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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

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.

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.