanks weekly throughout the study.
	Supplemental Figure S4. PFOS chemical verification. Solid line indicates the mean measured test concentration. Test concentrations were confirmed for all treatment tanks weekly throughout the study.
	Supplemental Figure S5. Thyroid hormone concentration in stage 62 plasma at varying mg/L concentrations of PFOS exposure (mean±SD, N=5 for control, N=3 for 0.3 mg/L, 0.6 mg/L, 1.25 mg/L, and 5 mg/L, N=4 for 2.5 mg/L). T4 was significantly decreased at 0.625 mg/L, 2.5 mg/L, and 5 mg/L.