Absorption, distribution, metabolism, excretion, and kinetics of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid ammonium salt following a single dose in rat, mouse, and cynomolgus monkey.

Ammonium, 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate has been developed as a processing aid used in the manufacture of fluoropolymers. The absorption, distribution, elimination, and distribution (ADME) and kinetic behavior of this substance has been evaluated in rats, mice, and cynomolgus monkeys by oral and intravenous routes of exposure and studied in both plasma and urine. The test substance is rapidly and completely absorbed in both rats and mice and both in vivo and in vitro experiments indicate that it is not metabolized.

Evaluation of chronic toxicity and carcinogenicity of ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate in Sprague-Dawley rats.

Ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate, developed for use as a polymerization processing aid in the manufacture of fluoropolymers, was tested for its potential chronic toxicity and carcinogenicity in a 2-year oral dosing study in Sprague-Dawley rats. Male rats were given daily doses of either 0, 0.1, 1 or 50 mg/kg; females were given either 0, 1, 50 or 500 mg/kg.

Comparative in vivo and in vitro analysis of possible estrogenic effects of perfluorooctanoic acid.

Previous studies suggested that perfluorooctanoate (PFOA) could activate the estrogen receptor (ER). The present study examined the hypothesis that PFOA can activate ER using an in vivo uterotrophic assay in CD-1 mice and an in vitro reporter assay. Pre-pubertal female CD-1 mice fed an estrogen-free diet from postnatal day (PND)14 through weaning on PND18 were administered 0, 0.

Pathology review of proliferative lesions of the exocrine pancreas in two chronic feeding studies in rats with ammonium perfluorooctanoate.

Two chronic dietary studies, conducted years apart, with ammonium perfluorooctanoate (APFO) in Sprague Dawley rats have been previously reported. Although both included male 300 ppm dietary dose groups, only the later study, conducted in 1990-1992 by Biegel et al., reported an increase in proliferative lesions (hyperplasia and adenoma) of the acinar pancreas.

Toxicological evaluation of 6:2 fluorotelomer alcohol.

6:2 fluorotelomer alcohol (6:2 FTOH; CF3[CF2]5[CH2]2OH, CAS# 647-42-7) was evaluated for acute, genetic, and subchronic toxicity using in vitro and in vivo methods. In rats, 6:2 FTOH was considered to be slightly toxic by the oral (LD50=1,750 mg/kg), and dermal (LD50 > 5,000 mg/kg) routes. In rabbits, 6:2 FTOH was not a primary skin or eye irritant, and it did not produce a dermal sensitization response in mice.

Thirteen week rodent feeding study with grain from molecular stacked trait lepidopteran and coleopteran protected (DP-ØØ4114-3) maize.

The results from a subchronic feeding study conducted in Sprague–Dawley rats fed with diets containing grain from 4114 (OECD unique identifier: DP-ØØ4114-3) maize that was untreated (4114) or sprayed in field with glufosinate ammonium (4114GLU) in a design similar to previous studies are reported. The test material, 4114 maize, is a hybrid maize produced by transformation with a DNA construct encoding 4 different transgenic proteins for resistance to lepidopteran pests, coleopteran pests, and tolerance to the herbicidal active ingredient glufosinate ammonium. There were a total of 144 rats divided into 12 groups of 12 rats/sex/group.

A species difference in the peroxisome proliferator-activated receptor α-dependent response to the developmental effects of perfluorooctanoic acid.

This study examined the effect of prenatal perfluorooctanoic acid (PFOA) administration on pre- and postnatal development using peroxisome proliferator-activated receptor α (PPARα)-humanized mice to determine if species differences in receptor activity might influence the developmental effects induced by PFOA. Pregnant mice were treated daily with water or PFOA (3mg/kg) by po gavage from gestation day 1 (GD1) until GD17 and then either euthanized on GD18 or allowed to give birth and then euthanized on postnatal day 20 (PND20). No changes in average fetal weight, crown-to-rump length, or placental weight were observed on GD18.

Ninety-day inhalation toxicity study with a vapor grown carbon nanofiber in rats.

A subchronic inhalation toxicity study of inhaled vapor grown carbon nanofibers (CNF) (VGCF-H) was conducted in male and female Sprague Dawley rats. The CNF test sample was composed of > 99.5% carbon with virtually no catalyst metals; Brunauer, Emmett, and Teller (BET) surface area measurements of 13.

Safety assessment of EPA-rich triglyceride oil produced from yeast: genotoxicity and 28-day oral toxicity in rats.

The 28-day repeat-dose oral and genetic toxicity of eicosapentaenoic acid triglyceride oil (EPA oil) produced from genetically modified Yarrowia lipolytica yeast were assessed. Groups of rats received 0 (olive oil), 940, 1880, or 2820 mg EPA oil/kg/day, or fish oil (sardine/anchovy source) by oral gavage. Lower total serum cholesterol was seen in all EPA and fish oil groups.

Safety assessment of EPA-rich oil produced from yeast: Results of a 90-day subchronic toxicity study.

The safety of eicosapentaenoic acid (EPA) oil produced from genetically modified Yarrowia lipolytica yeast was evaluated following 90 days of exposure. Groups of rats received 0 (olive oil), 98, 488, or 976 mg EPA/kg/day, or GRAS fish oil or deionized water by oral gavage. Rats were evaluated for in-life, neurobehavioral, anatomic and clinical pathology parameters.

Pathology Working Group review and evaluation of proliferative lesions of mammary gland tissues in female rats fed ammonium perfluorooctanoate (APFO) in the diet for 2 years.

Perfluorooctanoate (PFO) is a perfluorinated carboxylate that is widely distributed in the environment. A 2-year chronic study was conducted in rats fed either 30 or 300 ppm of ammonium perfluorooctanoate (APFO). To investigate the possible relationship of APFO exposure to proliferative mammary lesions, a Pathology Working Group (PWG) review of the original slides was performed.

Pulmonary exposures to Sepiolite nanoclay particulates in rats: resolution following multinucleate giant cell formation.

Sepiolite is a magnesium silicate-containing nanoclay mineral and is utilized as a nanofiller for nanocomposite applications. We postulated that lung exposures to Sepiolite clay samples could produce sustained effects. Accordingly, the pulmonary and extrapulmonary systemic impacts in rats of intratracheally instilled Sepiolite nanoclay samples were compared with quartz or ultrafine (uf) titanium dioxide particle-types at doses of 1mg/kg or 5mg/kg.

Toxicological evaluation of sodium perfluorohexanoate.

Sodium perfluorohexanoate [NaPFHx, F(CF(2))(5)CO(2)Na, CAS#2923-26-4] was evaluated in acute, 90-day subchronic, one-generation reproduction, developmental and in vitro genetic toxicity studies. In the subchronic/one-generation reproduction study, four groups of young adult male and female Crl:CD(SD) rats were administered NaPFHx daily for approximately 90 days by gavage at dosages of 0, 20, 100, or 500 mg/kg. Selected groups of rats were evaluated after 1- and 3-month recovery periods.

Immunotoxicity of perfluorooctanoic acid and perfluorooctane sulfonate and the role of peroxisome proliferator-activated receptor alpha.

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are environmentally widespread and persistent chemicals with multiple toxicities reported in experimental animals and humans. These compounds can trigger biological activity by activating the alpha isotype of peroxisome proliferator-activated receptors (PPARs), ligand-activated transcription factors that regulate gene expression; however, some biological effects may occur independently of the receptor. Activation of the peroxisome proliferator-activated receptor alpha (PPARalpha) modulates lipid and glucose homeostasis, cell proliferation and differentiation, and inflammation.

Subchronic, reproductive, and developmental toxicity of a fluorotelomer-based urethane polymeric product.

A commercial fluorotelomer-based urethane polymeric dispersion, consisting of polymer, surfactant, and water, was evaluated in subchronic, reproduction, and developmental toxicity studies. The dispersion was administered daily by gavage to rats at dosages of 0, 50, 250, or 1000 mg polymer/kg/day or with 70 mg/kg/day of the sulfonate surfactant. Dose levels of 0, 50, 250, or 1000 mg polymer/kg/day were also used for the reproductive and developmental studies.

Evaluation of the immune system in rats and mice administered linear ammonium perfluorooctanoate.

Repeated high doses of ammonium perfluorooctanoate (APFO) have been reported to affect immune system function in mice. To examine dose-response characteristics in both rats and mice, male CD rats and CD-1 mice were dosed by oral gavage with 0.3-30 mg/kg/day of linear APFO for 29 days.

90-day oral gavage toxicity study of 8-2 fluorotelomer alcohol in rats.

8-2 fluorotelomer alcohol is a fluorinated chemical intermediate used to manufacture specialty polymers and surfactants. The potential subchronic toxicity and the reversibility of the effects of this chemical were evaluated following approximately 90 days of oral gavage dosing to Crl:CD(SD)IGS BR rats. A complete toxicological profile, including neurobehavioral assessments and hepatic beta-oxidation, were conducted at selected intervals and a group of rats was included for a 90-day postdosing recovery period.

Characterization and reclassification of titanium dioxide-related pulmonary lesions.

Objective: Using current diagnostic criteria, this work summarizes the microscopic review of 16 proliferative squamous lesions, previously diagnosed as cystic keratinizing squamous cell carcinoma, in the lungs of rats from a 2-year inhalation study with pigment-grade titanium dioxide particles.

Methods: In the aftermath of two international pathology workshops designed, in part, to establish histological criteria for classifying pulmonary keratin lesions, these lesions were evaluated by four pathologists using current diagnostic criteria.

Results: Unanimous agreement was reached as to the diagnosis of each of the lesions.

Differential activation of nuclear receptors by perfluorinated fatty acid analogs and natural fatty acids: a comparison of human, mouse, and rat peroxisome proliferator-activated receptor-alpha, -beta, and -gamma, liver X receptor-beta, and retinoid X receptor-alpha.

Administration of ammonium salts of perfluorooctanoate (PFOA) to rats results in peroxisome proliferation and benign liver tumors, events associated with activation of the nuclear receptor (NR) peroxisome proliferator-activated receptor-alpha (PPARalpha). Due to its fatty acid structure, PFOA may activate other NRs, such as PPARbeta, PPARgamma, liver X receptor (LXR), or retinoid X receptor (RXR). In this study, the activation of human, mouse, and rat PPARalpha, PPARbeta, PPARgamma, LXRbeta, and RXRalpha by PFOA (including its linear and branched isomers) and perfluorooctane sulfonate (PFOS) was investigated and compared to several structural classes of natural fatty acids and appropriate positive control ligands.

Comparative responses of rats and mice exposed to linear/branched, linear, or branched ammonium perfluorooctanoate (APFO).

The purpose of this study was to compare the toxicity of linear/branched ammonium perfluorooctanoate (APFO) with that of linear and branched APFO. Linear/branched APFO (approximately 80% linear and 20% branched isomers) was formerly used in the production of commercial products. The extensive toxicologic database for APFO has been developed essentially using this mixture of isomers.

Acute, subchronic, and mutagenicity studies with norbornene fluoroalcohol.

The object of this study was to evaluate the toxicity of norbornene fluoroalcohol (NBFOH), which is used as an intermediate in the production of fluorinated monomers and polymers. NBFOH was evaluated for acute oral, dermal, and inhalation toxicity, dermal sensitization using the Local Lymph Node Assay (LLNA), mutagenesis by the Ames assay, and subchronic toxicity in a 4-week inhalation rat study. NBFOH demonstrated slight acute toxicity in oral, dermal, and inhalation studies.

Molecular characterization of thyroid toxicity: anchoring gene expression profiles to biochemical and pathologic end points.

Organic iodides have been shown to induce thyroid hypertrophy and increase alterations in colloid in rats, although the mechanism involved in this toxicity is unclear. To evaluate the effect that free iodide has on thyroid toxicity, we exposed rats for 2 weeks by daily gavage to sodium iodide (NaI). To compare the effects of compounds with alternative mechanisms (increased thyroid hormone metabolism and decreased thyroid hormone synthesis, respectively), we also examined phenobarbital (PB) and propylthiouracil (PTU) as model thyroid toxicants.

Inhalation toxicity of 1,3-propanediol in the rat.

1,3-Propanediol (504-63-2) was studied to determine the potential effects following repeated inhalation exposures to rats. Rats were exposed 6 hr/day, 5 days/wk for 2 wk (9 exposures) to vapor or vapor/aerosol mixtures of either 0, 41, 650, or 1800 mg 1,3-propanediol/m(3). In vivo responses were observed or measured daily.

The reproductive toxicology of ammonium perfluorooctanoate (APFO) in the rat.

Ammonium perfluorooctanoate (APFO) is a surfactant used primarily as an aid in processing various fluoropolymers. Many toxicology and epidemiological studies have been conducted with APFO; however, no specific information regarding functional reproduction was previously available. Therefore, the potential reproductive toxicity of APFO across two generations of offspring was studied using current EPA OPPTS 870.

Evaluation of a 15-day screening assay using intact male rats for identifying antiandrogens.

An in vivo screening assay using intact adult male rats has been evaluated for its ability to detect six antiandrogenic compounds via oral administration. The test compounds included cyproterone acetate (CPA), flutamide (FLUT), p,p'-DDE (DDE), di-n-butyl phthalate (DBP), linuron (LIN), and vinclozolin (VCZ). Two of the test compounds (DDE and FLUT) have been previously evaluated in the 15-day intact male assay with compound administration via intraperitoneal injection (ip).