Perfluoroheptanoic acid affects amphibian embryogenesis by inducing the phosphorylation of ERK and JNK

Kim, Miran; Park, Mi Seon; Son, Jungeun; Park, Inji; Lee, Hyun-Kyung; Kim, Chowon; Min, Byung-Hwa; Ryoo, Jaewoong; Choi, Kwang Shik; Lee, Dong‐Seok; Lee, Hyun‐Shik

doi:10.3892/ijmm.2015.2370

Cited by 7 publications

(4 citation statements)

References 39 publications

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“…Phosphorylation of histone protein H2A and mitogen-activated protein kinase JNK acts as a marker for reactive oxygen species (ROS) triggered DNA and cellular damage 26,27 and hence higher levels of phosphorylated variants following exposure to various PFAS suggested induction of oxidative stress. Relevant PFAS included PFHpA, which has been previously shown to mediate hepatic and cardiac toxicity via activation of the phosphorylated JNK pathway, 28 thus supporting the ToxCast finding. Upregulation of the collagenase MMP-1 is another oxidative stress marker 29 and was observed to be increased following ToxPi output: Plots and scores after integration of ToxCast data for the 23 per-and polyfluorinated alkyl substances.…”

Section: Oxidative Stresssupporting

confidence: 56%

Exploring Potential Carcinogenic Activity of Per- and Polyfluorinated Alkyl Substances Utilizing High-Throughput Toxicity Screening Data

Singh

Hsieh

2021

Int J Toxicol

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Per- and polyfluorinated alkyl substances (PFAS) are ubiquitous, persistent, and toxic chemicals that pose public health risks. Recent carcinogenicity concerns have arisen based on epidemiological studies, animal tumor findings, and mechanistic data. Thousands of PFAS exist; however, current understanding of their toxicity is informed by studies of a select few, namely, perfluorooctanoic acid and perfluorooctanesulfonic acid. Hence, the computational, high-throughput screening tool, the US EPA CompTox Chemical Dashboard’s ToxCast, was utilized to explore the carcinogenicity potential of PFAS. Twenty-three major PFAS that had sufficient in vitro ToxCast data and covered a range of structural subclasses were analyzed with the visual analytics software ToxPi, yielding a qualitative and quantitative assessment of PFAS activity in realms closely linked with carcinogenicity. A comprehensive literature search was also conducted to check the consistency of analyses with other mechanistic data streams. The PFAS were found to induce a vast range of biological perturbations, in line with several of the International Agency for Research on Cancer–defined key carcinogen characteristics. Patterns observed varied by length of fluorine-bonded chains and/or functional group within and between each key characteristic, suggesting some structure-based variability in activity. In general, the major conclusions drawn from the analysis, that is, the most notable activities being modulation of receptor-mediated effects and induction of oxidative stress, were supported by literature findings. The study helps enhance understanding of the mechanistic pathways that underlie the potential carcinogenicity of various PFAS and hence could assist in hazard identification and risk assessment for this emerging and relevant class of environmental toxicants.

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Section: Oxidative Stresssupporting

confidence: 56%

Exploring Potential Carcinogenic Activity of Per- and Polyfluorinated Alkyl Substances Utilizing High-Throughput Toxicity Screening Data

Singh

Hsieh

2021

Int J Toxicol

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“…Due to the nonmonotonic response for these endpoints, it may be that the doses examined in this study are below the LOAEL (lowest observable adverse effect level) in zebrafish. In Xenopus laevis, the lowest concentration of PFHxA that produced a reduction in body length was 1000 μM (Kim et al 2015). Similarly, chronic and subchronic studies in rats of exposures up to 200 mg/kg/day had no effects on growth (Chengelis et al 2009;Klaunig et al 2014).…”

Section: Toxicity Profile For Pfhxa Exposure In Zebrafishmentioning

confidence: 91%

Subtle morphometric, behavioral and gene expression effects in larval zebrafish exposed to PFHxA, PFHxS and 6:2 FTOH

et al. 2019

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Recent studies of perfluoroalkylated substances (PFASs) have focused on the toxicity of long chain PFASs, such as PFOS or PFOA, which have been demonstrated to cause an array of developmental and behavioral effects. However, less is known about low molecular weight PFASs and alternatives. This study examined the morphometric and behavioral effects in zebrafish following developmental exposures of C6 PFASs: perfluorohexanoic acid, PFHxA, perfluorohexane sulfonate, PFHxS, and 6:2 fluorotelomer alcohol, 6:2 FTOH. Embryos were exposed to 0.02 to 20 μM concentrations of these compounds from the high stage (~3 hours post fertilization, hpf) until 120 hpf. Morphometric and gene expression endpoints were examined at 120 hpf. Genes selected for analysis were previously shown to be altered in zebrafish developmentally exposed to PFOS and PFOA. Additionally, exposed larvae were transferred to clean water and reared until 14 days post fertilization, dpf, when behavioral assays were completed and morphometric endpoints examined. While PFHxA was found to be the most acutely toxic at 120 hpf, few morphometric effects were observed. Gene expression was the most sensitive endpoint with significant increased tgfb1a, bdnf, and ap1s1 expression observed with PFHxA exposure. PFHxS exposure produced morphometric effects in the larvae, specifically increased length and yolk sac area at 2 and 20 μM. This phenotype persisted to the 14 dpf time point, where these larvae additionally displayed decreased distance traveled and crosses through the center of the arena of the behavioral assay. Exposure to 6:2 FTOH caused no morphometric effects at 120 hpf, and this compound was the least acutely toxic. However, expression of both tgfb1a and bdnf were increased by greater than 2 fold change at this time point. Effects also persisted to 14 dpf where a significant increase in distance traveled and velocity were observed in the behavioral assay. This study demonstrates effects on behavioral, morphometric and gene expression endpoints with developmental PFHxA, PFHxS, and 6:2 FTOH exposures in zebrafish.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…Serious disorders in the liver and heart in Xenopus embryogenesis were observed during the evaluation of developmental toxicity and teratogenicity of PFHxA and PFHpA. PFHpA, which has one additional carbon atom with respect to PFHxA, produced more serious effects by increasing the phosphorylation of the signal-regulated extracellular kinase (ERK) and the N-terminal c-Jun (JNK) [150]. Conversely, tadpoles of Xenopus laevis exposed to increasing concentrations of PFOS and PFBS showed hepatohistological effects at concentrations of 100 and 1000 µg/L.…”

Section: Amphibiansmentioning

confidence: 99%

Bioaccumulation, Biodistribution, Toxicology and Biomonitoring of Organofluorine Compounds in Aquatic Organisms

Savoca

Pace

2021

IJMS

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This review is a survey of recent advances in studies concerning the impact of poly- and perfluorinated organic compounds in aquatic organisms. After a brief introduction on poly- and perfluorinated compounds (PFCs) features, an overview of recent monitoring studies is reported illustrating ranges of recorded concentrations in water, sediments, and species. Besides presenting general concepts defining bioaccumulative potential and its indicators, the biodistribution of PFCs is described taking in consideration different tissues/organs of the investigated species as well as differences between studies in the wild or under controlled laboratory conditions. The potential use of species as bioindicators for biomonitoring studies are discussed and data are summarized in a table reporting the number of monitored PFCs and their total concentration as a function of investigated species. Moreover, biomolecular effects on taxonomically different species are illustrated. In the final paragraph, main findings have been summarized and possible solutions to environmental threats posed by PFCs in the aquatic environment are discussed.

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Perfluoroheptanoic acid affects amphibian embryogenesis by inducing the phosphorylation of ERK and JNK

Cited by 7 publications

References 39 publications

Exploring Potential Carcinogenic Activity of Per- and Polyfluorinated Alkyl Substances Utilizing High-Throughput Toxicity Screening Data

Exploring Potential Carcinogenic Activity of Per- and Polyfluorinated Alkyl Substances Utilizing High-Throughput Toxicity Screening Data

Subtle morphometric, behavioral and gene expression effects in larval zebrafish exposed to PFHxA, PFHxS and 6:2 FTOH

Bioaccumulation, Biodistribution, Toxicology and Biomonitoring of Organofluorine Compounds in Aquatic Organisms

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