Dietary Perfluorohexanoic Acid (PFHxA) Exposures in Juvenile Zebrafish Produce Subtle Behavioral Effects across Generations

Abstract

Ubiquitous anthropogenic contaminants of concern, per- and polyfluoroalkyl substances (PFAS) are frequently detected in the environment and human populations around the world. Diet is a predominate route of human exposure, and PFAS are frequently measured in food. Manufacturing trends have shifted from legacy PFAS to shorter-chain alternatives that are suggested to be safer, such as perfluorohexanoic acid (PFHxA). However, the current amount of data to support safety assessments of these alternatives is not yet sufficient. The present study investigated the effects of a 42-day dietary exposure to 1, 10, or 100 ng/g PFHxA in juvenile zebrafish. The zebrafish model was leveraged to interrogate morphometrics, fecundity, and numerous behavior endpoints across multiple generations. Dietary PFHxA exposure did not result in measurable body burden and did not affect growth, fecundity, adult social perception behavior, or associative learning. PFHxA exposure did induce abnormal adult anxiety behaviors in the F0 generation that persisted transgenerationally in the F1 and F2. Abnormal larval and juvenile behavior was observed in the F1 generation, but not in the F2. PFHxA juvenile dietary exposure induced subtle and multigenerational behavior effects that warrant further investigation of this and other alternative short-chain PFAS.

Toxicity of Per- and Polyfluoroalkyl Substances to Nematodes

“…Additionally, D. rerio , with human genetic similarities as high as 87%, is the second-most-used animal model in medical sciences and life research, as it is an excellent vertebrate model for estimating the toxicity of chemicals with substantial advantages [ 61 ]. The toxic effects of PFASs on zebrafish have been studied for many years, revealing more extensive effects on the reproductive, developmental, cellular structure, neurologic, oxidative, metabolic, immune, and endocrine systems [ 62 , 63 , 64 ] than those achieved using C. elegans . Moreover, juvenile dietary exposure of D. rerio to PFASs could induce multigenerational behavioral effects similar to those observed in C. elegans [ 64 ].…”

“…The toxic effects of PFASs on zebrafish have been studied for many years, revealing more extensive effects on the reproductive, developmental, cellular structure, neurologic, oxidative, metabolic, immune, and endocrine systems [ 62 , 63 , 64 ] than those achieved using C. elegans . Moreover, juvenile dietary exposure of D. rerio to PFASs could induce multigenerational behavioral effects similar to those observed in C. elegans [ 64 ]. Furthermore, D. melanogaster is an invertebrate that cannot live in water or soil/sediments, and D. rerio is a higher vertebrate that lives in a water environment.…”

Advancing statistical treatment of photolocomotor behavioral response study data

“…Alternatively, it may be repeated several times for each individual light/dark period itself [ 9 – 11 ]. When assumptions for univariate one-way ANOVA are not met, Fisher’s Exact test [ 12 ] or the nonparametric Kruskal-Wallis test [ 4 , 13 , 14 ] are often used. Other approaches include repeated measures ANOVA [ 15 , 16 ]; multiple t -tests for each level of the factor against the control group [ 17 ]; t -tests for every time point [ 18 ]; and a Kolmogorov-Smirnov test comparing the area under the curve (AUC) of differential entropy between treatment and control groups [ 14 , 19 ].…”

“…If univariate ANOVA were to be performed on the means of these functions, no difference would be found. Similarly, the AUC used in [ 14 , 19 ] is a summary value and suffers from the same problem in that equal values of AUC can arise from two functions with very different patterns. However, functional ANOVA (FANOVA) would detect a difference in the functions.…”

Experimental and Theoretical Insight of Perfluorooctanoic Acid Destruction by Alkaline Hydrothermal Treatment Enhanced with Zero-Valent Iron in Biochar

“…Since the successful synthesis of poly- and perfluoroalkyl substances (PFASs) in the 1940s, this group of synthetic organic surfactants has been widely used in anti-fouling coatings and firefighting foams owing to excellent surface activity as well as strong chemical stability . As a result, PFASs, especially perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), have been widely detected in various environmental media, such as air, tap water, soil, and sediments. − Bioaccumulation of PFASs in fish, animals, and even human milk and serum has also been reported. − A growing number of studies have shown that long-term exposure to PFASs can cause various adverse effects on human and animal health, such as abnormal anxiety, hormone disruption, compromised immune systems, and even cancers. − Therefore, from the view of human health protection, the latest standards for drinking water quality in China stipulate water quality limits of 80 and 40 ng L –1 for PFOA and PFOS, respectively…”