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Sample records for benzene metabolite levels

  1. Benzene metabolite levels in blood and bone marrow of B6C3F{sub 1} mice after low-level exposure

    SciTech Connect

    Bechtold, W.E.; Strunk, M.R.; Thornton-Manning, J.R.

    1995-12-01

    Studies at the Inhalation Toxicology Research Institute (ITRI) have explored the species-specific uptake and metabolism of benzene. Results have shown that metabolism is dependent on both dose and route of administration. Of particular interest were shifts in the major metabolic pathways as a function of exposure concentration. In these studies, B6C3F{sub 1} mice were exposed to increasing levels of benzene by either gavage or inhalation. As benzene internal dose increased, the relative amounts of muconic acid and hydroquinone decreased. In contrast, the relative amount of catechol increased with increasing exposure. These results show that the relative levels of toxic metabolites are a function of exposure level. Based on these results and assuming a linear relationship between exposure concentration and levels of bone marrow metabolites, it would be difficult to detect an elevation of any phenolic metabolites above background after occupational exposures to the OSHA Permissible Exposure Limit of 1 ppm benzene.

  2. Exposure to benzene metabolites causes oxidative damage in Saccharomyces cerevisiae.

    PubMed

    Raj, Abhishek; Nachiappan, Vasanthi

    2016-06-01

    Hydroquinone (HQ) and benzoquinone (BQ) are known benzene metabolites that form reactive intermediates such as reactive oxygen species (ROS). This study attempts to understand the effect of benzene metabolites (HQ and BQ) on the antioxidant status, cell morphology, ROS levels and lipid alterations in the yeast Saccharomyces cerevisiae. There was a reduction in the growth pattern of wild-type cells exposed to HQ/BQ. Exposure of yeast cells to benzene metabolites increased the activity of the anti-oxidant enzymes catalase, superoxide dismutase and glutathione peroxidase but lead to a decrease in ascorbic acid and reduced glutathione. Increased triglyceride level and decreased phospholipid levels were observed with exposure to HQ and BQ. These results suggest that the enzymatic antioxidants were increased and are involved in the protection against macromolecular damage during oxidative stress; presumptively, these enzymes are essential for scavenging the pro-oxidant effects of benzene metabolites.

  3. Quinones as toxic metabolites of benzene

    SciTech Connect

    Irons, R.D.

    1985-01-01

    Occupational exposure to benzene has long been associated with toxicity to the blood and bone marrow, including lymphocytopenia, pancytopenia, aplastic anemia, acute myelogenous leukemia, and possible lymphoma. A variety of studies have established that benzene itself is not the toxic species but requires metabolism to reactive intermediates. The bioactivation of benzene is complex. Both primary and secondary oxidation of benzene and its metabolites are mediated via cytochrome P-450 in the liver, although the role of secondary metabolism in the bone marrow is not clear. Toxicity is associated with the dihydroxy metabolites, hydroquinone and catechol, which concentrate in bone marrow. Hydroquinone and its terminal oxidation product, p-benzoquinone, have been demonstrated to be potent suppressors of cell growth in culture. Suppression of lymphocyte blastogenesis by these compounds is a sulfhydryl-dependent process and occurs at concentrations that do not result in cell death, or in detectable alterations in energy metabolism, intracellular glutathione concentration, or protein synthesis. Recent studies suggest that these compounds and other membrane-penetrating sulfyhdryl alkylating agents, such as N-ethylmaleimide and cytochalasin A, and endogenous regulatory molecules, such as soluble immune response suppressor (SIRS), interfere with microtubule assembly in vitro and selectively interfere with microtubule-dependent cell functions at identical concentrations. These agents appear to react with nucleophilic sulfhydryl groups essential for guanosine triphosphate binding to tubulin that are particularly sensitive to sulfhydryl-alkylating agents.

  4. Reactive ring-opened aldehyde metabolites in benzene hematotoxicity.

    PubMed Central

    Witz, G; Zhang, Z; Goldstein, B D

    1996-01-01

    The hematotoxicity of benzene is mediated by reactive benzene metabolites and possibly by other intermediates including reactive oxygen species. We previously hypothesized that ring-opened metabolites may significantly contribute to benzene hematotoxicity. Consistent with this hypothesis, our studies initially demonstrated that benzene is metabolized in vitro to trans-trans-muconaldehyde (MUC), a reactive six-carbon diene dialdehyde, and that MUC is toxic to the bone marrow in a manner similar to benzene. Benzene toxicity most likely involves interactions among several metabolites that operate by different mechanisms to produce more than one biological effect. Our studies indicate that MUC coadministered with hydroquinone is a particularly potent metabolite combination that causes bone marrow damage, suggesting that the involvement of ring-opened metabolites in benzene toxicity may be related to their biological effects in combination with other benzene metabolites. Studies in our laboratory and by others indicate that MUC is metabolized to a variety of compounds by oxidation or reduction of the aldehyde groups. The aldehydic MUC metabolite 6-hydroxy-trans-trans-2,4-hexadienal (CHO-M-OH), similar to MUC but to a lesser extent, is reactive toward glutathione, mutagenic in V79 cells, and hematotoxic in mice. It is formed by monoreduction of MUC, a process that is reversible and could be of biological significance in benzene bone marrow toxicity. The MUC metabolite 6-hydroxy-trans-trans-2,4-hexadienoic (COOH-M-OH) is an end product of MUC metabolism in vitro. Our studies indicate that COOH-M-OH is a urinary metabolite of benzene in mice, a finding that provides further indirect evidence for the in vivo formation of MUC from benzene. Mechanistic studies showed the formation of cis-trans-muconaldehyde in addition to MUC from benzene incubated in a hydroxyl radical-generating Fenton system. These results suggest that the benzene ring is initially opened to cis

  5. In vivo genotoxic interactions among three phenolic benzene metabolites.

    PubMed

    Marrazzini, A; Chelotti, L; Barrai, I; Loprieno, N; Barale, R

    1994-11-01

    Three benzene metabolites, hydroquinone (HQ), cathecol (CAT) and phenol (PHE) were studied to define their possible interaction in inducing micronuclei (Mn) in mouse bone marrow polychromatic erythrocytes (PCEs). HQ and CAT, administered separately, induced Mn while PHE showed no genotoxic effects. Binary and ternary mixtures of two or three metabolites gave different results, causing considerable increase or decrease in Mn induction. HQ and PHE, in binary mixtures, as well as PHE and CAT, increased Mn synergistically, while HQ and CAT interacted negatively. The genotoxicity of ternary mixtures was mainly the consequence of two metabolites: HQ and CAT. The maximal effect obtained is far below the induction of Mn consequent to benzene treatment. These data suggest that toxic and genotoxic effects of benzene alone could be the result of more complex interactions among these and other metabolites.

  6. Modeling the formation and reactions of benzene metabolites.

    PubMed

    Golding, Bernard T; Barnes, Martine L; Bleasdale, Christine; Henderson, Alistair P; Jiang, Dong; Li, Xin; Mutlu, Esra; Petty, Hannah J; Sadeghi, Majid M

    2010-03-19

    One or more of the muconaldehyde isomers is a putative product of benzene metabolism. As muconaldehydes are highly reactive dienals and potentially mutagenic they might be relevant to the carcinogenicity of benzene. Muconaldehydes may be derived through the action of a cytochrome P450 mono-oxygenase on benzene oxide-oxepin, which are established metabolites of benzene. Oxidation of benzene oxide-oxepin either by the one-electron oxidant cerium(IV) ammonium nitrate (CAN) or by iron(III) tris(1,10-phenanthroline) hexafluorophosphate in acetone at -78 degrees C or acetonitrile at -40 degrees C gave (E,Z)-muconaldehyde, which was a single diastereoisomer according to analysis by (1)H NMR spectroscopy. Reaction of toluene-1,2-oxide/2-methyloxepin with CAN gave (2E,4Z)-6-oxo-hepta-2,4-dienal. Similarly, the action of CAN on 1,6-dimethylbenzene oxide-2,7-dimethyloxepin gave (3Z,5E)-octa-3,5-diene-2,7-dione. In vivo, benzene oxide-oxepin could suffer one-electron oxidation by cytochrome P450 mono-oxygenase giving (E,Z)-muconaldehyde. The observations presented may be relevant to the toxicology of benzene oxide-oxepin and other arene oxide-oxepins as we have previously shown that (E,Z)-muconaldehyde, analogously to (Z,Z)-muconaldehyde, affords pyrrole adducts with the exocyclic amino groups of the DNA bases adenine and guanine. Independent of their possible toxicological significance, the experiments described provide preparatively useful routes to (E,Z)-muconaldehyde and its congeners. Methods are also described for the trapping and analysis of reactive benzene metabolites, e.g. using the Diels-Alder reaction with the dienophile 4-phenyl-1,2,4-triazoline-3,5-dione to trap arene oxides and with the diene 1,3-diphenylisobenzofuran to trap enals.

  7. Benzene's metabolites alter c-MYB activity via reactive oxygen species in HD3 cells

    SciTech Connect

    Wan, Joanne; Winn, Louise M. . E-mail: winnl@queensu.ca

    2007-07-15

    Benzene is a known leukemogen that is metabolized to form reactive intermediates and reactive oxygen species (ROS). The c-Myb oncoprotein is a transcription factor that has a critical role in hematopoiesis. c-Myb transcript and protein have been overexpressed in a number of leukemias and cancers. Given c-Myb's role in hematopoiesis and leukemias, it is hypothesized that benzene interferes with the c-Myb signaling pathway and that this involves ROS. To investigate our hypothesis, we evaluated whether benzene, 1,4-benzoquinone, hydroquinone, phenol, and catechol generated ROS in chicken erythroblast HD3 cells, as measured by 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (DCFDA) and dihydrorhodamine-123 (DHR-123), and whether the addition of 100 U/ml of the antioxidating enzyme superoxide dismutase (SOD) could prevent ROS generation. Reduced to oxidized glutathione ratios (GSH:GSSG) were also assessed as well as hydroquinone and benzoquinone's effects on c-Myb protein levels and activation of a transiently transfected reporter construct. Finally we attempted to abrogate benzene metabolite mediated increases in c-Myb activity with the use of SOD. We found that benzoquinone, hydroquinone, and catechol increased DCFDA fluorescence, increased DHR-123 fluorescence, decreased GSH:GSSG ratios, and increased reporter construct expression after 24 h of exposure. SOD was able to prevent DCFDA fluorescence and c-Myb activity caused by benzoquinone and hydroquinone only. These results are consistent with other studies, which suggest metabolite differences in benzene-mediated toxicity. More importantly, this study supports the hypothesis that benzene may mediate its toxicity through ROS-mediated alterations in the c-Myb signaling pathway.

  8. DNA damage in lymphocytes of benzene exposed workers correlates with trans,trans-muconic acids and breath benzene levels.

    PubMed

    Sul, Donggeun; Lee, Eunil; Lee, Mi-Young; Oh, Eunha; Im, Hosub; Lee, Joohyun; Jung, Woon-Won; Won, Namhee; Kang, Hyung-Sik; Kim, Eun-Mi; Kang, Seong-Kyu

    2005-04-04

    Benzene causes many kinds of blood disorders in workers employed in many different environments. These diseases include myelodisplastic syndrome and acute and chronic myelocytic leukemia. In the present study, five occupational work places, including six industrial process types, namely, printing, shoe-making, methylene di-aniline (MDA), nitrobenzene, carbomer, and benzene production were selected, and the levels of breath benzene, and trans,trans-muconic acids (t,t-MA) and phenol in urine were evaluated, as well as hematological changes and lymphocyte DNA damage. The concentration of benzene in breath was less than 3 ppm in the workplaces, and benzene exposure was found to be higher in work places where benzene is used, than in those where benzene is produced. At low levels of benzene exposure, urinary t,t-MA correlated strongly with benzene in air. Highest Olive tail moments were found in workers producing carbomer. Levels of breathzone benzene were found to be strongly correlated with Olive tail moment values in the lymphocytes of workers, but not with hematological data in the six workplaces types. In conclusion, the highest benzene exposures found occurred in workers at a company, which utilized benzene in the production of carbomer. In terms of low levels of exposure to benzene, urinary t,t-MA and DNA damage exhibited a strong correlation with breath benzene, but not with hematological data. We conclude that breath benzene, t,t-MA and lymphocytic DNA damage are satisfactory biomonitoring markers with respect to benzene exposure in the workplace.

  9. In vitro conjugation of benzene metabolites by human liver: potential influence of interindividual variability on benzene toxicity.

    PubMed

    Seaton, M J; Schlosser, P; Medinsky, M A

    1995-07-01

    In addition to industrial sources, benzene is present in the environment as a component of cigarette smoke and automobile emissions. Toxicity of benzene most likely results from oxidative metabolism of benzene to reactive products. However, susceptibility to these toxic effects may be related to a balance between activation (phase I) and detoxication (phase II) reactions. In the present study, we have estimated kinetic parameters of the two major detoxication reactions for benzene metabolites--phenol sulfation and hydroquinone glucuronidation--in liver subcellular fractions from 10 humans, and single samples from mice and rats. The extent of oxidative metabolism of benzene by these liver samples has been reported previously. Here, initial rates of phenol sulfation varied 3-fold (range 0.309-0.919 nmol/mg protein/min) among human samples. Measured rates were faster in rats (1.195 nmol/mg protein/min) than in mice (0.458 nmol/mg protein/min). Initial rates of hydroquinone glucuronidation by human samples also varied 3-fold (range 0.101-0.281 nmol/mg protein/min). Hydroquinone glucuronidation was more rapid by mouse microsomes (0.218 nmol/mg protein/min) than by rat microsomes (0.077 nmol/mg protein/min). To integrate interindividual differences in various enzyme activities, a physiological compartmental model was developed that incorporates rates of both conjugation reactions and oxidation reactions. Model equations were solved for steady-state concentrations of phenol and hydroquinone attained in human, mouse and rat blood during continuous exposure to benzene (0.01 microM in blood). Among the 10 human subjects, steady-state concentrations of phenol varied 6-fold (range 0.38-2.17 nM) and steady-state concentrations of hydroquinone varied 5-fold (range 6.66-31.44 nM). Predicted steady-state concentrations of phenol were higher in mice compared with rats (2.28 and 0.83 nM respectively). Likewise, higher steady-state concentrations of hydroquinone were predicted in

  10. Cytochromes P450 in benzene metabolism and involvement of their metabolites and reactive oxygen species in toxicity

    SciTech Connect

    Gut, I.; Nedelcheva, V.; Soucek, P.

    1996-12-01

    Cytochrome P450 (CYP) 2E1 was the most efficient CYP enzyme that oxidized benzene to soluble and covalently bound metabolites in rat and human liver microsomes. The covalent binding was due mostly to the formation of benzoquinone (BQ), the oxidation product of hydroquinone (HQ), and was inversely related to the formation of soluble metabolites. In rats, inhalation of benzene K mgAiter of air caused a rapid destruction of CYP281 previously induced by phenobarbital. The ability of benzene metabolites to destroy liver microsomal CYP in vitro decreased in the order BQ > HQ > catechol > phenol. The destruction was reversed by ascorbate and diminished by {alpha}-tocopherol, suggesting that HQ was not toxic, whereas BO and serniquinone radical (SO) caused the effect. In the presence of nicotinamide adenine clinucleoticle phosphate, reduced (NADPH) the microsomes did not oxidize HQ to BQ, while the formation of superoxide anion radical from both HQ and BQ was markedly quenched. Destruction of CYP in vitro caused by HQ or BQ was not mediated by hydroxyl radical formation or by lipid peroxiclation. On the contrary, HQ and BQ inhibited NADPH-mediated lipid peroxidation. Ascorbate induced high levels of hydroxyl radical formation and lipid peroxidation, which were differentially affected by quinones, indicating different mechanisms. Despite reducing the toxicity of HQ and BQ, ascorbate appeared to induce its own toxicity, reflected in high levels of lipid peroxiclation. Iron redox cycling played a significant role in the NADPH-induced hydroxyl radical formation but not in that caused by ascorbate; however, lipid peroxiclation induced by NADPH or ascorbate was suppressed by ethylenediaminetraacetate, indicating a crucial role of iron. Thus, the data indicate that the quinones destroyed CYP directly and not via oxygen activation or lipid peroxiclation. 35 refs., 9 figs., 3 tabs.

  11. Structure-activity relationship in the mutagenicity and cytotoxicity of putative metabolites and related analogs of benzene derived from the valence tautomers benzene oxide and oxepin

    SciTech Connect

    Stark, A.A.; Rastetter, W.H.

    1996-12-31

    A series of putative metabolites and related analogs of benzene, derived from the valence tautomers benzene oxide and oxepin, was tested for mutagenicity (reversions to histidine prototrophy and forward mutations to resistance to 8-azaguanine) and for cytotoxicity by the Ames Salmonella mutagenicity test. Benzene was not mutagenic in either assay. The benzene oxide-oxepin system and benzene dihydrodial induced point mutations but not frameshifts. 4,5-sym-Oxepin oxide, which is a putative metabolite of the oxepin valence tautomer; 3,6-diazo-cyclohexane-1,6-3,4-dioxide, a synthetic precursor of sym-oxepin oxide; and transoid-4,11-dioxatricyclo(5.1 0)undeca-1,6-diene, a stable bridgehead diene analog of sym-oxepin oxide, were toxic but not mutagenic in both assays. 4H-Pyran-4-=carboxaldehyde, a stable acid catalyzed rearrangement product of sym-oxepin oxide, was not mutagenic and much less cytotoxic than sym-oxepin oxide. Stable analogs of the valence tautomer benzene oxide, namely syn-indan-3a,7a-oxide and syn-2-hydroxyindan-3a,7a-oxide, were mutagenic and induced point mutations. All compounds were cytotoxic to Salmonella. Firstly, the apparent decay times of these chemicals, especially that of sym-oxepin oxide, were surprisingly longer than expected, as judged by quantitative plate diffusion assays. Secondly, it is concluded that if benzene oxide is further metabolized in its oxepin tautomeric form, toxic but not mutagenic products are formed. Thirdly, the relatively weak mutagenicity of benzene oxide may be mainly due to its instability and corresponding low probability to reach intracellular polynucleotide targets, whereas stable analogs of benzene oxide are relatively more potent mutagens. 48 refs., 4 figs., 3 tabs.

  12. The molecular mechanisms of liver and islets of Langerhans toxicity by benzene and its metabolite hydroquinone in vivo and in vitro.

    PubMed

    Bahadar, Haji; Maqbool, Faheem; Mostafalou, Sara; Baeeri, Maryam; Gholami, Mahdi; Ghafour-Boroujerdi, Elmira; Abdollahi, Mohammad

    2015-01-01

    Benzene (C6H6) is one of the most commonly used industrial chemicals causing environmental pollution. This study aimed to examine the effect of benzene and its metabolite hydroquinone on glucose regulating organs, liver and pancreas, and to reveal the involved toxic mechanisms, in rats. In the in vivo part, benzene was dissolved in corn oil and administered through intragastric route at doses of 200, 400 and 800 mg/kg/day, for 4 weeks. And, in the in vitro part, toxic mechanisms responsible for weakening the antioxidant system in islets of Langerhans by hydroquinone at different concentrations (0.25, 0.5 and 1 mM), were revealed. Benzene exposure raised the activity of phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase) enzymes and increased fasting blood sugar (FBS) in comparison to control animals. Also, the activity of hepatic glucokinase (GK) was decreased significantly. Along with, a significant increase was observed in hepatic tumor necrosis factor (TNF-α) and plasma insulin in benzene treated rats. Moreover, benzene caused a significant rise in hepatic lipid peroxidation, DNA damage and oxidation of proteins. In islets of Langerhans, hydroquinone was found to decrease the capability of antioxidant system to fight free radicals. Also, the level of death proteases (caspase 3 and caspase 9) was found higher in hydroquinone exposed islets. The current study demonstrated that benzene and hydroquinone causes toxic effects on liver and pancreatic islets by causing oxidative impairment.

  13. Benzene

    Integrated Risk Information System (IRIS)

    EPA / 635 / R - 02 / 001F TOXICOLOGICAL REVIEW OF BENZENE ( NONCANCER EFFECTS ) ( CAS No . 71 - 43 - 2 ) In Support of Summary Information on the Integrated Risk Information System ( IRIS ) October 2002 U.S . Environmental Protection Agency Washington , DC DISCLAIMER This document has been reviewed

  14. Increase of sister chromatid exchanges and perturbations of cell division kinetics in human lymphocytes by benzene metabolites

    SciTech Connect

    Morimoto, K.; Wolff, S.

    1980-04-01

    Benzene, which has been associated with human cancers, is metabolized to produce several major metabolites that could be responsible for the biological effects. Tests have now been carried out on human lymphocytes in culture to determine if benzene or its metabolites, phenol, catechol, and hydroquinone, induce cytogenetic changes and affect the cell cycle. The results indicate that benzene itself does not induce sister chromatid exchanges or affect cell cycle kinetics over a wide range of doses. Catechol is a potent compound that induces sister chromatid exchanges and delays cell division very readily. Hydroquinone is also potent, but less so than catechol. Thus, the formation of catechol and hydroquinone is the most likely cause of benzene toxicity.

  15. In utero and in vitro effects of benzene and its metabolites on erythroid differentiation and the role of reactive oxygen species

    SciTech Connect

    Badham, Helen J.; Winn, Louise M.

    2010-05-01

    Benzene is a ubiquitous occupational and environmental toxicant. Exposures to benzene both prenatally and during adulthood are associated with the development of disorders such as aplastic anemia and leukemia. Mechanisms of benzene toxicity are unknown; however, generation of reactive oxygen species (ROS) by benzene metabolites may play a role. Little is known regarding the effects of benzene metabolites on erythropoiesis. Therefore, to determine the effects of in utero exposure to benzene on the growth and differentiation of fetal erythroid progenitor cells (CFU-E), pregnant CD-1 mice were exposed to benzene and CFU-E numbers were assessed in fetal liver (hematopoietic) tissue. In addition, to determine the effect of benzene metabolite-induced ROS generation on erythropoiesis, HD3 chicken erythroblast cells were exposed to benzene, phenol, or hydroquinone followed by stimulation of erythrocyte differentiation. Our results show that in utero exposure to benzene caused significant alterations in female offspring CFU-E numbers. In addition, exposure to hydroquinone, but not benzene or phenol, significantly reduced the percentage of differentiated HD3 cells, which was associated with an increase in ROS. Pretreatment of HD3 cells with polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) prevented hydroquinone-induced inhibition of erythropoiesis, supporting the hypothesis that ROS generation is involved in the development of benzene erythrotoxicity. In conclusion, this study provided evidence that ROS generated as a result of benzene metabolism may significantly alter erythroid differentiation, potentially leading to the development of Blood Disorders.

  16. Evaluation of assays for the identification and quantitation of muconic acid, a benzene metabolite in human urine

    SciTech Connect

    Bartczak, A.; Kline, S.A.; Yu, R.; Weisel, C.P.; Goldstein, B.D.; Witz, G.; Bechtold, W.E.

    1994-12-31

    Muconic acid (MA) is a urinary metabolite of benzene and has been used as a biomarker of exposure to benzene in humans exposed to levels as low as 1 ppm. We have modified a high-pressure liquid chromatography (HPLC) based assay for urinary MA by the use of a diode array detector. This modification increases the specificity of the HPLC-based assay by identifying false positives. In addition, we have developed a gas chromatography (GC) based assay that uses a flame ionization detector (GC-FID). Both assays identified and quantified MA in human urine at concentrations greater than 40-50 ng/ml. Assay precision was within 10% relative standard deviation for MA concentrations above 90 ng/ml using the HPLC assay and above 40 ng/ml using the GC-FID assay. Quantitative accuracy of the assays was evaluated by determining MA in human urine samples using both methods and also a gas chromatography-mass spectrometry (GC-MS) procedure. Numerical correlation among the three assays was good at MA concentrations above 100 ng/ml. 26 refs., 3 figs., 2 tabs.

  17. Effects of benzene and its metabolites on global DNA methylation in human normal hepatic L02 cells.

    PubMed

    Hu, Junjie; Ma, Huimin; Zhang, Wenbing; Yu, Zhiqing; Sheng, Guoying; Fu, Jiamo

    2014-01-01

    Benzene is an important industrial chemical that is also widely present in cigarette smoke, automobile exhaust, and gasoline. It is reported that benzene can cause hematopoietic disorders and has been recognized as a human carcinogen. However, the mechanisms by which it increases the risk of carcinogenesis are only partially understood. Aberrant DNA methylation is a major epigenetic mechanism associated with the toxicity of carcinogens. To understand the carcinogenic capacity of benzene, experiments were designed to investigate whether exposure to benzene and its metabolites would change the global DNA methylation status in human normal hepatic L02 cells and then to evaluate whether the changes would be induced by variation of DNA methyltransferase (DNMT) activity in HaeIII DNMT-mediated methylation assay in vitro. Our results showed that hydroquinone and 1,4-benzoquinone could induce global DNA hypomethylation with statistically significant difference from control (p < 0.05), but no significant global DNA methylation changes were observed in L02 cells with benzene, phenol, and 1,2,4-trihydroxybenzene exposure. Benzene metabolites could not influence HaeIII DNMT activity except that 1,4-benzoquinone shows significantly inhibiting effect on enzymatic methylation reaction at concentrations of 5 μM (p < 0.05). These results suggest that benzene metabolites, hydroquinone, and 1,4-benzoquinone can disrupt global DNA methylation, and the potential epigenetic mechanism by which that global DNA hypomethylation induced by 1,4-benzoquinone may work through the inhibiting effects of DNMT activity at 10 μM (p < 0.05).

  18. An investigation of the DNA-damaging ability of benzene and its metabolites in human lymphocytes, using the Comet assay

    SciTech Connect

    Anderson, D.; Yu, T.W.; Schmezer, P. |

    1995-12-31

    Benzene and five of its known metabolites-muconic acid, hydroquinone, catechol, p-benzoquinone, and benzentriol-were examined for DNA damage in human lymphocytes using the alkaline Comet assay, and conditions were optimised to determine responses. When comets were measured by eye after treatment with hydrogen peroxide (H{sup 2}O{sup 2}), the positive control, and each compound for 0.5 hr, only H{sup 2}O{sup 2} and benzenetrial induced pronounced DNA damage without metabolic activation. The effect of catechol was moderate compared, with that of benzenetriol. There was a very weak effect of benzene in the absence of rat liver S-9 mix. In the presence of S-9 mix, benzene was not activated. The effect of benzenetriol was greatly reduced by the external metabolishing system, but p-benzoquinone became activated o some extent. Catalase abolished the effect of benzenetriol, suggesting that H{sup 2}O{sup 2} formed during autoxidation may be responsible for the DNA-damaging ability of this metabolite. Mitogen-stimulated cycling cells were less sensitive to H{sup 2}O{sup 2} and benzenetrial than unstimulated G{sub O} lymphocytes. Effects tended to become more pronounced at high doses and after longer exposures, although this was not always consistent from experiment to experiment. In conclusion, benzene and all metabolites investigated gave positive responses. Where altered responses were observed, they were significantly different from the corresponding controls. 46 refs., 7 tabs.

  19. Benzene levels in ambient air and breath of smokers and nonsmokers in urban and pristine environments

    SciTech Connect

    Wester, R.C.; Maibach, H.I.; Gruenke, L.D.; Craig, J.C.

    1986-01-01

    Benzene levels in human breath and in ambient air were compared in the urban area of San Francisco (SF) and in a more remote coastal pristine setting of Stinson Beach, Calif. (SB). Benzene analysis was done by gas chromatography-mass spectroscopy (GC-MS). Ambient benzene levels were sevenfold higher in SF (2.6 +/- 1.3 ppb, n = 25) than SB (0.38 +/- 0.39 ppb, n = 21). In SF, benzene in smokers' breath (6.8 +/- 3.0 ppb) was greater than in nonsmokers' breath (2.5 +/- 0.8 ppb) and smokers' ambient air (3.3 +/- 0.8 ppb). In SB the same pattern was observed: benzene in smokers' breath was higher than in nonsmokers' breath and ambient air. Benzene in SF nonsmokers' breath was greater than in SB nonsmokers' breath. Marijuana-only smokers had benzene breath levels between those of smokers and nonsmokers. There was little correlation between benzene in breath and number of cigarettes smoked, or with other benzene exposures such as diet. Of special interest was the finding that benzene in breath of SF nonsmokers (2.5 +/- 0.8 ppb) was greater than that in nonsmokers ambient air (1.4 +/- 0.1 ppb). The same was true in SB, where benzene in nonsmokers breath was greater than ambient air (1.8 +/- 0.2 ppb versus 1.0 +/- 0.1 ppb on d 1 and 1.3 +/- 0.3 ppb versus 0.23 +/- 0.18 ppb on d 2). This suggests an additional source of benzene other than outdoor ambient air.

  20. Elevated Atmospheric Levels of Benzene and Benzene-Related Compounds from Unconventional Shale Extraction and Processing: Human Health Concern for Residential Communities

    PubMed Central

    Rich, Alisa L.; Orimoloye, Helen T.

    2016-01-01

    BACKGROUND The advancement of natural gas (NG) extraction across the United States (U.S.) raises concern for potential exposure to hazardous air pollutants (HAPs). Benzene, a HAP and a primary chemical of concern due to its classification as a known human carcinogen, is present in petroleum-rich geologic formations and is formed during the combustion of bypass NG. It is a component in solvents, paraffin breakers, and fuels used in NG extraction and processing (E&P). OBJECTIVES The objectives of this study are to confirm the presence of benzene and benzene-related compounds (benzene[s]) in residential areas, where unconventional shale E&P is occurring, and to determine if benzene[s] exists in elevated atmospheric concentrations when compared to national background levels. METHODS Ambient air sampling was conducted in six counties in the Dallas/Fort Worth Metroplex with passive samples collected in evacuated 6-L Summa canisters. Samples were analyzed by gas chromatography/mass spectrometry, with sampling performed at variable distances from the facility fence line. RESULTS Elevated concentrations of benzene[s] in the atmosphere were identified when compared to U.S. Environmental Protection Agency’s Urban Air Toxics Monitoring Program. The 24-hour benzene concentrations ranged from 0.6 parts per billion by volume (ppbv) to 592 ppbv, with 1-hour concentrations from 2.94 ppbv to 2,900.20 ppbv. CONCLUSION Benzene is a known human carcinogen capable of multisystem health effects. Exposure to benzene is correlated with bone marrow and blood-forming organ damage and immune system depression. Sensitive populations (children, pregnant women, elderly, immunocompromised) and occupational workers are at increased risk for adverse health effects from elevated atmospheric levels of benzene[s] in residential areas with unconventional shale E&P. PMID:27199565

  1. Global Gene Expression Profiling of a Population Exposed to a Range of Benzene Levels

    PubMed Central

    McHale, Cliona M.; Zhang, Luoping; Lan, Qing; Vermeulen, Roel; Li, Guilan; Hubbard, Alan E.; Porter, Kristin E.; Thomas, Reuben; Portier, Christopher J.; Shen, Min; Rappaport, Stephen M.; Yin, Songnian; Smith, Martyn T.; Rothman, Nathaniel

    2011-01-01

    Background Benzene, an established cause of acute myeloid leukemia (AML), may also cause one or more lymphoid malignancies in humans. Previously, we identified genes and pathways associated with exposure to high (> 10 ppm) levels of benzene through transcriptomic analyses of blood cells from a small number of occupationally exposed workers. Objectives The goals of this study were to identify potential biomarkers of benzene exposure and/or early effects and to elucidate mechanisms relevant to risk of hematotoxicity, leukemia, and lymphoid malignancy in occupationally exposed individuals, many of whom were exposed to benzene levels < 1 ppm, the current U.S. occupational standard. Methods We analyzed global gene expression in the peripheral blood mononuclear cells of 125 workers exposed to benzene levels ranging from < 1 ppm to > 10 ppm. Study design and analysis with a mixed-effects model minimized potential confounding and experimental variability. Results We observed highly significant widespread perturbation of gene expression at all exposure levels. The AML pathway was among the pathways most significantly associated with benzene exposure. Immune response pathways were associated with most exposure levels, potentially providing biological plausibility for an association between lymphoma and benzene exposure. We identified a 16-gene expression signature associated with all levels of benzene exposure. Conclusions Our findings suggest that chronic benzene exposure, even at levels below the current U.S. occupational standard, perturbs many genes, biological processes, and pathways. These findings expand our understanding of the mechanisms by which benzene may induce hematotoxicity, leukemia, and lymphoma and reveal relevant potential biomarkers associated with a range of exposures. PMID:21147609

  2. The relationship between low-level benzene exposure and leukemia in Canadian petroleum distribution workers

    SciTech Connect

    Schnatter, A.R.; Armstrong, T.W.; Nicolich, M.J.

    1996-12-01

    This study was conducted to evaluate the relationship between leukemia occurrence and long-term, low-level benzene exposures in petroleum distribution workers. Fourteen cases were identified among a previously studied cohort. Four controls per case were selected from the same cohort, controlling for birth year and time at risk. Industrial hygienists estimated workplace exposures for benzene, without knowledge of case-control status. Average benzene concentrations ranged from 0.01 to 6.2 ppm. Company medical records were used to abstract information on other potential confounders such as cigarette smoking. Odds ratios were calculated for several exposure metrics. Conditional logistic regression modeling was used to control for potential confounders. The risk of leukemia was not associated with increasing cumulative exposure to benzene for these exposure levels. Duration of benzene exposure was more closely associated with leukemia risk than other exposure metrics, although results were not statistically significant. A family history of cancer and cigarette smoking were the two strongest risk factors for leukemia, with cumulative benzene exposure showing no additional risk when considered in the same models. This study is consistent with other data in that it was unable to demonstrate a relationship between leukemia and long-term, low-level benzene exposures. The power of the study was limited. Thus, further study on benzene exposures in this concentration range are warranted. 20 refs., 1 fig., 6 tabs.

  3. Metabolism of trans, trans-muconaldehyde, a cytotoxic metabolite of benzene, in mouse liver by alcohol dehydrogenase Adh1 and aldehyde reductase AKR1A4

    SciTech Connect

    Short, Duncan M.; Lyon, Robert; Watson, David G.; Barski, Oleg A.; McGarvie, Gail; Ellis, Elizabeth M. . E-mail: Elizabeth.ellis@strath.ac.uk

    2006-01-15

    The reductive metabolism of trans, trans-muconaldehyde, a cytotoxic metabolite of benzene, was studied in mouse liver. Using an HPLC-based stopped assay, the primary reduced metabolite was identified as 6-hydroxy-trans, trans-2,4-hexadienal (OH/CHO) and the secondary metabolite as 1,6-dihydroxy-trans, trans-2,4-hexadiene (OH/OH). The main enzymes responsible for the highest levels of reductase activity towards trans, trans-muconaldehyde were purified from mouse liver soluble fraction first by Q-sepharose chromatography followed by either blue or red dye affinity chromatography. In mouse liver, trans, trans-muconaldehyde is predominantly reduced by an NADH-dependent enzyme, which was identified as alcohol dehydrogenase (Adh1). Kinetic constants obtained for trans, trans-muconaldehyde with the native Adh1 enzyme showed a V {sub max} of 2141 {+-} 500 nmol/min/mg and a K {sub m} of 11 {+-} 4 {mu}M. This enzyme was inhibited by pyrazole with a K {sub I} of 3.1 {+-} 0.57 {mu}M. Other fractions were found to contain muconaldehyde reductase activity independent of Adh1, and one enzyme was identified as the NADPH-dependent aldehyde reductase AKR1A4. This showed a V {sub max} of 115 nmol/min/mg and a K {sub m} of 15 {+-} 2 {mu}M and was not inhibited by pyrazole.

  4. Self-collected breath sampling for monitoring low-level benzene exposures among automobile mechanics.

    PubMed

    Egeghy, Peter P; Nylander-French, Leena; Gwin, Kristin K; Hertz-Picciotto, Irva; Rappaport, Stephen M

    2002-07-01

    Automobile mechanics are exposed to benzene through their contact with gasoline vapor and engine exhaust. This study investigated the benzene uptake associated with these exposures. We first evaluated the reliability of self-collected breath samples among a subset of subjects and found good agreement between these samples and those collected under expert supervision (intraclass correlation coefficient 0.79, n = 69). We then used self-monitoring together with a longitudinal sampling design (with up to three measurements per worker) to measure benzene in air and benzene in end-exhaled breath among 81 workers from 12 automobile repair garages in North Carolina. A statistically significant difference (P < 0.0001, Mann-Whitney rank sum test) was observed between non-smokers and smokers for post-exposure benzene concentration in breath (median values of 18.9 and 39.1 micro g/m(3), respectively). Comparing pre- and post-exposure breath concentrations within these two groups, the difference was significant among non-smokers (P < 0.0001) but not significant among smokers (P > 0.05). Mixed effects regression analysis using backwards elimination yielded five significant predictors of benzene concentration in breath, namely benzene exposure (P < 0.0001), pre-exposure benzene concentration in breath (P = 0.021), smoking status (P < 0.0001), fuel system work (P = 0.0043) and carburetor cleaner use (P < 0.0001). The between-person variance component comprised only 28% of the total variance in benzene levels in breath, indicating that differences among individuals related to physiological and metabolic characteristics had little influence on benzene uptake among these workers.

  5. The induction of monocytopoiesis in HL-60 promyelocytic leukemia cells is inhibited by hydroquinone, a toxic metabolite of benzene

    SciTech Connect

    Oliveira, N.L.

    1992-01-01

    Chronic exposure of humans to benzene has been shown to have a cytotoxic effect on hematopoietic progenitor cells in intermediate stages of differentiation which can lead to aplastic anemia and acute myelogenous leukemia. This thesis examined the effect of hydroquinone, a toxic metabolite of benzene found in the bone marrow, on the human promyelocytic leukemia cell line (HL-60) which can be induced to differentiate to both monocyte and myeloid cells, and thus has been used as a surrogate for a granulocyte/macrophage progenitor cell. Exposure of HL-60 cells to noncytotoxic concentrations of hydroquinone for three hours prior to induction with 12-O-tetradecanoyl phorbol-13-acetate caused a dose-dependent inhibition of the acquisition of characteristics of monocytic differentiation. These included adherence, nonspecific esterase activity and phagocytosis. Hydroquinone had no effect on cell proliferation. Hydroquinone appeared to be affecting maturation beyond the monoblast/promonocyte stages. Hydroquinone also prevented differentiation induced by 1, 25-dihydroxy vitamin D[sub 3], however, the block occurred after the acquisition of adherence. Hydroquinone at concentrations that inhibited monocytic differentiation had no effect on differentiation to granulocytes, suggesting that the block in the differentiation of these bipotential cells is at a step unique to the monocytic pathway. Hydroquinone was unable to prevent differentiation induced by the macrophage-derived cytokine interleukin-1, a differentiation factor for cells of the monocytic lineage. These data demonstrate that treatment of Hl-60 cells with hydroquinone prior to induction of differentiation prevents the acquisition of the monocytic phenotype induced by TPA or 1, 25(OH)[sub 2]D[sub 3] by a mechanism which at present is unknown, but which appears to be specific for the monocytic pathway. These results are of considerable significance for benzene hematotoxicity.

  6. Levels of selected urinary metabolites of volatile organic compounds among children aged 6-11 years.

    PubMed

    Jain, Ram B

    2015-10-01

    Data from National Health and Nutrition Examination Survey for the years 2011-2012 were used to evaluate variability in the observed levels of 20 urinary metabolites of volatile organic compounds (VOCs) by age, gender, and race/ethnicity among children aged 6-11 years. Exposure to environmental tobacco smoke was positively associated with the levels of selected metabolites of acrylonitrile, 1,3-butadiene, cyanide, and propylene oxide in a dose-response manner. Levels of the selected metabolites of acrolein, acrylonitrile, 1,3-butadiene, styrene, toluene, and xylene decreased with increase in age. Levels of 1-bromopropane decreased with number of rooms in the house but the reverse was true for 1,3-butadiene, carbon-disulfide, and N,N-dimethylformamide. Levels of most of the 20 metabolites did not vary with gender. Non-Hispanic white children had higher adjusted levels of N-Acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA), N-Acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCC), and phenylglyoxylic acid (PGA) than non-Hispanic black children. Non-Hispanic white children had statistically significantly higher adjusted levels of N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA), trans, trans-Muconic acid (MU), and N-Acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCC) than non-Hispanic Asian children but statistically significantly lower levels of N-Acetyl-S-(n-propyl)-L-cysteine (BPMA) than non-Hispanic Asian children. Non-Hispanic Asian children had the lowest levels of 13 of the 20 metabolites among four major racial/ethnic groups but highest levels for three metabolites. For selected metabolites of acrolein, acrylamide, acrylonitrile-vinyl chloride-ethylene oxide, benzene, 1,3-butadien, crotonaldehyde, cyanide, ethylbenzene-styrene, and toluene, children had statistically significantly higher levels than nonsmoking adults. These results demonstrate how vulnerable children are to being exposed to harmful chemicals like VOCs in their own homes.

  7. Acute myeloid and chronic lymphoid leukaemias and exposure to low-level benzene among petroleum workers

    PubMed Central

    Rushton, L; Schnatter, A R; Tang, G; Glass, D C

    2014-01-01

    Background: High benzene exposure causes acute myeloid leukaemia (AML). Three petroleum case–control studies identified 60 cases (241 matched controls) for AML and 80 cases (345 matched controls) for chronic lymphoid leukaemia (CLL). Methods: Cases were classified and scored regarding uncertainty by two haematologists using available diagnostic information. Blinded quantitative benzene exposure assessment used work histories and exposure measurements adjusted for era-specific circumstances. Statistical analyses included conditional logistic regression and penalised smoothing splines. Results: Benzene exposures were much lower than previous studies. Categorical analyses showed increased ORs for AML with several exposure metrics, although patterns were unclear; neither continuous exposure metrics nor spline analyses gave increased risks. ORs were highest in terminal workers, particularly for Tanker Drivers. No relationship was found between benzene exposure and risk of CLL, although the Australian study showed increased risks in refinery workers. Conclusion: Overall, this study does not persuasively demonstrate a risk between benzene and AML. A previously reported strong relationship between myelodysplastic syndrome (MDS) (potentially previously reported as AML) at our study's low benzene levels suggests that MDS may be the more relevant health risk for lower exposure. Higher CLL risks in refinery workers may be due to more diverse exposures than benzene alone. PMID:24357793

  8. Hydroquinone, a benzene metabolite, induces Hog1-dependent stress response signaling and causes aneuploidy in Saccharomyces cerevisiae.

    PubMed

    Shiga, Takeki; Suzuki, Hiroyuki; Yamamoto, Ayumi; Yamamoto, Hiroaki; Yamamoto, Kazuo

    2010-01-01

    Previously, we have shown that phenyl hydroquinone, a hepatic metabolite of the Ames test-negative carcinogen o-phenylphenol, efficiently induced aneuploidy in Saccharomyces cerevisiae by arresting the cell cycle at the G2/M transition as a result of the activation of the Hog1 (p38 MAPK homolog)-Swe1 (Wee1 homolog) pathway. In this experiment, we examined the aneuploidy forming effects of hydroquinone, a benzene metabolite, since both phenyl hydroquinone and hydroquinone are Ames-test negative carcinogens and share similar molecular structures. As was seen in phenyl hydroquinone, hydroquinone induced aneuploidy in yeast by delaying the cell cycle at the G2/M transition. Deficiencies in SWE1 and HOG1 abolished the hydroquinone-induced delay at the G2/M transition and aneuploidy formation. Furthermore, Hog1 was phosphorylated by hydroquinone, which may stabilize Swe1. These data indicate that the hydroquinone-induced G2/M transition checkpoint, which is activated by the Hog1-Swe1 pathway, plays a role in the formation of aneuploidy.

  9. Reducing Benzene and Cresol Levels in National Renewable Energy Laboratory's Pilot-Scale Biorefinergy Scrubber Water

    SciTech Connect

    Buzek, M.L.; Phillips, S.

    2004-01-01

    The Thermochemical Process Development Unit at the National Renewable Energy Laboratory converts biomass into energy by gasification or pyrolysis. The aqueous effluent generated in these processes must be disposed of as hazardous waste according to the Resource Conservation and Recovery Act because certain components exceed the regulatory concentration limit. Gas stripping of the scrubber water was investigated as a method of reducing benzene and cresol levels. A custom-designed packed-bed column was built and a half-factorial experimental design was implemented to determine the effects of gas flow rate, liquid flow rate, and column packing height on the final benzene concentration in the liquid. The experimental results show that packing height had a significant effect on final benzene concentration; gas flow rate and liquid flow rate had little effect. The effects of each design variable on final cresol concentration were not determined. Although the current column design did significantly reduce the benzene and cresol levels in the scrubber water, it did not reduce the concentrations below the regulatory limits. A full-factorial experimental design will be implemented with an increased packing height. Other variables, including column diameter and packing type, will be investigated to determine their effects on final benzene and cresol concentrations. Once the packed-bed column is determined to be effective in reducing contaminant concentrations below the regulatory limit, photocatalytic oxidation will be explored for remediating the benzene and cresol from the gas stream.

  10. Assimilation of benzene carbon through multiple trophic levels traced by different stable isotope probing methodologies.

    PubMed

    Bastida, Felipe; Jechalke, Sven; Bombach, Petra; Franchini, Alessandro G; Seifert, Jana; von Bergen, Martin; Vogt, Carsten; Richnow, Hans H

    2011-08-01

    The flow of benzene carbon along a food chain consisting of bacteria and eukaryotes, including larvae (Diptera: Chironomidae), was evaluated by total lipid fatty acids (TLFAs)-, amino acid- and protein-stable isotope probing (SIP). A coconut-fibre textile, colonized by a benzene-degrading biofilm, was sampled in a system established for the remediation of benzene, toluene, ethylbenzene and xylenes (BTEX)-polluted groundwater and incubated with (12)C- and [(13)C(6)]-benzene (>99 at.%) in a batch-scale experiment for 2-8 days. After 8 days, Chironomus sp. larvae were added to study carbon flow to higher trophic levels. Gas chromatography-combustion-isotope ratio monitoring mass spectrometry of TLFA showed increased isotope ratios in the (13)C-benzene-incubated biofilm. A higher (13)C-enrichment was observed in TLFAs, indicative of Gram-negative bacteria than for Gram-positive. Fatty acid indicators of eukaryotes showed significant (13)C-incorporation, but to a lower extent than bacterial indicators. Fatty acids extracted from larvae feeding on (13)C-biofilm reached an isotopic ratio of 1.55 at.%, illustrating that the larvae feed, to some extent, on labelled biomass. No (13)C-incorporation was detectable in larval proteins after their separation by sodium-dodecyl sulphate-polyacrylamide gel electrophoresis and analysis by nano-liquid-chromatography-mass spectrometry. The flow of benzene-derived carbon could be traced in a food web consisting of bacteria and eukaryotes.

  11. Inhibition of human DNA topoisomerase II by hydroquinone and p-benzoquinone, reactive metabolites of benzene

    SciTech Connect

    Hutt, A.M.; Kalf, G.F.

    1996-12-01

    Chronic exposure of humans to benzene (BZ) causes acute myeloid leukemia (AML). Both BZ and therapy-related secondary AML are characterized by chromosomal translocations that may occur by inappropriate recombinational events. DNA topoisomerase 11 (topo 11) is an essential sulfhydryl (SH)-dependent endonuclease required for replication, recombination, chromosome segregation, and chromosome structure. Topo 11 cleaves DNA at purine(R)/pyrimidine(Y) repeat sequences that have been shown to be highly recombinogenic in vivo. Certain antineoplastic drugs stabilize topo 11-DNA cleavage complexes at RY repeat sequences, which leads to translocations of the type observed in leukemia. Hydroquinone (HQ) is metabolized to p-benzoquinone (BQ) in a peroxidase-mediated reaction in myeloid progenitor cells. BO interacts with SH groups of SH-dependent enzymes. Consequently, the aims of this research were to determine whether HQ and BO are topo 11 inhibitors. The ability of the compounds to inhibit the activity of topo, 11 was tested using an assay system that depends on the conversion, by homogeneous human topo 11, of catenated kinetoplast DNA into open and/or nicked open circular DNA that can be separated from the catenated DNA by electrophoresis in a 1% agarose-ethidium bromide gel. We provide preliminary data that indicate that both HQ and BO cause a time and concentration (pM)-dependent inhibition of topo 11 activity. 32 refs., 5 figs.

  12. Characterization of changes in gene expression and biochemical pathways at low levels of benzene exposure.

    PubMed

    Thomas, Reuben; Hubbard, Alan E; McHale, Cliona M; Zhang, Luoping; Rappaport, Stephen M; Lan, Qing; Rothman, Nathaniel; Vermeulen, Roel; Guyton, Kathryn Z; Jinot, Jennifer; Sonawane, Babasaheb R; Smith, Martyn T

    2014-01-01

    Benzene, a ubiquitous environmental pollutant, causes acute myeloid leukemia (AML). Recently, through transcriptome profiling of peripheral blood mononuclear cells (PBMC), we reported dose-dependent effects of benzene exposure on gene expression and biochemical pathways in 83 workers exposed across four airborne concentration ranges (from <1 ppm to >10 ppm) compared with 42 subjects with non-workplace ambient exposure levels. Here, we further characterize these dose-dependent effects with continuous benzene exposure in all 125 study subjects. We estimated air benzene exposure levels in the 42 environmentally-exposed subjects from their unmetabolized urinary benzene levels. We used a novel non-parametric, data-adaptive model selection method to estimate the change with dose in the expression of each gene. We describe non-parametric approaches to model pathway responses and used these to estimate the dose responses of the AML pathway and 4 other pathways of interest. The response patterns of majority of genes as captured by mean estimates of the first and second principal components of the dose-response for the five pathways and the profiles of 6 AML pathway response-representative genes (identified by clustering) exhibited similar apparent supra-linear responses. Responses at or below 0.1 ppm benzene were observed for altered expression of AML pathway genes and CYP2E1. Together, these data show that benzene alters disease-relevant pathways and genes in a dose-dependent manner, with effects apparent at doses as low as 100 ppb in air. Studies with extensive exposure assessment of subjects exposed in the low-dose range between 10 ppb and 1 ppm are needed to confirm these findings.

  13. Characterization of Changes in Gene Expression and Biochemical Pathways at Low Levels of Benzene Exposure

    PubMed Central

    Thomas, Reuben; Hubbard, Alan E.; McHale, Cliona M.; Zhang, Luoping; Rappaport, Stephen M.; Lan, Qing; Rothman, Nathaniel; Vermeulen, Roel; Guyton, Kathryn Z.; Jinot, Jennifer; Sonawane, Babasaheb R.; Smith, Martyn T.

    2014-01-01

    Benzene, a ubiquitous environmental pollutant, causes acute myeloid leukemia (AML). Recently, through transcriptome profiling of peripheral blood mononuclear cells (PBMC), we reported dose-dependent effects of benzene exposure on gene expression and biochemical pathways in 83 workers exposed across four airborne concentration ranges (from <1 ppm to >10 ppm) compared with 42 subjects with non-workplace ambient exposure levels. Here, we further characterize these dose-dependent effects with continuous benzene exposure in all 125 study subjects. We estimated air benzene exposure levels in the 42 environmentally-exposed subjects from their unmetabolized urinary benzene levels. We used a novel non-parametric, data-adaptive model selection method to estimate the change with dose in the expression of each gene. We describe non-parametric approaches to model pathway responses and used these to estimate the dose responses of the AML pathway and 4 other pathways of interest. The response patterns of majority of genes as captured by mean estimates of the first and second principal components of the dose-response for the five pathways and the profiles of 6 AML pathway response-representative genes (identified by clustering) exhibited similar apparent supra-linear responses. Responses at or below 0.1 ppm benzene were observed for altered expression of AML pathway genes and CYP2E1. Together, these data show that benzene alters disease-relevant pathways and genes in a dose-dependent manner, with effects apparent at doses as low as 100 ppb in air. Studies with extensive exposure assessment of subjects exposed in the low-dose range between 10 ppb and 1 ppm are needed to confirm these findings. PMID:24786086

  14. A study of the hematologic effects of chronic low-level exposure to benzene

    SciTech Connect

    Collins, J.J.; Conner, P.; Friedlander, B.R.; Easterday, P.A.; Nair, R.S.; Braun, J. )

    1991-05-01

    A study of 200 persons working with benzene showed no differences in commonly measured hematologic outcomes when compared with 268 nonbenzene workers in the same plant. Exposures ranged from 0.01 ppm to a high of 1.40 ppm 8-hour time weighted average over a 10-year period. Several other factors (age, sex, race, and smoking), however, were associated with these outcomes, indicating the importance of considering confounding factors when comparing hematology results. Exposure to low levels of benzene does not appear to produce an increased level of abnormal hematology measures detectable in routine medical surveillance.

  15. In utero exposure to benzene increases embryonic c-Myb and Pim-1 protein levels in CD-1 mice

    SciTech Connect

    Wan, Joanne; Winn, Louise M.

    2008-05-01

    Benzene is a known human leukemogen, but its role as an in utero leukemogen remains controversial. Epidemiological studies have correlated parental exposure to benzene with an increased incidence of childhood leukemias. We hypothesize that in utero exposure to benzene may cause leukemogenesis by affecting the embryonic c-Myb/Pim-1 signaling pathway and that this is mediated by oxidative stress. To investigate this hypothesis, pregnant CD-1 mice were treated with either 800 mg/kg of benzene or corn oil (i.p.) on days 10 and 11 of gestation and in some cases pretreated with 25 kU/kg of PEG-catalase. Phosphorylated and total embryonic c-Myb and Pim-1 protein levels were assessed using Western blotting and maternal and embryonic oxidative stress were assessed by measuring reduced to oxidized glutathione ratios. Our results show increased oxidative stress at 4 and 24 h after exposure, increased phosphorylated Pim-1 protein levels 4 h after benzene exposure, and increased Pim-1 levels at 24 and 48 h after benzene exposure. Embryonic c-Myb levels were elevated at 24 h after exposure. PEG-catalase pretreatment prevented benzene-mediated increases in embryonic c-Myb and Pim-1 protein levels, and benzene-induced oxidative stress. These results support a role for ROS in c-Myb and Pim-1 alterations after in utero benzene exposure.

  16. An overview of benzene metabolism.

    PubMed Central

    Snyder, R; Hedli, C C

    1996-01-01

    Benzene toxicity involves both bone marrow depression and leukemogenesis caused by damage to multiple classes of hematopoietic cells and a variety of hematopoietic cell functions. Study of the relationship between the metabolism and toxicity of benzene indicates that several metabolites of benzene play significant roles in generating benzene toxicity. Benzene is metabolized, primarily in the liver, to a variety of hydroxylated and ring-opened products that are transported to the bone marrow where subsequent secondary metabolism occurs. Two potential mechanisms by which benzene metabolites may damage cellular macromolecules to induce toxicity include the covalent binding of reactive metabolites of benzene and the capacity of benzene metabolites to induce oxidative damage. Although the relative contributions of each of these mechanisms to toxicity remains unestablished, it is clear that different mechanisms contribute to the toxicities associated with different metabolites. As a corollary, it is unlikely that benzene toxicity can be described as the result of the interaction of a single metabolite with a single biological target. Continued investigation of the metabolism of benzene and its metabolites will allow us to determine the specific combination of metabolites as well as the biological target(s) involved in toxicity and will ultimately lead to our understanding of the relationship between the production of benzene metabolites and bone marrow toxicity. PMID:9118888

  17. Human CYP2E1-dependent and human sulfotransferase 1A1-modulated induction of micronuclei by benzene and its hydroxylated metabolites in Chinese hamster V79-derived cells.

    PubMed

    Jiang, Hao; Lai, Yanmei; Hu, Keqi; Wei, Qinzhi; Liu, Yungang

    2014-12-01

    Benzene is a ubiquitous environmental pollutant and a confirmed human carcinogen, which requires metabolic activation, primarily by CYP2E1, for most of its biological actions. Chromosome damages in benzene-exposed workers and rodents have been observed, and in their urine sulfo- and glucuronide-conjugates of phenol and hydroquinone were present. Yet, direct evidence for human CYP2E1-activated mutagenicity of benzene and the exact significance of phase II metabolism for inactivating benzene metabolites are still missing. In the present study, benzene and its oxidized metabolites (phenol, hydroquinone, catechol, 1,2,4-trihydroxybenzene and 1,4-benzoquinone) were investigated for induction of micronuclei in a V79-derived cell line genetically engineered for expression of both human CYP2E1 and human sulfotransferase (SULT) 1A1 (indicated by active micronuclei induction by 1-hydroxymethylpyrene). The results demonstrated concentration-dependent induction of micronuclei by benzene and phenol, though with lower potency or efficacy than the other metabolites. Inhibition of CYP2E1 by 1-aminobenzotriazole did not change the effect of benzoquinone, but completely abolished that of benzene and phenol, and attenuated that of the other compounds. Moreover, inhibition of SULT1A1 by pentachlorophenol potentiated the effects of benzene, hydroquinone, catechol and trihydroxybenzene. Ascorbic acid, a reducing and free radical-scavenging agent, significantly lowered the effects of hydroquinone, catechol, trihydroxybenzene as well as N-nitrosodimethylamine (a known CYP2E1-dependent promutagen), with that of benzoquinone unaffected. These results suggest that in addition to activating benzene and phenol, human CYP2E1 may further convert hydroquinone, catechol and trihydroxybenzene to more genotoxic metabolites, and sulfo-conjugation of the multi-hydroxylated metabolites of benzene by human SULT1A1 may represent an important detoxifying pathway.

  18. Ambient air benzene at background sites in China's most developed coastal regions: exposure levels, source implications and health risks.

    PubMed

    Zhang, Zhou; Wang, Xinming; Zhang, Yanli; Lü, Sujun; Huang, Zhonghui; Huang, Xinyu; Wang, Yuesi

    2015-04-01

    Benzene is a known human carcinogen causing leukemia, yet ambient air quality objectives for benzene are not available in China. The ambient benzene levels at four background sites in China's most developed coastal regions were measured from March 2012 to February 2013. The sites are: SYNECP, in the Northeast China Plain (NECP); YCNCP, in the North China Plain (NCP); THYRD, in the Yangtze River Delta (YRD) and DHPRD, in the Pearl River Delta (PRD). It was found that the mean annual benzene levels (578-1297 ppt) at the background sites were alarmingly higher, especially when compared to those of 60-480 pptv monitored in 28 cities in the United States. Wintertime benzene levels were significantly elevated at both sites (SYNECP and YCNCP) in northern China due to heating with coal/biofuels. Even at these background sites, the lifetime cancer risks of benzene (1.7-3.7E-05) all exceeded 1E-06 set by USEPA as acceptable for adults. At both sites in northern China, good correlations between benzene and CO or chloromethane, together with much lower toluene/benzene (T/B) ratios, suggested that benzene was largely related to coal combustion and biomass/biofuel burning. At the DHPRD site in the PRD, benzene revealed a highly significant correlation with methyl tert-butyl ether (MTBE), indicating that its source was predominantly from vehicle emissions. At the THYRD site in the YRD, higher T/B ratios and correlations between benzene and tetrachloroethylene, or MTBE, implied that benzene levels were probably affected by both traffic-related and industrial emissions.

  19. The putative benzene metabolite 2,3, 5-tris(glutathion-S-yl)hydroquinone depletes glutathione, stimulates sphingomyelin turnover, and induces apoptosis in HL-60 cells.

    PubMed

    Bratton, S B; Lau, S S; Monks, T J

    2000-07-01

    In this study, we show that 2,3,5-tris(glutathion-S-yl)hydroquinone (TGHQ), a putative metabolite of benzene, induces apoptosis in human promyelocytic leukemia (HL-60) cells. Prior to the onset of apoptosis, TGHQ depletes intracellular glutathione (GSH) in a reactive oxygen species (ROS)-independent manner. Neutral, Mg(2+)-dependent sphingomyelinases, which are normally inhibited by GSH, are subsequently activated, as evidenced by increases in intracellular ceramide and depletion of sphingomyelin. As ceramide levels rise, effector caspase (DEVDase) activity steadily increases. Interestingly, while catalase has no effect on TGHQ-mediated depletion of GSH, this hydrogen peroxide (H(2)O(2)) scavenger does inhibit DEVDase activity and apoptosis, provided the enzyme is added to HL-60 cells before an increase in ceramide can be observed. Since ceramide analogues inhibit the mitochondrial respiratory chain, these data imply that ceramide-mediated generation of H(2)O(2) is necessary for the activation of effector caspases-3 and/or -7, and apoptosis. In summary, these studies indicate that TGHQ, and perhaps many quinol-based toxicants and chemotherapeutics, may induce apoptosis in hematopoietic cells by depleting GSH and inducing the proapoptotic ceramide-signaling pathway.

  20. Benzene and its methyl-derivatives: derivation of maximum exposure levels in automobiles.

    PubMed

    Schupp, Thomas; Bolt, Hermann M; Jaeckh, Rudolf; Hengstler, Jan G

    2006-01-05

    Automobile drivers are exposed to several organic hydrocarbons. Concentrations measured in passenger compartments have been reported to range between 13 and 560 microg/m(3) for benzene, 33-258 microg/m(3) for toluene, 20-250 microg/m(3) for xylene (mixed isomers) and 3-23 microg/m(3) for trimethylbenzene (mixed isomers). These aromatic hydrocarbons are emitted from gasoline and from materials inside a car. In the present study we evaluated, whether these exposures pose a potential risk to the health of drivers. Therefore, we derived maximum exposure levels inside cars for chronic (ELIA(chronic)) and short-term (STELIA) exposure. The lowest ELIA's(chronic) for benzene, toluene, xylene and trimethylbenzene were 0.083, 1.2, 8.8 and 0.31 mg/m(3), respectively. The respective STELIA's were 16, 30, 29 and 25 mg/m(3). Obviously concentrations of toluene, xylene and trimethylbenzene inside cars do not exceed their individual STELIA's. In contrast, benzene seems to be problematic, since concentrations inside cars amount up to 0.56 mg/m(3), which exceeds the ELIA(chronic) derived for benzene. This should not be underestimated, since benzene is a genotoxic carcinogen that probably acts by non-threshold mechanisms. In conclusion, concentrations of toluene, xylene and trimethylbenzene usually observed inside cars are unlikely to pose a risk to the health of drivers. A systematic toxicological evaluation of the risk associated with benzene exposure in cars seems to be necessary.

  1. Synergistic action of the benzene metabolite hydroquinone on myelopoietic stimulating activity of granulocyte/macrophage colony-stimulating factor in vitro

    NASA Technical Reports Server (NTRS)

    Irons, R. D.; Stillman, W. S.; Colagiovanni, D. B.; Henry, V. A.; Clarkson, T. W. (Principal Investigator)

    1992-01-01

    The effects of in vitro pretreatment with benzene metabolites on colony-forming response of murine bone marrow cells stimulated with recombinant granulocyte/macrophage colony-stimulating factor (rGM-CSF) were examined. Pretreatment with hydroquinone (HQ) at concentrations ranging from picomolar to micromolar for 30 min resulted in a 1.5- to 4.6-fold enhancement in colonies formed in response to rGM-CSF that was due to an increase in granulocyte/macrophage colonies. The synergism equaled or exceeded that reported for the effects of interleukin 1, interleukin 3, or interleukin 6 with GM-CSF. Optimal enhancement was obtained with 1 microM HQ and was largely independent of the concentration of rGM-CSF. Pretreatment with other authentic benzene metabolites, phenol and catechol, and the putative metabolite trans, trans-muconaldehyde did not enhance growth factor response. Coadministration of phenol and HQ did not enhance the maximal rGM-CSF response obtained with HQ alone but shifted the optimal concentration to 100 pM. Synergism between HQ and rGM-CSF was observed with nonadherent bone marrow cells and lineage-depleted bone marrow cells, suggesting an intrinsic effect on recruitment of myeloid progenitor cells not normally responsive to rGM-CSF. Alterations in differentiation in a myeloid progenitor cell population may be of relevance in the pathogenesis of acute myelogenous leukemia secondary to drug or chemical exposure.

  2. Cerebrospinal Fluid Levels of Monoamine Metabolites in the Epileptic Baboon

    PubMed Central

    Szabó, C. Ákos; Patel, Mayuri; Uteshev, Victor V.

    2016-01-01

    The baboon represents a natural model for genetic generalized epilepsy and sudden unexpected death in epilepsy (SUDEP). In this retrospective study, cerebrospinal fluid (CSF) monoamine metabolites and scalp electroencephalography (EEG) were evaluated in 263 baboons of a pedigreed colony. CSF monoamine abnormalities have been linked to reduced seizure thresholds, behavioral abnormalities and SUDEP in various animal models of epilepsy. The levels of 3-hydroxy-4-methoxyphenylglycol, 5-hydroxyindolacetic acid and homovanillic acid in CSF samples drawn from the cisterna magna were analyzed using high-performance liquid chromatography. These levels were compared between baboons with seizures (SZ), craniofacial trauma (CFT) and asymptomatic, control (CTL) baboons, between baboons with abnormal and normal EEG studies. We hypothesized that the CSF levels of major monoaminergic metabolites (i.e., dopamine, serotonin and norepinephrine) associate with the baboons’ electroclinical status and thus can be used as clinical biomarkers applicable to seizures/epilepsy. However, despite apparent differences in metabolite levels between the groups, usually lower in SZ and CFT baboons and in baboons with abnormal EEG studies, we did not find any statistically significant differences using a logistic regression analysis. Significant correlations between the metabolite levels, especially between 5-HIAA and HVA, were preserved in all electroclinical groups. While we were not able to demonstrate significant differences in monoamine metabolites in relation to seizures or EEG markers of epilepsy, we cannot exclude the monoaminergic system as a potential source of pathogenesis in epilepsy and SUDEP. A prospective study evaluating serial CSF monoamine levels in baboons with recently witnessed seizures, and evaluation of abnormal expression and function of monoaminergic receptors and transporters within epilepsy-related brain regions, may impact the electroclinical status. PMID:26924854

  3. The toxicology of benzene.

    PubMed Central

    Snyder, R; Witz, G; Goldstein, B D

    1993-01-01

    Benzene is metabolized, primarily in the liver, to a series of phenolic and ring-opened products and their conjugates. The mechanism of benzene-induced aplastic anemia appears to involve the concerted action of several metabolites acting together on early stem and progenitor cells, as well as on early blast cells, such as pronormoblasts and normoblasts to inhibit maturation and amplification. Benzene metabolites also inhibit the function of microenvironmental stromal cells necessary to support the growth of differentiating and maturing marrow cells. The mechanism of benzene-induced leukemogenesis is less well understood. Benzene and its metabolites do not function well as mutagens but are highly clastogenic, producing chromosome aberrations, sister chromatid exchange, and micronuclei. Benzene has been shown to be a multi-organ carcinogen in animals. Epidemiological studies demonstrate that benzene is a human leukemogen. There is need to better define the lower end of the dose-response curve for benzene as a human leukemogen. The application of emerging methods in biologically based risk assessment employing pharmacokinetic and mechanistic data may help to clarify the uncertainties in low-dose risk assessment. PMID:8354177

  4. Spatial variability in levels of benzene, formaldehyde, and total benzene, toluene, ethylbenzene and xylenes in New York City: a land-use regression study

    PubMed Central

    2012-01-01

    Background Hazardous air pollutant exposures are common in urban areas contributing to increased risk of cancer and other adverse health outcomes. While recent analyses indicate that New York City residents experience significantly higher cancer risks attributable to hazardous air pollutant exposures than the United States as a whole, limited data exist to assess intra-urban variability in air toxics exposures. Methods To assess intra-urban spatial variability in exposures to common hazardous air pollutants, street-level air sampling for volatile organic compounds and aldehydes was conducted at 70 sites throughout New York City during the spring of 2011. Land-use regression models were developed using a subset of 59 sites and validated against the remaining 11 sites to describe the relationship between concentrations of benzene, total BTEX (benzene, toluene, ethylbenzene, xylenes) and formaldehyde to indicators of local sources, adjusting for temporal variation. Results Total BTEX levels exhibited the most spatial variability, followed by benzene and formaldehyde (coefficient of variation of temporally adjusted measurements of 0.57, 0.35, 0.22, respectively). Total roadway length within 100 m, traffic signal density within 400 m of monitoring sites, and an indicator of temporal variation explained 65% of the total variability in benzene while 70% of the total variability in BTEX was accounted for by traffic signal density within 450 m, density of permitted solvent-use industries within 500 m, and an indicator of temporal variation. Measures of temporal variation, traffic signal density within 400 m, road length within 100 m, and interior building area within 100 m (indicator of heating fuel combustion) predicted 83% of the total variability of formaldehyde. The models built with the modeling subset were found to predict concentrations well, predicting 62% to 68% of monitored values at validation sites. Conclusions Traffic and point source emissions

  5. Lack of sensitivity of urinary trans,trans-muconic acid in determining low-level (ppb) benzene exposure in children.

    PubMed

    Barbieri, Anna; Accorsi, Antonio; Raffi, Giovanni Battista; Nicoli, Luciana; Violante, Francesco Saverio

    2002-01-01

    Benzene is a widespread pollutant of which the main source in the outside environment is automotive traffic. Benzene is also present in cigarette smoke, and small quantities exist in drinking water and food; all of these sources contribute to pollution of indoor environments. Benzene exposure may be studied with biologic indicators. In the present study, the authors evaluated whether differences in urinary concentrations of trans,transmuconic acid (t,t-MA) were detectable in a sample of 150 children and if the chemical was correlated with environmental exposures to low levels of benzene. The children attended primary schools that had significantly different-but low-environmental benzene levels. Analysis of urinary t,t-MA was achieved with high-performance liquid chromatography (photodiode array detector), and analysis of passive air samplers for benzene was performed with gas chromatography-mass spectrometry. Statistical analysis (Kruskal-Wallis test) indicated that differences in urinary levels of t,t-MA in children from urban and rural areas were not statistically significant (p = .07), nor were there significant differences between children with and without relatives who smoked (p = .69). As has been shown in other studies of children and adults, results of our study evidenced (1) the difficulty of correlating concentrations of urinary biomarkers with environmental exposure to benzene at a parts-per-billion level (i.e., traffic and environmental tobacco smoke) and, consequently, (2) the lack of specificity of t,t-MA as a biological indicator for the study of a population's exposure.

  6. Preconcentrator-based sensor µ-system for low-level benzene detection

    NASA Astrophysics Data System (ADS)

    Ivanov, P.; Gràcia, I.; Blanco, F.; Raskin, J.-P.; Cumeras, R.; Sabaté, N.; Vilanova, X.; Correig, X.; Fonseca, L.; Figueras, E.; Santander, J.; Cané, C.

    2008-12-01

    In this paper, a preconcentrator-based sensor μ-system for low level benzene detection is presented. It consists of a spiral-shaped μ-reconcentrator with dimensions of 10cm × 300μm × 300μm, followed by a μ-hotplate sensor matrix. The μ-preconcentrator was fabricated on a silicon wafer by means of DRIE and anodic bonding techniques. To obtain the concentration factor of the fabricated devices, a GC/MS: Shimadzu-QP5000 equipment was used. The results obtained showed excellent repeatability and preconcentration factors up to 286. A considerable improvement (1500%) in the sensor responses was achieved with Pd doped SnO2 sensors. The small size of the manufactured devices enables their incorporation in an integrated GC/MS gas sensor system.

  7. 10 CFR 26.133 - Cutoff levels for drugs and drug metabolites.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Cutoff levels for drugs and drug metabolites. 26.133... § 26.133 Cutoff levels for drugs and drug metabolites. Subject to the provisions of § 26.31(d)(3)(iii), licensees and other entities may specify more stringent cutoff levels for drugs and drug metabolites...

  8. 10 CFR 26.133 - Cutoff levels for drugs and drug metabolites.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Cutoff levels for drugs and drug metabolites. 26.133... § 26.133 Cutoff levels for drugs and drug metabolites. Subject to the provisions of § 26.31(d)(3)(iii), licensees and other entities may specify more stringent cutoff levels for drugs and drug metabolites...

  9. 10 CFR 26.133 - Cutoff levels for drugs and drug metabolites.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Cutoff levels for drugs and drug metabolites. 26.133... § 26.133 Cutoff levels for drugs and drug metabolites. Subject to the provisions of § 26.31(d)(3)(iii), licensees and other entities may specify more stringent cutoff levels for drugs and drug metabolites...

  10. 10 CFR 26.133 - Cutoff levels for drugs and drug metabolites.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Cutoff levels for drugs and drug metabolites. 26.133... § 26.133 Cutoff levels for drugs and drug metabolites. Subject to the provisions of § 26.31(d)(3)(iii), licensees and other entities may specify more stringent cutoff levels for drugs and drug metabolites...

  11. 10 CFR 26.133 - Cutoff levels for drugs and drug metabolites.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Cutoff levels for drugs and drug metabolites. 26.133... § 26.133 Cutoff levels for drugs and drug metabolites. Subject to the provisions of § 26.31(d)(3)(iii), licensees and other entities may specify more stringent cutoff levels for drugs and drug metabolites...

  12. Estimating Benzene Exposure Level over Time and by Industry Type through a Review of Literature on Korea

    PubMed Central

    Park, Donguk; Choi, Sangjun; Ha, Kwonchul; Jung, Hyejung; Yoon, Chungsik; Koh, Dong-Hee; Ryu, Seunghun; Kim, Soogeun; Kang, Dongmug; Yoo, Kyemook

    2015-01-01

    The major purpose of this study is to construct a retrospective exposure assessment for benzene through a review of literature on Korea. Airborne benzene measurements reported in 34 articles were reviewed. A total of 15,729 individual measurements were compiled. Weighted arithmetic means [AM(w)] and their variance calculated across studies were summarized according to 5-year period intervals (prior to the 1970s through the 2010s) and industry type. Industries were classified according to Korea Standard Industrial Classification (KSIC) using information provided in the literature. We estimated quantitative retrospective exposure to benzene for each cell in the matrix through a combination of time and KSIC. Analysis of the AM(w) indicated reductions in exposure levels over time, regardless of industry, with mean levels prior to the 1980–1984 period of 50.4 ppm (n = 2,289), which dropped to 2.8 ppm (n = 305) in the 1990–1994 period, and to 0.1 ppm (n = 294) in the 1995–1999 period. There has been no improvement since the 2000s, when the AM(w) of 4.3 ppm (n = 6,211) for the 2005–2009 period and 4.5 ppm (n = 3,358) for the 2010–2013 period were estimated. A comparison by industry found no consistent patterns in the measurement results. Our estimated benzene measurements can be used to determine not only the possibility of retrospective exposure to benzene, but also to estimate the level of quantitative or semiquantitative retrospective exposure to benzene. PMID:26929825

  13. Combining regression analysis and air quality modelling to predict benzene concentration levels

    NASA Astrophysics Data System (ADS)

    Vlachokostas, Ch.; Achillas, Ch.; Chourdakis, E.; Moussiopoulos, N.

    2011-05-01

    State of the art epidemiological research has found consistent associations between traffic-related air pollution and various outcomes, such as respiratory symptoms and premature mortality. However, many urban areas are characterised by the absence of the necessary monitoring infrastructure, especially for benzene (C 6H 6), which is a known human carcinogen. The use of environmental statistics combined with air quality modelling can be of vital importance in order to assess air quality levels of traffic-related pollutants in an urban area in the case where there are no available measurements. This paper aims at developing and presenting a reliable approach, in order to forecast C 6H 6 levels in urban environments, demonstrated for Thessaloniki, Greece. Multiple stepwise regression analysis is used and a strong statistical relationship is detected between C 6H 6 and CO. The adopted regression model is validated in order to depict its applicability and representativeness. The presented results demonstrate that the adopted approach is capable of capturing C 6H 6 concentration trends and should be considered as complementary to air quality monitoring.

  14. BENZENE OXIDE PROTEIN ADDUCTS AS BIOMARKERS OF BENZENE EXPOSURE

    EPA Science Inventory

    Benzene is known to be hematotoxic and carcinogenic in animals and humans. While metabolism is required for toxicity, the identity of the ultimate carcinogen(s) remains unknown. Benzene oxide (BO) is the first and most abundant of the metabolites, but very little is known about...

  15. Serum Reactive Oxygen Metabolite Levels Predict Severe Exacerbations of Asthma

    PubMed Central

    Nakamoto, Keitaro; Watanabe, Masato; Sada, Mitsuru; Inui, Toshiya; Nakamura, Masuo; Honda, Kojiro; Wada, Hiroo; Mikami, Yu; Matsuzaki, Hirotaka; Horie, Masafumi; Noguchi, Satoshi; Yamauchi, Yasuhiro; Koyama, Hikari; Kogane, Toshiyuki; Kohyama, Tadashi; Takizawa, Hajime

    2016-01-01

    Background and Purpose Bronchial asthma (BA) is a chronic airway disease characterized by airway hyperresponsiveness and remodeling, which are intimately linked to chronic airway inflammation. Reactive oxygen species (ROS) such as hydrogen peroxide are generated by inflammatory cells that are involved in the pathogenesis of BA. However, the role of ROS in the management of BA patients is not yet clear. We attempted to determine the role of ROS as a biomarker in the clinical setting of BA. Subjects and Methods We enrolled patients with BA from 2013 through 2015 and studied the degrees of asthma control, anti-asthma treatment, pulmonary function test results, fractional exhaled nitric oxide (FeNO), serum reactive oxygen metabolite (ROM) levels, and serum levels of interleukin (IL)-6 and IL-8. Results We recruited 110 patients with BA. Serum ROM levels correlated with white blood cell (WBC) count (rs = 0.273, p = 0.004), neutrophil count (rs = 0.235, p = 0.014), CRP (rs = 0.403, p < 0.001), and IL-6 (rs = 0.339, p < 0.001). Serum ROM levels and IL-8 and CRP levels negatively correlated with %FEV1 (rs = -0.240, p = 0.012, rs = -0.362, p < 0.001, rs = -0.197, p = 0.039, respectively). Serum ROM levels were significantly higher in patients who experienced severe exacerbation within 3 months than in patients who did not (339 [302–381] vs. 376 [352–414] CARR U, p < 0.025). Receiver-operating characteristics analysis showed that ROM levels correlated significantly with the occurrence of severe exacerbation (area under the curve: 0.699, 95% CI: 0.597–0.801, p = 0.025). Conclusions Serum levels of ROM were significantly associated with the degrees of airway obstruction, WBC counts, neutrophil counts, IL-6, and severe exacerbations. This biomarker may be useful in predicting severe exacerbations of BA. PMID:27776186

  16. The use of S-phenylmercapturic acid as a biomarker in molecular epidemiology studies of benzene.

    PubMed

    Farmer, Peter B; Kaur, Balvinder; Roach, Jonathan; Levy, Len; Consonni, Dario; Bertazzi, Pietro A; Pesatori, Angela; Fustinoni, Silvia; Buratti, Marina; Bonzini, Matteo; Colombi, Antonio; Popov, Todor; Cavallo, Domenico; Desideri, Arianna; Valerio, Federico; Pala, Mauro; Bolognesi, Claudia; Merlo, Franco

    2005-05-30

    S-Phenylmercapturic acid (S-PMA), is a urinary metabolite of benzene, thought to be derived from the condensation product of benzene oxide with glutathione. S-PMA may be determined by GC, HPLC (UV or fluorescence detection), GC-MS, LC-MS/MS or immunoassays. The limit of sensitivities of most of these techniques is 1 microg/l urine or below. It has been suggested that S-PMA may have value as a biomarker for low level human exposure to benzene, in view of the facts that urinary excretion of S-PMA has been found to be related to airborne benzene in occupationally exposed workers, and that only low background levels of S-PMA have been found in control subjects. We have evaluated the use of S-PMA as a biomarker, using a commercially available analytical service, in a multicentre European study of populations exposed to varying levels of benzene, in Italy (Milan, Genoa) and in Bulgaria (Sofia). These were filling station attendants, urban policemen, bus drivers, petrochemical workers and referents (a total of 623 subjects). S-PMA was measured at the end of the work shift by an immunoassay procedure. Urinary benzene (in Milan only) and the benzene metabolite trans,trans-muconic acid (t,t-MA) were measured before and after the work shift. Air-borne benzene was measured as a monitor of exposure. Urinary benzene was the most discriminatory biomarker and showed a relationship with airborne benzene at all levels of exposure studied (including groups exposed to <0.1 ppm benzene), whereas t,t-MA and S-PMA, as determined by immunoassay, were suitable only in the highest exposed workers (petrochemical industry, geometric mean 1765 microg/m3 (0.55 ppm) benzene). All three biomarkers were positively correlated with smoking as measured by urinary cotinine).

  17. Benzene exposure, assessed by urinary trans,trans-muconic acid, in urban children with elevated blood lead levels.

    PubMed Central

    Weaver, V M; Davoli, C T; Heller, P J; Fitzwilliam, A; Peters, H L; Sunyer, J; Murphy, S E; Goldstein, G W; Groopman, J D

    1996-01-01

    A pilot study was performed to evaluate the feasibility of using trans,trans-muconic acid (MA) as a biomarker of environmental benzene exposure. A secondary aim was to provide data on the extent of exposure to selected toxicants in a unique population consisting of inner-city children who were already overexposed to one urban hazard, lead. Potential sources of benzene were assessed by a questionnaire. Exposure biomarkers included urinary MA and cotinine and blood lead. Mean MA was 176.6 +/- 341.7 ng/mg creatinine in the 79 children who participated. A wide range of values was found with as many as 10.1%, depending on the comparison study, above the highest levels reported in adults not exposed by occupation. Mean MA was increased in children evaluated in the afternoon compared to morning, those at or above the median for time spent playing near the street, and those studied in the first half of the investigation. MA levels were not associated with blood lead or, consistently, with either questionnaire environmental tobacco smoke (ETS) data or cotinine. As expected, the mean blood lead level was elevated (23.6 micrograms/dl). Mean cotinine was also increased at 79.2 ng/mg creatinine. We conclude that the use of MA as a biomarker for environmental benzene exposure is feasible since it was detectable in 72% of subjects with a wide range of values present. In future studies, correlation of MA with personal air sampling in environmental exposure will be essential to fully interpret the significance of these findings. In addition, these inner-city children comprise a high risk group for exposure to environmental toxicants including ETS, lead, and probably benzene, based on questionnaire sources and its presence in ETS. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 4. Figure 5. PMID:8919771

  18. 10 CFR 26.163 - Cutoff levels for drugs and drug metabolites.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Cutoff levels for drugs and drug metabolites. 26.163... the Department of Health and Human Services § 26.163 Cutoff levels for drugs and drug metabolites. (a) Initial drug testing. (1) HHS-certified laboratories shall apply the following cutoff levels for...

  19. 10 CFR 26.163 - Cutoff levels for drugs and drug metabolites.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Cutoff levels for drugs and drug metabolites. 26.163... the Department of Health and Human Services § 26.163 Cutoff levels for drugs and drug metabolites. (a) Initial drug testing. (1) HHS-certified laboratories shall apply the following cutoff levels for...

  20. 10 CFR 26.163 - Cutoff levels for drugs and drug metabolites.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Cutoff levels for drugs and drug metabolites. 26.163... the Department of Health and Human Services § 26.163 Cutoff levels for drugs and drug metabolites. (a) Initial drug testing. (1) HHS-certified laboratories shall apply the following cutoff levels for...

  1. 10 CFR 26.163 - Cutoff levels for drugs and drug metabolites.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Cutoff levels for drugs and drug metabolites. 26.163... the Department of Health and Human Services § 26.163 Cutoff levels for drugs and drug metabolites. (a) Initial drug testing. (1) HHS-certified laboratories shall apply the following cutoff levels for...

  2. 10 CFR 26.163 - Cutoff levels for drugs and drug metabolites.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Cutoff levels for drugs and drug metabolites. 26.163... the Department of Health and Human Services § 26.163 Cutoff levels for drugs and drug metabolites. (a) Initial drug testing. (1) HHS-certified laboratories shall apply the following cutoff levels for...

  3. Mechanistic considerations in benzene physiological model development

    SciTech Connect

    Medinsky, M.A.; Kenyon, E.M.; Seaton, M.J.; Schlosser, P.M.

    1996-12-01

    Benzene, an important industrial solvent, is also present in unleaded gasoline and cigarette smoke. The hematotoxic effects of benzene in humans are well documented and include aplastic anemia, pancytopenia, and acute myelogenous leukemia. However, the risks of leukemia at low exposure concentrations have not been established. A combination of metabolites (hydroquinone and phenol, for example) may be necessary to duplicate the hematotoxic effect of benzene, perhaps due in part to the synergistic effect of phenol on myeloperoxidase-mediated oxidation of hydroquinone to the reactive metabolite benzoquinone. Because benzene and its hydroxylated metabolites (phenol, hydroquinone, and catechol) are substrates for the same cytochrome P450 enzymes, competitive interactions among the metabolites are possible. In vivo data on metabolite formation by mice exposed to various benzene concentrations are consistent with competitive inhibition of phenol oxidation by benzene. In vitro studies of the metabolic oxidation of benzene, phenol, and hydroquinone are consistent with the mechanism of competitive interaction among the metabolites. The dosimetry of benzene and its metabolites in the target tissue, bone marrow, depends on the balance of activation processes such as enzymatic oxidation and deactivation processes such as conjugation and excretion. Phenol, the primary benzene metabolite, can undergo both oxidation and conjugation. Thus the potential exists for competition among various enzymes for phenol. Zonal localization of phase I and phase 11 enzymes in various regions of the liver acinus also impacts this competition. Biologically based dosimetry models that incorporate the important determinants of benzene flux, including interactions with other chemicals, will enable prediction of target tissue doses of benzene and metabolites at low exposure concentrations relevant for humans. 39 refs., 4 figs., 2 tabs.

  4. Leukemia and Benzene

    PubMed Central

    Snyder, Robert

    2012-01-01

    Excessive exposure to benzene has been known for more than a century to damage the bone marrow resulting in decreases in the numbers of circulating blood cells, and ultimately, aplastic anemia. Of more recent vintage has been the appreciation that an alternative outcome of benzene exposure has been the development of one or more types of leukemia. While many investigators agree that the array of toxic metabolites, generated in the liver or in the bone marrow, can lead to traumatic bone marrow injury, the more subtle mechanisms leading to leukemia have yet to be critically dissected. This problem appears to have more general interest because of the recognition that so-called “second cancer” that results from prior treatment with alkylating agents to yield tumor remissions, often results in a type of leukemia reminiscent of benzene-induced leukemia. Furthermore, there is a growing literature attempting to characterize the fine structure of the marrow and the identification of so called “niches” that house a variety of stem cells and other types of cells. Some of these “niches” may harbor cells capable of initiating leukemias. The control of stem cell differentiation and proliferation via both inter- and intra-cellular signaling will ultimately determine the fate of these transformed stem cells. The ability of these cells to avoid checkpoints that would prevent them from contributing to the leukemogenic response is an additional area for study. Much of the study of benzene-induced bone marrow damage has concentrated on determining which of the benzene metabolites lead to leukemogenesis. The emphasis now should be directed to understanding how benzene metabolites alter bone marrow cell biology. PMID:23066403

  5. Empty level structure and dissociative electron attachment cross section in (bromoalkyl)benzenes.

    PubMed

    Modelli, Alberto

    2005-07-21

    The gas-phase electron transmission (ET) and dissociative electron attachment (DEA) spectra are reported for the series of (bromoalkyl)benzenes C6H5(CH2)nBr (n = 0-3), where the bromine atom is directly bonded to a benzene ring or separated from it by 1-3 CH2 groups, and the dihalo derivative 1-Br-4-Cl-benzene. The relative DEA cross sections (essentially due to the Br- fragment) are reported, and the absolute cross sections are also evaluated. HF/6-31G and B3LYP/6-31G* calculations are employed to evaluate the virtual orbital energies (VOEs) for the optimized geometries of the neutral state molecules. The pi* VOEs, scaled with empirical equations, satisfactorily reproduce the corresponding experimental vertical electron attachment energies (VAEs). According to the calculated localization properties, the LUMO (as well as the singly occupied MO of the lowest lying anion state) of C6H5(CH2)3Br is largely localized on both the benzene ring and the C-Br bond, despite only a small pi*/sigma*C-Br interaction and in contrast to the chlorine analogue where the LUMO is predicted to possess essentially ring pi character. This would imply a less important role of intramolecular electron transfer in the bromo derivative for production of the halogen negative fragment through dissociation of the first resonant state. The VAEs calculated as the anion/neutral energy difference with the 6-31+G* basis set which includes diffuse functions are relatively close to the experimental values but do not parallel their sequence. In addition the SOMO of some compounds is not described as a valence MO with large pi* character but as a diffuse sigma* MO.

  6. Low level detection of Benzene in Food Grade Hexane by Ultraviolet Spectrophotometry.

    PubMed

    Emmandi, R; Sastry, M I S; Patel, M B

    2014-10-15

    A simple, sensitive, and accurate Ultraviolet Spectrophotometric method has been developed and validated for the determination of Benzene in Food Grade Hexane. Benzene in spectroscopic grade Hexane shows vibrational fine structure having four well resolved peaks. In the wavelength range 240-270nm, peak at 255nm is considered for the method development. Beer's law was obeyed in the concentration range of 0.6-10.0μLL(-1), with correlation coefficient, 0.9999, detection limit 0.2μLL(-1) and quantitation limit 0.6μLL(-1) are established. Percentage recovery studies showed that the method was not affected by the presence of other solvents having the similar boiling range with Hexane. The method was validated by determining its accuracy and precision which proves suitability of the developed method for the routine determination of Benzene in Food Grade Hexane. The proposed method has been applied successfully for the analysis of the Food Grade Hexane.

  7. Microminiature Monitor for Vital Electrolyte and Metabolite Levels of Astronauts

    NASA Technical Reports Server (NTRS)

    Tohda, Koji; Gratzl, Miklos

    2004-01-01

    Ions, such as proton (pH) and potassium, play a crucial role in body fluids to maintain proper basic functioning of cells and tissues. Metabolites, such as glucose, control the energy available to the entire human body in normal as well as stress situations, and before, during, and after meals. These molecules diffuse easily between blood in the capillaries and the interstitial fluid residing between cells and tissues. We have developed and approach to monitoring of critical ions (called electrolytes) and glucose in the interstitial fluid under the human skin. Proton and potassium levels sensed using optode technology that translates the respective ionic concentrations into variable colors of corresponding ionophore/dye/polymeric liquid membranes. Glucose is monitored indirectly, by coupling through immobilized glucose oxidase with local pH that is then detected using a similar color scheme. The monitor consists of a tiny plastic bar, 100-200 microns wide and 1-2 mm long, placed just under the skin, with color changing spots for each analyte as well as blanks. The colors are read and translated into concentration values by a CCD camera. Direct optical coupling between the in vivo sensing bar and the ex vivo detector device requires no power, and thus eliminates the need for wires or optical fibers crossing the skin. The microminiature bar penetrates the skin easily and painlessly, so that astronauts could insert it themselves. The approach is fully compatible with telemetry in space, and thus, in vivo clinical data will be available real time in the Earth based command center once the device is fully developed. The information provided can be used for collecting hitherto unavailable vital data on clinical effects of space travel. Managing clinical emergencies in space with the sensor already in place should also become much more efficient than without a continuous monitor, as is currently the case. Civilian applications may include better glucose control of

  8. Determinants of Organophosphorus Pesticide Urinary Metabolite Levels in Young Children Living in an Agricultural Community

    PubMed Central

    Bradman, Asa; Castorina, Rosemary; Barr, Dana Boyd; Chevrier, Jonathan; Harnly, Martha E.; Eisen, Ellen A.; McKone, Thomas E.; Harley, Kim; Holland, Nina; Eskenazi, Brenda

    2011-01-01

    Organophosphorus (OP) pesticides are used in agriculture and several are registered for home use. As young children age they may experience different pesticide exposures due to varying diet, behavior, and other factors. We measured six OP dialkylphosphate (DAP) metabolites (three dimethyl alkylphosphates (DMAP) and three diethyl alkylphosphates (DEAP)) in urine samples collected from ∼400 children living in an agricultural community when they were 6, 12, and 24 months old. We examined bivariate associations between DAP metabolite levels and determinants such as age, diet, season, and parent occupation. To evaluate independent impacts, we then used generalized linear mixed multivariable models including interaction terms with age. The final models indicated that DMAP metabolite levels increased with age. DMAP levels were also positively associated with daily servings of produce at 6- and 24-months. Among the 6-month olds, DMAP metabolite levels were higher when samples were collected during the summer/spring versus the winter/fall months. Among the 12-month olds, DMAP and DEAP metabolites were higher when children lived ≤60 meters from an agricultural field. Among the 24-month-olds, DEAP metabolite levels were higher during the summer/spring months. Our findings suggest that there are multiple determinants of OP pesticide exposures, notably dietary intake and temporal and spatial proximity to agricultural use. The impact of these determinants varied by age and class of DAP metabolite. PMID:21695029

  9. Benzene metabolism by human liver microsomes in relation to cytochrome P450 2E1 activity.

    PubMed

    Seaton, M J; Schlosser, P M; Bond, J A; Medinsky, M A

    1994-09-01

    Low levels of benzene from sources including cigarette smoke and automobile emissions are ubiquitous in the environment. Since the toxicity of benzene probably results from oxidative metabolites, an understanding of the profile of biotransformation of low levels of benzene is critical in making a valid risk assessment. To that end, we have investigated metabolism of a low concentration of [14C]benzene (3.4 microM) by microsomes from human, mouse and rat liver. The extent of phase I benzene metabolism by microsomal preparations from 10 human liver samples and single microsomal preparations from both mice and rats was then related to measured activities of cytochrome P450 (CYP) 2E1. Measured CYP 2E1 activities, as determined by hydroxylation of p-nitrophenol, varied 13-fold (0.253-3.266 nmol/min/mg) for human samples. The fraction of benzene metabolized in 16 min ranged from 10% to 59%. Also at 16 min, significant amounts of oxidative metabolites were formed. Phenol was the main metabolite formed by all but two human microsomal preparations. In those samples, both of which had high CYP 2E1 activity, hydroquinone was the major metabolite formed. Both hydroquinone and catechol formation showed a direct correlation with CYP 2E1 activity over the range of activities present. A simulation model was developed based on a mechanism of competitive inhibition between benzene and its oxidized metabolites, and was fit to time-course data for three human liver preparations. Model calculations for initial rates of benzene metabolism ranging from 0.344 to 4.442 nmol/mg/min are directly proportional to measured CYP 2E1 activities. The model predicted the dependence of benzene metabolism on the measured CYP 2E1 activity in human liver samples, as well as in mouse and rat liver samples. These results suggest that differences in measured hepatic CYP 2E1 activity may be a major factor contributing to both interindividual and interspecies variations in hepatic metabolism of benzene

  10. Low-dose metabolism of benzene in humans: science and obfuscation.

    PubMed

    Rappaport, Stephen M; Kim, Sungkyoon; Thomas, Reuben; Johnson, Brent A; Bois, Frederic Y; Kupper, Lawrence L

    2013-01-01

    Benzene is a ubiquitous air pollutant that causes human leukemia and hematotoxic effects. Although the mechanism by which benzene causes toxicity is unclear, metabolism is required. A series of articles by Kim et al. used air and biomonitoring data from workers in Tianjin, China, to investigate the dose-specific metabolism (DSM) of benzene over a wide range of air concentrations (0.03-88.9 p.p.m.). Kim et al. concluded that DSM of benzene is greatest at air concentrations <1 p.p.m. This provocative finding motivated the American Petroleum Institute to fund a study by Price et al. to reanalyze the original data. Although their formal 'reanalysis' reproduced Kim's finding of enhanced DSM at sub-p.p.m. benzene concentrations, Price et al. argued that Kim's methods were inappropriate for assigning benzene exposures to low exposed subjects (based on measurements of urinary benzene) and for adjusting background levels of metabolites (based on median values from the 60 lowest exposed subjects). Price et al. then performed uncertainty analyses under alternative approaches, which led them to conclude that '… the Tianjin data appear to be too uncertain to support any conclusions …' regarding the DSM of benzene. They also argued that the apparent low-dose metabolism of benzene could be explained by 'lung clearance.' In addressing these criticisms, we show that the methods and arguments presented by Price et al. are scientifically unsound and that their results are unreliable.

  11. Evidence That Humans Metabolize Benzene via Two Pathways

    PubMed Central

    Rappaport, Stephen M.; Kim, Sungkyoon; Lan, Qing; Vermeulen, Roel; Waidyanatha, Suramya; Zhang, Luoping; Li, Guilan; Yin, Songnian; Hayes, Richard B.; Rothman, Nathaniel; Smith, Martyn T.

    2009-01-01

    Background Recent evidence has shown that humans metabolize benzene more efficiently at environmental air concentrations than at concentrations > 1 ppm. This led us to speculate that an unidentified metabolic pathway was mainly responsible for benzene metabolism at ambient levels. Objective We statistically tested whether human metabolism of benzene is better fitted by a kinetic model having two pathways rather than one. Methods We fit Michaelis-Menten-like models to levels of urinary benzene metabolites and the corresponding air concentrations for 263 nonsmoking Chinese females. Estimated benzene concentrations ranged from less than 0.001 ppm to 299 ppm, with 10th and 90th percentile values of 0.002 ppm and 8.97 ppm, respectively. Results Using values of Akaike’s information criterion obtained under the two models, we found strong statistical evidence favoring two metabolic pathways, with respective affinities (benzene air concentrations analogous to Km values) of 301 ppm for the low-affinity pathway (probably dominated by cytochrome P450 enzyme 2E1) and 0.594 ppm for the high-affinity pathway (unknown). The exposure-specific metabolite level predicted by our two-pathway model at nonsaturating concentrations was 184 μM/ppm of benzene, a value close to an independent estimate of 194 μM/ppm for a typical nonsmoking Chinese female. Our results indicate that a nonsmoking woman would metabolize about three times more benzene from the ambient environment under the two-pathway model (184 μM/ppm) than under the one-pathway model (68.6 μM/ppm). In fact, 73% of the ambient benzene dose would be metabolized via the unidentified high-affinity pathway. Conclusion Because regulatory risk assessments have assumed nonsaturating metabolism of benzene in persons exposed to air concentrations well above 10 ppm, our findings suggest that the true leukemia risks could be substantially greater than currently thought at ambient levels of exposure—about 3-fold higher among

  12. Histone Deacetylase Inhibitors Trichostatin A and MCP30 Relieve Benzene-Induced Hematotoxicity via Restoring Topoisomerase IIα.

    PubMed

    Chen, Jingjing; Zheng, Zhouyi; Chen, Yi; Li, Jiaqi; Qian, Shanhu; Shi, Yifen; Sun, Lan; Han, Yixiang; Zhang, Shenghui; Yu, Kang

    2016-01-01

    Dysfunction of histone acetylation inhibits topoisomerase IIα (Topo IIα), which is implicated in benzene-induced hematotoxicity in patients with chronic benzene exposure. Whether histone deacetylase (HDAC) inhibitors can relieve benzene-induced hematotoxicity remains unclear. Here we showed that hydroquinone, a main metabolite of benzene, increased the HDAC activity, decreased the Topo IIα expression and induced apoptosis in human bone marrow mononuclear cells in vitro, and treatment with two HDAC inhibitors, namely trichostatin A (TSA) or a mixture of ribosome-inactivating proteins MCP30, almost completely reversed these effects. We further established a benzene poisoning murine model by inhaling benzene vapor in a container and found that benzene poisoning decreased the expression and activity of Topo IIα, and impaired acetylation of histone H4 and H3. The analysis of regulatory factors of Topo IIα promoter found that benzene poisoning decreased the mRNA levels of SP1 and C-MYB, and increased the mRNA level of SP3. Both TSA and MCP30 significantly enhanced the acetylation of histone H3 and H4 in Topo IIα promoter and increased the expression and activity of Topo IIα in benzene poisoning mice, which contributed to relieve the symptoms of hematotoxicity. Thus, treatment with HDAC inhibitors represents an attractive approach to reduce benzene-induced hematotoxicity.

  13. Personal reflections on 50 years of study of benzene toxicology.

    PubMed Central

    Parke, D V

    1996-01-01

    The metabolism of benzene is reviewed, and the objectives of a quantitative balance study begun in 1945 are outlined; problems of toxicology and metabolism research of some 50 years ago are considered. The quantitative metabolism of 14C-benzene in the rabbit is annotated and compared with that of unlabeled benzene quantified by nonisotopic methods. The anomalies of phenylmercapturic acid and trans-trans-muconic acid as metabolites of benzene are examined in detail by isotopic and nonisotopic methods; these compounds are true but minor metabolites of benzene. Oxygen radicals are involved in both the metabolism of benzene and its toxicity; the roles of CYP2E1, the redox cycling of quinone metabolites, glutathione oxidation, and oxidative stress in the unique radiomimetic, hematopoietic toxicity of benzene are discussed. Differences between the toxicity of benzene and the halobenzenes are related to fundamental differences in their electronic structures and to the consequent pathways of metabolic activation and detoxication. PMID:9118881

  14. Imprinted nanospheres based on precipitation polymerization for the simultaneous extraction of six urinary benzene metabolites from urine followed by injector port silylation and gas chromatography-tandem mass spectrometric analysis.

    PubMed

    Chauhan, Abhishek; Bhatia, Tejasvi; Gupta, Manoj Kumar; Pandey, Pathya; Pandey, Vivek; Saxena, Prem Narain; Mudiam, Mohana Krishna Reddy

    2015-09-15

    In the present communication, uniformly sized molecularly imprinted polymer (MIP) as nanospheres were synthesized based on precipitation polymerization using dual-template imprinting approach and used it as sorbent for solid phase extraction of six urinary benzene metabolites (UBMs). This approach in combination with injector port silylation (IPS) has been used for the quantitative determination of these UBMs by gas chromatography-tandem mass spectrometry. The MIP was synthesized by using t,t-muconic acid (t,t-MA) and 1,2,4-trihydroxybenzene (THB) as templates, methacrylic acid (MAA) as a monomer, ethyleneglycoldimethacrylate (EGDMA) as crosslinker, acetonitrile and dimethylsulphoxide as a porogen and azobisisobutyronitrile (AIBN) as an initiator. The factors affecting the performance of polymer and IPS were investigated and optimized for the simultaneous determination of UBMs in urine. Binding study of imprinted and non-imprinted polymer (NIP) shows that, MIP possesses higher affinity in comparison to NIP for these analytes. Under the optimum conditions, the method developed was found to be linear with regression coefficients falls in the range of 0.9721-0.9988 for all the analyzed metabolites. The percent recovery of the metabolites analyzed in urine was found to be in the range of 76-89%, while the limit of detection and limit of quantification were found to be in the range of 0.9-9.1ngmL(-1) and 2.8-27ngmL(-1) respectively. The validated method was successfully applied to the real urine samples collected from different groups (kitchen workers, smokers and petroleum workers) and found that the developed method has been promising applications in the routine analysis of urine samples of benzene exposed population.

  15. Pesticide Urinary Metabolite Levels of Children in Eastern North Carolina Farmworker Households

    PubMed Central

    Arcury, Thomas A.; Grzywacz, Joseph G.; Barr, Dana B.; Tapia, Janeth; Chen, Haiying; Quandt, Sara A.

    2007-01-01

    Background In this investigation we documented the pesticide urinary metabolite levels of farmworker children in North Carolina, determined the number of different metabolites detected for each child, and delineated risk factors associated with the number of metabolites. Methods Urine samples were collected from 60 Latino farmworker children 1–6 years of age (34 female, 26 male). Interviews were completed by their mothers in Spanish. We analyzed urine samples for 14 pesticide metabolites, including the organophosphate pesticides chlorpyrifos, coumaphos, diazinon, isazaphos, malathion, pirimiphos, and parathion and its methyl counterpart; a common metabolite of at least 18 pyrethroid insecticides; the repellent DEET; and the herbicides 2,4,5-trichlorphenoxyacetic acid, 2,4-dichlorophenoxyacetic acid, acetochlor, atrazine, and metolachlor. Predictors included measures of paraoccupational, residential, and environmental exposure, child characteristics, and mother characteristics. Results Thirteen metabolites were present in the urine samples. Organophosphate pesticide metabolites were detected in a substantial proportion of children, particularly metabolites of parathion/methyl parathion (90.0%; geometric mean 1.00 μg/L), chlorpyrifos/chlorpyrifos methyl (83.3%; geometric mean 1.92 μg/L), and diazinon (55.0%; geometric mean 10.56 μg/L). The number of metabolites detected ranged from 0 to 7, with a mode of 4 detected (28.3%). Boys, children living in rented housing, and children with mothers working part-time had more metabolites detected. Conclusions Children in farmworker homes experience multiple sources of pesticide exposure. Pesticides may remain in their environments for long periods. Environmental and occupational health changes are needed to address these exposures. Research is needed with more precise measures of exposure and on the health effects of concurrent exposure to multiple pesticides. PMID:17687456

  16. Benzene poisoning

    MedlinePlus

    ... Atlanta, GA. Mirkin DB. Benzene and related aromatic hydrocarbons. In: Shannon MW, Borron SW, Burns MJ, eds. ... PA: Elsevier Saunders; 2007:chap 94. Lee DC. Hydrocarbons. In: Marx JA, Hockberger RS, Walls RM, et ...

  17. Human Benzene Metabolism Following Occupational and Environmental Exposures

    PubMed Central

    Rappaport, Stephen M.; Kim, Sungkyoon; Lan, Qing; Li, Guilan; Vermeulen, Roel; Waidyanatha, Suramya; Zhang, Luoping; Yin, Songnian; Smith, Martyn T.; Rothman, Nathaniel

    2011-01-01

    We previously reported evidence that humans metabolize benzene via two enzymes, including a hitherto unrecognized high-affinity enzyme that was responsible for an estimated 73 percent of total urinary metabolites [sum of phenol (PH), hydroquinone (HQ), catechol (CA), E,E-muconic acid (MA), and S-phenylmercapturic acid (SPMA)] in nonsmoking females exposed to benzene at sub-saturating (ppb) air concentrations. Here, we used the same Michaelis-Menten-like kinetic models to individually analyze urinary levels of PH, HQ, CA and MA from 263 nonsmoking Chinese women (179 benzene-exposed workers and 84 control workers) with estimated benzene air concentrations ranging from less than 0.001 ppm to 299 ppm. One model depicted benzene metabolism as a single enzymatic process (1-enzyme model) and the other as two enzymatic processes which competed for access to benzene (2-enzyme model). We evaluated model fits based upon the difference in values of Akaike’s Information Criterion (ΔAIC), and we gauged the weights of evidence favoring the two models based upon the associated Akaike weights and Evidence Ratios. For each metabolite, the 2-enzyme model provided a better fit than the 1-enzyme model with ΔAIC values decreasing in the order 9.511 for MA, 7.379 for PH, 1.417 for CA, and 0.193 for HQ. The corresponding weights of evidence favoring the 2-enzyme model (Evidence Ratios) were: 116.2:1 for MA, 40.0:1 for PH, 2.0:1 for CA and 1.1:1 for HQ. These results indicate that our earlier findings from models of total metabolites were driven largely by MA, representing the ring-opening pathway, and by PH, representing the ring-hydroxylation pathway. The predicted percentage of benzene metabolized by the putative high-affinity enzyme at an air concentration of 0.001 ppm was 88% based upon urinary MA and was 80% based upon urinary PH. As benzene concentrations increased, the respective percentages of benzene metabolized to MA and PH by the high-affinity enzyme decreased successively

  18. Synthesis and characterization of composite polymer, polyethylene glycol grafted flower-like cupric nano oxide for solid phase microextraction of ultra-trace levels of benzene, toluene, ethyl benzene and o-xylene in human hair and water samples.

    PubMed

    Sarafraz-Yazdi, Ali; Zendegi-Shiraz, Amene; Es'haghi, Zarrin; Hassanzadeh-Khayyat, Mohammad

    2015-10-30

    In this research, poly (ethylene glycol)-poly (ethylene glycol) grafted flower-like cupric oxidenano particles (PEG-PEG-g-CuO NPs) as a novel fiber coating of solid-phase microextraction (SPME) were synthesized by using sol-gel technology. This fiber was successfully applied to extract and determine the ultra-trace levels of benzene, toluene, ethyl benzene and o-xylene in human hair using head space-solid-phase microextraction (HS-SPME) coupled to gas chromatography-flame ionization detector. Characterization and chemical composition of the nano particle was performed by Fourier transform infrared spectroscopy (FT-IR), energy dispersion spectroscopy (EDS) and back scatter analysis (BSA). These methods confirmed the successful fabrication of PEG-g-CuO NPs. The surface morphology of the fibers were inspected by scanning electron microscopy. The scanning electron microscopy (SEM) revealed many "crack-like" features and highly porous structure on the surface of fiber. The synthesized nanocomposites were used for preconcentration and extraction of benzene, toluene, ethyl benzene and o-xylene (BTEX). The effects of operating parameters such as: desorption temperature and time, extraction temperature, extraction time, stirring speed and salt effect were investigated and optimized. Under the optimal conditions, the method detection limits and the limits of quantification were between 0.00025-50.00000pgmL(-1) and 0.00200-200.00000pgmL(-1), respectively. Linearity was observed over a range 0.00200-200000.00000pgmL(-1). The relative standard deviations for one fiber (repeatability; n=5) were obtained from 3.30 up to 5.01% and between fibers or batch to batch (n=3; reproducibility) in the range of 3.63-6.21%. The developed method was successfully applied to simultaneous determination of BTEX in human hairs, tap water and distillate water.

  19. Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels.

    PubMed

    Draisma, Harmen H M; Pool, René; Kobl, Michael; Jansen, Rick; Petersen, Ann-Kristin; Vaarhorst, Anika A M; Yet, Idil; Haller, Toomas; Demirkan, Ayşe; Esko, Tõnu; Zhu, Gu; Böhringer, Stefan; Beekman, Marian; van Klinken, Jan Bert; Römisch-Margl, Werner; Prehn, Cornelia; Adamski, Jerzy; de Craen, Anton J M; van Leeuwen, Elisabeth M; Amin, Najaf; Dharuri, Harish; Westra, Harm-Jan; Franke, Lude; de Geus, Eco J C; Hottenga, Jouke Jan; Willemsen, Gonneke; Henders, Anjali K; Montgomery, Grant W; Nyholt, Dale R; Whitfield, John B; Penninx, Brenda W; Spector, Tim D; Metspalu, Andres; Eline Slagboom, P; van Dijk, Ko Willems; 't Hoen, Peter A C; Strauch, Konstantin; Martin, Nicholas G; van Ommen, Gert-Jan B; Illig, Thomas; Bell, Jordana T; Mangino, Massimo; Suhre, Karsten; McCarthy, Mark I; Gieger, Christian; Isaacs, Aaron; van Duijn, Cornelia M; Boomsma, Dorret I

    2015-06-12

    Metabolites are small molecules involved in cellular metabolism, which can be detected in biological samples using metabolomic techniques. Here we present the results of genome-wide association and meta-analyses for variation in the blood serum levels of 129 metabolites as measured by the Biocrates metabolomic platform. In a discovery sample of 7,478 individuals of European descent, we find 4,068 genome- and metabolome-wide significant (Z-test, P < 1.09 × 10(-9)) associations between single-nucleotide polymorphisms (SNPs) and metabolites, involving 59 independent SNPs and 85 metabolites. Five of the fifty-nine independent SNPs are new for serum metabolite levels, and were followed-up for replication in an independent sample (N = 1,182). The novel SNPs are located in or near genes encoding metabolite transporter proteins or enzymes (SLC22A16, ARG1, AGPS and ACSL1) that have demonstrated biomedical or pharmaceutical importance. The further characterization of genetic influences on metabolic phenotypes is important for progress in biological and medical research.

  20. Measurement of plasma levels of tricylic psychoactive drugs and their metabolites by UV reflectance photometry of thin layer chromatograms.

    PubMed

    Breyer, U; Villumsen, K

    1976-03-22

    A method has been developed for the determination of perazine, clozapine, imipramine and amitriptyline and their demethylated metabolites in plasma. Other metabolites measured were perazine sulfoxide and the N-oxides of clozapine and perazine, the latter two following their reduction to the parent drugs with ascorbic acid. 10-Hydroxynortriptyline was identified as an amitriptyline metabolite in plasma. The general procedure included extraction of alkalinized plasma samples (3 - 6 g) with benzene or toluene and thin layer chromatography of the extracts, followed by reflectance photometry of the plates at appropriate wave lengths in ultraviolet light. Spots of questionable identity were further characterized by two-dimensional chromatography and by colour reactions. Therecoveries of compounds added in therapeutic concentrations were between 70 and 98 %. The limits of detectability were 5 - 10 ng/g plasma.

  1. Application of the urinary S-phenylmercapturic acid test as a biomarker for low levels of exposure to benzene in industry.

    PubMed Central

    van Sittert, N J; Boogaard, P J; Beulink, G D

    1993-01-01

    Recently, the determination of S-phenylmercapturic acid (S-PMA) in urine has been proposed as a suitable biomarker for the monitoring of low level exposures to benzene. In the study reported here, the test has been validated in 12 separate studies in chemical manufacturing plants, oil refineries, and natural gas production plants. Parameters studied were the urinary excretion characteristics of S-PMA, the specificity and the sensitivity of the assay, and the relations between exposures to airborne benzene and urinary S-PMA concentrations and between urinary phenol and S-PMA concentrations. The range of exposures to benzene was highest in workers in chemical manufacturing plants and in workers cleaning tanks or installations containing benzene as a component of natural gas condensate. Urinary S-PMA concentrations were measured up to 543 micrograms/g creatinine. Workers' exposures to benzene were lowest in oil refineries and S-PMA concentrations were comparable with those in smoking or nonsmoking control persons (most below the detection limit of 1 to 5 micrograms/g creatinine). In most workers S-PMA was excreted in a single phase and the highest S-PMA concentrations were at the end of an eight hour shift. The average half life of elimination was 9.0 (SD 4.5) hours (31 workers). Tentatively, in five workers a second phase of elimination was found with an average half life of 45 (SD 4) hours. A strong correlation was found between eight hour exposure to airborne benzene of 1 mg/m3 (0.3 ppm) and higher and urinary S-PMA concentrations in end of shift samples. It was calculated that an eight hour benzene exposure of 3.25 mg/m3 (1 ppm) corresponds to an average S-PMA concentration of 46 micrograms/g creatinine (95% confidence interval 41-50 micrograms/g creatinine). A strong correlation was also found between urinary phenol and S-PMA concentrations. At a urinary phenol concentration of 50 mg/g creatinine, corresponding to an eight hour benzene exposure of 32.5 mg/m3 (10

  2. Fecal estradiol and progesterone metabolite levels in the three-toed sloth (Bradypus variegatus).

    PubMed

    Mühlbauer, M; Duarte, D P F; Gilmore, D P; Costa, C P da

    2006-02-01

    The present study was carried out to assess the possibility of measuring fecal steroid hormone metabolites as a noninvasive technique for monitoring reproductive function in the three-toed sloth, Bradypus variegatus. Levels of the estradiol (E2) and progesterone (P4) metabolites were measured by radioimmunoassay in fecal samples collected over 12 weeks from 4 captive female B. variegatus sloths. The validation of the radioimmunoassay for evaluation of fecal steroid metabolites was carried out by collecting 10 blood samples on the same day as defecation. There was a significant direct correlation between the plasma and fecal E2 and P4 levels (P < 0.05, Pearson's test), thereby validating this noninvasive technique for the study of the estrous cycle in these animals. Ovulation was detected in two sloths (SL03 and SL04) whose E2 levels reached 2237.43 and 6713.26 pg/g wet feces weight, respectively, for over four weeks, followed by an increase in P4 metabolites reaching 33.54 and 3242.68 ng/g wet feces weight, respectively. Interestingly, SL04, which presented higher levels of E2 and P4 metabolites, later gave birth to a healthy baby sloth. The results obtained indicate that this is a reliable technique for recording gonadal steroid secretion and thereby reproduction in sloths.

  3. Weight and Body Composition Compartments do Not Predict Therapeutic Thiopurine Metabolite Levels in Inflammatory Bowel Disease

    PubMed Central

    Holt, Darcy Q; Strauss, Boyd JG; Moore, Gregory T

    2016-01-01

    OBJECTIVES: Thiopurine drugs are the most commonly used steroid-sparing therapies in moderate-to-severe inflammatory bowel disease (IBD). Their complex metabolism and their narrow therapeutic windows means that optimal dosing is difficult. However, weight-based dosing is the norm. Similar antimetabolites are dosed by body composition parameters. In IBD, treatment response and toxicity has been shown to correlate with thiopurine metabolite levels. We sought to determine whether weight or body composition parameters predicted therapeutic 6-thioguanine nucleotide (6TGN) or toxic 6-methylmercaptopurine (6MMP) levels. METHODS: This single-center retrospective cohort study identified 66 IBD patients who had body composition analysis and thiopurine metabolite levels tested. Statistical analysis was performed using Spearman correlation, Kruskal–Wallis, Mann–Whitney, and unpaired t tests and receiver-operator operating characteristic curves. A P value of <0.05 was considered significant. RESULTS: No correlation was identified between 6TGN and any body composition parameters, absolute drug dose or drug dose/kg of fat mass, fat-free mass (FFM), subcutaneous adipose tissue area, or visceral adipose tissue area. However, 6MMP correlated with azathioprine dose, thiopurine dose/kg of body weight, and with several body composition parameters. CONCLUSIONS: No relationship was found between therapeutic metabolite levels and weight or body composition compartments. Higher thiopurine doses, especially in relation to FFM, are associated with higher levels of potentially hepatotoxic 6MMP and shunting toward this metabolite. Conventional weight-based dosing to attain therapeutic metabolite levels appears unreliable and may be replaced by metabolite level testing. PMID:27787512

  4. Pyometra in Bitches Induces Elevated Plasma Endotoxin and Prostaglandin F2α Metabolite Levels

    PubMed Central

    Hagman, R; Kindahl, H; Lagerstedt, A-S

    2006-01-01

    Endotoxemia in bitches with pyometra can cause severe systemic effects directly or via the release of inflammatory mediators. Plasma endotoxin concentrations were measured in ten bitches suffering from pyometra with moderately to severely deteriorated general condition, and in nine bitches admitted to surgery for non-infectious reasons. Endotoxin samples were taken on five occasions before, during and after surgery. In addition, urine and uterine bacteriology was performed and hematological, blood biochemical parameters, prostaglandin F2α metabolite 15-ketodihydro-PGF2α (PG-metabolite), progesterone and oestradiol (E2-17β) levels were analysed. The results confirm significantly increased plasma levels of endotoxin in bitches with pyometra and support previous reports of endotoxin involvement in the pathogenesis of the disease. Plasma concentrations of PG-metabolite were elevated in pyometra bitches and provide a good indicator of endotoxin release since the concentrations were significantly correlated to the endotoxin levels and many other hematological and chemistry parameters. The γ-globulin serum protein electrophoresis fraction and analysis of PG-metabolite can be valuable in the diagnosis of endotoxin involvement if a reliable, rapid and cost-effective test for PG-metabolite analysis becomes readily available in the future. Treatment inhibiting prostaglandin biosynthesis and related compounds could be beneficial for bitches suffering from pyometra. PMID:16722306

  5. Pyometra in bitches induces elevated plasma endotoxin and prostaglandin F2alpha metabolite levels.

    PubMed

    Hagman, R; Kindahl, H; Lagerstedt, A S

    2006-01-01

    Endotoxemia in bitches with pyometra can cause severe systemic effects directly or via the release of inflammatory mediators. Plasma endotoxin concentrations were measured in ten bitches suffering from pyometra with moderately to severely deteriorated general condition, and in nine bitches admitted to surgery for non-infectious reasons. Endotoxin samples were taken on five occasions before, during and after surgery. In addition, urine and uterine bacteriology was performed and hematological, blood biochemical parameters, prostaglandin F2alpha metabolite 15-ketodihydro-PGF2alpha (PG-metabolite), progesterone and oestradiol (E2-17beta) levels were analysed. The results confirm significantly increased plasma levels of endotoxin in bitches with pyometra and support previous reports of endotoxin involvement in the pathogenesis of the disease. Plasma concentrations of PG-metabolite were elevated in pyometra bitches and provide a good indicator of endotoxin release since the concentrations were significantly correlated to the endotoxin levels and many other hematological and chemistry parameters. The gamma-globulin serum protein electrophoresis fraction and analysis of PG-metabolite can be valuable in the diagnosis of endotoxin involvement if a reliable, rapid and cost-effective test for PG-metabolite analysis becomes readily available in the future. Treatment inhibiting prostaglandin biosynthesis and related compounds could be beneficial for bitches suffering from pyometra.

  6. Benzene: standards, occurrence, and exposure.

    PubMed

    Holmberg, B; Lundberg, P

    1985-01-01

    The national occupational standard values for benzene are 10 ppm for Australia, 10 ppm for Denmark, 10 ppm for Finland, 10 ppm for Japan, 10 ppm for The Netherlands, 10 ppm for the United States, and 5 ppm for Sweden; in the Federal Republic of Germany the technical guideline value is 8 ppm. Crude mineral oil contains benzene as a natural constituent of approximately 0.1%. Gasoline in Sweden may contain 4-5% benzene by volume. The 8-hour time-weighted average (TWA) exposure levels of Swedish petroleum refinery workers vary between 0.1 to 1 mg benzene/m3 in air. The exposures of benzene in various other occupations were measured and described. Other environmental exposures to benzene may have their origin in pyrolysis, such as tobacco smoking and burning of substances such as polyvinylchloride.

  7. Blood styrene and urinary metabolites in styrene polymerisation.

    PubMed Central

    Wolff, M S; Lorimer, W V; Lilis, R; Selikoff, I J

    1978-01-01

    The results of the analysis of blood and urine samples for styrene and its metabolites in 491 workers in a styrene polymerisation plant in the United States are reported. The levels of exposure to styrene were estimated to be less than 10 ppm, but nevertheless styrene and metabolites were detectable in more than 50% of workers in polymerisation jobs, within 4 h of exposure. Workers involved in the manufacture and purification of styrene from ethyl benzene also had detectable blood styrene and urinary metabolites in 83% of recently exposed subjects. The relationship between styrene in blood and in subcutaneous fat and urinary metabolites as pharmacokinetic variables is discussed. PMID:737139

  8. Benzene toxicity: emphasis on cytosolic dihydrodiol dehydrogenases

    SciTech Connect

    Bolcsak, L.E.

    1982-01-01

    Blood dyscrasias such as leukopenia and anemia have been clearly identified as consequences of chronic benzene exposure. The metabolites, phenol, catechol, and hydroquinone produced inhibition of /sup 59/Fe uptake in mice which followed the same time course as that produced by benzene. The inhibitor of benzene oxidation, 3-amino-1,2,4-triazole, mitigated the inhibitory effects of benzene and phenol only. These data support the contention that benzene toxicity is mediated by a metabolite and suggest that the toxicity of phenol is a consequence of its metabolism to hydroquinone and that the route of metabolism to catechol may also contribute to the production of toxic metabolite(s). The properties of mouse liver cytosolic dihydrodiol dehydrogenases were examined. These enzymes catalyze the NADP/sup +/-dependent oxidation of trans-1,2-dihydro-1,2-dihydroxybenzene (BDD) to catechol, a possible toxic metabolite of benzene produced via this metabolic route. Four distinct dihydrodiol dehydrogenases (DD1, DD2, DD3, and DD4) were purified to apparent homogeneity as judged by SDS polyacrylamide gel electrophoresis and isoelectric focusing. DD1 appeared to be identical to the major ketone reductase and 17..beta..-hydroxysteroid dehydrogenase activity in the liver. DD2 exhibited aldehyde reductase activity. DD3 and DD4 oxidized 17..beta..-hydroxysteroids, but no carbonyl reductase activity was detected. These relationships between BDD dehydrogenases and carbonyl reductase and/or 17..beta..-hydroxysteroid dehydrogenase activities were supported by several lines of evidence.

  9. A Unique Automation Platform for Measuring Low Level Radioactivity in Metabolite Identification Studies

    PubMed Central

    Krauser, Joel; Walles, Markus; Wolf, Thierry; Graf, Daniel; Swart, Piet

    2012-01-01

    Generation and interpretation of biotransformation data on drugs, i.e. identification of physiologically relevant metabolites, defining metabolic pathways and elucidation of metabolite structures, have become increasingly important to the drug development process. Profiling using 14C or 3H radiolabel is defined as the chromatographic separation and quantification of drug-related material in a given biological sample derived from an in vitro, preclinical in vivo or clinical study. Metabolite profiling is a very time intensive activity, particularly for preclinical in vivo or clinical studies which have defined limitations on radiation burden and exposure levels. A clear gap exists for certain studies which do not require specialized high volume automation technologies, yet these studies would still clearly benefit from automation. Use of radiolabeled compounds in preclinical and clinical ADME studies, specifically for metabolite profiling and identification are a very good example. The current lack of automation for measuring low level radioactivity in metabolite profiling requires substantial capacity, personal attention and resources from laboratory scientists. To help address these challenges and improve efficiency, we have innovated, developed and implemented a novel and flexible automation platform that integrates a robotic plate handling platform, HPLC or UPLC system, mass spectrometer and an automated fraction collector. PMID:22723932

  10. A unique automation platform for measuring low level radioactivity in metabolite identification studies.

    PubMed

    Krauser, Joel; Walles, Markus; Wolf, Thierry; Graf, Daniel; Swart, Piet

    2012-01-01

    Generation and interpretation of biotransformation data on drugs, i.e. identification of physiologically relevant metabolites, defining metabolic pathways and elucidation of metabolite structures, have become increasingly important to the drug development process. Profiling using (14)C or (3)H radiolabel is defined as the chromatographic separation and quantification of drug-related material in a given biological sample derived from an in vitro, preclinical in vivo or clinical study. Metabolite profiling is a very time intensive activity, particularly for preclinical in vivo or clinical studies which have defined limitations on radiation burden and exposure levels. A clear gap exists for certain studies which do not require specialized high volume automation technologies, yet these studies would still clearly benefit from automation. Use of radiolabeled compounds in preclinical and clinical ADME studies, specifically for metabolite profiling and identification are a very good example. The current lack of automation for measuring low level radioactivity in metabolite profiling requires substantial capacity, personal attention and resources from laboratory scientists. To help address these challenges and improve efficiency, we have innovated, developed and implemented a novel and flexible automation platform that integrates a robotic plate handling platform, HPLC or UPLC system, mass spectrometer and an automated fraction collector.

  11. Peripheral blood gene expression profiles linked to monoamine metabolite levels in cerebrospinal fluid

    PubMed Central

    Luykx, J J; Olde Loohuis, L M; Neeleman, M; Strengman, E; Bakker, S C; Lentjes, E; Borgdorff, P; van Dongen, E P A; Bruins, P; Kahn, R S; Horvath, S; de Jong, S; Ophoff, R A

    2016-01-01

    The blood–brain barrier separates circulating blood from the central nervous system (CNS). The scope of this barrier is not fully understood which limits our ability to relate biological measurements from peripheral to central phenotypes. For example, it is unknown to what extent gene expression levels in peripheral blood are reflective of CNS metabolism. In this study, we examine links between central monoamine metabolite levels and whole-blood gene expression to better understand the connection between peripheral systems and the CNS. To that end, we correlated the prime monoamine metabolites in cerebrospinal fluid (CSF) with whole-genome gene expression microarray data from blood (N=240 human subjects). We additionally applied gene-enrichment analysis and weighted gene co-expression network analyses (WGCNA) to identify modules of co-expressed genes in blood that may be involved with monoamine metabolite levels in CSF. Transcript levels of two genes were significantly associated with CSF serotonin metabolite levels after Bonferroni correction for multiple testing: THAP7 (P=2.8 × 10−8, β=0.08) and DDX6 (P=2.9 × 10−7, β=0.07). Differentially expressed genes were significantly enriched for genes expressed in the brain tissue (P=6.0 × 10−52). WGCNA revealed significant correlations between serotonin metabolism and hub genes with known functions in serotonin metabolism, for example, HTR2A and COMT. We conclude that gene expression levels in whole blood are associated with monoamine metabolite levels in the human CSF. Our results, including the strong enrichment of brain-expressed genes, illustrate that gene expression profiles in peripheral blood can be relevant for quantitative metabolic phenotypes in the CNS. PMID:27959337

  12. NON-RESIDENTIAL ORGANOPHOSPHOROUS PESTICIDE USE AS A PREDICTOR OF CHILDREN'S URINARY METABOLITE LEVELS

    EPA Science Inventory

    NON-RESIDENTIAL ORGANOPHOSPHORUS PESTICIDE USE AS A PREDICTOR OF CHILDREN'S URINARY METABOLITE LEVELS.
    Julie A. Baker, Pauline Mendola, Dana Barr, Debra Walsh, John Creason, and Larry Needham. (University at Buffalo, US Environmental Protection Agency, and Centers for Disease ...

  13. Correlation of thiamine metabolite levels with cognitive function in the non-demented elderly.

    PubMed

    Lu, Jingwen; Pan, Xiaoli; Fei, Guoqiang; Wang, Changpeng; Zhao, Lei; Sang, Shaoming; Liu, Huimin; Liu, Meng; Wang, Hui; Wang, Zhiliang; Zhong, Chunjiu

    2015-12-01

    Thiamine metabolism is critical for glucose metabolism and also vital for brain function, which is susceptible to decline in the elderly. This study aimed to investigate whether thiamine metabolites correlate with cognitive function in the non-demented elderly and their impact factors. Volunteers >60 years old were recruited and their blood thiamine metabolites and Mini-Mental State Examination (MMSE) scores were measured. The apolipoprotein E (APOE) genotype, routine blood parameters, liver and kidney function, and levels of fasting blood glucose and triglycerides were also measured. The results showed that the thiamine diphosphate (TDP) level weakly correlated with MMSE score in the non-demented elderly. Participants with high TDP levels performed better in Recall and Attention and Calculation than those with low TDP. TDP levels were associated with the APOE ε2 allele, body mass index, hemoglobin level, fasting blood glucose, and triglycerides. Our results suggest that TDP, which is easily affected by many factors, impacts cognitive function in the elderly.

  14. Quantitative analysis of trace-level benzene, toluene, ethylbenzene, and xylene in cellulose acetate tow using headspace heart-cutting multidimensional gas chromatography with mass spectrometry.

    PubMed

    Ji, Xiaorong; Zhang, Jing; Guo, Yinlong

    2016-06-01

    This study describes a method for the quantification of trace-level benzene, toluene, ethylbenzene, and xylene in cellulose acetate tow by heart-cutting multidimensional gas chromatography with mass spectrometry in selected ion monitoring mode. As the major volatile component in cellulose acetate tow samples, acetone would be overloaded when attempting to perform a high-resolution separation to analyze trace benzene, toluene, ethylbenzene, and xylene. With heart-cutting technology, a larger volume injection was achieved and acetone was easily cut off by employing a capillary column with inner diameter of 0.32 mm in the primary gas chromatography. Only benzene, toluene, ethylbenzene, and xylene were directed to the secondary column to result in an effective separation. The matrix interference was minimized and the peak shapes were greatly improved. Finally, quantitative analysis of benzene, toluene, ethylbenzene, and xylene was performed using an isotopically labeled internal standard. The headspace multidimensional gas chromatography mass spectrometry system was proved to be a powerful tool for analyzing trace volatile organic compounds in complex samples.

  15. Critical issues in benzene toxicity and metabolism: The effect of interactions with other organic chemicals on risk assessment

    SciTech Connect

    Medinsky, M.A.; Schlosser, P.M.; Bond, J.A.

    1994-11-01

    Benzene, an important industrial solvent, is also present in unleaded gasoline and cigarette smoke. The hematotoxic effects of benzene are well documented and include aplastic anemia and pancytopenia. Some individuals exposed repeatedly to cytotoxic concentrations of benzene develop acute myeloblastic anemia. It has been hypothesized that metabolism of benzene is required for its toxicity, although administration of no single benzene metabolite duplicates the toxicity of benzene. Several investigators have demonstrated that a combination of metabolites (hydroquinone and phenol, for example) is necessary to duplicate the hematotoxic effect of benzene. Enzymes implicated in the metabolic activation of benzene and its metabolites include the cytochrome P450 monooxygenases and myeloperoxidase. Since benzene and its hydroxylated metabolites (phenol, hydroquinone, and catechol) are substrates for the same cytochrome P450 enzymes, competitive interactions among the metabolites are possible. In vivo data on metabolite formation by mice exposed to various benzene concentrations are consistent with competitive inhibition of phenol oxidation by benzene. Other organic molecules that are substrates for cytochrome P450 can inhibit the metabolism of benzene. For example, toluene has been shown to inhibit the oxidation of benzene in a noncompetitive manner. Enzyme inducers, such as ethanol, can alter the target tissue dosimetry of benzene metabolites by inducing enzymes responsible for oxidation reactions involved in benzene metabolism. 24 refs., 6 figs., 2 tabs.

  16. Personal care product use and urinary levels of phthalate metabolites in Mexican women.

    PubMed

    Romero-Franco, Michelle; Hernández-Ramírez, Raúl U; Calafat, Antonia M; Cebrián, Mariano E; Needham, Larry L; Teitelbaum, Susan; Wolff, Mary S; López-Carrillo, Lizbeth

    2011-07-01

    Sources of phthalates other than Polyvinyl chloride (PVC) related products are scarcely documented in Mexico. The objective of our study was to explore the association between urinary levels of nine phthalate metabolites and the use of personal care products. Subjects included 108 women who participated as controls in an ongoing population-based case-control study of environmental factors and genetic susceptibility to breast cancer in northern Mexico. Direct interviews were performed to inquire about sociodemographic characteristics, reproductive history, use of personal care products, and diet. Phthalate metabolites measured in urine by high performance liquid chromatography-isotope dilution tandem mass spectrometry were monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), mono-3-carboxypropyl phthalate (MCPP) as well as mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP) that are metabolites of di-ethylhexyl phthalate (DEHP). Detectable urinary concentrations of phthalate metabolites varied from 75% (MEHP) to 100% (MEP, MBP, MEOHP, MEHHP and MECPP). Medians of urinary concentrations of some phthalate metabolites were significantly higher among users of the following personal care products compared to nonusers: body lotion (MEHHP, MECPP and sum of DEHP metabolites (ΣDEHP)), deodorant (MEHP and ΣDEHP), perfume (MiBP), anti-aging facial cream (MEP, MBP and MCPP) and bottled water (MCPP, MEHHP and MEOHP). Urinary concentrations of MEP showed a positive relationship with the number of personal care products used. Our results suggest that the use of some personal care products contributes to phthalate body burden that deserves attention due to its potential health impact.

  17. The relationship of the urinary ascorbate metabolites to specific levels of ascorbate supplementation in the monkey

    SciTech Connect

    Tillotson, J.A.; McGown, E.L.

    1981-11-01

    This study was designed to investigate urinary ascorbic acid (AA) and its metabolites derived from (1-14C) AA administered to trained monkeys fed different levels of ascorbate for extended periods of time. A chromatographic procedure was developed which rapidly separates the urinary compounds into four major fractions with minimal degradation. The distribution of 14C in the four peaks was dependent upon the ascorbate nutritional status of the monkey and remained constant for at least 30 days postlabel. The two major fractions were identified as oxalate and unmetabolized ascorbate. The ascorbate metabolites in the two minor fractions have not been identified. In monkeys maintained on low ascorbate intakes, unmetabolized ascorbate accounted for 10 to 20% and oxalate 25 to 48% of the urinary 14C. The average percentages of 14C in the urine of monkeys fed high levels of ascorbate were 75% for ascorbate and 7% for oxalate. The urine also contained an ascorbate metabolite which degraded during storage and/or chromatography, yielding 14CO2. Ascorbate sulfate was not detected as a urinary metabolite.

  18. Metabolic polymorphisms and biomarkers of effect in the biomonitoring of occupational exposure to low-levels of benzene: state of the art.

    PubMed

    De Palma, G; Manno, M

    2014-12-01

    Current levels of occupational exposure to benzene, a genotoxic human carcinogen, in Western countries are reduced by two-three orders of magnitude (from ppm to ppb) as compared to the past. However, as benzene toxicity is strongly dependent on biotransformation and recent evidence underlines a higher efficiency of bio-activation pathways at lower levels of exposure, toxic effects at low doses could be higher than expected, particularly in susceptible individuals. Currently, biological monitoring can allow accurate exposure assessment, relying on sensitive and specific enough biomarkers of internal dose. The availability of similarly reliable biomarkers of early effect or susceptibility could greatly improve the risk assessment process to such an extent that risk could even be assessed at the individual level. As to susceptibility biomarkers, functional genetic polymorphisms of relevant biotransformation enzymes may modulate the risk of adverse effects (NQO1) and the levels of biomarkers of internal dose, in particular S-phenylmercapturic acid (GSTM1, GSTT1, GSTA1). Among biomarkers of early effect, genotoxicity indicators, although sensitive in some cases, are too aspecific for routine use in occupational health surveillance programmes. Currently only the periodical blood cell count seems suitable enough to be applied in the longitudinal monitoring of effects from benzene exposure. Novel biomarkers of early effect are expected from higher collaboration among toxicologists and clinicians, also using advanced "omics" techniques.

  19. Impacts of rising tropospheric ozone on photosynthesis and metabolite levels on field grown soybean.

    PubMed

    Sun, Jindong; Feng, Zhaozhong; Ort, Donald R

    2014-09-01

    The response of leaf photosynthesis and metabolite profiles to ozone (O3) exposure ranging from 37 to 116 ppb was investigated in two soybean cultivars Dwight and IA3010 in the field under fully open-air conditions. Leaf photosynthesis, total non-structural carbohydrates (TNC) and total free amino acids (TAA) decreased linearly with increasing O3 levels in both cultivars with average decrease of 7% for an increase in O3 levels by 10 ppb. Ozone interacted with developmental stages and leaf ages, and caused higher damage at later reproductive stages and in older leaves. Ozone affected yield mainly via reduction of maximum rate of Rubisco carboxylation (Vcmax) and maximum rates of electron transport (Jmax) as well as a shorter growing season due to earlier onset of canopy senescence. For all parameters investigated the critical O3 levels (∼50 ppb) for detectable damage fell within O3 levels that occur routinely in soybean fields across the US and elsewhere in the world. Strong correlations were observed in O3-induced changes among yield, photosynthesis, TNC, TAA and many metabolites. The broad range of metabolites that showed O3 dose dependent effect is consistent with multiple interaction loci and thus multiple targets for improving the tolerance of soybean to O3.

  20. Plasma metabolite levels predict bird growth rates: A field test of model predictive ability.

    PubMed

    Albano, Noelia; Masero, José A; Villegas, Auxiliadora; Abad-Gómez, José María; Sánchez-Guzmán, Juan M

    2011-09-01

    Bird growth rates are usually derived from nonlinear relationships between age and some morphological structure, but this procedure may be limited by several factors. To date, nothing is known about the capacity of plasma metabolite profiling to predict chick growth rates. Based on laboratory-trials, we here develop predictive logistic models of body mass, and tarsus and wing length growth rates in Gull-billed Tern Gelochelidon nilotica chicks from measurements of plasma metabolite levels at different developmental stages. The predictive model obtained during the fastest growth period (at the age of 12 days) explained 65-68% of the chicks' growth rates, with fasting triglyceride level explaining most of the variation in growth rate. At the end of pre-fledging period, β-hydroxybutyrate level was also a good predictor of growth rates. Finally, we carried out a field test to check the predictive capacity of the models in two colonies of wild Gull-billed Tern, comparing field-measured and model-predicted growth rates between groups. Both, measured and predicted growth rates, matched statistically. Plasma metabolite levels can thus be applied in comparative studies of chick growth rates when semi-precocial birds can be captured only once.

  1. Methodological issues in the biological monitoring of urinary benzene and S-phenylmercapturic acid at low exposure levels.

    PubMed

    Fustinoni, Silvia; Campo, Laura; Mercadante, Rosa; Manini, Paola

    2010-10-01

    Biological monitoring of low level exposure to pollutants is a very challenging analytical activity, and the quality of results is difficult to assess, especially when a certified reference material is unavailable. The aim of this work was to evaluate the reliability of the assays used to measure urinary benzene (Benz-U) and S-phenylmercapturic acid (SPMA), by applying an internal quality control protocol. Urine spot samples from 705 subjects who were either members of the general urban population, gasoline station attendants, or refinery plant workers were assayed for Benz-U and SPMA, using GC/MS and LC/MS/MS, with quantification limits of 15 ng/L and 0.10 μg/L. The median Benz-U concentration was 263 ng/L (60-2789 ng/L, 5th-95th percentile), and the median SPMA concentration was 0.19 μg/L (<0.1-2.5 μg/L, 5th-95th percentile). Linearity of both assays was good, but a less-than-proportional response was found for SPMA concentrations below 1 μg/L. Between-run precision and accuracy for Benz-U concentration determination were assessed using quality controls at 120 ng/L and 1000 ng/L and were 10.3% and 4.8%, and 104.8% and 98.9%, respectively; while the precision and accuracy for SPMA concentration determination at 0.3 μg/L, 2.5 μg/L, and 20 μg/L were 40.3%, 6.2%, and 6.2%, and 48.3%, 96.3%, and 98.8%, respectively. Precision, estimated using duplicates of unknown samples, was 13.4% for Benz-U and 26.5% for SPMA analyses. Control charts for the means of the slope of the linear calibration curve of Benz-U showed good stability of the means over a five-year period. For SPMA, a two-laboratory comparison revealed acceptable agreement between ln-transformed data pairs, with a slope of the linear regression of 0.863 (confidence interval 0.774-0.952), null intercept, and a Pearson's r value of 0.844. Reliable results were obtained for Benz-U analyses over the entire concentration range, and for high and medium SPMA levels. However, the determination of SPMA

  2. Occurrence and levels of nitrofuran metabolites in sea cucumber from Dalian, China.

    PubMed

    Zhao, Hongxia; Guo, Wuxia; Quan, Wenna; Jiang, Jingqiu; Qu, Baocheng

    2016-11-01

    The occurrence and levels of nitrofuran metabolites (NFMs) in sea cucumber (SC) from Dalian, China, are reported. Four metabolites including 3-amino-5-morpholinomethyl-2-oxazolidinone (AMOZ), 3-amino-2-oxazolidinone (AOZ), semicarbazide (SEM) and 1-aminohydantoin (AHD) in different SC products (fresh, instant and dry salted SCs) were measured. The frequency of occurrence for NFMs in all SC samples was 42.7%. The total NFM concentrations ranged from non-detectable to 64.6 ng g(-)(1), with a mean of 3.59 ng g(-1). AOZ and SEM were the dominant congeners, accounting for 40.1% and 59.1% of the total NFMs, respectively. The concentrations and patterns varied among different regions. Higher levels of NFMs were found in the fresh SC products, and the order for the average concentration of ∑4NFM was fresh > dry salted > instant.

  3. Determination of benzene at trace levels in air by a novel method based on solid-phase microextraction gas chromatography/mass spectrometry.

    PubMed

    Saba, A; Cuzzola, A; Raffaelli, A; Pucci, S; Salvadori, P

    2001-01-01

    A new method for the determination of benzene at trace levels in air is presented. The method consists of the collection of air samples on adsorbent cartridges with simultaneous adsorption of pre-established amounts of D6-labeled internal standard. Desorption from the cartridge is performed by solid-phase microextraction (SPME) with analysis by gas chromatography/mass spectrometry (GC/MS) using an ion trap mass spectrometer. The influence of several parameters (type of SPME fiber, temperature, time, for example) was investigated, and good linearity in the range 10-400 ng of C6D6, with a coefficient of variance (CV) around 3-5%, was obtained. The method was tested by sampling air in a town center in Italy, and a benzene concentration of approximately 50 microg/m(3) was determined. The maximum limit recommended by the European Community is 10 microg/m(3).

  4. Diurnal Changes in Metabolite Levels and Crassulacean Acid Metabolism in Kalanchoë daigremontiana Leaves 1

    PubMed Central

    Kenyon, William H.; Holaday, A. Scott; Black, Clanton C.

    1981-01-01

    Diurnal changes in levels of selected metabolites associated with glycolysis, the C3 cycle, C4-organic acids, and storage carbohydrates were analyzed in active Kalanchoë daigremontiana Crassulacean acid metabolism leaves. Three metabolic transition periods occurred each day. During the first two hours of light, nearly all of the metabolite pools underwent transient changes. Beginning at daylight, stomata opened transiently and closed again within 30 minutes; malate synthesis continued for about 1 hour into the light; C3 photosynthesis began within 30 minutes; and net quantities of starch and glucan began to accumulate after 2 hours, continuing linearly throughout the rest of the day. The second transition occurred in midafternoon: stomata reopened; malate decarboxylation nearly terminated; and the assimilation of ambient CO2 occurred primarily via the C3 cycle. The third transition occurred at dark: stomata transiently closed before opening again; the C3 cycle stopped; malate synthesis started in about 1 hour; starch and glucan degradation began within 1 hour; and the bulk of carbon flow was through glycolysis leading to the synthesis and accumulation of malate throughout the night. At night, the levels of metabolites involved in acidification and glycolysis (except for phosphoenolpyruvate) generally accumulated. Phosphoenolpyruvate levels peaked near midday and were minimal at night. The ribulose 1,5-bisphosphate pool was depleted at night, while sedoheptulose 1,7-bisphosphate, fructose 1,6-bisphosphate, glucose 6-phosphate, and fructose 6-phosphate accumulated. Images PMID:16662040

  5. Levels of dichloro-dyphenyl-trichloroethane (DDT) metabolites in maternal milk and their determinant factors.

    PubMed

    Torres-Arreola, L; López-Carrillo, L; Torres-Sánchez, L; Cebrián, M; Rueda, C; Reyes, R; López-Cervantes, M

    1999-01-01

    To document the levels and the determinants of dichloro-dyphenyl-trichloroethane (DDT) metabolites in maternal milk, we conducted a cohort study of 50 adult females who lived in Mexico City. We measured social and dietary characteristics via interview. Levels of DDT metabolites were determined by gas-liquid chromatography. The mean values (lipid milk basis) were 0.162 ppm p,p'-DDT; 0.138 ppm o,p'-DDT; and 0.594 ppm 2,2(bis)p-chlorophyenyl-1-1-dichloroethylene (DDE). The main determinants of DDT metabolites were maternal age, lifetime lactation, history of living in an agricultural area, and consumption of salted meat and fish. We estimated that 6.0% of the breast-fed babies had daily intakes of DDT above the level of 0.005 mg/kg d recommended by the World Health Organization/Food and Agriculture Organization of the United Nations (WHO/FAO). Health-outcomes research among children is needed, and investigators should design or adjust current surveillance programs.

  6. Plasma Levels of Biotin Metabolites Are Elevated in Hemodialysis Patients with Cramps.

    PubMed

    Fujiwara, Masako; Ando, Itiro; Yagi, Shigeaki; Nishizawa, Manabu; Oguma, Shiro; Satoh, Keisuke; Sato, Hiroshi; Imai, Yutaka

    2016-01-01

    Patients with renal failure undergoing hemodialysis (HD) are susceptible to muscle cramps during and after HD. Muscle cramps are defined as the sudden onset of a prolonged involuntary muscle contraction accompanied by severe pain. Through HD, water-soluble vitamins are drawn out with water. Since biotin, a water-soluble vitamin, plays an essential role as one of the coenzymes in producing energy, we have hypothesized that deficiency of biotin may be responsible for HD-associated cramps. We previously reported that biotin administration ameliorated the muscle cramps, despite the elevated plasma biotin levels before HD and biotin administration, as judged by an enzyme-linked immunosorbent assay (ELISA). However, the ELISA measures not only biotin but also total avidin-binding substances (TABS) including biotin metabolites. In the present study, we determined biotin in HD patients as well as healthy controls, using a newly developed method with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The plasma samples were collected from 28 HD patients (16 patients with cramps and 12 patients without cramps) before HD and biotin administration and from 11 controls. The results showed that the accumulation of biotin and TABS in plasma of HD patients compared to controls. Importantly, the levels of biotin metabolites, i.e. TABS subtracted by biotin, increased significantly in patients with cramps over those without cramps. Moreover, the levels of biotin metabolites were significantly higher in patients with a poor response to administered biotin, compared to those with a good response. We propose that accumulated biotin metabolites impair biotin's functions as a coenzyme.

  7. Species-level assessment of secondary metabolite diversity among Hamigera species and a taxonomic note on the genus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Secondary metabolite phenotypes in nine species of the Hamigera clade were analysed to assess their correlations to a multi-gene species-level phylogeny. High-pressure-liquid-chromatography-based chemical analysis revealed three distinctive patterns of secondary metabolite production: (1) the nine s...

  8. A detailed view on sulphur metabolism at the cellular and whole-plant level illustrates challenges in metabolite flux analyses.

    PubMed

    Rennenberg, Heinz; Herschbach, Cornelia

    2014-11-01

    Understanding the dynamics of physiological process in the systems biology era requires approaches at the genome, transcriptome, proteome, and metabolome levels. In this context, metabolite flux experiments have been used in mapping metabolite pathways and analysing metabolic control. In the present review, sulphur metabolism was taken to illustrate current challenges of metabolic flux analyses. At the cellular level, restrictions in metabolite flux analyses originate from incomplete knowledge of the compartmentation network of metabolic pathways. Transport of metabolites through membranes is usually not considered in flux experiments but may be involved in controlling the whole pathway. Hence, steady-state and snapshot readings need to be expanded to time-course studies in combination with compartment-specific metabolite analyses. Because of species-specific differences, differences between tissues, and stress-related responses, the quantitative significance of different sulphur sinks has to be elucidated; this requires the development of methods for whole-sulphur metabolome approaches. Different cell types can contribute to metabolite fluxes to different extents at the tissue and organ level. Cell type-specific analyses are needed to characterize these contributions. Based on such approaches, metabolite flux analyses can be expanded to the whole-plant level by considering long-distance transport and, thus, the interaction of roots and the shoot in metabolite fluxes. However, whole-plant studies need detailed empirical and mathematical modelling that have to be validated by experimental analyses.

  9. Oregon Indigenous Farmworkers: Results of Promotor Intervention on Pesticide Knowledge and Organophosphate Metabolite Levels

    PubMed Central

    McCauley, Linda; Runkle, Jennifer D.; Samples, Julie; Williams, Bryan; Muniz, Juan F; Semple, Marie; Shadbeh, Nargess

    2013-01-01

    Objectives Examine changes in health beliefs, pesticide safety knowledge, and biomarkers of pesticide exposure in indigenous farmworker who received enhanced pesticide safety training compared to those receiving the standard training. Methods Farmworkers in Oregon were randomly assigned to either a promotores pesticide safety training program or a standard video-based training. Spot urine samples were analyzed for dialkylphosphate (DAP) urinary metabolites. Pre/post intervention questionnaires were used to measure pesticide safety knowledge, health beliefs and work practices. Results Baseline to follow-up improvements in total pesticide knowledge scores were higher in the promotor group compared to the video. Pairwise differences in mean concentrations of DAP metabolite levels showed declines from baseline to follow-up for both intervention groups. Conclusions Results showed reductions in pesticide exposure in indigenous-language speaking farmworkers who receive enhanced pesticide safety training. PMID:24064776

  10. Comment on a spurious prediction of a non-planar geometry for benzene at the MP2 level of theory

    NASA Astrophysics Data System (ADS)

    Samala, Nagaprasad Reddy; Jordan, Kenneth D.

    2017-02-01

    MP2 calculations with the full aug-cc-pVTZ basis set give a non-planar structure for benzene. Although this non-physical result can be avoided by using the smaller aug-cc-pVDZ basis set or by scaling or deleting selected functions from the aug-cc-pVTZ basis set, such changes to the basis set can result in calculated values of the frequencies of the b2g out-of-plane vibrations that are considerably underestimated. The origin of this behavior is traced to linear dependency problems with the aug-cc-pVDZ and aug-cc-pVTZ basis sets when used for benzene.

  11. Low-dose metabolism of benzene in humans: science and obfuscation

    PubMed Central

    Rappaport, Stephen M.

    2013-01-01

    Benzene is a ubiquitous air pollutant that causes human leukemia and hematotoxic effects. Although the mechanism by which benzene causes toxicity is unclear, metabolism is required. A series of articles by Kim et al. used air and biomonitoring data from workers in Tianjin, China, to investigate the dose-specific metabolism (DSM) of benzene over a wide range of air concentrations (0.03–88.9 p.p.m.). Kim et al. concluded that DSM of benzene is greatest at air concentrations <1 p.p.m. This provocative finding motivated the American Petroleum Institute to fund a study by Price et al. to reanalyze the original data. Although their formal ‘reanalysis’ reproduced Kim’s finding of enhanced DSM at sub-p.p.m. benzene concentrations, Price et al. argued that Kim’s methods were inappropriate for assigning benzene exposures to low exposed subjects (based on measurements of urinary benzene) and for adjusting background levels of metabolites (based on median values from the 60 lowest exposed subjects). Price et al. then performed uncertainty analyses under alternative approaches, which led them to conclude that ‘… the Tianjin data appear to be too uncertain to support any conclusions …’ regarding the DSM of benzene. They also argued that the apparent low-dose metabolism of benzene could be explained by ‘lung clearance.’ In addressing these criticisms, we show that the methods and arguments presented by Price et al. are scientifically unsound and that their results are unreliable. PMID:23222815

  12. Exposure of flight attendants to pyrethroid insecticides on commercial flights: urinary metabolite levels and implications.

    PubMed

    Wei, Binnian; Mohan, Krishnan R; Weisel, Clifford P

    2012-07-01

    Pyrethroid insecticides have been used for disinsection of commercial aircrafts. However, little is known about the pyrethroids exposure of flight attendants. The objective of the study was to assess pyrethroids exposure of flight attendants working on commercial aircrafts through monitoring the urinary pyrethroids metabolite levels. Eighty four urine samples were collected from 28 flight attendants, 18-65 years of age, with seventeen working on planes that were non-disinsected, and eleven working on planes that had been disinsected. Five urinary metabolites of pyrethroids were measured using gas chromatographic-mass spectrometric method: 3-phenoxybenzoic acid (3-PBA), cis-/trans-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclo-propane carboxylic acid (cis-/trans-Cl2CA), cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclo-propane-1-carboxylic acid (cis-Br2CA) and 4-fluoro-3-phenoxybenzoic acid (4F-3-PBA). Flight attendants working on disinsected planes had significantly higher urinary levels of 3-PBA, cis- and trans-Cl2CA in pre, post- and 24-h-post flight samples than those on planes which did not report having been disinsected. Urinary levels of cis-Br2CA and 4F-3-PBA did not show significant differences between the two groups. Flight attendants working on international flights connected to Australia had higher urinary levels of 3-PBA, cis- and trans-Cl2CA than those on either domestic and other international flights flying among Asia, Europe and North America. Post-disinsection duration (number of days from disinsection date to flight date) was the most significant factor affecting the urinary pyrethroid metabolites levels of 3-PBA, cis- and trans-Cl2CA of the group flying on disinsected aircraft. It was concluded that working on commercial aircraft disinsected by pyrethroids resulted in elevated body burdens of 3-PBA, cis- and trans-Cl2CA.

  13. Serum Tryptophan Metabolite Levels During Sleep in Patients With and Without Irritable Bowel Syndrome (IBS).

    PubMed

    Heitkemper, Margaret M; Han, Claire Jungyoun; Jarrett, Monica E; Gu, Haiwei; Djukovic, Danijel; Shulman, Robert J; Raftery, Daniel; Henderson, Wendy A; Cain, Kevin C

    2016-03-01

    Poor sleep and stress are more frequently reported by women with irritable bowel syndrome (IBS) than by healthy control (HC) women. The pathophysiology linking poor sleep and stress to gastrointestinal symptoms remains poorly understood. We used a metabolomic approach to determine whether tryptophan (TRP) metabolites differ between women with and without IBS and whether the levels are associated with sleep indices and serum cortisol levels. This study sample included 38 women with IBS and 21 HCs. The women were studied in a sleep laboratory for three consecutive nights. On the third night of the study, a social stressor was introduced, then blood samples were drawn every 20 min and sleep indices were measured. Metabolites were determined by targeted liquid chromatography tandem mass spectrometry in a sample collected 1 hr after the onset of sleep. The ratios of each metabolite to TRP were used for analyses. Correlations were controlled for age and oral contraceptive use. Melatonin/TRP levels were lower (p = .005) in the IBS-diarrhea group versus the IBS-constipation and HC groups, and kynurenine/TRP ratios tended to be lower (p = .067) in the total IBS and IBS-diarrhea groups compared to HCs. Associations within the HC group included melatonin/TRP with polysomnography-sleep efficiency (r = .61, p = .006) and weaker positive correlations with the other ratios for either sleep efficiency or percentage time in rapid eye movement sleep (r > .40, p = .025-.091). This study suggests that reductions in early nighttime melatonin/TRP levels may be related to altered sleep quality in IBS, particularly those with diarrhea.

  14. Metabolite profiling during cold acclimation of Lolium perenne genotypes distinct in the level of frost tolerance.

    PubMed

    Bocian, Aleksandra; Zwierzykowski, Zbigniew; Rapacz, Marcin; Koczyk, Grzegorz; Ciesiołka, Danuta; Kosmala, Arkadiusz

    2015-11-01

    Abiotic stresses, including low temperature, can significantly reduce plant yielding. The knowledge on the molecular basis of stress tolerance could help to improve its level in species of relatively high importance to agriculture. Unfortunately, the complex research performed so far mainly on model species and also, to some extent, on cereals does not fully cover the demands of other agricultural plants of temperate climate, including forage grasses. Two Lolium perenne (perennial ryegrass) genotypes with contrasting levels of frost tolerance, the high frost tolerant (HFT) and the low frost tolerant (LFT) genotypes, were selected for comparative metabolomic research. The work focused on the analysis of leaf metabolite accumulation before and after seven separate time points of cold acclimation. Gas chromatography-mass spectrometry (GC/MS) was used to identify amino acids (alanine, proline, glycine, glutamic and aspartic acid, serine, lysine and asparagine), carbohydrates (fructose, glucose, sucrose, raffinose and trehalose) and their derivatives (mannitol, sorbitol and inositol) accumulated in leaves in low temperature. The observed differences in the level of frost tolerance between the analysed genotypes could be partially due to the time point of cold acclimation at which the accumulation level of crucial metabolite started to increase. In the HFT genotype, earlier accumulation was observed for proline and asparagine. The increased amounts of alanine, glutamic and aspartic acids, and asparagine during cold acclimation could be involved in the regulation of photosynthesis intensity in L. perenne. Among the analysed carbohydrates, only raffinose revealed a significant association with the acclimation process in this species.

  15. Increased biogenic catecholamine and metabolite levels in two patients with malignant catatonia.

    PubMed

    Nisijima, Koichi

    2013-01-01

    The pathophysiology of malignant catatonia, a rare life-threatening psychiatric syndrome, has not yet been elucidated. This paper reports on two patients with malignant catatonia who showed elevated urinary or plasma catecholamine levels. Patient 1 had high catecholamine and metabolite levels in a 24-hour urine sample, and patient 2 had elevated plasma catecholamine levels. These findings indicate the presence of peripheral sympathetic nervous system hyperactivity in malignant catatonia. Symptoms of autonomic dysfunction, including tachycardia, labile blood pressure, and diaphoresis, are typical features of malignant catatonia and may be related to the increased levels of biogenic amines in these cases. Although the findings in the present study cannot entirely explain the pathophysiology of malignant catatonia, they do indicate that hyperactivity of the sympathetic nervous system may be involved in the pathology of this condition.

  16. A modified acidic approach for DNA extraction from plant species containing high levels of secondary metabolites.

    PubMed

    Cavallari, M M; Siqueira, M V B M; Val, T M; Pavanelli, J C; Monteiro, M; Grando, C; Pinheiro, J B; Zucchi, M I; Gimenes, M A

    2014-08-25

    Purified genomic DNA can be difficult to obtain from some plant species because of the presence of impurities such as polysaccharides, which are often co-extracted with DNA. In this study, we developed a fast, simple, and low-cost protocol for extracting DNA from plants containing high levels of secondary metabolites. This protocol does not require the use of volatile toxic reagents such as mercaptoethanol, chloroform, or phenol and allows the extraction of high-quality DNA from wild and cultivated tropical species.

  17. Biomarkers of susceptibility following benzene exposure: influence of genetic polymorphisms on benzene metabolism and health effects.

    PubMed

    Carbonari, Damiano; Chiarella, Pieranna; Mansi, Antonella; Pigini, Daniela; Iavicoli, Sergio; Tranfo, Giovanna

    2016-01-01

    Benzene is a ubiquitous occupational and environmental pollutant. Improved industrial hygiene allowed airborne concentrations close to the environmental context (1-1000 µg/m(3)). Conversely, new limits for benzene levels in urban air were set (5 µg/m(3)). The biomonitoring of exposure to such low benzene concentrations are performed measuring specific and sensitive biomarkers such as S-phenylmercapturic acid, trans, trans-muconic acid and urinary benzene: many studies referred high variability in the levels of these biomarkers, suggesting the involvement of polymorphic metabolic genes in the individual susceptibility to benzene toxicity. We reviewed the influence of metabolic polymorphisms on the biomarkers levels of benzene exposure and effect, in order to understand the real impact of benzene exposure on subjects with increased susceptibility.

  18. Intracellular metabolite levels shape sulfur isotope fractionation during microbial sulfate respiration

    PubMed Central

    Wing, Boswell A.; Halevy, Itay

    2014-01-01

    We present a quantitative model for sulfur isotope fractionation accompanying bacterial and archaeal dissimilatory sulfate respiration. By incorporating independently available biochemical data, the model can reproduce a large number of recent experimental fractionation measurements with only three free parameters: (i) the sulfur isotope selectivity of sulfate uptake into the cytoplasm, (ii) the ratio of reduced to oxidized electron carriers supporting the respiration pathway, and (iii) the ratio of in vitro to in vivo levels of respiratory enzyme activity. Fractionation is influenced by all steps in the dissimilatory pathway, which means that environmental sulfate and sulfide levels control sulfur isotope fractionation through the proximate influence of intracellular metabolites. Although sulfur isotope fractionation is a phenotypic trait that appears to be strain specific, we show that it converges on near-thermodynamic behavior, even at micromolar sulfate levels, as long as intracellular sulfate reduction rates are low enough (<<1 fmol H2S⋅cell−1⋅d−1). PMID:25362045

  19. Intracellular metabolite levels shape sulfur isotope fractionation during microbial sulfate respiration

    NASA Astrophysics Data System (ADS)

    Wing, Boswell A.; Halevy, Itay

    2014-12-01

    We present a quantitative model for sulfur isotope fractionation accompanying bacterial and archaeal dissimilatory sulfate respiration. By incorporating independently available biochemical data, the model can reproduce a large number of recent experimental fractionation measurements with only three free parameters: (i) the sulfur isotope selectivity of sulfate uptake into the cytoplasm, (ii) the ratio of reduced to oxidized electron carriers supporting the respiration pathway, and (iii) the ratio of in vitro to in vivo levels of respiratory enzyme activity. Fractionation is influenced by all steps in the dissimilatory pathway, which means that environmental sulfate and sulfide levels control sulfur isotope fractionation through the proximate influence of intracellular metabolites. Although sulfur isotope fractionation is a phenotypic trait that appears to be strain specific, we show that it converges on near-thermodynamic behavior, even at micromolar sulfate levels, as long as intracellular sulfate reduction rates are low enough (<<1 fmol H2Sṡcell-1ṡd-1).

  20. Intracellular metabolite levels shape sulfur isotope fractionation during microbial sulfate respiration.

    PubMed

    Wing, Boswell A; Halevy, Itay

    2014-12-23

    We present a quantitative model for sulfur isotope fractionation accompanying bacterial and archaeal dissimilatory sulfate respiration. By incorporating independently available biochemical data, the model can reproduce a large number of recent experimental fractionation measurements with only three free parameters: (i) the sulfur isotope selectivity of sulfate uptake into the cytoplasm, (ii) the ratio of reduced to oxidized electron carriers supporting the respiration pathway, and (iii) the ratio of in vitro to in vivo levels of respiratory enzyme activity. Fractionation is influenced by all steps in the dissimilatory pathway, which means that environmental sulfate and sulfide levels control sulfur isotope fractionation through the proximate influence of intracellular metabolites. Although sulfur isotope fractionation is a phenotypic trait that appears to be strain specific, we show that it converges on near-thermodynamic behavior, even at micromolar sulfate levels, as long as intracellular sulfate reduction rates are low enough (<1 fmol H2S⋅cell(-1)⋅d(-1)).

  1. Levels of seven urinary phthalate metabolites in a human reference population.

    PubMed Central

    Blount, B C; Silva, M J; Caudill, S P; Needham, L L; Pirkle, J L; Sampson, E J; Lucier, G W; Jackson, R J; Brock, J W

    2000-01-01

    Using a novel and highly selective technique, we measured monoester metabolites of seven commonly used phthalates in urine samples from a reference population of 289 adult humans. This analytical approach allowed us to directly measure the individual phthalate metabolites responsible for the animal reproductive and developmental toxicity while avoiding contamination from the ubiquitous parent compounds. The monoesters with the highest urinary levels found were monoethyl phthalate (95th percentile, 3,750 ppb, 2,610 microg/g creatinine), monobutyl phthalate (95th percentile, 294 ppb, 162 microg/g creatinine), and monobenzyl phthalate (95th percentile, 137 ppb, 92 microg/g creatinine), reflecting exposure to diethyl phthalate, dibutyl phthalate, and benzyl butyl phthalate. Women of reproductive age (20-40 years) were found to have significantly higher levels of monobutyl phthalate, a reproductive and developmental toxicant in rodents, than other age/gender groups (p < 0.005). Current scientific and regulatory attention on phthalates has focused almost exclusively on health risks from exposure to only two phthalates, di-(2-ethylhexyl) phthalate and di-isononyl phthalate. Our findings strongly suggest that health-risk assessments for phthalate exposure in humans should include diethyl, dibutyl, and benzyl butyl phthalates. PMID:11049818

  2. Reference range levels of polycyclic aromatic hydrocarbons in the US population by measurement of urinary monohydroxy metabolites

    SciTech Connect

    Grainger, James . E-mail: jag2@cdc.gov; Huang, Wenlin; Patterson, Donald G.; Turner, Wayman E.; Pirkle, James; Caudill, Samuel P.; Wang, Richard Y.; Needham, Larry L.; Sampson, Eric J.

    2006-03-15

    We developed a gas chromatography isotope-dilution high-resolution mass spectrometry (GC/Id-HRMS) method for measuring 14 polycyclic aromatic hydrocarbon (PAH) metabolites representing seven parent PAHs in 3 mL of urine at low parts-per-trillion levels. PAH levels were determined in urine samples collected in 1999 and 2000 from approximately 2400 participants in the National Health and Nutrition Examination Survey, and, for the first time, reference range values were calculated for these metabolites in the US population. Using this GC/ID-HRMS method, we found detectable concentrations for monohydroxy metabolite isomers of fluorene, phenanthrene, fluoranthene, pyrene, and chrysene, benzo[c]phenanthrene, and benz[a]anthracene. Some monohydroxy metabolite isomers of benzo[c]phenanthrene, chrysene, and benz[a]anthracene exhibited low detection frequencies that did not allow for geometric mean calculations. Our study results enabled us to establish a reference range for the targeted PAHs in the general US population.

  3. Exposure to carbon monoxide, methyl-tertiary butyl ether (MTBE), and benzene levels inside vehicles traveling on an urban area in Korea.

    PubMed

    Jo, W K; Park, K H

    1998-01-01

    This study was designed to allow systematic comparison of exposure on public (40-seater buses) and private (four passengers cars) transport modes for carbon monoxide (CO), methyl-tertiary butyl ether (MTBE), and benzene by carrying out simultaneous measurements along the same routes. There were statistically significant differences (p < 0.05) in the concentrations of all target compounds among the three microenvironments; inside autos; inside buses; and in ambient air. The target compounds were significantly correlated for all the three environments, with at least p < 0.05. The in-vehicle concentrations of MTBE and benzene were significantly higher (p < 0.0001), on the average 3.5 times higher, in the car with a carbureted engine than in the other three electronic fuel-injected cars. On the other hand, the CO concentrations were not significantly different among the four cars. The in-auto MTBE levels (48.5 micrograms/m3 as a median) measured during commutes in this study was 2-3 times higher than the New Jersey and Connecticut's results. The in-auto concentration of CO (4.8 ppm as a median) in this study was comparable with those in later studies in some American cities, but much lower than those in earlier studies in other American cities. The in-bus CO concentration was 3.6 ppm as a median. As a median, the in-auto concentration of benzene was 44.9 micrograms/m3, while the in-bus concentration 17.0 micrograms/m3. The in-auto/in-bus exposure ratios for all the target compounds was 31-40% higher than the corresponding concentration ratios, due to the higher travel speed on buses in the specified commute route as compared to the autos.

  4. Benzene in blood and phenol in urine in monitoring benzene exposure in industry

    SciTech Connect

    Braier, L.; Levy, A.; Dror, K.; Pardo, A.

    1981-01-01

    Determinations of benzene concentration in blood and of phenol in urine were made by head-space gas chromatography techniques on samples taken near the end of the work day from two groups of workers potentially exposed to low levels of benzene in the work-place atmosphere. Preliminary results suggest that benzene in blood is more reliable than phenol tests for assessing both exposure and uptake of benzene. Normal values of phenol in urine (10 mg/liter or less) were found in nearly all those cases in which benzene was detected in the blood.

  5. Prenatal urinary phthalate metabolites levels and neurodevelopment in children at two and three years of age

    PubMed Central

    Téllez-Rojo, Martha M.; Cantoral, Alejandra; Cantonwine, David E.; Schnaas, Lourdes; Peterson, Karen; Hu, Howard; Meeker, John D.

    2013-01-01

    Background Previous studies suggest that prenatal phthalate exposure affects neurodevelopment and behavior during the first years of life. Objectives To evaluate the effect of maternal urinary concentrations of phthalate metabolites during pregnancy on mental and psychomotor development in children 24-36 months of age. Methods This analysis was conducted on the first three years of life among a subsample of 136 mother-child pairs from the ELEMENT cohort studies conducted in Mexico City. Maternal urine samples collected during the third trimester of pregnancy were analyzed for 9 phthalate metabolites: Mono-ethyl phthalate (MEP), Mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP), Mono-3-carboxypropyl phthalate (MCPP), and four di-2-ethylhexyl phthalate (DEHP) metabolites [mono-2-ethylhexyl-phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP)]. Among the 136 children, 135 (99.3%) completed the study period. Child neurodevelopment was assessed using mental and psychomotor development indexes (MDI and PDI) from a Bayley (BSID II) test at 24, 30, and 36 months of age. The effect of prenatal phthalate exposure on neurodevelopment was estimated using linear regression models for longitudinal data clustered at the individual level. Results No significant associations were observed among all children combined, but differential effects by gender were found. Among girls, there was a negative association between MDI and DEHP metabolites MEHP (β = −2.11 [95% CI: −3.73, −0.49]), MEHHP (β = −1.89 [95% CI: −3.64, −0.15]), MEOHP (β = −1.80 [95% CI: −3.58, −0.03]) MECPP (β = −2.52 [95% CI: −4.44, −0.61]), and DEHP (β = −3.41 [95% CI: −5.26, −1.55]); there was no significant effect among boys. Male PDI was positively related to MBzP (β = 1.79 [95% CI: 0.14, 3.45]) and MCPP (β = 1.64 [95% CI: 0

  6. Protozoan growth rates on secondary-metabolite-producing Pseudomonas spp. correlate with high-level protozoan taxonomy.

    PubMed

    Pedersen, Annette L; Winding, Anne; Altenburger, Andreas; Ekelund, Flemming

    2011-03-01

    Different features can protect bacteria against protozoan grazing, for example large size, rapid movement, and production of secondary metabolites. Most papers dealing with these matters focus on bacteria. Here, we describe protozoan features that affect their ability to grow on secondary-metabolite-producing bacteria, and examine whether different bacterial secondary metabolites affect protozoa similarly. We investigated the growth of nine different soil protozoa on six different Pseudomonas strains, including the four secondary-metabolite-producing Pseudomonas fluorescens DR54 and CHA0, Pseudomonas chlororaphis MA342 and Pseudomonas sp. DSS73, as well as the two nonproducers P. fluorescens DSM50090(T) and P. chlororaphis ATCC43928. Secondary metabolite producers affected protozoan growth differently. In particular, bacteria with extracellular secondary metabolites seemed more inhibiting than bacteria with membrane-bound metabolites. Interestingly, protozoan response seemed to correlate with high-level protozoan taxonomy, and amoeboid taxa tolerated a broader range of Pseudomonas strains than did the non-amoeboid taxa. This stresses the importance of studying both protozoan and bacterial characteristics in order to understand bacterial defence mechanisms and potentially improve survival of bacteria introduced into the environment, for example for biocontrol purposes.

  7. No increased levels of the nicotine metabolite cotinine in smokers with schizophrenia.

    PubMed

    Bozikas, Vasilis P; Niopas, Ioannis; Kafantari, Anna; Kanaze, Feraz Imad; Gabrieli, Chrysi; Melissidis, Petros; Gamvrula, Katerina; Fokas, Kostas; Karavatos, Athanasios

    2005-01-01

    The prevalence of smoking cigarettes has repeatedly been found to be greater in schizophrenia as compared with other psychiatric patients and the general population. Patients with schizophrenia have been found to engage in heavy smoking and consumption of higher doses of nicotine, probably by deeper inhalation of cigarettes. The aim of the current study was to assess nicotine exposure through smoking by measuring urinary cotinine, the major nicotine metabolite, in a group of smokers from Greece of smokers with schizophrenia and smokers from the general population. Participants were current smokers and belonged to one of two groups: 35 patients with schizophrenia and 48 healthy controls matched in age, education, and gender. The quantitative analysis of cotinine, the major metabolite of nicotine, in urine samples was performed by a modified high performance liquid chromatography (HPLC). Patients with schizophrenia who smoke presented a significantly larger time interval between last cigarette smoked and urine sample collection, as well as a significantly higher average number of cigarettes consumed daily than normal smokers. Urinary cotinine levels of patients with schizophrenia who smoke did not significantly differ from that of normal smokers when adjusted for average number of cigarettes per day and time interval between last cigarette smoked and urine collection. These results suggest that patients with schizophrenia did not present higher nicotine exposure through smoking compared with smokers from the community. The pharmacokinetic or pharmacodynamic properties of nicotine, as well as patient medications of the patients may explain our findings.

  8. Semen quality and insulin-like factor 3: Associations with urinary and seminal levels of phthalate metabolites in adult males.

    PubMed

    Chang, Wei-Hsiang; Wu, Meng-Hsing; Pan, Hsien-An; Guo, Pao-Lin; Lee, Ching-Chang

    2017-04-01

    Certain phthalates have adverse effects on male reproductive functions in animals, and potentially affect human testicular function and spermatogenesis, but little is known about the active mechanisms. We measured the urinary and seminal phthalate metabolites and explored their associations on insulin-like factor 3 (INSL3) and semen quality. Urine, blood, and semen samples were collected from the male partners of subfertile (n = 253) and fertile (n = 37) couples in a reproductive center in southern Taiwan. INSL3, reproductive hormones, semen-quality, and 11 phthalate metabolites in urine and semen were measured. There were significant correlations in the distribution pattern of metabolites, such as the relative contribution of low or high molecular weight phthalate metabolites. The significantly monotonic trends in semen volume, sperm concentration and motility were associated with increasing quartiles of INSL3 (all p-trend < 0.001). In adjusted regression models, increases in urinary phthalate metabolites levels were adversely associated with sperm concentration (monobenzyl phthalate [MBzP], mono-2-ethylhexyl phthalate [MEHP] and MEHP%), motility (MBzP and MEHP) and INSL3 (MBzP, MEHP and MEHP%) (all p < 0.01). Higher seminal phthalate metabolite levels were associated with decreases in sperm concentration (MEHP and mono-2-ethyl-5-hydroxyhexyl phthalate), motility (mono-ethyl phthalate [MEP] and di-(2-ethylhexyl) phthalate [DEHP] metabolites), normal morphology (MEP), and INSL3 (monomethyl phthalate and MEP) (all p < 0.05). Our data suggest that INSL3 secretion, reproductive hormone balance, and sperm production and quality might be simultaneously adversely affected for individuals excreting increasing levels of phthalates metabolites (especially di-ethyl phthalate, butylbenzyl phthalate, and DEHP) in urine and semen samples.

  9. Validation of Armadillo officinalis Dumèril, 1816 (Crustacea, Isopoda, Oniscidea) as a bioindicator: in vivo study of air benzene exposure.

    PubMed

    Agodi, A; Oliveri Conti, G; Barchitta, M; Quattrocchi, A; Lombardo, B M; Montesanto, G; Messina, G; Fiore, M; Ferrante, M

    2015-04-01

    This study tests the potential for using Armadillo officinalis as a bioindicator of exposure to and activation of benzene metabolic pathways using an in vivo model. A. officinalis specimens collected in a natural reserve were divided into a control and three test groups exposed to 2.00, 5.32 or 9.09 µg/m(3) benzene for 24h. Three independent tests were performed to assess model reproducibility. Animals were dissected to obtain three pooled tissue samples per group: hepatopancreas (HEP), other organs and tissues (OOT), and exoskeleton (EXO). Muconic acid (MA), S-phenylmercapturic acid (S-PMA), two human metabolites of benzene, and changes in mtDNA copy number, a human biomarker of benzene exposure, were determined in each sample; benzene was determined only in EXO. MA was measured by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection, S-PMA by triple quadrupole mass spectrometer liquid chromatography with electro spray ionization (LC-MS-ESI-TQD), mtDNA by real-time quantitative PCR and end-point PCR, and benzene by quadrupole mass spectrometer head-space gas chromatography (HSGC-MS). MA and S-PMA levels rose both in HEP and OOT; EXO exhibited increasing benzene concentrations; and mtDNA copy number rose in HEP but not in OOT samples. Overall, our findings demonstrate that A. officinalis is a sensitive bioindicator of air benzene exposure and show for the first time its ability to reproduce human metabolic dynamics.

  10. Firefighters' exposure biomonitoring: Impact of firefighting activities on levels of urinary monohydroxyl metabolites.

    PubMed

    Oliveira, Marta; Slezakova, Klara; Alves, Maria José; Fernandes, Adília; Teixeira, João Paulo; Delerue-Matos, Cristina; Pereira, Maria do Carmo; Morais, Simone

    2016-11-01

    The concentrations of six urinary monohydroxyl metabolites (OH-PAHs) of polycyclic aromatic hydrocarbons, namely 1-hydroxynaphthalene, 1-hydroxyacenaphthene, 2-hydroxyfluorene, 1-hydroxyphenanthrene, 1-hydroxypyrene (1OHPy), and 3-hydroxybenzo[a]pyrene, were assessed in the post-shift urine of wildland firefighters involved in fire combat activities at six Portuguese fire corporations, and compared with those of non-exposed subjects. Overall, median levels of urinary individual and total OH-PAHs (ΣOH-PAHs) suggest an increased exposure to polycyclic aromatic hydrocarbons during firefighting activities with ΣOH-PAH levels in exposed firefighters 1.7-35 times higher than in non-exposed ones. Urinary 1-hydroxynaphthalene and/or 1-hydroxyacenapthene were the predominant compounds, representing 63-98% of ΣOH-PAHs, followed by 2-hydroxyfluorene (1-17%), 1-hydroxyphenanthrene (1-13%), and 1OHPy (0.3-10%). A similar profile was observed when gender discrimination was considered. Participation in fire combat activities promoted an increase of the distribution percentage of 1-hydroxynaphthalene and 1-hydroxyacenaphthene, while contributions of 1-hydroxyphenanthrene and 1OHPy decreased. The detected urinary 1OHPy concentrations (1.73×10(-2) to 0.152μmol/mol creatinine in exposed subjects versus 1.21×10(-2) to 5.44×10(-2)μmol/mol creatinine in non-exposed individuals) were lower than the benchmark level (0.5μmol/mol creatinine) proposed by the American Conference of Governmental Industrial Hygienists. This compound, considered the biomarker of exposure to PAHs, was the less abundant one from the six analyzed biomarkers. Thus the inclusion of other metabolites, in addition to 1OHPy, in future studies is suggested to better estimate firefighters' occupational exposure to PAHs. Moreover, strong to moderate Spearman correlations were observed between individual compounds and ΣOH-PAHs corroborating the prevalence of an emission source.

  11. Effects of dietary protein levels for gestating gilts on reproductive performance, blood metabolites and milk composition.

    PubMed

    Jang, Y D; Jang, S K; Kim, D H; Oh, H K; Kim, Y Y

    2014-01-01

    This experiment was conducted to evaluate the effects of dietary CP levels in gestation under equal lysine content on reproductive performance, blood metabolites and milk composition of gilts. A total of 25 gilts (F1, Yorkshire×Landrace) were allotted to 4 dietary treatments at breeding in a completely randomized design, and fed 1 of 4 experimental diets containing different CP levels (11%, 13%, 15%, or 17%) at 2.0 kg/d throughout the gestation. Body weight of gilts at 24 h postpartum tended to increase linearly (p = 0.09) as dietary CP level increased. In lactation, backfat thickness, ADFI, litter size and weaning to estrus interval (WEI) did not differ among dietary treatments. There were linear increases in litter and piglet weight at 21 d of lactation (p<0.05) and weight gain of litter (p<0.01) and piglet (p<0.05) throughout the lactation as dietary CP level increased. Plasma urea nitrogen levels of gilts in gestation and at 24 h postpartum were linearly elevated as dietary CP level increased (p<0.05). Free fatty acid (FFA) levels in plasma of gestating gilts increased as dietary CP level increased up to 15%, and then decreased with quadratic effects (15 d, p<0.01; 90 d, p<0.05), and a quadratic trend (70 d, p = 0.06). There were no differences in plasma FFA, glucose levels and milk composition in lactation. These results indicate that increasing dietary CP level under equal lysine content in gestation increases BW of gilts and litter performance but does not affect litter size and milk composition. Feeding over 13% CP diet for gestating gilts could be recommended to improve litter growth.

  12. Selenium metabolite levels in human urine after dosing selenium in different chemical forms

    SciTech Connect

    Hasunuma, Ryoichi; Tsuda, Morizo; Ogawa, Tadao; Kawanishi, Yasuhiro

    1993-11-01

    It has been well known that selenium in marine fish such as tuna and swordfish protects the toxicity of methylmercury in vivo. The protective potency might depend on the chemical forms of selenium in the meat of marine fish sebastes and sperm whale. Little has been revealed, however, on the chemical forms of selenium in the meat of these animals or the selenium metabolites in urine, because the amount of the element is very scarce. Urine is the major excretory route for selenium. The chemical forms of urinary selenium may reflect the metabolism of the element. We have developed methodology for analysis of selenium-containing components in human urine. Using this method, we have observed the time courses of excretory levels of urinary selenium components after a single dose of selenium as selenious acid, selenomethionine, trimethylselenonium ion or tuna meat. 14 refs., 6 figs., 1 tab.

  13. Levels of Urinary Metabolites of Organophosphate Flame Retardants, TDCIPP, and TPHP, in Pregnant Women in Shanghai

    PubMed Central

    Ouyang, Fengxiu; Liu, Liangpo; Wang, Xu; Wang, Xia; Li, Yi-Ju; Murtha, Amy; Shen, Heqing; Zhang, Junfeng; Zhang, Jun Jim

    2016-01-01

    Flame retardants are widely used in consumer products to reduce their flammability. Previously used flame retardants have been sequentially banned due to their environmental and human toxicity. Currently, tris(1,3-dichloropropyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) are among the most commonly used flame retardants. TDCIPP and TPHP are reproductive toxins and have carcinogenic, neurotoxic, and endocrine-disrupting properties. Although high levels of TDCIPP and TPHP have been found in drinking water, seawater, and office air in China, data regarding human exposure are lacking. In this study, we assessed the level of urinary TPHP and TDCIPP metabolites (DPHP and BDCIPP, resp.) in a cohort of pregnant women (N = 23) from Shanghai, China, using liquid chromatography-tandem mass spectrometry. DPHP were detected in 100% urine samples, while only four urine samples had detectable level of BDCIPP in this cohort (17% detected). Geometric means of DPHP and BDCIPP concentrations were 1.1 ng/mL (interquartile range [IQR]: 0.6, 1.5 ng/mL) and 1.2 ng/mL (IQR: 0.6, 2.2 ng/mL), respectively. In this small cohort, urinary DPHP and BDCIPP levels were not significantly correlated with miscarriages, neonatal birthweight, gestational diabetes, or maternal age. These data suggest that exposure to TPHP is widespread, and they demonstrate the feasibility of using urinary biomarkers to measure exposures to modern flame-retardant chemicals. PMID:28115951

  14. Plasma PGF 2 alpha metabolite levels in cats with uterine disease.

    PubMed

    Hagman, R; Karlstam, E; Persson, S; Kindahl, H

    2009-12-01

    Uterine disease induces PGF(2 alpha) increase in many animal species, which can be measured by the metabolite 15-keto-(13,14)-dihydro-PGF(2 alpha) (PGFM). Plasma PGFM levels are associated with severity of the uterine disease and presence of systemic inflammatory response syndrome (SIRS) in dogs. The objectives in this study were to investigate PGFM levels, presence of SIRS, and clinical and laboratory parameters in female cats as possible indicators for severity of uterine disease. In total, 7 female cats with pyometra, 2 with mucometra, 7 with cystic endometrial hyperplasia (CEH), and 14 healthy control cats were included. Physical examination, ovariohysterectomy, and histopathology were performed, laboratory parameters were analyzed, and PGFM levels were analyzed by radioimmunoassay. Analysis of variance, Fisher's exact test, Student's t-test and Pearson's product moment correlation coefficient were used for data analysis. In cats with pyometra, mean PGFM levels were increased (21.1 nmol L(-1)) but were decreased in cats with CEH (0.4 nmol L(-1)) compared with control cats (0.6 nmol L(-1)). In cats with mucometra, the mean PGFM level was 8.8 nmol L(-1). Systemic inflammatory response syndrome was present in 6 (85%) cats with pyometra, 1 cat with mucometra, and 1 cat with CEH. Hospitalization length was negatively correlated with albumin and positively correlated with total white blood cell count (WBC), neutrophils, band neutrophils (BN), percentage BN (PBN), and monocytes. Pyometra and mucometra were associated with increased plasma levels of PGFM. The parameters albumin, WBC, neutrophils, BN, PBN, and monocytes may be useful to determine morbidity as measured by hospitalization length.

  15. Oxidative sulfonation of benzene

    SciTech Connect

    Kashnikova, L.V.; Golodov, V.A.; Vozdvizhenskii, V.F.; Levintova, T.D.

    1988-02-10

    The oxidative sulfonation of benzene with sulfur dioxide was studied in the presence of copper(II) chloride. The relation of the reaction rate to the amount of sulfur dioxide absorbed and the relation of the initial reaction rate to the benzene concentration is shown. With rise in benzene concentration, the initial reaction rate rose linearly and the amount of SO/sub 2/ absorbed remained practically constant. A mechanism was proposed that included the stage of the successive formation of an intermediate containing Cu(II) with benzene and sulfur dioxide and its subsequent redox breakdown to the final products as a result of attack by a Cu(II) benzene complex.

  16. Species-level assessment of secondary metabolite diversity among Hamigera species and a taxonomic note on the genus

    PubMed Central

    Igarashi, Yasuhiro; Hanafusa, Tomoaki; Gohda, Fumiya; Peterson, Stephen; Bills, Gerald

    2014-01-01

    Secondary metabolite phenotypes in nine species of the Hamigera clade were analysed to assess their correlations to a multi-gene species-level phylogeny. High-pressure-liquid-chromatography-based chemical analysis revealed three distinctive patterns of secondary metabolite production: (1) the nine species could be divided into two groups on the basis of production of the sesquiterpene tricinonoic acid; (2) the tricinonoic acid-producing group produced two cyclic peptides avellanins A and B; (3) the tricinonoic acid-non-producing group could be further divided into two groups according to the production of avellanins A and B. The chemical phenotype was consistent with the phylogeny of the species, although metabolite patterns were not diagnostic at the species level. In addition, the taxonomy of the Hamigera clade was updated with the new combination Hamigera ingelheimensis proposed for Merimbla ingelheimensis, so that all species in the clade are now in the same genus. PMID:25379334

  17. Benzene formation in electronic cigarettes

    PubMed Central

    Pankow, James F.; Kim, Kilsun; McWhirter, Kevin J.; Luo, Wentai; Escobedo, Jorge O.; Strongin, Robert M.; Duell, Anna K.; Peyton, David H.

    2017-01-01

    Background/Objective The heating of the fluids used in electronic cigarettes (“e-cigarettes”) used to create “vaping” aerosols is capable of causing a wide range of degradation reaction products. We investigated formation of benzene (an important human carcinogen) from e-cigarette fluids containing propylene glycol (PG), glycerol (GL), benzoic acid, the flavor chemical benzaldehyde, and nicotine. Methods/Main results Three e-cigarette devices were used: the JUULTM “pod” system (provides no user accessible settings other than flavor cartridge choice), and two refill tank systems that allowed a range of user accessible power settings. Benzene in the e-cigarette aerosols was determined by gas chromatography/mass spectrometry. Benzene formation was ND (not detected) in the JUUL system. In the two tank systems benzene was found to form from propylene glycol (PG) and glycerol (GL), and from the additives benzoic acid and benzaldehyde, especially at high power settings. With 50:50 PG+GL, for tank device 1 at 6W and 13W, the formed benzene concentrations were 1.9 and 750 μg/m3. For tank device 2, at 6W and 25W, the formed concentrations were ND and 1.8 μg/m3. With benzoic acid and benzaldehyde at ~10 mg/mL, for tank device 1, values at 13W were as high as 5000 μg/m3. For tank device 2 at 25W, all values were ≤~100 μg/m3. These values may be compared with what can be expected in a conventional (tobacco) cigarette, namely 200,000 μg/m3. Thus, the risks from benzene will be lower from e-cigarettes than from conventional cigarettes. However, ambient benzene air concentrations in the U.S. have typically been 1 μg/m3, so that benzene has been named the largest single known cancer-risk air toxic in the U.S. For non-smokers, chronically repeated exposure to benzene from e-cigarettes at levels such as 100 or higher μg/m3 will not be of negligible risk. PMID:28273096

  18. p-Benzoquinone, a reactive metabolite of benzene, prevents the processing of pre-interleukins-1{alpha} and -1{beta} to active cytokines by inhibition of the processing enzymes, calpain, and interleukin-1{beta} converting enzyme

    SciTech Connect

    Kalf, G.F.; Renz, J.F.; Niculescu, R.

    1996-12-01

    Chronic exposure of humans to benzene affects hematopoietic stem and progenitor cells and leads to aplastic anemia. The stromal macrophage, a target of benzene toxicity, secretes interieukin-1 (IL-1), which induces the stromal fibroblast to synthesize hematopoietic colony-stimulating factors. In a mouse model, benzene causes an acute marrow hypocellularity that can be prevented by the concomitant administration of IL-1{alpha}. The ability of benzene to interfere with the production and secretion of IL-1{alpha} was tested. Stromal macrophages from benzene-treated mice were capable of the transcription of the IL-1{alpha} gene and the translation of the message but showed an inability to process the 34-kDa pre-IL-1{alpha} precursor to the 17-kDa biologically active cytokine. Treatment of normal murine stromal macrophages in culture with hydroquinone (HQ) also showed an inhibition in processing of pre-IL-1{alpha}. Hydroquinone is oxidized by a peroxidase-mediated reaction in the stromal macrophage to p-benzoquinone, which interacts with the sulfhydryl (SH) groups of proteins and was shown to completely inhibit the activity of calpain, the SH-dependent protease that cleaves pre-IL-1{alpha}. In a similar manner, HQ, via peroxidase oxidation to p-benzoquinone, was capable of preventing the IL-1{beta} autocrine stimulation of growth of human B1 myeloid tumor cells by preventing the processing of pre-IL-1{beta} to mature cytokine. Benzoquinone was also shown to completely inhibit the ability of the SH-dependent IL-1{beta} converting enzyme. Thus benzene-induced bone marrow hypocellularity may result from apoptosis of hematopoietic progenitor cells brought about by lack of essential cylokines and deficient IL-1{alpha} production subsequent to the inhibition of calpain by p-benzoquinone and the prevention of pre-IL-1 processing. 34 refs., 8 figs.

  19. Systems biology of human benzene exposure

    PubMed Central

    Zhang, Luoping; McHale, Cliona M.; Rothman, Nathaniel; Li, Guilan; Ji, Zhiying; Vermeulen, Roel; Hubbard, Alan E.; Ren, Xuefeng; Shen, Min; Rappaport, Stephen M.; North, Matthew; Skibola, Christine F.; Yin, Songnian; Vulpe, Christopher; Chanock, Stephen J.; Smith, Martyn T.; Lan, Qing

    2010-01-01

    Toxicogenomic studies, including genome-wide analyses of susceptibility genes (genomics), gene expression (transcriptomics), protein expression (proteomics), and epigenetic modifications (epigenomics), of human populations exposed to benzene are crucial to understanding gene-environment interactions, providing the ability to develop biomarkers of exposure, early effect and susceptibility. Comprehensive analysis of these toxicogenomic and epigenomic profiles by bioinformatics in the context of phenotypic endpoints, comprises systems biology, which has the potential to comprehensively define the mechanisms by which benzene causes leukemia. We have applied this approach to a molecular epidemiology study of workers exposed to benzene. Hematotoxicity, a significant decrease in almost all blood cell counts, was identified as a phenotypic effect of benzene that occurred even below 1ppm benzene exposure. We found a significant decrease in the formation of progenitor colonies arising from bone marrow stem cells with increasing benzene exposure, showing that progenitor cells are more sensitive to the effects of benzene than mature blood cells, likely leading to the observed hematotoxicity. Analysis of transcriptomics by microarray in the peripheral blood mononuclear cells of exposed workers, identified genes and pathways (apoptosis, immune response, and inflammatory response) altered at high (>10ppm) and low (<1ppm) benzene levels. Serum proteomics by SELDI-TOF-MS revealed proteins consistently down-regulated in exposed workers. Preliminary epigenomics data showed effects of benzene on the DNA methylation of specific genes. Genomic screens for candidate genes involved in susceptibility to benzene toxicity are being undertaken in yeast, with subsequent confirmation by RNAi in human cells, to expand upon the findings from candidate gene analyses. Data on these and future biomarkers will be used to populate a large toxicogenomics database, to which we will apply bioinformatic

  20. Urinary testosterone-metabolite levels and dominance rank in male and female bonobos (Pan paniscus).

    PubMed

    Sannen, Adinda; Van Elsacker, Linda; Heistermann, Michael; Eens, Marcel

    2004-04-01

    The correlation between testosterone (T) and dominance rank may vary among species, and is expected to become stronger as the importance of aggressive competition for rank increases. However, it may also vary among social situations within a species, showing a stronger correlation during socially unstable periods. Knowledge on this topic in great apes, especially in females, is scant. This study presents the first data on the relationship between T and dominance rank in both sexes of the bonobo ( Pan paniscus). For each period (four socially unstable and two stable ones), linear rank orders were determined and subsequently correlated with the accompanying mean urinary T-metabolite concentrations (measured as immunoreactive 5alpha-androstan-17alpha-ol-3-one). No correlation between these two variables was found for either sex among individuals during socially unstable or stable periods. Also, within an individual over the six periods, no relationship of T with rank could be demonstrated. These results suggest that either the outcomes of aggressions have no influence on T levels, or such clear outcomes appear insufficiently frequent to affect T levels over longer periods. Even during the unstable periods, the rate of aggressions was not higher than during stable periods, suggesting that frequencies of aggression have little effect on rank. Further analyses indeed demonstrated no correlation between frequencies of overall aggressions or any type of aggressive behavior separately, or rank. Perhaps factors other than the frequency of displayed aggressions alone have a marked influence on a bonobo's rank, for example, coalition partners. Overall, in bonobos, T apparently does not form a physiological reflection of social status.

  1. Benzene toxicity of the occurrence of benzene in the ambient air of the Houston area

    SciTech Connect

    Lin, Y.C.

    1980-01-01

    This study was conducted by either literature review or actual field survey. Results are summarized as follows: (1) long-term occupational exposure of workers to benzene vapor at levels of 3 to 7 ppM, 2 to 3 ppM and 1.6 ppM may result in a decreased level of leucocyte alkaline phosphates, an increased incidence of chromosome aberrations and an increased level of ALA in erythrocytes, respectively; (2) benzene is capable of causing fetotoxic effects in animals at levels as low as 10 ppM by volume; (3) exposure of animals to or less than 1 ppM benzene vapor may result in leucopenia, an inverse ratio of muscle antagonist chronaxy and a decreased level of ascorbic acid in fetus's and mother's liver as well as whole embryo; (4) benzene is causally associated with the increased incidence of pancytopenia, including unicytopenia, bicytopenia and aplastic anemia, and chromosome aberrations in occupational exposure population, and at best benzene must also be considered as a leukemogen; (5) since it can be emitted into the atmosphere from both man-made and natural sources, benzene in some concentrations is presented everywhere in the various compartments of the environment; (6) the findings of the emission of benzene from certain natural sources indicate that reducing benzene to a zero-level of exposure is theoretically impossible; (7) the annual average of benzene concentration detected in the Houston ambient air is 2.50 ppB, which is about 2.4 times higher than the nation-wide annual average exposure level and may have some health implications to the general public; and (8) in the Houston area, stationary sources are more important than mobile sources in contributing to benzene in the ambient air.

  2. Fecal cortisol metabolite levels in free-ranging North American red squirrels: Assay validation and the effects of reproductive condition.

    PubMed

    Dantzer, Ben; McAdam, Andrew G; Palme, Rupert; Fletcher, Quinn E; Boutin, Stan; Humphries, Murray M; Boonstra, Rudy

    2010-06-01

    Patterns in stress hormone (glucocorticoid: GC) levels and their relationship to reproductive condition in natural populations are rarely investigated. In this study, we (1) validate an enzyme-immunoassay to measure fecal cortisol metabolite (FCM) levels in North American red squirrels (Tamiasciurus hudsonicus), and (2) examine relationships between FCM levels and reproductive condition in a free-ranging red squirrel population. Injected radiolabeled cortisol was entirely metabolized and excreted in both the urine (mean+/-SE; 70.3+/-0.02%) and feces (29.7+/-0.02%), with a lag time to peak excretion in the feces of 10.9+/-2.3h. Our antibody reacted with several cortisol metabolites, and an adrenocorticotropic injection significantly increased FCM levels above baseline levels at 8h post-injection. Relative to baseline levels, manipulation by handling also tended to increase FCM levels at 8h post-manipulation, but this difference was not significant. FCM levels did not differ significantly between samples frozen immediately and 5h after collection. Reproductive condition significantly affected FCM levels in free-ranging females (pregnant>lactating>post-lactating>non-breeding) but not males (scrotal testes vs. abdominal testes). Among females with known parturition dates, FCM levels increased during gestation, peaked at parturition, and declined during lactation. The difference between pregnant and lactating females was therefore dependent upon when the fecal samples were obtained during these periods, suggesting caution in categorizing reproductive stages. This study demonstrates the utility of fecal hormone metabolite assays to document patterns of glucocorticoid levels in free-ranging animals.

  3. Behavior of polychlorinated benzenes, PCDD/Fs and dioxin-like PCBs during incineration of solid waste contaminated with mg/kg levels of hexachlorobenzene.

    PubMed

    Watanabe, Mafumi; Noma, Yukio

    2010-01-01

    Hexachlorobenzene (HCB), one of the well-known Persistent Organic Pollutants (POPs), is present in some pigments and these raw materials with maximum level of several thousand of mg/kg. Considering that these pigments have been used in long-life products, such as car parts, construction materials and electrical and electronic equipments, the articles containing HCB at a concentration of several hundred mg/kg still have to undergo waste management. In this study, we performed a combustion experiment involving solid waste containing 300 mg/kg of HCB as the input material using a pilot-scale incinerator to determine the destruction of HCB and its influence on the behavior of other polychlorinated benzenes (CBzs) and unintentionally produced POPs, such as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs). HCB at a concentration of 300 mg/kg in the input material was destroyed mainly in the primary combustion zone. Overall the destruction efficiency of HCB was > 99.9985%. The input concentration of HCB did not significantly affect the formation and destruction or the final emissions of other CBzs, PCDD/Fs and dl-PCBs. These results indicate that incineration, when operated and structured to minimize emissions of dioxin-related compounds, is considered to be one of the Best Available Technologies for the appropriate treatment of waste containing HCB with a concentration in the order of mg/kg.

  4. Levels of compounds and metabolites in wheat ears and grains in organic and conventional agriculture.

    PubMed

    Zörb, Christian; Niehaus, Karsten; Barsch, Aiko; Betsche, Thomas; Langenkämper, Georg

    2009-10-28

    In this work, wheat from two farming systems, organic and conventional, was analyzed. Organic agriculture is one of the fastest growing sectors in the food industry of Europe and the United States. It is an open question, whether organic or conventional agricultural management influences variables such as metabolism, nutrient supply, seed loading and metabolite composition of wheat. Our aim was to detect if organic or conventional farming systems would affect concentrations of metabolites and substances in developing ears and in corresponding matured grain. Therefore, broadband metabolite profiles together with lipids, cations, starch and protein concentrations of wheat ears in the last phase of grain development and of matured grain from organic and conventional agriculture of a rigorously controlled field trial with two organic and two conventional systems were examined. It appears that seed metabolism and supply of developing ears differ in organic and conventional agriculture. However, the differences in 62 metabolite concentrations become marginal or disappear in the matured grains, indicating an adjustment of nutrients in the matured grain from organic agriculture. This result suggests a high degree of homeostasis in the final seed set independent of the growing regime.

  5. Impacts of rising tropospheric ozone on photosynthesis and metabolite levels on field grown soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The response of leaf photosynthesis and metabolite profiles to ozone (O3) exposure ranging from 37 to 116 nL L-1 was investigated in two soybean cultivars Dwight and IA3010 in the field under fully open-air conditions. Leaf photosynthesis, total non-structural carbohydrates (TNC) and total free amin...

  6. Dose-, route-, and sex-dependent urinary excretion of phenol metabolites in B6C3F, mice

    SciTech Connect

    Kenyon, E.M.; Seeley, M.E.; Janszen, D.; Medinsky, M.A.

    1995-07-01

    Phenol is the major oxidized metabolite of benzene, a known human leukemogen and ubiquitous environmental pollutant. Unlike benzene, phenol does not induce tumors in mice following oral exposure; benzene also exhibits sex-related differences in genotoxicity to bone marrow cells that are not observed following phenol administration. We studied the urinary excretion of phenol metabolites in mice as a means to further investigate the metabolic basis for differences in benzene- and phenol-induced toxicity. Male and female B6C3F, mice (n = 3/group) were exposed to 15, 40, 100, or 225 {mu}mol [{sup 14}C]phenol/kg by iv tail vein injection (6 {mu}Ci/mouse). First-pass intestinal metabolism of phenol was evaluated by comparison of urinary excretion of phenol metabolites following iv administration with additional groups of male mice that received the same dose levels by oral gavage. Mice were placed in glass metabolism cages, and urine was collected over dry ice for 48 h. Urinary metabolites were separated by high-pressure liquid chromatography (HPLC) and quantified by liquid scintillation spectrometry. Urinary excretion of conjugated metabolites of phenol was dose-dependent in both male and female mice administered phenol by iv injection or gavage. The major urinary metabolites of phenol were phenol sulfate (PS), phenol glucuronide (PG), and hydroquinone glucoronide (HQG). Sulfation was the dominant pathway at all dose levels, but decreased as a percent of the excreted dose with a concomitant increase in glucorodination as the dose level increased. Male mice consistently excreted a higher proportion of phenol as the oxidized conjugated metabolite, HQG, compared to female mice, suggesting that male mice oxidize phenol to hydroquinone more rapidly than female mice. 31 refs., 6 figs., 2 tabs.

  7. Activity levels of tamoxifen metabolites at the estrogen receptor and the impact of genetic polymorphisms of phase I and II enzymes on their concentration levels in plasma.

    PubMed

    Mürdter, T E; Schroth, W; Bacchus-Gerybadze, L; Winter, S; Heinkele, G; Simon, W; Fasching, P A; Fehm, T; Eichelbaum, M; Schwab, M; Brauch, H

    2011-05-01

    The therapeutic effect of tamoxifen depends on active metabolites, e.g., cytochrome P450 2D6 (CYP2D6) mediated formation of endoxifen. To test for additional relationships, 236 breast cancer patients were genotyped for CYP2D6, CYP2C9, CYP2B6, CYP2C19, CYP3A5, UGT1A4, UGT2B7, and UGT2B15; also, plasma concentrations of tamoxifen and 22 of its metabolites, including the (E)-, (Z)-, 3-, and 4'-hydroxymetabolites as well as their glucuronides, were quantified using liquid chromatography-tandem mass spectrometry (MS). The activity levels of the metabolites were measured using an estrogen response element reporter assay; the strongest estrogen receptor inhibition was found for (Z)-endoxifen and (Z)-4-hydroxytamoxifen (inhibitory concentration 50 (IC50) 3 and 7 nmol/l, respectively). CYP2D6 genotypes explained 39 and 9% of the variability of steady-state concentrations of (Z)-endoxifen and (Z)-4-hydroxytamoxifen, respectively. Among the poor metabolizers, 93% had (Z)-endoxifen levels below IC90 values, underscoring the role of CYP2D6 deficiency in compromised tamoxifen bioactivation. For other enzymes tested, carriers of reduced-function CYP2C9 (*2, *3) alleles had lower plasma concentrations of active metabolites (P < 0.004), pointing to the role of additional pathways.

  8. In vitro cytotoxicity of BTEX metabolites in HeLa cells.

    PubMed

    Shen, Y

    1998-04-01

    Fuel leakage from underground storage tanks is a major source of groundwater contamination. Although the toxicity of regulated compounds such as benzene, toluene, ethylbenzene, and xylene (BTEX) are well recognized, the cytotoxicity of their metabolites has not been studied extensively. In this study, Hela cells, propagated at 37 degrees C in an atmosphere of 5% CO2-95% air, served as a target for evaluation of cytotoxicity of BTEX metabolites 3-methylcatechol, 4-methylcatechol, 4-hydroxybenzoic acid, and 4-hydroxy-3-methoxybenzoic acid. The cells were exposed to different concentrations of the metabolites, which subsequently showed inhibition of cell growth and produced dose-related decreases in cell viability and cell protein content. The BTEX metabolites affected the levels of the polyamines spermidine, spermine, and putrescine, which are known to be important in cell proliferation. The cytotoxic effects for these BTEX metabolites to Hela cells were 3-methylcatechol > 4-methylcatechol > 4-hydroxy-3-methoxybenzoic acid > 4-hydroxybenzoic acid.

  9. [Exposure to benzene of service station employees and composition of benzene].

    PubMed

    Lagorio, S; Fuselli, S; Iavarone, I; Vanacore, N; Carere, A

    1994-01-01

    The International Agency for Research on Cancer (IARC) classifies gasoline vapours and exhaust fumes from gasoline fueled automobiles as potential human carcinogens. Data on the chemical composition of gasoline marketed in Italy and especially on the concentration of benzene, are rather poor. Within the framework of an investigation aimed at assessing the mean annual level of exposure to aromatic hydrocarbons among gasoline pump attendants, made on a sample of attendants in Rome between December 1991 and November 1992, samples of gasoline were also collected so as to determine the benzene content of the gasoline over the investigation period, assess the variability of benzene concentration in the various gasolines and according to the season of the year, and take account of gasoline composition in analysing the factors determining individual exposure levels of pump attendants. Benzene exposure was measured via gas chromatography of air samples obtained with personal pumps in the breathing zone. The mean benzene exposure level (8 h TWA) of the 27 subjects under study was 1.73 mg/m3 (SD = 5.53). The benzene concentration in the samples of gasoline, which were collected on the same day as personal exposure monitoring was performed, was measured by means of high resolution gas chromatography (hr-GC). Mean benzene levels of 25.03 g/l (SD = 3.47), equivalent to 2.86% by volume, were measured in 24 samples of alkylated gasoline, and mean levels of 23.18 g/l (SD = 3.93), equivalent to 2.65% v/v, were measured in 10 samples of lead-free gasoline. Statistically significant associations were found between individual exposure to benzene and the quantity of gasoline pumped (r = 0.69) and the quantity of benzene present in the gasoline sold on the day monitoring was performed (r = 0.70). Using regression analysis, the estimated increase in the level of personal benzene exposure was 0.01 mg/m3 for every increase of 100 g in the benzene content of the total amount of gasoline sold

  10. Differential metabolite levels in response to spawning-induced inappetence in Atlantic salmon Salmo salar.

    PubMed

    Cipriano, Rocco C; Smith, McKenzie L; Vermeersch, Kathleen A; Dove, Alistair D M; Styczynski, Mark P

    2015-03-01

    Atlantic salmon Salmo salar undergo months-long inappetence during spawning, but it is not known whether this inappetence is a pathological state or one for which the fish are adapted. Recent work has shown that inappetent whale sharks can exhibit circulating metabolite profiles similar to ketosis known to occur in humans during starvation. In this work, metabolite profiling was used to explore differences in analyte profiles between a cohort of inappetent spawning run Atlantic salmon and captively reared animals that were fed up to and through the time of sampling. The two classes of animals were easily distinguished by their metabolite profiles. The sea-run fish had elevated ɷ-9 fatty acids relative to the domestic feeding animals, while other fatty acid concentrations were reduced. Sugar alcohols were generally elevated in inappetent animals, suggesting potentially novel metabolic responses or pathways in fish that feature these compounds. Compounds expected to indicate a pathological catabolic state were not more abundant in the sea-run fish, suggesting that the animals, while inappetent, were not stressed in an unnatural way. These findings demonstrate the power of discovery-based metabolomics for exploring biochemistry in poorly understood animal models.

  11. Dexamethasone decreases plasma levels of the prochiral fenbendazole and its chiral and achiral metabolites in sheep.

    PubMed

    Sánchez, S; Small, J; Jones, D G; McKellar, Q A

    2003-07-01

    1. The effect of co-administration of either short- or long-acting formulations of DXM on hepatic function and the plasma pharmacokinetic behaviour of prochiral fenbendazole (FBZ) and its metabolites was evaluated in sheep. 2. Neither DXM treatment markedly affected any of the biochemical markers of hepatic function tested. In contrast, both formulations significantly modified the plasma pharmacokinetic behaviour of FBZ and its metabolites. 3. Plasma FBZ concentrations and the associated area under the time-concentration curves were significantly lower, although the plasma detection period was longer (72 versus 48 h) in the DXM pretreated animals compared with those given FBZ alone. 4. DXM also appeared to alter the pattern of FBZ absorption, possibly through effects on abomasal pH. The shape of the plasma concentration-time curves for oxfendazole (OFZ) and fenbendazole sulphone (FBZSO(2)) were similar to FBZ, raising the possibility that DXM treatment may have altered the liver biotransformation of the parent drug. 5. The concentrations of the (+) chiral metabolite of OFZ were significantly lower in DXM pretreated animals compared with those given FBZ alone. The trend was similar for the (-) antipode, although the differences between DXM pretreated and non-pretreated animals were not statistically significant.

  12. Accumulation of secondary metabolites in healthy and diseased barley, grown under future climate levels of CO2, ozone and temperature.

    PubMed

    Mikkelsen, B L; Olsen, C E; Lyngkjær, M F

    2015-10-01

    Plants produce secondary metabolites promoting adaptation to changes in the environment and challenges by pathogenic microorganisms. A future climate with increased temperature and CO2 and ozone levels will likely alter the chemical composition of plants and thereby plant-pathogen interactions. To investigate this, barley was grown at elevated CO2, temperature and ozone levels as single factors or in combination resembling future climatic conditions. Increased basal resistance to the powdery mildew fungus was observed when barley was grown under elevated CO2, temperature and ozone as single factors. However, this effect was neutralized in the combination treatments. Twenty-five secondary metabolites were putatively identified in healthy and diseased barley leaves, including phenylpropanoids, phenolamides and hydroxynitrile glucosides. Accumulation of the compounds was affected by the climatic growth conditions. Especially elevated temperature, but also ozone, showed a strong impact on accumulation of many compounds, suggesting that these metabolites play a role in adaptation to unfavorable growth conditions. Many compounds were found to increase in powdery mildew diseased leaves, in correlation with a strong and specific influence of the climatic growth conditions. The observed disease phenotypes could not be explained by accumulation of single compounds. However, decreased accumulation of the powdery mildew associated defense compound p-coumaroylhydroxyagmatine could be implicated in the increased disease susceptibility observed when barley was grown under combination of elevated CO2, temperature and ozone. The accumulation pattern of the compounds in both healthy and diseased leaves from barley grown in the combination treatments could not be deduced from the individual single factor treatments. This highlights the complex role and regulation of secondary metabolites in plants' adaptation to unfavorable growth conditions.

  13. Benzene exposure is associated with epigenetic changes (Review).

    PubMed

    Fenga, Concettina; Gangemi, Silvia; Costa, Chiara

    2016-04-01

    Benzene is a volatile aromatic hydrocarbon solvent and is known as one of the predominant air pollutants in the environment. Chronic exposure to benzene is known to cause aplastic anemia and increased risk of acute myelogenous leukemia in humans. Although the mechanisms by which benzene causes toxicity remain to be fully elucidated, it is widely accepted that its metabolism is crucial to its toxicity, with involvement of one or more reactive metabolites. Novel approaches aimed at evaluating different mechanisms by which benzene can impact on human health by altering gene regulation have been developed. Among these novel approaches, epigenetics appears to be promising. The present review article summarizes the most important findings, reported from the literature, on epigenetic modifications correlated to benzene exposure. A computerized search in PubMed was performed in November 2014, using search terms, including 'benzene', 'epigenetic', 'histone modifications', 'DNA methylation' and 'microRNA'. Epidemiological and experimental studies have demonstrated the potential epigenetic effects of benzene exposure. Several of the epigenomic changes observed in response to environmental exposures may be mechanistically associated with susceptibility to diseases. However, further elucidation of the mechanisms by which benzene alters gene expression may improve prediction of the toxic potential of novel compounds introduced into the environment, and allow for more targeted and appropriate disease prevention strategies.

  14. PTEN methylation involved in benzene-induced hematotoxicity.

    PubMed

    Yang, Jing; Zuo, Xin; Bai, Wenlin; Niu, Piye; Tian, Lin; Gao, Ai

    2014-06-01

    It is well known that benzene is a hematotoxic carcinogen. PTEN promoter methylation is a representative example of transcriptional silencing of tumor suppressor genes. However, the effect of PTEN methylation on benzene-induced hematotoxicity has not yet been elucidated. In this study, the animal model of benzene hematotoxicity was successfully established. WBC significantly decreased in experimental groups (P < 0.01). Compared with the control group, the weight of rats increased slowly and even declined with increasing doses of benzene in the benzene-treated groups. An increase in the level of PTEN methylation was observed in the low dose group, and PTEN methylation level increased significantly in a dose-dependent manner. However, it was interesting that PTEN mRNA expression increased in the low dose group, but declined with increasing doses of benzene. The decrease of tumor suppressor function caused by PTEN methylation may be an important mechanism of benzene hematotoxicity. Furthermore, lymphoblast cell line F32 was incubated by benzene and then treated with 5-aza and TSA, alone or in combination. A dramatic decrease in the PTEN mRNA expression and a significant increase of PTEN methylation level in benzene-treated cells were also shown. PTEN mRNA expression was up regulated and PTEN methylation level was reduced by the epigenetic inhibitors, 5-aza and TSA. In conclusion, PTEN methylation is involved in benzene-induced hematotoxicity through suppressing PTEN mRNA expression.

  15. Measurement of children's exposure to pesticides: analysis of urinary metabolite levels in a probability-based sample.

    PubMed Central

    Adgate, J L; Barr, D B; Clayton, C A; Eberly, L E; Freeman, N C; Lioy, P J; Needham, L L; Pellizzari, E D; Quackenboss, J J; Roy, A; Sexton, K

    2001-01-01

    The Minnesota Children's Pesticide Exposure Study is a probability-based sample of 102 children 3-13 years old who were monitored for commonly used pesticides. During the summer of 1997, first-morning-void urine samples (1-3 per child) were obtained for 88% of study children and analyzed for metabolites of insecticides and herbicides: carbamates and related compounds (1-NAP), atrazine (AM), malathion (MDA), and chlorpyrifos and related compounds (TCPy). TCPy was present in 93% of the samples, whereas 1-NAP, MDA, and AM were detected in 45%, 37%, and 2% of samples, respectively. Measured intrachild means ranged from 1.4 microg/L for MDA to 9.2 microg/L for TCPy, and there was considerable intrachild variability. For children providing three urine samples, geometric mean TCPy levels were greater than the detection limit in 98% of the samples, and nearly half the children had geometric mean 1-NAP and MDA levels greater than the detection limit. Interchild variability was significantly greater than intrachild variability for 1-NAP (p = 0.0037) and TCPy (p < 0.0001). The four metabolites measured were not correlated within urine samples, and children's metabolite levels did not vary systematically by sex, age, race, household income, or putative household pesticide use. On a log scale, mean TCPy levels were significantly higher in urban than in nonurban children (7.2 vs. 4.7 microg/L; p = 0.036). Weighted population mean concentrations were 3.9 [standard error (SE) = 0.7; 95% confidence interval (CI), 2.5, 5.3] microg/L for 1-NAP, 1.7 (SE = 0.3; 95% CI, 1.1, 2.3) microg/L for MDA, and 9.6 (SE = 0.9; 95% CI, 7.8, 11) microg/L for TCPy. The weighted population results estimate the overall mean and variability of metabolite levels for more than 84,000 children in the census tracts sampled. Levels of 1-NAP were lower than reported adult reference range concentrations, whereas TCPy concentrations were substantially higher. Concentrations of MDA were detected more frequently

  16. Metabolite profiling reveals novel multi-level cold responses in the diploid model Fragaria vesca (woodland strawberry).

    PubMed

    Rohloff, Jens; Kopka, Joachim; Erban, Alexander; Winge, Per; Wilson, Robert C; Bones, Atle M; Davik, Jahn; Randall, Stephen K; Alsheikh, Muath K

    2012-05-01

    Winter freezing damage is a crucial factor in overwintering crops such as the octoploid strawberry (Fragaria × ananassa Duch.) when grown in a perennial cultivation system. Our study aimed at assessing metabolic processes and regulatory mechanisms in the close-related diploid model woodland strawberry (Fragaria vescaL.) during a 10-days cold acclimation experiment. Based on gas chromatography/time-of-flight-mass spectrometry (GC/TOF-MS) metabolite profiling of three F. vesca genotypes, clear distinctions could be made between leaves and non-photosynthesizing roots, underscoring the evolvement of organ-dependent cold acclimation strategies. Carbohydrate and amino acid metabolism, photosynthetic acclimation, and antioxidant and detoxification systems (ascorbate pathway) were strongly affected. Metabolic changes in F. vesca included the strong modulation of central metabolism, and induction of osmotically-active sugars (fructose, glucose), amino acids (aspartic acid), and amines (putrescine). In contrast, a distinct impact on the amino acid proline, known to be cold-induced in other plant systems, was conspicuously absent. Levels of galactinol and raffinose, key metabolites of the cold-inducible raffinose pathway, were drastically enhanced in both leaves and roots throughout the cold acclimation period of 10 days. Furthermore, initial freezing tests and multifaceted GC/TOF-MS data processing (Venn diagrams, independent component analysis, hierarchical clustering) showed that changes in metabolite pools of cold-acclimated F. vesca were clearly influenced by genotype.

  17. Benzene Monitor System report

    SciTech Connect

    Livingston, R.R.

    1992-10-12

    Two systems for monitoring benzene in aqueous streams have been designed and assembled by the Savannah River Technology Center, Analytical Development Section (ADS). These systems were used at TNX to support sampling studies of the full-scale {open_quotes}SRAT/SME/PR{close_quotes} and to provide real-time measurements of benzene in Precipitate Hydrolysis Aqueous (PHA) simulant. This report describes the two ADS Benzene Monitor System (BMS) configurations, provides data on system operation, and reviews the results of scoping tests conducted at TNX. These scoping tests will allow comparison with other benzene measurement options being considered for use in the Defense Waste Processing Facility (DWPF) laboratory. A report detailing the preferred BMS configuration statistical performance during recent tests has been issued under separate title: Statistical Analyses of the At-line Benzene Monitor Study, SCS-ASG-92-066. The current BMS design, called the At-line Benzene Monitor (ALBM), allows remote measurement of benzene in PHA solutions. The authors have demonstrated the ability to calibrate and operate this system using peanut vials from a standard Hydragard{trademark} sampler. The equipment and materials used to construct the ALBM are similar to those already used in other applications by the DWPF lab. The precision of this system ({+-}0.5% Relative Standard Deviation (RSD) at 1 sigma) is better than the purge & trap-gas chromatograpy reference method currently in use. Both BMSs provide a direct measurement of the benzene that can be purged from a solution with no sample pretreatment. Each analysis requires about five minutes per sample, and the system operation requires no special skills or training. The analyzer`s computer software can be tailored to provide desired outputs. Use of this system produces no waste stream other than the samples themselves (i.e. no organic extractants).

  18. [Epigenic modifications associated with low benzene exposure].

    PubMed

    Fustinoni, Silvia; Bollati, Valentina; Bertazzi, Pier Alberto

    2013-01-01

    DNA methylation, mitochondrial DNA copy number and telomeres shortening are cellular modifications associated with an increasing number of tumors, cardiovascular and aging diseases. In our studies these modifications were evaluated in subjects occupationally exposed to low levels of benzene and in the general population. In peripheral blood lymphocytes a decrease of DNA methylation with the increase of personal benzene exposure was found, both in Alu and LINE-1 repetitive elements, and in the global DNA. Telomere length shortening in subjects exposed to traffic exhausts and an increase in mitochondrial DNA copy number correlated to benzene exposure was also found. DNA methylation measured in specimen repeats collected at intervals of 8 years decreased more markedly in exposed subjects than in controls. Our studies highlighted the association of epigenetic modifications of DNA with low benzene exposure.

  19. FORMATION OF HEMOGLOBIN AND ALBUMIN ADDUCTS OF BENZENE OXIDE IN MOUSE, RAT, AND HUMAN BLOOD

    EPA Science Inventory

    Little is known about the formation and disposition of benzene oxide (BO), the initial metabolite arising from oxidation of benzene by cytochrome P450. In this study, reactions of BO with hemoglobin (Hb) and albumin (Alb) were investigated in blood from B6C3F1 mice, F344 rats, ...

  20. Ovariectomy lowers urine levels of unconjugated (+)-catechin, (-)-epicatechin, and their methylated metabolites in rats fed grape seed extract.

    PubMed

    Cutts, John K; Peavy, Thomas R; Moore, Doyle R; Prasain, Jeevan; Barnes, Stephen; Kim, Helen

    2013-12-01

    Abstract Steroid hormones modulate expression of enzymes that metabolize xenobiotics, including dietary supplements. Half of the human population undergoes menopause, yet the effect of this age-related loss of ovarian steroid hormones on the metabolism of dietary supplements has yet to be determined. Grape seed extract (GSE) is a dietary supplement comprised of monomeric and oligomeric catechins and has health benefits in models of age-related diseases. We hypothesized that surgically-induced loss of ovarian hormones would increase methylation, glucuronidation, and/or sulfation of the grape seed polyphenols (+)-catechin and (-)-epicatechin. Fourteen-week-old spontaneously hypertensive rats (SHRs) were ovariectomized (OVX) or sham-OVX. At 17 weeks of age, SHRs were gavaged with vehicle (water) or GSE (300 mg/kg body weight) once daily for 6 days. Urinary excretion of (+)-catechin, (-)-epicatechin, and their metabolites was analyzed by liquid chromatography-mass spectrometry. Although total urinary output of (+)-catechin, (-)-epicatechin, and their methylated metabolites was unaffected by OVX, the amounts of (+)-catechin, (-)-epicatechin and their methylated metabolites that were not conjugated with glucuronic acid or sulfate were lowered by OVX. Specifically, urine from OVX SHRs administered GSE contained 30% higher proportions (91.8% vs. 62.3%) of glucuronidated (+)-catechin and (-)-epicatechin and glucuronidated methyl (+)-catechin and methyl (-)-epicatechin than urine from sham-OVX SHRs. However, there were no differences in urinary levels of total methylated or sulfated catechins in OVX SHRs. This is the first quantitative characterization of metabolites of grape seed polyphenols in a model of menopause; it indicates that ovariectomy causes either an increase in expression and/or activity of select uridine 5'-diphospho-glucuronosyltransferase(s).

  1. Determinants of indoor benzene in Europe

    NASA Astrophysics Data System (ADS)

    Lai, H. K.; Jantunen, M. J.; Künzli, N.; Kulinskaya, E.; Colvile, R.; Nieuwenhuijsen, M. J.

    This study identified the key determinants associated with the indoor benzene concentrations that were measured between 1996 and 2000 using the EXPOLIS protocol in the residences of six European cities, including Athens (Greece), Basel (Switzerland), Helsinki (Finland), Milan (Italy), Oxford (United Kingdom), and Prague (Czech Republic). Two consecutive days of home indoor and home outdoor measurements of benzene were carried out at the homes of adult participants on different dates and seasons during the sampling period. Regression models, with interactions searched by all-possible subset method, were used to assess the city effects and the determinants of home indoor benzene (adjusted R2=0.57, n=412). Outdoor benzene concentrations, outdoor temperature, wind speed, the use of anti-moth products, and indoor smoking in terms of number of cigarettes consumed per day were shown to be the key determinants of indoor benzene concentrations. The model was further used to predict the indoor benzene levels in cities. Non-linear relationships were commonly found, indicating that a unit change in the indoor concentration cannot be simply estimated by a proportional change of the determinant, and the pattern of relationships could be differed in different places. This finding is important in formulating indoor air quality guidelines as well as calculating an accurate health risk estimate based on the estimates of population's lifetime exposure levels.

  2. Significant difference in active metabolite levels of ginseng in humans consuming Asian or Western diet: The link with enteric microbiota.

    PubMed

    Wan, Jin-Yi; Wang, Chong-Zhi; Zhang, Qi-Hui; Liu, Zhi; Musch, Mark W; Bissonnette, Marc; Chang, Eugene B; Li, Ping; Qi, Lian-Wen; Yuan, Chun-Su

    2017-04-01

    After ingestion of ginseng, the bioavailability of its parent compounds is low and enteric microbiota plays an important role in parent compound biotransformation to their metabolites. Diet type can influence the enteric microbiota profile. When human subjects on different diets ingest ginseng, their different gut microbiota profiles may influence the metabolism of ginseng parent compounds. In this study, the effects of different diet type on gut microbiota metabolism of American ginseng saponins were investigated. We recruited six healthy adults who regularly consumed different diet types. These subjects received 7 days' oral American ginseng, and their biological samples were collected for LC-Q-TOF-MS analysis. We observed significant ginsenoside Rb1 (a major parent compound) and compound K (a major active metabolite) level differences in the samples from the subjects consuming different diets. Subjects on an Asian diet had much higher Rb1 levels but much lower compound K levels compared with those on a Western diet. Since compound K possesses much better cancer chemoprevention potential, our data suggested that consumers on a Western diet should obtain better cancer prevention effects with American ginseng intake compared with those on an Asian diet. Ginseng compound levels could be enhanced or reduced via gut microbiota manipulation for clinical utility.

  3. Nanostructure imaging mass spectrometry: the role of fluorocarbons in metabolite analysis and yoctomole level sensitivity.

    PubMed

    Kurczy, Michael E; Northen, Trent R; Trauger, Sunia A; Siuzdak, Gary

    2015-01-01

    Nanostructure imaging mass spectrometry (NIMS) has become an effective technology for generating ions in the gas phase, providing high sensitivity and imaging capabilities for small molecules, metabolites, drugs, and drug metabolites. Specifically, laser desorption from the nanostructure surfaces results in efficient energy transfer, low background chemical noise, and the nondestructive release of analyte ions into the gas phase. The modification of nanostructured surfaces with fluorous compounds, either covalent or non-covalent, has played an important role in gaining high efficiency/sensitivity by facilitating analyte desorption from the nonadhesive surfaces, and minimizing the amount of laser energy required. In addition, the hydrophobic fluorinated nanostructure surfaces have aided in concentrating deposited samples into fine micrometer-sized spots, a feature that further facilitates efficient desorption/ionization. These fluorous nanostructured surfaces have opened up NIMS to very broad applications including enzyme activity assays and imaging, providing low background, efficient energy transfer, nondestructive analyte ion generation, super-hydrophobic surfaces, and ultra-high detection sensitivity.

  4. Leukemia in benzene workers.

    PubMed

    Rinsky, R A; Young, R J; Smith, A B

    1981-01-01

    To evaluate the possible association between occupational exposure to benzene and subsequent death from leukemia, the National Institute for Occupational Safety and Health (NIOSH) conducted a retrospective cohort mortality study of workers who had been exposed to benzene in the manufacture of rubber hydrochloride at two locations in Ohio. Ascertainment of vital status was accomplished for 98% of the cohort. Among 748 workers who had at least one day of exposure to benzene between 1940 and 1950, seven deaths from leukemia occurred; from United States death rates standardized for sex, age, and calendar time period, only 1.25 leukemia deaths would have been expected (standardized mortality ratio = 560; p less than 0.001). Mean duration of exposure to benzene was brief, and 437 (58%) of the cohort were exposed for less than 1 year. Evaluation of leukemia mortality for those workers exposed five or more years showed an SMR of 2100. All leukemia deaths were myelocytic or monocytic in cell type. Four additional cases of leukemia have been reorganized in workers at the study locations, but occurred in persons not encompassed by the strict definition of the cohort. Reconstruction of past exposures to benzene at the two locations indicates that in some areas of the plant airborne benzene concentrations rose occasionally to several hundred parts per million (ppm), but that for the most part, employee eight-hour time-weighted averages (TWA) fell within the limits considered permissible at the time of exposure. These data corroborate an initial analysis of the same cohort by Infante et al, and indicate that benzene is a human carcinogen at a range of exposures not greatly above the current legal standard.

  5. [Materials for the substantiation of the biological MAC of benzene].

    PubMed

    Ulanova, I P; Avilova, G G; Karpukhina, E A; Karimova, L K; Boĭko, V I; Makar'eva, L M

    1990-09-01

    Relatively great amount of benzene-originated phenol, the presence of a definite relationship between phenol amount in the urine and benzene content in the air indicate that it is reasonable to use a phenol sample as an exposure test. To determine the intensity of benzene exposure, data on phenol content in the urine of people working at some big-tonnage enterprises has been analyzed. On the basis of the national and foreign literature data on the correlation between the phenol urine concentration and the level of benzene exposure a regression equation was deduced, which has made it possible to calculate phenol content in the urine on the level of average working day benzene concentration adopted in the USSR. This value equals 15 mg/l, which was proposed as a biological benzene MAC.

  6. Anaerobic degradation of benzene by marine sulfate-reducing bacteria

    NASA Astrophysics Data System (ADS)

    Musat, Florin; Wilkes, Heinz; Musat, Niculina; Kuypers, Marcel; Widdel, Friedrich

    2010-05-01

    analyses of metabolites with benzene-grown cultures, suggesting an activation of benzene via carboxylation.

  7. Understanding Metabolic Regulation at a Systems Level: Metabolite Sensing, Mathematical Predictions, and Model Organisms.

    PubMed

    Watson, Emma; Yilmaz, L Safak; Walhout, Albertha J M

    2015-01-01

    Metabolic networks are extensively regulated to facilitate tissue-specific metabolic programs and robustly maintain homeostasis in response to dietary changes. Homeostatic metabolic regulation is achieved through metabolite sensing coupled to feedback regulation of metabolic enzyme activity or expression. With a wealth of transcriptomic, proteomic, and metabolomic data available for different cell types across various conditions, we are challenged with understanding global metabolic network regulation and the resulting metabolic outputs. Stoichiometric metabolic network modeling integrated with "omics" data has addressed this challenge by generating nonintuitive, testable hypotheses about metabolic flux rewiring. Model organism studies have also yielded novel insight into metabolic networks. This review covers three topics: the feedback loops inherent in metabolic regulatory networks, metabolic network modeling, and interspecies studies utilizing Caenorhabditis elegans and various bacterial diets that have revealed novel metabolic paradigms.

  8. The effects of dietary omega fatty acids on pregnancy rate, plasma prostaglandin metabolite levels, serum progesterone levels, and milk fatty-acid profile in beef cows.

    PubMed

    Richardson, Gavin F; McNiven, Mary A; Petit, Hélène V; Duynisveld, John L

    2013-10-01

    The objectives were to determine the effects of feeding supplements rich in omega-6 or omega-3 fatty acids (FA) during the late gestation to the early postpartum and breeding periods on reproduction and milk FA profile in beef cows. For each of two years, at the beginning of period 1 (mid-December), 72 beef cows, calving in January or February, were assigned to diets supplemented with roasted flaxseed (Flax) or roasted soybean (Soybean). For each of two years, after 11 wk (end of period 1), 18 cows of 36 in the Flax group were switched to the soybean supplement and 18 cows of 36 in the Soybean group were switched to the flax supplement (start of Period 2). Cows were bred by timed artificial insemination (TAI) in week 5 of period 2. The FA composition of the milk reflected the FA profile of the oilseed supplements. There were no differences in pregnancy rates among the 4 groups. The treatments had no effect on plasma prostaglandin metabolite levels or ratios at 4 to 11 d postpartum. At 5 to 6 d post- TAI, pregnant cows fed Flax in period 1 had lower (P < 0.05) plasma prostaglandin F metabolite (PGFM) levels and PGFM to prostaglandin E metabolite (PGEM) ratio than cows fed Soybean, but there were no significant differences at 19 to 20 d post-TAI. Cows pregnant from TAI and fed Flax in period 2 had higher (P < 0.05) serum progesterone levels at 5 to 6 d post-TAI than cows fed Soybean, but there was no difference at 19 to 20 d post-TAI. The dietary treatments had no effect on pregnancy rates, but there were some effects on plasma PGFM levels, PGFM to PGEM ratios, and serum progesterone levels. The FA supplements influenced the FA composition of milk.

  9. Prediagnostic levels of serum one-carbon metabolites and risk of hepatocellular carcinoma

    PubMed Central

    Butler, Lesley M.; Arning, Erland; Wang, Renwei; Bottiglieri, Teodoro; Govindarajan, Sugantha; Gao, Yu-Tang; Yuan, Jian-Min

    2013-01-01

    Background Rats fed diets deficient in choline develop hepatocellular carcinoma (HCC). Tumor DNA from these animals is characteristically hypomethylated, suggesting that disruption of the one-carbon metabolism pathway is an underlying mechanism for hepatocarcinogenesis. Prospective studies in humans on circulating choline and other one-carbon metabolites and HCC risk have been lacking. Methods We prospectively examined the association between prediagnostic serum concentrations of one-carbon metabolites including betaine, choline, cystathionine, homocysteine, methionine, 5-methyltetrahydrofolate (5-MTHF), pyridoxal-5-phosphate (PLP, the bioactive form of vitamin B6) and S-adenosylmethionine (SAM), and risk of developing HCC based on a nested case-control study of 297 incident cases and 631 matched controls from a cohort of 18,244 men in Shanghai, China. Logistic regression methods were used to calculate odds ratios (OR) and 95% confidence intervals (CI) adjusted for established risk factors for HCC. Results Serum choline and PLP were associated with statistically significant reduced risk of HCC, while serum cystathionine, methionine and SAM were associated with increased HCC risk (all Ptrend<0.05). The inverse associations for HCC risk with choline and PLP remained statistically significant after adjusting for all potential confounders. The multivariate-adjusted ORs (95% CIs) for the highest versus lowest quintiles of serum choline and PLP were 0.35 (0.16, 0.78) (P=0.010) and 0.44 (0.25, 0.78) (P=0.005), respectively. There were no associations for HCC risk with 5-MTHF, betaine, or homocysteine. Conclusion The inverse associations between choline and vitamin B6 and the risk of HCC development are novel and warrant further investigation. Impact Identifying new modifiable factors for HCC prevention are warranted. PMID:23897582

  10. Modifications in the metabolism and myeloclastogenic effect of benzene

    SciTech Connect

    Gad-El-Karim, M.; Harper, B.L.; Sadagopa Ramanujam, V.M.; Legator, M.S.

    1982-01-01

    Toxicity of benzene was studied in the bone marrow with the micronucleus test and metaphase analysis. Male and female CD-1 mice were subjected to pretreatments with phenobarbital, 3-methylcholanthrene (3-MCA), SKF-525A, or Aroclor-1254. The animals were then treated with benzene (440 or 880 mg/kg), or toluene (860 or 1720 mg/kg), or their mixture by gavage or I.P. in 2 doses 24 hours apart and sacrificed 6 hours or 24 hours after the second dose. Toluene showed no clastogenic activity and reduced the clastogenic effect of benzene when mixture was given. None of the pretreatments protected against the clastogenic effect of benzene. 3-MCA pretreatment caused a tremendous enhancement of benzene myeloclastogenicity. Dose-response curves with benzene treatment alone and with 3-MCA induced groups were generated. Urine fractions were collected from animals gavaged with benzene, either non-induced, PB- or 3MCA induced. The metabolites were quantitated by HPLC, and confirmed by GC/MS.

  11. Comparison of prorenoate potassium and spironolactone after repeated doses and steady state plasma levels of active metabolites.

    PubMed Central

    McInnes, G T; Shelton, J R; Harrison, I R; Perkins, R M; Palmer, R F

    1982-01-01

    1 After repeated single daily doses, the aldosterone antagonists prorenoate potassium and spironolactone were compared with regard to renal antimineralocorticoid activity, plasma potassium concentration and steady state plasma levels of their active metabolites, prorenone and canrenone respectively, in a balanced crossover study of twelve healthy subjects. 2 Following challenge with the mineralocorticoid, fludrocortisone, best estimates of the potency of prorenoate potassium relative to spironolactone were 3.6 (95% confidence limits 1.6-10.4) for urinary sodium excretion and 3.4 (95% confidence limits 2.0-6.5) for urinary log10 10Na/K. Estimates with respect to urinary potassium excretion and plasma potassium concentration were imprecise, confirming the limitations of the fludrocortisone model in the evaluation of aldosterone antagonists at steady state. 3 Both compounds exhibited directly proportional relationships between daily dose and steady state plasma levels of active metabolites. The approximate mean terminal elimination half-life of prorenone at steady state was 32.6 h (range 18-80 h). PMID:7059416

  12. Influence of parenting style on the offspring's behaviour and CSF monoamine metabolite levels in crossfostered and noncrossfostered female rhesus macaques.

    PubMed

    Maestripieri, Dario; McCormack, Kai; Lindell, Stephen G; Higley, J Dee; Sanchez, Mar M

    2006-11-25

    We investigated the association between variation in parenting style and the offspring's behaviour and CSF monoamine metabolite (5-HIAA, HVA, and MHPG) levels in rhesus monkeys. Study subjects were 25 two-year-old females reared by their biological mothers and 15 same-aged females that were crossfostered at birth and reared by unrelated mothers. Subjects that were rejected more by their mothers in the first 6 months of life engaged in more solitary play and had lower CSF concentrations of 5-HIAA than subjects that were rejected less. The relation between these variables was generally similar in crossfostered and noncrossfostered females. CSF levels of 5-HIAA were negatively correlated with rates of scratching, a behavioural indicator of anxiety. These results suggest that that early exposure to high rates of maternal rejection can result in higher anxiety later in life, and that this effect may be mediated by serotonergic mechanisms. Variation in maternal protectiveness did not affect offspring behaviour and neither protectiveness nor rejection affected CSF levels of HVA and MHPG. CSF levels of MHPG, however, were negatively correlated with solitary play behaviour and avoidance of other individuals, suggesting that individuals with lower CSF MHPG were more fearful and socially phobic than those with higher CSF MHPG. Taken together, these findings suggest that individual differences in anxiety and fearfulness in young rhesus monkeys are accounted for, at least in part, by variation in CSF levels of monoamine metabolites, and that the development of brain monoamine systems, particularly serotonin, can be affected by early exposure to variable maternal behaviour.

  13. Lower Vitamin D Metabolites Levels Were Associated With Increased Coronary Artery Diseases in Type 2 Diabetes Patients in India

    PubMed Central

    Adela, Ramu; Borkar, Roshan M; Bhandi, Murali Mohan; Vishwakarma, Gayatri; Reddy, P. Naveen Chander; Srinivas, R.; Banerjee, Sanjay K

    2016-01-01

    The purpose of the present study was to measure six vitamin D metabolites and to find the association between vitamin D deficiency and coronary artery diseases in diabetes (T2DM_CAD). Four groups [control (n = 50), type 2 diabetes (T2DM, n = 71), coronary artery diseases (CAD, n = 28), T2DM_CAD (n = 38)] of total 187 subjects were included in the study. Six vitamin D metabolites (D2, D3, 25(OH)D2, 25(OH)D3, 1,25(OH)2D2, 1,25(OH)2D3), total 25(OH)D and total 1,25(OH)2D were measured by UPLC/APCI/HRMS method in these subjects. Although all the vitamin D metabolites were significantly decreased in T2DM_CAD as compared to both control and T2DM subjects (p < 0.05), only two metabolites i.e., 25(OH)D3 and total 25(OH)D were significantly (p < 0.05) decreased in the T2DM subjects as compared with the control subjects (p < 0.05). Vitamin D3, 1,25(OH)2D2, 25(OH)D, and 1,25(OH)2D levels were significantly decreased in T2DM_CAD subjects as compared with CAD subjects (p < 0.05). Further, multiple logistic regression analysis revealed that total 25(OH)D and total 1,25(OH)2D can be used to predict T2DM (OR 0.82.95% CI 0.68–0.99; p = 0.0208) and T2DM with CAD (OR 0.460, 95% CI 0.242–0.874; p = 0.0177), respectively. Our data concludes that lower concentration of 1,25(OH)2D is associated with type 2 diabetes coexisting with coronary artery diseases in South Indian subjects. PMID:27883024

  14. Differences in intestinal microbial metabolites in laying hens with high and low levels of repetitive feather-pecking behavior.

    PubMed

    Meyer, Beatrice; Zentek, Jürgen; Harlander-Matauschek, Alexandra

    2013-02-17

    Feather pecking in laying hens is a serious behavioral problem and is often associated with feather eating. There is some evidence that ingested feathers affect gut function. The aim of the present study was to explore whether differences in intestinal microbial metabolites in laying hens with high and low levels of repetitive feather-pecking behavior exist. Sixty high feather-pecking birds (H) and sixty low feather-pecking birds (L) of the White Leghorn breed were used for behavioral recordings of feather pecking. Feather pecking activity was observed for 5 weeks, after which 22 H birds with the highest and 22 L birds with the lowest feather pecking activity were chosen. The number of whole feathers and feather parts in the gizzard and intestinal microbial metabolites in the ileum and ceca of these laying hens was examined. Biogenic amines, short-chain fatty acids, ammonia and lactate were measured as microbial metabolites. A higher number of feather parts and particles were found in H than in L birds. Putrescine and cadaverine concentrations were higher in the ileum of the hens with low pecking activity (P<0.001 and P=0.012). In the cecum the amounts of l-lactate, d-lactate and total lactate and SCFA were higher in H birds (P=0.007, P=0.005, P=0.006, and P<0.001). Acetate, i-butyrate, i-valeriate and n-valeriate all displayed significantly higher molar ratios in the cecal contents of L birds (P=0.001, P=0.003, P=0.001, and P<0.001). Propionate and n-butyrate showed higher molar ratios in H birds (P<0.001 and P=0.034). Ammonia was higher in the ileum and cecum of the L birds (P<0.001 and P=0.004). For the first time, this study shows that birds with high and low numbers of repetitive pecking movements to the plumage of other birds differ in their intestinal microbial metabolism. Further experiments should be conducted to investigate whether these differences alter behavior in H and L feather pecking birds. The present results, however, open new avenues of research

  15. Effect of Methanolic Leaf Extract of Ocimum basilicum L. on Benzene-Induced Hematotoxicity in Mice.

    PubMed

    Saha, S; Mukhopadhyay, M K; Ghosh, P D; Nath, D

    2012-01-01

    The aim of the present study was to investigate the protective role of methanolic leaf extract of Ocimum basilicum L. against benzene-induced hematotoxicity in Swiss albino mice. GC analysis and subacute toxicity level of the extract were tested. Mice were randomly divided into three groups among which II and III were exposed to benzene vapour at a dose 300 ppm × 6 hr/day × 5 days/week for 2 weeks and group I was control. Group III of this experiment was treated with the leaf methanolic extract at a dose of 100 mg/kg body weight, a dose in nontoxic range. Hematological parameters (Hb%, RBC and WBC counts), cell cycle regulatory proteins expression and DNA fragmentation analysis of bone marrow cells was performed. There was an upregulation of p53 and p21 and downregulation of levels of CDK2, CDK4, CDK6, and cyclins D1 and E in leaf extract-treated group. DNA was less fragmented in group III compared to group II (P < 0.05). The present study indicates that the secondary metabolites of O. basilicum L. methanolic leaf extract, comprising essential oil monoterpene geraniol and its oxidized form citral as major constituents, have modulatory effect in cell cycle deregulation and hematological abnormalities induced by benzene in mice.

  16. Effect of Methanolic Leaf Extract of Ocimum basilicum L. on Benzene-Induced Hematotoxicity in Mice

    PubMed Central

    Saha, S.; Mukhopadhyay, M. K.; Ghosh, P. D.; Nath, D.

    2012-01-01

    The aim of the present study was to investigate the protective role of methanolic leaf extract of Ocimum basilicum L. against benzene-induced hematotoxicity in Swiss albino mice. GC analysis and subacute toxicity level of the extract were tested. Mice were randomly divided into three groups among which II and III were exposed to benzene vapour at a dose 300 ppm × 6 hr/day × 5 days/week for 2 weeks and group I was control. Group III of this experiment was treated with the leaf methanolic extract at a dose of 100 mg/kg body weight, a dose in nontoxic range. Hematological parameters (Hb%, RBC and WBC counts), cell cycle regulatory proteins expression and DNA fragmentation analysis of bone marrow cells was performed. There was an upregulation of p53 and p21 and downregulation of levels of CDK2, CDK4, CDK6, and cyclins D1 and E in leaf extract-treated group. DNA was less fragmented in group III compared to group II (P < 0.05). The present study indicates that the secondary metabolites of O. basilicum L. methanolic leaf extract, comprising essential oil monoterpene geraniol and its oxidized form citral as major constituents, have modulatory effect in cell cycle deregulation and hematological abnormalities induced by benzene in mice. PMID:22988471

  17. Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii.

    PubMed

    Maifiah, Mohd Hafidz Mahamad; Cheah, Soon-Ee; Johnson, Matthew D; Han, Mei-Ling; Boyce, John D; Thamlikitkul, Visanu; Forrest, Alan; Kaye, Keith S; Hertzog, Paul; Purcell, Anthony W; Song, Jiangning; Velkov, Tony; Creek, Darren J; Li, Jian

    2016-02-29

    Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03-149.1 (polymyxin-susceptible) and 03-149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii.

  18. Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii

    PubMed Central

    Mahamad Maifiah, Mohd Hafidz; Cheah, Soon-Ee; Johnson, Matthew D.; Han, Mei-Ling; Boyce, John D.; Thamlikitkul, Visanu; Forrest, Alan; Kaye, Keith S.; Hertzog, Paul; Purcell, Anthony W.; Song, Jiangning; Velkov, Tony; Creek, Darren J.; Li, Jian

    2016-01-01

    Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03–149.1 (polymyxin-susceptible) and 03–149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii. PMID:26924392

  19. Vitamin D metabolites and bioactive parathyroid hormone levels during Spacelab 2

    NASA Technical Reports Server (NTRS)

    Morey-Holton, Emily R.; Schnoes, Heinrich K.; Deluca, Hector F.; Phelps, Mary E.; Klein, Robert F.

    1988-01-01

    The effect of an 8-day space flight (Spacelab mission 2) on plasma levels of the vitamin D and parathyroid hormones is investigated experimentally in four crew members. The results are presented in tables and graphs and briefly characterized. Parathyroid hormone levels remained normal throughout the flight, whereas vitamin D hormone levels increased significantly on day 1 but returned to normal by day 7.

  20. IN VITRO CYTOTOXICITY OF BTEX METABOLITES IN HELA CELL LINES

    EPA Science Inventory

    Fuel leakage from underground storage tanks is a major source of groundwater contamination. Although the toxicity of regulated compounds such as benzene, toluene, ethylbenzene, and xylene (BTEX) are well recognized, the cytotoxicity of their metabolites has not been studied exte...

  1. Modifications in the metabolism and myeloclastogenic effect of benzene

    SciTech Connect

    Gad-El Karim, M.M.; Harper, B.L.; Ramanujam, S.V.M.; Legator, M.S.

    1982-02-01

    Benzene was studied in its target organ of effect, the bone marrow, with the micronucleus test and metaphase analysis. In a series of experiments, male and female CD-1 mice were subjected to various pretreatments: phenobarbital (PB) (0.1% in drinking water x 7 days or 80 mg/kg/day (I.P.) x 3 days before treatment), 3-methylcholanthrene (3-MCA) (30 mg/kg/day (I.P.) x 2 days), SKF-525A (80 mg/kg (I.P.) 2 hours before each treatment dose), or Aroclor-1254 (100 mg/kg) (I.P.) once, 5 days before treatment. The animals were then treated with benzene (440 or 880 mg/kg) or toluene (860 or 1720 mg/kg) or their mixture in 2 doses 24 hours apart and sacrificed 6 hours or 24 hours after the second dose. Toluene showed no clastogenic activity and reduced the clastogenic effect of benzene when the mixture was given. None of the pretreatments protected against the clastogenic effect of benzene. 3-MCA pretreatment caused a tremendous enhancement of benzene myeloclastogenicity. The sex difference, with females constantly more resistant than males to benzene, was retained among the 3-MCA pretreated group. Toluene, in mixture with benzene, lowered the clastogenic effect in 3-MCA pretreated mice. Dose-response curves with benzene treatment alone and with 3-MCA induced groups were generated in which the former curve was lower for each dose than the latter. Urine fractions were collected at 12-hour intervals from 3-groups of 10 males gavaged with benzene, either non-induced, PB- or 3MCA induced. Catechol was the major metabolite, phenol the minor one, and hydroquinone and semiquinones were present in trace amounts.

  2. Effects of physical exercise on serum levels of serotonin and its metabolite in fibromyalgia: a randomized pilot study.

    PubMed

    Valim, Valéria; Natour, Jamil; Xiao, Yangming; Pereira, Abraão Ferraz Alves; Lopes, Beatriz Baptista da Cunha; Pollak, Daniel Feldman; Zandonade, Eliana; Russell, Irwin Jon

    2013-01-01

    To evaluate the effects of aerobic training and stretching on serum levels of serotonin (5HT) and its main metabolite 5-hydroxindolacetic acid (5HIAA). Twenty-two women with FM were randomized into one of two exercise modalities (aerobic walking exercise or stretching exercise) to be accomplished three times a week for 20 weeks. The serum levels of 5HT and 5HIAA were evaluated before and after the exercise program by high performance liquid chromatography (HPLC) with colorimetric detection. Within group analysis (pre-post) showed that serum levels of both 5HT and 5HIAA changed significantly in the aerobic group during the 20-week course of therapy (5HT: P = 0,03; 5HIAA: P = 0,003). In the stretching group, however, no statistically significant change was observed (5HT: P=0,491; 5HIAA: P=0,549). Between group statistical comparisons of laboratory measures disclosed that aerobic training was superior to stretching in that it significantly increased the levels of 5HIAA (F test = 6.61; P = 0.01), but the average difference between groups on the levels of 5HT did not meet significance criteria (F test = 3.42; P = 0.08). Aerobic training increases the 5HIAA and 5HT levels and it could explain why aerobic exercise can improve symptoms in fibromyalgia syndrome patient more than stretching exercise.

  3. Influence of CYP2D6 Polymorphisms on Serum Levels of Tamoxifen Metabolites in Spanish Women with Breast Cancer

    PubMed Central

    Zafra-Ceres, Mercedes; de Haro, Tomas; Farez-Vidal, Esther; Blancas, Isabel; Bandres, Fernando; de Dueñas, Eduardo Martinez; Ochoa-Aranda, Enrique; Gomez-Capilla, Jose A.; Gomez-Llorente, Carolina

    2013-01-01

    Background Estrogen receptor-positive breast cancer tumors depend on estrogen signaling for their growth and replication and can be treated by anti-estrogen therapy with tamoxifen. Polymorphisms of the CYP2D6 and CYP2C19 genes are associated with an impaired response to tamoxifen. The study objective was to investigate the impact of genetic polymorphisms in CYP2D6 and CYP2C19 on the pharmacokinetics of tamoxifen and its metabolites in Spanish women with estrogen receptor-positive breast cancer who were candidates for tamoxifen therapy. Methods: We studied 90 women with estrogen receptor-positive breast cancer, using the AmpliChip CYP450 test to determine CYP2D6 and CYP2C19 gene variants. Plasma levels of tamoxifen and its metabolites were quantified by high-performance liquid chromatography. Results The CYP2D6 phenotype was extensive metabolizer in 80%, intermediate metabolizer in 12.2%, ultra-rapid metabolizer in 2.2%, and poor metabolizer in 5.6% of patients, and the allele frequency was 35.0% for allele *1, 21.0% for *2, and 18.9% for *4. All poor metabolizers in this series were *4/*4, and their endoxifen and 4-hydroxy tamoxifen levels were 25% lower than those of extensive metabolizers. CYP2C19*2 allele, which has been related to breast cancer outcomes, was detected in 15.6% of the studied alleles. Conclusion CYP2D6*4/*4 genotype was inversely associated with 4-hydroxy tamoxifen and endoxifen levels. According to these results, CYP2D6 and CYP2C19 genotyping appears advisable before the prescription of tamoxifen therapy. PMID:23781139

  4. Effects of Elevated Atmospheric CO2 on Primary Metabolite Levels in Arabidopsis thaliana Col-0 Leaves: An Examination of Metabolome Data.

    PubMed

    Noguchi, Ko; Watanabe, Chihiro K; Terashima, Ichiro

    2015-11-01

    Elevated atmospheric CO(2) concentrations ([CO(2)]) affect primary metabolite levels because CO(2) is a direct substrate for photosynthesis. In several studies, the responses of primary metabolite levels have been examined using Arabidopsis thaliana leaves, but these results have not been comprehensively discussed. Here, we examined metabolome data for A. thaliana accession Col-0 leaves that were grown at elevated [CO(2)] with sufficient nitrogen (N) nutrition. At elevated [CO(2)], starch, monosaccharides and several major amino acids accumulated in leaves. The degree of accumulation depended on whether the rooting medium contained NH(4) (+) or only NO(3) (-). Because low N conditions induce an increase in carbohydrates similar to that of elevated [CO(2)], we compared the responses of primary metabolite levels between elevated [CO(2)] and low N conditions. Levels of the tricarboxylic acid (TCA) cycle-associated organic acids and major amino acids decreased with low N, but not with elevated [CO(2)]. Even at elevated [CO(2)], the low N induced the decreases in the levels of organic acids and major amino acids. A small sink size also affects the primary metabolite response patterns in leaves under elevated [CO(2)] conditions. Thus, care is necessary when interpreting primary metabolite changes in leaves of field-grown plants.

  5. Development of an immunoassay to detect benzene adducts in hemoglobin

    SciTech Connect

    Grassman, J.A.

    1993-01-01

    The purpose of this project was to develop an immunoassay to detect the adducts formed in hemoglobin after exposure to benzene, which is known to cause bone marrow degeneration and acute myelogenous leukemia. The use of benzene-adduct detection as a biological monitoring method would permit measurement of low exposures and exposures sustained weeks earlier. The reactivity of hydroquinone, an important benzene metabolite, with blood proteins and amino acids was investigated in order to decide which antigens and analytes were likely to be suitable for immunoassay development. The second section determined the combination of benzene-metabolite and antigen need to produce an immunoassay with the requisite low detection limit and specificity. The immunoassays with the best performance were tested on hemoglobin from benzene-exposed mice. In vitro studies showed that hydroquinone efficiently formed adducts with erythrocyte membranes and hemoglobin but not with albumin. Adduction efficiency was greater in incubations using purified hemoglobin than whole blood. Cysteine accounted for 15 to 27% of the adducts formed by hydroquinone. The site of the other adducts were not identified although there was evidence that the hemoglobin heme was adducted. Adducts were found on only 1 of the 2 globin chains. Tryptic digestion of the globin failed to associate the adducts with a specific peptide. Antigens made from hydroquinone-adducted hemoglobin but not hydroquinone-adducted cysteines coupled to carrier proteins effectively elicited adduct-specific antibodies. Interference due to reactivity to hemoglobin was controlled by using uniform quantities of hemoglobin in all wells. The mid-range of the best assays were approximately 12 pmoles HQ per well. Antibodies directed toward hemoglobin adducted with the benzene metabolites phenol, catechol and 1,2,4-trihydroxybenzene were also made. The performance of the anti-1,2,4-trihydroxybenzene were suitable for quantitative immunoassays.

  6. Benzene as a Chemical Hazard in Processed Foods

    PubMed Central

    Salviano dos Santos, Vânia Paula; Medeiros Salgado, Andréa; Guedes Torres, Alexandre; Signori Pereira, Karen

    2015-01-01

    This paper presents a literature review on benzene in foods, including toxicological aspects, occurrence, formation mechanisms, and mitigation measures and analyzes data reporting benzene levels in foods. Benzene is recognized by the IARC (International Agency for Research on Cancer) as carcinogenic to humans, and its presence in foods has been attributed to various potential sources: packaging, storage environment, contaminated drinking water, cooking processes, irradiation processes, and degradation of food preservatives such as benzoates. Since there are no specific limits for benzene levels in beverages and food in general studies have adopted references for drinking water in a range from 1–10 ppb. The presence of benzene has been reported in various food/beverage substances with soft drinks often reported in the literature. Although the analyses reported low levels of benzene in most of the samples studied, some exceeded permissible limits. The available data on dietary exposure to benzene is minimal from the viewpoint of public health. Often benzene levels were low as to be considered negligible and not a consumer health risk, but there is still a need of more studies for a better understanding of their effects on human health through the ingestion of contaminated food. PMID:26904662

  7. Benzene as a Chemical Hazard in Processed Foods.

    PubMed

    Salviano Dos Santos, Vânia Paula; Medeiros Salgado, Andréa; Guedes Torres, Alexandre; Signori Pereira, Karen

    2015-01-01

    This paper presents a literature review on benzene in foods, including toxicological aspects, occurrence, formation mechanisms, and mitigation measures and analyzes data reporting benzene levels in foods. Benzene is recognized by the IARC (International Agency for Research on Cancer) as carcinogenic to humans, and its presence in foods has been attributed to various potential sources: packaging, storage environment, contaminated drinking water, cooking processes, irradiation processes, and degradation of food preservatives such as benzoates. Since there are no specific limits for benzene levels in beverages and food in general studies have adopted references for drinking water in a range from 1-10 ppb. The presence of benzene has been reported in various food/beverage substances with soft drinks often reported in the literature. Although the analyses reported low levels of benzene in most of the samples studied, some exceeded permissible limits. The available data on dietary exposure to benzene is minimal from the viewpoint of public health. Often benzene levels were low as to be considered negligible and not a consumer health risk, but there is still a need of more studies for a better understanding of their effects on human health through the ingestion of contaminated food.

  8. Anaerobic benzene degradation by bacteria

    PubMed Central

    Vogt, Carsten; Kleinsteuber, Sabine; Richnow, Hans‐Hermann

    2011-01-01

    Summary Benzene is a widespread and toxic contaminant. The fate of benzene in contaminated aquifers seems to be primarily controlled by the abundance of oxygen: benzene is aerobically degraded at high rates by ubiquitous microorganisms, and the oxygen‐dependent pathways for its breakdown were elucidated more than 50 years ago. In contrast, benzene was thought to be persistent under anoxic conditions until 25 years ago. Nevertheless, within the last 15 years, several benzene‐degrading cultures have been enriched under varying electron acceptor conditions in laboratories around the world, and organisms involved in anaerobic benzene degradation have been identified, indicating that anaerobic benzene degradation is a relevant environmental process. However, only a few benzene degraders have been isolated in pure culture so far, and they all use nitrate as an electron acceptor. In some highly enriched strictly anaerobic cultures, benzene has been described to be mineralized cooperatively by two or more different organisms. Despite great efforts, the biochemical mechanism by which the aromatic ring of benzene is activated in the absence of oxygen is still not fully elucidated; methylation, hydroxylation and carboxylation are discussed as likely reactions. This review summarizes the current knowledge about the ‘key players’ of anaerobic benzene degradation under different electron acceptor conditions and the possible pathway(s) of anaerobic benzene degradation. PMID:21450012

  9. High levels of PAH-metabolites in urine of e-waste recycling workers from Agbogbloshie, Ghana.

    PubMed

    Feldt, Torsten; Fobil, Julius N; Wittsiepe, Jürgen; Wilhelm, Michael; Till, Holger; Zoufaly, Alexander; Burchard, Gerd; Göen, Thomas

    2014-01-01

    The informal recycling of electronic waste (e-waste) is an emerging source of environmental pollution in Africa. Among other toxins, polycyclic aromatic hydrocarbons (PAHs) are a major health concern for exposed individuals. In a cross-sectional study, the levels of PAH metabolites in the urine of individuals working on one of the largest e-waste recycling sites of Africa, and in controls from a suburb of Accra without direct exposure to e-waste recycling activities, were investigated. Socioeconomic data, basic health data and urine samples were collected from 72 exposed individuals and 40 controls. In the urine samples, concentrations of the hydroxylate PAH metabolites (OH-PAH) 1-hydroxyphenanthrene (1-OH-phenanthrene), the sum of 2- and 9-hydroxyphenanthrene (2-/9-OH-phenanthrene), 3-hydroxyphenanthrene (3-OH-phenanthrene), 4-hydroxyphenanthrene (4-OH-phenanthrene) and 1-hydroxypyrene (1-OH-pyrene), as well as cotinine and creatinine, were determined. In the exposed group, median urinary concentrations were 0.85 μg/g creatinine for 1-OH-phenanthrene, 0.54 μg/g creatinine for 2-/9-OH-phenanthrene, 0.99 μg/g creatinine for 3-OH-phenanthrene, 0.22 μg/g creatinine for 4-OH-phenanthrene, and 1.33 μg/g creatinine for 1-OH-pyrene, all being significantly higher compared to the control group (0.55, 0.37, 0.63, 0.11 and 0.54 μg/g creatinine, respectively). Using a multivariate linear regression analysis including sex, cotinine and tobacco smoking as covariates, exposure to e-waste recycling activities was the most important determinant for PAH exposure. On physical examination, pathological findings were rare, but about two thirds of exposed individuals complained about cough, and one quarter about chest pain. In conclusion, we observed significantly higher urinary PAH metabolite concentrations in individuals who were exposed to e-waste recycling compared to controls who were not exposed to e-waste recycling activities. The impact of e-waste recycling on exposure to

  10. Age and Gender Differences in Urinary Levels of Eleven Phthalate Metabolites in General Taiwanese Population after a DEHP Episode

    PubMed Central

    Huang, Po-Chin; Tsai, Chih-Hsin; Liang, Wei-Yen; Li, Sih-Syuan; Pan, Wen-Harn; Chiang, Hung-Che

    2015-01-01

    Introduction In 2011, the Taiwan FDA disclosed illegal di(2-ethylhexyl phthalate) (DEHP) and dibutyl phthalate (DBP) use in beverage and nutrition supplements. We aim to determine phthalate exposure and other relevant factors in a sample of the general Taiwanese population in order to evaluate actual phthalate exposure levels after this disclosure of DEHP use. Method We selected subjects aged 7 years old and older in 2013 from the general Taiwanese population. First morning urine samples from each participant were collected to analyze 11 phthalate metabolites representing 7 parent phthalates using on-line liquid chromatography/ tandem mass spectrometry. An interview questionnaire was applied to obtain participant demographic characteristics, lifestyle, and other relevant factors. Results The median levels of metabolites of DEHP, including mono-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), DBP (DnBP and DiBP), including mono-n-butyl phthalate (MnBP) and mono-iso-butyl phthalate (MiBP), and mono-ethyl phthalate (MEP) in urine samples of 290 adults/ 97 minors (<18 years) were 7.9/ 6.1, 12.6/ 17.8, 22.0/ 25.8, 25.4/ 30.8, 18.1/ 23.6, 9.4/ 13.6 and 14.5/ 12.4 μg/g creatinine, respectively. Women (≧18 years) were exposed to significantly higher levels of MEHHP (P=0.011), MECPP (P=0.01), MnBP (P=0.001) and MEP (P<0.001) than men (≧18 years), whereas no gender difference was observed in minors. We found significant higher level of MEP (creatinine-unadjusted) in subject aged between 18 to 40 years old (P<0.001), especially for women. Exposure levels of MEOHP (P<0.001), MECPP (P=0.002) and MnBP (P=0.044) in minors were significantly higher than those of adults. High frequency usage of food preservation film and bags, and personal care products are potential sources of phthalates exposure in general Taiwanese. Conclusion Our findings indicated

  11. Urinary Level of Prostaglandin E2 Metabolite and Risk of Incident Breast Cancer

    DTIC Science & Technology

    2012-01-01

    p=0.08) [Table 3]. On the other hand, women with rheumatoid arthritis had lower levels of PGE-M compared to those who didn’t report having the...8.07) 0.012 6.33 (5.27-7.6) 0.078 Rheumatoid arthritis Yes 569 5.47 (5.19-5.77) Ref 5.47 (5.2-5.77) Ref No 35 4.44 (3.59-5.51) 0.064 4.44 (3.59...through various venues, incorporating new understanding of breast cancer etiology in the analyses of epidemiologic data. These experiences have

  12. Effect of 14 days of bed rest on urine metabolite excretion and plasma enzyme levels

    NASA Technical Reports Server (NTRS)

    Pace, N.; Grunbaum, B. W.; Kodama, A. M.; Rahlmann, D. F.; Newsom, B. D.

    1974-01-01

    After 1 week of ambulatory base-line measurement, a group of 8 men 19-26 years of age remained continuously recumbent for 14 days. Studies were continued for 1 week following the prolonged recumbency. Urine excretion rates for a number of constituents were determined 2 days before bed rest, on day 14 of bed rest, and day 6 after bed rest. Blood plasma samples were also obtained at these times, and analyzed for several enzymes. On day 14 of bed rest significant increases were observed in urine excretion of total osmotically-active substances, magnesium, calcium, phosphate, creatinine, hydroxyproline, and 17-OH corticosteroids. A decrease occurred in urinary glucose excretion. Plasma levels of alkaline phosphatase and LDH-3 were depressed, while plasma GPT was elevated. Many of these changes persisted on day 6 after bed rest, and are interpreted as concomitants of the disuse atrophy of the musculoskeletal system that characterizes prolonged bed rest and weightlessness.

  13. Urinary Levels of Cigarette Smoke Constituent Metabolites Are Prospectively Associated with Lung Cancer Development in Smokers

    PubMed Central

    Yuan, Jian-Min; Gao, Yu-Tang; Murphy, Sharon E.; Carmella, Steven G.; Wang, Renwei; Zhong, Yan; Moy, Kristin A.; Davis, Andrew B.; Tao, Li; Chen, Menglan; Han, Shaomei; Nelson, Heather H.; Yu, Mimi C.; Hecht, Stephen S.

    2012-01-01

    Polycyclic aromatic hydrocarbons (PAH) are believed to be among the principal causative agents for lung cancer in smokers, but no epidemiologic studies have evaluated the relationship of PAH uptake and metabolism to lung cancer. In this study, we quantified prediagnostic urinary levels of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydro-phenanthrene (PheT), a validated biomarker of PAH uptake and metabolism, as well as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL), and cotinine and its glucuronides (total cotinine), validated biomarkers of uptake of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, and nicotine, respectively, in relation to lung cancer risk among current smokers in a nested case–control study within a cohort of 18,244 Chinese men in Shanghai, China. Urinary levels of PheT, total NNAL, and total cotinine were significantly higher in cases than controls (N = 476 matched pairs). ORs (95% confidence intervals) for lung cancer in the second, third, fourth, and fifth quintiles of PheT were 1.70 (1.00–2.88), 1.07 (0.62–1.84), 1.48 (0.86–2.53), and 2.34 (1.33–4.11), respectively, relative to the lowest quartile (Ptrend = 0.023) after adjustment for self-reported smoking intensity and duration and urinary total NNAL and total cotinine. This study also confirmed that urinary total NNAL and total cotinine are independently related to lung cancer risk. PMID:22028322

  14. Blood levels of polychlorinated biphenyls and their hydroxylated metabolites in Baikal seals (Pusa sibirica): emphasis on interspecies comparison, gender difference and association with blood thyroid hormone levels.

    PubMed

    Imaeda, Daisuke; Nomiyama, Kei; Kunisue, Tatsuya; Iwata, Hisato; Tsydenova, Oyuna; Amano, Masao; Petrov, Evgeny A; Batoev, Valeriy B; Tanabe, Shinsuke

    2014-11-01

    We have previously demonstrated that Baikal seals (Pusa sibirica) are still being exposed to polychlorinated biphenyls (PCBs), and the population is at risk. In the present study, we measured the residue levels of PCBs and their hydroxylated metabolites (OH-PCBs) in the blood of Baikal seals and assessed the impact of OH-PCBs on the thyroid function. Blood concentrations of PCBs and OH-PCBs were in the range of 2.8-130 ng g(-1)wet wt. and 0.71-4.6 ng g(-1)wetwt., respectively. Concentrations of higher-chlorinated OH-PCBs (hexa- to octa-PCBs) were more than 70% to total OH-PCB concentrations, indicating Baikal seals are mostly risked by higher-chlorinated OH-PCBs. High levels of 4OH-CB146 and 4OH-CB187 and low levels of 4OH-CB107/4'OH-CB108 found in Baikal seals were different from those in other phocidae species, suggesting the unique drug-metabolizing enzyme activities and/or contamination sources in this species. Concentrations of some OH-PCBs in males were significantly higher than those in females. These results suggest that these isomers may be preferentially transferred from mother to pup via cord blood. However, concentrations of almost all the isomers were not significantly correlated with the levels of blood total T3 and T4, implying less impact of PCB-related compounds on the thyroid hormone circulation.

  15. Metabolism of benzene and phenol by a reconstituted purified phenobarbital induced rat liver mixed function oxidase system

    SciTech Connect

    Griffiths, J.C.

    1986-01-01

    Cytochrome P-450 and the electron-donor, NADPH-cytochrome c reductase were isolated from phenobarbital induced rat liver microsomes. Both benzene and its primary metabolite phenol, were substrates for the reconstituted purified phenobarbital induced rat liver mixed function oxidase system. Benzene was metabolized to phenol and the polyhydroxylated metabolites; catechol, hydroquinone and 1,2,4 benzenetriol. Benzene elicited a Type I spectral change upon its interaction with the cytochrome P-450 while phenol's interaction with the cytochrome P-450 produced a reverse Type I spectra. The formation of phenol showed a pH optimum of 7.0 compared with 6.6-6.8 for the production of the polyhyrdoxylated metabolites. Cytochrome P-450 inhibitors, such as metyrapone and SKF 525A, diminished the production of phenol from benzene but not the production of the polyhydroxylated metabolites from phenol. The radical trapping agents, DMSO, KTBA and mannitol, decreased the recovery of polyhydroxylated metabolites, from /sup 14/C-labeled benzene and/or phenol. As KTBA and DMSO interacted with OH. There was a concomitant release of ethylene and methane, which was measured. Desferrioxamine, an iron-chelator and catalase also depressed the recovery of polyhydroxylated metabolites. In summary, benzene and phenol were both substrates for this reconstituted purified enzyme system, but they differed in binding to cytochrome P-450, pH optima and mode of hydroxylation.

  16. CYP3A7*1C allele is associated with reduced levels of 2-hydroxylation pathway oestrogen metabolites

    PubMed Central

    Sood, Deepti; Johnson, Nichola; Jain, Pooja; Siskos, Alexandros P; Bennett, Mark; Gilham, Clare; Busana, Marta Cecilia; Peto, Julian; dos-Santos-Silva, Isabel; Keun, Hector C; Fletcher, Olivia

    2017-01-01

    Background: Endogenous sex hormones are well-established risk factors for breast cancer; the contribution of specific oestrogen metabolites (EMs) and/or ratios of specific EMs is less clear. We have previously identified a CYP3A7*1C allele that is associated with lower urinary oestrone (E1) levels in premenopausal women. The purpose of this analysis was to determine whether this allele was associated with specific pathway EMs. Methods: We measured successfully 12 EMs in mid-follicular phase urine samples from 30 CYP3A7*1C carriers and 30 non-carriers using HPLC-MS/MS. Results: In addition to having lower urinary E1 levels, CYP3A7*1C carriers had significantly lower levels of four of the 2-hydroxylation pathway EMs that we measured (2-hydroxyestrone, P=1.1 × 10−12; 2-hydroxyestradiol, P=2.7 × 10−7; 2-methoxyestrone, P=1.9 × 10−12; and 2-methoxyestradiol, P=0.0009). By contrast, 16α-hydroxylation pathway EMs were slightly higher in carriers and significantly so for 17-epiestriol (P=0.002). Conclusions: The CYP3A7*1C allele is associated with a lower urinary E1 levels, a more pronounced reduction in 2-hydroxylation pathway EMs and a lower ratio of 2-hydroxylation:16α-hydroxylation EMs in premenopausal women. To further characterise the association between parent oestrogens, EMs and subsequent risk of breast cancer, characterisation of additional genetic variants that influence oestrogen metabolism and large prospective studies of a broad spectrum of EMs will be required. PMID:28072767

  17. [Benzene in soft drinks: a study in Florence (Italy)].

    PubMed

    Bonaccorsi, Guglielmo; Perico, Andrea; Colzi, Alessio; Bavazzano, Paolo; Di Giusto, Maurizio; Lamberti, Ilaria; Martino, Gianrocco; Puggelli, Francesco; Lorini, Chiara

    2012-01-01

    The aim of this study was to determine the amount of benzene present in soft drinks sold in Florence (Italy). We analyzed 28 different types of soft drinks, by measuring concentrations of benzoic acid, sorbic acid, ascorbic acid (using high performance liquid chromatography with UV detection) and benzene (using gas chromatography and mass spectrometry). Data was analysed by using SPSS 18.0.Traces of benzene were detected in all analyzed beverages, with a mean concentration of 0.45 µg/L (range: 0.15-2.36 µg/L). Statistically significant differences in mean benzene concentrations were found between beverages according to the type of additive indicated on the drink label, with higher concentrations found in beverages containing both ascorbic acid and sodium benzoate. Two citrus fruit-based drinks were found to have benzene levels above the European limit for benzene in drinking water of 1 µg /L. Sodium benzoate and ascorbic acid were also detected in the two drinks.In conclusion, not all soft drink producers have taken steps to eliminate benzoic acid from their soft drinks and thereby reduce the risk of formation of benzene, as recommended by the European Commission. Furthermore, the presence of benzene in trace amounts in all beverages suggests that migration of constituents of plastic packaging materials or air-borne contamination may be occurring.

  18. The excited state antiaromatic benzene ring: a molecular Mr Hyde?

    PubMed

    Papadakis, Raffaello; Ottosson, Henrik

    2015-09-21

    The antiaromatic character of benzene in its first ππ* excited triplet state (T1) was deduced more than four decades ago by Baird using perturbation molecular orbital (PMO) theory [J. Am. Chem. Soc. 1972, 94, 4941], and since then it has been confirmed through a range of high-level quantum chemical calculations. With focus on benzene we now first review theoretical and computational studies that examine and confirm Baird's rule on reversal in the electron count for aromaticity and antiaromaticity of annulenes in their lowest triplet states as compared to Hückel's rule for the ground state (S0). We also note that the rule according to quantum chemical calculations can be extended to the lowest singlet excited state (S1) of benzene. Importantly, Baird, as well as Aihara [Bull. Chem. Soc. Jpn. 1978, 51, 1788], early put forth that the destabilization and excited state antiaromaticity of the benzene ring should be reflected in its photochemical reactivity, yet, today these conclusions are often overlooked. Thus, in the second part of the article we review photochemical reactions of a series of benzene derivatives that to various extents should stem from the excited state antiaromatic character of the benzene ring. We argue that benzene can be viewed as a molecular "Dr Jekyll and Mr Hyde" with its largely unknown excited state antiaromaticity representing its "Mr Hyde" character. The recognition of the "Jekyll and Hyde" split personality feature of the benzene ring can likely be useful in a range of different areas.

  19. Benzene oxidation coupled to sulfate reduction

    USGS Publications Warehouse

    Lovley, D.R.; Coates, J.D.; Woodward, J.C.; Phillips, E.J.P.

    1995-01-01

    Highly reduced sediments from San Diego Bay, Calif., that were incubated under strictly anaerobic conditions metabolized benzene within 55 days when they were exposed initially to I ??M benzene. The rate of benzene metabolism increased as benzene was added back to the benzene-adapted sediments. When a [14C]benzene tracer was included with the benzene added to benzene-adapted sediments, 92% of the added radioactivity was recovered as 14CO2. Molybdate, an inhibitor of sulfate reduction, inhibited benzene uptake and production of 14CO2 from [14C]benzene. Benzene metabolism stopped when the sediments became sulfate depleted, and benzene uptake resumed when sulfate was added again. The stoichiometry of benzene uptake and sulfate reduction was consistent with the hypothesis that sulfate was the principal electron acceptor for benzene oxidation. Isotope trapping experiments performed with [14C]benzene revealed that there was no production of such potential extracellular intermediates of benzene oxidation as phenol, benzoate, p-hydroxybenzoate, cyclohexane, catechol, and acetate. The results demonstrate that benzene can be oxidized in the absence of O2, with sulfate serving as the electron acceptor, and suggest that some sulfate reducers are capable of completely oxidizing benzene to carbon dioxide without the production of extracellular intermediates. Although anaerobic benzene oxidation coupled to chelated Fe(III) has been documented previously, the study reported here provides the first example of a natural sediment compound that can serve as an electron acceptor for anaerobic benzene oxidation.

  20. Relation between clopidogrel active metabolite levels and different platelet aggregation methods in patients receiving clopidogrel and aspirin.

    PubMed

    Liang, Yan; Johnston, Marilyn; Hirsh, Jack; Pare, Guillaume; Li, Chunjian; Mehta, Shamir; Teo, Koon K; Sloane, Debi; Yi, Qilong; Zhu, Jun; Eikelboom, John W

    2012-11-01

    Clopidogrel is a prodrug that undergoes bioconversion via cytochrome P450 system to form an active metabolite (AM) that binds to the platelet ADP receptor. The antiplatelet effect of clopidogrel is commonly assessed by measuring the aggregatory response to 5 μM ADP by light transmission aggregation (LTA) or multiple electrode aggregometry (MEA) or by the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI). To determine which of these three tests of platelet ADP receptor pathway inhibition most closely correlates with clopidogrel AM levels. We analyzed blood samples from 82 patients with coronary artery disease who were randomized to receive double-dose or standard dose clopidogrel for 2 weeks. We measured peak clopidogrel AM levels, platelet aggregation in response to ADP and VASP-PRI on days 1, and repeated all the measures on days 7 and 14. Linear regression analysis was used to examine the correlation between clopidogrel AM and LTA, MEA and VASP-PRI. Bland-Altman plots were used to explore the agreement between tests of the antiplatelet effects of clopidogrel. Clopidogrel AM on day 1 correlated most closely with VASP-PRI (r = -0.5767) and demonstrated weaker correlations with LTA (r = -0.4656) and MEA (r = -0.3384) (all p < 0.01). Intra-class correlation (ICC) between VASP-PRI and LTA was 0.6446; VASP-PRI and MEA was 0.4720; and LTA and MEA was 0.4693. Similar results were obtained on days 7 and 14. Commonly used pharmacodynamic measures of clopidogrel response are only moderately correlated with clopidogrel AM levels and may not be suitable to measure the adequacy of clopidogrel therapy.

  1. Urinary t,t-muconic acid, S-phenylmercapturic acid and benzene as biomarkers of low benzene exposure.

    PubMed

    Fustinoni, Silvia; Buratti, Marina; Campo, Laura; Colombi, Antonio; Consonni, Dario; Pesatori, Angela C; Bonzini, Matteo; Farmer, Peter; Garte, Seymour; Valerio, Federico; Merlo, Domenico F; Bertazzi, Pier A

    2005-05-30

    This research compared the capability of urinary trans,trans-muconic acid (t,t-MA), S-phenylmercapturic acid (S-PMA) and benzene excreted in urine (U-benzene) to monitor low benzene exposure and evaluated the influence of smoking habit on these indices. Gasoline attendants, urban policemen, bus drivers and two groups of referents working in two large Italian cities (415 people) were studied. Median benzene exposure was 61, 22, 21, 9 and 6 microg/m3, respectively, with higher levels in workers than in referents. U-benzene, but not t,t-MA and S-PMA, showed an exposure-related increase. All the biomarkers were strongly influenced by cigarette smoking, with values up to five-fold higher in smokers compared to non-smokers. In conclusion, in the range of investigated benzene exposure (<478 microg/m3 or <0.15 ppm), the smoking habit may be regarded as a major source of benzene intake; among the study indices, U-benzene is the marker of choice for the biological monitoring of occupational and environmental exposure.

  2. Hematotoxicity and carcinogenicity of benzene

    SciTech Connect

    Aksoy, M. )

    1989-07-01

    The hematotoxicity of benzene exposure has been well known for a century. Benzene causes leukocytopenia, thrombocytopenia, pancytopenia, etc. The clinical and hematologic picture of aplastic anemia resulting from benzene exposure is not different from classical aplastic anemia; in some cases, mild bilirubinemia, changes in osmotic fragility, increase in lactic dehydrogenase and fecal urobilinogen, and occasionally some neurological abnormalities are found. Electromicroscopic findings in some cases of aplastic anemia with benzene exposure were similar to those observed by light microscopy. Benzene hepatitis-aplastic anemia syndrome was observed in a technician with benzene exposure. Ten months after occurrence of hepatitis B, a severe aplastic anemia developed. The first epidemiologic study proving the leukemogenicity of benzene was performed between 1967 and 1973 to 1974 among shoe workers in Istanbul. The incidence of leukemia was 13.59 per 100,000, which is a significant increase over that of leukemia in the general population. Following the prohibition and discontinuation of the use of benzene in Istanbul, there was a striking decrease in the number of leukemic shoe workers in Istanbul. In 23.7% of the series, consisting of 59 leukemic patients with benzene exposure, there was a preceding pancytopenic period. Furthermore, a familial connection was found in 10.2% of them. The 89.8% of the series showed the findings of acute leukemia. The possible factors that may determine the types of leukemia in benzene toxicity are discussed. The possible role of benzene exposure is presented in the development of malignant lymphoma, multiple myeloma, and lung cancer.

  3. Benzene stripping in a flotation unit

    SciTech Connect

    Hillquist, D.; Litchfield, J.; Willet, S.; Whiteford, R.

    1994-12-31

    An induced gas flotation unit is used as a combination stripping/flotation vessel with fuel gas as the stripping/flotation medium. The gas bubbles simultaneously float the oils and solids, and strip out and recover the benzene and other volatile components from wastewater and from the floated oils and solids. The effluent stripping gas is then either used as fuel gas, or recycled to the process for product recovery. The induced gas flotation stripper, IGFS, is self-cleaning and normally experiences no sludge build up or fouling. The unit requires a minimum of operator attention and maintenance. It is sealed to eliminate emissions, has a high stripping efficiency, and has a significantly wider operating range than conventional strippers. The unit does not experience the biological fouling and disposal problems of air strippers, or the fouling and higher capital and operating costs of steam strippers. The IGFS unit was installed at the BF Goodrich ethylene plant in Calvert City in 1991. The unit was designed to treat a combined stream consisting of quench water, neutralized spent caustic, and a number of intermittent smaller oily water streams. The unit is operating effectively in stripping the benzene to levels below the NESHAP requirements. The average benzene removal efficiency is above 97%. Operating data indicate that the benzene removal efficiency can be further enhanced by increasing temperature, increasing stripping flow, reducing oil emulsions in the influent and eliminating dilution from recycled water. This paper presents performance and operating experience of the IGFS unit.

  4. Comparison of Current-Use Pesticide and Other Toxicant Urinary Metabolite Levels among Pregnant Women in the CHAMACOS Cohort and NHANES

    PubMed Central

    Castorina, Rosemary; Bradman, Asa; Fenster, Laura; Barr, Dana Boyd; Bravo, Roberto; Vedar, Michelle G.; Harnly, Martha E.; McKone, Thomas E.; Eisen, Ellen A.; Eskenazi, Brenda

    2010-01-01

    Background We measured 34 metabolites of current-use pesticides and other precursor compounds in urine samples collected twice during pregnancy from 538 women living in the Salinas Valley of California, a highly agricultural area (1999–2001). Precursors of these metabolites included fungicides, carbamate, organochlorine, organophosphorus (OP), and pyrethroid insecticides, and triazine and chloroacetanilide herbicides. We also measured ethylenethiourea, a metabolite of the ethylene-bisdithiocarbamate fungicides. Repeat measurements of the compounds presented here have not been reported in pregnant women previously. To understand the impact of the women’s regional environment on these findings, we compared metabolite concentrations from the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) cohort with U.S. national reference data for 342 pregnant women sampled by the National Health and Nutrition Examination Survey (1999–2002). Results The eight metabolites detected in > 50% of samples [2,4-dichlorophenol (2,4-DCP); 2,5-dichlorophenol (2,5-DCP); 1- and 2-naphthol; ortho-phenylphenol (ORTH); para-nitrophenol (PNP); 2,4,6-trichlorophenol (2,4,6-TCP); and 3,4,6-trichloro-2-pyridinol (TCPy)] may be related to home or agricultural pesticide use in the Salinas Valley, household products, and other sources of chlorinated phenols. More than 78% of women in this study had detectable levels of at least one of the OP pesticide-specific metabolites that we measured, and > 30% had two or more. The 95th percentile values of six of the most commonly detected (> 50%) compounds were significantly higher among the CHAMACOS women after controlling for age, race, socioeconomic status, and smoking [(2,4-DCP; 2,5-DCP; ORTH; PNP; 2,4,6-TCP; and TCPy); quantile regression p < 0.05]. Conclusions Findings suggest that the CHAMACOS cohort has an additional burden of precursor pesticide exposure compared with the national sample, possibly from living and

  5. Induction of granulocytic differentiation in a mouse model by benzene and hydroquinone

    SciTech Connect

    Hazel, B.A.; O`Connor, A.; Niculescu, R.; Kalf, G.F.

    1996-12-01

    Chronic exposure of humans to benzene causes acute myelogenous leukemia (AML). The studies presented here were undertaken to determine whether benzene, or its reactive metabolite, hydroquinone (HQ), affects differentiation of myeloblasts. Benzene or HQ administered to C57BL/6J mice specifically induced granulocytic differentiation of myeloblasts. The ability of these compounds to induce differentiation of the myeloblast was tested directly using the murine interleukin 3 (IL-3)-dependent 32D.3 (G) myeloblastic cell line, and the human HL-60 promyelocytic leukemia cell line. 37 refs., 8 figs., 4 tabs.

  6. Benzene exposure and the effect of traffic pollution in Copenhagen, Denmark

    NASA Astrophysics Data System (ADS)

    Skov, Henrik; Hansen, Asger B.; Lorenzen, Gitte; Andersen, Helle Vibeke; Løfstrøm, Per; Christensen, Carsten S.

    Benzene is a carcinogenic compound, which is emitted from petrol-fuelled cars and thus is found ubiquitous in all cities. As part of the project Monitoring of Atmospheric Concentrations of Benzene in European Towns and Homes (MACBETH) six campaigns were carried out in the Municipality of Copenhagen, Denmark. The campaigns were distributed over 1 year. In each campaign, the personal exposure to benzene of 50 volunteers (non-smokers living in non-smoking families) living and working in Copenhagen was measured. Simultaneously, benzene was measured in their homes and in an urban network distributed over the municipality. The Radiello diffusive sampler was applied to sample 5 days averages of benzene and other hydrocarbons. Comparison of the results with those from a BTX-monitor showed excellent agreement. The exposure and the concentrations in homes and in the urban area were found to be close to log-normal distribution. The annual averages of the geometrical mean values were 5.22, 4.30 and 2.90 μg m -3 for personal exposure, home concentrations and urban concentrations, respectively. Two main parameters are controlling the general level of benzene in Copenhagen: firstly, the emission from traffic and secondly, dispersion due to wind speed. The general level of exposure to benzene and home concentrations of benzene were strongly correlated with the outdoor level of benzene, which indicated that traffic is an important source for indoor concentrations of benzene and for the exposure to benzene.

  7. Phenylalanine and tyrosine levels are rate-limiting factors in production of health promoting metabolites in Vitis vinifera cv. Gamay Red cell suspension

    PubMed Central

    Manela, Neta; Oliva, Moran; Ovadia, Rinat; Sikron-Persi, Noga; Ayenew, Biruk; Fait, Aaron; Galili, Gad; Perl, Avichai; Weiss, David; Oren-Shamir, Michal

    2015-01-01

    Environmental stresses such as high light intensity and temperature cause induction of the shikimate pathway, aromatic amino acids (AAA) pathways, and of pathways downstream from AAAs. The induction leads to production of specialized metabolites that protect the cells from oxidative damage. The regulation of the diverse AAA derived pathways is still not well understood. To gain insight on that regulation, we increased AAA production in red grape Vitis vinifera cv. Gamay Red cell suspension, without inducing external stress on the cells, and characterized the metabolic effect of this induction. Increased AAA production was achieved by expressing a feedback-insensitive bacterial form of 3-deoxy- D-arabino-heptulosonate 7-phosphate synthase enzyme (AroG*) of the shikimate pathway under a constitutive promoter. The presence of AroG* protein led to elevated levels of primary metabolites in the shikimate and AAA pathways including phenylalanine and tyrosine, and to a dramatic increase in phenylpropanoids. The AroG* transformed lines accumulated up to 20 and 150 fold higher levels of resveratrol and dihydroquercetin, respectively. Quercetin, formed from dihydroquercetin, and resveratrol, are health promoting metabolites that are induced due to environmental stresses. Testing the expression level of key genes along the stilbenoids, benzenoids, and phenylpropanoid pathways showed that transcription was not affected by AroG*. This suggests that concentrations of AAAs, and of phenylalanine in particular, are rate-limiting in production of these metabolites. In contrast, increased phenylalanine production did not lead to elevated concentrations of anthocyanins, even though they are also phenylpropanoid metabolites. This suggests a control mechanism of this pathway that is independent of AAA concentration. Interestingly, total anthocyanin concentrations were slightly lower in AroG* cells, and the relative frequencies of the different anthocyanins changed as well. PMID:26236327

  8. Fuel Dependence of Benzene Pathways

    SciTech Connect

    Zhang, H; Eddings, E; Sarofim, A; Westbrook, C

    2008-07-14

    The relative importance of formation pathways for benzene, an important precursor to soot formation, was determined from the simulation of 22 premixed flames for a wide range of equivalence ratios (1.0 to 3.06), fuels (C{sub 1}-C{sub 12}), and pressures (20 to 760 torr). The maximum benzene concentrations in 15 out of these flames were well reproduced within 30% of the experimental data. Fuel structural properties were found to be critical for benzene production. Cyclohexanes and C{sub 3} and C{sub 4} fuels were found to be among the most productive in benzene formation; and long-chain normal paraffins produce the least amount of benzene. Other properties, such as equivalence ratio and combustion temperatures, were also found to be important in determining the amount of benzene produced in flames. Reaction pathways for benzene formation were examined critically in four premixed flames of structurally different fuels of acetylene, n-decane, butadiene, and cyclohexane. Reactions involving precursors, such as C{sub 3} and C{sub 4} species, were examined. Combination reactions of C{sub 3} species were identified to be the major benzene formation routes with the exception of the cyclohexane flame, in which benzene is formed exclusively from cascading fuel dehydrogenation via cyclohexene and cyclohexadiene intermediates. Acetylene addition makes a minor contribution to benzene formation, except in the butadiene flame where C{sub 4}H{sub 5} radicals are produced directly from the fuel, and in the n-decane flame where C{sub 4}H{sub 5} radicals are produced from large alkyl radical decomposition and H atom abstraction from the resulting large olefins.

  9. Plasma levels of brain derived-neurotrophic factor and catecholamine metabolites are increased during active phase of psychotic symptoms in CNS lupus: a case report.

    PubMed

    Ikenouchi, Atsuko; Yoshimura, Reiji; Ikemura, Naomi; Utsunomiya, Kensuke; Mitoma, Masae; Nakamura, Jun

    2006-09-30

    In the present study, the authors reported a case of systemic lupus erythematosus (SLE) with central nervous system involvement (CNS lupus). The authors also longitudinally investigated plasma levels of brain-derived neurotrophic factor (BDNF) and catecholamine metabolites in the patient, and found that plasma levels of BDNF, 3-methoxy-4-hydroxyphenylglycol (MHPG), and homovanillic acid (HVA) were raised in accordance with the severity of psychotic symptoms in this case of CNS lupus. These results suggest that it is useful to measure plasma levels of BDNF and the catecholamine metabolites in order to predict the severity of psychotic symptoms in CNS lupus and to provide a differential diagnosis from that of steroid-induced psychosis.

  10. Dehydrin, alcohol dehydrogenase, and central metabolite levels are associated with cold tolerance in diploid strawberry (Fragaria spp.).

    PubMed

    Davik, Jahn; Koehler, Gage; From, Britta; Torp, Torfinn; Rohloff, Jens; Eidem, Petter; Wilson, Robert C; Sønsteby, Anita; Randall, Stephen K; Alsheikh, Muath

    2013-01-01

    The use of artificial freezing tests, identification of biomarkers linked to or directly involved in the low-temperature tolerance processes, could prove useful in applied strawberry breeding. This study was conducted to identify genotypes of diploid strawberry that differ in their tolerance to low-temperature stress and to investigate whether a set of candidate proteins and metabolites correlate with the level of tolerance. 17 Fragaria vesca, 2 F. nilgerrensis, 2 F. nubicola, and 1 F. pentaphylla genotypes were evaluated for low-temperature tolerance. Estimates of temperatures where 50 % of the plants survived (LT₅₀) ranged from -4.7 to -12.0 °C between the genotypes. Among the F. vesca genotypes, the LT₅₀ varied from -7.7 °C to -12.0 °C. Among the most tolerant were three F. vesca ssp. bracteata genotypes (FDP821, NCGR424, and NCGR502), while a F. vesca ssp. californica genotype (FDP817) was the least tolerant (LT₅₀) -7.7 °C). Alcohol dehydrogenase (ADH), total dehydrin expression, and content of central metabolism constituents were assayed in select plants acclimated at 2 °C. The LT₅₀ estimates and the expression of ADH and total dehydrins were highly correlated (r(adh) = -0.87, r (dehyd) = -0.82). Compounds related to the citric acid cycle were quantified in the leaves during acclimation. While several sugars and acids were significantly correlated to the LT₅₀ estimates early in the acclimation period, only galactinol proved to be a good LT₅₀ predictor after 28 days of acclimation (r(galact) = 0.79). It is concluded that ADH, dehydrins, and galactinol show great potential to serve as biomarkers for cold tolerance in diploid strawberry.

  11. Variability of Organophosphorous Pesticide Metabolite Levels in Spot and 24-hr Urine Samples Collected from Young Children during 1 Week

    PubMed Central

    Kogut, Katherine; Eisen, Ellen A.; Jewell, Nicholas P.; Quirós-Alcalá, Lesliam; Castorina, Rosemary; Chevrier, Jonathan; Holland, Nina T.; Barr, Dana Boyd; Kavanagh-Baird, Geri; Eskenazi, Brenda

    2012-01-01

    Background: Dialkyl phosphate (DAP) metabolites in spot urine samples are frequently used to characterize children’s exposures to organophosphorous (OP) pesticides. However, variable exposure and short biological half-lives of OP pesticides could result in highly variable measurements, leading to exposure misclassification. Objective: We examined within- and between-child variability in DAP metabolites in urine samples collected during 1 week. Methods: We collected spot urine samples over 7 consecutive days from 25 children (3–6 years of age). On two of the days, we collected 24-hr voids. We assessed the reproducibility of urinary DAP metabolite concentrations and evaluated the sensitivity and specificity of spot urine samples as predictors of high (top 20%) or elevated (top 40%) weekly average DAP metabolite concentrations. Results: Within-child variance exceeded between-child variance by a factor of two to eight, depending on metabolite grouping. Although total DAP concentrations in single spot urine samples were moderately to strongly associated with concentrations in same-day 24-hr samples (r ≈ 0.6–0.8, p < 0.01), concentrations in spot samples collected > 1 day apart and in 24-hr samples collected 3 days apart were weakly correlated (r ≈ –0.21 to 0.38). Single spot samples predicted high (top 20%) and elevated (top 40%) full-week average total DAP excretion with only moderate sensitivity (≈ 0.52 and ≈ 0.67, respectively) but relatively high specificity (≈ 0.88 and ≈ 0.78, respectively). Conclusions: The high variability we observed in children’s DAP metabolite concentrations suggests that single-day urine samples provide only a brief snapshot of exposure. Sensitivity analyses suggest that classification of cumulative OP exposure based on spot samples is prone to type 2 classification errors. PMID:23052012

  12. Lower Serum Vitamin D Metabolite Levels in Relation to Circulating Cytokines/Chemokines and Metabolic Hormones in Pregnant Women with Hypertensive Disorders

    PubMed Central

    Adela, Ramu; Borkar, Roshan M.; Mishra, Navneeta; Bhandi, Murali Mohan; Vishwakarma, Gayatri; Varma, B. Aparna; Ragampeta, Srinivas; Banerjee, Sanjay K.

    2017-01-01

    The aim of this study was to investigate whether lower serum vitamin D metabolite levels were associated with altered cytokine/chemokine and metabolic hormone levels in three different hypertensive disorders in pregnancy (HDP). Healthy pregnancy (n = 30) and hypertensive disorders in pregnancy (HDP) (n = 30), i.e., gestational hypertension (GH), preeclampsia (PE), and eclampsia (EC) subjects were enrolled. Vitamin D metabolites were measured by UPLC/APCI/HRMS method. Circulatory 27 cytokines/chemokines and 10 metabolic hormones were measured. Significantly decreased 25(OH)D and 1,25(OH)2D levels were observed in HDP. The levels of 25(OH)D were significantly lower in PE and EC, whereas the serum levels of 1,25(OH)2D significantly decreased only in EC subjects. Serum 25(OH)D and 1,25(OH)2D levels were negatively correlated with systolic- and diastolic blood pressure, creatinine, and uric acid levels. Serum interleukin (IL)-6 and IL-13 decreased, and GIP levels were increased in gestational hypertensive subjects. Platelet-derived growth factor-BB and IL-8 levels were increased and macrophage inflammatory protein-1beta levels were decreased in EC subjects. IL-8 and IL-10 increased, and rantes and GIP levels decreased in the EC group as compared with the GH group. Multivariate logistic regression analysis showed that eotaxin, monocyte chemotactic protein-1, 25(OH)D, and 1,25(OH)2D were predictors of HDP. Our analyses suggest that lower vitamin D metabolites are associated with altered cytokines/chemokines and metabolic hormones in HDP. PMID:28348564

  13. Spatial and temporal variations in atmospheric VOCs, NO2, SO2, and O3 concentrations at a heavily industrialized region in Western Turkey, and assessment of the carcinogenic risk levels of benzene

    NASA Astrophysics Data System (ADS)

    Civan, Mihriban Yılmaz; Elbir, Tolga; Seyfioglu, Remzi; Kuntasal, Öznur Oğuz; Bayram, Abdurrahman; Doğan, Güray; Yurdakul, Sema; Andiç, Özgün; Müezzinoğlu, Aysen; Sofuoglu, Sait C.; Pekey, Hakan; Pekey, Beyhan; Bozlaker, Ayse; Odabasi, Mustafa; Tuncel, Gürdal

    2015-02-01

    Ambient concentrations of volatile organic compounds (VOCs), nitrogen dioxide (NO2), sulphur dioxide (SO2) and ground-level ozone (O3) were measured at 55 locations around a densely populated industrial zone, hosting a petrochemical complex (Petkim), a petroleum refinery (Tupras), ship-dismantling facilities, several iron and steel plants, and a gas-fired power plant. Five passive sampling campaigns were performed covering summer and winter seasons of 2005 and 2007. Elevated concentrations of VOCs, NO2 and SO2 around the refinery, petrochemical complex and roads indicated that industrial activities and vehicular emissions are the main sources of these pollutants in the region. Ozone concentrations were low at the industrial zone and settlement areas, but high in rural stations downwind from these sources due to NO distillation. The United States Environmental Protection Agency's positive matrix factorization receptor model (EPA PMF) was employed to apportion ambient concentrations of VOCs into six factors, which were associated with emissions sources. Traffic was found to be highest contributor to measured ∑VOCs concentrations, followed by the Petkim and Tupras. Median cancer risk due to benzene inhalation calculated using a Monte Carlo simulation was approximately 4 per-one-million population, which exceeded the U.S. EPA benchmark of 1 per one million. Petkim, Tupras and traffic emissions were the major sources of cancer risk due to benzene inhalation in the Aliaga airshed. Relative contributions of these two source groups changes significantly from one location to another, demonstrating the limitation of determining source contributions and calculating health risk using data from one or two permanent stations in an industrial area.

  14. Genotoxic monitoring and benzene exposure assessment of gasoline station workers in metropolitan Bangkok: sister chromatid exchange (SCE) and urinary trans, trans-muconic acid (t,t-MA).

    PubMed

    Tunsaringkarn, Tanasorn; Suwansaksri, Jamsai; Soogarun, Suphan; Siriwong, Wattasit; Rungsiyothin, Anusorn; Zapuang, Kalaya; Robson, Mark

    2011-01-01

    Early warning of the potential of mutagens or carcinogens caused by benzene exposure that might occur in gasoline station workers can be achieved by examining 2 major biomarkers: sister chromatid exchange (SCE) and trans, trans-muconic acid (t,t-MA), a urinary metabolite of benzene. The main objective of this study was to assess benzene exposure and monitor the genotoxic effect of gasoline station workers in Bangkok, Thailand. Blood and urine samples were collected from 33 gasoline station workers, working in Pathumwan district area, central Bangkok, Thailand, for SCE and t,t-MA analysis, from April to June 2009. Control samples were collected from 30 office workers and students in the same area at the same period. Our results indicated significantly higher frequencies of SCE in gasoline exposed workers were than in controls (p<0.01), independent of gender. Urinary t,t-MA and t,t-MA/creatinine levels of gasoline exposed workers were also significantly higher than the control groups (p<0.05) were significantly higher in women than men workers (p<0.01). Calculated chromosomal damage relative risk (RR) of gasoline station workers was 3.00 (95% CI = 1.81 - 4.98, p<0.001) compared to controls. The gasoline exposed workers had potentially higher risk of chromosomal damage and cancer development because of direct contact to benzene.

  15. Effects of sequential feeding with low- and high-protein diets on growth performances and plasma metabolite levels in geese.

    PubMed

    Ho, S-Y; Chen, Y-H; Yang, S-K

    2015-06-01

    This study was conducted by two trials to investigate effects of sequential feeding with low- and high-protein diets on growth traits and plasma metabolites in geese. In Trial I, the effect of sequential feeding under time-restricted feeding system was investigated. Seventy-two White Roman goslings were randomly allotted into either sequential feeding (S1) or control feeding (C1) group. All goslings were fed for 1 h at morning and at evening, respectively, from 2 to 8 weeks of age. S1 group was offered 13% CP diet at morning and 19% CP diet at evening. C1 group was offered the same diet (16% CP; mixed equally with the two diets mentioned above) at both morning and evening. Blood samples were hourly collected for 4 h after feeding at both morning and evening for the determination of the postprandial plasma levels of glucose, triacylglycerol and uric acid at the end of experiment. Results showed that BW, average daily gain (ADG), and daily feed intake (FI) were not different between groups, but the feed efficiency (FE) in S1 group was significantly higher than that in C1 group (P<0.05). The areas under curve (AUC) of plasma postprandial levels of glucose, triacylglycerol and uric acid were not affected by treatment, but the AUC of triacylglycerol and uric acid in morning were lower than those in evening (P<0.05). In Trial II, the effect of sequential feeding under ad libitum feeding system was investigated. Twenty-four goslings were randomly allotted into either sequential feeding (S2) or control feeding (C2) group. Diets were altered at 0600 and 1800 h, respectively, and geese were fed ad libitum from 4 to 8 weeks of age. S2 group was offered 14% CP diet at morning and 20% CP diet at evening. C2 group was supplied the same diet (mixed with the two diets according to the ratio of diets consumed by S2 group on the preceded day) at both morning and evening. Results showed that the ADG in S2 group was higher than those in C2 group (P<0.05). Summarized data from both

  16. Effect of prepartal and postpartal dietary fat level on performance and plasma concentration of metabolites in transition dairy cows.

    PubMed

    Karimian, M; Khorvash, M; Forouzmand, M A; Alikhani, M; Rahmani, H R; Ghaffari, M H; Petit, H V

    2015-01-01

    The objective of this study was to determine the effects of 2 levels of dietary fat (low and high) offered during the prepartal and postpartal periods on dry matter intake (DMI), plasma concentration of metabolites, and milk yield and composition. Twenty-four Holstein dry cows were assigned on d 21 relative to expected parturition date to 1 of 4 treatments in a 2×2 factorial arrangement of 2 levels of fat fed during the prepartal period and 2 levels of fat fed during the postpartal period: prepartal low fat and postpartal low fat (LF-LF), prepartal low fat and postpartal high fat (LF-HF), prepartal high fat and postpartal low fat (HF-LF), or prepartal high fat and postpartal high fat (HF-HF). Prepartal and postpartal LF diets contained no fat supplement. Prepartal HF diets contained 1.60% calcium salts of soybean oil. The proportion of calcium salts of soybean oil was increased to 1.70% of DM for the first 21 d of lactation and to 2.27% of DM from d 21 to 56 of lactation in the HF diet. Diets were fed for ad libitum intake from d 21 before calving until d 56 of gestation. Prepartal DMI was lower for cows fed the HF diet compared with those fed the LF diet (12.6 vs. 16.2kg/d). Postpartum, cows fed the HF-HF and HF-LF diets had, respectively, the lowest and highest DMI, although no significant differences existed between HF-LF and LF-LF. Net energy intake was higher for cows fed the postpartal HF diets compared with those fed the LF diets. Prepartal fat level had no effect on net energy intake. Cows offered the prepartal HF diet had higher milk yield when offered the postpartal LF diet compared with those offered the postpartal HF diet and no effect of the postpartal fat level was detected when cows were fed the prepartal LF diet. Milk composition was similar among treatments. Plasma cholesterol concentration postpartum was higher for cows fed the prepartal LF diet than for those fed the prepartal HF diet (5.16 vs. 3.74mmol/L) and postpartal fat level had no effect

  17. Temporal variability of pyrethroid metabolite levels in bedtime, morning, and 24-hr urine samples for 50 adults in North Carolina

    EPA Science Inventory

    Pyrethroid insecticides are widely used to control insects in both agricultural and residential settings worldwide. Few data are available on the temporal variability of pyrethroid metabolites in the urine of non-occupationally exposed adults. In this work, we describe the study ...

  18. Systemic exposure to PAHs and benzene in firefighters suppressing controlled structure fires.

    PubMed

    Fent, Kenneth W; Eisenberg, Judith; Snawder, John; Sammons, Deborah; Pleil, Joachim D; Stiegel, Matthew A; Mueller, Charles; Horn, Gavin P; Dalton, James

    2014-08-01

    Turnout gear provides protection against dermal exposure to contaminants during firefighting; however, the level of protection is unknown. We explored the dermal contribution to the systemic dose of polycyclic aromatic hydrocarbons (PAHs) and other aromatic hydrocarbons in firefighters during suppression and overhaul of controlled structure burns. The study was organized into two rounds, three controlled burns per round, and five firefighters per burn. The firefighters wore new or laundered turnout gear tested before each burn to ensure lack of PAH contamination. To ensure that any increase in systemic PAH levels after the burn was the result of dermal rather than inhalation exposure, the firefighters did not remove their self-contained breathing apparatus until overhaul was completed and they were >30 m upwind from the burn structure. Specimens were collected before and at intervals after the burn for biomarker analysis. Urine was analyzed for phenanthrene equivalents using enzyme-linked immunosorbent assay and a benzene metabolite (s-phenylmercapturic acid) using liquid chromatography/tandem mass spectrometry; both were adjusted by creatinine. Exhaled breath collected on thermal desorption tubes was analyzed for PAHs and other aromatic hydrocarbons using gas chromatography/mass spectrometry. We collected personal air samples during the burn and skin wipe samples (corn oil medium) on several body sites before and after the burn. The air and wipe samples were analyzed for PAHs using a liquid chromatography with photodiode array detection. We explored possible changes in external exposures or biomarkers over time and the relationships between these variables using non-parametric sign tests and Spearman tests, respectively. We found significantly elevated (P < 0.05) post-exposure breath concentrations of benzene compared with pre-exposure concentrations for both rounds. We also found significantly elevated post-exposure levels of PAHs on the neck compared with pre

  19. Systemic Exposure to PAHs and Benzene in Firefighters Suppressing Controlled Structure Fires

    PubMed Central

    Fent, Kenneth W.; Eisenberg, Judith; Snawder, John; Sammons, Deborah; Pleil, Joachim D.; Stiegel, Matthew A.; Mueller, Charles; Horn, Gavin P.; Dalton, James

    2014-01-01

    Turnout gear provides protection against dermal exposure to contaminants during firefighting; however, the level of protection is unknown. We explored the dermal contribution to the systemic dose of polycyclic aromatic hydrocarbons (PAHs) and other aromatic hydrocarbons in firefighters during suppression and overhaul of controlled structure burns. The study was organized into two rounds, three controlled burns per round, and five firefighters per burn. The firefighters wore new or laundered turnout gear tested before each burn to ensure lack of PAH contamination. To ensure that any increase in systemic PAH levels after the burn was the result of dermal rather than inhalation exposure, the firefighters did not remove their self-contained breathing apparatus until overhaul was completed and they were >30 m upwind from the burn structure. Specimens were collected before and at intervals after the burn for biomarker analysis. Urine was analyzed for phenanthrene equivalents using enzyme-linked immunosorbent assay and a benzene metabolite (s-phenylmercapturic acid) using liquid chromatography/tandem mass spectrometry; both were adjusted by creatinine. Exhaled breath collected on thermal desorption tubes was analyzed for PAHs and other aromatic hydrocarbons using gas chromatography/mass spectrometry. We collected personal air samples during the burn and skin wipe samples (corn oil medium) on several body sites before and after the burn. The air and wipe samples were analyzed for PAHs using a liquid chromatography with photodiode array detection. We explored possible changes in external exposures or biomarkers over time and the relationships between these variables using non-parametric sign tests and Spearman tests, respectively. We found significantly elevated (P < 0.05) post-exposure breath concentrations of benzene compared with pre-exposure concentrations for both rounds. We also found significantly elevated post-exposure levels of PAHs on the neck compared with pre

  20. Fast method for simultaneous quantification of tamoxifen and metabolites in dried blood spots using an entry level LC-MS/MS system.

    PubMed

    Tré-Hardy, Marie; Capron, Arnaud; Antunes, Marina Venzon; Linden, Rafael; Wallemacq, Pierre

    2016-11-01

    The purpose of this study was to develop and validate a new liquid chromatography-tandem mass spectrometric (LC-MSMS) assay for the simultaneous quantification of tamoxifen (TAM) and its main therapeutically active metabolites, N-desmethyltamoxifen (NDT), 4-hydroxytamoxifen (4HT) and endoxifen (END) in dried blood spots. Ultrasound assisted methanolic extraction was used for TAM and metabolites extraction from dried blood spot. After evaporation and methanol reconstitution, the extract was injected into a LC-MSMS system. Reversed phase chromatography was performed on a C18 grafted column in gradient mode. TAM, metabolites, and internal standard (diazepam-d5; IS) were identified in positive electrospray ionization mode using m/z transition of 372.5>72.1 (TAM); 374.23>58.10 (END); 358.27>58.10 (NDT); 388.23>44.80 (4HT) and 290.00>198.00 (IS). Total analytical run time was 6.5min. Assay was linear from 1 to 500ng/mL for all substances and presented intra and inter-assay precision and accuracy <15%. TAM, NDT, 4HT and END limits of quantification and detection were of 1 and 0.5ng/mL; 1 and 3ng/mL; 1.7 and 3ng/mL; 0.6 and 2ng/mL, respectively. Recovery ranged from 83.8 to 96.3% with matrix effect ranged from 4.3 to 29.8% for TAM and its metabolites. Hematocrit value ≤40% appeared to negatively influence accuracy of the method. In conclusion, the method described here is somewhat accessible, relatively fast, sensitive and selective with no interference. This assay might be used to investigate the level of TAM and its metabolites in DBS for therapeutic drug monitoring purposes.

  1. Collision lifetimes of polyatomic molecules at low temperatures: Benzene-benzene vs benzene-rare gas atom collisions

    NASA Astrophysics Data System (ADS)

    Cui, Jie; Li, Zhiying; Krems, Roman V.

    2014-10-01

    We use classical trajectory calculations to study the effects of the interaction strength and the geometry of rigid polyatomic molecules on the formation of long-lived collision complexes at low collision energies. We first compare the results of the calculations for collisions of benzene molecules with rare gas atoms He, Ne, Ar, Kr, and Xe. The comparison illustrates that the mean lifetimes of the collision complexes increase monotonically with the strength of the atom-molecule interaction. We then compare the results of the atom-benzene calculations with those for benzene-benzene collisions. The comparison illustrates that the mean lifetimes of the benzene-benzene collision complexes are significantly reduced due to non-ergodic effects prohibiting the molecules from sampling the entire configuration space. We find that the thermally averaged lifetimes of the benzene-benzene collisions are much shorter than those for Xe with benzene and similar to those for Ne with benzene.

  2. Collision lifetimes of polyatomic molecules at low temperatures: benzene-benzene vs benzene-rare gas atom collisions.

    PubMed

    Cui, Jie; Li, Zhiying; Krems, Roman V

    2014-10-28

    We use classical trajectory calculations to study the effects of the interaction strength and the geometry of rigid polyatomic molecules on the formation of long-lived collision complexes at low collision energies. We first compare the results of the calculations for collisions of benzene molecules with rare gas atoms He, Ne, Ar, Kr, and Xe. The comparison illustrates that the mean lifetimes of the collision complexes increase monotonically with the strength of the atom-molecule interaction. We then compare the results of the atom-benzene calculations with those for benzene-benzene collisions. The comparison illustrates that the mean lifetimes of the benzene-benzene collision complexes are significantly reduced due to non-ergodic effects prohibiting the molecules from sampling the entire configuration space. We find that the thermally averaged lifetimes of the benzene-benzene collisions are much shorter than those for Xe with benzene and similar to those for Ne with benzene.

  3. Quantitative Profiling of Hydroxy Lipid Metabolites in Mouse Organs Reveals Distinct Lipidomic Profiles and Modifications Due to Elevated n-3 Fatty Acid Levels

    PubMed Central

    Chiu, Cheng-Ying; Smyl, Christopher; Dogan, Inci; Rothe, Michael; Weylandt, Karsten-H.

    2017-01-01

    Polyunsaturated fatty acids (PUFA) are precursors of bioactive metabolites and mediators. In this study, the profile of hydroxyeicosatetraenoic (HETE), hydroxyeicosapentaenoic (HEPE) and hydroxydocosahexaenoic (HDHA) acids derived from arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in colon, liver, lung, spleen, muscle, heart and kidney tissue of healthy wildtype mice were characterized, and compared to profiles in organs from transgenic fat-1 mice engineered to express the Caenorhabditis elegans fat-1 gene encoding an n-3 desaturase and thereby with endogenously elevated n-3 PUFA levels. PUFAs were measured using gas chromatography. The lipid metabolites were assayed using LC-MS/MS. AA and DHA were the prominent PUFAs in wildtype and fat-1 mice. EPA levels were low in both groups even though there was a significant increase in fat-1 organs with an up to 12-fold increase in fat-1 spleen and kidney. DHA levels increased by approximately 1.5-fold in fat-1 as compared to wildtype mice. While HETEs remained the same or decreased moderately and HDHAs increased 1- to 3-fold, HEPE formation in fat-1 tissues increased from 8- (muscle) to 44-fold (spleen). These findings indicate distinct profiles of monohydroxy lipid metabolites in different organs and strong utilization of EPA for HEPE formation, by which moderate EPA supplementation might trigger formation of biologically active EPA-derived resolvins. PMID:28165385

  4. Evaluation of toluene exposure via drinking water on levels of regional brain biogenic monoamines and their metabolites in CD-1 mice

    SciTech Connect

    Hsieh, G.C.; Sharma, R.P.; Parker, R.D.; Coulombe, R.A. Jr. )

    1990-10-01

    Toluene, a potentially neurotoxic substance, is found in trace amounts in groundwater. Adult male CD-1 mice were continuously fed drinking water ad libitum containing 0, 17, 80, and 405 mg/liter toluene. After a 28-day treatment, animals were tested for endogenous levels of the biogenic monoamines norepinephrine (NE), dopamine (DA), and serotonin (5-HT) and their respective metabolites, 3-methoxy-4-hydroxymandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), in six discrete brain regions. The maximum toluene-induced increases of biogenic amines and their metabolites generally occurred at a toluene concentration of 80 mg/liter. In the hypothalamus, a major NE-containing compartment, the concentrations of NE significantly increased by 51, 63, and 34% in groups dosed with 17, 80, and 405 mg/liter, respectively. Significant increases of NE were also observed in the medulla oblongata and midbrain. Concomitantly, concentrations of VMA increased in various brain regions. Concentrations of DA were significantly higher in the corpus striatum and hypothalamus. Alterations in levels of DA metabolites, DOPAC and HVA, were marginal. Toluene significantly increased concentrations of 5-HT in all dissected brain regions, except cerebellum, and increased the 5-HIAA levels in the hypothalamus, corpus striatum, and cerebral cortex.

  5. Levels of heroin and its metabolites in blood and brain extracellular fluid after i.v. heroin administration to freely moving rats

    PubMed Central

    Gottås, A; Øiestad, E L; Boix, F; Vindenes, V; Ripel, Å; Thaulow, C H; Mørland, J

    2013-01-01

    BACKGROUND AND PURPOSE Heroin, with low affinity for μ-opioid receptors, has been considered to act as a prodrug. In order to study the pharmacokinetics of heroin and its active metabolites after i.v. administration, we gave a bolus injection of heroin to rats and measured the concentration of heroin and its metabolites in blood and brain extracellular fluid (ECF). EXPERIMENTAL APPROACH After an i.v. bolus injection of heroin to freely moving Sprague–Dawley rats, the concentrations of heroin and metabolites in blood samples from the vena jugularis and in microdialysis samples from striatal brain ECF were measured by ultraperformance LC-MS/MS. KEY RESULTS Heroin levels decreased very fast, both in blood and brain ECF, and could not be detected after 18 and 10 min respectively. 6-Monoacetylmorphine (6-MAM) increased very rapidly, reaching its maximal concentrations after 2.0 and 4.3 min, respectively, and falling thereafter. Morphine increased very slowly, reaching its maximal levels, which were six times lower than the highest 6-MAM concentrations, after 12.6 and 21.3 min, with a very slow decline during the rest of the experiment and only surpassing 6-MAM levels at least 30 min after injection. CONCLUSIONS AND IMPLICATIONS After an i.v. heroin injection, 6-MAM was the predominant opioid present shortly after injection and during the first 30 min, not only in the blood but also in rat brain ECF. 6-MAM might therefore mediate most of the effects observed shortly after heroin intake, and this finding questions the general assumption that morphine is the main and most important metabolite of heroin. PMID:23865556

  6. Monitoring low benzene exposure: comparative evaluation of urinary biomarkers, influence of cigarette smoking, and genetic polymorphisms.

    PubMed

    Fustinoni, Silvia; Consonni, Dario; Campo, Laura; Buratti, Marina; Colombi, Antonio; Pesatori, Angela C; Bonzini, Matteo; Bertazzi, Pier A; Foà, Vito; Garte, Seymour; Farmer, Peter B; Levy, Leonard S; Pala, Mauro; Valerio, Federico; Fontana, Vincenzo; Desideri, Arianna; Merlo, Domenico F

    2005-09-01

    Benzene is a human carcinogen and an ubiquitous environmental pollutant. Identification of specific and sensitive biological markers is critical for the definition of exposure to low benzene level and the evaluation of the health risk posed by this exposure. This investigation compared urinary trans,trans-muconic acid (t,t-MA), S-phenylmercapturic acid, and benzene (U-benzene) as biomarkers to assess benzene exposure and evaluated the influence of smoking and the genetic polymorphisms CYP2E1 (RsaI and DraI) and NADPH quinone oxidoreductase-1 on these indices. Gas station attendants, urban policemen, bus drivers, and two groups of controls were studied (415 subjects). Median benzene exposure was 61, 22, 21, 9 and 6 microg/m(3), respectively, with higher levels in workers than in controls. U-benzene, but not t,t-MA and S-phenylmercapturic acid, showed an exposure-related increase. All the biomarkers were strongly influenced by cigarette smoking, with values up to 8-fold higher in smokers compared with nonsmokers. Significant correlations of the biomarkers with each other and with urinary cotinine were found. A possible influence of genetic polymorphism of CYP2E1 (RsaI and/or DraI) on t,t-MA and U-benzene in subjects with a variant allele was found. Multiple linear regression analysis correlated the urinary markers with exposure, smoking status, and CYP2E1 (RsaI; R(2) up to 0.55 for U-benzene). In conclusion, in the range of investigated benzene levels (<478 micro/m(3) or <0.15 ppm), smoking may be regarded as the major source of benzene intake; among the study indices, U-benzene is the marker of choice for biomonitoring low-level occupational and environmental benzene exposure.

  7. Environmental exposure to benzene: an update.

    PubMed Central

    Wallace, L

    1996-01-01

    During the 1990s, several large-scale studies of benzene concentrations in air, food, and blood have added to our knowledge of its environmental occurrence. In general, the new studies have confirmed the earlier findings of the U.S. Environmental Protection Agency Total Exposure Assessment Methodology (TEAM) studies and other large-scale studies in Germany and the Netherlands concerning the levels of exposure and major sources. For example, the new studies found that personal exposures exceeded indoor concentrations of benzene, which in turn exceeded outdoor concentrations. The new studies of food concentrations have confirmed earlier indications that food is not an important pathway for benzene exposure. The results of the National Health and Nutrition Examination Survey on blood levels in a nationwide sample of 883 persons are in good agreement with the concentrations in exhaled breath measured in about 800 persons a decade earlier in the TEAM studies. Major sources of exposure continue to be active and passive smoking, auto exhaust, and driving or riding in automobiles. New methods in breath and blood sampling and analysis offer opportunities to investigate short-term peak exposures and resulting body burden under almost any conceivable field conditions. PMID:9118882

  8. Process for the preparation of ethyl benzene

    DOEpatents

    Smith, L.A. Jr.; Arganbright, R.P.; Hearn, D.

    1995-12-19

    Ethyl benzene is produced in a catalyst bed under 0.25 to 50 atmospheres of pressure and at temperatures in the range of 50 C to 300 C, using as the catalyst a mole sieve characterized as acidic by feeding ethylene to the catalyst bed while benzene is conveniently added through the reflux to result in a molar excess present in the reactor to that required to react with ethylene, thereby reacting substantially all of the ethylene and recovering benzene as the principal overhead and ethyl benzene and diethyl benzene in the bottoms. The bottoms are fractionated, the ethyl benzene recovered and the bottoms are contacted with benzene in the liquid phase in a fixed bed straight pass reactor under conditions to transalkylate the benzene thereby converting most of the diethyl benzene to ethyl benzene which is again separated and recovered. 2 figs.

  9. Process for the preparation of ethyl benzene

    DOEpatents

    Smith, Jr., Lawrence A.; Arganbright, Robert P.; Hearn, Dennis

    1995-01-01

    Ethyl benzene is produced in a catalyst bed under 0.25 to 50 atmospheres of pressure and at temperatures in the range of 50.degree. C. to 300.degree. C., using as the catalyst a mole sieve characterized as acidic by feeding ethylene to the catalyst bed while benzene is conveniently added through the reflux to result in a molar excess present in the reactor to that required to react with ethylene, thereby reacting substantially all of the ethylene and recovering benzene as the principal overhead and ethyl benzene and diethyl benzene in the bottoms. The bottoms are fractionated, the ethyl benzene recovered and the bottoms are contacted with benzene in the liquid phase in a fixed bed straight pass reactor under conditions to transalkylate the benzene thereby converting most of the diethyl benzene to ethyl benzene which is again separated and recovered.

  10. Plasma level monitoring of the major metabolites of diacetylmorphine (heroin) by the "chasing the dragon" route in severe heroin addicts.

    PubMed

    Dubois, N; Demaret, I; Ansseau, M; Rozet, E; Hubert, Ph; Charlier, C

    2013-01-01

    The objective of the present study was to verify if severe physical health problems frequently encountered in heroin addicts and the concomitant use of alcohol and legal or illegal drugs other than heroin influenced the pharmacokinetics of the major metabolites of heroin. We conducted a 90 minutes follow-up of the plasma concentrations of the pharmaceutical heroin, named diacetylmorphine (DAM), in patients recruited in a DAM assisted treatment centre. TADAM (Traitement Assisté par DiAcétylMorphine) aimed to compare the efficacy of heroin-assisted treatment (HAT) compared with methadone maintenance treatment (MMT) for heroin users considered as treatment resistant patients and who have severe physical and mental health problems. Eleven patients were recruited. Blood samples were collected at baseline and 15, 45 and 90 minutes after DAM administration. All patients received DAM by the "chasing the dragon" route. Plasma samples were analyzed by a previously described ultra-high pressure liquid chromatography coupled to tandem mass spectrometry (UHPLC/MS-MS) method. A principal component analysis (PCA) was performed and 8 metabolite concentrations ratios were calculated to evaluate the influence of various factors (DAM dose, patient pathologies, concomitant use of medications, methadone, street heroin, alcohol and cocaine) on heroin metabolite pharmacokinetics. It seemed to be not affected by the DAM dose, patient pathologies and the concomitant use of medications, methadone, street heroin and alcohol. Cocaine use was the only parameter which showed differences in heroin pharmacokinetics.

  11. A survey of personal exposures to benzene in Mexico City.

    PubMed

    Meneses, F; Romieu, I; Ramirez, M; Colome, S; Fung, K; Ashley, D; Hernandez-Avila, M

    1999-01-01

    Benzene is a widely distributed environmental contaminant that causes leukemia. It is an important component in gasoline, it is used frequently as a solvent or chemical feedstock in industry, and it is emitted as a product of incomplete combustion. In Mexico City, investigators suspect that benzene exposure might be elevated and may pose a risk to the population; however, no published data are available to confirm or disconfirm this suspicion. We, therefore, conducted a survey in 3 occupational groups in Mexico City. Forty-five volunteers who used portable passive monitors measured their personal exposure to benzene during a workshift. None of the participants smoked during the monitoring period. Benzene exposure was significantly higher among service-station attendants (mean = 359.5 microg/m3 [standard deviation = 170.4 microg/m3]) than among the street vendors (83.7 microg/m3 and 45.0 microg/m3, respectively) and office workers (45.2 microg/m3 and 13.3 microg/m3, respectively). However, the benzene exposure levels observed among office workers were substantially higher than levels reported elsewhere for general populations. Our results highlight the need for more complete studies by investigators who should assess the potential benefits of setting environmental standards for benzene in Mexico.

  12. Drug metabolism in human brain: high levels of cytochrome P4503A43 in brain and metabolism of anti-anxiety drug alprazolam to its active metabolite.

    PubMed

    Agarwal, Varsha; Kommaddi, Reddy P; Valli, Khader; Ryder, Daniel; Hyde, Thomas M; Kleinman, Joel E; Strobel, Henry W; Ravindranath, Vijayalakshmi

    2008-06-11

    Cytochrome P450 (P450) is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are also present in brain where drug metabolism can take place and modify therapeutic action of drugs at the site of action. We have earlier demonstrated an intrinsic difference in the biotransformation of alprazolam (ALP) in brain and liver, relatively more alpha-hydroxy alprazolam (alpha-OHALP) is formed in brain as compared to liver. In the present study we show that recombinant CYP3A43 metabolizes ALP to both alpha-OHALP and 4-hydroxy alprazolam (4-OHALP) while CYP3A4 metabolizes ALP predominantly to its inactive metabolite, 4-OHALP. The expression of CYP3A43 mRNA in human brain samples correlates with formation of relatively higher levels of alpha-OH ALP indicating that individuals who express higher levels of CYP3A43 in the brain would generate larger amounts of alpha-OHALP. Further, the expression of CYP3A43 was relatively higher in brain as compared to liver across different ethnic populations. Since CYP3A enzymes play a prominent role in the metabolism of drugs, the higher expression of CYP3A43 would generate metabolite profile of drugs differentially in human brain and thus impact the pharmacodynamics of psychoactive drugs at the site of action.

  13. Influence of a five-day vegetarian diet on urinary levels of antibiotics and phthalate metabolites: a pilot study with "Temple Stay" participants.

    PubMed

    Ji, Kyunghee; Lim Kho, Young; Park, Yoonsuk; Choi, Kyungho

    2010-05-01

    Diet is purported to be means of exposure to many environmental contaminants. The purpose of this study is to understand the influence of dietary change on the levels of exposure to several environmental chemicals - in particular, antibiotics and phthalates. For this purpose, we examined the extent to which short-term changes in diet influenced the inadvertent exposure levels to these chemicals in an adult population. We recruited participants (n=25) of a five-day 'Temple Stay' program in Korea and collected urine samples before and after the program. We also conducted a questionnaire survey on participants' dietary patterns prior to their participation. During the program, participants followed the daily routines of Buddhist monks and maintained a vegetarian diet. Urinary levels of three antibiotics and their major metabolites, metabolites of four major phthalates, and malondialdehyde (MDA) as an oxidative stress biomarker were analyzed. The frequency and levels of detection for antibiotics and phthalates noticeably decreased during the program. Urinary MDA levels were significantly lower than before program participation (0.16 versus 0.27mg/g creatinine). Although the exposure to target compounds might be influenced by other behavioral patterns, these results suggest that even short-term changes in dietary behavior may significantly decrease inadvertent exposure to antibiotics and phthalates and hence may reduce oxidative stress levels.

  14. Network Analysis of Enzyme Activities and Metabolite Levels and Their Relationship to Biomass in a Large Panel of Arabidopsis Accessions[C][W][OA

    PubMed Central

    Sulpice, Ronan; Trenkamp, Sandra; Steinfath, Matthias; Usadel, Bjorn; Gibon, Yves; Witucka-Wall, Hanna; Pyl, Eva-Theresa; Tschoep, Hendrik; Steinhauser, Marie Caroline; Guenther, Manuela; Hoehne, Melanie; Rohwer, Johann M.; Altmann, Thomas; Fernie, Alisdair R.; Stitt, Mark

    2010-01-01

    Natural genetic diversity provides a powerful resource to investigate how networks respond to multiple simultaneous changes. In this work, we profile maximum catalytic activities of 37 enzymes from central metabolism and generate a matrix to investigate species-wide connectivity between metabolites, enzymes, and biomass. Most enzyme activities change in a highly coordinated manner, especially those in the Calvin-Benson cycle. Metabolites show coordinated changes in defined sectors of metabolism. Little connectivity was observed between maximum enzyme activities and metabolites, even after applying multivariate analysis methods. Measurements of posttranscriptional regulation will be required to relate these two functional levels. Individual enzyme activities correlate only weakly with biomass. However, when they are used to estimate protein abundances, and the latter are summed and expressed as a fraction of total protein, a significant positive correlation to biomass is observed. The correlation is additive to that obtained between starch and biomass. Thus, biomass is predicted by two independent integrative metabolic biomarkers: preferential investment in photosynthetic machinery and optimization of carbon use. PMID:20699391

  15. Multiresidue method for N-methyl carbamates and metabolite pesticide residues at the parts-per-billion level in selected representative commodities of fruit and vegetable crop groups.

    PubMed

    Podhorniak, Lynda V; Schenck, Frank J; Krynitsky, Alexander; Griffith, Francis

    2004-01-01

    A reversed-phase liquid chromatographic method with both fluorescence and mass spectrometric detection is presented for the determination of 13 parent N-methyl carbamate pesticides and their metabolites, as well as piperonyl butoxide, for a total of 24 compounds in selected fruits and vegetables. The commodities chosen were of special concern to the U.S. Environmental Protection Agency (EPA) because they had the least amount of monitoring data for dietary exposure estimates used in risk assessment. The method is based on a judicious selection of procedures from U.S. Food and Drug Administration sources such as the Pesticide Analytical Manual (Volume I), and Laboratory Information Bulletins, plus additional material from the chemical literature combined in a manner to recover the N-methyl carbamates and their metabolites at the 1 microg/kg or 1 part-per-billion level. The method uses an acetone extraction, followed by an aminopropyl solid-phase extraction cleanup. Determination of residues is by RP-LC, in which the liquid chromatograph is interfaced with either a fluorescence or a mass spectrometric detector. The method is designed so that a set of 6 samples can be prepared in 1 working day for overnight instrumental analysis. Recovery data are presented from analyses of selected commodities in some of EPA's fruit and vegetable crop groupings. A table listing relative retention times is presented for the N-methyl carbamates and their metabolites.

  16. Determination of benzene in soft drinks and other beverages by isotope dilution headspace gas chromatography/mass spectrometry.

    PubMed

    Cao, Xu-Liang; Casey, Valerie; Seaman, Steve; Tague, Brett; Becalski, Adam

    2007-01-01

    An automated, simple, and reproducible method was developed for the determination of benzene in soft drinks, based on isotope dilution headspace gas chromatography/mass spectrometry in the selected-ion monitoring mode. The method was used to assess benzene levels in samples of 124 soft drinks and beverages. Benzene was not detected in 60% of the 124 products. The average benzene levels in 6 products exceeded the Canadian maximum acceptable concentration of 5 microg/L for benzene in drinking water, and 2 of the 6 products had benzene levels above the World Health Organization guideline of 10 microg/L. The highest level of benzene, 23 microg/L, was found in a soft drink product specifically marketed to children.

  17. Use of allopurinol with low-dose 6-mercaptopurine in inflammatory bowel disease to achieve optimal active metabolite levels: A review of four cases and the literature

    PubMed Central

    Witte, Todd N; Ginsberg, Allen L

    2008-01-01

    BACKGROUND: At least one-third of patients with inflammatory bowel disease do not respond or are intolerant to therapy with 6-mercaptopurine (6-MP). A subgroup fails to attain optimal levels of 6-thioguanine nucleotide (6-TGN) and instead shunts to 6-methylmercaptopurine nucleotide (6-MMPN). PATIENTS AND METHODS: A retrospective chart review was conducted, and four patients are described who had been previously unable to achieve optimal 6-TGN metabolite levels until allopurinol was added to their treatment. RESULTS: All four patients achieved optimal 6-TGN levels and undetectable 6-MMPN with a mean 6-MP dose of 0.49 mg/kg. Three achieved steroid-free clinical remission. Two of those three patients had normalization of liver enzymes; one patient had baseline normal liver enzymes despite an initial 6-MMPN level of 27,369 pmol/8×108 red blood cells. Two patients experienced reversible leukopenia. CONCLUSIONS: Combination allopurinol and low-dose 6-MP is an effective means to achieve optimal metabolite levels and steroid-free clinical remission in previously refractory patients. Caution is advised. PMID:18299738

  18. Seasonal variation of toxic benzene emissions in petroleum refinery.

    PubMed

    Rao, P S; Ansari, M F; Gavane, A G; Pandit, V I; Nema, P; Devotta, S

    2007-05-01

    Petroleum refineries are largest chemical industries that are responsible for the emission of several pollutants into the atmosphere. Benzene is among the most important air pollutants that are emitted by petroleum refineries, since they are involved in almost every refinery process. Volatile organic compounds (VOCs) are a major group of air pollutants, which play a critical role in atmospheric chemistry. These contribute to toxic oxidants, which are harmful to ecosystem, human health and atmosphere. The variability of pollutants is an important factor in determining human exposure to these chemicals. The ambient air concentrations of benzene were measured in several sites around the Digboi petroleum refinery, near the city of Gowahati in northeast India, during winter and summer 2004. The seasonal and spatial variations of the ambient air concentrations of this benzene were investigated and analyzed. An estimation of the contribution of the refinery to the measured atmospheric levels of benzene was also performed. The ambient air mixing ratios of benzene in a large area outside the refinery was generally low, in ppbv range, much lower than the ambient air quality standards. This article presents the temporal and spatial variation of air pollution in and around petroleum refinery and showed that no health risk due to benzene is present in the areas adjacent to the refinery.

  19. Acetyl-l-carnitine partially prevents benzene-induced hematotoxicity and oxidative stress in C3H/He mice.

    PubMed

    Sun, Rongli; Zhang, Juan; Wei, Haiyan; Meng, Xing; Ding, Qin; Sun, Fengxia; Cao, Meng; Yin, Lihong; Pu, Yuepu

    2017-02-13

    Benzene is an environmental pollutant and occupational toxicant which induces hematotoxicity. Our previous metabonomics study suggested that acetyl-l-carnitine (ALCAR) decreased in the mouse plasma and bone marrow (BM) cells due to benzene exposure. In the present study, the topic on whether ALCAR influences hematotoxicity caused by benzene exposure was explored. Thirty-two male C3H/He mice were divided into four groups: control group (C: vehicle, oil), benzene group (150mg/kg body weight (b.w.) benzene), benzene+A1 group (150mg/kg b.w. benzene+100mg/kg b.w. ALCAR), and benzene+A2 group (150mg/kg b.w. benzene+200mg/kg b.w. ALCAR). Benzene was injected subcutaneously, and ALCAR was orally administrated via gavage once daily for 4 weeks consecutively. After the experimental period, the blood routine, BM cell number and frequency of hematopoietic stem/progenitor cell (HS/PC) were assessed. The mitochondrial membrane potential and ATP level were determined to evaluate the mitochondrial function. Reactive oxygen species (ROS), hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels were also examined, and the comet assay was performed to measure oxidative stress. Results showed that ALCAR intervention can partially reduce the benzene-induced damage on BM and HS/PCs and can simultaneously alleviate the DNA damage by reducing benzene-induced H2O2, ROS, and MDA.

  20. ITP Filtrate Benzene Removal Alternatives

    SciTech Connect

    Dworjanyn, L.O.

    1993-05-21

    Existing ITP filtrate hold tanks may provide sufficient capacity and residence time to strip dissolved benzene from the incoming filtrate using nitrogen sparging in the bottom of the old tanks. This is based on equilibrium supported by late Wash test data using aged washed slurry. Theoretical considerations indicate that benzene stripping will be more difficult from the ITP unwashed high salt filtrates due to reduced mass transfer. Therefore experimental sparging data is needed to quantify the theoretical effects.Foaming limits which dictate allowable sparging rate will also have to be established. Sparging in the hold tanks will require installation of sintered metal spargers, and possibly stirrers and foam monitoring/disengagement equipment. The most critical sparging needs are at the start of the precipitation/concentration cycle, when the filtrate flux rate is the highest,and at the end of wash cycle where Henry`s equilibrium constant falls off,requiring more gas to sparge the dissolved benzene. With adequate recycle (for proper distribution) or sparging in the old tanks, the 30 inch column could be used for the complete ITP process. A courser packing would reduce back pressure while enabling benzene stripping. The Late Wash Tests indicate adequate benzene stripping even at reduced gas flow. This will require experimental verification under ITP conditions. Using the 30 in. column vs 18 in. during the wash cycle will enhance stripping without need for additional sparging provided the minimum flow requirements are met.

  1. A lack of consensus in the literature findings on the removal of airborne benzene by houseplants: Effect of bacterial enrichment

    NASA Astrophysics Data System (ADS)

    Sriprapat, Wararat; Strand, Stuart E.

    2016-04-01

    Removal rates of benzene and formaldehyde gas by houseplants reported by several laboratories varied by several orders of magnitude. We hypothesized that these variations were caused by differential responses of soil microbial populations to the high levels of pollutant used in the studies, and tested responses to benzene by plants and soils separately. Five houseplant species and tobacco were exposed to benzene under hydroponic conditions and the uptake rates compared. Among the test plants, Syngonium podophyllum and Chlorophytum comosum and Epipremnum aureum had the highest benzene removal rates. The effects of benzene addition on populations of soil bacteria were determined using reverse transcription quantitative PCR (RT-qPCR) assays targeting microbial genes involved in benzene degradation. The total bacterial population increased as shown by increases in the levels of eubacteria 16S rRNA, which was significantly higher in the high benzene incubations than in the low benzene incubations. Transcripts (mRNA) of genes encoding phenol monooxygenases, catechol-2,3-dioxygenase and the housekeeping gene rpoB increased in all soils incubated with high benzene concentrations. Therefore the enrichment of soils with benzene gas levels typical of experiments with houseplants in the literature artificially increased the levels of total soil bacterial populations, and especially the levels and activities of benzene-degrading bacteria.

  2. A simple HPLC method for plasma level monitoring of mitotane and its two main metabolites in adrenocortical cancer patients.

    PubMed

    Garg, Madhu B; Sakoff, Jennette A; Ackland, Stephen P

    2011-08-01

    Mitotane (o,p'-DDD or (1,1-dichloro-2-[o-chlorophenyl]-2-[p-chlorophenyl]ethane, DDD) is the drug of choice for non-resectable and metastatic adrenocortical carcinomas (ACC). Measurement of mitotane and metabolites, o,p'-DDE (1,1-dichloro-2-[p-chlorophenyl]-2-[o-chlorophenyl]ethene, DDE) and o,p'-DDA (1,1-[o,p'-dichlorodiphenyl] acetic acid, DDA) provides a better understanding of mitotane pharmacokinetics and pharmacodynamics. We have developed a simple, robust and efficient high performance liquid chromatography (HPLC) method to measure mitotane and its two main metabolites, DDE and DDA. The method involves a single ethanol extraction of mitotane, DDE, DDA, and an internal standard (int std) p,p'-DDD (1,1-dichloro-2,2-bis(p-chlorophenyl)ethane) with an extraction efficiency of 77-88%. All compounds are measured simultaneously using a reversed-phase phenyl HPLC column with an isocratic elution of mobile phase at a flow rate of 0.6 ml/min followed by UV detection at λ 226 nm. Inter and intra-day validation demonstrates good reproducibility and accuracy. Limits of quantitation are 0.2 μg/ml for mitotane and DDE, and 0.5 μg/ml for DDA. The method has been evaluated in plasma from 23 patients on mitotane therapy, revealing DDA concentrations 1-18 times higher than the parent compound.

  3. DNA Extraction Protocol for Plants with High Levels of Secondary Metabolites and Polysaccharides without Using Liquid Nitrogen and Phenol.

    PubMed

    Sahu, Sunil Kumar; Thangaraj, Muthusamy; Kathiresan, Kandasamy

    2012-01-01

    Mangroves and salt marsh species are known to synthesize a wide spectrum of polysaccharides and polyphenols including flavonoids and other secondary metabolites which interfere with the extraction of pure genomic DNA. Although a plethora of plant DNA isolation protocols exist, extracting DNA from mangroves and salt marsh species is a challenging task. This study describes a rapid and reliable cetyl trimethylammonium bromide (CTAB) protocol suited specifically for extracting DNA from plants which are rich in polysaccharides and secondary metabolites, and the protocol also excludes the use of expensive liquid nitrogen and toxic phenols. Purity of extracted DNA was excellent as evident by A260/A280 ratio ranging from 1.78 to 1.84 and A260/A230 ratio was >2, which also suggested that the preparations were sufficiently free of proteins and polyphenolics/polysaccharide compounds. DNA concentration ranged from 8.8 to 9.9 μg μL(-1). The extracted DNA was amenable to RAPD, restriction digestion, and PCR amplification of plant barcode genes (matK and rbcl). The optimized method is suitable for both dry and fresh leaves. The success of this method in obtaining high-quality genomic DNA demonstrated the broad applicability of this method.

  4. A comparative study on diurnal changes in metabolite levels in the leaves of three crassulacean acid metabolism (CAM) species, Ananas comosus, Kalanchoë daigremontiana and K. pinnata.

    PubMed

    Chen, Li-Song; Lin, Qin; Nose, Akihiro

    2002-02-01

    A comparative study on diurnal changes in metabolite levels associated with crassulacean acid metabolism (CAM) in the leaves of three CAM species, Ananas comosus (pineapple), a hexose-utilizing species, and Kalanchoë daigremontiana and K. pinnata, two starch-utilizing species, were made. All three CAM species showed a typical feature of CAM with nocturnal malate increase. In the two Kalanchoë species, isocitrate levels were higher than citrate levels; the reverse was the case in pineapple. In the two Kalanchoë species, a small nocturnal citrate increase was found and K. daigremontiana showed a small nocturnal isocitrate increase. Glucose 6-phosphate (G-6-P), fructose 6-phosphate (F-6-P) and glucose 1-phosphate (G-1-P) levels in the three CAM species rose rapidly during the first part of the dark period and decreased during the latter part of the dark period. The levels of the metabolites also decreased during the first 3 h of the light period, then, remained little changed through the rest of the light period. Absolute levels of G-6-P, F-6-P and G-1-P were higher in pineapple than in the two Kalanchoë species. Fructose 1,6-bisphosphate (F-1,6-P(2)) levels in the three CAM species increased during the dark period, then dramatically decreased during the first 3 h of the light period and remained unchanged through the rest of the light period. The extent of nocturnal F-1,6-P(2) increase was far greater in the two Kalanchoë species than in pineapple. Absolute levels of F-1,6-P(2) were higher in the two Kalanchoë species than in pineapple, especially during dark period. Diurnal changes in oxaloacetate (OAA), pyruvate (Pyr) and phosphoenolpyruvate (PEP) levels in the three CAM species were similar.

  5. Identification of genes specifically required for the anaerobic metabolism of benzene in Geobacter metallireducens

    PubMed Central

    Zhang, Tian; Tremblay, Pier-Luc; Chaurasia, Akhilesh K.; Smith, Jessica A.; Bain, Timothy S.; Lovley, Derek R.

    2014-01-01

    Although the biochemical pathways for the anaerobic degradation of many of the hydrocarbon constituents in petroleum reservoirs have been elucidated, the mechanisms for anaerobic activation of benzene, a very stable molecule, are not known. Previous studies have demonstrated that Geobacter metallireducens can anaerobically oxidize benzene to carbon dioxide with Fe(III) as the sole electron acceptor and that phenol is an intermediate in benzene oxidation. In an attempt to identify enzymes that might be involved in the conversion of benzene to phenol, whole-genome gene transcript abundance was compared in cells metabolizing benzene and cells metabolizing phenol. Eleven genes had significantly higher transcript abundance in benzene-metabolizing cells. Five of these genes had annotations suggesting that they did not encode proteins that could be involved in benzene metabolism and were not further studied. Strains were constructed in which one of the remaining six genes was deleted. The strain in which the monocistronic gene Gmet 0232 was deleted metabolized phenol, but not benzene. Transcript abundance of the adjacent monocistronic gene, Gmet 0231, predicted to encode a zinc-containing oxidoreductase, was elevated in cells metabolizing benzene, although not at a statistically significant level. However, deleting Gmet 0231 also yielded a strain that could metabolize phenol, but not benzene. Although homologs of Gmet 0231 and Gmet 0232 are found in microorganisms not known to anaerobically metabolize benzene, the adjacent localization of these genes is unique to G. metallireducens. The discovery of genes that are specifically required for the metabolism of benzene, but not phenol in G. metallireducens is an important step in potentially identifying the mechanisms for anaerobic benzene activation. PMID:24904558

  6. Benzene exposure assessment for use of a mineral spirits-based degreaser.

    PubMed

    Fedoruk, Marion J; Bronstein, Rod; Kerger, Brent D

    2003-10-01

    This study examines benzene emissions from the use of a metal parts washer ("degreaser") supplied with a mineral spirits solvent containing either 9 or 58 ppm benzene. Air samples were obtained during a one-hour session of relatively vigorous parts cleaning activity using a degreaser station equipped with wet brush and sprayer attachments and a compressed air hose. Two methods were utilized to assess airborne benzene levels: U.S. EPA TO-14 (summa stainless steel canister) and NIOSH 1501 (charcoal tube). Overall, both methods provided similar results, excepting detection limit differences. The first simulation was performed with recycled solvent (9 ppm benzene in solvent) showing average one-hour airborne benzene levels < or =33 ppbv in the worker's breathing zone and directly above the parts cleaning tank. Average airborne benzene concentrations 18 inches away from the tank were below 2 ppbv during the 60-minute cleaning protocol. The second simulation with benzene-spiked recycled solvent (58 ppm benzene) showed airborne benzene levels averaging 500 ppbv measured over the 60-minute cleaning period in the worker's breathing zone and directly above the tank, while average concentrations 18 inches from the tank perimeter were 63 ppbv. The data indicate that average and peak exposures to airborne benzene were roughly proportional to the solvent benzene content, although the brief peak exposures exhibited greater variance probably related to aerosol generation associated with the use of the brush and/or spraying attachment. Under this selected upper bound exposure simulation, we found that cleaning parts using a recycled mineral spirits-based solvent in an open warehouse setting did not result in exposures in excess of the current occupational exposure limit of 0.5 ppm averaged over 8 hours for solvent benzene content between 9 and 58 ppm.

  7. Benzene Uptake and Glutathione S-transferase T1 Status as Determinants of S-Phenylmercapturic Acid in Cigarette Smokers in the Multiethnic Cohort

    PubMed Central

    Haiman, Christopher A.; Patel, Yesha M.; Stram, Daniel O.; Carmella, Steven G.; Chen, Menglan; Wilkens, Lynne R.; Le Marchand, Loic; Hecht, Stephen S.

    2016-01-01

    Research from the Multiethnic Cohort (MEC) demonstrated that, for the same quantity of cigarette smoking, African Americans and Native Hawaiians have a higher lung cancer risk than Whites, while Latinos and Japanese Americans are less susceptible. We collected urine samples from 2,239 cigarette smokers from five different ethnic groups in the MEC and analyzed each sample for S-phenylmercapturic acid (SPMA), a specific biomarker of benzene uptake. African Americans had significantly higher (geometric mean [SE] 3.69 [0.2], p<0.005) SPMA/ml urine than Whites (2.67 [0.13]) while Japanese Americans had significantly lower levels than Whites (1.65 [0.07], p<0.005). SPMA levels in Native Hawaiians and Latinos were not significantly different from those of Whites. We also conducted a genome-wide association study in search of genetic risk factors related to benzene exposure. The glutathione S-transferase T1 (GSTT1) deletion explained between 14.2–31.6% (p = 5.4x10-157) and the GSTM1 deletion explained between 0.2%-2.4% of the variance (p = 1.1x10-9) of SPMA levels in these populations. Ethnic differences in levels of SPMA remained strong even after controlling for the effects of these two deletions. These results demonstrate the powerful effect of GSTT1 status on SPMA levels in urine and show that uptake of benzene in African American, White, and Japanese American cigarette smokers is consistent with their lung cancer risk in the MEC. While benzene is not generally considered a cause of lung cancer, its metabolite SPMA could be a biomarker for other volatile lung carcinogens in cigarette smoke. PMID:26959369

  8. The Impact of Glyphosate, Its Metabolites and Impurities on Viability, ATP Level and Morphological changes in Human Peripheral Blood Mononuclear Cells

    PubMed Central

    Kwiatkowska, Marta; Jarosiewicz, Paweł; Michałowicz, Jaromir; Koter-Michalak, Maria; Huras, Bogumiła; Bukowska, Bożena

    2016-01-01

    The toxicity of herbicides to animals and human is an issue of worldwide concern. The present study has been undertaken to assess toxic effect of widely used pesticide—glyphosate, its metabolites: aminomethylphosphonic acid (AMPA) and methylphosphonic acid and its impurities: N-(phosphonomethyl)iminodiacetic acid (PMIDA), N-methylglyphosate, hydroxymethylphosphonic acid and bis-(phosphonomethyl)amine on human peripheral blood mononuclear cells (PBMCs). We have evaluated the effect of those compounds on viability, ATP level, size (FSC-A parameter) and granulation (SSC-A parameter) of the cells studied. Human peripheral blood mononuclear cells were exposed to different concentrations of glyphosate, its metabolites and impurities (0.01–10 mM) for 4 and 24 h. It was found that investigated compounds caused statistically significant decrease in viability and ATP level of PBMCs. The strongest changes in cell viability and ATP level were observed after 24 h incubation of PBMCs with bis-(phosphonomethyl)amine, and particularly PMIDA. Moreover, all studied compounds changed cell granularity, while PMIDA and bis-(phosphonomethyl)amine altered PBMCs size. It may be concluded that bis-(phosphonomethyl)amine, and PMIDA caused a slightly stronger damage to PBMCs than did glyphosate. Changes in the parameters studied in PBMCs were observed only at high concentrations of the compounds examined, which clearly shows that they may occur in this cell type only as a result of acute poisoning of human organism with these substances. PMID:27280764

  9. Investigation of abiogenic stress-induced alterations in the level of secondary metabolites in poppy plants (Papaver somniferum L.).

    PubMed

    Szabó, Beáta; Lakatos, A; Koszegi, T; Botz, L

    2008-12-01

    We aimed to understand the effects of water stress on the alkaloid production in various developmental stages of poppy plants and the effect of stress on the alkaloids content in the capsules. Three stages of the life cycle of Papaver somniferum L. were selected in our studies: Rosette, Flowering and Lancing developmental stages. Four types of water conditions were examined: Control, Withdrawal of Water, 50% Water Supply and Inundation. The morphological monitoring, results of Relative Water Content and proline content were used as indicators of stress. The result of the measurements in poppy leaves show that the secondary metabolites dramatically respond to these stress conditions. The constant water supply was beneficial for the accumulation of alkaloids in the capsules.

  10. Effects of exposure to amphetamine derivatives on passive avoidance performance and the central levels of monoamines and their metabolites in mice: correlations between behavior and neurochemistry

    PubMed Central

    Murnane, Kevin Sean; Perrine, Shane Alan; Finton, Brendan James; Galloway, Matthew Peter; Howell, Leonard Lee; Fantegrossi, William Edward

    2011-01-01

    Rationale Considerable evidence indicates that amphetamine derivatives can deplete brain monoaminergic neurotransmitters. However, the behavioral and cognitive consequences of neurochemical depletions induced by amphetamines are not well established. Objectives In this study, mice were exposed to dosing regimens of 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine (METH), or para-chloroamphetamine (PCA) known to deplete the monoamine neurotransmitters dopamine and serotonin, and the effects of these dosing regimens on learning and memory were assessed. Methods In the same animals, we determined deficits in learning and memory via passive avoidance (PA) behavior and changes in tissue content of monoamine neurotransmitters and their primary metabolites in the striatum, frontal cortex, cingulate, hippocampus, and amygdala via ex vivo high pressure liquid chromatography. Results Consistent with previous studies, significant reductions in tissue content of dopamine and serotonin were readily apparent. In addition, exposure to METH and PCA impaired PA performance and resulted in significant depletions of dopamine, serotonin, and their metabolites in several brain regions. Multiple linear regression analysis revealed that the tissue concentration of dopamine in the anterior striatum was the strongest predictor of PA performance, with an additional significant contribution by the tissue concentration of the serotonin metabolite 5-hydroxyindoleacetic acid in the cingulate. In contrast to the effects of METH and PCA, exposure to MDMA did not deplete anterior striatal dopamine levels or cingulate levels of 5-hydroxyindoleacetic acid, and it did not impair PA performance. Conclusions These studies demonstrate that certain amphetamines impair PA performance in mice and that these impairments may be attributable to specific neurochemical depletions. PMID:21993877

  11. Brassica napus L. cultivars show a broad variability in their morphology, physiology and metabolite levels in response to sulfur limitations and to pathogen attack

    PubMed Central

    Weese, Annekathrin; Pallmann, Philip; Papenbrock, Jutta; Riemenschneider, Anja

    2015-01-01

    Under adequate sulfur supply, plants accumulate sulfate in the vacuoles and use sulfur-containing metabolites as storage compounds. Under sulfur-limiting conditions, these pools of stored sulfur-compounds are depleted in order to balance the nitrogen to sulfur ratio for protein synthesis. Stress conditions like sulfur limitation and/or pathogen attack induce changes in the sulfate pool and the levels of sulfur-containing metabolites, which often depend on the ecotypes or cultivars. We are interested in investigating the influence of the genetic background of canola (Brassica napus) cultivars in sulfur-limiting conditions on the resistance against Verticillium longisporum. Therefore, four commercially available B. napus cultivars were analyzed. These high-performing cultivars differ in some characteristics described in their cultivar pass, such as several agronomic traits, differences in the size of the root system, and resistance to certain pathogens, such as Phoma and Verticillium. The objectives of the study were to examine and explore the patterns of morphological, physiological and metabolic diversity in these B. napus cultivars at different sulfur concentrations and in the context of plant defense. Results indicate that the root systems are influenced differently by sulfur deficiency in the cultivars. Total root dry mass and length of root hairs differ not only among the cultivars but also vary in their reaction to sulfur limitation and pathogen attack. As a sensitive indicator of stress, several parameters of photosynthetic activity determined by PAM imaging showed a broad variability among the treatments. These results were supported by thermographic analysis. Levels of sulfur-containing metabolites also showed large variations. The data were interrelated to predict the specific behavior during sulfur limitation and/or pathogen attack. Advice for farming are discussed. PMID:25699060

  12. Extracellular dopamine and its metabolites in the nucleus accumbens of Fisher and Lewis rats: Basal levels and cocaine-induced changes

    SciTech Connect

    Strecker, R.E.; Eberle, W.F.; Ashby, C.R. Jr.

    1995-11-01

    Rats of the Lewis (LEW) strain show a greater preference for drugs of abuse than do Fisher 344 (F344) rats. The in vivo microdialysis procedure was used to examine basal and cocaine-evoked extracellular (EC) levels of dopamine (DA), DOPAC, and HVA in the nucleus accumbens (NAc) of F344 and LEW rats. The basal EC levels of the DA metabolites DOPAC and HVA in the NAc were markedly lower in LEW than in F344 rats. Although the increase in ECDA after 3, 10 or 30 mg/kg, i/p. of cocaine was similar in both strains, LEW rats had a smaller peak DA elevation followed by a slower return to basal DA levels at the 30 mg/kg dose. The neurochemical differences observed may contribute to the strain differences in the behavioral response to cocaine. 20 refs., 3 figs.

  13. Genotype-phenotype modeling considering intermediate level of biological variation: a case study involving sensory traits, metabolites and QTLs in ripe tomatoes.

    PubMed

    Wang, Huange; Paulo, Joao; Kruijer, Willem; Boer, Martin; Jansen, Hans; Tikunov, Yury; Usadel, Björn; van Heusden, Sjaak; Bovy, Arnaud; van Eeuwijk, Fred

    2015-11-01

    Modeling genotype-phenotype relationships is a central objective in plant genetics and breeding. Commonly, variations in phenotypic traits are modeled directly in relation to variations at the DNA level, regardless of intermediate levels of biological variation. Here we present an integrative method for the simultaneous modeling of a set of multilevel phenotypic responses to variations at the DNA level. More specifically, for ripe tomato fruits, we use Gaussian graphical models and causal inference techniques to learn the dependencies of 24 sensory traits on 29 metabolites and the dependencies of those sensory and metabolic traits on 21 QTLs. The inferred dependency network which, though not essentially representing biological pathways, suggests how the effects of allele substitutions propagate through multilevel phenotypes. Such simultaneous study of the underlying genetic architecture and multifactorial interactions is expected to enhance the prediction and manipulation of complex traits.

  14. Iron regulation through the back door: iron-dependent metabolite levels contribute to transcriptional adaptation to iron deprivation in Saccharomyces cerevisiae.

    PubMed

    Ihrig, Jessica; Hausmann, Anja; Hain, Anika; Richter, Nadine; Hamza, Iqbal; Lill, Roland; Mühlenhoff, Ulrich

    2010-03-01

    Budding yeast (Saccharomyces cerevisiae) responds to iron deprivation both by Aft1-Aft2-dependent transcriptional activation of genes involved in cellular iron uptake and by Cth1-Cth2-specific degradation of certain mRNAs coding for iron-dependent biosynthetic components. Here, we provide evidence for a novel principle of iron-responsive gene expression. This regulatory mechanism is based on the modulation of transcription through the iron-dependent variation of levels of regulatory metabolites. As an example, the LEU1 gene of branched-chain amino acid biosynthesis is downregulated under iron-limiting conditions through depletion of the metabolic intermediate alpha-isopropylmalate, which functions as a key transcriptional coactivator of the Leu3 transcription factor. Synthesis of alpha-isopropylmalate involves the iron-sulfur protein Ilv3, which is inactivated under iron deficiency. As another example, decreased mRNA levels of the cytochrome c-encoding CYC1 gene under iron-limiting conditions involve heme-dependent transcriptional regulation via the Hap1 transcription factor. Synthesis of the iron-containing heme is directly correlated with iron availability. Thus, the iron-responsive expression of genes that are downregulated under iron-limiting conditions is conferred by two independent regulatory mechanisms: transcriptional regulation through iron-responsive metabolites and posttranscriptional mRNA degradation. Only the combination of the two processes provides a quantitative description of the response to iron deprivation in yeast.

  15. Alterations in leukocyte telomere length in workers occupationally exposed to benzene.

    PubMed

    Bassig, Bryan A; Zhang, Luoping; Cawthon, Richard M; Smith, Martyn T; Yin, Songnian; Li, Guilan; Hu, Wei; Shen, Min; Rappaport, Stephen; Barone-Adesi, Francesco; Rothman, Nathaniel; Vermeulen, Roel; Lan, Qing

    2014-10-01

    Exposure to benzene, a known leukemogen and probable lymphomagen, has been demonstrated to result in oxidative stress, which has previously been associated with altered telomere length (TL). TL specifically has been associated with several health outcomes in epidemiologic studies, including cancer risk, and has been demonstrated to be altered following exposure to a variety of chemical agents. To evaluate the association between benzene exposure and TL, we measured TL by monochrome multiplex quantitative PCR in 43 workers exposed to high levels of benzene and 43 age and sex-matched unexposed workers in Shanghai, China. Benzene exposure levels were monitored using organic vapor passive dosimetry badges before phlebotomy. The median benzene exposure level in exposed workers was 31 ppm. The mean TL in controls, workers exposed to levels of benzene below the median (≤31 ppm), and above the median (>31 ppm) was 1.26 ± 0.17, 1.25 ± 0.16, and 1.37 ± 0.23, respectively. Mean TL was significantly elevated in workers exposed to >31 ppm of benzene compared with controls (P = 0.03). Our findings provide evidence that high levels of occupational benzene exposure are associated with TL. Environ.

  16. 27 CFR 21.97 - Benzene.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Benzene. 21.97 Section 21... TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specifications for Denaturants § 21.97 Benzene. (a..., Standard No. D 836-77; for incorporation by reference, see § 21.6(b).) When 100 ml of benzene are...

  17. 27 CFR 21.97 - Benzene.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Benzene. 21.97 Section 21... TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specifications for Denaturants § 21.97 Benzene. (a..., Standard No. D 836-77; for incorporation by reference, see § 21.6(b).) When 100 ml of benzene are...

  18. 27 CFR 21.97 - Benzene.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Benzene. 21.97 Section 21... TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specifications for Denaturants § 21.97 Benzene. (a..., Standard No. D 836-77; for incorporation by reference, see § 21.6(b).) When 100 ml of benzene are...

  19. 27 CFR 21.97 - Benzene.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Benzene. 21.97 Section 21... TREASURY ALCOHOL FORMULAS FOR DENATURED ALCOHOL AND RUM Specifications for Denaturants § 21.97 Benzene. (a..., Standard No. D 836-77; for incorporation by reference, see § 21.6(b).) When 100 ml of benzene are...

  20. 27 CFR 21.97 - Benzene.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Benzene. 21.97 Section 21... TREASURY ALCOHOL FORMULAS FOR DENATURED ALCOHOL AND RUM Specifications for Denaturants § 21.97 Benzene. (a..., Standard No. D 836-77; for incorporation by reference, see § 21.6(b).) When 100 ml of benzene are...

  1. Benzene exposure in industries using or manufacturing paint in China--a literature review, 1956-2005.

    PubMed

    Liu, Hong; Liang, Youxin; Bowes, Stephen; Xu, Hongzhi; Zhou, Yimei; Armstrong, Thomas W; Wong, Otto; Schnatter, A R; Fang, Jinbin; Wang, Laiming; Nie, Liping; Fu, Hua; Irons, Richard

    2009-11-01

    A systematic review of the Chinese literature was conducted from 1956 to 2005. The survey included both online and manual searching, as well as expert discussions aimed at providing insight into factors affecting benzene exposure levels in paint/coatings industries. Data extracted from 204 papers included: (1) year of occurrence, (2) type of paint/coatings products, (3) type of industries where the products were used or produced, (4) job titles and work activities, (5) type of literature searched, (6) working conditions whenever data were available, and (7) exposure levels. Most benzene measurements were short-term samples for comparison with the Chinese maximum allowable concentration standard. The accuracy and precision of the sampling and analytical methods were not reported. The distribution of benzene concentrations was tested and found to fit neither normal nor lognormal distributions. Analysis of variance (comparison for more than two groups) and t-test (comparison for two groups) were conducted on Blom-transformed benzene concentration data. The overall median benzene exposure levels were 215, 82, 31, and 6 mg/m(3) during the periods 1956-1978, 1979-1989, 1990-2001, and 2002-2005, respectively. Mean benzene exposure was significantly lower for paint manufacturing than paint spraying. No significant difference was found among paint types and benzene exposure for paint application. Benzene exposure was significantly higher in workplaces judged to have poor ventilation. No significant differences were found in benzene exposure as a function of industry type. Even though substantially lower when compared with levels in the past, recent benzene exposure measurements suggested that many facilities in the paint/coatings industries in China still have benzene concentrations that are above the current China occupational exposure limit for benzene (6 mg/m(3) as a time-weighted average). Benzene concentrations from the present exercise, while not directly supporting

  2. Effect of finasteride on serum levels of androstenedione, testosterone and their 5α-reduced metabolites in men at risk for prostate cancer.

    PubMed

    Stanczyk, Frank Z; Azen, Colleen G; Pike, Malcolm C

    2013-11-01

    Studies show that treatment of men with 5α-reductase inhibitors such as finasteride is effective for the primary prevention of prostate cancer. Although it is known that finasteride treatment suppresses serum levels of dihydrotestosterone (DHT) and its distal metabolite, 5α-androstane-3α,17β-diol glucuronide (3α-diol G), and increases serum testosterone (T) levels, little is known about its effect on other precursors and metabolites of DHT, as well as on the relationship of these androgens to prostate specific antigen (PSA), a marker of prostatic intraepithelial neoplasia. The present study provides new data on the effect of finasteride on precursors and metabolites of DHT. Fifty-three men, ages 57-79 years, with elevated PSA levels (>4ng/ml), were randomized to treatment with finasteride (5mg/day) or observation (controls) for 12 months. Blood samples were obtained at baseline, 1, 3, 6 and 12 months for measurement of PSA, androstenedione (A), T, DHT, 3α-diol G, androsterone glucuronide (ADT G) and DHT sulfate (DHT S) in serum by validated, highly specific radioimmunoassays. Statistical analysis was carried out using mixed model ANOVA and t-tests. In the control group, PSA and androgen levels were unchanged throughout the 12 months of treatment. In the finasteride group, PSA, DHT, DHT S, 3α-diol G and ADT G decreased from baseline to 1 month by 23.2%, 78.7%, 71.0%, 75.7% and 43.0%, respectively. The change in PSA decreased further to 46.1% and 55.1% at 3 and 12 months of treatment, respectively, whereas the decrease in androgens observed at 1 month did not change by more than 6.9% for DHT, DHT S and 3α-diol G in the subsequent months of sampling. However, the decline in ADT G was only 22.2% at month 3, and remained essentially at this level after that time. In contrast, T and A increased significantly from baseline, and the increase in A of approximately 34.5% was about 1.9 times the increase in T (approximately 18.3%). The present data suggest that either

  3. Biomass fuels and coke plants are important sources of human exposure to polycyclic aromatic hydrocarbons, benzene and toluene.

    PubMed

    Fan, Ruifang; Li, Junnan; Chen, Laiguo; Xu, Zhencheng; He, Dechun; Zhou, Yuanxiu; Zhu, Yuanyuan; Wei, Fusheng; Li, Jihua

    2014-11-01

    Large amounts of carcinogenic polycyclic aromatic hydrocarbons (PAHs), benzene and toluene (BT) might be emitted from incomplete combustion reactions in both coal tar factories and biomass fuels in rural China. The health effects arising from exposure to PAHs and BT are a concern for residents of rural areas close to coal tar plants. To assess the environmental risk and major exposure sources, 100 coke plant workers and 25 farmers in Qujing, China were recruited. The levels of 10 mono-hydroxylated PAHs (OH-PAHs), four BT metabolites and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the urine collected from the subjects were measured. The 8-OHdG levels in the urine were determined to evaluate the oxidative DNA damage induced by the PAHs and BT. The results showed that the levels of the OH-PAHs, particularly those of 1-hydroxynathalene and 1-hydroxypyrene, in the farmers were 1-7 times higher than those in the workers. The concentrations of the BT metabolites were comparable between the workers and farmers. Although the exact work location within a coke oven plant might affect the levels of the OH-PAHs, one-way ANOVA revealed no significant differences for either the OH-PAHs levels or the BT concentrations among the three groups working at different work sites. The geometric mean concentration (9.17 µg/g creatinine) of 8-OHdG was significantly higher in the farmers than in the plant workers (6.27 µg/g creatinine). The levels of 8-OHdG did not correlate with the total concentrations of OH-PAHs and the total levels of BT metabolites. Incompletely combusted biomass fuels might be the major exposure source, contributing more PAHs and BT to the local residents of Qujing. The estimated daily intakes (EDIs) of naphthalene and fluorene for all of the workers and most of the farmers were below the reference doses (RfDs) recommended by the U.S. Environmental Protection Agency (EPA), except for the pyrene levels in two farmers. However, the EDIs of benzene in the workers and local

  4. Changing Dietary Calcium-Phosphorus Level and Cereal Source Selectively Alters Abundance of Bacteria and Metabolites in the Upper Gastrointestinal Tracts of Weaned Pigs

    PubMed Central

    Mann, Evelyne; Schmitz-Esser, Stephan; Wagner, Martin; Ritzmann, Mathias; Zebeli, Qendrim

    2013-01-01

    Several dietary ingredients may affect the bacterial community structure and metabolism in the porcine gut and may therefore influence animals' health and performance. This study investigated the effects of cereal source and calcium-phosphorus (CaP) level in the diet on bacterial microbiota and metabolites, nutrient intake, and gut environment in weaned pigs. Pigs (n = 8/treatment) were fed wheat-barley- or corn-based diets with an adequate or high CaP level for 14 days. Effects on microbiota in the stomach, ileum, and midcolon were assessed using quantitative PCR. Data showed that Enterobacteriaceae, Campylobacter spp., and Helicobacter spp., which all contain highly immune reactive lipopolysaccharide (LPS), were abundant at all gut sites. Diet effects on bacteria and metabolites were moderate and occurred mainly in the upper gut, whereas no effects on bacteria, fermentation products, and LPS could be observed in the colon. Differences in carbohydrate intake with corn versus wheat-barley diets selectively stimulated Bifidobacterium in the stomach and ileum. There was a growth advantage for a few bacterial groups in the stomach and ileum of pigs fed the high versus adequate CaP level (i.e., gastric Enterobacteriaceae and ileal Enterococcus, Bacteroides-Prevotella-Porphyromonas, and Campylobacter). Interestingly, gastrointestinal pH was not affected by dietary CaP level. The present findings demonstrate the stability of the bacterial community and gut environment toward dietary changes even in young pigs. The results on stimulation of gastric and ileal Bifidobacterium by corn diets may be employed in nutritional strategies to support gut health after weaning. PMID:24038702

  5. Serotonin, dopamine, noradrenaline and their metabolites: levels in the brain of the house cricket (Acheta domesticus L.) during a 24-hour period and after administration of quipazine--a 5-HT2 receptor agonist.

    PubMed

    Pyza, E; Gołembiowska, K; Antkiewicz-Michaluk, L

    1991-01-01

    1. The levels of 5-HT, DA, NA and DA metabolites (NADA, DOPAC) measured by HPLC (with electrochemical detection) in the brain of the house cricket did not change over a 24-hr period. The level of 5-HIAA, a 5-HT metabolite, was below the limit of detection. 2. The 5-HT and DOPAC levels decreased and NADA increased after quipazine injection but DA and NA levels did not change after it. 3. [3H]Ketanserin was used to identify serotonin receptors bound to sites in the house cricket brain with a KD of 5 nM and a concentration of Bmax 180 fmol/mg protein.

  6. 46 CFR 151.05-2 - Compliance with requirements for tank barges carrying benzene and benzene containing cargoes, or...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... benzene and benzene containing cargoes, or butyl acrylate cargoes. 151.05-2 Section 151.05-2 Shipping... Compliance with requirements for tank barges carrying benzene and benzene containing cargoes, or butyl acrylate cargoes. A tank barge certificated to carry benzene and benzene containing cargoes or...

  7. 46 CFR 151.05-2 - Compliance with requirements for tank barges carrying benzene and benzene containing cargoes, or...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... benzene and benzene containing cargoes, or butyl acrylate cargoes. 151.05-2 Section 151.05-2 Shipping... Compliance with requirements for tank barges carrying benzene and benzene containing cargoes, or butyl acrylate cargoes. A tank barge certificated to carry benzene and benzene containing cargoes or...

  8. 46 CFR 151.05-2 - Compliance with requirements for tank barges carrying benzene and benzene containing cargoes, or...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... benzene and benzene containing cargoes, or butyl acrylate cargoes. 151.05-2 Section 151.05-2 Shipping... Compliance with requirements for tank barges carrying benzene and benzene containing cargoes, or butyl acrylate cargoes. A tank barge certificated to carry benzene and benzene containing cargoes or...

  9. 46 CFR 151.05-2 - Compliance with requirements for tank barges carrying benzene and benzene containing cargoes, or...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... benzene and benzene containing cargoes, or butyl acrylate cargoes. 151.05-2 Section 151.05-2 Shipping... Compliance with requirements for tank barges carrying benzene and benzene containing cargoes, or butyl acrylate cargoes. A tank barge certificated to carry benzene and benzene containing cargoes or...

  10. 46 CFR 151.05-2 - Compliance with requirements for tank barges carrying benzene and benzene containing cargoes, or...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... benzene and benzene containing cargoes, or butyl acrylate cargoes. 151.05-2 Section 151.05-2 Shipping... Compliance with requirements for tank barges carrying benzene and benzene containing cargoes, or butyl acrylate cargoes. A tank barge certificated to carry benzene and benzene containing cargoes or...

  11. Ab initio investigation of benzene clusters: Molecular tailoring approach

    NASA Astrophysics Data System (ADS)

    Mahadevi, A. Subha; Rahalkar, Anuja P.; Gadre, Shridhar R.; Sastry, G. Narahari

    2010-10-01

    An exhaustive study on the clusters of benzene (Bz)n, n =2-8, at MP2/6-31++G∗∗ level of theory is reported. The relative strengths of CH-π and π-π interactions in these aggregates are examined, which eventually govern the pattern of cluster formation. A linear scaling method, viz., molecular tailoring approach (MTA), is efficiently employed for studying the energetics and growth patterns of benzene clusters consisting up to eight benzene (Bz) units. Accuracy of MTA-based calculations is appraised by performing the corresponding standard calculations wherever possible, i.e., up to tetramers. For benzene tetramers, the error introduced in energy is of the order of 0.1 mH (˜0.06 kcal/mol). Although for higher clusters the error may build up, further corrections based on many-body interaction energy analysis substantially reduce the error in the MTA-estimate. This is demonstrated for a prototypical case of benzene hexamer. A systematic way of building up a cluster of n monomers (n-mer) which employs molecular electrostatic potential of an (n -1)-mer is illustrated. The trends obtained using MTA method are essentially identical to those of the standard methods in terms of structure and energy. In summary, this study clearly brings out the possibility of effecting such large calculations, which are not possible conventionally, by the use of MTA without a significant loss of accuracy.

  12. Accumulation of chlorinated benzenes in earthworms

    USGS Publications Warehouse

    Beyer, W.N.

    1996-01-01

    Chlorinated benzenes are widespread in the environment. Hexachlorobenzene, pentachlorobenzene and all isomers of dichlorobenzenes, trichlorobenzenes, and tetrachlorobenzenes, have been detected in fish, water, and sediments from the Great Lakes. This paper describes a long-term (26 week) experiment relating the concentrations of chlorinated benzenes in earthworms to 1) the length of exposure, and it describes three 8-week experiments relating concentrations of chlorinated benzenes in earthworms to 2) their concentration in soil 3) the soil organic matter content and, 4) the degree of chlorination. In the 26-week experiment, the concentration of 1,2,4 - trichlorobenzene in earthworms fluctuated only slightly about a mean of 0.63 ppm (Fig. 1). Although a statistically significant decrease can be demonstrated over the test (Pearson correlation coefficient, r = -0.62 p < 0.05), the decrease was minor. Hexachlorobenzene in earthworms showed a cyclical trend that coincided with replacement of the media, and a slight but statistically significant tendency to increase from about 2 to 3 ppm over the 26 weeks (r = 0.55, p < 0.05). Concentrations of both trichlorobenzene and hexachlorobenzene in earthworms increased as the concentrations in the soil increased (Fig. 2), but leveled off at the highest soil concentrations. The most surprising result of this study was the relatively low concentrations in earthworms compared to those in soils. The average concentration of each of the six isomers of trichlorobenzene and tetrachlorobenzene in earthworms was only about 1 ppm (Table 2); the isomeric structure did not affect accumulation. The concentration of organic matter in soil had a prominent effect on hexachlorobenzene concentrations in earthworms (Fig. 3). Hexachlorobenzene concentrations decreased steadily from 9.3 ppm in earthworms kept in soil without any peat moss added to about 1 ppm in soil containing 16 or 32% organic matter.

  13. Levels of prostaglandin E metabolite and leukotriene E(4) are increased in the urine of smokers: evidence that celecoxib shunts arachidonic acid into the 5-lipoxygenase pathway.

    PubMed

    Duffield-Lillico, Anna J; Boyle, Jay O; Zhou, Xi Kathy; Ghosh, Aradhana; Butala, Geera S; Subbaramaiah, Kotha; Newman, Robert A; Morrow, Jason D; Milne, Ginger L; Dannenberg, Andrew J

    2009-04-01

    Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) play a role in inflammation and carcinogenesis. Biomarkers that reflect tobacco smoke-induced tissue injury are needed. In this study, levels of urinary prostaglandin E metabolite (PGE-M) and leukotriene E(4) (LTE(4)), biomarkers of the COX and 5-LO pathways, were compared in never smokers, former smokers, and current smokers. The effects of celecoxib, a selective COX-2 inhibitor, on levels of PGE-M and LTE(4) were determined. Baseline levels of PGE-M and LTE(4) were positively associated with smoking status; levels of PGE-M and LTE(4) were higher in current versus never smokers. Treatment with 200 mg celecoxib twice daily for 6 +/- 1 days led to a reduction in urinary PGE-M levels in all groups but exhibited the greatest effect among subjects with high baseline PGE-M levels. Thus, high baseline PGE-M levels in smokers reflected increased COX-2 activity. In individuals with high baseline PGE-M levels, treatment with celecoxib led to a significant increase in levels of urinary LTE(4), an effect that was not found in individuals with low baseline PGE-M levels. In conclusion, increased levels of urinary PGE-M and LTE(4) were found in human smokers, a result that may reflect subclinical lung inflammation. In individuals with high baseline levels of PGE-M (elevated COX-2 activity), celecoxib administration shunted arachidonic acid into the proinflammatory 5-LO pathway. Because 5-LO activity and LTE(4) have been suggested to play a role in cardiovascular disease, these results may help to explain the link between use of COX-2 inhibitors and cardiovascular complications.

  14. Association of blood glucose, blood lactate, serum cortisol levels, muscle metabolites, muscle fiber type composition, and pork quality traits.

    PubMed

    Choe, J H; Kim, B C

    2014-06-01

    The objective of this study was to investigate the relationship of blood glucose levels with blood lactate, serum cortisol levels, postmortem muscle glycogen and lactate content, muscle fiber type composition, and pork quality traits. Compared to pigs with lower blood glucose levels, pigs with higher blood glucose levels showed higher blood lactate and serum cortisol levels at exsanguination, and they had lower residual glycogen and higher lactate content in the muscle at 45min postmortem. In addition, pigs with higher blood glucose levels had higher type IIB and lower type I area composition and finally exhibited lower muscle pH, paler color, and excessive loss of fluid on surface. These results imply that measuring blood glucose levels at exsanguination can be useful to indicate early glycolytic rates during postmortem and thus may be of value in the identification of pork with undesirable quality traits.

  15. MiR-34a, a promising novel biomarker for benzene toxicity, is involved in cell apoptosis triggered by 1,4-benzoquinone through targeting Bcl-2.

    PubMed

    Chen, Yujiao; Sun, Pengling; Guo, Xiaoli; Gao, Ai

    2017-02-01

    Exposure to benzene is inevitable, and concerns regarding the adverse health effects of benzene have been raised. Most investigators found that benzene exposure induced hematotoxicity. In this regard, Our study aimed to explore a novel potential biomarker of adverse health effects following benzene exposure and the toxic mechanisms of benzene metabolites in vitro. This study consisted of 314 benzene-exposed workers and 288 control workers, an air benzene concentration of who were 2.64 ± 1.60 mg/m(3) and 0.05 ± 0.01 mg/m(3), respectively. In this population-based study, miR-34a expression was elevated in benzene-exposed workers. The correlation of miR-34a with the airborne benzene concentration, S-phenylmercapturic acid (S-PMA) and trans, trans-muconic acid (t, t-MA), all of which reflect benzene exposure, was found. Correlation analysis indicated that miR-34a was associated with peripheral blood count, alanine transaminase (ALT) and oxidative stress. Furthermore, multivariate analysis demonstrated that miR-34a expression was strongly associated with white blood cell count (structure loadings = 0.952). In population-based study, miR-34a had the largest contribution to altered peripheral blood counts, which reflect benzene-induced hematotoxicity. The role of miR-34a in benzene toxicity was assessed using lentiviral vector transfection. Results revealed that 1,4-benzoquinone induced abnormal cell apoptosis and simultaneously upregulated miR-34a accompanied with decreased Bcl-2. Finally, inhibition of miR-34a elevated Bcl-2 and decreased 1,4-benzoquinone-induced apoptosis. In conclusion, miR-34a was observed to be involved in benzene-induced hematotoxicity by targeting Bcl-2 and could be regarded as a potential novel biomarker for benzene toxicity.

  16. Endogenous Levels of Five Fatty Acid Metabolites in Exhaled Breath Condensate to Monitor Asthma by High-Performance Liquid Chromatography: Electrospray Tandem Mass Spectrometry

    PubMed Central

    Nording, Malin L.; Yang, Jun; Hegedus, Christine M.; Bhushan, Abhinav; Kenyon, Nicholas J.; Davis, Cristina E.; Hammock, Bruce D.

    2010-01-01

    Airway inflammation characterizing asthma and other airway diseases may be monitored through biomarker analysis of exhaled breath condensate (EBC). In an attempt to discover novel EBC biomarkers, a high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method was used to analyze EBC from ten control non-asthmatics and one asthmatic individual for five fatty acid metabolites: 9,12,13-trihydroxyoctadecenoic acid (9,12,13-TriHOME), 9,10,13-TriHOME, 12,13-dihydroxyoctadecenoic acid (12,13-DiHOME), 12-hydroxyeicosatetraenoic acid (12-HETE), and 12(13)-epoxyoctadecenoic acid (12(13)-EpOME). The method was shown to be sensitive, with an on-column limit of quatitation (LOQ) in the pg range (corresponding to pM concentrations in EBC), and linear over several orders of magnitude for each analyte in the calibrated range. Analysis of EBC spiked with the five fatty acid metabolites was within 81%–119% with only a few exceptions. Endogenous levels in EBC exhibited intra- and inter-assay precision of 10%–22%, and 12%–36%, respectively. EBC from the healthy subjects contained average analyte levels between 15 and 180 pM with 12-HETE present above the LOQ in only one of the subjects at a concentration of 240 pM. Exposure of the asthmatic subject to allergen led to increased EBC concentrations of 9,12,13-TriHOME, 9,10,13-TriHOME, 12,13-DiHOME, and 12(13)-EpOME when compared to levels in EBC collected prior to allergen exposure (range =40–510 pM). 12,13-DiHOME was significantly increased (Student's t-test, p < 0.05). In conclusion, we have developed a new HPLC-ESI-MS/MS method for the analysis of five fatty acid metabolites in EBC, which are potential biomarkers for asthma monitoring and diagnosis. PMID:21103452

  17. Cerebrospinal fluid levels of catecholamines and its metabolites in Parkinson's disease: Effect of L-DOPA treatment and changes in levodopa-induced dyskinesia.

    PubMed

    Andersen, A D; Blaabjerg, M; Binzer, M; Kamal, A; Thagesen, H; Kjaer, T W; Stenager, E; Gramsbergen, J B

    2017-02-28

    Levodopa (L-DOPA, L-3,4-dihydroxyphenylalanine) is the most effective drug in the symptomatic treatment of Parkinson's disease (PD), but chronic use initiates a maladaptive process leading to L-DOPA-induced dyskinesia (LID). Risk factors for early onset LID include younger age, more severe disease at baseline and higher daily L-DOPA dose, but biomarkers to predict the risk of motor complications are not yet available. Here we investigated whether CSF levels of catecholamines and its metabolites are altered in PD patients with LID (PD-LID, n=8)) as compared to non-dyskinetic PD patients receiving L-DOPA (PD-L, n=6), or not receiving L-DOPA (PD-N, n=7) as well as non-PD controls (n=16). PD patients were clinically assessed using the Unified Parkinson's Disease Rating Scale and Unified Dyskinesia Rating Scale and CSF was collected after overnight fasting and 1-2 hours after oral intake of L-DOPA or other anti-Parkinson medication. CSF catecholamines and its metabolites were analyzed by HPLC with electrochemical detection. We observed (1) decreased levels of dihydroxyphenylacetic acid and homovanillic acid in PD patients not receiving L-DOPA (2) higher DA levels in LID as compared to controls (3) higher DA/L-DOPA and lower DOPAC/DA ratio's in LID as compared to PDL and (4) an age-dependent increase of DA and decrease of DOPAC/DA ratio in controls. These results suggest increased DA release from non-DA cells and deficient DA re-uptake in PD-LID. Monitoring DA and DOPAC in CSF of L-DOPA-treated PD patients may help identify patients at risk of developing LID. This article is protected by copyright. All rights reserved.

  18. Hydrogen bonding in the benzene-ammonia dimer

    NASA Technical Reports Server (NTRS)

    Rodham, David A.; Suzuki, Sakae; Suenram, Richard D.; Lovas, Frank J.; Dasgupta, Siddharth; Goddard, William A., III; Blake, Geoffrey A.

    1993-01-01

    High-resolution optical and microwave spectra of the gas-phase benzene-ammonia dimer were obtained, showing that the ammonia molecule resides above the benzene plane and undergoes free, or nearly free, internal rotation. To estimate the binding energy (De) and other global properties of the intermolecular potential, theoretical calculations were performed for the benzene-ammonia dimer, using the Gaussian 92 (Fritsch, 1992) program at the MP2/6-31G** level. The predicted De was found to be at the lowest end of the range commonly accepted for hydrogen bonding and considerably below that of C6H6-H2O, consistent with the gas-phase acidities of ammonia and water. The observed geometry greatly resembles the amino-aromatic interaction found naturally in proteins.

  19. Double photoionization of halogenated benzene

    SciTech Connect

    AlKhaldi, Mashaal Q.; Wehlitz, Ralf

    2016-01-28

    We have experimentally investigated the double-photoionization process in C{sub 6}BrF{sub 5} using monochromatized synchrotron radiation. We compare our results with previously published data for partially deuterated benzene (C{sub 6}H{sub 3}D{sub 3}) over a wide range of photon energies from threshold to 270 eV. A broad resonance in the ratio of doubly to singly charged parent ions at about 65 eV appears shifted in energy compared to benzene data. This shift is due to the difference in the bond lengths in two molecules. A simple model can explain the shape of this resonance. At higher photon energies, we observe another broad resonance that can be explained as a second harmonic of the first resonance.

  20. Functionalization of benzene by superhalogens

    NASA Astrophysics Data System (ADS)

    Srivastava, Ambrish Kumar; Kumar, Abhishek; Misra, Neeraj

    2017-03-01

    We perform ab initio MP2/6-311++G(d,p) calculations to analyze the molecular properties and aromaticity of NO3, BO2 as well as BF4 superhalogen substituted benzene and compare them with well known electron withdrawing group substituted benzene such as C6H5F and C6H5CN in neutral and ionic forms. It has been noticed that the properties (including aromaticity) of C6H5BO2 closely resemble those of C6H5F and C6H5CN. On the contrary, C6H5NO3 possesses some quite different properties such as high electron affinity, small frontier orbital energy gap and enhanced aromaticity. It is also revealed that C6H5BF4 exists only in the form of C6H5F⋯BF3 complex.

  1. Induction of micronuclei and aneuploidy by the quinone-forming agents benzene and o-phenylphenol.

    PubMed

    Eastmond, D A

    1993-04-01

    A number of carcinogens appear to exert their tumorigenic effects through the formation of quinone metabolites. These quinone-forming carcinogens are generally inactive or weakly active in standard gene mutation assays. Accumulating evidence indicates that this class of compounds may exert their genotoxic and carcinogenic effects through the induction of large-scale gene alterations. This article presents an overview of work that has been performed using recently developed molecular cytogenic techniques to investigate the aneuploidy-inducing and clastogenic properties of the major quinone-forming metabolites of benzene, a widely used industrial chemical, and o-phenylphenol, a fungicide and disinfectant. These metabolites of benzene (hydroquinone, catechol, and benzenetriol) and o-phenylphenol (phenylhydroquinone) have each been shown to be capable of interfering with chromosome segregation and inducing chromosomal breakage. These results indicate that both numerical and structural chromosomal aberrations induced by the quinone metabolites of benzene and o-phenylphenol may play a role in the carcinogenic effects of these two agents.

  2. Atmospheric benzene observations from oil and gas production in the Denver-Julesburg Basin in July and August 2014

    NASA Astrophysics Data System (ADS)

    Halliday, Hannah S.; Thompson, Anne M.; Wisthaler, Armin; Blake, Donald R.; Hornbrook, Rebecca S.; Mikoviny, Tomas; Müller, Markus; Eichler, Philipp; Apel, Eric C.; Hills, Alan J.

    2016-09-01

    High time resolution measurements of volatile organic compounds (VOCs) were collected using a proton-transfer-reaction quadrupole mass spectrometry (PTR-QMS) instrument at the Platteville Atmospheric Observatory (PAO) in Colorado to investigate how oil and natural gas (O&NG) development impacts air quality within the Wattenburg Gas Field (WGF) in the Denver-Julesburg Basin. The measurements were carried out in July and August 2014 as part of NASA's "Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality" (DISCOVER-AQ) field campaign. The PTR-QMS data were supported by pressurized whole air canister samples and airborne vertical and horizontal surveys of VOCs. Unexpectedly high benzene mixing ratios were observed at PAO at ground level (mean benzene = 0.53 ppbv, maximum benzene = 29.3 ppbv), primarily at night (mean nighttime benzene = 0.73 ppbv). These high benzene levels were associated with southwesterly winds. The airborne measurements indicate that benzene originated from within the WGF, and typical source signatures detected in the canister samples implicate emissions from O&NG activities rather than urban vehicular emissions as primary benzene source. This conclusion is backed by a regional toluene-to-benzene ratio analysis which associated southerly flow with vehicular emissions from the Denver area. Weak benzene-to-CO correlations confirmed that traffic emissions were not responsible for the observed high benzene levels. Previous measurements at the Boulder Atmospheric Observatory (BAO) and our data obtained at PAO allow us to locate the source of benzene enhancements between the two atmospheric observatories. Fugitive emissions of benzene from O&NG operations in the Platteville area are discussed as the most likely causes of enhanced benzene levels at PAO.

  3. Intermolecular interactions in solid benzene.

    PubMed

    Kearley, G J; Johnson, M R; Tomkinson, J

    2006-01-28

    The lattice dynamics and molecular vibrations of benzene and deuterated benzene crystals are calculated from force constants derived from density-functional theory (DFT) calculations and compared with measured inelastic neutron-scattering spectra. A very small change (0.5%) in lattice parameter is required to obtain real lattice-mode frequencies across the Brillouin zone. There is a strong coupling between wagging and breathing modes away from the zone center. This coupling and sensitivity to cell size arises from two basic interactions. Firstly, comparatively strong interactions that hold the benzene molecules together in layers. These include an intermolecular interaction in which H atoms of one molecule link to the center of the aromatic ring of a neighboring molecule. The layers are held to each other by weaker interactions, which also have components that hold molecules together within a layer. Small changes in the lattice parameters change this second type of interaction and account for the changes to the lattice dynamics. The calculations also reveal a small auxetic effect in that elongation of the crystal along the b axis leads to an increase in internal pressure in the ac plane, that is, elongation in the b direction induces expansion in the a and c directions.

  4. Effects of a short-course MDMA binge on dopamine transporter binding and on levels of dopamine and its metabolites in adult male rats.

    PubMed

    Biezonski, Dominik K; Piper, Brian J; Shinday, Nina M; Kim, Peter J; Ali, Syed F; Meyer, Jerrold S

    2013-02-15

    Although the recreational drug 3,4-methylenedioxymethamphetamine (MDMA) is often described as a selective serotonergic neurotoxin, some research has challenged this view. The objective of this study was to determine the influence of MDMA on subsequent levels of two different markers of dopaminergic function, the dopamine transporter (DAT) as well as dopamine and its major metabolites. In experiment I, adult male Sprague-Dawley rats were administered either a low or moderate dose MDMA binge (2.5 or 5.0mg/kg×4 with an inter-dose interval of 1h) or saline, and were killed 1 week later. The moderate dose dramatically reduced [(3)H]WIN 35,428 binding to striatal DAT by 73.7% (P≤0.001). In experiment II, animals were binged with a higher dose of MDMA (10mg/kg×4) to determine the drug's effects on concentrations of serotonin (5-HT), dopamine, and their respective major metabolites 5-hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum and frontal cortex 1 week later. As expected, MDMA significantly reduced 5-HT and 5-HIAA (≥50%) in these structures, while only a marginal decrease in dopamine was noted in the striatum. In contrast, levels of DOPAC (34.3%, P<0.01) and HVA (33.5%, P<0.001) were reduced by MDMA treatment, suggesting a decrease in dopamine turnover. Overall, these findings indicate that while serotonergic markers are particularly vulnerable to MDMA-induced depletion, significant dopaminergic deficits may also occur under some conditions. Importantly, DAT expression may be more vulnerable to perturbation by MDMA than dopamine itself.

  5. Liver glucose-6-phosphatase proteins in suckling and weaned grey seal pups: structural similarities to other mammals and relationship to nutrition, insulin signalling and metabolite levels.

    PubMed

    Bennett, K A; Hammill, M; Currie, S

    2013-12-01

    Phocid seals have been proposed as models for diabetes because they exhibit limited insulin response to glucose, high blood glucose and increasing insulin resistance when fasting. Liver glucose-6-phosphatase (G6Pase) catalyses the final step in glucose production and is central to glucose regulation in other animals. G6Pase comprises a translocase (SLC37A4) and a catalytic subunit (G6PC). G6PC and SLC37A4 expression and activity are normally regulated by nutritional state and glucostatic hormones, particularly insulin, and are elevated in diabetes. We tested the hypotheses that (1) grey seal G6PC and SLC37A4 cDNA and predicted protein sequences differ from other species' at functional sites, (2) relative G6Pase protein abundances are lower during feeding than fasting and (3) relative G6Pase protein abundances are related to insulin, insulin receptor phosphorylation and key metabolite levels. We show that G6PC and partial SLC37A4 cDNA sequences encode proteins sharing 82-95 % identity with other mammals. Seal G6PC contained no differences in sites responsible for activity, stability or subcellular location. Several substitutions in seal SLC37A4 were predicted to be tolerated with low probability, which could affect glucose production. Suckling pups had higher relative abundance of both subunits than healthy, postweaned fasting pups. Furthermore, relative G6PC abundance was negatively related to glucose levels. These findings contrast markedly with the response of relative hepatic G6Pase abundance to feeding, fasting, insulin, insulin sensitivity and key metabolites in other animals, and highlight the need to understand the regulation of enzymes involved in glucose control in phocids if these animals are to be informative models of diabetes.

  6. Effects of a short-course MDMA binge on dopamine transporter binding and on levels of dopamine and its metabolites in adult male rats

    PubMed Central

    Biezonski, Dominik K.; Piper, Brian J.; Shinday, Nina M.; Kim, Peter J.; Ali, Syed F.; Meyer, Jerrold S.

    2013-01-01

    Although the recreational drug 3,4-methylenedioxymethamphetamine (MDMA) is often described as a selective serotonergic neurotoxin, some research has challenged this view. The objective of this study was to determine the influence of MDMA on subsequent levels of two different markers of dopaminergic function, the dopamine transporter (DAT) as well as dopamine and its major metabolites. In experiment I, adult male Sprague–Dawley rats were administered either a low or moderate dose MDMA binge (2.5 or 5.0 mg/kg × 4 with an inter-dose interval of 1 h) or saline, and were killed 1 week later. The moderate dose dramatically reduced [3H]WIN 35,428 binding to striatal DAT by 73.7% (P ≤ 0.001). In experiment II, animals were binged with a higher dose of MDMA (10 mg/kg × 4) to determine the drug’s effects on concentrations of serotonin (5-HT), dopamine, and their respective major metabolites 5-hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum and frontal cortex 1 week later. As expected, MDMA significantly reduced 5-HT and 5-HIAA (≥ 50%) in these structures, while only a marginal decrease in dopamine was noted in the striatum. In contrast, levels of DOPAC (34.3%, P < 0.01) and HVA (33.5%, P < 0.001) were reduced by MDMA treatment, suggesting a decrease in dopamine turnover. Overall, these findings indicate that while serotonergic markers are particularly vulnerable to MDMA-induced depletion, significant dopaminergic deficits may also occur under some conditions. Importantly, DAT expression may be more vulnerable to perturbation by MDMA than dopamine itself. PMID:23276666

  7. Short-echo 3D H-1 Magnetic Resonance Spectroscopic Imaging of patients with glioma at 7T for characterization of differences in metabolite levels

    PubMed Central

    Li, Yan; Larson, Peder; Chen, Albert P.; Lupo, Janine M.; Ozhinsky, Eugene; Kelley, Douglas; Chang, Susan M.; Nelson, Sarah J.

    2014-01-01

    Purpose The purpose of this study was to evaluate the feasibility of using a short echo time, 3D H-1 magnetic resonance spectroscopic imaging (MRSI) sequence at 7T to assess the metabolic signature of lesions for patients with glioma. Materials and Methods 29 patients with glioma were studied. MRSI data were obtained using CHESS water suppression, spectrally-selective adiabatic inversion-recovery pulses and automatically prescribed outer-volume-suppression for lipid suppression, and spin echo slice selection (TE=30ms). An interleaved flyback echo-planar trajectory was applied to shorten the total acquisition time (~10min). Relative metabolite ratios were estimated in tumor and in normal-appearing white and gray matter (NAWM, GM). Results Levels of glutamine, myo-inositol, glycine and glutathione relative to total creatine (tCr) were significantly increased in the T2 lesions for all tumor grades compared to those in the NAWM (p < 0.05), while N-acetyl aspartate to tCr were significantly decreased (p < 0.05). In grade 2 gliomas, level of total choline-containing-compounds to tCr was significantly increased (p = 0.0137), while glutamate to tCr was significantly reduced (p = 0.0012). Conclusion The improved sensitivity of MRSI and the increased number of metabolites that can be evaluated using 7T MR scanners is of interest for evaluating patients with glioma. This study has successfully demonstrated the application of a short-echo spin-echo MRSI sequence to detect characteristic differences in regions of tumor versus normal appearing brain. PMID:24935758

  8. Benzene exposure in childhood: Role of living environments and assessment of available tools.

    PubMed

    Protano, Carmela; Guidotti, Maurizio; Manini, Paola; Petyx, Marta; La Torre, Giuseppe; Vitali, Matteo

    2010-10-01

    Benzene is a widespread air pollutant and a well-known human carcinogen. Evidence is needed regarding benzene intake in the pediatric age group. We investigated the use of urinary (u) trans,trans-muconic acid (t,t-MA), S-phenylmercapturic acid (SPMA), and unmodified benzene (UB) for assessing exposure to low concentrations of environmental benzene and the role of living environment on benzene exposure in childhood. u-t,t-MA, u-SPMA, u-UB and u-cotinine were measured in urine samples of 243 Italian children (5-11 years) recruited in a cross-sectional study. Analytical results were compared with data obtained from questionnaires about participants' main potential exposure factors. u-UB, u-t,t-MA and u-SPMA concentrations were about 1.5-fold higher in children living in urban areas than in those in the rural group. Univariate analyses showed that u-UB was the only biomarker able to discriminate secondhand smoke (SHS) exposure in urban and rural children (medians=411.50 and 210.50 ng/L, respectively); these results were confirmed by the strong correlation between u-UB and u-cotinine in the SHS-exposed group and by multivariate analyses. A regression model on u-SPMA showed that the metabolite is related to residence area (p<0.001), SHS exposure (p=0.048) and gender (p=0.027). u-UB is the best marker of benzene exposure in children in the present study, and it can be used as a good carcinogen-derived biomarker of exposure to passive smoking, especially related to benzene, when urine sample is collected at the end of the day. In addition, it is important to highlight that SHS resulted the most important contributor to benzene exposure, underlining the need for an information campaign against passive smoking exposure.

  9. Sex-Related Difference in Nitric Oxide Metabolites Levels after Nephroprotectant Supplementation Administration against Cisplatin-Induced Nephrotoxicity in Wistar Rat Model: The Role of Vitamin E, Erythropoietin, or N-Acetylcysteine.

    PubMed

    Nematbakhsh, Mehdi; Pezeshki, Zahra

    2013-01-01

    Background. Nitric oxide (NO) concentration in serum is altered by cisplatin (CP), and NO influences CP-induced nephrotoxicity. The effect of nephroprotectant agent supplementation (vitamin E, human recombinant erythropoietin (EPO), or n-acetylcysteine (NAC)) on the NO metabolites levels after CP administration in the two genders was determined. Methods. Sixty-four adult Wistar rats were randomly divided into 10 groups. Male and female rats in different groups received vehicle (saline), CP (7 mg/kg) alone, CP plus EPO (100 IU/kg), CP plus vitamin E (250 mg/kg), and CP plus NAC (600 mg/kg). CP was administrated as a single dose, but the supplementations were given for a period of 7 days. Results. In male rats, the serum levels of total NO metabolites (NO x ) and nitrite were increased significantly (P < 0.05) by CP. However, vitamin E significantly reduced the serum levels of these metabolites, which was increased by administration of CP (P < 0.05), and such findings were not observed for female rats. The EPO or NAC did not influence NO metabolites neither in male rats nor in female rats. Conclusion. Although vitamin E, EPO, and NAC are reported to be nephroprotectant agents against CP-induced nephrotoxicity, only vitamin E could reduce the level of all NO metabolites only in male rats.

  10. Concomitant aerobic biodegradation of benzene and thiophene

    SciTech Connect

    Dyreborg, S.; Arvin, E.; Broholm, K.

    1998-05-01

    The concomitant aerobic biodegradation of benzene and thiophene was investigated in microcosm experiments using a groundwater enrichment culture. Benzene was biodegraded within 1 d, whereas thiophene could not be biodegraded as the sole source of carbon and energy. Some interesting phenomena were observed when both benzene and thiophene were present. In most cases, removal of thiophene was observed, and the removal occurred concomitantly with the biodegradation of benzene, suggesting that benzene was used as a primary substrate in the cometabolic biodegradation of thiophene. No biodegradation of the two compounds was observed for some combinations of concentrations, suggesting that thiophene could act as an inhibitor to benzene biodegradation. However, this effect could be overcome if more benzene was added to the microcosm. Residual concentrations of benzene and thiophene were observed in some microcosms and the data indicated that the biodegradation of the two compounds stopped when a critical threshold ratio between the concentrations of thiophene and benzene was reached. This ratio varied between 10 and 20. Results from modeling the biodegradation data suggested that thiophene was cometabolized concomitantly with the biodegradation of benzene and that the biodegradation may be described by a modified model based on a traditional model with an inhibition term incorporated.

  11. Impact of a new gasoline benzene regulation on ambient air pollutants in Anchorage, Alaska

    NASA Astrophysics Data System (ADS)

    Yano, Yuriko; Morris, Stephen S.; Salerno, Christopher; Schlapia, Anne M.; Stichick, Mathew

    2016-05-01

    The purpose of this study was to quantify the impact of a new U.S. Environmental Protection Agency (EPA) standard that limits the amount of benzene allowed in gasoline on ambient benzene concentrations. This new standard, together with two companion regulations that limit cold-temperature automotive emissions and the permeability of portable fuel containers, was expected to lower the levels of ambient benzene and other volatile organic compounds (VOCs) nationwide. In this study the impact of the gasoline benzene standard was evaluated in Anchorage, Alaska in a two-phase ambient air monitoring study conducted before and after the new gasoline standard was implemented. Gasoline sold by Anchorage retailers was also evaluated in each phase to determine the content of benzene and other gasoline components. The average benzene content in Anchorage gasoline was reduced by 70%, from 5.05% (w/w) to 1.53% (w/w) following the implementation of the standard. The annual mean ambient benzene concentration fell by 51%, from 0.99 ppbv in Phase 1 to 0.49 ppbv in Phase 2. Analysis suggests the change in gasoline benzene content alone reduced benzene emissions by 46%. The changes in toluene, ethylbenzene, and xylene content in gasoline between Phase 1 and 2 were relatively small and the differences in the mean ambient concentrations of these compounds between phases were modest. Our results suggest that cold winter communities in high latitude and mountainous regions may benefit more from the gasoline benzene standard because of high benzene emissions resulting from vehicle cold start and a tendency to develop atmospheric stagnation conditions in the winter.

  12. Serum nitric oxide metabolite (NO(x)) levels in hypertensive patients at rest: a comparison of age, gender, blood pressure and complications using normotensive controls.

    PubMed

    Higashino, Hideaki; Miya, Hirohisa; Mukai, Hidenori; Miya, Yoshihisa

    2007-08-01

    1. Hypertensive patients have pathophysiological changes such as atherosclerosis, endothelial dysfunction and inflammations. The patients' serum nitric oxide metabolite (nitrate/nitrite; NO(x)) levels were measured in peripheral blood using normotensive controls for comparison. 2. The NO(x) levels in 175 hypertensive patients with or without comorbid diseases (aged 37-95 years; average 50.6 +/- 0.8 years) were compared with those in 80 normotensive controls (aged 25-73 years; average 37.1 +/- 1.8 years). 3. The NO(x) levels increased with age in both the normotensive and hypertensive women, but not in men. No difference was noted in the NO(x) levels between the normotensive and hypertensive patients without comorbid diseases. The mean value of NO(x) in male hypertensive patients aged under 50 years was close to that of female patients aged 51-60 years. Hypertensive males aged 61-70 years showed almost the same NO(x) levels as those of female patients aged over 81 years. A male group of hypertensive patients with diabetes, hyperlipaemia and renal disorder had a significantly higher NO(x) level compared with a normotensive control group. However, in female groups, only hypertensive patients with hyperlipaemia showed higher serum NO(x) values compared with the normotensive group. 4. These findings suggest that: (i) the occurrence of NO(x) in the serum is not solely the outcome of high blood pressure; (ii) higher serum NO(x) levels in older women are because of an oestrogen deficiency-induced cardiovascular disease; (iii) ageing effects on the circulation system are more apparent in men than in women; and (iv) measurement of NO(x) levels in the serum is helpful for understanding the pathological progress in male hypertensive patients with diseases such as diabetes mellitus, hyperlipaemia and renal disorder.

  13. Can volatile organic metabolites be used to simultaneously assess microbial and mite contamination level in cereal grains and coffee beans?

    PubMed

    Salvador, Angelo C; Baptista, Inês; Barros, António S; Gomes, Newton C M; Cunha, Angela; Almeida, Adelaide; Rocha, Silvia M

    2013-01-01

    A novel approach based on headspace solid-phase microextraction (HS-SPME) combined with comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC×GC-ToFMS) was developed for the simultaneous screening of microbial and mite contamination level in cereals and coffee beans. The proposed approach emerges as a powerful tool for the rapid assessment of the microbial contamination level (ca. 70 min versus ca. 72 to 120 h for bacteria and fungi, respectively, using conventional plate counts), and mite contamination (ca. 70 min versus ca. 24 h). A full-factorial design was performed for optimization of the SPME experimental parameters. The methodology was applied to three types of rice (rough, brown, and white rice), oat, wheat, and green and roasted coffee beans. Simultaneously, microbiological analysis of the samples (total aerobic microorganisms, moulds, and yeasts) was performed by conventional plate counts. A set of 54 volatile markers was selected among all the compounds detected by GC×GC-ToFMS. Principal Component Analysis (PCA) was applied in order to establish a relationship between potential volatile markers and the level of microbial contamination. Methylbenzene, 3-octanone, 2-nonanone, 2-methyl-3-pentanol, 1-octen-3-ol, and 2-hexanone were associated to samples with higher microbial contamination level, especially in rough rice. Moreover, oat exhibited a high GC peak area of 2-hydroxy-6-methylbenzaldehyde, a sexual and alarm pheromone for adult mites, which in the other matrices appeared as a trace component. The number of mites detected in oat grains was correlated to the GC peak area of the pheromone. The HS-SPME/GC×GC-ToFMS methodology can be regarded as the basis for the development of a rapid and versatile method that can be applied in industry to the simultaneous assessment the level of microbiological contamination and for detection of mites in cereals grains and coffee beans.

  14. Can Volatile Organic Metabolites Be Used to Simultaneously Assess Microbial and Mite Contamination Level in Cereal Grains and Coffee Beans?

    PubMed Central

    Salvador, Ângelo C.; Baptista, Inês; Barros, António S.; Gomes, Newton C. M.; Cunha, Ângela; Almeida, Adelaide; Rocha, Silvia M.

    2013-01-01

    A novel approach based on headspace solid-phase microextraction (HS-SPME) combined with comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry (GC×GC–ToFMS) was developed for the simultaneous screening of microbial and mite contamination level in cereals and coffee beans. The proposed approach emerges as a powerful tool for the rapid assessment of the microbial contamination level (ca. 70 min versus ca. 72 to 120 h for bacteria and fungi, respectively, using conventional plate counts), and mite contamination (ca. 70 min versus ca. 24 h). A full-factorial design was performed for optimization of the SPME experimental parameters. The methodology was applied to three types of rice (rough, brown, and white rice), oat, wheat, and green and roasted coffee beans. Simultaneously, microbiological analysis of the samples (total aerobic microorganisms, moulds, and yeasts) was performed by conventional plate counts. A set of 54 volatile markers was selected among all the compounds detected by GC×GC–ToFMS. Principal Component Analysis (PCA) was applied in order to establish a relationship between potential volatile markers and the level of microbial contamination. Methylbenzene, 3-octanone, 2-nonanone, 2-methyl-3-pentanol, 1-octen-3-ol, and 2-hexanone were associated to samples with higher microbial contamination level, especially in rough rice. Moreover, oat exhibited a high GC peak area of 2-hydroxy-6-methylbenzaldehyde, a sexual and alarm pheromone for adult mites, which in the other matrices appeared as a trace component. The number of mites detected in oat grains was correlated to the GC peak area of the pheromone. The HS-SPME/GC×GC–ToFMS methodology can be regarded as the basis for the development of a rapid and versatile method that can be applied in industry to the simultaneous assessment the level of microbiological contamination and for detection of mites in cereals grains and coffee beans. PMID:23613710

  15. Benzene solubility in water: A reassessment

    NASA Astrophysics Data System (ADS)

    Graziano, Giuseppe

    2006-09-01

    It is shown that the results of molecular dynamics simulations on the hydration thermodynamics of benzene at room temperature [Schravendijk and van der Vegt, J. Chem. Theory Comput. 1 (2005) 643] are in line with a former theoretical analysis [Graziano and Lee, J. Phys. Chem. B 105 (2001) 10367]. In fact: (a) the benzene-water van der Waals interaction energy proves to be larger in magnitude than the work of cavity creation and is able to account for the experimental finding that the hydration of benzene is a spontaneous process under the Ben-Naim standard conditions around room temperature; (b) the weak benzene-water H-bonds do not provide a significant contribution to benzene solubility in water because the favorable enthalpic component is almost entirely compensated for by an unfavorable entropic component. This enthalpy-entropy compensation occurs because the H-bonding potential of benzene is not strong.

  16. Density functional theory study of the interaction of vinyl radical, ethyne, and ethene with benzene, aimed to define an affordable computational level to investigate stability trends in large van der Waals complexes.

    PubMed

    Maranzana, Andrea; Giordana, Anna; Indarto, Antonius; Tonachini, Glauco; Barone, Vincenzo; Causà, Mauro; Pavone, Michele

    2013-12-28

    Our purpose is to identify a computational level sufficiently dependable and affordable to assess trends in the interaction of a variety of radical or closed shell unsaturated hydro-carbons A adsorbed on soot platelet models B. These systems, of environmental interest, would unavoidably have rather large sizes, thus prompting to explore in this paper the performances of relatively low-level computational methods and compare them with higher-level reference results. To this end, the interaction of three complexes between non-polar species, vinyl radical, ethyne, or ethene (A) with benzene (B) is studied, since these species, involved themselves in growth processes of polycyclic aromatic hydrocarbons (PAHs) and soot particles, are small enough to allow high-level reference calculations of the interaction energy ΔEAB. Counterpoise-corrected interaction energies ΔEAB are used at all stages. (1) Density Functional Theory (DFT) unconstrained optimizations of the A-B complexes are carried out, using the B3LYP-D, ωB97X-D, and M06-2X functionals, with six basis sets: 6-31G(d), 6-311 (2d,p), and 6-311++G(3df,3pd); aug-cc-pVDZ and aug-cc-pVTZ; N07T. (2) Then, unconstrained optimizations by Møller-Plesset second order Perturbation Theory (MP2), with each basis set, allow subsequent single point Coupled Cluster Singles Doubles and perturbative estimate of the Triples energy computations with the same basis sets [CCSD(T)//MP2]. (3) Based on an additivity assumption of (i) the estimated MP2 energy at the complete basis set limit [EMP2/CBS] and (ii) the higher-order correlation energy effects in passing from MP2 to CCSD(T) at the aug-cc-pVTZ basis set, ΔECC-MP, a CCSD(T)/CBS estimate is obtained and taken as a computational energy reference. At DFT, variations in ΔEAB with basis set are not large for the title molecules, and the three functionals perform rather satisfactorily even with rather small basis sets [6-31G(d) and N07T], exhibiting deviation from the computational

  17. Density functional theory study of the interaction of vinyl radical, ethyne, and ethene with benzene, aimed to define an affordable computational level to investigate stability trends in large van der Waals complexes

    SciTech Connect

    Maranzana, Andrea E-mail: anna.giordana@hotmail.com E-mail: mauro.causa@unina.it Giordana, Anna E-mail: anna.giordana@hotmail.com E-mail: mauro.causa@unina.it Indarto, Antonius Tonachini, Glauco; Barone, Vincenzo E-mail: anna.giordana@hotmail.com E-mail: mauro.causa@unina.it; Causà, Mauro E-mail: anna.giordana@hotmail.com E-mail: mauro.causa@unina.it; Pavone, Michele E-mail: anna.giordana@hotmail.com E-mail: mauro.causa@unina.it

    2013-12-28

    Our purpose is to identify a computational level sufficiently dependable and affordable to assess trends in the interaction of a variety of radical or closed shell unsaturated hydro-carbons A adsorbed on soot platelet models B. These systems, of environmental interest, would unavoidably have rather large sizes, thus prompting to explore in this paper the performances of relatively low-level computational methods and compare them with higher-level reference results. To this end, the interaction of three complexes between non-polar species, vinyl radical, ethyne, or ethene (A) with benzene (B) is studied, since these species, involved themselves in growth processes of polycyclic aromatic hydrocarbons (PAHs) and soot particles, are small enough to allow high-level reference calculations of the interaction energy ΔE{sub AB}. Counterpoise-corrected interaction energies ΔE{sub AB} are used at all stages. (1) Density Functional Theory (DFT) unconstrained optimizations of the A−B complexes are carried out, using the B3LYP-D, ωB97X-D, and M06-2X functionals, with six basis sets: 6-31G(d), 6-311 (2d,p), and 6-311++G(3df,3pd); aug-cc-pVDZ and aug-cc-pVTZ; N07T. (2) Then, unconstrained optimizations by Møller-Plesset second order Perturbation Theory (MP2), with each basis set, allow subsequent single point Coupled Cluster Singles Doubles and perturbative estimate of the Triples energy computations with the same basis sets [CCSD(T)//MP2]. (3) Based on an additivity assumption of (i) the estimated MP2 energy at the complete basis set limit [E{sub MP2/CBS}] and (ii) the higher-order correlation energy effects in passing from MP2 to CCSD(T) at the aug-cc-pVTZ basis set, ΔE{sub CC-MP}, a CCSD(T)/CBS estimate is obtained and taken as a computational energy reference. At DFT, variations in ΔE{sub AB} with basis set are not large for the title molecules, and the three functionals perform rather satisfactorily even with rather small basis sets [6-31G(d) and N07T], exhibiting

  18. Antioxidant Compounds in Traditional Indian Pickles May Prevent the Process-Induced Formation of Benzene.

    PubMed

    Kharat, Mahesh M; Adiani, Vanshika; Variyar, Prasad; Sharma, Arun; Singhal, Rekha S

    2016-01-01

    Pickles in the Indian market contain ascorbic acid from the raw material used and benzoate as an added preservative that are involved in the formation of benzene in soft drinks. In this work, 24 market pickle samples were surveyed for benzene content, as well as its precursors and other constituents that influence its formation. The analysis showed that pickle samples were high in acid content (low pH) and showed significant amount of ascorbic acid, minerals (Cu and Fe), and benzoic acid present in them. Also, most samples exhibited high antioxidant activity that might be attributed to the ingredients used, such as fruits and spices. The solid-phase microextraction headspace gas chromatography-mass spectrometry method was developed in-house for benzene analysis. Eleven of 24 samples had benzene, with the highest concentration of 4.36 ± 0.82 μg of benzene per kg of pickle for a lime pickle that was also reported to have highest benzoic acid and considerably less hydroxyl radical ((•)OH) scavenging activity. However, benzene levels for all 11 samples were considerably below the World Health Organization regulatory limit of 10 μg/kg for benzene in mineral water. Studies on model systems revealed that the high antioxidant activity of Indian pickles may have had a strong inhibitory effect on benzene formation.

  19. The effects of sex, age and commensal way of life on levels of fecal glucocorticoid metabolites in spiny mice (Acomys cahirinus).

    PubMed

    Nováková, M; Palme, R; Kutalová, H; Janský, L; Frynta, D

    2008-09-03

    We studied levels of fecal glucocorticoid metabolites (GCM) in a social rodent - Egyptian spiny mouse. As breeding adults are socially dominant over subadults, and adolescent males are driven away by the dominant males, we addressed the question whether animals within extended families are stressed differently depending upon their social category. In addition, we evaluated whether there are differences between non-commensal (outdoor) and commensal (adapted to human settlements) populations. Concentrations of fecal GCM were assessed from samples collected in a special cage that allowed continuous individual sampling of undisturbed mice housed as a semi-natural social unit. First we performed an ACTH challenge test to validate two enzyme immunoassays (EIA): a 5alpha-pregnane-3beta,11beta,21-triol-20-one EIA and an 11-oxoetiocholanolone EIA to measure a group of fecal GCM in this species. Next we monitored concentrations of fecal GCM in 68 individuals belonging to 10 family groups and two populations. Commensal spiny mice showed higher fecal GCM levels than non-commensal ones. No effect of age (i.e., social dominance) and only a small effect of sex (in the commensal population only, with males exhibiting lower values) on fecal GCM levels were found. On the other hand, considerable variations in measured fecal GCM between family groups were revealed, indicating that the social settings of the particular group play an important role.

  20. Impact of Increasing Dietary Calcium Levels on Calcium Excretion and Vitamin D Metabolites in the Blood of Healthy Adult Cats

    PubMed Central

    Paßlack, Nadine; Schmiedchen, Bettina; Raila, Jens; Schweigert, Florian J.; Stumpff, Friederike; Kohn, Barbara; Neumann, Konrad; Zentek, Jürgen

    2016-01-01

    Background Dietary calcium (Ca) concentrations might affect regulatory pathways within the Ca and vitamin D metabolism and consequently excretory mechanisms. Considering large variations in Ca concentrations of feline diets, the physiological impact on Ca homeostasis has not been evaluated to date. In the present study, diets with increasing concentrations of dicalcium phosphate were offered to ten healthy adult cats (Ca/phosphorus (P): 6.23/6.02, 7.77/7.56, 15.0/12.7, 19.0/17.3, 22.2/19.9, 24.3/21.6 g/kg dry matter). Each feeding period was divided into a 10-day adaptation and an 8-day sampling period in order to collect urine and faeces. On the last day of each feeding period, blood samples were taken. Results Urinary Ca concentrations remained unaffected, but faecal Ca concentrations increased (P < 0.001) with increasing dietary Ca levels. No effect on whole and intact parathyroid hormone levels, fibroblast growth factor 23 and calcitriol concentrations in the blood of the cats were observed. However, the calcitriol precursors 25(OH)D2 and 25(OH)D3, which are considered the most useful indicators for the vitamin D status, decreased with higher dietary Ca levels (P = 0.013 and P = 0.033). Increasing dietary levels of dicalcium phosphate revealed an acidifying effect on urinary fasting pH (6.02) and postprandial pH (6.01) (P < 0.001), possibly mediated by an increase of urinary phosphorus (P) concentrations (P < 0.001). Conclusions In conclusion, calcitriol precursors were linearly affected by increasing dietary Ca concentrations. The increase in faecal Ca excretion indicates that Ca homeostasis of cats is mainly regulated in the intestine and not by the kidneys. Long-term studies should investigate the physiological relevance of the acidifying effect observed when feeding diets high in Ca and P. PMID:26870965

  1. Macromolecular and elemental composition analysis and extracellular metabolite balances of Pichia pastoris growing at different oxygen levels

    PubMed Central

    2009-01-01

    Background Analysis of the cell operation at the metabolic level requires collecting data of different types and to determine their confidence level. In addition, the acquired information has to be combined in order to obtain a consistent operational view. In the case of Pichia pastoris, information of its biomass composition at macromolecular and elemental level is scarce particularly when different environmental conditions, such as oxygen availability or, genetic backgrounds (e.g. recombinant protein production vs. non production conditions) are compared. Results P. pastoris cells growing in carbon-limited chemostat cultures under different oxygenation conditions (% O2 in the bioreactor inlet gas: 21%, 11% and 8%, corresponding to normoxic, oxygen-limiting and hypoxic conditions, respectively), as well as under recombinant protein (antibody fragment, Fab) producing and non-producing conditions, were analyzed from different points of view. On the one hand, the macromolecular and elemental composition of the biomass was measured using different techniques at the different experimental conditions and proper reconciliation techniques were applied for gross error detection of the measured substrates and products conversion rates. On the other hand, fermentation data was analyzed applying elemental mass balances. This allowed detecting a previously missed by-product secreted under hypoxic conditions, identified as arabinitol (aka. arabitol). After identification of this C5 sugar alcohol as a fermentation by-product, the mass balances of the fermentation experiments were validated. Conclusions After application of a range of analytical and statistical techniques, a consistent view of growth parameters and compositional data of P. pastoris cells growing under different oxygenation conditions was obtained. The obtained data provides a first view of the effects of oxygen limitation on the physiology of this microorganism, while recombinant Fab production seems to have

  2. Effect of nitrogen narcosis on extracellular levels of dopamine and its metabolites in the rat striatum, using intracerebral microdialysis.

    PubMed

    Barthelemy-Requin, M; Semelin, P; Risso, J J

    1994-12-19

    In man, nitrogen narcosis is characterized by euphoria, impaired cognitive function, neuromuscular incoordination and, ultimately, loss of consciousness. Because of the motor movement disorders, we chose to study the nigrostriatal system, whose major function is to regulate the extrapyramidal nervous system. The purpose of this investigation was to monitor changes in extracellular levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum of conscious rats, using intracerebral microdialysis. Results show a 40% decrease in extracellular DA concentration, a 59% increase in extracellular DOPAC and an increase in HVA starting with exposure to the nitrogen mixture. Thirty minutes after the beginning of the exposure, a compensation phase took place. HVA returns to its initial basal value, and levels of DOPAC and DA returned towards normal but never reached their initial values. These results contrast with those observed during the High Pressure Neurological Syndrome (HPNS, 5.1 MPa of helium pressure) in which there is a significant increase in extracellular DA. Therefore, some of the symptoms of nitrogen narcosis may be linked with the decrease in the extracellular DA levels.

  3. Production of Phenol from Benzene via Cumene

    ERIC Educational Resources Information Center

    Daniels, D. J.; And Others

    1976-01-01

    Describes an undergraduate chemistry laboratory experiment involving the production of phenol from benzene with the intermediate production of isopropylbenzene and isopropylbenzene hydroperoxide. (SL)

  4. Detailed mechanism of benzene oxidation

    NASA Technical Reports Server (NTRS)

    Bittker, David A.

    1987-01-01

    A detailed quantitative mechanism for the oxidation of benzene in both argon and nitrogen diluted systems is presented. Computed ignition delay time for argon diluted mixtures are in satisfactory agreement with experimental results for a wide range of initial conditions. An experimental temperature versus time profile for a nitrogen diluted oxidation was accurately matched and several concentration profiles were matched qualitatively. Application of sensitivity analysis has given approximate rate constant expressions for the two dominant heat release reactions, the oxidation of C6H5 and C5H5 radicals by molecular oxygen.

  5. Volatile Metabolites

    PubMed Central

    Rowan, Daryl D.

    2011-01-01

    Volatile organic compounds (volatiles) comprise a chemically diverse class of low molecular weight organic compounds having an appreciable vapor pressure under ambient conditions. Volatiles produced by plants attract pollinators and seed dispersers, and provide defense against pests and pathogens. For insects, volatiles may act as pheromones directing social behavior or as cues for finding hosts or prey. For humans, volatiles are important as flavorants and as possible disease biomarkers. The marine environment is also a major source of halogenated and sulfur-containing volatiles which participate in the global cycling of these elements. While volatile analysis commonly measures a rather restricted set of analytes, the diverse and extreme physical properties of volatiles provide unique analytical challenges. Volatiles constitute only a small proportion of the total number of metabolites produced by living organisms, however, because of their roles as signaling molecules (semiochemicals) both within and between organisms, accurately measuring and determining the roles of these compounds is crucial to an integrated understanding of living systems. This review summarizes recent developments in volatile research from a metabolomics perspective with a focus on the role of recent technical innovation in developing new areas of volatile research and expanding the range of ecological interactions which may be mediated by volatile organic metabolites. PMID:24957243

  6. Serum level of reactive oxygen metabolites (ROM) at 12 weeks of treatment with biologic agents for rheumatoid arthritis is a novel predictor for 52-week remission.

    PubMed

    Nakajima, Arata; Aoki, Yasuchika; Sonobe, Masato; Takahashi, Hiroshi; Saito, Masahiko; Nakagawa, Koichi

    2017-02-01

    We have shown that serum levels of reactive oxygen metabolites (ROM) were associated with C-reactive protein (CRP) and disease activity score based on the examination of 28 joints (DAS28) in patients with rheumatoid arthritis (RA); however, their clinical significance as biomarkers has not been elucidated. Forty-eight biologic agent (BA)-naïve RA patients were included in this study. Associations between serum levels of ROM, CRP, matrix metalloproteinase-3 (MMP-3), DAS28-erythrocyte sedimentation rate (ESR), and Health Assessment Questionnaire (HAQ) at 12 weeks of treatment and DAS28 (ESR) remission at 52 weeks (52-week remission) were investigated. The ROM serum level at baseline in the remission group (n = 34) was 527 ± 132 Carratelli units (U.Carr) (normal range <300), decreased to 335 ± 79.1 at 4 weeks, and remained low thereafter. In the non-remission group (n = 14), the ROM serum level at baseline was 592 ± 113 U.Carr, decreased to 450 ± 152 at 4 weeks, but gradually increased thereafter. Among significantly different factors at 12 weeks between the remission and non-remission groups, ROM and DAS28 (ESR) were identified as predictors of 52-week remission (p = 0.045, odds ratio 0.985, 95% confidence interval 0.97-1.000 for ROM). The cutoff value of ROM was determined to be 381.5 U.Carr (sensitivity 0.833, specificity 0.871). These results show that serum ROM levels can predict remission with high accuracy and could be a useful biomarker for achieving remission in the current treat-to-target strategy for RA.

  7. Chronic psychosocial stress in mice leads to changes in brain functional connectivity and metabolite levels comparable to human depression.

    PubMed

    Grandjean, Joanes; Azzinnari, Damiano; Seuwen, Aline; Sigrist, Hannes; Seifritz, Erich; Pryce, Christopher R; Rudin, Markus

    2016-11-15

    Human depression, for which chronic psychosocial stress is a major risk factor, is characterized by consistent alterations in neurocircuitry. For example, there is increased functional connectivity (FC) within and between regions comprising the default mode network (DMN) including prefrontal cortex and cingulate cortex. Alterations in network FC are associated with specific aspects of psychopathology. In mice, chronic psychosocial stress (CPS) leads to depression-relevant behavior, including increased fear learning, learned helplessness, fatigue and decreased motivation for reward. Using multimodal in vivo magnetic resonance imaging (MRI) and spectroscopy (MRS), we investigated CPS effects on function and structure in the mouse brain under light anesthesia. Mice underwent a baseline MRI/MRS session, followed by 15-day CPS (n=26) or control handling (n=27), and a post-treatment MRI/MRS session. In BOLD fMRI, relative to controls, CPS mice exhibited robust, reproducible increases in FC within 8 of 9 identified cortical networks, including the prefrontal and cingulate cortices that contribute to the "mouse DMN". CPS mice exhibited increases in between-network FC, including amygdala - prefrontal cortex and amygdala - cingulate cortex. MRS identified metabolic alterations in CPS mice as increased inositol levels in amygdala and increased glycerophosphorylcholine levels in prefrontal cortex. Diffusion-weighted MRI detected increased fractional anisotropic values in the cingulum. This study demonstrates that chronic psychosocial stress induces FC states in the mouse brain analogous to those observed in depression, as well as cerebral metabolism and white matter pathway alterations that contribute to understanding of pathological processes. It also demonstrates the importance of brain imaging to the establishment of valid animal models in translational psychiatry.

  8. Leukemia-related chromosomal loss detected in hematopoietic progenitor cells of benzene-exposed workers

    PubMed Central

    Zhang, Luoping; Lan, Qing; Ji, Zhiying; Li, Guilan; Shen, Min; Vermeulen, Roel; Guo, Weihong; Hubbard, Alan E.; McHale, Cliona M.; Rappaport, Stephen M.; Hayes, Richard B.; Linet, Martha S.; Yin, Songnian; Smith, Martyn T.; Rothman, Nathaniel

    2012-01-01

    Benzene exposure causes acute myeloid leukemia, and hematotoxicity, shown as suppression of mature blood and myeloid progenitor cell numbers. As the leukemia-related aneuploidies monosomy 7 and trisomy 8 previously had been detected in the mature peripheral blood cells of exposed workers, we hypothesized that benzene could cause leukemia through the induction of these aneuploidies in hematopoietic stem and progenitor cells. We measured loss and gain of chromosomes 7 and 8 by fluorescence in situ hybridization in interphase colony-forming unit-granulocyte-macrophage (CFU-GM) cells cultured from otherwise healthy benzene-exposed (n=28) and unexposed (n=14) workers. CFU-GM monosomy 7 and 8 levels (but not trisomy) were significantly increased in subjects exposed to benzene overall, compared to levels in the control subjects (p=0.0055 and p=0.0034, respectively). Levels of monosomy 7 and 8 were significantly increased in subjects exposed to <10 ppm (20%, p=0.0419 and 28%, p=0.0056, respectively) and ≥10 ppm (48%, p=0.0045 and 32%, p=0.0354) benzene, compared with controls, and significant exposure-response trends were detected (ptrend=0.0033 and 0.0057). These data show that monosomies 7 and 8 are produced in a dose-dependent fashion in the blood progenitor cells of workers exposed to benzene and may be mechanistically relevant biomarkers of early effect for benzene and other leukemogens. PMID:22643707

  9. Attenuation of Thrombosis by Crude Rice (Oryza sativa) Bran Policosanol Extract: Ex Vivo Platelet Aggregation and Serum Levels of Arachidonic Acid Metabolites

    PubMed Central

    Ismail, Maznah; Tohit, Eusni Rahayu Mohd; Abdullah, Rasedee; Zhang, Yi-Da

    2016-01-01

    Background. Vascular occlusion or thrombosis was often attributed to uncontrolled platelet activation. Influence of sugarcane policosanol extract on platelet was reported but little was known of rice bran policosanol, particularly its mechanisms of actions on platelet activities. Objective. Antiplatelet mechanisms of rice bran policosanol extract (RBE) were studied using hyperlipidemic Sprague Dawley rats. Ex vivo platelet aggregation, platelet count (PC), bleeding time (BT), and coagulation time were assayed. Serum eicosanoids and other aggregation-related metabolites levels were quantified. Design. Rats were divided into 6 groups for comparisons (vehicle control Tween 20/H2O, high dose policosanol 500 mg/kg, middle dose policosanol 250 mg/kg, low dose policosanol 100 mg/kg, and positive control aspirin 30 mg/kg). Results. Low dose 100 mg/kg of RBE inhibited aggregation by 42.32 ± 4.31% and this was comparable with the effect of 30 mg/kg aspirin, 43.91 ± 5.27%. Results showed that there were no significant differences in PC, BT, and coagulation time among various groups after RBE treatment. Serum thromboxane A2 was attenuated while prostacyclin level increased upon RBE treatment. Conclusions. RBE reduced ex vivo ADP-induced platelet aggregation without giving adverse effects. No changes in full blood count suggested that rice bran policosanol did not disturb biological blood cell production and destruction yet it reduced aggregation through different mechanisms. PMID:27800004

  10. Effects of mannan level and β-mannanase supplementation on growth performance, apparent total tract digestibility and blood metabolites of growing pigs.

    PubMed

    Kim, J S; Ingale, S L; Hosseindoust, A R; Lee, S H; Lee, J H; Chae, B J

    2017-02-01

    The exogenous enzymes are less consistent in their effects as their beneficial effects depend upon the types and level non-starch polysaccharides (NSP) present in the diets. Therefore, exogenous enzymes should be selected on the basis of types and amount of the NSP in the pig diets. The objectives of the present experiments were to investigate the effects of dietary level of mannan and β-mannanase supplementation on growth performance, apparent total tract digestibility (ATTD) of energy and nutrients, and blood metabolites of growing pigs. In Exp. 1, 96 barrows were randomly allotted to four treatments on the basis of BW. There were four replicates in each treatment with six pigs per replicate. The dietary treatments were a corn-soybean meal (SBM)-based control diet and three other diets consisted of the control diet supplemented with 400, 800 or 1600 U of β-mannanase/kg diet. The final BW, average daily gain (ADG) and blood glucose increased (linear, P0.05) on the concentrations of blood total cholesterol, triacylglycerides and blood urea nitrogen. These results indicate that supplementation of β-mannanase to low- or high-mannan diets have potential to improve the performance of growing pigs. In addition, palm kernel meal may partially replace corn and SBM without reducing pig performance if β-mannanase is added to diet.

  11. Patterns of Behaviour, Group Structure and Reproductive Status Predict Levels of Glucocorticoid Metabolites in Zoo-Housed Ring-Tailed Lemurs, Lemur catta.

    PubMed

    Smith, Tessa E; McCusker, Cara M; Stevens, Jeroen M G; Elwood, Robert W

    2015-01-01

    In ring-tailed lemurs, Lemur catta, the factors modulating hypothalamic-pituitary-adrenal (HPA) activity differ between wild and semi-free-ranging populations. Here we assess factors modulating HPA activity in ring-tailed lemurs housed in a third environment: the zoo. First we validate an enzyme immunoassay to quantify levels of glucocorticoid (GC) metabolites in the faeces of L. catta. We determine the nature of the female-female dominance hierarchies within each group by computing David's scores and examining these in relation to faecal GC (fGC). Relationships between female age and fGC are assessed to evaluate potential age-related confounds. The associations between fGC, numbers of males in a group and reproductive status are explored. Finally, we investigate the value of 7 behaviours in predicting levels of fGC. The study revealed stable linear dominance hierarchies in females within each group. The number of males in a social group together with reproductive status, but not age, influenced fGC. The 7 behavioural variables accounted for 68% of the variance in fGC. The amounts of time an animal spent locomoting and in the inside enclosure were both negative predictors of fGC. The study highlights the flexibility and adaptability of the HPA system in ring-tailed lemurs.

  12. Anaerobic benzene oxidation by Geobacter species.

    PubMed

    Zhang, Tian; Bain, Timothy S; Nevin, Kelly P; Barlett, Melissa A; Lovley, Derek R

    2012-12-01

    The abundance of Geobacter species in contaminated aquifers in which benzene is anaerobically degraded has led to the suggestion that some Geobacter species might be capable of anaerobic benzene degradation, but this has never been documented. A strain of Geobacter, designated strain Ben, was isolated from sediments from the Fe(III)-reducing zone of a petroleum-contaminated aquifer in which there was significant capacity for anaerobic benzene oxidation. Strain Ben grew in a medium with benzene as the sole electron donor and Fe(III) oxide as the sole electron acceptor. Furthermore, additional evaluation of Geobacter metallireducens demonstrated that it could also grow in benzene-Fe(III) medium. In both strain Ben and G. metallireducens the stoichiometry of benzene metabolism and Fe(III) reduction was consistent with the oxidation of benzene to carbon dioxide with Fe(III) serving as the sole electron acceptor. With benzene as the electron donor, and Fe(III) oxide (strain Ben) or Fe(III) citrate (G. metallireducens) as the electron acceptor, the cell yields of strain Ben and G. metallireducens were 3.2 × 10(9) and 8.4 × 10(9) cells/mmol of Fe(III) reduced, respectively. Strain Ben also oxidized benzene with anthraquinone-2,6-disulfonate (AQDS) as the sole electron acceptor with cell yields of 5.9 × 10(9) cells/mmol of AQDS reduced. Strain Ben serves as model organism for the study of anaerobic benzene metabolism in petroleum-contaminated aquifers, and G. metallireducens is the first anaerobic benzene-degrading organism that can be genetically manipulated.

  13. Resonant photodissociation in substituted benzenes

    NASA Astrophysics Data System (ADS)

    Scarborough, Tim; McAcy, Collin; Foote, David; Uiterwaal, Cornelis

    2011-05-01

    Cyclic aromatic molecules are abundant in organic chemistry, with a wide variety of applications, including pharmacology, pollution studies and genetic research. Among the simplest of these molecules is benzene (C6H6) , with many relevant molecules being benzene-like with a single atomic substitution. In such a substitution, the substituent determines a characteristic perturbation of the electronic structure of the molecule. We discuss the substitution of halogens into the ring (C6H5X), and its effects on the dynamics of ionization and dissociation of the molecule without the focal volume effect. In particular, using 800-nm, 50-fs laser pulses, we present results in the dissociation of fluorobenzene, chlorobenzene, bromobenzene and iodobenzene into the phenyl ring (C6H5) and the atomic halogen, and the subsequent ionization of these fragments. The impact of the ``heavy atom effect'' on a 1 (π , π*) -->3 (n , σ*) singlet-triplet intersystem crossing will be emphasized. Currently under investigation is whether such a dissociation can be treated as an effective source of the neutral substituent. This material is based upon work supported by the National Science Foundation under Grant No. PHY-0355235.

  14. Major sources of benzene exposure.

    PubMed Central

    Wallace, L A

    1989-01-01

    Data from EPA's TEAM Study allow us to identify the major sources of exposure to benzene for much of the U.S. population. These sources turn out to be quite different from what had previously been considered the important sources. The most important source of exposure for 50 million smokers is the mainstream smoke from their cigarettes, which accounts for about half of the total population burden of exposure to benzene. Another 20% of nationwide exposure is contributed by various personal activities, such as driving and using attached garages. (Emissions from consumer products, building materials, paints, and adhesives may also be important, although data are largely lacking.) The traditional sources of atmospheric emissions (auto exhaust and industrial emissions) account for only about 20% of total exposure. Environmental tobacco smoke is an important source, accounting for about 5% of total nationwide exposure. A number of sources sometimes considered important, such as petroleum refining operations, petrochemical manufacturing, oil storage tanks, urban-industrial areas, service stations, certain foods, groundwater contamination, and underground gasoline leaks, appear to be unimportant on a nationwide basis. PMID:2477239

  15. Population sequencing of two endocannabinoid metabolic genes identifies rare and common regulatory variants associated with extreme obesity and metabolite level

    PubMed Central

    2010-01-01

    Background Targeted re-sequencing of candidate genes in individuals at the extremes of a quantitative phenotype distribution is a method of choice to gain information on the contribution of rare variants to disease susceptibility. The endocannabinoid system mediates signaling in the brain and peripheral tissues involved in the regulation of energy balance, is highly active in obese patients, and represents a strong candidate pathway to examine for genetic association with body mass index (BMI). Results We sequenced two intervals (covering 188 kb) encoding the endocannabinoid metabolic enzymes fatty-acid amide hydrolase (FAAH) and monoglyceride lipase (MGLL) in 147 normal controls and 142 extremely obese cases. After applying quality filters, we called 1,393 high quality single nucleotide variants, 55% of which are rare, and 143 indels. Using single marker tests and collapsed marker tests, we identified four intervals associated with BMI: the FAAH promoter, the MGLL promoter, MGLL intron 2, and MGLL intron 3. Two of these intervals are composed of rare variants and the majority of the associated variants are located in promoter sequences or in predicted transcriptional enhancers, suggesting a regulatory role. The set of rare variants in the FAAH promoter associated with BMI is also associated with increased level of FAAH substrate anandamide, further implicating a functional role in obesity. Conclusions Our study, which is one of the first reports of a sequence-based association study using next-generation sequencing of candidate genes, provides insights into study design and analysis approaches and demonstrates the importance of examining regulatory elements rather than exclusively focusing on exon sequences. PMID:21118518

  16. Small scale spatial gradients of outdoor and indoor benzene in proximity of an integrated steel plant.

    PubMed

    Licen, Sabina; Tolloi, Arianna; Briguglio, Sara; Piazzalunga, Andrea; Adami, Gianpiero; Barbieri, Pierluigi

    2016-05-15

    Benzene is known as a human carcinogen, whose annual mean concentration exceeded the EU limit value (5 μg/m(3)) only in very few locations in Europe during 2012. Nevertheless 10% to 12% of the EU-28 urban population was still exposed to benzene concentrations above the WHO reference level of 1.7 μg/m(3). WHO recommended a wise choice of monitoring stations positioning in proximity of "hot spots" to define and assess the representativeness of each site paying attention to micro-scale conditions. In this context benzene and other VOCs of health concern (toluene, ethylbenzene, xylenes) concentrations have been investigated, with weekly passive sampling for one year, both in outdoor and indoor air in inhabited buildings in close proximity (180 m far up to 1100 m) of an integrated steel plant in NE of Italy. Even though the outdoor mean annual benzene concentration was below the EU limit in every site, in the site closest to the works the benzene concentration was above 5 μg/m(3) in 14 weeks. These events were related to a benzene over toluene ratio above one, which is diagnostic for the presence of an industrial source, and to meteorological factors. These information pointed at the identification of the coke ovens of the plant as the dominant outdoor source of benzene. Benzene gradients with the increasing distance from coke ovens have been found for both outdoor and indoor air. Linear models linking outdoor to indoor benzene concentrations have been then identified, allowing to estimate indoor exposure from ambient air benzene data. In the considered period, a narrow area of about 250 m appeared impacted at a higher degree than the other sites both considering outdoor and indoor air. Passive BTEX sampling permits to collect information on both ambient air and daily life settings, allowing to assemble a valuable data support for further environmental cost-benefit analyses.

  17. Integrated Analysis of Metabolite and Transcript Levels Reveals the Metabolic Shifts That Underlie Tomato Fruit Development and Highlight Regulatory Aspects of Metabolic Network Behavior1[W

    PubMed Central

    Carrari, Fernando; Baxter, Charles; Usadel, Björn; Urbanczyk-Wochniak, Ewa; Zanor, Maria-Ines; Nunes-Nesi, Adriano; Nikiforova, Victoria; Centero, Danilo; Ratzka, Antje; Pauly, Markus; Sweetlove, Lee J.; Fernie, Alisdair R.

    2006-01-01

    Tomato (Solanum lycopersicum) is a well-studied model of fleshy fruit development and ripening. Tomato fruit development is well understood from a hormonal-regulatory perspective, and developmental changes in pigment and cell wall metabolism are also well characterized. However, more general aspects of metabolic change during fruit development have not been studied despite the importance of metabolism in the context of final composition of the ripe fruit. In this study, we quantified the abundance of a broad range of metabolites by gas chromatography-mass spectrometry, analyzed a number of the principal metabolic fluxes, and in parallel analyzed transcriptomic changes during tomato fruit development. Metabolic profiling revealed pronounced shifts in the abundance of metabolites of both primary and secondary metabolism during development. The metabolite changes were reflected in the flux analysis that revealed a general decrease in metabolic activity during ripening. However, there were several distinct patterns of metabolite profile, and statistical analysis demonstrated that metabolites in the same (or closely related) pathways changed in abundance in a coordinated manner, indicating a tight regulation of metabolic activity. The metabolite data alone allowed investigations of likely routes through the metabolic network, and, as an example, we analyze the operational feasibility of different pathways of ascorbate synthesis. When combined with the transcriptomic data, several aspects of the regulation of metabolism during fruit ripening were revealed. First, it was apparent that transcript abundance was less strictly coordinated by functional group than metabolite abundance, suggesting that posttranslational mechanisms dominate metabolic regulation. Nevertheless, there were some correlations between specific transcripts and metabolites, and several novel associations were identified that could provide potential targets for manipulation of fruit compositional traits

  18. Infants' indoor and outdoor residential exposure to benzene and respiratory health in a Spanish cohort.

    PubMed

    Ferrero, Amparo; Esplugues, Ana; Estarlich, Marisa; Llop, Sabrina; Cases, Amparo; Mantilla, Enrique; Ballester, Ferran; Iñiguez, Carmen

    2017-03-01

    Benzene exposure represents a potential risk for children's health. Apart from being a known carcinogen for humans (group 1 according to IARC), there is scientific evidence suggesting a relationship between benzene exposure and respiratory problems in children. But results are still inconclusive and inconsistent. This study aims to assess the determinants of exposure to indoor and outdoor residential benzene levels and its relationship with respiratory health in infants. Participants were 1-year-old infants (N = 352) from the INMA cohort from Valencia (Spain). Residential benzene exposure levels were measured inside and outside dwellings by means of passive samplers in a 15-day campaign. Persistent cough, low respiratory tract infections and wheezing during the first year of life, and covariates (dwelling traits, lifestyle factors and sociodemographic data) were obtained from parental questionnaires. Multiple Tobit regression and logistic regression models were performed to assess factors associated to residential exposure levels and health associations, respectively. Indoor levels were higher than outdoor ones (1.46 and 0.77 μg/m(3), respectively; p < 0.01). A considerable percentage of dwellings, 42% and 21% indoors and outdoors respectively, surpassed the WHO guideline of 1.7 μg/m(3) derived from a lifetime risk of leukemia above 1/100 000. Monitoring season, maternal country of birth and parental tobacco consumption were associated with residential benzene exposure (indoor and outdoors). Additionally, indoor levels were associated with mother's age and type of heating, and outdoor levels were linked with zone of residence and distance from industrial areas. After adjustment for confounding factors, no significant associations were found between residential benzene exposure levels and respiratory health in infants. Hence, our study did not support the hypothesis for the benzene exposure effect on respiratory health in children. Even so, it highlights a

  19. Aromatic pi-pi interaction mediated by a metal atom: structure and ionization of the bis(eta(6)-benzene)chromium-benzene cluster.

    PubMed

    Han, Songhee; Singh, N Jiten; Kang, Tae Yeon; Choi, Kyo-Won; Choi, Sunyoung; Baek, Sun Jong; Kim, Kwang S; Kim, Sang Kyu

    2010-07-21

    Aromatic pi-pi interaction in the presence of a metal atom has been investigated experimentally and theoretically with the model system of bis(eta(6)-benzene)chromium-benzene cluster (Cr(Bz)(2)-Bz) in which a free solvating benzene is non-covalently attached to the benzene moiety of Cr(Bz)(2). One-photon mass-analyzed threshold ionization (MATI) spectroscopy and first principles calculations are employed to identify the structure of Cr(Bz)(2)-Bz which adopts the parallel-displaced configuration. The decrease in ionization potential for Cr(Bz)(2)-Bz compared with Cr(Bz)(2), resulting from the increase of the cation-pi stabilization energy upon ionization, is consistent with the parallel-displaced structure of the cluster. Theoretical calculations give the detailed cluster structures with associated energetics, thus revealing the nature of pi-pi-metal or pi-pi-cation interactions at the molecular level.

  20. 46 CFR 30.25-3 - Benzene.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 1 2014-10-01 2014-10-01 false Benzene. 30.25-3 Section 30.25-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Commodities Regulated § 30.25-3 Benzene. The provisions contained in 46 CFR part 197, subpart C, apply to liquid cargoes containing 0.5% or more...

  1. 29 CFR 1915.1028 - Benzene.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 7 2012-07-01 2012-07-01 false Benzene. 1915.1028 Section 1915.1028 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED... Benzene. Note: The requirements applicable to shipyard employment under this section are identical...

  2. 46 CFR 151.50-60 - Benzene.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Benzene. 151.50-60 Section 151.50-60 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-60 Benzene. The person in charge of...

  3. 46 CFR 30.25-3 - Benzene.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 1 2013-10-01 2013-10-01 false Benzene. 30.25-3 Section 30.25-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Commodities Regulated § 30.25-3 Benzene. The provisions contained in 46 CFR part 197, subpart C, apply to liquid cargoes containing 0.5% or more...

  4. 29 CFR 1915.1028 - Benzene.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Benzene. 1915.1028 Section 1915.1028 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED... Benzene. Note: The requirements applicable to shipyard employment under this section are identical...

  5. 29 CFR 1926.1128 - Benzene.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 8 2010-07-01 2010-07-01 false Benzene. 1926.1128 Section 1926.1128 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Toxic and Hazardous Substances § 1926.1128 Benzene....

  6. 29 CFR 1926.1128 - Benzene.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 8 2014-07-01 2014-07-01 false Benzene. 1926.1128 Section 1926.1128 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Toxic and Hazardous Substances § 1926.1128 Benzene....

  7. 46 CFR 30.25-3 - Benzene.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Benzene. 30.25-3 Section 30.25-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Commodities Regulated § 30.25-3 Benzene. The provisions contained in 46 CFR part 197, subpart C, apply to liquid cargoes containing 0.5% or more...

  8. 46 CFR 151.50-60 - Benzene.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Benzene. 151.50-60 Section 151.50-60 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-60 Benzene. The person in charge of...

  9. 29 CFR 1926.1128 - Benzene.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 8 2011-07-01 2011-07-01 false Benzene. 1926.1128 Section 1926.1128 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Toxic and Hazardous Substances § 1926.1128 Benzene....

  10. 46 CFR 30.25-3 - Benzene.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Benzene. 30.25-3 Section 30.25-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Commodities Regulated § 30.25-3 Benzene. The provisions contained in 46 CFR part 197, subpart C, apply to liquid cargoes containing 0.5% or more...

  11. 29 CFR 1926.1128 - Benzene.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 8 2012-07-01 2012-07-01 false Benzene. 1926.1128 Section 1926.1128 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Toxic and Hazardous Substances § 1926.1128 Benzene....

  12. 29 CFR 1915.1028 - Benzene.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 7 2014-07-01 2014-07-01 false Benzene. 1915.1028 Section 1915.1028 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED... Benzene. Note: The requirements applicable to shipyard employment under this section are identical...

  13. 29 CFR 1926.1128 - Benzene.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 8 2013-07-01 2013-07-01 false Benzene. 1926.1128 Section 1926.1128 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Toxic and Hazardous Substances § 1926.1128 Benzene....

  14. 46 CFR 151.50-60 - Benzene.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Benzene. 151.50-60 Section 151.50-60 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-60 Benzene. The person in charge of...

  15. 46 CFR 30.25-3 - Benzene.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 1 2012-10-01 2012-10-01 false Benzene. 30.25-3 Section 30.25-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Commodities Regulated § 30.25-3 Benzene. The provisions contained in 46 CFR part 197, subpart C, apply to liquid cargoes containing 0.5% or more...

  16. 29 CFR 1915.1028 - Benzene.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 7 2013-07-01 2013-07-01 false Benzene. 1915.1028 Section 1915.1028 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED... Benzene. Note: The requirements applicable to shipyard employment under this section are identical...

  17. 46 CFR 151.50-60 - Benzene.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Benzene. 151.50-60 Section 151.50-60 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-60 Benzene. The person in charge of...

  18. 46 CFR 151.50-60 - Benzene.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Benzene. 151.50-60 Section 151.50-60 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-60 Benzene. The person in charge of...

  19. 29 CFR 1915.1028 - Benzene.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 7 2011-07-01 2011-07-01 false Benzene. 1915.1028 Section 1915.1028 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED... Benzene. Note: The requirements applicable to shipyard employment under this section are identical...

  20. Hematological effect of benzene exposure with emphasis of muconic acid as a biomarker.

    PubMed

    Ibrahim, Khadiga S; Amer, Nagat M; El-dossuky, Elsaid A; Emara, Ahmed M; El-Fattah, Abd El-Samei M Abd; Shahy, Eman Mohamed

    2014-06-01

    Human exposure to benzene in work environment is a global occupational health problem. It is established that benzene requires to be metabolized to induce its effects. Benzene has been associated with various hematotoxins and carcinogens. The aim of this study was to investigate the effect of benzene on complete blood picture, with emphasis of trans, trans-muconic acid (t,t-MA) as a biomarker of benzene in urine, considering the influence of cigarette smoke. A total of 81 workers (61 males and 20 females) have been occupationally exposed to benzene. In addition, 83 workers (55males and 28 females) were also recruited as a control group. Complete blood picture was analyzed and urinary t,t-MA was determined by liquid chromatography. In addition, creatinine in the urine samples was determined. Levels of blood elements (white blood cells, red blood cells and platelets) were decreased among exposed workers compared with the controls. The urinary level of t,t-MA/creatinine of the exposed workers was elevated especially in the smoking group compared to the controls. This study recommends that complete blood picture and t,t-MA are helpful biomarker tests that should be done to detect the early effects of benzene exposure.

  1. The use of biomonitoring data in exposure and human health risk assessment: benzene case study

    PubMed Central

    Angerer, Juergen; Boogaard, Peter J.; Hughes, Michael F.; O’Lone, Raegan B.; Robison, Steven H.; Robert Schnatter, A.

    2013-01-01

    A framework of “Common Criteria” (i.e. a series of questions) has been developed to inform the use and evaluation of biomonitoring data in the context of human exposure and risk assessment. The data-rich chemical benzene was selected for use in a case study to assess whether refinement of the Common Criteria framework was necessary, and to gain additional perspective on approaches for integrating biomonitoring data into a risk-based context. The available data for benzene satisfied most of the Common Criteria and allowed for a risk-based evaluation of the benzene biomonitoring data. In general, biomarker (blood benzene, urinary benzene and urinary S-phenylmercapturic acid) central tendency (i.e. mean, median and geometric mean) concentrations for non-smokers are at or below the predicted blood or urine concentrations that would correspond to exposure at the US Environmental Protection Agency reference concentration (30 µg/m3), but greater than blood or urine concentrations relating to the air concentration at the 1 × 10−5 excess cancer risk (2.9 µg/m3). Smokers clearly have higher levels of benzene exposure, and biomarker levels of benzene for non-smokers are generally consistent with ambient air monitoring results. While some biomarkers of benzene are specific indicators of exposure, the interpretation of benzene biomonitoring levels in a health-risk context are complicated by issues associated with short half-lives and gaps in knowledge regarding the relationship between the biomarkers and subsequent toxic effects. PMID:23346981

  2. Effect of startup circuit exercise on derivatives reactive oxygen metabolites, biological antioxidant potential levels and physical fitness of adolescents boys with intellectual disabilities

    PubMed Central

    Kim, Chang-Gyun; Lee, Jin-Seok

    2016-01-01

    The purpose of this study was to examine the effect of starup circuit exercise program on derivatives reactive oxygen metabolite (d-ROM) and biological antioxidant potential (BAP) levels and physical fitness of adolescents with intellectual disabilities, and to sugesst exercise programs to promote the health and physical development of such adolescents. Twelve students with intellectual disabilities were divided into two groups; circuit exercise group (CE group: n=6; age, 14.83±0.98 years; height, 163.83±5.78 cm; body mass, 67.08±3.32 kg; %Fat, 25.68±2.42), control group (CON group: n=6; age: 15.00±0.63 years; height, 162.33±4.41 cm; body mass, 67.50±3.62 kg; %Fat, 26.96±2.06). The CE group performed the CE program 4 times a week over a 12-week period. The CON group maintained their activities of daily living. The following were measured before and after intervention: physical fitness by before and after the completion of the training programm, and were measured and blood samples were assessed. The results of the study indicate that the 12-week CE program increased significantly physical fitness (P<0.05). Furthermore, This study proved that the CE program improved physical fitness, and reduced the d-ROM levels, and increased the BAP levels of the adolescents with intellectual disabilities. Therefore, it may enhance the health and physical development of adolescents boys with intellectual disabilities. PMID:27807529

  3. Coupled-column liquid chromatography applied to the trace-level determination of triazine herbicides and some of their metabolites in water samples.

    PubMed

    Hernández, F; Hidalgo, C; Sancho, J V; López, F J

    1998-08-01

    In the present work, a study is reported of the potential of coupled-column liquid chromatography (LC) applied to the determination of triazine residues in environmental water samples. For this purpose, two different techniques have been compared: on-line trace enrichment followed by LC (SPE-LC) and coupled-column liquid chromatography (LC-LC). First, a completely automated liquid chromatographic method based on on-line trace enrichment in a prepacked precolumn and using diode array detection has been developed for the simultaneous trace-level determination of six triazine herbicides (simazine, cyanazine, atrazine, terbumeton, terbuthylazine, and terbutryn) and the main atrazine metabolites (desisopropylatrazine, desethylatrazine, and hydroxyatrazine). After preconcentration parameters were optimized by testing two different sorbents (C18 and PRP-1) in three cartridges with different dimensions, a sample volume of 100 mL was selected in order to achieve maximal solute preconcentration. Detection limits lower than 0.1 microgram.L-1 were obtained even for the most polar analyte (desisopropylatrazine), which presented recoveries of around 30%. The method was validated by means of recovery experiments in groundwater and surface water samples spiked with the analytes at different levels (0.2-2 micrograms.L-1). Afterward, the procedure was successfully applied in a program for monitoring of triazine residues in surface water carried out in a wet area of Castellón, Spain. Different triazine herbicides such as simazine, terbumeton, terbuthylazine, and terbutryn were identified and quantified. The identity of these compounds was confirmed by their absorption UV spectra and by GC/MS analysis. Finally, two rapid, sensitive, and selective procedures, previously developed in our laboratory for the trace-level determination of triazine compounds, both based on LC-LC, were compared with the former procedure. The SPE-LC approach showed a considerable improvement in the global

  4. Drought and air warming affect the species-specific levels of stress-related foliar metabolites of three oak species on acidic and calcareous soil.

    PubMed

    Hu, Bin; Simon, Judy; Rennenberg, Heinz

    2013-05-01

    Climate change as projected for Central Europe will lead to prolonged periods of summer drought and enhanced air temperature. Thus, forest management practices are required to take into account how species performance is adapted to cope with these climate changes. Oak trees may play a major role in future forests because of their relative drought-tolerance compared with other species like beech. Therefore, this study investigated the stress responses (i.e., anti-oxidants, free amino acids) in the leaves of three widely distributed oak species in Central Europe (i.e., Quercus robur L., Q. petraea [Matt.] Libel., Q. pubescens Willd.) to drought, air warming and the combination of drought plus air warming under controlled conditions after periods of spring drought, a short rewetting and summer drought. We quantified foliar levels of thiols, ascorbate, and free amino compounds in Q robur, Q. petraea and Q. pubescens. Our study showed that oak saplings had increased levels of γ-glutamylcysteine and total glutathione and proline with drought and air warming. Foliar ascorbate, glutathione disulfide and dehydroascorbic acid levels were not affected. The comparison of stress responses to drought and/or air warming between the three species showed higher foliar thiol levels in Q. robur and Q. pubescens compared with Q. petraea. For total and reduced ascorbic acid and γ-aminobutyric acid, the highest levels were found in Q. robur. In conclusion, our study showed that foliar anti-oxidant and free amino acid levels were significantly affected by drought plus air warming; however, this effect was species-dependent with the drought-tolerant species of Q. pubescens having the highest reactive oxygen species scavenging capacity among three tested oak species. Furthermore, stress responses as shown by increased levels of foliar anti-oxidants and free amino acids differ between calcareous and acidic soil indicating that the capacities of anti-oxidative defense and osmotic stress

  5. A simple LC-MS/MS method to determine plasma and cerebrospinal fluid levels of albendazole metabolites (albendazole sulfoxide and albendazole sulfone) in patients with neurocysticercosis.

    PubMed

    González-Hernández, Iliana; Ruiz-Olmedo, María Isabel; Cárdenas, Graciela; Jung-Cook, Helgi

    2012-02-01

    The development and validation of an LC-MS/MS method for the simultaneous determination of albendazole metabolites (albendazole sulfoxide and albendazole sulfone) in human plasma are described. Samples of 200 μL were extracted with ether-dichloromethane-chloroform (60:30:10, v/v/v). The chromatographic separation was performed using a C(18) column with methanol-formic acid 20 mmol/L (70:30) as the mobile phase. The method was linear in a range of 20-5000 ng/mL for albendazole sulfoxide and 10-1500 ng/mL for albendazole sulfone. For both analytes the method was precise (RSD < 12%) and accurate (RE <7%) with high recovery (>90%). The method was successfully applied to determine the plasma and cerebrospinal fluid levels of albendazole sulfoxide and albendazole sulfone in patients with subarachnoidal neurocysticercosis who received albendazole at 30 mg/kg per day for 7 days. This LC-MS/MS method yielded a quick, simple and reliable protocol for determining albendazole sulfoxide and albendazole sulfone concentrations in plasma and cerebrospinal fluid samples and is applicable to therapeutic monitoring.

  6. Growth, feed efficiency and blood profile of buffalo calves consuming high levels of fluoride: growth and blood metabolites in buffaloes fed high fluoride.

    PubMed

    Madan, Jyotsana; Puri, J P; Singh, J K

    2009-03-01

    Twelve male buffalo calves of 10 to 12 months of age were divided into 3 groups of four each. They were fed wheat straw+concentrate mixture +3 Kg greens. The chemical composition of the diet was same in all the three groups except fluoride which was added (as NaF) in concentrate mixture of group B and C to make the final fluoride concentration 30 ppm and 60 ppm respectively. The animals were kept on scheduled diet for a period of 90 days. Body weights were recorded at the start of the experiment and at fortnightly interval thereafter. Analysis of data revealed that the dry matter intake decreased non significantly in group B and C as compared to control group. A significant decrease in serum calcium and a significant increase in phosphorus concentration were observed in group C animals. A significant increase was observed in alkaline phosphatase activity in group C animals. A non significant decrease was observed in T4 values in group C animals. On the basis of these results it could be concluded that fluoride in the diet of buffalo calves @ 30 ppm is a safe level whereas 60 ppm has affected the blood metabolites.

  7. Lack of the COMPASS Component Ccl1 Reduces H3K4 Trimethylation Levels and Affects Transcription of Secondary Metabolite Genes in Two Plant–Pathogenic Fusarium Species

    PubMed Central

    Studt, Lena; Janevska, Slavica; Arndt, Birgit; Boedi, Stefan; Sulyok, Michael; Humpf, Hans-Ulrich; Tudzynski, Bettina; Strauss, Joseph

    2017-01-01

    In the two fungal pathogens Fusarium fujikuroi and Fusarium graminearum, secondary metabolites (SMs) are fitness and virulence factors and there is compelling evidence that the coordination of SM gene expression is under epigenetic control. Here, we characterized Ccl1, a subunit of the COMPASS complex responsible for methylating lysine 4 of histone H3 (H3K4me). We show that Ccl1 is not essential for viability but a regulator of genome-wide trimethylation of H3K4 (H3K4me3). Although, recent work in Fusarium and Aspergillus spp. detected only sporadic H3K4 methylation at the majority of the SM gene clusters, we show here that SM profiles in CCL1 deletion mutants are strongly deviating from the wild type. Cross-complementation experiments indicate high functional conservation of Ccl1 as phenotypes of the respective △ccl1 were rescued in both fungi. Strikingly, biosynthesis of the species-specific virulence factors gibberellic acid and deoxynivalenol produced by F. fujikuroi and F. graminearum, respectively, was reduced in axenic cultures but virulence was not attenuated in these mutants, a phenotype which goes in line with restored virulence factor production levels in planta. This suggests that yet unknown plant-derived signals are able to compensate for Ccl1 function during pathogenesis. PMID:28119673

  8. Reassessing benzene risks using internal doses and Monte-Carlo uncertainty analysis.

    PubMed Central

    Cox, L A

    1996-01-01

    Human cancer risks from benzene have been estimated from epidemiological data, with supporting evidence from animal bioassay data. This article reexamines the animal-based risk assessments using physiologically based pharmacokinetic (PBPK) models of benzene metabolism in animals and humans. Internal doses (total benzene metabolites) from oral gavage experiments in mice are well predicted by the PBPK model. Both the data and the PBPK model outputs are also well described by a simple nonlinear (Michaelis-Menten) regression model, as previously used by Bailer and Hoel [Metabolite-based internal doses used in risk assessment of benzene. Environ Health Perspect 82:177-184 (1989)]. Refitting the multistage model family to internal doses changes the maximum-likelihood estimate (MLE) dose-response curve for mice from linear-quadratic to purely cubic, so that low-dose risk estimates are smaller than in previous risk assessments. In contrast to Bailer and Hoel's findings using interspecies dose conversion, the use of internal dose estimates for humans from a PBPK model reduces estimated human risks at low doses. Sensitivity analyses suggest that the finding of a nonlinear MLE dose-response curve at low doses is robust to changes in internal dose definitions and more consistent with epidemiological data than earlier risk models. A Monte-Carlo uncertainty analysis based on maximum-entropy probabilities and Bayesian conditioning is used to develop an entire probability distribution for the true but unknown dose-response function. This allows the probability of a positive low-dose slope to be quantified: It is about 10%. An upper 95% confidence limit on the low-dose slope of excess risk is also obtained directly from the posterior distribution and is similar to previous q1* values. This approach suggests that the excess risk due to benzene exposure may be nonexistent (or even negative) at sufficiently low doses. Two types of biological information about benzene effects

  9. Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity

    PubMed Central

    Hosgood, HD; Zhang, L; Shen, M; Berndt, SI; Vermeulen, R; Li, G; Yin, S; Yeager, M; Yuenger, J; Rothman, N; Chanock, S; Smith, M; Lan, Q

    2010-01-01

    Introduction Benzene is an established human haematotoxin, with substantial interindividual variation in benzene-induced toxicity. Methods To further examine if genetic variation contributes to benzene haematotoxicity, we analysed 1023 tagSNPs in 121 gene regions important for benzene metabolism, haematopoiesis, leukaemia and lymphoma among 250 workers exposed to benzene and 140 unexposed controls in a cross-sectional study carried out in China. Linear regression was used to analyse the relationship between genetic polymorphisms and total white blood cell (WBC) count and its subtypes, adjusting for potential confounders and occupational exposure to benzene and toluene among exposed workers. The minp test assessed the association on the gene region level. The false discovery rate method was used to control for multiple comparisons. Results VEGF (minp = 0.0030) and ERCC3 (minp = 0.0042) were the most significantly associated gene regions with altered WBC counts among benzene-exposed workers, after accounting for multiple comparisons. Highly significant changes were also found for WBC subtype counts, including granulocytes, CD4+ T cells and lymphocytes for VEGF and granulocytes and NK cells for ERCC3. Further, in workers exposed to <1 ppm, a SNP in VEGF was associated with changes in WBC and granulocyte counts, and SNPs in ERCC3 were associated with changes in WBC, NK cell and granulocyte counts. Discussion Our findings suggest that genetic variation in VEGF, which plays an important role in blood vessel growth, and ERCC3, which is a member of the DNA repair pathway and is responsible for repairing bulky DNA adducts formed by chemicals, may contribute to individual susceptibility to benzene-induced haematotoxicity at relatively low levels of benzene exposure. PMID:19773279

  10. Prognostic Aspects of Benzene Poisoning

    PubMed Central

    Hernberg, S.; Savilahti, M.; Ahlman, K.; Asp, S.

    1966-01-01

    In 1955, a benzene mass-poisoning was detected in a shoe factory in Finland. One hundred and forty-seven persons were heavily exposed, and more than 100 had abnormal blood counts. One died and 10 required hospital treatment. This paper deals with a re-examination of the involved workers nine years later. One hundred and twenty-five persons attended for re-examination. Eight had died, two refused, and 11 could not be located. The possibility of death due to benzene poisoning having occurred among these persons was ruled out by checking the national death register. Each of the subjects underwent a haematological examination which included the haemoglobin value and the erythrocyte, reticulocyte, leucocyte, and thrombocyte counts. A differential count of the leucocytes was also made. A randomly chosen group of 86 persons served as a control group. The thrombocytes of the whole patient group and the erythrocytes of the men were significantly lower than those of the controls, whereas the leucocytes of the whole group and the erythrocytes of the women failed to show any statistical difference. In a multiple discriminant function analysis, considering all three counts at the same time, only the men differed slightly from the controls at the re-examination. The analysis also showed that the prognosis of the severe cases did not differ from that of the mild ones, provided the acute stage had been passed. Some illustrative case reports are added. One patient developed leukaemia after a latency of seven years, whereas most of the others—chosen because of grave symptoms in the initial stage—have recovered. The results are discussed from the point of view of prognosis. PMID:5946130

  11. Effect of feeding different levels of wheat roti on nutrient utilization and blood metabolite profile in semi-captive Asian elephants (Elephas maximus).

    PubMed

    Das, A; Saini, M; Katole, S; Kullu, S S; Swarup, D; Sharma, A K

    2015-04-01

    This experiment was conducted to study the effect of different levels of wheat roti (WR) on nutrient utilization and blood metabolites in Asian elephants fed roughages ad libitum. Nine (3 M, 6 F) Asian elephants (14-52 years of age, 1909-3968 kg BW) were used in an experiment based on replicated Latin square design. Animals in each group (n = 3) were assigned to one of the three dietary treatments in a manner that animals in all the three groups were exposed to all the three treatments in three different periods. Each feeding trial comprised 30 days (25 days of adaptation and 5 days collection period). The amount of WR fed to the elephants was 0.18, 0.12 and 0.06% of BW in groups I, II and III, respectively. They were allowed to forage in the nearby forests for 6 h/day and to bathe for 2 h/day. The animals had ad libitum access to cut Rohini (Mallotus philippensis) trees in their night shelter. Intake and apparent digestibility of dry matter (DM), crude protein (CP), gross energy (GE), Ca, P, Fe, Cu and Zn were measured. Feed consumption was not significantly different among the groups. Significant (p < 0.01) decrease in digestibility of DM and GE and blood glucose concentration was observed with decreased level of WR in the diet. Feeding of WR at 0.06% of BW supplied adequate amount of DE, CP, Ca, P, Fe, Cu and Zn to meet requirement for adult maintenance. Feeding of WR in excess of 0.06% of BW supplied DE in excess of requirement, increased blood glucose concentration which may cause obesity and other associated health problems. It was concluded that the amount of WR should be restricted to 0.06% of BW in the diet of captive Asian elephants.

  12. Diets high in resistant starch increase plasma levels of trimethylamine-N-oxide, a gut microbiome metabolite associated with CVD risk

    SciTech Connect

    Bergeron, Nathalie; Williams, Paul T.; Lamendella, Regina; Faghihnia, Nastaran; Grube, Alyssa; Li, Xinmin; Wang, Zeneng; Knight, Rob; Jansson, Janet K.; Hazen, Stanley L.; Krauss, Ronald M.

    2016-12-20

    Production of trimethylamine-N-oxide (TMAO), a biomarker of CVD risk, is dependent on intestinal microbiota, but little is known of dietary conditions promoting changes in gut microbial communities. Resistant starches (RS) alter the human microbiota. We sought to determine whether diets varying in RS and carbohydrate (CHO) content affect plasma TMAO levels. We also assessed postprandial glucose and insulin responses and plasma lipid changes to diets high and low in RS. In a cross-over trial, fifty-two men and women consumed a 2-week baseline diet (41 percentage of energy (%E) CHO, 40 % fat, 19 % protein), followed by 2-week high- and low-RS diets separated by 2-week washouts. RS diets were assigned at random within the context of higher (51–53 %E)v. lower CHO (39–40 %E) intake. Measurements were obtained in the fasting state and, for glucose and insulin, during a meal test matching the composition of the assigned diet. With lower CHO intake, plasma TMAO, carnitine, betaine andγ-butyrobetaine concentrations were higher after the high-v. low-RS diet (P<0·01 each). These metabolites were not differentially affected by highv. low RS when CHO intake was high. Although the high-RS meal reduced postprandial insulin and glucose responses when CHO intake was low (P<0·01 each), RS did not affect fasting lipids, lipoproteins, glucose or insulin irrespective of dietary CHO content. In conclusion, a lower-CHO diet high in RS was associated with higher plasma TMAO levels. These findings, together with the absence of change in fasting lipids, suggest that short-term high-RS diets do not improve markers of cardiometabolic health.

  13. Environmental and biological monitoring of benzene during self-service automobile refueling.

    PubMed Central

    Egeghy, P P; Tornero-Velez, R; Rappaport, S M

    2000-01-01

    Although automobile refueling represents the major source of benzene exposure among the nonsmoking public, few data are available regarding such exposures and the associated uptake of benzene. We repeatedly measured benzene exposure and uptake (via benzene in exhaled breath) among 39 self-service customers using self-administered monitoring, a technique rarely used to obtain measurements from the general public (130 sets of measurements were obtained). Benzene exposures averaged 2.9 mg/m(3) (SD = 5.8 mg/m(3); median duration = 3 min) with a range of < 0.076-36 mg/m(3), and postexposure breath levels averaged 160 microg/m(3) (SD = 260 microg/m(3)) with a range of < 3.2-1,400 microg/m(3). Log-transformed exposures and breath levels were significantly correlated (r = 0.77, p < 0.0001). We used mixed-effects statistical models to gauge the relative influences of environmental and subject-specific factors on benzene exposure and breath levels and to investigate the importance of various covariates obtained by questionnaire. Model fitting yielded three significant predictors of benzene exposure, namely, fuel octane grade (p = 0.0011), duration of exposure (p = 0.0054), and season of the year (p = 0.032). Likewise, another model yielded three significant predictors of benzene concentration in breath, specifically, benzene exposure (p = 0.0001), preexposure breath concentration (p = 0.0008), and duration of exposure (p = 0.038). Variability in benzene concentrations was remarkable, with 95% of the estimated values falling within a 274-fold range, and was comprised entirely of the within-person component of variance (representing exposures of the same subject at different times of refueling). The corresponding range for benzene concentrations in breath was 41-fold and was comprised primarily of the within-person variance component (74% of the total variance). Our results indicate that environmental rather than interindividual differences are primarily responsible for

  14. Single Silver Adatoms on Nanostructured Manganese Oxide Surfaces: Boosting Oxygen Activation for Benzene Abatement.

    PubMed

    Chen, Yaxin; Huang, Zhiwei; Zhou, Meijuan; Ma, Zhen; Chen, Jianmin; Tang, Xingfu

    2017-02-21

    The involvement of a great amount of active oxygen species is a crucial requirement for catalytic oxidation of benzene, because complete mineralization of one benzene molecule needs 15 oxygen atoms. Here, we disperse single silver adatoms on nanostructured hollandite manganese oxide (HMO) surfaces by using a thermal diffusion method. The single-atom silver catalyst (Ag1/HMO) shows high catalytic activity in benzene oxidation, and 100% conversion is achieved at 220 °C at a high space velocity of 23 000 h(-1). The Mars-van Krevelen mechanism is valid in our case as the reaction orders for both benzene and O2 approach one, according to reaction kinetics data. Data from H2 temperature-programmed reduction and O core-level X-ray photoelectron spectra (XPS) reveal that Ag1/HMO possesses a great amount of active surface lattice oxygen available for benzene oxidation. Valence-band XPS and density functional theoretical calculations demonstrate that the single Ag adatoms have the upshifted 4d orbitals, thus facilitating the activation of gaseous oxygen. Therefore, the excellent activation abilities of Ag1/HMO toward both surface lattice oxygen and gaseous oxygen account for its high catalytic activity in benzene oxidation. This work may assist with the rational design of efficient metal-oxide catalysts for the abatement of volatile organic compounds such as benzene.

  15. Endohedral and exohedral complexes of substituted benzenes with carbon nanotubes and graphene

    NASA Astrophysics Data System (ADS)

    Munusamy, Elango; Wheeler, Steven E.

    2013-09-01

    Non-covalent complexes of cyclohexane and a series of substituted benzenes with short carbon nanotube (CNT) models are investigated primarily at the B97-D3/TZV(2d,2p) level of theory. Understanding non-covalent interactions of arenes with CNTs is vital for the development of next-generation organic electronic materials and for harnessing CNTs as nano-reactors and vehicles for drug delivery. The interaction of benzene and cyclohexane with the interior and exterior of CNTs depends on the nanotube diameter, particularly for endohedral complexes. Both benzene and cyclohexane interact more strongly with the interior of CNTs than the outside, with benzene exhibiting stronger interactions than cyclohexane for CNTs larger than (8,8). Studies of two benzenes inside of CNTs predict the formation of one-dimensional sandwich and parallel-displaced stacks of benzenes within certain sized CNTs, which could have interesting optoelectronic properties. Concerning the impact of substituents on the interaction of benzene with CNTs, we find that electrostatic interactions do not control substituent effects. That is, the electron-donating or -withdrawing character of the substituents is not correlated with the predicted interaction energies. Moreover, substituent effects are the same for both endohedral and exohedral complexes, despite the different electronic character of the interior and exterior CNT walls. Ultimately, substituent effects in π-stacking interactions with CNTs and graphene are explained by differences in dispersion interactions between the substituents and CNT walls or graphene surface.

  16. Prevention of benzene-induced myelotoxicity by nonsteroidal anti-inflammatory drugs.

    PubMed Central

    Kalf, G F; Schlosser, M J; Renz, J F; Pirozzi, S J

    1989-01-01

    Benzene affects hematopoietic progenitor cells leading to bone marrow depression and genotoxic effects such as micronucleus formation. Progenitor cell proliferation and differentiation are inhibited by prostaglandins produced by macrophages. Administration of benzene to DBA/2 or C57BL/6 mice caused a dose-dependent bone marrow depression and a significant increase in marrow prostaglandin E level and both were prevented by the coadministration of indomethacin and other inhibitors of the cyclooxygenase component of prostaglandin H synthase. Levels of benzene that decreased bone marrow cellularity also caused genotoxic effects measured as increased micronucleated polychromatic erythrocytes in peripheral blood, which was also prevented by the coadministration of indomethacin. These results suggest a possible role for prostaglandin synthase in benzene myelotoxicity; a mechanism by which this might occur is presented. PMID:2792051

  17. Reduction of benzene toxicity by toluene

    SciTech Connect

    Plappert, U.; Barthel, E.; Seidel, H.J.

    1994-12-31

    BDF{sub 1} mice were exposed in inhalation chambers to benzene (900 ppm, 300 ppm) and/or toluene (500 ppm, 250 ppm) 6 hr per day, 5 days per week, for up to 8 weeks. Benzene alone induced a slight anemia after 4 and 8 weeks and a reduction of BFU-E and CFU-E numbers in the marrow. The coexposure to toluene reduced the degree of anemia. These results confirm previous studies where toluene was found to reduce benzene toxicity. This protective effect was most pronounced when DNA damage was studied in peripheral blood cells, bone marrow, and liver using the single cell gel (SCG) assay. With benzene alone, either with 300 or 900 ppm, a significant increase in DNA damage was detected in cells sampled from all three organs. Toluene alone did not induce a significant increase in DNA damage. The coexposure of benzene and toluene reduced the extent of DNA damage to about 50% of benzene alone. This result is considered a clear indication for a protective effect of toluene on the genetic toxicity of benzene. 18 refs., 7 figs., 3 tabs.

  18. Excited state of protonated benzene and toluene

    SciTech Connect

    Esteves-López, Natalia; Dedonder-Lardeux, Claude; Jouvet, Christophe

    2015-08-21

    We present photo-fragmentation electronic spectra of the simplest protonated aromatic molecules, protonated benzene and toluene, recorded under medium resolution conditions and compared with the photo-fragmentation spectrum of protonated pyridine. Despite the resolution and cold temperature achieved in the experiment, the electronic spectra of protonated benzene and toluene are structure-less, thus intrinsically broadened. This is in agreement with the large geometrical changes and the fast dynamic toward internal conversion predicted by ab initio calculations for protonated benzene [Rode et al., J. Phys. Chem. A 113, 5865–5873 (2009)].

  19. Lidar Measurements of Industrial Benzene Emissions

    NASA Astrophysics Data System (ADS)

    Berkhout, A. J. C.; van der Hoff, G. R.; Gast, L. F. L.

    2016-06-01

    The ability to measure benzene concentrations was added to the RIVM mobile DIAL system. In a ten-days campaign, it was used to measure benzene emissions in the Rijnmond, a heavily industrialised area in the South-west of the Netherlands with petrochemical industry, petrochemical products storage and the port of Rotterdam. On two of the ten days, benzene emissions were found. Combined with measurements of wind speed and wind direction, the Lidar measurements indicated the possible origins of these emissions. This makes the Lidar a valuable tool, augmenting the data collected at fixed monitoring stations.

  20. Sensorimotor impairment and elevated levels of dopamine metabolites in the neostriatum occur rapidly after intranigral injection of 6-hydroxydopamine or gamma-hydroxybutyrate in awake rats.

    PubMed

    Altar, C A; O'Neil, S; Marshall, J F

    1984-03-01

    The unilateral injection of 6-hydroxydopamine (8 micrograms) into the ventral tegmental area of awake rats produced a rapidly developing and irreversible sensory neglect to contralateral tactile stimuli. This neglect developed in a caudal to rostral direction on the affected body surface and coincided with significant elevation in the concentrations of dopamine and two of its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the ipsilateral neostriatum. The unilateral injection of procaine or gamma-hydroxybutyric acid (GHB) into the substantia nigra of awake animals also produced a contralateral neglect that developed in a caudal to rostral direction, but the behavioral effect of these drugs diminished within 1 hr. Concentrations of dopamine, dihydroxyphenylacetic acid and homovanillic acid in the neostriatum were markedly elevated during continuous infusions of procaine or gamma-hydroxybutyric acid. The extent of sensory neglect and changes in dopamine metabolism in the neostriatum varied according to the amount of gamma-hydroxybutyric acid injected into the nigra and according to the proximity of injections of gamma-hydroxybutyric acid to the pars compacta. The rapid onset of sensory neglect following microinjections of 6-hydroxydopamine, procaine or gamma-hydroxybutyric acid is consistent with the ability of each of these drugs to block the conduction of impulses in mesostriatal neurons and suggests that concomitant increases in levels of dopamine, dihydroxyphenylacetic acid and homovanillic acid in the neostriatum resulted from decreases in the release of dopamine coupled with increased synthesis of dopamine. These findings also indicate that the catabolism of dopamine to dihydroxyphenylacetic acid or homovanillic acid may originate intraneuronally, without prior release of dopamine and its recapture by mesostriatal terminals, if the flow of impulses in this pathway has been blocked.

  1. In-vivo assessment of tissue metabolite levels using 1H MRS and the Electric REference To access In vivo Concentrations (ERETIC) method.

    PubMed

    Heinzer-Schweizer, S; De Zanche, N; Pavan, M; Mens, G; Sturzenegger, U; Henning, A; Boesiger, P

    2010-05-01

    Quantitative values of metabolite concentrations in (1)H magnetic resonance spectroscopy have been obtained using the Electric REference To access In vivo Concentrations (ERETIC) method, whereby a synthetic reference signal is injected during the acquisition of spectra. The method has been improved to enable quantification of metabolite concentrations in vivo. Optical signal transmission was used to eliminate random fluctuations in ERETIC signal coupling to the receiver coil due to changes in position of cables and highly dielectric human tissue. Stability and reliability of the signal were tested in vitro, achieving stability with a mean error of 2.83%. Scaling of the signal in variable loading conditions was demonstrated and in-vivo measurements of brain were acquired on a 3T Philips system using a transmit/receive coil. The quantitative brain water and metabolite concentration values are in good agreement with those in the literature.

  2. 46 CFR 197.565 - Notifying personnel of benzene hazards.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Notifying personnel of benzene hazards. 197.565 Section... AND HEALTH STANDARDS GENERAL PROVISIONS Benzene § 197.565 Notifying personnel of benzene hazards. (a) Material safety data sheet. A material safety data sheet (MSDS) addressing benzene must be made...

  3. 46 CFR 197.565 - Notifying personnel of benzene hazards.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Notifying personnel of benzene hazards. 197.565 Section... AND HEALTH STANDARDS GENERAL PROVISIONS Benzene § 197.565 Notifying personnel of benzene hazards. (a) Material safety data sheet. A material safety data sheet (MSDS) addressing benzene must be made...

  4. 46 CFR 197.565 - Notifying personnel of benzene hazards.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Notifying personnel of benzene hazards. 197.565 Section... AND HEALTH STANDARDS GENERAL PROVISIONS Benzene § 197.565 Notifying personnel of benzene hazards. (a) Material safety data sheet. A material safety data sheet (MSDS) addressing benzene must be made...

  5. 46 CFR 197.565 - Notifying personnel of benzene hazards.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Notifying personnel of benzene hazards. 197.565 Section... AND HEALTH STANDARDS GENERAL PROVISIONS Benzene § 197.565 Notifying personnel of benzene hazards. (a) Material safety data sheet. A material safety data sheet (MSDS) addressing benzene must be made...

  6. 46 CFR 197.565 - Notifying personnel of benzene hazards.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Notifying personnel of benzene hazards. 197.565 Section... AND HEALTH STANDARDS GENERAL PROVISIONS Benzene § 197.565 Notifying personnel of benzene hazards. (a) Material safety data sheet. A material safety data sheet (MSDS) addressing benzene must be made...

  7. Oxidation Mechanisms of Toluene and Benzene

    NASA Technical Reports Server (NTRS)

    Bittker, David A.

    1995-01-01

    An expanded and improved version of a previously published benzene oxidation mechanism is presented and shown to model published experimental data fairly successfully. This benzene submodel is coupled to a modified version of a toluene oxidation submodel from the recent literature. This complete mechanism is shown to successfully model published experimental toluene oxidation data for a highly mixed flow reactor and for higher temperature ignition delay times in a shock tube. A comprehensive sensitivity analysis showing the most important reactions is presented for both the benzene and toluene reacting systems. The NASA Lewis toluene mechanism's modeling capability is found to be equivalent to that of the previously published mechanism which contains a somewhat different benzene submodel.

  8. Simultaneous determination of 8 neurotransmitters and their metabolite levels in rat brain using liquid chromatography in tandem with mass spectrometry: Application to the murine Nrf2 model of depression.

    PubMed

    Wojnicz, Aneta; Avendaño Ortiz, José; Casas, Ana I; Freitas, Andiara E; G López, Manuela; Ruiz-Nuño, Ana

    2016-01-30

    Analysis of neurotransmitters and their metabolites is useful for the diagnosis of central nervous system diseases. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with protein precipitation was developed to monitor levels of adrenaline (AD), noradrenaline (NA), glutamic acid (Glu), γ-aminobutyric acid (GABA), dopamine (DA), 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in rat brain tissue. Isoprenaline was used as an internal standard (IS). Neurotransmitters and metabolites were eluted with a reverse phase column under gradient conditions through a mobile phase consisting of 0.2% formic acid water solution/acetonitrile. The compounds were detected and quantified by LC-MS/MS with positive or negative electrospray ionization, which operates in multiple-reaction monitoring mode. The method was linear or polynomial (R(2)>0.99) for AD, NA, Glu, GABA, DA, 5-HT, 5-HIAA, and MHPG in the range of 0.25-200, 0.5-200, 250-20,000, 250-20,000, 0.25-200, 10-3000, 1-50, and 1-50ng/mL, respectively. The validation assays for accuracy and precision, matrix effect, extraction recovery, stability and carry-over of the samples for neurotransmitters and metabolites were consistent with the requirements of regulatory agencies. The method enables rapid quantification of neurotransmitters and their metabolites and has been applied in the nuclear factor (erythroid 2-derived)-like 2 (Nrf2) knockout mouse model of depression.

  9. Theoretical study of transition-metal ions bound to benzene

    NASA Technical Reports Server (NTRS)

    Bauschlicher, Charles W., Jr.; Partridge, Harry; Langhoff, Stephen R.

    1992-01-01

    Theoretical binding energies are reported for all first-row and selected second-row transition metal ions (M+) bound to benzene. The calculations employ basis sets of at least double-zeta plus polarization quality and account for electron correlation using the modified coupled-pair functional method. While the bending is predominantly electrostatic, the binding energies are significantly increased by electron correlation, because the donation from the metal d orbitals to the benzene pi* orbitals is not well described at the self-consistent-field level. The uncertainties in the computed binding energies are estimated to be about 5 kcal/mol. Although the calculated and experimental binding energies generally agree to within their combined uncertainties, it is likely that the true binding energies lie in the lower portion of the experimental range. This is supported by the very good agreement between the theoretical and recent experimental binding energies for AgC6H6(+).

  10. Service station attendants' exposure to benzene and gasoline vapors.

    PubMed

    McDermott, H J; Vos, G A

    1979-04-01

    Service station attendants' exposure to benzene, based on 85 TWA results at 7 stations, were well below 1 ppm except one exposure of 2.08 ppm. Short term exposures were 1.21 ppm or less over 15 minutes. Attendants' TWA exposures to total gasoline vapor were 114 ppm or less, with measured 15 minute exposures no higher than 100 ppm during actual filling operations. One station had vapor recovery nozzles; exposures here were below the detectable level (0.01 ppm benzene) on 10% more days than the next lowest station. Still, the magnitude of overall exposures and the degree of reduction indicate that vapor recovery is not needed to control exposures. Some attendants had consistently higher exposures than others. This is felt to be due to work practices, such as standing close to the fill opening, plus local wind conditions around the car as it is filled with gasoline.

  11. Transport and phase equilibria of benzene in FAU type zeolites

    NASA Astrophysics Data System (ADS)

    Saravanan, Chandra

    performed to reveal this vapor-liquid transition. Finally, we study the influence of adsorbate coupling on the self-diffusion of benzene in Na-X and Na-Y zeolites. We propose a simple model for determining how adsorbate-adsorbate interactions modify activation energies of site-to-site jumps. We have calculated diffusion isotherms for a wide range of system parameters at different levels of theory viz., MFT, MFA and MSD, and segregated the resulting diffusion isotherms into supercritical and subcritical isotherms. The supercritical systems exhibit three characteristic diffusion isotherms, depending upon the degree of degeneracy of lattice sites, whereas the subcritical diffusion systems are dominated by cluster formation, exhibiting diffusion isotherms with broad regions of constant diffusivity. Our model for benzene in Na-X is in excellent qualitative agreement with pulsed field gradient NMR diffusivities, and in qualitative disagreement with tracer zero-length column (TZLC) data. We suggest that high temperature TZLC experiments should be performed, to test whether the coverage of maximum diffusivity decreases with increasing temperature.

  12. Biomarkers of leukemia risk: benzene as a model.

    PubMed Central

    Smith, M T; Zhang, L

    1998-01-01

    Although relatively rare, leukemias place a considerable financial burden on society and cause psychologic trauma to many families. Leukemia is the most common cancer in children. The causes of leukemia in adults and children are largely unknown, but occupational and environmental factors are strongly suspected. Genetic predisposition may also play a major role. Our aim is to use molecular epidemiology and toxicology to find the cause of leukemia and develop biomarkers of leukemia risk. We have studied benzene as a model chemical leukemogen, and we have identified risk factors for susceptibility to benzene toxicity. Numerous studies have associated exposure to benzene with increased levels of chromosome aberrations in circulating lymphocytes of exposed workers. Increased levels of chromosome aberrations have, in turn, been correlated with a heightened risk of cancer, especially for hematologic malignancy, in two recent cohort studies in Europe. Conventional chromosome analysis is laborious, however, and requires highly trained personnel. Further, it lacks statistical power, as only a small number of cells can be examined. The recently developed fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR)-based technologies have allowed the detection of specific chromosome aberrations. These techniques are far less time consuming and are more sensitive than classical chromosomal analysis. Because leukemias commonly show a variety of specific chromosome aberrations, detection of these aberrations by FISH and PCR in peripheral blood may provide improved biomarkers of leukemia risk. PMID:9703476

  13. Combined effects of CO2 enrichment, changes in diurnal light level and water stress on foliar metabolites of potato plants grown in naturally sunlit controlled environment chambers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Potato plants (Solanum tuberosum L. cv Kennebec) were grown in outdoor, naturally sunlit, soil-plant-atmosphere research (SPAR) chambers. Drought treatments were imposed at post-tuber initiation stage to assess water stress effects on leaf metabolites, and interactions with enriched CO2 concentrati...

  14. Apo-10'-lycopenoic acid, a lycopene 1 metabolite, increases sirtuin 1 mRNA and protein levels and decreases hepatic fat accumulation in ob/ob mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lycopene has been shown to be beneficial in protecting against high-fat diet-induced fatty liver. The recent demonstration that lycopene can be converted by carotene 99,10’-oxygenase into a biologically active metabolite, ALA, led us to propose that the function of lycopene can be mediated by ALA. I...

  15. Evaluation of accelerated UV and thermal testing for benzene formation in beverages containing benzoate and ascorbic acid.

    PubMed

    Nyman, Patricia J; Wamer, Wayne G; Begley, Timothy H; Diachenko, Gregory W; Perfetti, Gracia A

    2010-04-01

    Under certain conditions, benzene can form in beverages containing benzoic and ascorbic acids. The American Beverage Assn. (ABA) has published guidelines to help manufacturers mitigate benzene formation in beverages. These guidelines recommend accelerated testing conditions to test product formulations, because exposure to ultraviolet (UV) light and elevated temperature over the shelf life of the beverage may result in benzene formation in products containing benzoic and ascorbic acids. In this study, the effects of UVA exposure on benzene formation were determined. Benzene formation was examined for samples contained in UV stabilized and non-UV stabilized packaging. Additionally, the usefulness of accelerated thermal testing to simulate end of shelf-life benzene formation was evaluated for samples containing either benzoic or ascorbic acid, or both. The 24 h studies showed that under intense UVA light benzene levels increased by as much as 53% in model solutions stored in non-UV stabilized bottles, whereas the use of UV stabilized polyethylene terephthalate bottles reduced benzene formation by about 13% relative to the non-UV stabilized bottles. Similar trends were observed for the 7 d study. Retail beverages and positive and negative controls were used to study the accelerated thermal testing conditions. The amount of benzene found in the positive controls and cranberry juice suggests that testing at 40 degrees C for 14 d may more reliably simulate end of shelf-life benzene formation in beverages. Except for cranberry juice, retail beverages were not found to contain detectable amounts of benzene (<0.05 ng/g) at the end of their shelf lives.

  16. Sensitive high-performance liquid chromatography method for the simultaneous determination of low levels of dichloroacetic acid and its metabolites in blood and urine.

    PubMed

    Narayanan, L; Moghaddam, A P; Taylor, A G; Sudberry, G L; Fisher, J W

    1999-06-11

    Dichloroacetic acid (DCA) is a contaminant found in treated drinking water due to chlorination. DCA has been shown to be a complete hepatocarcinogen in both mice and rats. In this study we developed a rapid and sensitive high-performance liquid chromatography (HPLC) method to simultaneously detect DCA and its metabolites, oxalic acid, glyoxylic acid and glycolic acid in blood and urine samples of animals sub-chronically administered with DCA (2 g/l) in drinking water. Both urine and plasma samples were treated minimally before HPLC analysis. Separation and detection of DCA and its metabolites were achieved using an anion-exchange column and a conductivity detector. The mobile phase consisted of an initial concentration of 0.01 mM sodium hydroxide in 40% methanol followed by a linear gradient from 0.01 mM to 60 mM sodium hydroxide in 40% methanol for 30 min. The lower detection limit for DCA and each of its three major metabolites was 0.05 microg/ml. DCA and its metabolites gave a linear response range from 0.05 to 100 microg/ml. Plasma DCA was also analyzed by gas chromatography (GC), and the results obtained correlated with those from the HPLC method (correlation coefficient=0.999). While available HPLC techniques offer sensitive procedures to detect either glycolic acid or oxalic acid, the described HPLC method has the unique advantage of determining simultaneously the parent compound (DCA) and its three major metabolites (oxalic acid, glyoxylic acid and glycolic acid) in biological samples, without complex sample preparation.

  17. A non-invasive biomonitoring method for assessing levels of urinary pyrethroid metabolites in diapered children by gas chromatography-mass spectrometry.

    PubMed

    Saito, Shun; Ueyama, Jun; Kondo, Takaaki; Saito, Isao; Shibata, Eiji; Gotoh, Masahiro; Nomura, Hiroshi; Wakusawa, Shinya; Nakai, Kunihiko; Kamijima, Michihiro

    2014-01-01

    The aim of this study was to develop a method for quantitative measurement of urinary metabolites of pyrethroid (PYR) insecticides, trans-chrysanthemumdicarboxylic acid (CDCA) and 3-phenoxybenzoic acid (3-PBA), extracted from disposable diapers. This study was approved by the university ethics committees, and informed consent was obtained from all the parents for their children and from adult volunteers. After extraction of PYR metabolites in the absorber of diapers with 5 ml acetone, the metabolites in the eluents were extracted with tert-butyl methyl ether, derivatized with 1,1,1,3,3,3-hexafluoroisopropanol and analyzed by gas chromatography-mass spectrometry. The limits of quantitation (LOQs) were 0.55 μg/l for CDCA and 0.09 μg/l for 3-PBA in 2 ml urine extracted from diapers. Within-series and between-day precisions were <14% (CV%) over the concentration range of metabolites from 0.4 to 20.4 μg/l urine. When concentrations of each metabolite were measured with the developed method after pouring 2 ml urine, which was obtained from adults both in a general population and pest control operators, on diapers, good correlations were shown between the measured results and the concentrations measured directly for the respective urine with the conventional method (Spearman's rank correlation coefficient 0.889 for CDCA and 0.989 for 3-PBA; n=27-28). The developed method would be applicable to epidemiological studies.

  18. Dynamics of Na(+)(Benzene) + Benzene Association and Ensuing Na(+)(Benzene)2* Dissociation.

    PubMed

    Paul, Amit K; Kolakkandy, Sujitha; Hase, William L

    2015-07-16

    Chemical dynamics simulations were used to study Bz + Na(+)(Bz) → Na(+)(Bz)2* association and the ensuing dissociation of the Na(+)(Bz)2* cluster (Bz = benzene). An interesting and unexpected reaction found from the simulations is direct displacement, for which the colliding Bz molecule displaces the Bz molecule attached to Na(+), forming Na(+)(Bz). The rate constant for Bz + Na(+)(Bz) association was calculated at 750 and 1000 K, and found to decrease with increase in temperature. By contrast, the direct displacement rate constant increases with temperature. The cross section and rate constant for direct displacement are approximately an order of magnitude lower than those for association. The Na(+)(Bz)2* cluster, formed by association, dissociates with a biexponential probability, with the rate constant for the short-time component approximately an order of magnitude larger than that for the longer time component. The latter rate constant agrees with that of Rice-Ramsperger-Kassel-Marcus (RRKM) theory, consistent with rapid intramolecular vibrational energy redistribution (IVR) and intrinsic RRKM dynamics for the Na(+)(Bz)2* cluster. A coupled phase space model was used to analyze the biexponential dissociation probability.

  19. Effects of Temperature, Oxygen Level, Ionic Strength, and pH on the Reaction of Benzene with Hydroxyl Radicals at the Air-Water Interface in Comparison to the Bulk Aqueous Phase.

    PubMed

    Heath, Aubrey A; Valsaraj, Kalliat T

    2015-08-06

    Atmospheric aerosols (e.g., fog droplets) are complex, multiphase mediums. Depending on location, time of day, and/or air mass source, there can be considerable variability within these droplets, relating to temperature, pH, and ionic strength. Due to the droplets' inherently small size, the reactions that occur within these droplets are determined by bulk aqueous phase and air-water interfacial conditions. In this study, the reaction of benzene and hydroxyl radicals is examined kinetically in a thin-film flow-tube reactor. By varying the aqueous volume (e.g., film thickness) along the length of the reactor, both bulk and interfacial reaction rates are measured from a single system. Temperature, pH, and ionic strength are varied to model conditions typical of fog events. Oxygen-poor conditions are measured to study oxygen's overall effect on the reaction pathway. Initial rate activation energies and the bulk aqueous phase and interfacial contributions to the overall rate constant are also obtained.

  20. Effects of forage level and chromium-methionine chelate supplementation on performance, carcass characteristics and blood metabolites in Korean native (Hanwoo) steers.

    PubMed

    Sung, Kyung-Il; Ghassemi Nejad, Jalil; Hong, Seok-Man; Ohh, Sang-Jip; Lee, Bae-Hun; Peng, Jing-Lun; Ji, Do-Hyeon; Kim, Byong-Wan

    2015-01-01

    A feeding trial was carried out to determine the effects of chromium methionine (Cr-Met) chelate and forage level over two years, 1(st) fattening and 2(nd) fattening period on growth parameters, carcass characteristics and blood metabolites of 46 Korean native (Hanwoo, Bos Taurus, BW = 183 ± 44 kg) steers. Treatments were: 1) Steers in the low forage (LF) group were fed diets that consisted of 60% concentrate and 40% forage; 2) Steers in the high forage (HF) group were fed diets that consisted of 40% concentrate and 60% forage. Following the 1(st) fattening period, steers (BW = 480 ± 37.6 kg) were randomly assigned to four treatment groups: LF (40 F plus no Cr-Met supplementation in the 2(nd) fattening period), LFCM (40LF plus added 400 ppb of Cr-Met during the 2(nd) fattening period), HF (60 F plus no added Cr-Met during the 2(nd) fattening period) and HFCM (60 F plus added 400 ppb of Cr-Met in the 2(nd) fattening period). Dry matter intake of the treatment diets did not differ during the raising and 1(th) fattening period (P > 0.05). The ADG in the raising period showed no difference between the 40 F and 60 F groups (P > 0.05). Carcass characteristics including rib-eye area and meat yield index were higher in HF than the other treatment groups (P < 0.05). The HF group tended to show a higher (P = 0.08) marbling score than the LF group whereas the HFCM group showed a higher marbling score than the LFCM group (P < 0.05). HDL was higher and LDL lower in groups fed with Cr-Met than in other groups whereas glucose showed the lowest value in HF group (P < 0.05). Triglyceride (TG), Cholesterol, PUN and total protein (TP) were the same among all treatment groups (P > 0.05). The Insulin concentration in the blood was significantly higher for the HFCM group than for the LF, LFCM and HF groups (P < 0.05). It is concluded that supplementation of chromium-methionine chelate could improve meat quality in beef steers.

  1. Effect of graded levels of niacin supplementation of a semipurified diet on energy and nitrogen balance, growth performance, diarrhea occurrence, and niacin metabolite excretion by growing swine.

    PubMed

    Ivers, D J; Veum, T L

    2012-01-01

    Thirty-six crossbred barrows with an average initial age of 42 d and BW of 13.8 kg were placed in individual metabolism crates in a 35-d experiment to evaluate the supplementation of a semipurified diet with graded levels of crystalline niacin. Response criteria were energy and N balance, growth performance, occurrence of niacin deficiency diarrhea, and urinary excretion of the niacin metabolite N(1)-methyl-2-pyridone-5-carboxylamide (PYR). The basal diet met the true ileal Trp requirement of growing swine, and supplementation with 6, 10, 14, 18, 22, or 44 mg of niacin/kg made 6 treatments. Pigs were observed for scours twice daily, and pig BW and feed consumption were determined weekly. Total urine collections and fecal grab samples were made twice daily from each pig from d 28 to 35. Pigs fed the diet containing 14 mg of niacin/kg absorbed and retained more (P < 0.05) grams of N/d, had a greater N digestibility (%, P < 0.05), a greater ADFI and ADG (P < 0.10), and no diarrhea (P < 0.05) compared with pigs fed the diet containing 6 mg of niacin/kg, and pigs fed the diet containing 10 mg of niacin/kg were intermediate in ADG. There were no additional improvements in the response criteria with niacin supplementation greater than 14 mg/kg. Urinary PYR criteria (mg/L and mg/d) were greater (P < 0.001) for pigs fed the diet containing 44 mg of niacin/kg than for pigs fed the diets containing 6 to 22 mg of niacin/kg. However, urinary PYR criteria for pigs fed the diets containing 6 to 22 mg of niacin/kg did not differ from each other, indicating that PYR was not a sensitive indicator of niacin status for growing swine. Niacin treatment did not affect the percentages of N retained/N absorbed, N retained/N intake, DE, or ME. In conclusion, 14 mg of crystalline niacin/kg of semipurified diet adequate in Trp was the minimum concentration of niacin that maximized N utilization and growth performance, and prevented niacin deficiency diarrhea of growing swine in the current

  2. Changes in DNA methylation patterns in subjects exposed to low-dose benzene.

    PubMed

    Bollati, Valentina; Baccarelli, Andrea; Hou, Lifang; Bonzini, Matteo; Fustinoni, Silvia; Cavallo, Domenico; Byun, Hyang-Min; Jiang, Jiayi; Marinelli, Barbara; Pesatori, Angela C; Bertazzi, Pier A; Yang, Allen S

    2007-02-01

    Aberrant DNA methylation patterns, including global hypomethylation, gene-specific hypermethylation/hypomethylation, and loss of imprinting (LOI), are common in acute myelogenous leukemia (AML) and other cancer tissues. We investigated for the first time whether such epigenetic changes are induced in healthy subjects by low-level exposure to benzene, a widespread pollutant associated with AML risk. Blood DNA samples and exposure data were obtained from subjects with different levels of benzene exposure, including 78 gas station attendants, 77 traffic police officers, and 58 unexposed referents in Milan, Italy (personal airborne benzene range, < 6-478 microg/m(3)). Bisulfite-PCR pyrosequencing was used to quantitate DNA methylation in long interspersed nuclear element-1 (LINE-1) and AluI repetitive elements as a surrogate of genome-wide methylation and examine gene-specific methylation of MAGE-1 and p15. Allele-specific pyrosequencing of the H19 gene was used to detect LOI in 96 subjects heterozygous for the H19 imprinting center G/A single-nucleotide polymorphism. Airborne benzene was associated with a significant reduction in LINE-1 (-2.33% for a 10-fold increase in airborne benzene levels; P = 0.009) and AluI (-1.00%; P = 0.027) methylation. Hypermethylation in p15 (+0.35%; P = 0.018) and hypomethylation in MAGE-1 (-0.49%; P = 0.049) were associated with increasing airborne benzene levels. LOI was found only in exposed subjects (4 of 73, 5.5%) and not in referents (0 of 23, 0.0%). However, LOI was not significantly associated with airborne benzene (P > 0.20). This is the first human study to link altered DNA methylation, reproducing the aberrant epigenetic patterns found in malignant cells, to low-level carcinogen exposure.

  3. Influence of Benzene on the Optical Properties of Titan Haze Laboratory Analogs in the Mid-Visible

    NASA Technical Reports Server (NTRS)

    Yoon, Y. Heidi; Trainer, Melissa G.; Tolbert, Margaret A.

    2012-01-01

    The Cassini Ion and Neutral Mass Spectrometer (Waite, Jr., et al., 2007) and the Composite Infrared Spectrometer (Coustenis, A., et al., 2007) have detected benzene in the upper atmosphere and stratosphere of Titan. Photochemical reactions involving benzene in Titan's atmosphere may influence polycyclic aromatic hydrocarbon formation, aerosol formation, and the radiative balance of Titan's atmosphere. We measure the effect of benzene on the optical properties of Titan analog particles in the laboratory. Using cavity ring-down aerosol extinction spectroscopy, we determine the real and imaginary refractive index at 532 nm of particles formed by benzene photolysis and Titan analog particles formed with ppm-levels of benzene. These studies are compared to the previous study by Hasenkopf, et a1. (2010) of Titan analog particles formed by methane photolysis.

  4. Isotope fractionation of benzene during partitioning - Revisited.

    PubMed

    Kopinke, F-D; Georgi, A; Imfeld, G; Richnow, H-H

    2017-02-01

    Isotope fractionation between benzene-D0 and benzene-D6 caused by multi-step partitioning of the benzenes between water and two organic solvents, n-octane and 1-octanol, as well as between water and the gas phase, was measured. The obtained fractionation factors αH = KH/KD are αH = 1.080 ± 0.015 and αH = 1.074 ± 0.015 for extraction into n-octane and 1-octanol, respectively, and αH = 1.049 ± 0.010 for evaporation from aqueous solution. The comparison of solvent- and gas-phase partitioning reveals that about 2/3 of the driving force of fractionation is due to different interactions in the aqueous phase, whereas 1/3 is due to different interactions in the organic phase. The heavy benzene isotopologue behaves more 'hydrophilically' and the light one more 'hydrophobically'. This synergistic alignment gives rise to relatively large fractionation effects in partitioning between water and non-polar organic matter. In contrast to a previous study, there is no indication of strong fractionation by specific interactions between benzene and octanol. Partitioning under non-equilibrium conditions yields smaller apparent fractionation effects due to opposite trends of thermodynamic and kinetic fractionation parameters, i.e. partition and diffusion coefficients of the isotopologues. This may have consequences which should be taken into account when considering isotope fractionation due to sorption in environmental compartments.

  5. Pollution characteristics and health risk assessment of benzene homologues in ambient air in the northeastern urban area of Beijing, China.

    PubMed

    Li, Lei; Li, Hong; Zhang, Xinmin; Wang, Li; Xu, Linghong; Wang, Xuezhong; Yu, Yanting; Zhang, Yujie; Cao, Guan

    2014-01-01

    Ambient benzene homologues were measured at a site in the northeastern urban area of Beijing, China, from August 24 to September 4, 2012 by SUMMA canister sampling followed by laboratory determination using cryogenic cold trap pre-concentration-GC-MS/FID, and their health risks were also assessed. Daily total benzene homologues ranged from 0.99 to 49.71 microg/m3 with an average of 11.98 microg/m3. Benzene homologues showed higher concentrations in the morning and evening than that at noontime. Comparison with previous studies revealed a trend of decrease for ambient benzene homologues probably due to the effective emission control in Beijing in recent years. Vehicular exhaust was the main source while volatilization of paints and solvents also made substantial contributions. Health risk assessment showed that BTEX (benzene, toluene, ethylbenzene, o-xylene, m-xylene and p-xylene) and styrene had no appreciable adverse non-cancer health risks for the exposed population, while benzene has potential cancer risk of 1.34E-05. Available data from cities in China all implied that benzene imposes relatively higher cancer risk on the exposed populations and therefore strict control measures should be taken to further lower ambient benzene levels in China.

  6. Urinary biomarkers of exposure and of oxidative damage in children exposed to low airborne concentrations of benzene.

    PubMed

    Andreoli, R; Spatari, G; Pigini, D; Poli, D; Banda, I; Goldoni, M; Riccelli, M G; Petyx, M; Protano, C; Vitali, M; Barbaro, M; Mutti, A

    2015-10-01

    The aim of this work was to evaluate the oxidative damage to nucleic acids in children (5-11 years) associated with exposure to environmental pollutants and tobacco smoke (ETS). For each subject, urinary sampling was done twice (evening and next morning) to measure by tandem LC-MS-MS such oxidated products of nucleic acids as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and 8-oxo-7,8-dihydroguanine (8-oxoGua). Methyl tert-butyl ether (U-MTBE), benzene (U-Benz), and its metabolites (t,t-muconic and S-phenylmercapturic acids, t,t-MA and S-PMA, respectively) were determined as biomarkers of exposure to air pollution, and cotinine as a biomarker of exposure to ETS. Biomarkers of exposure (S-PMA and U-MTBE) and of DNA oxidation (8-oxodGuo) were dependent on the urbanization and industrialization levels and increased in the evening sample as compared to next morning (p<0.05). In both evening and next morning samples, 8-oxodGuo and 8-oxoGuo correlated with each other (r=0.596 and r=0.537, respectively, p<0.01) and with biomarkers of benzene exposure, particularly S-PMA (r=0.59 and r=0.45 for 8-oxodGuo and r=0.411 and r=0.383 for 8-oxoGuo, p<0.01). No such correlations were observed for U-MTBE and cotinine. Multiple linear regression analyses showed that 8-oxodGuo was positively associated with S-PMA at both sampling times (β=0.18 and β=0.14 for evening and next morning sampling, respectively; p<0.02) and weakly with U-MTBE (β=0.07, p=0.020) only in the evening urines. These results suggest that the selected biomarkers of exposure to benzene, particularly S-PMA, are good tracers of exposure to complex mixtures of oxidative pollutants and that the associated oxidative damage to nucleic acids is detectable even at very low levels of exposure.

  7. Determination of benzene residues in recycled polyethylene terephthalate (PETE) by dynamic headspace-gas chromatography.

    PubMed

    Komolprasert, V; Hargraves, W A; Armstrong, D J

    1994-01-01

    A dynamic headspace-gas chromatography (HS/GC) method was developed to quantitate benzene in recycled PETE material derived from 21 PETE beverage bottles. The analytical system consisted of a purge-and-trap apparatus which was interfaced directly with a gas chromatograph/flame ionization detector. Cryofocusing and non-cryofocusing GC systems were used. The technique was applied to spiked PETE test samples which were prepared at various benzene concentrations ranging from 100 ppb to 117 ppm. The initial spiked benzene concentration in the PETE test samples was determined gravimetrically. The HS/GC technique was limited by the slow desorption rate of benzene from the PETE matrix; as a result, multipurges were performed at 60 degrees C. Regression analysis was done on the multipurge data to develop a desorption model which would predict the total amount of benzene in the PETE. The calculated results agreed with the experimental recoveries within +/- 10%. Recovery depended on the initial benzene level in the PETE and ranged from 70 to 90% after the first five purges.

  8. Anaerobic benzene oxidation via phenol in Geobacter metallireducens.

    PubMed

    Zhang, Tian; Tremblay, Pier-Luc; Chaurasia, Akhilesh Kumar; Smith, Jessica A; Bain, Timothy S; Lovley, Derek R

    2013-12-01

    Anaerobic activation of benzene is expected to represent a novel biochemistry of environmental significance. Therefore, benzene metabolism was investigated in Geobacter metallireducens, the only genetically tractable organism known to anaerobically degrade benzene. Trace amounts (<0.5 μM) of phenol accumulated in cultures of Geobacter metallireducens anaerobically oxidizing benzene to carbon dioxide with the reduction of Fe(III). Phenol was not detected in cell-free controls or in Fe(II)- and benzene-containing cultures of Geobacter sulfurreducens, a Geobacter species that cannot metabolize benzene. The phenol produced in G. metallireducens cultures was labeled with (18)O during growth in H2(18)O, as expected for anaerobic conversion of benzene to phenol. Analysis of whole-genome gene expression patterns indicated that genes for phenol metabolism were upregulated during growth on benzene but that genes for benzoate or toluene metabolism were not, further suggesting that phenol was an intermediate in benzene metabolism. Deletion of the genes for PpsA or PpcB, subunits of two enzymes specifically required for the metabolism of phenol, removed the capacity for benzene metabolism. These results demonstrate that benzene hydroxylation to phenol is an alternative to carboxylation for anaerobic benzene activation and suggest that this may be an important metabolic route for benzene removal in petroleum-contaminated groundwaters, in which Geobacter species are considered to play an important role in anaerobic benzene degradation.

  9. The enhanced spin-polarized transport behaviors through cobalt benzene-porphyrin-benzene molecular junctions: the effect of functional groups.

    PubMed

    Cheng, Jue-Fei; Zhou, Liping; Wen, Zhongqian; Yan, Qiang; Han, Qin; Gao, Lei

    2017-05-04

    The modification effects of the groups amino (NH2) and nitro (NO2) on the spin polarized transport properties of the cobalt benzene-porphyrin-benzene (Co-BPB) molecule coupled to gold (Au) nanowire electrodes are investigated by the nonequilibrium Green's function method combined with the density functional theory. The calculation results show that functional groups can lead to the significant spin-filter effect, enhanced low-bias negative differential resistance (NDR) behavior and novel reverse rectifying effect in Co-BPB molecular junction. The locations and types of functional groups have distinct influences on spin-polarized transport performances. The configuration with NH2 group substituting H atom in central porphyrin ring has larger spin-down current compared to that with NO2 substitution. And Co-BPB molecule junction with NH2 group substituting H atom in side benzene ring shows reverse rectifying effect. Detailed analyses confirm that NH2 and NO2 group substitution change the spin-polarized transferred charge, which makes the highest occupied molecular orbitals (HOMO) of spin-down channel of Co-BPB closer to the Fermi level. And the shift of HOMO strengthens the spin-polarized coupling between the molecular orbitals and the electrodes, leading to the enhanced spin-polarized behavior. Our findings might be useful in the design of multi-functional molecular devices in the future.

  10. Enzyme-catalysed synthesis and reactions of benzene oxide/oxepine derivatives of methyl benzoates.

    PubMed

    Boyd, Derek R; Sharma, Narain D; Harrison, John S; Malone, John F; McRoberts, W Colin; Hamilton, John T G; Harper, David B

    2008-04-07

    A series of twelve benzoate esters was metabolised, by species of the Phellinus genus of wood-rotting fungi, to yield the corresponding benzyl alcohol derivatives and eight salicylates. The isolation of a stable oxepine metabolite, from methyl benzoate, allied to evidence of the migration and retention of a carbomethoxy group (the NIH Shift), during enzyme-catalysed ortho-hydroxylation of alkyl benzoates to form salicylates, is consistent with a mechanism involving an initial arene epoxidation step. This mechanism was confirmed by the isolation of a remarkably stable, optically active, substituted benzene oxide metabolite of methyl 2-(trifluoromethyl)benzoate, which slowly converted into the racemic form. The arene oxide was found to undergo a cycloaddition reaction with 4-phenyl-1,2,4-triazoline-3,5-dione to yield a crystalline cycloadduct whose structure and racemic nature was established by X-ray crystallography. The metabolite was also found to undergo some novel benzene oxide reactions, including epoxidation to give an anti-diepoxide, base-catalysed hydrolysis to form a trans-dihydrodiol and acid-catalysed aromatisation to yield a salicylate derivative via the NIH Shift of a carbomethoxy group.

  11. Quantitative assessment of lives lost due to delay in the regulation of occupational exposure to benzene

    SciTech Connect

    Nicholson, W.J.; Landrigan, P.J. )

    1989-07-01

    Benzene exposure can cause leukemia, aplastic anemia, and possibly lymphoma. In 1978, on the basis of strong but incomplete data then available on the risk of benzene-induced leukemia, the U.S. Occupational Safety and Health Administration (OSHA) reduced the permissible occupational exposure standard for benzene from 10 ppm to 1 ppm. Shortly thereafter, the Fifth Circuit Court of Appeals stayed this ruling, and in 1980, the Supreme Court overturned the regulation, citing insufficient evidence of benefit. Thus, from 1978 until the standard was again lowered to 1 ppm in 1987, American workers were exposed to benzene at levels in excess of 1 ppm. An estimated 9600 were exposed to levels between 1 and 10 ppm, and an additional 370 were exposed at levels above 10 ppm. To assess the risk resulting from this delay in regulation, we have conducted an epidemiologic risk analysis. We merged data on numbers of persons (238,000) exposed to benzene in seven occupational categories with dose-response data from three epidemiologic studies. The range of risk in these studies indicates that 44 to 152 excess leukemia deaths will ultimately result from exposure to benzene at 10 ppm over a working lifetime (45 years) and that lower or briefer exposures will result in proportionately fewer deaths. On this basis, we calculated that between 30 and 490 excess leukemia deaths will ultimately result from occupational exposures to benzene greater than 1 ppm that occurred between 1978 and 1987. Deaths from aplastic anemia and lymphoma will likely add to this toll. These data confirm the risk of regulatory delay. They suggest that the courts, in reviewing public health regulations, must beware of facile cost-benefit arguments and be willing to accept strong evidence of health risk even when such evidence is incomplete.

  12. Effect of Initial Headspace O2 Level on the Growth and Volatile Metabolite Production of Leuconostoc Mesenteriodes and the Microbial and Sensorial Quality of Modified Atmosphere Packaged Par-Fried French Fries.

    PubMed

    Samapundo, Simbarashe; Mujuru, Felix Mugove; de Baenst, Ilse; Denon, Quenten; Devlieghere, Frank

    2016-02-01

    This study evaluated the effect of residual O2 level (0% to 5%) on microbial growth and volatile metabolite production on par-fried French fries packaged in a modified atmosphere with 60% CO2 (rest N2 ) at 4 °C. The results obtained showed that the initial headspace (IH) O2 level had an effect on growth of Leuconostoc mesenteroides on French fry simulation agar, whereby growth was slightly faster under 5% O2 . In terms of quantity, ethanol, 2-methyl-1-propanol, and dimethyl disulphide were the most significant volatile metabolites produced by L. mesenteroides. The production of ethanol by L. mesenteroides was highest on simulation agar packaged under low IH O2 levels (0% to 1%), indicating that the fermentative metabolism was induced under these conditions. In agreement with the results observed on the simulation medium, growth of native lactic acid bacteria was faster under an IH O2 level of 5%. In addition, ethanol, 2-methyl-1-propanol, and dimethyl disulphide were also quantitatively the most important volatile metabolites. However, in contrast, greater quantities of ethanol and dimethyl disulphide were produced on par-fried French fries packaged under 5% O2 . This was attributed to the limited growth of the native flora on the par-fried French fries under residual O2 levels of 0% and 1%. Although some significant differences (P < 0.05) occurred between the French fries packaged in 0%, 1%, and 5 % residual O2 during storage, all products were considered to be acceptable for consumption. The results of this study can be used to optimize the shelf-life of packaged chill stored potato products.

  13. Complicating factors in safety testing of drug metabolites: Kinetic differences between generated and preformed metabolites

    SciTech Connect

    Prueksaritanont, Thomayant . E-mail: thomayant_prueksaritanont@merck.com; Lin, Jiunn H.; Baillie, Thomas A.

    2006-12-01

    This paper aims to provide a scientifically based perspective on issues surrounding the proposed toxicology testing of synthetic drug metabolites as a means of ensuring adequate nonclinical safety evaluation of drug candidates that generate metabolites considered either to be unique to humans or are present at much higher levels in humans than in preclinical species. We put forward a number of theoretical considerations and present several specific examples where the kinetic behavior of a preformed metabolite given to animals or humans differs from that of the corresponding metabolite generated endogenously from its parent. The potential ramifications of this phenomenon are that the results of toxicity testing of the preformed metabolite may be misleading and fail to characterize the true toxicological contribution of the metabolite when formed from the parent. It is anticipated that such complications would be evident in situations where (a) differences exist in the accumulation of the preformed versus generated metabolites in specific tissues, and (b) the metabolite undergoes sequential metabolism to a downstream product that is toxic, leading to differences in tissue-specific toxicity. Owing to the complex nature of this subject, there is a need to treat drug metabolite issues in safety assessment on a case-by-case basis, in which a knowledge of metabolite kinetics is employed to validate experimental paradigms that entail administration of preformed metabolites to animal models.

  14. Large-scale evaluation of candidate genes identifies associations between DNA repair and genomic maintenance and development of benzene hematotoxicity

    PubMed Central

    Lan, Qing; Zhang, Luoping; Shen, Min; Jo, William J.; Vermeulen, Roel; Li, Guilan; Vulpe, Christopher; Lim, Sophia; Ren, Xuefeng; Rappaport, Stephen M.; Berndt, Sonja I.; Yeager, Meredith; Yuenger, Jeff; Hayes, Richard B.; Linet, Martha; Yin, Songnian; Chanock, Stephen; Smith, Martyn T.; Rothman, Nathaniel

    2009-01-01

    Benzene is an established human hematotoxicant and leukemogen but its mechanism of action is unclear. To investigate the role of single-nucleotide polymorphisms (SNPs) on benzene-induced hematotoxicity, we analyzed 1395 SNPs in 411 genes using an Illumina GoldenGate assay in 250 benzene-exposed workers and 140 unexposed controls. Highly significant findings clustered in five genes (BLM, TP53, RAD51, WDR79 and WRN) that play a critical role in DNA repair and genomic maintenance, and these regions were then further investigated with tagSNPs. One or more SNPs in each gene were associated with highly significant 10–20% reductions (P values ranged from 0.0011 to 0.0002) in the white blood cell (WBC) count among benzene-exposed workers but not controls, with evidence for gene–environment interactions for SNPs in BLM, WRN and RAD51. Further, among workers exposed to benzene, the genotype-associated risk of having a WBC count <4000 cells/μl increased when using individuals with progressively higher WBC counts as the comparison group, with some odds ratios >8-fold. In vitro functional studies revealed that deletion of SGS1 in yeast, equivalent to lacking BLM and WRN function in humans, caused reduced cellular growth in the presence of the toxic benzene metabolite hydroquinone, and knockdown of WRN using specific short hairpin RNA increased susceptibility of human TK6 cells to hydroquinone toxicity. Our findings suggest that SNPs involved in DNA repair and genomic maintenance, with particular clustering in the homologous DNA recombination pathway, play an important role in benzene-induced hematotoxicity. PMID:18978339

  15. Polyfunctional catalyst for processiing benzene fractions

    SciTech Connect

    G. Byakov; B.D. Zubitskii; B.G. Tryasunov; I.Ya. Petrov

    2009-05-15

    A by-product of the coke industry is a raw benzene fraction benzene- 1 which may serve as for catalytic processes. The paper reports a study on the influence of the composition and temperatures on the activity and selectivity of NiO-V{sub 2}O{sub 6}-MoO{sub 3}/{gamma}-Al{sub 2}O{sub 3} catalysts and the corresponding binary and tertiary subsystems are studied by a pulse method in model reactions; the hydrodealkylating of toluene and the hydrodesulfurizing of thioprhene. The optimal catalyst composition is established. The new catalyst is compared with industrial catalysts.

  16. The pyrolysis of toluene and ethyl benzene

    NASA Technical Reports Server (NTRS)

    Sokolovskaya, V. G.; Samgin, V. F.; Kalinenko, R. A.; Nametkin, N. S.

    1987-01-01

    The pyrolysis of toluene at 850 to 950 C gave mainly H2, CH4, and benzene; PhEt at 650 to 750 C gave mainly H2, CH4, styrene, benzene, and toluene. The rate constants for PhEt pyrolysis were 1000 times higher than those for toluene pyrolysis; the chain initiation rate constants differed by the same factor. The activation energy differences were 46 kJ/mole for the total reaction and 54 kJ/mole for chain initiation. The chain length was evaluated for the PhEt case (10 + or - 2).

  17. Carbon disulfide assisted polymerization of benzene.

    PubMed

    Zhou, Mi; Li, Zhanlong; Men, Zhiwei; Gao, Shuqin; Li, Zuowei; Lu, Guohui; Sun, Chenglin

    2012-03-01

    The chemical transformation of benzene (C(6)H(6)) and carbon disulfide (CS(2)) binary solution under high pressure condition is investigated by means of Raman spectroscopy up to 6.8 GPa. On increasing the pressure, all the Raman bands of benzene decrease in intensity, whereas new broad bands start to be observed at 1520 and 1450 cm(-1), indicating that a highly cross-linked polymer is formed. The recovered sample is analyzed through Raman and FT-IR spectroscopy and is identified as a saturated hydrocarbon and element sulfur.

  18. Benzene partial hydrogenation: advances and perspectives.

    PubMed

    Foppa, Lucas; Dupont, Jairton

    2015-04-07

    The partial hydrogenation of benzene to cyclohexene is an economically interesting and technically challenging reaction. Over the last four decades, a lot of work has been dedicated to the development of an exploitable process and several approaches have been investigated. However, environmental constraints often represent a limit to their industrial application, making further research in this field necessary. The goal of this review is to highlight the main findings of the different disciplines involved in understanding the governing principles of this reaction from a sustainable chemistry standpoint. Special emphasis is given to ruthenium-catalyzed liquid phase batch hydrogenation of benzene.

  19. Active Metabolites of Isoxazolylpenicillins in Humans

    PubMed Central

    Thijssen, H. H. W.; Mattie, H.

    1976-01-01

    Metabolites of the isoxazolylpenicillins that still possessed antibacterial activity were shown to be present in urine and serum. In healthy subjects, the amounts excreted in urine were low; 10 to 23% of the excreted penicillin activities represented the metabolites. The highest amount of metabolite in urine was found for oxacillin, and the lowest was found for flucloxacillin. No extreme differences in the amounts of metabolite excreted were observed when the compounds were administered orally or intravenously. In one healthy subject metabolite levels were estimated for cloxacillin in serum. Very low levels were found, i.e., about 9% of the activity. In subjects with highly impaired renal function, the metabolite may represent up to 50% of the total level of penicillin in serum. The antibacterial activities of the different metabolites were of the same order of magnitude as those of the respective parent compounds. Also, the activity against benzylpenicillin-resistant staphylococci was retained. It is not likely that the formation of the active metabolites should influence therapeutic results. PMID:825029

  20. Lymphocyte toxicity and T cell receptor excision circles in workers exposed to benzene.

    PubMed

    Lan, Qing; Zhang, Luoping; Hakim, Fran; Shen, Min; Memon, Sarfraz; Li, Guilan; Vermeulen, Roel; Smith, Martyn T; Rappaport, Stephen M; Hayes, Richard; Linet, Martha; Yin, Songnian; Rothman, Nathaniel; Rabkin, Charles S

    2005-05-30

    We have previously reported that benzene decreases peripheral white blood cell and platelet counts and specifically lowers subsets of several blood cell types, including CD4+-T cells, B cells, NK cells, and granulocytes. Diminished thymus function has been implicated as a mechanism for CD4+-T cell loss in other conditions such as AIDS by assays of T cell receptor excision circles (TRECs), a marker of naive T cells that have recently emigrated from the thymus. To evaluate alteration of thymic function as a mechanism for benzene's effects on CD4+-T cell counts, we measured total TREC levels in 45 benzene-exposed workers and 45 unexposed controls. There was no significant difference in TREC levels per 10(6) peripheral blood leukocytes in the benzene-exposed workers compared to the controls. Although our study does not rule out counterbalancing alterations of TREC levels in specific T cell subsets, benzene's lymphotoxicity does not appear to be mediated through diminished thymus function.

  1. Benzene and naphthalene in air and breath as indicators of exposure to jet fuel

    PubMed Central

    Egeghy, P; Hauf-Cabalo, L; Gibson, R; Rappaport, S

    2003-01-01

    Aims: To estimate exposures to benzene and naphthalene among military personnel working with jet fuel (JP-8) and to determine whether naphthalene might serve as a surrogate for JP-8 in studies of health effects. Methods: Benzene and naphthalene were measured in air and breath of 326 personnel in the US Air Force, who had been assigned a priori into low, moderate, and high exposure categories for JP-8. Results: Median air concentrations for persons in the low, moderate, and high exposure categories were 3.1, 7.4, and 252 µg benzene/m3 air, 4.6, 9.0, and 11.4 µg benzene/m3 breath, 1.9, 10.3, and 485 µg naphthalene/m3 air, and 0.73, 0.93, and 1.83 µg naphthalene/m3 breath, respectively. In the moderate and high exposure categories, 5% and 15% of the benzene air concentrations, respectively, were above the 2002 threshold limit value (TLV) of 1.6 mg/m3. Multiple regression analyses of air and breath levels revealed prominent background sources of benzene exposure, including cigarette smoke. However, naphthalene exposure was not unduly influenced by sources other than JP-8. Among heavily exposed workers, dermal contact with JP-8 contributed to air and breath concentrations along with several physical and environmental factors. Conclusions: Personnel having regular contact with JP-8 are occasionally exposed to benzene at levels above the current TLV. Among heavily exposed workers, uptake of JP-8 components occurs via both inhalation and dermal contact. Naphthalene in air and breath can serve as useful measures of exposure to JP-8 and uptake of fuel components in the body. PMID:14634191

  2. Investigating the effects of in utero benzene exposure on epigenetic modifications in maternal and fetal CD-1 mice.

    PubMed

    Philbrook, Nicola A; Winn, Louise M

    2015-11-15

    Exposure to the ubiquitous environmental pollutant benzene is positively correlated with leukemia in adults and may be associated with childhood leukemia following in utero exposure. While numerous studies implicate oxidative stress and DNA damage as playing a role in benzene-mediated carcinogenicity, emerging evidence suggests that alterations in epigenetic regulations may be involved. The present study aimed to determine whether DNA methylation and/or various histone modifications were altered following in utero benzene exposure in CD-1 mice. Global DNA methylation and promoter-specific methylation of the tumor suppressor gene, p15, were assessed. Additionally, levels of acetylated histones H3, H4, and H3K56, as well as methylated histones H3K9 and H3K27 were assessed by Western blotting. A significant decrease in global DNA methylation of maternal bone marrow was observed following benzene exposure; however no effect on global DNA methylation was detected in fetal livers. Additionally, no effect of benzene exposure was observed on p15 promoter methylation or any measured histone modifications in both maternal bone marrow and fetal livers. These results suggest that the methodology used in the present study did not reveal alterations in DNA methylation and histone modifications following in utero exposure to benzene; however further experimentation investigating these modifications at the whole genome/epigenome level, as well as at later stages of benzene-induced carcinogenesis, are warranted.

  3. A case report of motor neuron disease in a patient showing significant level of DDTs, HCHs and organophosphate metabolites in hair as well as levels of hexane and toluene in blood

    SciTech Connect

    Kanavouras, Konstantinos; Tzatzarakis, Manolis N.; Mastorodemos, Vasileios; Plaitakis, Andreas; Tsatsakis, Aristidis M.

    2011-11-15

    Motor neuron disease is a devastating neurodegenerative condition, with the majority of sporadic, non-familial cases being of unknown etiology. Several epidemiological studies have suggested that occupational exposure to chemicals may be associated with disease pathogenesis. We report the case of a patient developing progressive motor neuron disease, who was chronically exposed to pesticides and organic solvents. The patient presented with leg spasticity and developed gradually clinical signs suggestive of amyotrophic lateral sclerosis, which was supported by the neurophysiologic and radiological findings. Our report is an evidence based case of combined exposure to organochlorine (DDTs), organophosphate pesticides (OPs) and organic solvents as confirmed by laboratory analysis in samples of blood and hair confirming systematic exposure. The concentration of non-specific dialkylphosphates metabolites (DAPs) of OPs in hair (dimethyphopshate (DMP) 1289.4 pg/mg and diethylphosphate (DEP) 709.4 pg/mg) and of DDTs (opDDE 484.0 pg/mg, ppDDE 526.6 pg/mg, opDDD 448.4 pg/mg, ppDDD + opDDT 259.9 pg/mg and ppDDT 573.7 pg/mg) were considerably significant. Toluene and n-hexane were also detected in blood on admission at hospital and quantified (1.23 and 0.87 {mu}g/l, respectively), while 3 months after hospitalization blood testing was found negative for toluene and n-hexane and hair analysis was provided decrease levels of HCHs, DDTs and DAPs. -- Highlights: Black-Right-Pointing-Pointer Exposure to pesticides and organic solvents might be a risk factor for sporadic MND. Black-Right-Pointing-Pointer We report a patient who developed progressive upper and lower motor neuron disease. Black-Right-Pointing-Pointer The patient had a history of occupational exposure to pesticides and solvents. Black-Right-Pointing-Pointer High DDTs' levels and increased levels of DMP and DEP were measured in his hair. Black-Right-Pointing-Pointer The patients' exposure to chemicals might have played

  4. Resolving uncertainty in the spatial relationships between passive benzene exposure and risk of non-Hodgkin lymphoma

    PubMed Central

    Switchenko, Jeffrey M.; Bulka, Catherine; Ward, Kevin; Koff, Jean L.; Bayakly, A. Rana; Ryan, P. Barry; Waller, Lance A.; Flowers, Christopher R.

    2016-01-01

    Background Benzene is a known occupational carcinogen associated with increased risk of hematologic cancers, but the relationships between quantity of passive benzene exposure through residential proximity to toxic release sites, duration of exposure, lag time from exposure to cancer development, and lymphoma risk remain unclear. Methods We collected release data through the Environmental Protection Agency’s Toxics Release Inventory (TRI) from 1989 to 2003, which included location of benzene release sites, years when release occurred, and amount of release. We also collected data on incident cases of non-Hodgkin lymphoma (NHL) from the Georgia Comprehensive Cancer Registry (GCCR) for the years 1999–2008. We constructed distance-decay surrogate exposure metrics and Poisson and negative binomial regression models of NHL incidence to quantify associations between passive exposure to benzene and NHL risk and examined the impact of amount, duration of exposure, and lag time on cancer development. Akaike’s information criteria (AIC) were used to determine the scaling factors for benzene dispersion and exposure periods that best predicted NHL risk. Results Using a range of scaling factors and exposure periods, we found that increased levels of passive benzene exposure were associated with higher risk of NHL. The best fitting model, with a scaling factor of 4 kilometers (km) and exposure period of 1989–1993, showed that higher exposure levels were associated with increased NHL risk (Level 4 (1.1–160 kilograms (kg)) vs. Level 1: risk ratio 1.56 [1.44–1.68], Level 5 (>160 kg) vs. Level 1: 1.60 [1.48–1.74]). Conclusions Higher levels of passive benzene exposure are associated with increased NHL risk across various lag periods. Additional epidemiological studies are needed to refine these models and better quantify the expected total passive benzene exposure in areas surrounding release sites. PMID:26949112

  5. Peer Review Comments on the IRIS Assessment of Benzene

    EPA Pesticide Factsheets

    Attachment to IRIS file for benzene, January 19, 2000, RESPONSE TO THE PEER REVIEW COMMENTS, II. Extrapolation of the Benzene Inhalation Unit Risk Estimate to the Oral Route of Exposure (EPA/NCEA-W-0517, July 1999)

  6. Subcellular-level resolution MALDI-MS imaging of maize leaf metabolites by MALDI-linear ion trap-Orbitrap mass spectrometer

    DOE PAGES

    Korte, Andrew R.; Yandeau-Nelson, Marna D.; Nikolau, Basil J.; ...

    2015-01-25

    A significant limiting factor in achieving high spatial resolution for matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS) imaging is the size of the laser spot at the sample surface. We present modifications to the beam-delivery optics of a commercial MALDI-linear ion trap-Orbitrap instrument, incorporating an external Nd:YAG laser, beam-shaping optics, and an aspheric focusing lens, to reduce the minimum laser spot size from ~50 μm for the commercial configuration down to ~9 μm for the modified configuration. This improved system was applied for MALDI-MS imaging of cross sections of juvenile maize leaves at 5-μm spatial resolution using an oversampling method. Theremore » are a variety of different metabolites including amino acids, glycerolipids, and defense-related compounds were imaged at a spatial resolution well below the size of a single cell. Such images provide unprecedented insights into the metabolism associated with the different tissue types of the maize leaf, which is known to asymmetrically distribute the reactions of C4 photosynthesis among the mesophyll and bundle sheath cell types. The metabolite ion images correlate with the optical images that reveal the structures of the different tissues, and previously known and newly revealed asymmetric metabolic features are observed.« less

  7. Subcellular-level resolution MALDI-MS imaging of maize leaf metabolites by MALDI-linear ion trap-Orbitrap mass spectrometer

    SciTech Connect

    Korte, Andrew R.; Yandeau-Nelson, Marna D.; Nikolau, Basil J.; Lee, Young Jin

    2015-01-25

    A significant limiting factor in achieving high spatial resolution for matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS) imaging is the size of the laser spot at the sample surface. We present modifications to the beam-delivery optics of a commercial MALDI-linear ion trap-Orbitrap instrument, incorporating an external Nd:YAG laser, beam-shaping optics, and an aspheric focusing lens, to reduce the minimum laser spot size from ~50 μm for the commercial configuration down to ~9 μm for the modified configuration. This improved system was applied for MALDI-MS imaging of cross sections of juvenile maize leaves at 5-μm spatial resolution using an oversampling method. There are a variety of different metabolites including amino acids, glycerolipids, and defense-related compounds were imaged at a spatial resolution well below the size of a single cell. Such images provide unprecedented insights into the metabolism associated with the different tissue types of the maize leaf, which is known to asymmetrically distribute the reactions of C4 photosynthesis among the mesophyll and bundle sheath cell types. The metabolite ion images correlate with the optical images that reveal the structures of the different tissues, and previously known and newly revealed asymmetric metabolic features are observed.

  8. Benzene derivatives produced by Fusarium graminearum - Short communication.

    PubMed

    Ntushelo, Khayalethu; Setshedi, Itumeleng

    2015-06-01

    Using NMR spectroscopy benzene derivatives were detected in mycelia of Fusarium graminearum, a pathogen of wheat and maize. In previous studies F. graminearum was found to cause cancer to humans and benzene derivatives were detected in breath of cancer sufferers. Surprisingly, no study found benzene derivatives to be the cancerous agents in F. graminearum. In this study we detected benzene derivatives in F. graminearum and propose to study their role as cancer agents.

  9. A model to predict threshold concentrations for toxic effects of chlorinated benzenes in sediment

    SciTech Connect

    Fuchsman, P.C.; Duda, D.J.; Barber, T.R.

    1999-09-01

    A probabilistic model was developed to predict effects threshold concentrations for chlorinated benzenes in sediment. Based on published quantitative structure-activity relationships relating the toxicity of chlorinated benzenes to the degree of chlorination, congeners with the same number of chlorine substitutions were considered toxicologically equivalent. Hexachlorobenzene was excluded from the assessment based on a lack of aquatic toxicity at the water solubility limit. The equilibrium partitioning approach was applied in a probabilistic analysis to derive predicted effects thresholds (PETs) for each chlorinated benzene group, with model input distributions defined by published log K{sub ow} values and aquatic toxicity data extracted from the published literature. The probabilistic distributions of PETs generally increased with chlorination, with 20th percentile values ranging from 3.2 mg/kg{sub 1{degree}OC} for chlorobenzene to 67 mg/kg{sub 1%OC} for tetrachlorobenzene congeners. The toxicity of total chlorinated benzenes in sediment can be assessed by applying the PETs in a toxic index model, based on the assumption that multiple chlorinated benzene congeners will show approximately additive toxicity, as characteristic of nonpolar narcotic toxicants. The 20th percentile PET values are one to two orders of magnitude higher than published screening-level guidelines, suggesting that the screening-level guidelines will provide overly conservative assessments in most cases. Relevant spiked sediment toxicity data are very limited but seem consistent with the probabilistic model; additional testing could be conducted to confirm the model's predictions.

  10. Results of animal studies suggest a nonlinear dose-response relationship for benzene effects

    SciTech Connect

    Parodi, S.; Taningher, M. ); Lutz, W.K. ); Colacci, A.; Mazzullo, M.; Grilli, S. )

    1989-07-01

    Considering the very large industrial usage of benzene, studies in risk assessment aimed at the evaluation of carcinogenic risk at low levels of exposure are important. Animal data can offer indications about what could happen in humans and provide more diverse information than epidemiological data with respect to dose-response consideration. The authors have considered experiments investigating metabolism, short-term genotoxicity tests, DNA adduct formation, and carcinogenicity long-term tests. According to the different experiments, a saturation of benzene metabolism and benzene effects in terms of genotoxicity seems evident above 30 to 100 ppm. Below 30 to 60 ppm the initiating effect of benzene seems to be linear for a large interval of dosages, at least judging from DNA adduct formation. Potential lack of a promoting effect of benzene (below 10 ppm) could generate a sublinear response at nontoxic levels of exposure. This possibility was suggested by epidemiological data in humans and is not confirmed or excluded by their observations with animals.

  11. 46 CFR 153.1060 - Benzene.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Benzene. 153.1060 Section 153.1060 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo Procedures § 153.1060...

  12. Formation of Benzene in the Interstellar Medium

    NASA Technical Reports Server (NTRS)

    Jones, Brant M.; Zhang, Fangtong; Kaiser, Ralf I.; Jamal, Adeel; Mebel, Alexander M.; Cordiner, Martin A.; Charnley, Steven B.; Crim, F. Fleming (Editor)

    2010-01-01

    Polycyclic aromatic hydrocarbons and related species have been suggested to play a key role in the astrochemical evolution of the interstellar medium, but the formation mechanism of even their simplest building block-the aromatic benzene molecule-has remained elusive for decades. Here we demonstrate in crossed molecular beam experiments combined with electronic structure and statistical calculations that benzene (C6H6) can be synthesized via the barrierless, exoergic reaction of the ethynyl radical and 1,3- butadiene, C2H + H2CCHCHCH2 --> C6H6, + H, under single collision conditions. This reaction portrays the simplest representative of a reaction class in which aromatic molecules with a benzene core can be formed from acyclic precursors via barrierless reactions of ethynyl radicals with substituted 1,3-butadlene molecules. Unique gas-grain astrochemical models imply that this low-temperature route controls the synthesis of the very first aromatic ring from acyclic precursors in cold molecular clouds, such as in the Taurus Molecular Cloud. Rapid, subsequent barrierless reactions of benzene with ethynyl radicals can lead to naphthalene-like structures thus effectively propagating the ethynyl-radical mediated formation of aromatic molecules in the interstellar medium.

  13. 46 CFR 153.1060 - Benzene.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Benzene. 153.1060 Section 153.1060 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo Procedures § 153.1060...

  14. 46 CFR 153.1060 - Benzene.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Benzene. 153.1060 Section 153.1060 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo Procedures § 153.1060...

  15. 46 CFR 153.1060 - Benzene.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Benzene. 153.1060 Section 153.1060 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo Procedures § 153.1060...

  16. 46 CFR 153.1060 - Benzene.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Benzene. 153.1060 Section 153.1060 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo Procedures § 153.1060...

  17. Formation of benzene in the interstellar medium

    PubMed Central

    Jones, Brant M.; Zhang, Fangtong; Kaiser, Ralf I.; Jamal, Adeel; Mebel, Alexander M.; Cordiner, Martin A.; Charnley, Steven B.

    2011-01-01

    Polycyclic aromatic hydrocarbons and related species have been suggested to play a key role in the astrochemical evolution of the interstellar medium, but the formation mechanism of even their simplest building block—the aromatic benzene molecule—has remained elusive for decades. Here we demonstrate in crossed molecular beam experiments combined with electronic structure and statistical calculations that benzene (C6H6) can be synthesized via the barrierless, exoergic reaction of the ethynyl radical and 1,3-butadiene, C2H + H2CCHCHCH2 → C6H6 + H, under single collision conditions. This reaction portrays the simplest representative of a reaction class in which aromatic molecules with a benzene core can be formed from acyclic precursors via barrierless reactions of ethynyl radicals with substituted 1,3-butadiene molecules. Unique gas-grain astrochemical models imply that this low-temperature route controls the synthesis of the very first aromatic ring from acyclic precursors in cold molecular clouds, such as in the Taurus Molecular Cloud. Rapid, subsequent barrierless reactions of benzene with ethynyl radicals can lead to naphthalene-like structures thus effectively propagating the ethynyl-radical mediated formation of aromatic molecules in the interstellar medium. PMID:21187430

  18. Contrastive analysis of the Raman spectra of polychlorinated benzene: hexachlorobenzene and benzene.

    PubMed

    Zhang, Xian; Zhou, Qin; Huang, Yu; Li, Zhengcao; Zhang, Zhengjun

    2011-01-01

    Detection of persistent pollutants such as polychlorinated benzene in environment in trace amounts is challenging, but important. It is more difficult to distinguish homologues and isomers of organic pollutantd when present in trace amounts because of their similar physical and chemical properties. In this work we simulate the Raman spectra of hexachlorobenzene and benzene, and figure out the vibration mode of each main peak. The effect on the Raman spectrum of changing substituents from H to Cl is analyzed to reveal the relations between the Raman spectra of homologues and isomers of polychlorinated benzene, which should be helpful for distinguishing one kind of polychlorinated benzene from its homologues and isomers by surface enhanced Raman scattering.

  19. 40 CFR 721.1350 - Benzene, (1-methylethyl)(2-phenylethyl)-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Benzene, (1-methylethyl)(2-phenylethyl... Substances § 721.1350 Benzene, (1-methylethyl)(2-phenylethyl)-. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified as benzene,...

  20. 40 CFR 721.1187 - Bis(imidoethylene) benzene.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Bis(imidoethylene) benzene. 721.1187... Substances § 721.1187 Bis(imidoethylene) benzene. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance bis(imidoethylene)benzene (PMN P-93-1447) is subject to...

  1. 40 CFR 721.1350 - Benzene, (1-methylethyl)(2-phenylethyl)-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Benzene, (1-methylethyl)(2-phenylethyl... Substances § 721.1350 Benzene, (1-methylethyl)(2-phenylethyl)-. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified as benzene,...

  2. 40 CFR 721.1350 - Benzene, (1-methylethyl)(2-phenylethyl)-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Benzene, (1-methylethyl)(2-phenylethyl... Substances § 721.1350 Benzene, (1-methylethyl)(2-phenylethyl)-. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified as benzene,...

  3. 40 CFR 721.1187 - Bis(imidoethylene) benzene.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Bis(imidoethylene) benzene. 721.1187... Substances § 721.1187 Bis(imidoethylene) benzene. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance bis(imidoethylene)benzene (PMN P-93-1447) is subject to...

  4. 40 CFR 721.1210 - Benzene, (2-chloroethoxy)-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Benzene, (2-chloroethoxy)-. 721.1210... Substances § 721.1210 Benzene, (2-chloroethoxy)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as benzene, (2-chloroethoxy)- (PMN P-87-1471) is subject...

  5. 40 CFR 721.1187 - Bis(imidoethylene) benzene.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Bis(imidoethylene) benzene. 721.1187... Substances § 721.1187 Bis(imidoethylene) benzene. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance bis(imidoethylene)benzene (PMN P-93-1447) is subject to...

  6. 40 CFR 721.1210 - Benzene, (2-chloroethoxy)-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Benzene, (2-chloroethoxy)-. 721.1210... Substances § 721.1210 Benzene, (2-chloroethoxy)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as benzene, (2-chloroethoxy)- (PMN P-87-1471) is subject...

  7. 40 CFR 721.1350 - Benzene, (1-methylethyl)(2-phenylethyl)-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Benzene, (1-methylethyl)(2-phenylethyl... Substances § 721.1350 Benzene, (1-methylethyl)(2-phenylethyl)-. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified as benzene,...

  8. 40 CFR 721.1187 - Bis(imidoethylene) benzene.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Bis(imidoethylene) benzene. 721.1187... Substances § 721.1187 Bis(imidoethylene) benzene. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance bis(imidoethylene)benzene (PMN P-93-1447) is subject to...

  9. 40 CFR 721.1210 - Benzene, (2-chloroethoxy)-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Benzene, (2-chloroethoxy)-. 721.1210... Substances § 721.1210 Benzene, (2-chloroethoxy)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as benzene, (2-chloroethoxy)- (PMN P-87-1471) is subject...

  10. 40 CFR 721.1350 - Benzene, (1-methylethyl)(2-phenylethyl)-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Benzene, (1-methylethyl)(2-phenylethyl... Substances § 721.1350 Benzene, (1-methylethyl)(2-phenylethyl)-. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified as benzene,...

  11. 40 CFR 721.1210 - Benzene, (2-chloroethoxy)-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Benzene, (2-chloroethoxy)-. 721.1210... Substances § 721.1210 Benzene, (2-chloroethoxy)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as benzene, (2-chloroethoxy)- (PMN P-87-1471) is subject...

  12. 40 CFR 721.1210 - Benzene, (2-chloroethoxy)-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Benzene, (2-chloroethoxy)-. 721.1210... Substances § 721.1210 Benzene, (2-chloroethoxy)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as benzene, (2-chloroethoxy)- (PMN P-87-1471) is subject...

  13. 40 CFR 721.1187 - Bis(imidoethylene) benzene.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Bis(imidoethylene) benzene. 721.1187... Substances § 721.1187 Bis(imidoethylene) benzene. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance bis(imidoethylene)benzene (PMN P-93-1447) is subject to...

  14. 40 CFR 721.10028 - Disubstituted benzene metal salts (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Disubstituted benzene metal salts... Specific Chemical Substances § 721.10028 Disubstituted benzene metal salts (generic). (a) Chemical... as disubstituted benzene metal salts (PMNs P-01-901 and P-01-902) are subject to reporting under...

  15. 40 CFR 721.10028 - Disubstituted benzene metal salts (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Disubstituted benzene metal salts... Specific Chemical Substances § 721.10028 Disubstituted benzene metal salts (generic). (a) Chemical... as disubstituted benzene metal salts (PMNs P-01-901 and P-01-902) are subject to reporting under...

  16. 40 CFR 721.10028 - Disubstituted benzene metal salts (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Disubstituted benzene metal salts... Specific Chemical Substances § 721.10028 Disubstituted benzene metal salts (generic). (a) Chemical... as disubstituted benzene metal salts (PMNs P-01-901 and P-01-902) are subject to reporting under...

  17. 40 CFR 721.10028 - Disubstituted benzene metal salts (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Disubstituted benzene metal salts... Specific Chemical Substances § 721.10028 Disubstituted benzene metal salts (generic). (a) Chemical... as disubstituted benzene metal salts (PMNs P-01-901 and P-01-902) are subject to reporting under...

  18. 40 CFR 721.10028 - Disubstituted benzene metal salts (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Disubstituted benzene metal salts... Specific Chemical Substances § 721.10028 Disubstituted benzene metal salts (generic). (a) Chemical... as disubstituted benzene metal salts (PMNs P-01-901 and P-01-902) are subject to reporting under...

  19. Structure of the Sevoflurane-Benzene Complex as Determined by Chirped-Pulse Ftmw Spectroscopy

    NASA Astrophysics Data System (ADS)

    Seifert, Nathan A.; Zaleski, Daniel P.; Neill, Justin L.; Pate, Brooks H.; Lesarri, Alberto; Vallejo, Montserrat; Cocinero, Emilio J.; Castano, Fernando

    2012-06-01

    Following previous microwave studies on sevoflurane monomer by Suenram {et al.} and Vega-Toribio et al. we report the broadband rotational spectrum of sevoflurane clustered with benzene. The structure assigned is consistent with a C-H...π interaction between the benzene ring and the (CF_3)_2C-H hydrogen on sevoflurane. The spectrum of this species is complicated by the six-fold internal rotation of the benzene ring over the C_1 framework of sevoflurane. The six-fold tunneling falls into a high effective barrier case where there are several bound torsional levels. The tunneling spectrum has been successfully analyzed using the BELGI internal rotation program and a barrier to internal rotation of the benzene against sevoflurane of 32.5 cm-1 has been determined. Structural information about the complex has been obtained by studying the complex of sevoflurane with benzene-{d_1}. For this complex, six unique isomers are observed making it possible to determine the positions of the benzene H-atoms in the complex. Combination of these hydrogen r_s positions with the sevoflurane monomer r_s coordinates reported by Lesarri {et al.} results in a substitution structure in excellent agreement with the ab initio results. Finally, initial microwave results on two sevoflurane dimer species will also be presented. R. D. Suenram, D. J. Brugh, F. J. Lovas and C. Chu, 51st OSU Int. Symp. On Mol. Spectrosc., Columbus, OH, 1999, RB07. A. Vega-Toribio, A. Lesarri, R.D. Suenram, J. Grabow, 64th OSU Int. Symp. On Mol. Spectrosc., Columbus, OH, 2009, MH07. A. Lesarri, A. Vega-Toribio, R. D. Suenram, D. J. Brugh, J.-U. Grabow, Phys. Chem. Chem. Phys., 12, 9624-9631 (2010).

  20. A semiconductor gas sensor system for high throughput screening of heterogeneous catalysts for the production of benzene derivatives

    NASA Astrophysics Data System (ADS)

    Yamada, Yusuke; Ueda, Atsushi; Shioyama, Hiroshi; Maekawa, Toru; Kanda, Keisen; Suzuki, Kengo; Kobayashi, Tetsuhiko

    2005-01-01

    We used a semiconductor gas sensor system developed for odour discrimination for a rapid quantification of benzene derivatives which can be formed as the product of a catalytic reaction. Phenol can be obtained by the selective oxidation of benzene. The sensor system shows higher sensitivity to phenol than benzene. In particular, a SnO2 sensor sensitized with ZrO2 responds selectively to phenol. Aniline is provided as a reaction product between ammonia and benzene. The output signal of the gas sensor system increases when it is exposed to air containing aniline at the ppm level; on the other hand, the sensor output resulting from 1% ammonia in air does not increase so much. Cumene formation can be observed by the reaction of propane and benzene. The sensitivity of a SnO2 sensor sensitized with 12%SiO2-Al2O3 to cumene was about ten times higher than that to benzene. These results indicate that the semiconductor gas sensor system is useful for rapid screening of the catalyst for benzene functionalization.

  1. Assessment and prediction of exposure to benzene of filling station employees

    NASA Astrophysics Data System (ADS)

    Karakitsios, Spyros P.; Papaloukas, Costas L.; Kassomenos, Pavlos A.; Pilidis, Georgios A.

    In the present study, the exposure to benzene of employees working in two filling stations (one urban and one rural) was estimated, through the method of passive sampling. Additional data (30' measurements of benzene exposure through active sampling to employees dealing with different activities, meteorological and traffic data) were collected. The measurements campaign was performed in both summer and wintertime to determine the seasonal variation of the exposure pattern. In addition, a set of artificial neural networks (ANNs) was developed to predict benzene exposure pattern for the filling station employees based on active sampling data and the parameters related to the employees' exposure. The quantification of the contribution of each parameter to the overall exposure pattern was also attempted. The results showed that although vapour recovery technologies are installed in the refuelling systems and benzene emissions are significantly reduced compared to the past, filling station employees are still highly exposed to benzene (52-15 μg m -3). Benzene exposure is strongly correlated to car refuelling (exposure levels up to 85 μg m -3), while activities like car washing or working in cash machine inside an office contribute to lower exposure levels (up to 44 and 24 μg m -3 respectively). In rural filling station, exposure levels were in general lower compared to the urban ones, due to the smaller amount of gasoline that was traded and the absence of any significant traffic effect or urban background concentration. The developed ANN seemed to be a promising technique in the prediction of the exposure pattern giving very good results, and the quantification of the parameters affirmed the importance of the refueling procedure to the exposure levels.

  2. Pre- and post-catalyst-, fuel-, velocity- and acceleration-dependent benzene emission data of gasoline-driven EURO-2 passenger cars and light duty vehicles

    NASA Astrophysics Data System (ADS)

    Heeb, Norbert V.; Forss, Anna-Maria; Weilenmann, Martin

    The benzene emission characteristics of six gasoline-driven EURO-2 vehicles, three passenger cars and three light duty vehicles, have been determined by time-resolved chemical ionization mass spectrometry. Aliquots of the exhaust gas were monitored pre- and post-catalyst with two independently operating mass spectrometers. Each vehicle was driven with two different fuels having benzene contents of 1 and 2 vol%. Seven driving cycles—including the European (EDC) and the US (FTP-75) driving cycle—with a total driving time of about 8800 s were studied. Herein, we discuss the average emission characteristics of the entire fleet at transient driving in the velocity range of 0-150 km h -1. The conversion efficiencies of the involved catalytic systems were deduced from the pre- and post-catalyst data. On average, the vehicles showed optimal benzene conversion efficiencies (>95%) in the velocity range of 30-90 km h -1. When driving below 20 or above 100 km h -1 reduced benzene conversion was found (80-82%). No benzene conversion was observed when driving above 130 km h -1. In contrast, the post-catalyst benzene emissions exceeded those of the untreated exhaust gas by 19-49%. Thus on an average, benzene was formed across the catalysts under these conditions. In addition, the influence of the benzene content of the gasoline on the tail-pipe emissions was also studied. The use of the gasoline with 1 vol% benzene instead of 2 vol% induced a 20-30% reduction of the post-catalyst emissions when driving below 50 km h -1. The fuel effect became smaller above 100 km h -1 and was even negative at high engine load (>130 km h -1). Thus under these conditions, when benzene is formed across the catalyst, the amount of the emitted benzene was independent of the benzene level of the fuel.

  3. Using multi-walled carbon nanotubes as solid phase extraction adsorbents to determine dichlorodiphenyltrichloroethane and its metabolites at trace level in water samples by high performance liquid chromatography with UV detection.

    PubMed

    Zhou, Qingxiang; Xiao, Junping; Wang, Weidong

    2006-09-01

    Carbon nanotubes (CNTs) are a kind of new carbon-based nano-materials which have drawn great attention in many application fields. The potential of multi-walled carbon nanotubes (MWNTs) as solid-phase extraction (SPE) adsorbents for the preconcentration of environmental pollutants has been investigated in recent years. The goal of this work was to investigate the feasibility of MWNTs used as SPE adsorbents to enrich dichlorodiphenyltrichloroethane (DDT) and its metabolites including 1,1-dichloro-2,2-bis-(4'-chlorophenyl)ethane (DDD) and 1,1-dichloro-2,2-bis-(4'-chlorophenyl)ethane (DDE) at trace level which are typical persistent organic pollutants in environment. Parameters that maybe influence the extraction efficiency such as the eluent volume, sample flow rate, sample pH and the sample volume were optimized in detail. The experimental results showed the excellent linear relationship between peak area and the concentration of DDT and its metabolites over the range of 0.2-60 microg L(-1), and the precisions (RSD) were 2.3-2.5% under the optimal conditions. The detection limits of proposed method could reach 4-13 ng L(-1) based on the ratio of chromatographic signal to base line noise (S/N = 3). Satisfied results were achieved when the proposed method was applied to determine the four target compounds in realworld water samples with spiked recoveries over the range of 89.7-115.5%. All these facts indicated that MWCNTs as SPE packing materials coupled to HPLC was an excellent alternative for the routine analysis of DDT and its metabolites at trace level in environment.

  4. Environmental exposure to benzene, micronucleus formation and polymorphisms in DNA-repair genes: a pilot study.

    PubMed

    Angelini, Sabrina; Maffei, Francesca; Bermejo, Justo Lorenzo; Ravegnini, Gloria; L'insalata, Domenica; Cantelli-Forti, Giorgio; Violante, Francesco Saverio; Hrelia, Patrizia

    2012-03-18

    This report is part of a biomarker study conducted in an Italian population with exposure to environmental benzene ranging from 1.43 to 31.41 μg/m³ (values from personal sampling). DNA damage induced by benzene is the crucial mechanism of its genotoxicity, which leads to chronic benzene poisoning, haematotoxicity and leukaemia. Therefore, genetic variation in DNA-repair genes may modulate susceptibility to benzene-induced DNA damage. In light of this, the effects of polymorphisms in DNA-repair genes (APEX1, hOGG1, NBS1, XPD, XRCC1, and XRCC3) on micronucleus (MN) formation as a biomarker of early biological effects were evaluated. A significantly higher median MN frequency was recorded in traffic wardens than in controls. However, none of the analysed polymorphisms was significantly associated with the median MN frequency. A gene-gender interaction was observed for the APEX1 genotype. The APEX1 variant genotype was associated with significantly lower median MN frequency in men, not in women. Statistical analysis did not reveal any association between the score of the protective alleles - hypothetically pushing the pathway towards optimal DNA-damage repair - and MN. Even though there are some limitations in the study, our results indicate that the general population may be exposed to benzene concentrations higher than the threshold level for air-quality standards in the European Union of 10 μg/m³. Furthermore, urban traffic wardens are exposed to significantly higher levels of benzene than individuals spending most of the time indoors. This higher exposure may contribute to DNA damage, suggesting that benzene might be implicated both as an environmental and occupational risk factor in leukaemia and other haematological diseases. In conclusion, this study suggest the need for (i) regular monitoring of traffic wardens for possible exposure to benzene, as a precautionary step to reduce the associated health risks, and (ii) more comprehensive studies in order to

  5. Phytotoxicity of chlorinated benzenes to Typha angustifolia and Phragmites communis.

    PubMed

    Ma, Xingmao; Havelka, Megan M

    2009-02-01

    Healthy growth of plants is a prerequisite for successful application of phytoremediation technologies. Typha angustifolia and Phragmites communis are common wetland plants and have shown potential for phytoremediation of hexachlorobenzene (HCB). However, the lack of phytotoxicity data impedes their application in field sites. This study investigated the phytotoxicity of HCB, and its two metabolites: 1,3,5-trichlorobenzene (1,3,5-TCB) and 1,4-dichlorobenzene (1,4-DCB) to Typha and the phytotoxicity of 1,3,5-TCB to Phragmites. The phytotoxicity of 1,3,5-TCB is species-dependent, with Typha demonstrating significantly higher tolerance than Phragmites. The concentration of 1,3,5-TCB causing zero growth of Phragmites was determined to be 1575 mg TCB/kg dry sediment. The concentration has to be doubled to completely inhibit the growth of Typha. Adverse effects of chlorinated benzenes in sediments on Typha increased with decreasing chlorine atoms. The concentrations causing zero growth of Typha are 5765 mg HCB/kg dry soil, 3157 mg 1,3,5-TCB/kg dry soil, and 1325 mg 1,4-DCB/kg dry soil. The higher toxicity of 1,4-DCB than 1,3,5-TCB and HCB in sediment was ascribed to its higher availability and easiness to be taken up by plants. The conclusion was supported by both growth rate calculations and plant height measurements. (c) 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009.

  6. Levels of pros-methylimidazoleacetic acid: correlation with severity of Parkinson's disease in CSF of patients and with the depletion of striatal dopamine and its metabolites in MPTP-treated mice.

    PubMed

    Prell, G D; Khandelwal, J K; Burns, R S; Blandina, P; Morrishow, A M; Green, J P

    1991-01-01

    The cerebrospinal fluid (CSF) levels of pros-methylimidazoleacetic acid (p-MIAA) in thirteen medication-free patients with mild to moderate Parkinson's disease were highly correlated (Spearman's rho = 0.749, p less than 0.005) with the severity of signs of the disease as scored on the Columbia University Rating Scale. Levels of p-MIAA in males (n = 8) and females (n = 5) were each significantly correlated with scores of severity (rho = 0.78, p less than 0.05 and rho = 1.0, p less than 0.05, respectively). In C57BL/6 mice treated with 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP), levels of p-MIAA were significantly correlated with the depleted levels of dopamine (r = 0.85, p less than 0.01), homovanillic acid (r = 0.79, p less than 0.02), 3,4-dihydroxyphenylacetic acid (r = 0.84, p less than 0.01) and norepinephrine (r = 0.91, p less than 0.002) in striatum, but not in cortex of the same mice. No such correlations were observed in either striatum or cortex of saline-treated control mice. Mean levels of p-MIAA in CSF did not differ significantly between patients and age-matched controls; and mean levels of p-MIAA in striatum did not differ between MPTP-treated mice and controls. The simplest hypothesis to account for these strong correlations in the absence of differences in mean levels of p-MIAA is that accumulation of p-MIAA [or process(es) that govern its accumulation] influences a failing nigrostriatal system. It is also possible (in analogy with findings in other diseases and with other drugs) that measurements of the putative metabolite(s) of p-MIAA may distinguish the patients and the MPTP-treated mice from their respective controls. Elucidation of the processes that regulate formation and disposition of p-MIAA in brain and information on the neural effects of p-MIAA, its precursors and its putative metabolites may yield insight into factors that regulate the progression of Parkinson's disease, and may shed additional light on the cause(s) of this

  7. Benzene, benzo(a)pyrene, and lead in smoke from tobacco products other than cigarettes.

    PubMed Central

    Appel, B R; Guirguis, G; Kim, I S; Garbin, O; Fracchia, M; Flessel, C P; Kizer, K W; Book, S A; Warriner, T E

    1990-01-01

    Benzene, benzo(a)pyrene (BaP), and lead in mainstream smoke from cigars, roll-your-own (RYO) cigarette and pipe tobaccos were sampled to evaluate their potential health significance. Results with reference cigarettes were consistent with published values, providing support for the methodology employed. The emissions of benzene and BaP, expressed as mass emitted per gram of tobacco consumed, were similar for all products evaluated; for benzene, the mean values for cigars, RYO cigarette and pipe tobaccos were 156 +/- 52, 68 +/- 11, and 242 +/- 126 micrograms/g, respectively. Mean values for BaP were 42 +/- 7 and 48 +/- 4 ng/g for cigars and RYO cigarette tobacco, respectively. Lead values were below the limit of reliable quantitation in all cases. The mean benzene concentrations in a puff ranged from 1 to 2 x 10(5) micrograms/m3 for cigars, RYO cigarette and pipe tobaccos. For BaP, the puff concentration averaged about 60 micrograms/m3 for cigars and RYO cigarette tobacco. The results suggest that smoking cigars, pipes or RYO cigarettes leads to potential exposures which exceed the No Significant Risk levels of benzene and BaP set pursuant to California's Proposition 65. These tobacco products are now required to bear a health hazard warning when sold in California. We recommend that this be adopted as national policy. PMID:2327532

  8. THE INFLUENCE OF BENZENE AS A TRACE REACTANT IN TITAN AEROSOL ANALOGS

    SciTech Connect

    Trainer, Melissa G.; Sebree, Joshua A.; Heidi Yoon, Y.; Tolbert, Margaret A.

    2013-03-20

    Benzene has been detected in Titan's atmosphere by Cassini instruments, with concentrations ranging from sub-ppb in the stratosphere to ppm in the ionosphere. Sustained levels of benzene in the haze formation region could signify that it is an important reactant in the formation of Titan's organic aerosol. To date, there have not been laboratory investigations to assess the influence of benzene on aerosol properties. We report a laboratory study on the chemical composition of organic aerosol formed from C{sub 6}H{sub 6}/CH{sub 4}/N{sub 2} via far ultraviolet irradiation (120-200 nm). The compositional results are compared to those from aerosol generated by a more ''traditional Titan'' mixture of CH{sub 4}/N{sub 2}. Our results show that even a trace amount of C{sub 6}H{sub 6} (10 ppm) has significant impact on the chemical composition and production rates of organic aerosol. There are several pathways by which photolyzed benzene may react to form larger molecules, both with and without the presence of CH{sub 4}, but many of these reaction mechanisms are only beginning to be explored for the conditions at Titan. Continued work investigating the influence of benzene in aerosol growth will advance understanding of this previously unstudied reaction system.

  9. 54 FR 38044: National Emission Standards for Hazardous Air Pollutants; Benzene Emissions From Maleic Anhydride Plants, Ethylbenzene/Styrene Plants, Benzene Storage Vessels, Benzene Equipment Leaks, and Coke By- Product Recovery Plants

    EPA Pesticide Factsheets

    Final Rule on National Emission Standards for Hazardous Air Pollutants; Benzene Emissions From Maleic Anhydride Plants, Ethylbenzene/Styrene Plants, Benzene Storage Vessels, Benzene Equipment Leaks, and Coke By-Product Recovery Plants.

  10. Pulsed (13)C2-Acetate Protein-SIP Unveils Epsilonproteobacteria as Dominant Acetate Utilizers in a Sulfate-Reducing Microbial Community Mineralizing Benzene.

    PubMed

    Starke, Robert; Keller, Andreas; Jehmlich, Nico; Vogt, Carsten; Richnow, Hans H; Kleinsteuber, Sabine; von Bergen, Martin; Seifert, Jana

    2016-05-01

    In a benzene-degrading and sulfate-reducing syntrophic consortium, a clostridium affiliated to the genus Pelotomaculum was previously described to ferment benzene while various sulfate-reducing Deltaproteobacteria and a member of the Epsilonproteobacteria were supposed to utilize acetate and hydrogen as key metabolites derived from benzene fermentation. However, the acetate utilization network within this community was not yet unveiled. In this study, we performed a pulsed (13)C2-acetate protein stable isotope probing (protein-SIP) approach continuously spiking low amounts of acetate (10 μM per day) in addition to the ongoing mineralization of unlabeled benzene. Metaproteomics revealed high abundances of Clostridiales followed by Syntrophobacterales, Desulfobacterales, Desulfuromonadales, Desulfovibrionales, Archaeoglobales, and Campylobacterales. Pulsed acetate protein-SIP results indicated that members of the Campylobacterales, the Syntrophobacterales, the Archaeoglobales, the Clostridiales, and the Desulfobacterales were linked to acetate utilization in descending abundance. The Campylobacterales revealed the fastest and highest (13)C incorporation. Previous experiments suggested that the activity of the Campylobacterales was not essential for anaerobic benzene degradation in the investigated community. However, these organisms were consistently detected in various hydrocarbon-degrading and sulfate-reducing consortia enriched from the same aquifer. Here, we demonstrate that this member of the Campylobacterales is the dominant acetate utilizer in the benzene-degrading microbial consortium.

  11. Tangeretin and its metabolite 4′-hydroxytetramethoxyflavone attenuate EGF-stimulated cell cycle progression in hepatocytes; role of inhibition at the level of mTOR/p70S6K

    PubMed Central

    Cheng, Z; Surichan, S; Ruparelia, K; Arroo, R; Boarder, MR

    2011-01-01

    BACKGROUND AND PURPOSE The mechanisms by which the dietary compound tangeretin has anticancer effects may include acting as a prodrug, forming an antiproliferative product in cancer cells. Here we show that tangeretin also inhibits cell cycle progression in hepatocytes and investigate the role of its primary metabolite 4′-hydroxy-5,6,7,8-tetramethoxyflavone (4′-OH-TMF) in this effect. EXPERIMENTAL APPROACH We used epidermal growth factor (EGF)-stimulated rat hepatocytes, with [3H]-thymidine incorporation into DNA as an index of progression to S-phase of the cell cycle, and Western blots for phospho-proteins involved in the cell signalling cascade. KEY RESULTS Incubation of tangeretin with microsomes expressing CYP1A, or with hepatocytes, generated a primary product we identified as 4′-OH-TMF. Low micromolar concentrations of tangeretin or 4′-OH-TMF gave a concentration-dependent inhibition of EGF-stimulated progression to S-phase while having little effect on cell viability. To determine whether time for conversion of tangeretin to an active metabolite would enhance the inhibitory effect we used long pre-incubations; this reduced the inhibitory effect, in parallel with a reduction in the concentration of tangeretin. The EGF-stimulation of hepatocyte cell cycle progression requires signalling through Akt/mTOR/p70S6K kinase cascades. The tangeretin metabolite 4′-OH-TMF selectively inhibited S6K phosphorylation in the absence of significant inhibition of upstream Akt activity, suggesting an effect at the level of mTOR. CONCLUSIONS AND IMPLICATIONS Tangeretin and 4′-OH-TMF both inhibit cell cycle progression in primary hepatocytes. The inhibition of p70S6K phosphorylation by 4′-OH-TMF raises the possibility that inhibition of the mTOR pathway may contribute to the anticancer influence of a flavonoid-rich diet. PMID:21198542

  12. Structural basis of enzymatic benzene ring reduction.

    PubMed

    Weinert, Tobias; Huwiler, Simona G; Kung, Johannes W; Weidenweber, Sina; Hellwig, Petra; Stärk, Hans-Joachim; Biskup, Till; Weber, Stefan; Cotelesage, Julien J H; George, Graham N; Ermler, Ulrich; Boll, Matthias

    2015-08-01

    In chemical synthesis, the widely used Birch reduction of aromatic compounds to cyclic dienes requires alkali metals in ammonia as extremely low-potential electron donors. An analogous reaction is catalyzed by benzoyl-coenzyme A reductases (BCRs) that have a key role in the globally important bacterial degradation of aromatic compounds at anoxic sites. Because of the lack of structural information, the catalytic mechanism of enzymatic benzene ring reduction remained obscure. Here, we present the structural characterization of a dearomatizing BCR containing an unprecedented tungsten cofactor that transfers electrons to the benzene ring in an aprotic cavity. Substrate binding induces proton transfer from the bulk solvent to the active site by expelling a Zn(2+) that is crucial for active site encapsulation. Our results shed light on the structural basis of an electron transfer process at the negative redox potential limit in biology. They open the door for biological or biomimetic alternatives to a basic chemical synthetic tool.

  13. The thermal conductivity of benzene and toluene

    NASA Astrophysics Data System (ADS)

    Ramires, M. L. V.; Vieira Dos Santos, F. J.; Mardolcar, U. V.; de Castro, C. A. Nieto

    1989-09-01

    The thermal conductivity of liquid toluene and benzene was measured in the temperature range 298 to 370 K, near the saturation line, using an absolute transient hot-wire technique. The measurements were made in a modified version of an existing instrument, equipped with a new automatic Wheatstone bridge, computer controlled. The bridge measures the time that the resistance of a 7- μm-diameter platinum wire takes to reach predetermined values, programmed by the computer. The computer can generate up to 1024 analog voltages, via a 12-bit D/A converter. The accuracy of the measurements with this new arrangement was assessed by measuring the thermal conductivity of a primary standard, toluene, at several temperatures and was found to be of the order of 0.3%. Benzene was chosen because it is under study as a possible secondary standard for liquid thermal conductivity by the Subcommittee on Transport Properties of IUPAC.

  14. Risk analysis for worker exposure to benzene

    NASA Astrophysics Data System (ADS)

    Hallenbeck, William H.; Flowers, Roxanne E.

    1992-05-01

    Cancer risk factors (characterized by route, dose, dose rate per kilogram, fraction of lifetime exposed, species, and sex) were derived for workers exposed to benzene via inhalation or ingestion. Exposure at the current Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) and at leaking underground storage tank (LUST) sites were evaluated. At the current PEL of 1 ppm, the theoretical lifetime excess risk of cancer from benzene inhalation is ten per 1000. The theoretical lifetime excess risk for worker inhalation exposure at LUST sites ranged from 10 to 40 per 1000. These results indicate that personal protection should be required. The theoretical lifetime excess risk due to soil ingestion is five to seven orders of magnitude less than the inhalation risks.

  15. Health risk assessment for exposure to benzene in petroleum refinery environments.

    PubMed

    Edokpolo, Benjamin; Yu, Qiming Jimmy; Connell, Des

    2015-01-12

    The health risk resulting from benzene exposure in petroleum refineries was calculated using data from the scientific literature from various countries throughout the world. The exposure data was collated into four scenarios from petroleum refinery environments and plotted as cumulative probability distributions (CPD) plots. Health risk was evaluated for each scenario using the Hazard Quotient (HQ) at 50% (CEXP50) and 95% (CEXP95) exposure levels. Benzene levels were estimated to pose a significant risk with HQ50 > 1 and HQ95 > 1 for workers exposed to benzene as base estimates for petroleum refinery workers (Scenario 1), petroleum refinery workers evaluated with personal samplers in Bulgarian refineries (Scenario 2B) and evaluated using air inside petroleum refineries in Bulgarian refineries (Scenario 3B). HQ50 < 1 were calculated for petroleum refinery workers with personal samplers in Italian refineries (Scenario 2A), air inside petroleum refineries (Scenario 3A) and air outside petroleum refineries (Scenario 4) in India and Taiwan indicating little possible adverse health effects. Also, HQ95 was < 1 for Scenario 4 however potential risk was evaluated for Scenarios 2A and 3A with HQ95 > 1. The excess Cancer risk (CR) for lifetime exposure to benzene for all the scenarios was evaluated using the Slope Factor and Overall Risk Probability (ORP) methods. The result suggests a potential cancer risk for exposure to benzene in all the scenarios. However, there is a higher cancer risk at 95% (CEXP95) for petroleum refinery workers (2B) with a CR of 48,000 per 106 and exposure to benzene in air inside petroleum refineries (3B) with a CR of 28,000 per 106.

  16. Mean fecal glucocorticoid metabolites are associated with vigilance, whereas immediate cortisol levels better reflect acute anti-predator responses in meerkats.

    PubMed

    Voellmy, Irene K; Goncalves, Ines Braga; Barrette, Marie-France; Monfort, Steven L; Manser, Marta B

    2014-11-01

    Adrenal hormones likely affect anti-predator behavior in animals. With experimental field studies, we first investigated associations between mean fecal glucocorticoid metabolite (fGC) excretion and vigilance and with behavioral responses to alarm call playbacks in free-ranging meerkats (Suricata suricatta). We then tested how vigilance and behavioral responses to alarm call playbacks were affected in individuals administered exogenous cortisol. We found a positive association between mean fGC concentrations and vigilance behavior, but no relationship with the intensity of behavioral responses to alarm calls. However, in response to alarm call playbacks, individuals administered cortisol took slightly longer to resume foraging than control individuals treated with saline solution. Vigilance behavior, which occurs in the presence and absence of dangerous stimuli, serves to detect and avoid potential dangers, whereas responses to alarm calls serve to avoid immediate predation. Our data show that mean fGC excretion in meerkats was associated with vigilance, as a re-occurring anti-predator behavior over long time periods, and experimentally induced elevations of plasma cortisol affected the response to immediate threats. Together, our results indicate an association between the two types of anti-predator behavior and glucocorticoids, but that the underlying mechanisms may differ. Our study emphasizes the need to consider appropriate measures of adrenal activity specific to different contexts when assessing links between stress physiology and different anti-predator behaviors.

  17. Investigation of the feasibility of TiO(2) nanotubes for the enrichment of DDT and its metabolites at trace levels in environmental water samples.

    PubMed

    Zhou, Qingxiang; Ding, Yujie; Xiao, Junping; Liu, Guoguang; Guo, Xiaoyang

    2007-04-13

    TiO(2) nanotubes, novel nanomaterials synthesized from hydrothermal treatment, were investigated for being used as a new solid-phase extraction adsorbent with o,p'-DDT, [1,1,1-trichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane, p,p'-DDT, [1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane] and its principle metabolites p,p'-DDD, [1,1-dichloro-2,2-bis(4-chlorophenyl)ethane] and p,p'-DDE [1,1-(2,2-dichloro-ethanylidene)-bis(4-chlorobenzene)] as the target analytes. Several factors such as eluant and its volume, the sample pH, sample volume and the flow rate of samples, were optimized. The effect of humic acid, which is often present in natural water system, was also investigated. Under the optimal conditions, lower detection limits of 0.0031, 0.0037, 0.0053 and 0.0025 ng mL(-1) for p,p'-DDD, p,p'-DDT, o,p'-DDT and p,p'-DDE, respectively, were obtained. The proposed method was successfully applied to the analysis of the target compounds in several environmental water samples. Good recoveries over the range of 81.2-115% were obtained. These results indicated that titanium nanotubes had enormous potential in environmental field as a novel SPE adsorbent material.

  18. Determination of plasma and urine levels of Delta9-tetrahydrocannabinol and its main metabolite by liquid chromatography after solid-phase extraction.

    PubMed

    Mercolini, Laura; Musenga, Alessandro; Comin, Irene; Baccini, Cesare; Conti, Matteo; Raggi, Maria Augusta

    2008-05-12

    Delta9-Tetrahydrocannabinol is the most widespread drug of abuse in the world and it is also currently available as the active principle of formulations for the treatment of chronic pain. Its main metabolite, 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid, is the most important marker of Delta9-tetrahydrocannabinol consumption. An original liquid chromatographic method has been developed for the determination of these two analytes in human plasma and urine. Separation was obtained on a C8 column using a mobile phase with 35% phosphate buffer at pH 2.7 and 65% acetonitrile. The UV detector was set at 220 nm and indomethacin was used as the internal standard. Sample pre-treatment was carried out by solid-phase extraction with C8 cartridges; urine samples were subjected to basic hydrolysis before extraction. Both extraction yields (>91%) and precision values were highly satisfactory. The method was successfully applied to biological samples collected from Cannabis users. Accuracy and selectivity results were satisfactory. This is the first HPLC-UV method developed for the simultaneous quantification of Delta9-tetrahydrocannabinol and 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid in both plasma and urine for the monitoring of either therapeutic or recreational use.

  19. Test of electron beam technology on Savannah River Laboratory low-activity aqueous waste for destruction of benzene, benzene derivatives, and bacteria

    SciTech Connect

    Dougal, R.A.

    1993-08-01

    High energy radiation was studied as a means for destroying hazardous organic chemical wastes. Tests were conducted at bench scale with a {sup 60}Co source, and at full scale (387 l/min) with a 1.5 MV electron beam source. Bench scale tests for both benzene and phenol included 32 permutations of water quality factors. For some water qualities, as much as 99.99% of benzene or 90% of phenol were removed by 775 krads of {sup 60}Co irradiation. Full scale testing for destruction of benzene in a simulated waste-water mix showed loss of 97% of benzene following an 800 krad dose and 88% following a 500 krad dose. At these loss rates, approximately 5 Mrad of electron beam irradiation is required to reduce concentrations from 100 g/l to drinking water quality (5 {mu}g/l). Since many waste streams are also inhabited by bacterial populations which may affect filtering operations, the effect of irradiation on those populations was also studied. {sup 60}Co and electron beam irradiation were both lethal to the bacteria studied at irradiation levels far lower than were necessary to remove organic contaminants.

  20. The Self-Assembly Properties of a Benzene-1,3,5-tricarboxamide Derivative

    ERIC Educational Resources Information Center

    Stals, Patrick J. M.; Haveman, Jan F.; Palmans, Anja R. A.; Schenning, Albertus P. H. J.

    2009-01-01

    A series of experiments involving the synthesis and characterization of a benzene-1,3,5-tricarboxamide derivative and its self-assembly properties are reported. These laboratory experiments combine organic synthesis, self-assembly, and physical characterization and are designed for upper-level undergraduate students to introduce the topic of…

  1. Benzene contamination at a metal plating facility

    NASA Astrophysics Data System (ADS)

    Memon, B. A.; Burston, M. R.

    2005-08-01

    A metal plating facility in central Kentucky was required to complete a RCRA Facility Investigation to address a number of Solid Waste Management Units at the site. Twenty monitoring wells were installed at the facility. Ground water from the wells was sampled for total and dissolved metals, polychlorinated biphenyls, acid extractable compounds, base neutral compounds, and volatile organic compounds. Unexpectedly, relatively large concentrations of benzene, up to 120 μg/l, were detected in samples from some of the wells, including wells that should have been hydraulically upgradient from the facility. As a result of the detection of benzene, the facility completed an investigation to identify the source. A nearby facility had completed a gasoline underground storage tank (UST) closure at about the time of the installation of the 20 wells. Reportedly the UST had small holes when removed. Three potential pathways of migration (a ditch, sanitary sewer, and a sink hole) from the nearby facility to the metal-plating facility and residual soils with very large concentrations of benzene, toluene, ethylbenzene, and xylenes have been identified.

  2. Matrix-free UV-laser desorption/ionization (LDI) mass spectrometric imaging at the single-cell level: distribution of secondary metabolites of Arabidopsis thaliana and Hypericum species.

    PubMed

    Hölscher, Dirk; Shroff, Rohit; Knop, Katrin; Gottschaldt, Michael; Crecelius, Anna; Schneider, Bernd; Heckel, David G; Schubert, Ulrich S; Svatos, Ales

    2009-12-01

    The present paper describes matrix-free laser desorption/ionisation mass spectrometric imaging (LDI-MSI) of highly localized UV-absorbing secondary metabolites in plant tissues at single-cell resolution. The scope and limitations of the method are discussed with regard to plants of the genus Hypericum. Naphthodianthrones such as hypericin and pseudohypericin are traceable in dark glands on Hypericum leaves, placenta, stamens and styli; biflavonoids are also traceable in the pollen of this important phytomedical plant. The highest spatial resolution achieved, 10 microm, was much higher than that achieved by commonly used matrix-assisted laser desorption/ionization (MALDI) imaging protocols. The data from imaging experiments were supported by independent LDI-TOF/MS analysis of cryo-sectioned, laser-microdissected and freshly cut plant material. The results confirmed the suitability of combining laser microdissection (LMD) and LDI-TOF/MS or LDI-MSI to analyse localized plant secondary metabolites. Furthermore, Arabidopsis thaliana was analysed to demonstrate the feasibility of LDI-MSI for other commonly occurring compounds such as flavonoids. The organ-specific distribution of kaempferol, quercetin and isorhamnetin, and their glycosides, was imaged at the cellular level.

  3. [The influence of N-stearoylethanolamine on the activity of antioxidant enzymes and on the level of stable NO metabolites in the rat testes and blood plasma at the early stages of streptozotocine-induced diabetes].

    PubMed

    Gorid'ko, T M; Kosiakova, H V; Berdyshev, A H; Bazylians'ka, V R; Margitych, V M; Gula, N M

    2012-01-01

    The influence of N-stearoylethanolamine was investigated on the activity of enzymes of antioxidant protection and content of stable metabolites of nitric oxide (NO) in the testes and plasma of rats at the early stages of development of streptozotocine-induced diabetes mellitus. It was shown that the activity of superoxide dismutase, catalase is reduced in the plasma and testes of animals with streptozotocin-induced (50 mg/kg) diabetes (blood glucose 8-10 mmol/L). A significant increase in the amount of nitrite and nitrate anions was revealed in the plasma of rats, while only the level of nitrite was significantly changed in the testes of animals. The per os administration of the NSE aqueous suspension in a dose of 50 mg/kg during 10 days to the rats with induced diabetes contributed to the normalization of catalase activity in the testis, which correlated with a decrease in the amount of TBA-reacting products and activity of superoxide dismutase and catalase in the blood plasma of animals; the use of NSE also contributed to the reduction of nitrite content in the gonads and to normalization of both nitrite and nitrate in the blood plasma of rats. The NSE administration to intact animals caused an increase in superoxide dismutase activity and significantly reduced the content of stable NO metabolites in the blood plasma of animals.

  4. At-line benzene monitor for measuring benzene in precipitate hydrolysis aqueous

    SciTech Connect

    Jenkins, W.J.

    1992-10-14

    A highly accurate and repeatable at-line benzene monitor (ALBM) has been developed to measure the benzene concentration in precipitate hydrolysis aqueous (PHA) in the DWPF. This analyzer was conceived and jointly developed within SRTC by the Analytical Development and the Defense Waste Process Technology Sections with extensive support from the Applied Statistics Group and the TNX Operations Section. It is recommended that an ALBM specifically adapted to DWPF analytical requirements be used to measure benzene in PHA; calibrations be performed using a 10% methanol solution matrix (for standard stability); and based on experience gained in development at TNX, the services of ADS and ASG be employed to both adapt the ALBM to DWPF requirements and develop statistical control procedures.

  5. Health Risk Assessment of Inhalation Exposure to Formaldehyde and Benzene in Newly Remodeled Buildings, Beijing

    PubMed Central

    Huang, Lihui; Mo, Jinhan; Sundell, Jan; Fan, Zhihua; Zhang, Yinping

    2013-01-01

    Objective To assess health risks associated with inhalation exposure to formaldehyde and benzene mainly emitted from building and decoration materials in newly remodeled indoor spaces in Beijing. Methods We tested the formaldehyde and benzene concentrations in indoor air of 410 dwellings and 451 offices remodeled within the past year, in which the occupants had health concerns about indoor air quality. To assess non-carcinogenic health risks, we compared the data to the health guidelines in China and USA, respectively. To assess carcinogenic health risks, we first modeled indoor personal exposure to formaldehyde and benzene using the concentration data, and then estimated the associated cancer risks by multiplying the indoor personal exposure by the Inhalation Unit Risk values (IURs) provided by the U.S. EPA Integrated Risk Information System (U.S. EPA IRIS) and the California Office of Environmental Health Hazard Assessment (OEHHA), respectively. Results (1) The indoor formaldehyde concentrations of 85% dwellings and 67% offices were above the acute Reference Exposure Level (REL) recommended by the OEHHA and the concentrations of all tested buildings were above the chronic REL recommended by the OEHHA; (2) The indoor benzene concentrations of 12% dwellings and 32% offices exceeded the reference concentration (RfC) recommended by the U.S. EPA IRIS; (3) The median cancer risks from indoor exposure to formaldehyde and benzene were 1,150 and 106 per million (based on U.S. EPA IRIS IURs), 531 and 394 per million (based on OEHHA IURs). Conclusions In the tested buildings, formaldehyde exposure may pose acute and chronic non-carcinogenic health risks to the occupants, whereas benzene exposure may pose chronic non-carcinogenic risks to the occupants. Exposure to both compounds is associated with significant carcinogenic risks. Improvement in ventilation, establishment of volatile organic compounds (VOCs) emission labeling systems for decorating and refurbishing materials