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PFHxA (307-24-4)


87 References Were Found:

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Addendum to Iwai and Hoberman (2014)-Reassessment of developmental toxicity of PFHxA in mice

Authors: Iwai, H; Hoberman, AM; Goodrum, PE; Mendelsohn, E; Anderson, JK (2019) International Journal of Toxicology 38:183-191. HERO ID: 5097907

[Less] This article presents a supplemental data analysis and evaluation of the findings from an oral (gavage) . . . [More] This article presents a supplemental data analysis and evaluation of the findings from an oral (gavage) combined developmental and perinatal/postnatal reproduction toxicity study of the ammonium salt of perfluorohexanoic acid (CASRN: 21615-47-4) in Crl: CD-1(ICR) mice. The original study has been cited as supporting a lowest-observed-adverse-effects level of 175 mg/kg/d and no-observed-adverse-effects level of 35 mg/kg/d for developmental effects from perfluorohexanoic acid (PFHxA, CASRN: 307-24-4) in mice. The statistical analysis reported in 2014 was accurate in terms of quantifying statistical significance within phase 2 of the study. However, given the low incidence of findings, the purpose of this article is to extend the analysis and interpretation of findings by pooling the control group information from both phases of the same study, comparing the study findings to the incidence rates for stillbirths and postpartum viability for this species and strain of mouse observed for similar studies conducted by the same laboratory, and evaluating data on the incidence and range of spontaneous eye abnormalities reported in the literature. Based on this supplemental evaluation, the original study supports a NOAEL of 175 mg/kg/d for PFHxA in mice, which is a factor of 5-fold higher than previously reported. Furthermore, to the extent that this study may be considered in the selection of a point of departure for PFHxA in mice, it is noted that 175 mg/kg/d for maternal exposure is an unbounded NOAEL for developmental effects, meaning that the study did not establish a dose at which developmental effects may occur.

Technical Report
Technical Report

NTP technical report on the toxicity studies of perfluoroalkyl carboxylates (perfluorohexanoic acid, perfluorooctanoic acid, perfluorononanoic acid, and perfluorodecanoic acid) administered by gavage to Sprague Dawley (Hsd:Sprague Dawley SD) rats

Author: NTP (2019) (Toxicity Report 97). Research Triangle Park, NC: National Toxicology Program. HERO ID: 5400977


Archival Material
Archival Material

28-day evaluation of the toxicity (C20613) of perfluorohexanoic acid (PFHxA) (307-24-4) on Harlan Sprague-Dawley rats exposed via gavage

Author: NTP (2018) Available online at https://tools.niehs.nih.gov/cebs3/views/?action=main.dataReview&bin_id=3879. [Website] HERO ID: 4309149

[Less] On 05 April 2018 indirect bilirubin measurements were added to the clinical chemistry tables. No changes . . . [More] On 05 April 2018 indirect bilirubin measurements were added to the clinical chemistry tables. No changes were made to existing data.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Plasma concentration of 14 perfluoroalkyl acids (PFAAs) among children from seven cities in Guangdong, China

Authors: Zhang, R; Ye, J; Wei, Q; Li, M; Xu, K; Li, Z; Lin, W; Liu, P; Chen, R; Ma, A; Zhou, Z (2018) Science of the Total Environment 616-617:1469-1476. HERO ID: 4238457

[Less] The toxicity and persistence of perfluoroalkyl acids (PFAAs) in humans have drawn growing concerns, . . . [More] The toxicity and persistence of perfluoroalkyl acids (PFAAs) in humans have drawn growing concerns, particularly for children. However, data regarding the concentrations of PFAAs in children are limited. In this study, we measured the concentrations of 14 PFAAs in plasma samples collected from 1192 children aged 0-7years from 7 cities in Guangdong Province: Guangzhou, Shenzhen, Foshan, Dongguan, Zhaoqing, Zhongshan and Zhanjiang. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were detected in >99.5% of the analysed samples. PFOS had the highest median concentration (23.6ng/mL) in the total samples, followed by PFOA (2.8ng/mL). The median concentrations of the other PFAAs were lower than 0.4ng/mL. The concentrations of perfluorohexanoic acid, perfluorononanoic acid, perfluorodecanoic acid, perfluorododecanoic acid, perfluorohexane sulfonate, PFOA and PFOS in children from Foshan were significantly higher than those found in other cities (p<0.001). Negative correlations between most of the PFAA concentrations and age (r=-0.06--0.45) were found in all children. Weak to moderate correlations (r=0.080-0.698) were observed between all PFAA concentrations. Our findings indicated a high exposure of children to PFAAs in the early life-stage. The exposure sources and pathways of PFAAs in different regions are different. Considering a lack of information on the exposure pathways and health status, more studies are needed to evaluate the exposure resources and assess the health risk of PFAA exposure in children.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Relationship between peroxisome proliferator-activated receptor alpha activity and cellular concentration of 14 perfluoroalkyl substances in HepG2 cells

Authors: Rosenmai, AK; Ahrens, L; le Godec, T; Lundqvist, J; Oskarsson, A (2018) Journal of Applied Toxicology 38:219-226. HERO ID: 4220319

[Less] Peroxisome proliferator-activated receptor alpha (PPARα) is a molecular target for perfluoroalkyl substances . . . [More] Peroxisome proliferator-activated receptor alpha (PPARα) is a molecular target for perfluoroalkyl substances (PFASs). Little is known about the cellular uptake of PFASs and how it affects the PPARα activity. We investigated the relationship between PPARα activity and cellular concentration in HepG2 cells of 14 PFASs, including perfluoroalkyl carboxylates (PFCAs), perfluoroalkyl sulfonates and perfluorooctane sulfonamide (FOSA). Cellular concentrations were determined by high-performance liquid chromatography-tandem mass spectrometry and PPARα activity was determined in transiently transfected cells by reporter gene assay. Cellular uptake of the PFASs was low (0.04-4.1%) with absolute cellular concentrations in the range 4-2500 ng mg-1 protein. Cellular concentration of PFCAs increased with perfluorocarbon chain length up to perfluorododecanoate. PPARα activity of PFCAs increased with chain length up to perfluorooctanoate. The maximum induction of PPARα activity was similar for short-chain (perfluorobutanoate and perfluoropentanoate) and long-chain PFCAs (perfluorododecanoate and perfluorotetradecanoate) (approximately twofold). However, PPARα activities were induced at lower cellular concentrations for the short-chain homologs compared to the long-chain homologs. Perfluorohexanoate, perfluoroheptanoate, perfluorooctanoate, perfluorononanoate (PFNA) and perfluorodecanoate induced PPARα activities >2.5-fold compared to controls. The concentration-response relationships were positive for all the tested compounds, except perfluorooctane sulfonate PFOS and FOSA, and were compound-specific, as demonstrated by differences in the estimated slopes. The relationships were steeper for PFCAs with chain lengths up to and including PFNA than for the other studied PFASs. To our knowledge, this is the first report establishing relationships between PPARα activity and cellular concentration of a broad range of PFASs.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Influence of exposure to perfluoroalkyl substances (PFASs) on the Korean general population: 10-year trend and health effects

Authors: Seo, SH; Son, MH; Choi, SD; Lee, DH; Chang, YS (2018) Environment International 113:149-161. HERO ID: 4238334

[Less] This study demonstrated the 10-year trend of 13 perfluoroalkyl substances (PFASs) serum levels among . . . [More] This study demonstrated the 10-year trend of 13 perfluoroalkyl substances (PFASs) serum levels among 786 adults living in Seoul, Korea. PFAS levels gradually increased from 2006 to 2013, decreasing thereafter. We found that PFAS levels were higher in male than in female participants and were positively correlated with age. PFASs were not significantly correlated with body mass index, although we observed positive correlations with total cholesterol, low-density lipoprotein cholesterol, and triglycerides and negative correlations with high-density lipoprotein cholesterol. Uric acid and free thyroxine (fT4) also showed positive correlations with major congeners while correlations between thyroid stimulating hormone and PFASs were inconsistent. We demonstrated significant correlations between fT4 and perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorodecanoic acid (PFDA). There were significant differences in PFHxS and perfluorododecanoic acid (PFDoDA) levels between participants with and without diabetes. Furthermore, principal component analysis suggested possible differences in disease manifestation based on the congener distribution of PFASs. This study is the first study of temporal trends of 13 PFAS congeners in serum samples obtained from the Korean general population; it is currently longest and largest scale study of this type.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Biomonitoring PFAAs in blood and semen samples: Investigation of a potential link between PFAAs exposure and semen mobility in China

Authors: Song, X; Tang, S; Zhu, H; Chen, Z; Zang, Z; Zhang, Y; Niu, X; Wang, X; Yin, H; Zeng, F; He, C (2018) Environment International 113:50-54. HERO ID: 4220306

[Less] Perfluoroalkyl acids (PFAAs) have been suspected to act as endocrine disruptors and adversely affect . . . [More] Perfluoroalkyl acids (PFAAs) have been suspected to act as endocrine disruptors and adversely affect human reproductive health. We aimed to investigate the association between PFAAs in blood and semen, explore a potential link between PFAAs exposure and semen quality in the population of the Pearl River Delta (PRD) region in China, one of the "world factories". The monitoring results demonstrated that the population (103 male participants) from the PRD region in this study had higher PFAAs levels in blood and semen than some other areas in China. PFOS was found at the highest mean concentrations of 118.16 ng/mL in blood and 5.31 ng/mL in semen among the nine PFAAs. Significant associations were found between concentrations of several analytes in blood and semen, including Σ9 PFAAs (r = 0.475, P < .01), PFOA (r = 0.215, P = .029), PFHS (r = 0.458, P < .01) and PFOS (r = 0.981, P < .01). BMI was the most important factor to PFAAs, but there was no significant difference in PFAAs concentrations in blood and semen collected from participants with different smoking and drinking habits, education background and occupations. Negative correlations were significantly observed between sperm motility and PFBA, PFPeA, PFHxA, PFBS, PFOA, PFHS, PFOS and Σ9PFAAs in semen. Therefore, exposure to PFAAs may result in a decline in semen mobility in participants from the PRD region.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

A hypothesis-driven weight-of-evidence analysis to evaluate potential endocrine activity of perfluorohexanoic acid

Authors: Borghoff, SJ; Fitch, S; Rager, JE; Huggett, D (2018) Regulatory Toxicology and Pharmacology 99:168-181. [Review] HERO ID: 5017765

[Less] Perfluorohexanoic acid (PFHxA) is a potential impurity and environmental degradation product of C6-based . . . [More] Perfluorohexanoic acid (PFHxA) is a potential impurity and environmental degradation product of C6-based fluorotelomer products. Considering the potential endocrine activity of perfluoroalkyl acids, a hypothesis-driven weight-of-evidence (WoE) analysis was conducted to evaluate the potential endocrine disruptor activity of PFHxA, as defined by World Health Organization (WHO), across estrogen (E), androgen (A), thyroid (T), and steroidogenesis (S) pathways. A comprehensive literature search identified primary and secondary studies across species for review. The ToxCast/Tox21 database provided in vitro data. Studies identified were reviewed for reliability, and relevance, with endocrine endpoints ranked, and lines of evidence evaluated across pathways. Overall, PFHxA showed no endocrine effects in Japanese medaka, juvenile rainbow trout, chickens or reproductive parameters in northern bobwhite with no significant activity in rodent repeated-dose toxicity, lifetime cancer, or reproductive and developmental studies. In vitro, there was weak or negative activity for T transport protein or activation of E, A or T receptors. PFHxA was also negative in vitro and in vivo for disrupting steroidogenesis. Based on this WoE endocrine analysis, PFHxA exposure did not cause adverse effects associated with alterations in endocrine activity in these models, as such would not be characterized as an endocrine disruptor according to the WHO definition.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Cellular accumulation and lipid binding of perfluorinated alkylated substances (PFASs) - A comparison with lysosomotropic drugs

Authors: Sanchez Garcia, D; Sjödin, M; Hellstrandh, M; Norinder, U; Nikiforova, V; Lindberg, J; Wincent, E; Bergman, Å; Cotgreave, I; Munic Kos, V (2018) Chemico-Biological Interactions 281:1-10. HERO ID: 4234856

[Less] Many chemicals accumulate in organisms through a variety of different mechanisms. Cationic amphiphilic . . . [More] Many chemicals accumulate in organisms through a variety of different mechanisms. Cationic amphiphilic drugs (CADs) accumulate in lysosomes and bind to membranes causing phospholipidosis, whereas many lipophilic chemicals target adipose tissue. Perfluoroalkyl substances (PFASs) are widely used as surfactants, but many of them are highly bioaccumulating and persistent in the environment, making them notorious environmental toxicants. Understanding the mechanisms of their bioaccumulation is, therefore, important for their regulation and substitution with new, less harmful chemicals. We compared the highly bioaccumulative perfluorooctanesulfonic acid PFOS to its three less bioaccumulative alternatives perfluorooctanoic acid (PFOA), perfluorohexanoic acid (PFHxA) and perfluorobutane sulfonic acid (PFBS), in their ability to accumulate and remain in lung epithelial cells (NCI-H292) and adipocytes (3T3-L1K) in vitro. As a reference point we tested a set of cationic amphiphilic drugs (CADs), known to highly accumulate in cells and strongly bind to phospholipids, together with their respective non-CAD controls. Finally, all compounds were examined for their ability to bind to neutral lipids and phospholipids in cell-free systems. Cellular accumulation and retention of the test compounds were highly correlated between the lung epithelial cells and adipocytes. Interestingly, although an anion itself, intensities of PFOS accumulation and retention in cells were comparable to those of CAD compounds, but PFOS failed to induce phospholipidosis or alter lysosomal volume. Compared to other lipophilicity measures, phospholipophilicity shows the highest correlation (Rˆ2 = 0.75) to cellular accumulation data in both cell types and best distinguishes between high and low accumulating compounds. This indicates that binding to phospholipids may be the most important component in driving high cellular accumulation in lung epithelial cells, as well as in adipocytes, and for both CADs and bioaccumulating PFASs. Obtained continuous PLS models based on compound's affinity for phospholipids and neutral lipids can be used as good prediction models of cellular accumulation and retention of PFASs and CADs.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Comparing the toxic potency in vivo of long-chain perfluoroalkyl acids and fluorinated alternatives

Authors: Gomis, MI; Vestergren, R; Borg, D; Cousins, IT (2018) Environment International 113:1-9. HERO ID: 4220321

[Less] Since 2000, long-chain perfluoroalkyl acids (PFAAs) and their respective precursors have been replaced . . . [More] Since 2000, long-chain perfluoroalkyl acids (PFAAs) and their respective precursors have been replaced by numerous fluorinated alternatives. The main rationale for this industrial transition was that these alternatives were considered less bioaccumulative and toxic than their predecessors. In this study, we evaluated to what extent differences in toxicological effect thresholds for PFAAs and fluorinated alternatives, expressed as administered dose, were confounded by differences in their distribution and elimination kinetics. A dynamic one-compartment toxicokinetic (TK) model for male rats was constructed and evaluated using test data from toxicity studies for perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorobutane sulfonic acid (PFBS), perfluorooctanoic acid (PFOA), perfluoroctanesulfonic acid (PFOS) and ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate (GenX). Dose-response curves of liver enlargement from sub-chronic oral toxicity studies in male rats were converted to internal dose in serum and in liver to examine the toxicity ranking of PFAAs and fluorinated alternatives. Converting administered doses into equivalent serum and liver concentrations reduced the variability in the dose-response curves for PFBA, PFHxA, PFOA and GenX. The toxicity ranking using modeled serum (GenX > PFOA > PFHxA > PFBA) and liver (GenX > PFOA ≈ PFHxA ≈ PFBA) concentrations indicated that some fluorinated alternatives have similar or higher toxic potency than their predecessors when correcting for differences in toxicokinetics. For PFOS and perfluorobutane sulfonic acid (PFBS) the conversion from administered dose to serum concentration equivalents did not change the toxicity ranking. In conclusion, hazard assessment based on internal exposure allows evaluation of toxic potency and bioaccumulation potential independent of kinetics and should be considered when comparing fluorinated alternatives with their predecessors.