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86 References Were Found:

Archival Material
Archival Material

TOX-96: 1-Perfluorobutanesulfonic acid (375-73-5), potassium perfluorohexanesulfonate (3871-99-6), perfluorooctane sulfonate (1763-23-1), WY-14643 (50892-23-4). Chemical Effects in Biological Systems (CEBS)

Author: NTP (2018) Available online at https://manticore.niehs.nih.gov/cebssearch/publication/TOX-96. (Aug 2, 2018). [Website] HERO ID: 4309557


Technical Report
Technical Report

28-day evaluation of the toxicity (C20615) of perfluorodecanoic acid (PFDA) (335-76-2) on Harlan Sprague-Dawley rats exposed via gavage

Author: NTP (2018) U.S. Department of Health and Human Services. [NTP] HERO ID: 4309127


Technical Report
Technical Report

28-day evaluation of the toxicity (C04049) of perfluorononaoic acid (PFNA) (375-95-1) on Harlan Sprague-Dawley rats exposed via gavage

Author: NTP (2018) U.S. Department of Health and Human Services. [NTP] HERO ID: 4309103


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

Immunotoxic and hepatotoxic effects of perfluoro-n-decanoic acid (PFDA) on female Harlan Sprague-Dawley rats and B6C3F1/N mice when administered by oral gavage for 28 days

Authors: Frawley, RP; Smith, M; Cesta, MF; Hayes-Bouknight, S; Blystone, C; Kissling, GE; Harris, S; Germolec, D (2018) Journal of Immunotoxicology 15:41-52. HERO ID: 4287119

[Less] Poly- and perfluoroalkyl substances (PFAS) are chemically and thermally stable, hydrophobic, lipophobic . . . [More] Poly- and perfluoroalkyl substances (PFAS) are chemically and thermally stable, hydrophobic, lipophobic compounds used in stain repellants and water and oil surfactants, and associated with immunosuppression and peroxisome proliferator activity. Perfluoro-n-decanoic acid (PFDA, (CF3(CF2)8COOH), a fluorinated straight chain fatty acid compound, is reported to induce thymic atrophy and reversible bone marrow hypocellularity in rodent models. The objective of this study was to assess potential immunotoxicity of PFDA, due to its structural similarity to other immunosuppressive PFASs. Female Harlan Sprague-Dawley rats were exposed to 0-2.0 mg PFDA/kg by oral gavage daily for 28 d. Female B6C3F1/N mice were exposed once/week to 0-5.0 mg PFDA/kg by gavage for 4 weeks. Animals were evaluated for effects on immune cell populations in spleen and bone marrow, and innate, humoral-, and cell-mediated immunity. Mice were also evaluated for resistance to Influenza virus. Treatment-related hepatocyte necrosis and hepatomegaly were observed in rats treated with 0.5 mg PFDA/kg/d. In mice, hepatomegaly (26-89%) was observed following exposure to ≥0.625 mg PFDA/kg/week, while splenic atrophy (20%) was observed at 5.0 mg PFDA/kg/week. At 5.0 mg PFDA/kg/week, total spleen cells, and Ig + and NK + cells were decreased (17.6-27%). At ≥ 1.25 mg PFDA/kg/week the numbers of splenic CD3+, CD4+, CD8+, and Mac3+cells were decreased (10.5-39%). No changes were observed in leukocyte subpopulations in PFDA-exposed rats. Phagocytosis by fixed-tissue macrophages was decreased in liver (specific activity, 24-39%) at ≥0.25 mg PFDA/kg/d in rats. PFDA-induced effects on humoral- and cell-mediated immunity, host resistance, and bone marrow progenitor cells were limited. These data suggest that exposure to PFDA may induce adverse effects in rat liver in a manner consistent with the PFAS class, and may also alter the balance of immune cell populations in lymphoid tissues in mice.

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

Reproductive and developmental toxicity of potassium perfluorohexanesulfonate in CD-1 mice

Authors: Chang, S; Butenhoff, JL; Parker, GA; Coder, PS; Zitzow, JD; Krisko, RM; Bjork, JA; Wallace, KB; Seed, JG (2018) Reproductive Toxicology 78:150-168. HERO ID: 4409324

[Less] Potassium perfluorohexanesulfoante (K+PFHxS) was evaluated for reproductive/developmental toxicity in . . . [More] Potassium perfluorohexanesulfoante (K+PFHxS) was evaluated for reproductive/developmental toxicity in CD-1 mice. Up to 3 mg/kg-d K+PFHxS was administered (n = 30/sex/group) before mating, for at least 42 days in F0 males, and for F0 females, through gestation and lactation. F1 pups were directly dosed with K+PFHxS for 14 days after weaning. There was an equivocal decrease in live litter size at 1 and 3 mg/kg-d, but the pup-born-to-implant ratio was unaffected. Adaptive hepatocellular hypertrophy was observed, and in 3 mg/kg-d F0 males, it was accompanied by concomitant decreased serum cholesterol and increased alkaline phosphatase. There were no other toxicologically significant findings on reproductive parameters, hematology/clinical pathology/TSH, neurobehavioral effects, or histopathology. There were no treatment-related effects on postnatal survival, development, or onset of preputial separation or vaginal opening in F1 mice. Consistent with previous studies, our data suggest that the potency of PFHxS is much lower than PFOS in rodents.

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

Perfluorohexane Sulfonate (PFHxS) and a Mixture of Endocrine Disrupters Reduce Thyroxine Levels and Cause Anti-Androgenic Effects in Rats

Authors: Ramhøj, L; Hass, U; Boberg, J; Scholze, M; Christiansen, S; Nielsen, F; Axelstad, M (2018) Toxicological Sciences. HERO ID: 4442260

[Less] The developmental toxicity of perfluorohexane sulfonate (PFHxS) is largely unknown despite widespread . . . [More] The developmental toxicity of perfluorohexane sulfonate (PFHxS) is largely unknown despite widespread environmental contamination and presence in human serum, tissues and milk.To thoroughly investigate PFHxS toxicity in developing rats and to mimic a realistic human exposure situation, we examined a low dose close to human relevant PFHxS exposure, and combined the dose-response studies of PFHxS with a fixed dose of twelve environmentally relevant endocrine disrupting chemicals (EDmix).Two reproductive toxicity studies in time-mated Wistar rats exposed throughout gestation and lactation were performed. Study 1 included control, two doses of PFHxS and two doses of PFHxS+EDmix (n = 5-7). Study 2 included control, 0.05, 5 or 25 mg/kg body weight/day PFHxS, EDmix-only, 0.05, 5 or 25 mg PFHxS/kg plus EDmix (n = 13-20).PFHxS caused no overt toxicity in dams and offspring but decreased male pup birth weight and slightly increased liver weights at high doses and in combination with the EDmix. A marked effect on T4 levels was seen in both dams and offspring, with significant reductions from 5 mg/kg/day. The EDmix caused anti-androgenic effects in male offspring, manifested as slight decreases in anogenital distance, increased nipple retention and reductions of the weight of epididymides, ventral prostrate and vesicular seminalis.PFHxS can induce developmental toxicity and in addition results of the co-exposure studies indicated that PFHxS and the EDmix potentiate the effect of each other on various endpoints, despite their different modes of action. Hence, risk assessment may underestimate toxicity when mixture toxicity and background exposures are not taken into account.

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

Correlation between mast cell-mediated allergic inflammation and length of perfluorinated compounds

Authors: Lee, JK; Kim, SH (2018) Journal of Toxicology and Environmental Health, Part A: Current Issues 1-12. HERO ID: 4238305

[Less] Perfluorinated compounds (PFC) have widely been used in numerous applications including clothing, food . . . [More] Perfluorinated compounds (PFC) have widely been used in numerous applications including clothing, food packaging, and nonstick coating. With the widespread use of PFC, concerns regarding potential adverse health effects in humans and wildlife have increased. In spite of the known PFC-mediated immunotoxiciy, correlation with PFC and allergic inflammation still requires elucidation. The aim of this study was to examine the effect of four types of PFC (perfluoroheptanoic acid [PFHpA], perfluorononanoic acid [PFNA], perfluorodecanoic acid [PFDA], and perfluoroundecanoic acid [PFUnA]) on mast cell-mediated allergic inflammation in the presence of high-affinity immunoglobulin (Ig) E receptor (FcεRI) cross-linking. Among PFC family, long-chain PFDA and PFUnA increased release of histamine and β-hexosaminidase by up-regulation of intracellular calcium levels in IgE-stimulated mast cells. In addition, PFDA and PFUnA enhanced gene expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 by activation of nuclear factor-κB in IgE-stimulated mast cells. In ovalbumin (OVA)-induced model of systemic anaphylaxis in the presence of hypothermia, PFNA, PFDA, and PFUnA exacerbated allergic symptoms accompanied by elevation in serum histamine, TNF-α, IgE, and IgG1. Our data indicate that some PFC aggravated high-affinity IgE receptor (FcεRI)-mediated mast cell degranulation and allergic symptoms. Consequently, the results demonstrated that carbon-chain length of PFC may serve as a factor in allergic inflammation.

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

Perfluoroalkyl acids-induced liver steatosis: Effects on genes controlling lipid homeostasis

Authors: Das, KP; Wood, CR; Lin, MT; Starkov, AA; Lau, C; Wallace, KB; Corton, JC; Abbott, BD (2017) Toxicology 378:37-52. HERO ID: 3859817

[Less] Persistent presence of perfluoroalkyl acids (PFAAs) in the environment is due to their extensive use . . . [More] Persistent presence of perfluoroalkyl acids (PFAAs) in the environment is due to their extensive use in industrial and consumer products, and their slow decay. Biochemical tests in rodent demonstrated that these chemicals are potent modifiers of lipid metabolism and cause hepatocellular steatosis. However, the molecular mechanism of PFAAs interference with lipid metabolism remains to be elucidated. Currently, two major hypotheses are that PFAAs interfere with mitochondrial beta-oxidation of fatty acids and/or they affect the transcriptional activity of peroxisome proliferator-activated receptor α (PPARα) in liver. To determine the ability of structurally-diverse PFAAs to cause steatosis, as well as to understand the underlying molecular mechanisms, wild-type (WT) and PPARα-null mice were treated with perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), or perfluorohexane sulfonate (PFHxS), by oral gavage for 7days, and their effects were compared to that of PPARα agonist WY-14643 (WY), which does not cause steatosis. Increases in liver weight and cell size, and decreases in DNA content per mg of liver, were observed for all compounds in WT mice, and were also seen in PPARα-null mice for PFOA, PFNA, and PFHxS, but not for WY. In Oil Red O stained sections, WT liver showed increased lipid accumulation in all treatment groups, whereas in PPARα-null livers, accumulation was observed after PFNA and PFHxS treatment, adding to the burden of steatosis observed in control (untreated) PPARα-null mice. Liver triglyceride (TG) levels were elevated in WT mice by all PFAAs and in PPARα-null mice only by PFNA. In vitro β-oxidation of palmitoyl carnitine by isolated rat liver mitochondria was not inhibited by any of the 7 PFAAs tested. Likewise, neither PFOA nor PFOS inhibited palmitate oxidation by HepG2/C3A human liver cell cultures. Microarray analysis of livers from PFAAs-treated mice indicated that the PFAAs induce the expression of the lipid catabolism genes, as well as those involved in fatty acid and triglyceride synthesis, in WT mice and, to a lesser extent, in PPARα-null mice. These results indicate that most of the PFAAs increase liver TG load and promote steatosis in mice We hypothesize that PFAAs increase steatosis because the balance of fatty acid accumulation/synthesis and oxidation is disrupted to favor accumulation.

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

Exposure of pregnant mice to perfluorobutanesulfonate causes hypothyroxinemia and developmental abnormalities in female offspring

Authors: Feng, X; Cao, X; Zhao, S; Wang, X; Hua, X; Chen, L; Chen, L (2017) Toxicological Sciences 155:409-419. HERO ID: 3856465

[Less] Perfluorobutanesulfonate (PFBS) is widely used in many industrial products. We evaluated the influence . . . [More] Perfluorobutanesulfonate (PFBS) is widely used in many industrial products. We evaluated the influence of prenatal PFBS exposure on perinatal growth and development, pubertal onset, and reproductive and thyroid endocrine system in female mice. Here, we show that when PFBS (200 and 500 mg/kg/day) was orally administered to pregnant mice (PFBS-dams) on days 1-20 of gestation; their female offspring (PFBS-offspring) exhibited decreased perinatal body weight and delayed eye opening compared with control offspring. Vaginal opening and first estrus were also significantly delayed in PFBS-offspring, and diestrus was prolonged. Ovarian and uterine size, as well as follicle and corpus luteum numbers, were reduced in adult PFBS-offspring. Furthermore, pubertal and adult PFBS-offspring exhibited decreases in serum estrogen (E2) and progesterone (P4) levels with the elevation of luteinizing hormone levels. Notably, decreases in serum total thyroxine (T4) and 3,3', 5-triiodothyronine (T3) levels were observed in fetal, pubertal, and adult PFBS-offspring in conjunction with slight increases in thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone levels. In addition, PFBS-dams exhibited significant decreases in total T4 and T3 levels and free T4 levels and increases in TSH levels, but no changes in E2 and P4 levels. These results indicate that prenatal PFBS exposure (≥200 mg/kg/day) causes permanent hypothyroxinemia accompanied by deficits in perinatal growth, pubertal onset, and reproductive organ development in female mice.