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Robert C Buck - One of the best experts on this subject based on the ideXlab platform.

  • Oral repeated-dose systemic and reproductive toxicity of 6:2 Fluorotelomer Alcohol in mice.
    Toxicology reports, 2014
    Co-Authors: Pushkor Mukerji, Robert C Buck, Jessica Caverly Rae, John C. O'connor
    Abstract:

    6:2 Fluorotelomer Alcohol (6:2 FTOH) was evaluated for potential systemic repeated-dose and reproductive toxicity in mice. 6:2 FTOH was administered by oral gavage to CD-1 mice as a suspension in 0.5% aqueous methylcellulose with 0.1% Tween-80 at dosages of 1, 5, 25, or 100 mg/kg/day. The no-observed-adverse-effect level (NOAEL) for systemic toxicity was 25 mg/kg/day (males) and 5 mg/kg/day (females), based on effects at higher doses on mortality, clinical observations, body weight, nutritional parameters, hematology (red and white blood cell), clinical chemistry (liver-related), liver weights, and histopathology (liver, teeth, reproductive tract, and mammary gland). However, 6:2 FTOH was not a selective reproductive toxicant. The NOAEL for reproductive toxicity was >100 mg/kg/day; no effects on reproductive outcome were observed at any dosage. The NOAEL for viability and growth of the offspring was 25 mg/kg/day, based on clinical signs of delayed maturation in pups, and reductions in pup survival and pup body weight during lactation at 100 mg/kg/day. While the severity of the effects was generally greater in mice than previously reported in CD rats, the overall NOAELs were identical in both species, 5 mg/kg/day for systemic toxicity and 25 mg/kg/day for offspring viability/growth. 6:2 FTOH was not a selective reproductive toxicant in either species; no effects on reproductive outcome occurred at any dose level, and any effects observed in offspring occurred at dose levels that induced mortality and severe toxicity in maternal animals.

  • 6:2 Fluorotelomer iodide in vitro metabolism by rat liver microsomes: Comparison with [1,2-14C] 6:2 Fluorotelomer Alcohol
    Chemosphere, 2014
    Co-Authors: Ting Ruan, Lisa M Sulecki, Ning Wang, Barry W. Wolstenholme, Guibin Jiang, Robert C Buck
    Abstract:

    6:2 Fluorotelomer iodide [6:2 FTI, F(CF2)(6)CH2CH2I] is the industrial raw material used to manufacture 6:2 Fluorotelomer Alcohol [6:2 FTOH, F(CF2)(6)CH2CH2OH] and 6:2 FTOH-based products. During its manufacture and industrial use, workers may be exposed to via oral, dermal or inhalation of 6:2 FTI. Therefore it is useful to understand how 6:2 HI may be metabolized and into what transformation products. 6:2 FTI in vitro rat liver microsomal metabolism was explored for the first time to compare its biotransformation potential with that of [1,2-C-14] 6:2 FTOH [F(CF2)(6)(CH2CH2OH)-C-14-C-14]. 6:2 FTI and 6:2 FTOH metabolite yields were determined in closed-bottle systems using Sprague Dawley and Wistar Han rat microsomes after incubation at 37 C for up to 6 h with NADPH (reduced form of nicotinamide adenine dinucleotide phosphate)-addition and NADPH-regenerating systems, respectively. 5:3 acid [F(CF2)(5)CH2CH2COOH] was the most abundant metabolite for 6:2 FTI (3.3-6.3 mol%) and 6:2 FTOH (9-12 mol%). Perfluorobutanoic acid (PFBA), perfluoropentanoic acid (PFPeA), and perfluorohexanoic acid (PFHxA) in sum accounted for 1.3-2.2 mol% from 6:2 FTI and 2.7-4.4 mol% from 6:2 FTOH biotransformation. Perfluoroheptanoic acid (PFHpA) accounted for 0.14-0.36 mol% from 6:2 FTI but only 0.01-0.06 mol% from 6:2 FTOH biotransformation. These results suggest that mammalian systems exposed to 6:2 FTI or 6:2 FTOH would form 5:3 acid, PFBA, PFPeA, PFHxA as the primary stable metabolites, whereas more PFHpA would be expected from 6:2 FTI biotransformation. (C) 2014 Elsevier Ltd. All rights reserved.

  • Toxicological evaluation of 6:2 Fluorotelomer Alcohol
    Toxicology, 2014
    Co-Authors: Tessa L. Serex, Robert C Buck, S. Satheesh Anand, Susan M. Munley, E. Maria Donner, Steven R. Frame, Scott E. Loveless
    Abstract:

    Abstract 6:2 Fluorotelomer Alcohol (6:2 FTOH; CF 3 [CF 2 ] 5 [CH 2 ] 2 OH, 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 (LD 50  = 1750 mg/kg), and dermal (LD 50  > 5000 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. In a 90-day subchronic study, 6:2 FTOH was administered to rats by oral gavage (0, 5, 25, 125, 250 mg/kg/day). Mortality was observed at 125 and 250 mg/kg/day; deaths occurred after approximately three weeks of dosing and continued sporadically. The NOAEL in the subchronic study was 5 mg/kg/day based on hematology and liver effects. 6:2 FTOH was not mutagenic in the bacterial reverse mutation test or in the mouse lymphoma assay and was not clastogenic in a chromosome aberration assay in human lymphocytes. The hazard classification for human health endpoints of 6:2 FTOH according to the United Nations Globally Harmonized System of Classification and Labeling of Chemicals (GHS) is Category 4 for acute oral toxicity based on an LD 50 of 1750 mg/kg. Other acute health endpoints including eye and skin irritation, skin sensitization, as well as genotoxicity, did not meet the criteria for hazard classification. Benchmark Dose Analysis was performed on the most sensitive endpoints from the 90-day oral gavage study and these levels were all above the study NOAEL of 5 mg/kg/day. For risk assessment purposes, the recommended point of departure is the more conservative study NOAEL of 5 mg/kg/day.

  • Evaluation of the reproductive and developmental toxicity of 6:2 Fluorotelomer Alcohol in rats.
    Toxicology, 2014
    Co-Authors: John C. O'connor, Susan M. Munley, Tessa L. Serex, Robert C Buck
    Abstract:

    6:2 Fluorotelomer Alcohol (6:2 FTOH) was evaluated for potential developmental and reproductive toxicity. 6:2 FTOH was administered by oral gavage to Sprague-Dawley rats as a suspension in 0.5% aqueous methylcellulose at dosages of 5, 25, 125, or 250 mg/kg/day. The developmental toxicity study was performed in accordance with the Organization for Economic Development (OECD) Test Guideline 414, and the one-generation reproductive toxicity study was performed in accordance with the OECD Test Guideline 415. For the developmental toxicity study, adverse maternal toxicity observed at 250 mg/kg/day included reductions in body weight parameters and food consumption. Evidence of developmental toxicity was limited to increases in skeletal variations (ossification delays in the skull and rib alterations) at 250 mg/kg/day. There were no adverse maternal or developmental effects observed at 5, 25, or 125 mg/kg/day and there were no effects on reproductive outcome or quantitative litter data at any dose level. For the one-generation reproduction toxicity study, systemic parental and developmental toxicity were observed at 125 and 250 mg/kg/day. At 250 mg/kg/day, there was increased mortality among male and female parental rats, effects on body weight parameters, food consumption, and clinical signs, and there were effects on offspring survival indices and body weights. At 125 mg/kg/day, there was an increase in mortality in parental males only, and parental toxicity was limited to effects on body weight gain, food consumption (lactation), and clinical signs. Uterine weights were decreased at 125 and 250 mg/kg/day, although there were no corroborative histopathological changes. At 125 mg/kg/day, pup mortality was increased on lactation day 1, and body weights of the offspring were decreased during the second half of lactation. There was no evidence of either parental or developmental toxicity at 5 or 25mg/kg/day, and there were no effects on reproductive outcome at any dose level. Based on these data, 6:2 FTOH is not a selective reproductive or developmental toxicant at dosages that induce clear maternal/parental toxicity. Therefore, 6:2 FTOH would not be classified for reproductive/developmental toxicity under the United Nations' Globally Harmonized System of Classification and Labeling of Chemicals.

  • 6 2 and 8 2 Fluorotelomer Alcohol anaerobic biotransformation in digester sludge from a wwtp under methanogenic conditions
    Environmental Science & Technology, 2013
    Co-Authors: Shu Zhang, Bogdan Szostek, Ning Wang, Patricia K. Mccausland, Barry W. Wolstenholme, Robert C Buck
    Abstract:

    6:2 FTOH and 8:2 FTOH [FTOHs, F(CF2)nCH2CH2OH, n = 6, 8] are the principal polyfluorinated raw materials used to manufacture FTOH-based products, which may be released to WWTPs during their product life cycle. For the first time, anaerobic biotransformation of FTOHs and key biotransformation intermediates in WWTP digester sludge under methanogenic conditions was investigated. 6:2 FTOH was transformed to 6:2 FTCA, [F(CF2)6CH2COOH, 32–43 mol %], 6:2 FTUCA [F(CF2)5CF═CHCOOH, 1.8–8.0 mol %], and 5:3 acid [F(CF2)5CH2CH2COOH, 18–23 mol %] by day 90 and day 176 in two separate studies. 8:2 FTOH was transformed by day 181 to 8:2 FTCA (18 mol %), 8:2 FTUCA (5.1 mol %), and 7:3 acid (27 mol %). 6:2 and 8:2 FTOH anaerobic biotransformation led to low levels of perfluorohexanoic acid (PFHxA, ≤0.4 mol %) and perfluorooctanoic acid (PFOA, 0.3 mol %), respectively. 6:2 FTUCA anaerobic biotransformation led to a newly identified novel transient intermediate 3-fluoro 5:3 acid [F(CF2)5CFHCH2COOH] and 5:3 acid, but not 5:2 ...

Ning Wang - One of the best experts on this subject based on the ideXlab platform.

  • Impact of 6:2 Fluorotelomer Alcohol aerobic biotransformation on a sediment microbial community.
    The Science of the total environment, 2016
    Co-Authors: Shu Zhang, Ning Wang, Nancy Merino, Ting Ruan
    Abstract:

    Abstract Sediment microbial communities are responsible for many chemical biotransformation processes in the aquatic environment and play a critical role in various ecosystems and biogeochemical cycling. However, the impact of polyfluoroalkyl substances on sediment microbial communities remains unclear. These substances are increasingly being used in consumer and industrial products to replace environmentally persistent perfluoroalkyl substances. In this study, we investigated the effects of low (5 mg/L) and high (15 mg/L) doses of 6:2 Fluorotelomer Alcohol [6:2 FTOH, F(CF 2 ) 6 CH 2 CH 2 OH] on the structure of a sediment microbial community. 6:2 FTOH biotransformation was rapid in the sediment mixture with a half-life 2 ) 5 CH(OH)CH 3 ], 9.6 mol% 5:3 Acid [F(CF 2 ) 5 CH 2 CH 2 COOH] and 11 mol% PFHxA [F(CF 2 ) 5 COOH], while 73 mol% 5:2 sFTOH, 23 mol% 5:3 Acid and 26 mol% PFHxA were observed in the low dose condition. In the original (control) sediment without 6:2 FTOH dosing, Proteobacteria was the predominant microorganism (18%), followed by Chloroflexi (14%), Verrucomicrobia (13%), Firmicutes (3.4%), Bacterioidetes (2.4%), Actinobacteria (1.7%) and Planctomycetes (1.3%). The presence of 6:2 FTOH and the accumulation of transient transformation products in the sediment exerted selection pressure on the microbial taxonomic distribution and diversity. Our observations indicate that potential 6:2 FTOH degraders and tolerant strains, such as Dokdonella spp ., Thauera spp., Albidovulum spp. and Caldanaerovirga spp., existed in the sediment mixture and began to dominate over time. This suggests that these genera might have higher tolerance towards elevated 6:2 FTOH and its transformation products. These findings on the characterization of sediment microbial community stability and dynamics will help predict changes in response to perfluoroalkyl and polyfluoroalkyl substances and also help identify robust microbial strains to degrade polyfluoroalkyl substances in the environment.

  • Engineering artificial communities for enhanced FTOH degradation
    The Science of the total environment, 2016
    Co-Authors: Matthew Lewis, Ning Wang, Myunghee Kim, Kung-hui Chu
    Abstract:

    Fluorotelomer Alcohols (FTOHs, [F(CF2)nCH2CH2OH]) are concerned environmental pollutants with perfluorinated carbon chains. FTOHs can be biotransformed; however, the extent, the pace of the defluorination, and types of metabolites produced vary depending on degradative microorganisms under different environment. In this study, we examined ways to increase the effectiveness of the FTOH defluorination process to less persistent major metabolites. Defined mixed cultures and bioaugmented microbial cultures were engineered to study their ability to biotransform 6:2 Fluorotelomer Alcohol [F(CF2)6CH2CH2OH]. The effects of carbon sources and the concentration of carbon sources were also examined. All experiments resulted in 5:2 sFTOH [F(CF2)5CH(OH)CH3] as the primary metabolite at the end point. The carbon sources resulted in different amounts of pathway utilization as well as overall changes in effectiveness. The best overall effectiveness was observed when cosubstrate carbon was kept at low concentrations. Pathway II was best utilized by the P. butanovora + P. fluorescens mixed culture, with lactate having a slight negative impact on pathway II utilization. Additional carbon to augmented activated sludge resulted in decreased 6:2 FTOH biotransformation by 60%. Enrichment cultures showed that shorter chain FTOHs are easier to degrade, with the n-octane enriched culture transforming 20% of 8:2 FTOH, 60% of 6:2 FTOH and 70% of 4:2 FTOH. The microbial communities of the enrichment cultures and the alkane hydroxylase gene were also examined to help understand FTOH biotransformation mechanisms.

  • 6:2 Fluorotelomer iodide in vitro metabolism by rat liver microsomes: Comparison with [1,2-14C] 6:2 Fluorotelomer Alcohol
    Chemosphere, 2014
    Co-Authors: Ting Ruan, Lisa M Sulecki, Ning Wang, Barry W. Wolstenholme, Guibin Jiang, Robert C Buck
    Abstract:

    6:2 Fluorotelomer iodide [6:2 FTI, F(CF2)(6)CH2CH2I] is the industrial raw material used to manufacture 6:2 Fluorotelomer Alcohol [6:2 FTOH, F(CF2)(6)CH2CH2OH] and 6:2 FTOH-based products. During its manufacture and industrial use, workers may be exposed to via oral, dermal or inhalation of 6:2 FTI. Therefore it is useful to understand how 6:2 HI may be metabolized and into what transformation products. 6:2 FTI in vitro rat liver microsomal metabolism was explored for the first time to compare its biotransformation potential with that of [1,2-C-14] 6:2 FTOH [F(CF2)(6)(CH2CH2OH)-C-14-C-14]. 6:2 FTI and 6:2 FTOH metabolite yields were determined in closed-bottle systems using Sprague Dawley and Wistar Han rat microsomes after incubation at 37 C for up to 6 h with NADPH (reduced form of nicotinamide adenine dinucleotide phosphate)-addition and NADPH-regenerating systems, respectively. 5:3 acid [F(CF2)(5)CH2CH2COOH] was the most abundant metabolite for 6:2 FTI (3.3-6.3 mol%) and 6:2 FTOH (9-12 mol%). Perfluorobutanoic acid (PFBA), perfluoropentanoic acid (PFPeA), and perfluorohexanoic acid (PFHxA) in sum accounted for 1.3-2.2 mol% from 6:2 FTI and 2.7-4.4 mol% from 6:2 FTOH biotransformation. Perfluoroheptanoic acid (PFHpA) accounted for 0.14-0.36 mol% from 6:2 FTI but only 0.01-0.06 mol% from 6:2 FTOH biotransformation. These results suggest that mammalian systems exposed to 6:2 FTI or 6:2 FTOH would form 5:3 acid, PFBA, PFPeA, PFHxA as the primary stable metabolites, whereas more PFHpA would be expected from 6:2 FTI biotransformation. (C) 2014 Elsevier Ltd. All rights reserved.

  • biotransformation of 6 2 Fluorotelomer Alcohol 6 2 ftoh by a wood rotting fungus
    Environmental Science & Technology, 2014
    Co-Authors: Nancy Tseng, Bogdan Szostek, Ning Wang, Shaily Mahendra
    Abstract:

    Biotransformation of 6:2 FTOH [F(CF2)6CH2CH2OH] by the white-rot fungus, Phanerochaete chrysosporium, was investigated in laboratory studies. 6:2 FTOH is a raw material increasingly being used to replace products that can lead to long-chain perfluoroalkyl carboxylic acids (PFCAs, ≥ 8 carbons). During a product’s life cycle and after final disposal, 6:2 FTOH-derived compounds may be released into the environment and potentially biotransformed. In this study, P. chrysosporium transformed 6:2 FTOH to perfluorocarboxylic acids (PFCAs), polyfluorocarboxylic acids, and transient intermediates within 28 days. 5:3 Acid [F(CF2)5CH2CH2COOH] was the most abundant transformation product, accounting for 32–43 mol % of initially applied 6:2 FTOH in cultures supplemented with lignocellulosic powder, yeast extract, cellulose, and glucose. PFCAs, including perfluoropentanoic (PFPeA) and perfluorohexanoic (PFHxA) acids, accounted for 5.9 mol % after 28-day incubation. Furthermore, four new transformation products as 6:2 FT...

  • 6:2 Fluorotelomer Alcohol (6:2 FTOH) biodegradation by multiple microbial species under different physiological conditions
    Applied microbiology and biotechnology, 2013
    Co-Authors: Myunghee Kim, Ning Wang, Kung-hui Chu
    Abstract:

    Factors affecting microbial aerobic biodegradation of 6:2 Fluorotelomer Alcohol [6:2 FTOH, F(CF₂)₆CH₂CH₂OH] were investigated using three alkane-degrading bacteria (Mycobacterium vaccae JOB5, Pseudomonas oleovorans, and Pseudomonas butanovora) and one fluoroacetate-degrading bacterium (Pseudomonas fluorescens DSM 8341). In the presence of formate (an external reducing energy source), P. fluorescens DSM 8341 produced perfluorobutanoic acid by removing three -CF₂- groups from 6:2 FTOH. Only P. fluorescens DSM 8341 transformed 5:3 acid to 4:3 acid and perfluoropentanoic acid. However, formate showed no effects on the degradation rates, patterns, or transformation products of 6:2 FTOH by M. vaccae JOB5. When dicyclopropylketone (an alkane hydroxylase inducer) or formate was added, P. oleovorans rapidly degraded 6:2 FTOH and produced PFPeA. In the presence of lactate, P. butanovora degraded 6:2 FTOH slowly but produced diverse metabolites. Our results demonstrate that the extent and mechanisms of 6:2 FTOH biotransformation are affected by strain types, enzyme inducers, and levels of reducing energy.

B. Zhou - One of the best experts on this subject based on the ideXlab platform.

  • effects of Fluorotelomer Alcohol 8 2 ftoh on steroidogenesis in h295r cells targeting the camp signalling cascade
    Toxicology and Applied Pharmacology, 2010
    Co-Authors: Xiaowei Zhang, Steve Wiseman, Jonathan E Naile, Hong Chang, Paul D. Jones, Markus Hecker, John P Giesy, B. Zhou
    Abstract:

    Previous studies have demonstrated that perfluorinated chemicals (PFCs) can affect reproduction by disruption of steroidogenesis in experimental animals. However, the underlying mechanism(s) of this disruption remain unknown. Here we investigated the effects and mechanisms of action of 1H, 1H, 2H, 2H-perfluoro-decan-1-ol (8:2 FTOH) on steroidogenesis using a human adrenocortical carcinoma cell line (H295R) as a model. H295R cells were exposed to 0, 7.4, 22.2 or 66.6 mu M 8:2 FTOH for 24 h and productions of progesterone, 17 alpha-OH-progesterone, androstenedione, testosterone, deoxycorticosterone, corticosterone and cortisol were quantified by HPLC-MS/MS. With the exception of progesterone, 8:2 FTOH treatment significantly decreased production of all hormones in the high dose group. Exposure to 8:2 FTOH significantly down-regulated cAMP-dependent mRNA expression and protein abundance of several key steroidogenic enzymes, including StAR, CYP11A, CYP11B1, CYP11B2, CYP17 and CYP21. Furthermore, a dose-dependent decrease of cellular cAMP levels was observed in H295R cells exposed to 8:2 FTOH. The observed responses are consistent with reduced cellular CAMP levels. Exposure to 8:2 FTOH resulted in significantly less basal (+GTP) and isoproterenol-stimulated adenylate cyclase activities, but affected neither total cellular ATP level nor basal (-GTP) or NaF-stimulated adenylate cyclase activities, suggesting that inhibition of steroidogenesis may be due to an alteration in membrane properties. Metabolites of 8:2 FTOH were not detected by HPLC-MS/MS, suggesting that 8:2 FTOH was not metabolized by H295R cells. Overall, the results show that 8:2 FTOH may inhibit steroidogenesis by disrupting the cAMP signalling cascade. (C) 2010 Elsevier Inc. All rights reserved.

  • combined effects of polyfluorinated and perfluorinated compounds on primary cultured hepatocytes from rare minnow gobiocypris rarus using toxicogenomic analysis
    Aquatic Toxicology, 2009
    Co-Authors: Hongxia Zhang, Jianshe Wang, B. Zhou
    Abstract:

    Polyfluorinated and perfluorinated compounds (PFCs) are used in numerous commercial products and have been ubiquitously detected in the environment as well as in the blood of humans and wildlife. To assess the combined effects caused by PFCs in mixtures, gene expression profiles were generated using a custom cDNA microarray to detect changes in primary cultured hepatocytes of rare minnows exposed to six individual PFCs (perfluorooctanoic acid, perfluorononanoic acid, perfluorodecanoic acid, perfluorododecanoic acid, perfluorooctane sulfonate, and 8:2 Fluorotelomer Alcohol) and four formulations of the PFCs mixtures. Mixtures as well as individual compounds consistently regulated a particular gene set, which suggests that these conserved genes may play a central role in the toxicity mediated by PFCs. Specifically, a number of genes regulated by the mixtures were identified in this study, which were not affected by exposure to any single component. These genes are implicated in multiple biological functions and processes, including fatty acid metabolism and transport, xenobiotic metabolism, immune responses, and oxidative stress. More than 80% of the altered genes in the PFOA- and PFOS-dominant mixture groups were of the same gene set, while the gene expression profiles from single PFOA and PFOS exposures were not as similar. This work contributes to the development of toxicogenomic approaches in combined toxicity assessment and allows for comprehensive insights into the combined action of PFCs mixtures in multiple environmental matrices. (C) 2009 Elsevier B.V. All rights reserved.

  • Endocrine disruption and reproductive impairment in zebrafish by exposure to 8:2 Fluorotelomer Alcohol
    Aquatic toxicology (Amsterdam Netherlands), 2009
    Co-Authors: Chunsheng Liu, Jun Deng, Mathan Ramesh, B. Zhou
    Abstract:

    The Fluorotelomer Alcohols (FTOHs) have been detected in the aquatic environment and shown potential estrogenic activity, but the effects on fish reproduction remain unknown. In the present study, 4-month-old zebrafish were exposed to different concentrations of 8:2 FTOH (0, 10, 30, 90, 270 mu g/L) for 4 weeks, and the impact on reproduction was investigated. The plasma testosterone (T) and estradiol (E2) levels were significantly increased in the females, while T and E2 levels were decreased and increased in the males, respectively. The average number of eggs spawned and sperm production were reduced upon exposure to the chemical,which also resulted in thinning of eggshell, and reduced protein content and egg diameter. Histological examination showed promotion of oocyte maturation and retarded spermiation in female and male fish, respectively. The gene transcription of follicle-stimulating hormone beta (FSH beta) and luteinizing hormone beta (LH beta) in the pituitary were up- and down-regulated in female and male fish, respectively. Up-regulation of vitellogenin (VTG1) and zona pellucida protein 2 (ZP2a) gene transcription was observed in the males, indicating estrogenic activity. However, down-regulation of gene transcription of VTG1 and ZP2a was measured in the females, associated with decreased fecundity. In addition, exposure of adult zebrafish to 8:2 FTOH caused reduced hatching rates in the offspring. The results demonstrated that waterborne exposure to 8:2 FTOH caused disruption of sex hormone biosynthesis and impaired reproduction in adult zebrafish, ultimately resulting in decreased hatching rates in the offspring. (C) 2009 Elsevier B.V. All rights reserved.

  • waterborne exposure to Fluorotelomer Alcohol 6 2 ftoh alters plasma sex hormone and gene transcription in the hypothalamic pituitary gonadal hpg axis of zebrafish
    Aquatic Toxicology, 2009
    Co-Authors: Liqin Yu, Jun Deng, Rudolf S S Wu, B. Zhou
    Abstract:

    Fluorotelomer Alcohols (FTOHs) have shown estrogenic activity in vitro and in vivo, but the mechanism of this activity is not known. In this study, 18-week-old zebrafish (Danio rerio) were exposed to 0, 0.03, 0.3 and 3.0 mg/l 1H, 1H, 2H, 2H-perfluorooctan-1-ol (6:2 ETCH) for 7 days, and the effects on plasma sex hormone levels were measured followed by use of real-time PCR to examine selected gene expression in hypothalamic-pituitary-gonadal (HPG) axis and liver. Exposure to 6:2 FTOH significantly increased plasma estradiol (E2) and testosterone (T) levels in both males and females. Furthermore, the ratio of T/E2 was reduced in females while increased in males. In females, the increase of E2 was accompanied by up-regulated hepatic estrogenic receptor alpha (ER alpha) and vitellogenin (VTG1 and VTG3) expression. In males, the elevation of the T level is consistent with the up-regulation of cytochrome P450 c17 alpha-hydroxylase, 17, 20-lase (CYP17) and the down-regulation of cytochrome P450 aromatase A (CYP19A). The present study demonstrated that waterborne exposure to 6:2 FTOH alter plasma sex hormone levels and the ratio of T/E2, as well as the transcriptional profiles of some genes in the HPG axis and liver. The results suggested that FTOHs may disturb fish reproduction through endocrine disrupted activity. (C) 2009 Elsevier B.V. All rights reserved.

  • Waterborne exposure to Fluorotelomer Alcohol 6:2 FTOH alters plasma sex hormone and gene transcription in the hypothalamic–pituitary–gonadal (HPG) axis of zebrafish
    Aquatic Toxicology, 2009
    Co-Authors: Chunsheng Liu, Jun Deng, Paul K S Lam, B. Zhou
    Abstract:

    Fluorotelomer Alcohols (FTOHs) have shown estrogenic activity in vitro and in vivo, but the mechanism of this activity is not known. In this study, 18-week-old zebrafish (Danio rerio) were exposed to 0, 0.03, 0.3 and 3.0 mg/l 1H, 1H, 2H, 2H-perfluorooctan-1-ol (6:2 ETCH) for 7 days, and the effects on plasma sex hormone levels were measured followed by use of real-time PCR to examine selected gene expression in hypothalamic-pituitary-gonadal (HPG) axis and liver. Exposure to 6:2 FTOH significantly increased plasma estradiol (E2) and testosterone (T) levels in both males and females. Furthermore, the ratio of T/E2 was reduced in females while increased in males. In females, the increase of E2 was accompanied by up-regulated hepatic estrogenic receptor alpha (ER alpha) and vitellogenin (VTG1 and VTG3) expression. In males, the elevation of the T level is consistent with the up-regulation of cytochrome P450 c17 alpha-hydroxylase, 17, 20-lase (CYP17) and the down-regulation of cytochrome P450 aromatase A (CYP19A). The present study demonstrated that waterborne exposure to 6:2 FTOH alter plasma sex hormone levels and the ratio of T/E2, as well as the transcriptional profiles of some genes in the HPG axis and liver. The results suggested that FTOHs may disturb fish reproduction through endocrine disrupted activity. (C) 2009 Elsevier B.V. All rights reserved.

Ting Ruan - One of the best experts on this subject based on the ideXlab platform.

  • Impact of 6:2 Fluorotelomer Alcohol aerobic biotransformation on a sediment microbial community.
    The Science of the total environment, 2016
    Co-Authors: Shu Zhang, Ning Wang, Nancy Merino, Ting Ruan
    Abstract:

    Abstract Sediment microbial communities are responsible for many chemical biotransformation processes in the aquatic environment and play a critical role in various ecosystems and biogeochemical cycling. However, the impact of polyfluoroalkyl substances on sediment microbial communities remains unclear. These substances are increasingly being used in consumer and industrial products to replace environmentally persistent perfluoroalkyl substances. In this study, we investigated the effects of low (5 mg/L) and high (15 mg/L) doses of 6:2 Fluorotelomer Alcohol [6:2 FTOH, F(CF 2 ) 6 CH 2 CH 2 OH] on the structure of a sediment microbial community. 6:2 FTOH biotransformation was rapid in the sediment mixture with a half-life 2 ) 5 CH(OH)CH 3 ], 9.6 mol% 5:3 Acid [F(CF 2 ) 5 CH 2 CH 2 COOH] and 11 mol% PFHxA [F(CF 2 ) 5 COOH], while 73 mol% 5:2 sFTOH, 23 mol% 5:3 Acid and 26 mol% PFHxA were observed in the low dose condition. In the original (control) sediment without 6:2 FTOH dosing, Proteobacteria was the predominant microorganism (18%), followed by Chloroflexi (14%), Verrucomicrobia (13%), Firmicutes (3.4%), Bacterioidetes (2.4%), Actinobacteria (1.7%) and Planctomycetes (1.3%). The presence of 6:2 FTOH and the accumulation of transient transformation products in the sediment exerted selection pressure on the microbial taxonomic distribution and diversity. Our observations indicate that potential 6:2 FTOH degraders and tolerant strains, such as Dokdonella spp ., Thauera spp., Albidovulum spp. and Caldanaerovirga spp., existed in the sediment mixture and began to dominate over time. This suggests that these genera might have higher tolerance towards elevated 6:2 FTOH and its transformation products. These findings on the characterization of sediment microbial community stability and dynamics will help predict changes in response to perfluoroalkyl and polyfluoroalkyl substances and also help identify robust microbial strains to degrade polyfluoroalkyl substances in the environment.

  • 6:2 Fluorotelomer iodide in vitro metabolism by rat liver microsomes: Comparison with [1,2-14C] 6:2 Fluorotelomer Alcohol
    Chemosphere, 2014
    Co-Authors: Ting Ruan, Lisa M Sulecki, Ning Wang, Barry W. Wolstenholme, Guibin Jiang, Robert C Buck
    Abstract:

    6:2 Fluorotelomer iodide [6:2 FTI, F(CF2)(6)CH2CH2I] is the industrial raw material used to manufacture 6:2 Fluorotelomer Alcohol [6:2 FTOH, F(CF2)(6)CH2CH2OH] and 6:2 FTOH-based products. During its manufacture and industrial use, workers may be exposed to via oral, dermal or inhalation of 6:2 FTI. Therefore it is useful to understand how 6:2 HI may be metabolized and into what transformation products. 6:2 FTI in vitro rat liver microsomal metabolism was explored for the first time to compare its biotransformation potential with that of [1,2-C-14] 6:2 FTOH [F(CF2)(6)(CH2CH2OH)-C-14-C-14]. 6:2 FTI and 6:2 FTOH metabolite yields were determined in closed-bottle systems using Sprague Dawley and Wistar Han rat microsomes after incubation at 37 C for up to 6 h with NADPH (reduced form of nicotinamide adenine dinucleotide phosphate)-addition and NADPH-regenerating systems, respectively. 5:3 acid [F(CF2)(5)CH2CH2COOH] was the most abundant metabolite for 6:2 FTI (3.3-6.3 mol%) and 6:2 FTOH (9-12 mol%). Perfluorobutanoic acid (PFBA), perfluoropentanoic acid (PFPeA), and perfluorohexanoic acid (PFHxA) in sum accounted for 1.3-2.2 mol% from 6:2 FTI and 2.7-4.4 mol% from 6:2 FTOH biotransformation. Perfluoroheptanoic acid (PFHpA) accounted for 0.14-0.36 mol% from 6:2 FTI but only 0.01-0.06 mol% from 6:2 FTOH biotransformation. These results suggest that mammalian systems exposed to 6:2 FTI or 6:2 FTOH would form 5:3 acid, PFBA, PFPeA, PFHxA as the primary stable metabolites, whereas more PFHpA would be expected from 6:2 FTI biotransformation. (C) 2014 Elsevier Ltd. All rights reserved.

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  • Impact of 6:2 Fluorotelomer Alcohol aerobic biotransformation on a sediment microbial community
    2017
    Co-Authors: Zhang Shu, Merino Nancy, Wang Ning, Ruan Ting, Lu Xiaoxia
    Abstract:

    Sediment microbial communities are responsible for many chemical biotransformation processes in the aquatic environment and play a critical role in various ecosystems and biogeochemical cycling. However, the impact of polyfluoroalkyl substances on sediment microbial communities remains unclear. These substances are increasingly being used in consumer and industrial products to replace environmentally persistent perfluoroalkyl substances. In this study, we investigated the effects of low (5 mg/L) and high (15 mg/L) doses of 6:2 Fluorotelomer Alcohol [6:2 FTOH, F(CF2)(6)CH2CH2OH] on the structure of a sediment microbial community. 6:2 FTOH biotrans-formation was rapid in the sediment mixture with a half-life

  • Impact of 6:2 Fluorotelomer Alcohol aerobic biotransformation on a sediment microbial community
    SCIENCE OF THE TOTAL ENVIRONMENT, 2017
    Co-Authors: Zhang Shu, Merino Nancy, Wang Ning, Ruan Ting, Lu Xiaoxia
    Abstract:

    Sediment microbial communities are responsible for many chemical biotransformation processes in the aquatic environment and play a critical role in various ecosystems and biogeochemical cycling. However, the impact of polyfluoroalkyl substances on sediment microbial communities remains unclear. These substances are increasingly being used in consumer and industrial products to replace environmentally persistent perfluoroalkyl substances. In this study, we investigated the effects of low (5 mg/L) and high (15 mg/L) doses of 6:2 Fluorotelomer Alcohol [6:2 FTOH, F(CF2)(6)CH2CH2OH] on the structure of a sediment microbial community. 6:2 FTOH biotrans-formation was rapid in the sediment mixture with a half-life <3 days, regardless of the initial doses. After 28 days, major products produced in the high dose condition included 28mol% 5:2 sFTOH [F(CF2)(5)CH(OH)CH3], 9.6 mol% 5:3 Acid [F(CF2)(5)CH2CH2COOH] and 11 mol% PFHxA [F(CF2)(5)COOH], while 73 mol% 5:2 sFTOH, 23 mol% 5:3 Acid and 26 mol% PFHxA were observed in the low dose condition. In the original (control) sediment without 6:2 FTOH dosing, Proteobacteria was the predominant microorganism (18%), followed by Chloroflexi (14%), Verrucomicrobia (13%), Firmicutes (3.4%), Bacterioidetes (2.4%), Actinobacteria (1.7%) and Planctomycetes (1.3%). The presence of 6:2 FTOH and the accumulation of transient transformation products in the sediment exerted selection pressure on themicrobial taxonomic distribution and diversity. Our observations indicate that potential 6: 2 FTOH degraders and tolerant strains, such as Dokdonella spp., Thauera spp., Albidovulum spp. and Caldanaerovirga spp., existed in the sediment mixture and began to dominate over time. This suggests that these genera might have higher tolerance towards elevated 6: 2 FTOH and its transformation products. These findings on the characterization of sediment microbial community stability and dynamics will help predict changes in response to perfluoroalkyl and polyfluoroalkyl substances and also help identify robust microbial strains to degrade polyfluoroalkyl substances in the environment. (C) 2016 Elsevier B.V. All rights reserved.John Templeton Foundation; National Natural Science Foundation of China [41471391, 40871214, 40830746]; Fok Ying Tung Education Foundation via the Ministry of Education, China [114043]; 111 Project [B14001]; Ministry of Education Program for New Century Excellent Talents in University [NCET-10-0200]SCI(E)PubMedARTICLE1361-136857

  • Biotransformation potential of 6:2 Fluorotelomer sulfonate (6:2 FTSA) in aerobic and anaerobic sediment
    CHEMOSPHERE, 2016
    Co-Authors: Zhang Shu, Wang Ning, Lu Xiaoxia, Buck, Robert C.
    Abstract:

    Aqueous film-forming foam (AFFF) products are used in industrial and military firefighting around the globe. These products contain fiuoroalkylthioamido sulfonates, fluoroalkylthiobetaine, and other related substances as the major ingredients, which can be biotransformed in the environment to form 6:2 Fluorotelomer sulfonate (6:2 FTSA, F(CF2)(6)CH2CH2SO3-) as one of the major initial biotransformation products. Limited information is available on 6:2 FTSA aerobic biotransformation in activated sludge and pure microbial culture. This is the first study to report 6:2 FTSA biotransformation in aerobic and anaerobic sediment. 6:2 FTSA was rapidly biotransformed in aerobic river sediment with a half-life less than 5 d. Major stable transformation products observed after 90 d included 5:3 Acid [F(CF2)(5)CH2CH2COOH), 16 mol%), PFPeA [F(CF2)(4)COOH, 21 mol%1 and PFHxA (F(CF2)(5)COOH, 20 mol%). 6:2 Fluorotelomer Alcohol [6:2 FTOH, F(CF2)(6)CH2CH2OH] was readily biotransfomed whereas 6:2 FTSA biotransformation did not occur in anaerobic sediment over 100 d, indicating that the enzymatic desulfonation step limited 6:2 FTSA biotransformation in anaerobic sediment. These results suggest that 6:2 FTSA related products, after release to the aerobic environment, is likely to biodegrade forming 5:3 Acid, PFPeA and PFHxA. This study also indicates that 6:2 FTSA formed from its aforementioned precursors may be persistent in the anaerobic environment after their potential release. This work provides insight to understanding the fate and environmental loading of AFFF-related products and their major transformation products in the environment. (C) 2016 Elsevier Ltd. All rights reserved.National Natural Science Foundation of China [41471391]SCI(E)EIPubMedARTICLEluxx@pku.edu.cn; nwang.2@verizon.net224-23015