Health & Environmental Research Online (HERO)


PFHxA (307-24-4)


334 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.

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

Toxicokinetics of perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) in male and female Hsd:Sprague dawley SD rats following intravenous or gavage administration

Authors: Dzierlenga, AL; Robinson, VG; Waidyanatha, S; Devito, MJ; Eifrid, MA; Gibbs, ST; Granville, CA; Blystone, CR (2019) Xenobiotica 1-11. HERO ID: 5916078

[Less] Poly- and perfluorinated alkyl substances (PFAS) are environmentally persistent chemicals associated . . . [More] Poly- and perfluorinated alkyl substances (PFAS) are environmentally persistent chemicals associated with many adverse health outcomes. The National Toxicology Program evaluated the toxicokinetics (TK) of several PFAS to provide context for toxicologic findings.Plasma TK parameters and tissue (liver, kidney, brain) concentrations are reported for perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA) or perfluorodecanoic acid (PFDA) after single-dose administration in male and female Hsd:Sprague-Dawley® (SD) rats.Generally, longer Tmax and elimination half-lives, and slower clearance f, were correlated with longer chain length. Male rats administered PFOA had a prolonged half-life compared to females (215 h vs. 2.75), while females had faster clearance and smaller plasma area under the curve (AUC). Females administered PFHxA had a shorter half-life (2 h vs. 9) than males and faster clearance with a smaller plasma AUC, although this was less pronounced than PFOA. There was no sex difference in PFDA half-life. Female rats administered PFDA had a higher plasma AUC/dose than males, and a slower clearance. PFDA had the highest levels in the liver of the PFAS evaluated.Profiling the toxicokinetics of these PFAS allows for comparison among subclasses, and more direct translation of rodent toxicity to human populations.

Data/Software
Data/ Software

ChemView

Author: U.S. EPA (2019) [Searchable database to access health and safety data about a chemical known and assessed by EPA.]. [Database] HERO ID: 2991004

[Less] Use this database to get information on chemical health and safety data received by EPA and EPA's assessments . . . [More] Use this database to get information on chemical health and safety data received by EPA and EPA's assessments and regulatory actions for specific chemicals under the Toxic Substances Control Act (TSCA). ChemView contains no confidential business information (CBI).

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


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

Perfluorohexanoic acid toxicity, part I: Development of a chronic human health toxicity value for use in risk assessment

Authors: Luz, AL; Anderson, JK; Goodrum, P; Durda, J (2019) Regulatory Toxicology and Pharmacology 103:41-55. HERO ID: 5080589

[Less] Perfluorohexanoic acid (PFHxA) is a short-chain, six-carbon perfluoroalkyl acid (PFAA) and is a primary . . . [More] Perfluorohexanoic acid (PFHxA) is a short-chain, six-carbon perfluoroalkyl acid (PFAA) and is a primary impurity, degradant, and metabolite associated with the short-chain fluorotelomer-based chemistry used globally today. The transition to short-chain fluorotelomer-based products as a cornerstone in replacement fluorochemistry has raised questions regarding potential human health risks associated with exposure to fluorotelomer-based substances and therefore, PFHxA. Here, we present a critical review of data relevant to such a risk assessment, including epidemiological studies and in vivo and in vitro toxicity studies that examined PFHxA acute, subchronic, and chronic toxicity. Key findings from toxicokinetic and mode-of-action studies are also evaluated. Sufficient data exist to conclude that PFHxA is not carcinogenic, is not a selective reproductive or developmental toxicant, and does not disrupt endocrine activity. Collectively, effects caused by PFHxA exposure are largely limited to potential kidney effects, are mild and/or reversible, and occur at much higher doses than observed for perfluorooctanoic acid (PFOA). A chronic human-health-based oral reference dose (RfD) for PFHxA of 0.25 mg/kg-day was calculated using benchmark dose modeling of renal papillary necrosis from a chronic rat bioassay. This RfD is four orders of magnitude greater than the chronic oral RfD calculated by the U.S. Environmental Protection Agency for PFOA. The PFHxA RfD can be used to inform public health decisions related to PFHxA and fluorotelomer precursors for which PFHxA is a terminal degradant. These findings clearly demonstrate that PFHxA is less hazardous to human health than PFOA. The analyses presented support site-specific risk assessments as well as product stewardship initiatives for current and future short-chain fluorotelomer-based products.

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

Magnetic covalent triazine-based frameworks as magnetic solid-phase extraction adsorbents for sensitive determination of perfluorinated compounds in environmental water samples

Authors: Ren, JY; Wang, XL; Li, XL; Wang, ML; Zhao, RS; Lin, JM (2018) Analytical and Bioanalytical Chemistry 410:1657-1665. HERO ID: 4220307

[Less] Covalent organic frameworks (COFs), which are a new type of carbonaceous polymeric material, have attracted . . . [More] Covalent organic frameworks (COFs), which are a new type of carbonaceous polymeric material, have attracted great interest because of their large surface area and high chemical and thermal stability. However, to the best of our knowledge, no work has reported the use of magnetic COFs as adsorbents for magnetic solid-phase extraction (MSPE) to enrich and determine environmental pollutants. This work aims to investigate the feasibility of using covalent triazine-based framework (CTF)/Fe2O3 composites as MSPE adsorbents to enrich and analyze perfluorinated compounds (PFCs) at trace levels in water samples. Under the optimal conditions, the method developed exhibited low limits of detection (0.62-1.39 ng·L-1), a wide linear range (5-4000 ng L-1), good repeatability (1.12-9.71%), and good reproducibility (2.45-7.74%). The new method was successfully used to determine PFCs in actual environmental water samples. MSPE based on CTF/Fe2O3 composites exhibits potential for analysis of PFCs at trace levels in environmental water samples. Graphical abstract Magnetic covalent triazine-based frameworks (CTFs) were used as magnetic solid-phase extraction adsorbents for the sensitive determination of perfluorinated compounds in environmental water samples. PFBA perfluorobutyric acid, PFBS perfluorobutane sulfonate, PFDA perfluorodecanoic acid, PFDoA perfluorododecanoic acid, PFHpA perfluoroheptanoic acid, PFHxA perfluorohexanoic acid, PFHxS perfluorohexane sulfonate, PFNA perfluorononanoic acid, PFOA perfluorooctanoic acid, PFPeA perfluoropentanoic acid, PFUdA Perfluoroundecanoic acid.

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

Internal exposure-based pharmacokinetic evaluation of potential for biopersistence of 6:2 fluorotelomer alcohol (FTOH) and its metabolites

Authors: Kabadi, SV; Fisher, J; Aungst, J; Rice, P (2018) Food and Chemical Toxicology 112:375-382. HERO ID: 4238377

[Less] Polyfluorinated compounds (PFCs) are authorized for use as greaseproofing agents in food contact paper. . . . [More] Polyfluorinated compounds (PFCs) are authorized for use as greaseproofing agents in food contact paper. As C8-PFCs (8-carbons) are known to accumulate in tissues, shorter-chain C6-PFCs (6-carbons) have replaced C8-PFCs in many food contact applications. However, the potential of C6-PFCs for human biopersistence has not been fully evaluated. For the first time, we provide internal exposure estimates to key metabolites of 6:2 fluorotelomer alcohol (6:2 FTOH), a monomeric component of C6-PFCs, to extend our understanding of exposure beyond estimates of external exposure. Pharmacokinetic data from published rat and human studies on 6:2 FTOH were used to estimate clearance and area under the curve (AUC) for its metabolites: 5:3 fluorotelomer carboxylic acid (5:3 A), perfluorohexanoic acid (PFHxA) and perfluoroheptanoic acid (PFHpA). Internal exposure to 5:3 A was the highest of evaluated metabolites across species and it had the slowest clearance. Additionally, 5:3 A clearance decreased with increasing 6:2 FTOH exposure. Our analysis provides insight into association of increased internal 5:3 A exposure with high biopersistence potential of 6:2 FTOH. Our results identify 5:3 A as an important biomarker of internal 6:2 FTOH exposure for use in biomonitoring studies, and are potentially useful for toxicological assessment of chronic dietary 6:2 FTOH exposure.

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

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.