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Differential developmental toxicity of perfluorohexanesulfonamide (FHxSA) and perfluorooctanesulfonamide (FOSA) in mummichog (Fundulus heteroclitus) associated with fluorinated chain length
Citation:
Heyder, C., T. Burke, Y. Rericha, K. Wells, L. Mills, D. Nacci, AND B. Clark. Differential developmental toxicity of perfluorohexanesulfonamide (FHxSA) and perfluorooctanesulfonamide (FOSA) in mummichog (Fundulus heteroclitus) associated with fluorinated chain length. 29th NAC SETAC Annual Meeting 2023, Amherst, MA, June 20 - 21, 2023.
Impact/Purpose:
Per- and polyfluoroalkyl substances (PFAS) are long lasting environmental contaminants that have known adverse impacts in fish and other taxa, including humans. However, understanding of their impacts on coastal environments is lacking, and data are needed to classify PFAS according to structure, mechanism, and effects. This presentation provides an overview of embryonic exposure assays using perfluorohexanesulfonamide (FHxSA) and perfluorooctanesulfonamide (FOSA) and examines the role of chain length on the effect of sulfonamide PFAS. These findings demonstrate the importance of understanding the variations between the organismal effects of this varied class of compounds and provide insight to how PFAS may be classified according to structure and size.
Description:
Per- and polyfluoroalkyl substances (PFAS) are long lasting environmental contaminants that have known adverse impacts in fish and other taxa, as well as humans. However, understanding of their impacts on coastal environments is lacking, and data are needed to classify PFAS according to structure, mechanism, and effects. Previous work has shown that fluorinated chain length and functional head group may play a role in the toxicity of these compounds. Perfluorohexanesulfonamide (FHxSA) and perfluorooctanesulfonamide (FOSA) both have sulfonamide functional heads but differ in length (FHxSA has 6 fluorinated carbons and FOSA has 8). To examine their effects and the role of these structural differences, we conducted exposures to each with embryos of an ecologically important estuarine minnow, the mummichog (Fundulus heteroclitus). Understanding developmental toxicity in fish embryos is critical because it is both a sensitive and ecologically important life stage. Embryos were aqueously exposed to FHxSA or FOSA (0, 1, 10, and 100 µM) from 1-7 days post fertilization (dpf). Non-destructive measurements of growth and development were monitored in individuals after exposure until 16 days post-hatching (dph). A variety of biological endpoints were measured, including embryonic survival, hatching, phenotypic abnormalities, larval survival, and growth. Microscopic phenotyping was conducted 10 days post-fertilization (10 dpf) and used to examine embryos for developmental abnormalities, including irregular head or body size, hemorrhages of the tail, head, and pericardial area, and heart abnormalities. Larval growth was measured at 0 dph, 7 dph, and 16 dph. In FHxSA exposures, 100 µM induced 34% mortality at 10 dpf and only 16% of embryos successfully hatched by 30 dpf relative to 94% in controls. The high treatment also experienced 94% pericardial edema, 56% elongated sinus venosus, and 61% abnormal body/head size. In a replicate experiment, fish exposed to 10 µM FHxSA also exhibited mild phenotypic effects with 22% pericardial edema, 28% elongated sinus venosus, and 25% offset chambers. The high concentration of FOSA (100 µM) elicited 100% mortality at 7 dpf. However, fish exposed to 10 µM FOSA experienced no significant treatment-based hatch, larvae survivability,or phenotype effect by treatment. Differences in phenotype, hatch rate, and survivability of exposed embryos suggest a role for chain length in developmental toxicity of PFAS for mummichogs. Further work in understanding the basis for this variation may aid in efforts to classify PFAS. Ongoing work investigating the mechanistic basis for these organismal effects will contribute to the larger goal of connecting modes of action to apical adverse outcomes, which can be used to extrapolate across species and predict population and ecological impacts of PFAS contamination.
