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Sample records for benzene metabolite levels

  1. Prolonged ethanol ingestion enhances benzene myelotoxicity and lowers urinary concentrations of benzene metabolite levels in CD-1 male mice.

    PubMed

    Marrubini, Giorgio; Castoldi, Anna F; Coccini, Teresa; Manzo, Luigi

    2003-09-01

    Benzene toxicity is attributed to its metabolism, which is primarily mediated by the ethanol-inducible cytochrome P450 2E1 isoform (CYP2E1). The present study investigated the myelotoxicity and urinary concentrations of major benzene metabolites in adult CD-1 male mice treated with low levels of benzene vapors, ethanol, or a combination of the two. Groups of ethanol-treated (5% in a Lieber-DeCarli liquid diet, 3 weeks) or pair-fed control mice were exposed to 10 ppm benzene, 6 h per day, 5 days per week for 2 weeks, starting from the second week of ethanol administration. On the last day of treatment, the number of early and late erythroid progenitors (BFU-E and CFU-E) was reduced by 55%, while the number of granulocyte/macrophage progenitors (CFU-GM) was reduced by 36% in benzene-treated mice. Ethanol lowered the CFU-E, BFU-E, and CFU-GM colony formation by 33, 28, and 12%, respectively. In animals coexposed to benzene and ethanol, the CFU-E colony counts were decreased by 70%, the BFU-E by 80%, and the CFU-GM by 45%. Phenol (Ph), hydroquinone (HQ), catechol (Cat), and trans,trans-muconic acid (MA) were measured by HPLC-UV in urine samples collected weekly during the last 6-h benzene/air exposure session. In benzene-exposed mice urinary metabolite levels peaked at the end of the first week of treatment (microg/kg body weight (bw): Ph: 4931 +/- 1055; Cat: 109 +/- 17; HQ: 784 +/- 137; MA: 534 +/- 92) and significantly decreased at the end of the second week (microg/kg bw: Ph: 3909 +/- 984; Cat: 82 +/- 24; HQ: 337 +/- 72; MA: 235 +/- 55). In mice given benzene and ethanol, the urinary levels of Ph, Cat, HQ, and MA were significantly lower than those measured in the group given benzene alone. The urinary levels of Ph and Cat showed a decreasing trend, again, from the first to the second week of benzene exposure. These data indicate that chronic ethanol ingestion exacerbates benzene myelotoxicity and, in addition, reduces the urinary excretion of benzene metabolites in

  2. Polyphenolic metabolites in the blood and bone marrow of mice exposed to low levels of benzene

    SciTech Connect

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

    1996-12-31

    Exposure to benzene can cause an increased incidence of leukemia in humans, possibly through the formation of polyphenolic metabolites. To define exposure-dose relationships, male B6C3F1 mice were exposed by inhalation for 6 hr to benzene at 60 ppm or {sup 13}C-benzene at 8 ppm. Levels of phenol, catechol, and hydroquinone were measured in blood and bone marrow by gas chromatography/mass spectrometry, and compared with unexposed controls. Levels of all three metabolites, after background correction, were significantly increased in both the blood and bone marrow of the mice exposed to 60 ppm relative to those exposed to 8 ppm. However, levels of the {sup 13}C metabolites in blood and bone marrow were consistently lower than background levels of the equivalent {sup 12}C polyphenolics in unexposed controls. These results demonstrate that single exposures of benzene of less than 10 ppm add little to the blood and bone marrow burdens of polyphenolic metabolites.

  3. 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.

  4. The effect of dose, dose rate, route of administration, and species on tissue and blood levels of benzene metabolites.

    PubMed Central

    Henderson, R F; Sabourin, P J; Bechtold, W E; Griffith, W C; Medinsky, M A; Birnbaum, L S; Lucier, G W

    1989-01-01

    Studies were completed in F344/N rats and B6C3F1 mice to determine the effect of dose, dose rate, route of administration, and rodent species on formation of total and individual benzene metabolites. Oral doses of 50 mg/kg or higher saturated the capacity for benzene metabolism in both rats and mice, resulting in an increased proportion of the administered dose being exhaled as benzene. The saturating air concentration for benzene metabolism during 6-hr exposures was between 130 and 900 ppm. At the highest exposure concentration, rats exhaled approximately half of the internal dose retained at the end of the 6-hr exposure as benzene; mice exhaled only 15% as benzene. Mice were able to convert more of the inhaled benzene to metabolites than were rats. In addition, mice metabolized more of the benzene by pathways leading to the putative toxic metabolites, benzoquinone and muconaldehyde, than did rats. In both rats and mice, the effect of increasing dose, administered orally or by inhalation, was to increase the proportion of the total metabolites that were the products of detoxification pathways relative to the products of pathways leading to putative toxic metabolites. This indicates low-affinity, high-capacity pathways for detoxification and high-affinity, low-capacity pathways leading to putative toxic metabolites. If the results of rodent studies performed at high doses were used to assess the health risk at low-dose exposures to benzene, the toxicity of benzene would be underestimated. PMID:2792053

  5. 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. PMID:27016252

  6. Benzene toxicokinetics in humans: exposure of bone marrow to metabolites.

    PubMed Central

    Watanabe, K H; Bois, F Y; Daisey, J M; Auslander, D M; Spear, R C

    1994-01-01

    A three compartment physiologically based toxicokinetic model was fitted to human data on benzene disposition. Two separate groups of model parameter derivations were obtained, depending on which data sets were being fitted. The model was then used to simulate five environmental or occupational exposures. Predicted values of the total bone marrow exposure to benzene and cumulative quantity of metabolites produced by the bone marrow were generated for each scenario. The relation between cumulative quantity of metabolites produced by the bone marrow and continuous benzene exposure was also investigated in detail for simulated inhalation exposure concentrations ranging from 0.0039 ppm to 150 ppm. At the level of environmental exposures, no dose rate effect was found for either model. The occupational exposures led to only slight dose rate effects. A 32 ppm exposure for 15 minutes predicted consistently higher values than a 1 ppm exposure for eight hours for the total exposure of bone marrow to benzene and the cumulative quantity of metabolites produced by the bone marrow. The general relation between the cumulative quantity of metabolites produced by the bone marrow and the inhalation concentration of benzene is not linear. An inflection point exists in some cases leading to a slightly S shaped curve. At environmental levels (0.0039-10 ppm) the curve bends upward, and it saturates at high experimental exposures (greater than 100 ppm). PMID:8044234

  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. Peroxidase-dependent metabolism of benzene's phenolic metabolites and its potential role in benzene toxicity and carcinogenicity.

    PubMed Central

    Smith, M T; Yager, J W; Steinmetz, K L; Eastmond, D A

    1989-01-01

    The metabolism of two of benzene's phenolic metabolites, phenol and hydroquinone, by peroxidase enzymes has been studied in detail. Studies employing horseradish peroxidase and human myeloperoxidase have shown that in the presence of hydrogen peroxide phenol is converted to 4,4'-diphenoquinone and other covalent binding metabolites, whereas hydroquinone is converted solely to 1,4-benzoquinone. Surprisingly, phenol stimulates the latter conversion rather than inhibiting it, an effect that may play a role in the in vivo myelotoxicity of benzene. Indeed, repeated coadministration of phenol and hydroquinone to B6C3F1 mice results in a dramatic and significant decrease in bone marrow cellularity similar to that observed following benzene exposure. A mechanism of benzene-induced myelotoxicity is therefore proposed in which the accumulation and interaction of phenol and hydroquinone in the bone marrow and the peroxidase-dependent formation of 1,4-benzoquinone are important components. This mechanism may also be responsible, at least in part, for benzene's genotoxic effects, as 1,4-benzoquinone has been shown to damage DNA and is shown here to induce multiple micronuclei in human lymphocytes. Secondary activation of benzene's phenol metabolites in the bone marrow may therefore play an important role in benzene's myelotoxic and carcinogenic effects. PMID:2551665

  9. Genome-Wide Functional Profiling Reveals Genes Required for Tolerance to Benzene Metabolites in Yeast

    PubMed Central

    North, Matthew; Tandon, Vickram J.; Thomas, Reuben; Loguinov, Alex; Gerlovina, Inna; Hubbard, Alan E.; Zhang, Luoping; Smith, Martyn T.; Vulpe, Chris D.

    2011-01-01

    Benzene is a ubiquitous environmental contaminant and is widely used in industry. Exposure to benzene causes a number of serious health problems, including blood disorders and leukemia. Benzene undergoes complex metabolism in humans, making mechanistic determination of benzene toxicity difficult. We used a functional genomics approach to identify the genes that modulate the cellular toxicity of three of the phenolic metabolites of benzene, hydroquinone (HQ), catechol (CAT) and 1,2,4-benzenetriol (BT), in the model eukaryote Saccharomyces cerevisiae. Benzene metabolites generate oxidative and cytoskeletal stress, and tolerance requires correct regulation of iron homeostasis and the vacuolar ATPase. We have identified a conserved bZIP transcription factor, Yap3p, as important for a HQ-specific response pathway, as well as two genes that encode putative NAD(P)H:quinone oxidoreductases, PST2 and YCP4. Many of the yeast genes identified have human orthologs that may modulate human benzene toxicity in a similar manner and could play a role in benzene exposure-related disease. PMID:21912624

  10. Reverse isotope dilution method for determining benzene and metabolites in tissues

    SciTech Connect

    Bechtold, W.E.; Sabourin, P.J.; Henderson, R.F.

    1988-07-01

    A method utilizing reverse isotope dilution for the analysis of benzene and its organic soluble metabolites in tissues of rats and mice is presented. Tissues from rats and mice that had been exposed to radiolabeled benzene were extracted with ethyl acetate containing known, excess quantities of unlabeled benzene and metabolites. Butylated hydroxytoluene was added as an antioxidant. The ethyl acetate extracts were analyzed with semipreparative reversed-phase HPLC. Isolated peaks were collected and analyzed for radioactivity (by liquid scintillation spectrometry) and for mass (by UV absorption). The total amount of each compound present was calculated from the mass dilution of the radiolabeled isotope. This method has the advantages of high sensitivity, because of the high specific activity of benzene, and relative stability of the analyses, because of the addition of large amounts of unlabeled carrier analogue.

  11. 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.

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

    PubMed

    Gut, I; Nedelcheva, V; Soucek, P; Stopka, P; Tichavská, B

    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 (4 mg/liter of air) caused a rapid destruction of CYP2B1 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 BQ and semiquinone radical (SQ) caused the effect. In the presence of nicotinamide adenine dinucleotide 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 peroxidation. 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 peroxidation. Iron redox cycling played a significant role in the NADPH-induced hydroxyl radical formation but not in that caused by ascorbate; however, lipid peroxidation 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 peroxidation.

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

    PubMed Central

    Gut, I; Nedelcheva, V; Soucek, P; Stopka, P; Tichavská, B

    1996-01-01

    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 (4 mg/liter of air) caused a rapid destruction of CYP2B1 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 BQ and semiquinone radical (SQ) caused the effect. In the presence of nicotinamide adenine dinucleotide 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 peroxidation. 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 peroxidation. Iron redox cycling played a significant role in the NADPH-induced hydroxyl radical formation but not in that caused by ascorbate; however, lipid peroxidation 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 peroxidation. PMID:9118895

  14. Anaerobic digestion of linear alkyl benzene sulfonates: biodegradation kinetics and metabolite analysis.

    PubMed

    García, M T; Campos, E; Ribosa, I; Latorre, A; Sánchez-Leal, J

    2005-09-01

    In the present work the effect of the alkyl chain length and the position of the sulfophenyl substituent of the linear alkylbenzene sulfonates (LAS) on their anaerobic biodegradability have been investigated. Degradation kinetics of the linear alkyl benzene sulfonates homologues, 2phiC10LAS, 2phiC12LAS and 2phiC14LAS, have been studied. It has been also investigated the effect of the isomer type on the degradation rate of the LAS molecule through the comparative study of the 2phiC10LAS and 5phiC10LAS isomers. Batch anaerobic biodegradation tests were performed using sludge from the anaerobic digester of a wastewater treatment plant as microorganisms source. Ultimate biodegradation was evaluated from the biogas production whereas primary biodegradation was determined by specific analysis of the surfactant. LAS homologues and isomers showed a negligible primary biodegradation under anaerobic conditions. Furthermore, analysis of sulfophenyl carboxilates (SPC) by LC-MS indicated a low and constant level of these LAS degradation metabolites over the test period. These data are consistent with a minimal transformation of the LAS parent molecule in the anaerobic digesters. On the other hand, the addition of the shortest alkyl chain length homologues, decyl and dodecylbenzene sulfonates, reduces the biogas production whereas the most hydrophobic homologue, the tetradecylbenzene sulfonate, enhances the biogas production. This LAS homologue seems to increase the availability of organic compounds sorbed on the anaerobic sludge promoting their biodegradation.

  15. Inhibitory effect of benzene metabolites on nuclear DNA synthesis in bone marrow cells

    SciTech Connect

    Lee, E.W.; Johnson, J.T.; Garner, C.D. )

    1989-01-01

    Effects of endogenously produced and exogenously added benzene metabolites on the nuclear DNA synthetic activity were investigated using a culture system of mouse bone marrow cells. Effects of the metabolites were evaluated by a 30-min incorporation of ({sup 3}H)thymidine into DNA following a 30-min interaction with the cells in McCoy's 5a medium with 10% fetal calf serum. Phenol and muconic acid did not inhibit nuclear DNA synthesis. However, catechol, 1,2,4-benzenetriol, hydroquinone, and p-benzoquinone were able to inhibit 52, 64, 79, and 98% of the nuclear DNA synthetic activity, respectively, at 24 {mu}M. In a cell-free DNA synthetic system, catechol and hydroquinone did not inhibit the incorporation of ({sup 3}H)thymidine triphosphate into DNA up to 24 {mu}M but 1,2,4-benzenetriol and p-benzoquinone did. The effect of the latter two benzene metabolites was completely blocked in the presence of 1,4-dithiothreitol (1 mM) in the cell-free assay system. Furthermore, when DNA polymerase {alpha}, which requires a sulfhydryl (SH) group as an active site, was replaced by DNA polymerase 1, which does not require an SH group for its catalytic activity, p-benzoquinone and 1,2,4-benzenetriol were unable to inhibit DNA synthesis. Thus, the data imply the p-benzoquinone and 1,2,4-benzenetriol inhibited DNA polymerase {alpha}, consequently resulting in inhibition of DNA synthesis in both cellular and cell-free DNA synthetic systems. The present study identifies catechol, hydroquinone, p-benzoquinone, and 1,2,4-benzenetriol as toxic benzene metabolites in bone marrow cells and also suggests that their inhibitory action on DNA synthesis is mediated by mechanism(s) other than that involving DNA damage as a primary cause.

  16. 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.

  17. 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.

  18. Variability of albumin adducts of 1,4-benzoquinone, a toxic metabolite of benzene, in human volunteers.

    PubMed

    Lin, Y S; McKelvey, W; Waidyanatha, S; Rappaport, S M

    2006-01-01

    A putative haematotoxic and leukaemogenic metabolite of benzene, 1,4-benzoquinone (1,4-BQ), reacts rapidly with macromolecules. The authors previously characterized levels of the albumin (Alb) adduct (1,4-BQ-Alb) of this reactive species in populations of workers exposed to benzene. Since high levels of 1,4-BQ-Alb were also measured in unexposed workers from those investigations, the current study was initiated to determine potential sources of 1,4-BQ in the general population. A single blood sample was collected from 191 healthy subjects from the Research Triangle area, NC, USA, to determine the baseline 1,4-BQ-Alb levels and contributing sources. The median 1,4-BQ-Alb at baseline was 550?pmol?g(-1) Alb (interquartile range 435-814?pmol?g(-1)). A second blood sample was collected approximately 3 months later from a subgroup of 33 subjects to estimate the within- and between-person variation in 1,4-BQ-Alb. Standardized questionnaires were administered to collect information about demographic, dietary and lifestyle factors. Multiple linear regression models identified several significant contributors to 1,4-BQ-Alb levels, including gender, body mass index (BMI), the gender-BMI interaction, automobile refuelling, smoking status, and consumption of fruit and the artificial sweetener, aspartame. The authors predicted that these background levels of 1,4-BQ-Alb were equivalent to occupational exposures between 1 and 3 parts per million of benzene. Mixed effects linear models indicated that the random variation in adduct levels was about equally divided between and within subjects. The observations indicate that levels of 1,4-BQ-Alb cover a wide range in the general population, and they support the hypotheses that demographic, diet and lifestyle factors are contributing sources.

  19. 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

  20. Effects of the principal hydroxy-metabolites of benzene on microtubule polymerization.

    PubMed

    Irons, R D; Neptun, D A

    1980-10-01

    The principal hydroxy-metabolites of benzene - phenol, catechol and hydroquinone - possess characteristics and produce toxicity similar to those reported for certain inhibitors of microtubule polymerization. In this study we examined the effects of phenol, catechol and hydroquinone on purified microtubule polymerization and the decay of tubulin-colchicine binding activity. Hydroquinone, but not catechol or phenol, inhibited microtubule polymerization and accelerated the decay of tubulin-colchicine binding activity. The latter effect was shown to be dependent on the concentration of GTP. Hydroquinone did not directly complex with GTP or ATP but bound to the high molecular weight fraction of tubulin. concentration ratios of hydroquinone to tubulin resulting in altered activity were low, suggesting a specific interaction, presumably at the tubulin-GTP binding site. The acceleration of tubulin-colchicine binding activity decay was completely prevented under anaerobic conditions, indicative of an oxidative mechanism. These studies suggest that hydroquinone, which auto-oxidizes, may interfere with microtubule function, nucleotide binding or both and that this mechanism may be involved in eliciting the wide range of cytoskeletal-related abnormalities observed in cells exposed to benzene in vivo or its metabolites in vitro. PMID:7447702

  1. MiR-133a regarded as a potential biomarker for benzene toxicity through targeting Caspase-9 to inhibit apoptosis induced by benzene metabolite (1,4-Benzoquinone).

    PubMed

    Chen, Yujiao; Sun, Pengling; Bai, Wenlin; Gao, Ai

    2016-11-15

    Benzene is an environmental and industrial chemical which is widely utilized in various applications. Our previous study showed that miR-133a expression was down-regulated in chronic benzene poisoning workers, but the mechanism of miR-133a in benzene-induced hematotoxicity remains unclear. In this population-based study, benzene-exposed group recruited workers whose concentration of air benzene was 3.50±1.60mg/m(3), and control workers who were exposed to 0.06±0.01mg/m(3) air benzene. By comparison, Caspase-9 and Caspase-3 was up-regulated while miR-133a expression decreased in benzene-exposed workers. Pearson correlation analysis showed that miR-133a was reversely correlated with pro-apoptotic gene Caspase-9 in population-based study. Moreover, multiple linear regressions indicated that miR-133a was positively associated with blood cells count. To explore the underlying mechanism of miR-133a in benzene-induced hematotoxicity, AO/EB staining and TEM ultrastructural analysis were conducted to verify the activation of apoptosis in Human Leukemic U937 Cells induced by benzene metabolites (1,4-Benzoquinone, 1,4-BQ), while the mechanism of miR-133a in 1,4-BQ-induced apoptosis was performed using lentivirus vectors transfection. The results demonstrated that 1,4-BQ evidently induced mitochondria-mediated apoptosis and increased pro-apoptotic genes (Caspase-9 and Caspase-3) expression in a dose-dependent manner. The mechanistic study showed 1,4-BQ decreased miR-133a expression and miR-133a over-expression attenuated 1, 4-BQ-caused upregulation of Caspase-9, Caspase-3 and apoptosis. In conclusion, our research suggested that benzene induced hematotoxicity by decreasing miR-133a and caspase-dependent apoptosis which might contribute to the underlying mechanism of miR-133a in benzene-induced hematotoxicity.

  2. 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.

  3. 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).

  4. Cell-specific activation and detoxification of benzene metabolites in mouse and human bone marrow: Identification of target cells and a potential role for modulation of apoptosis in benzene toxicity

    SciTech Connect

    Ross, D.; Siegel, D.; Schattenberg, D.G.

    1996-12-01

    The role of cell-specific metabolism in benzene toxicity was examined in both murine and human bone marrow. Hemopoietic progenitor cells and stromal cells are important control points for regulation of hemopoiesis. We show that the selective toxicity of hydroquinone at the level of the macrophage in murine bone marrow stroma may be explained by a high peroxidase/nicotanimicle adenine dinucleotide phosphate, reduced [NAD(P)H]:quinone oxidoreductase (NQO1) ratio. Peroxidases metabolize hydroquinone to the reactive 1,4-benzoquinone, whereas NQO1 reduces the quinones formed, resulting in detoxification. Peroxidase and NQO1 activity in human stromal cultures vary as a function of time in culture, with peroxidase activity decreasing and NQO1 activity increasing with time. Peroxidase activity and, more specifically, myeloperoxidase, which had previously been considered to be expressed at the promyelocyte level, was detected in murine lineage-negative and human CD34{sup +} progenitor cells. This provides a metabolic mechanism whereby phenolic metabolites of benzene can be bioactivated in progenitor cells, which are considered initial target cells for the development of leukemias. Consequences of a high peroxidase/NQO1 ratio in HL-60 cells were shown to include hydroquinone-induced apoptosis. Hydroquinone can also inhibit proteases known to play a role in induction of apoptosis, suggesting that it may be able to inhibit apoptosis induced by other stimuli. Modulation of apoptosis may lead to aberrant hemopoiesis and neoplastic progression. This enzyme-directed approach has identified target cells of the phenolic metabolites of benzene in bone marrow and provided a metabolic basis for benzene-induced toxicity at the level of the progenitor cell in both murine and human bone marrow. 60 refs., 8 figs.

  5. 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.

  6. Identification of 6-hydroxy-trans,trans-2,4-hexadienoic acid, a novel ring-opened urinary metabolite of benzene.

    PubMed Central

    Kline, S A; Robertson, J F; Grotz, V L; Goldstein, B D; Witz, G

    1993-01-01

    We studied the in vivo metabolism of benzene in mice to ring-opened compounds excreted in urine. Male CD-1 mice were treated intraperitoneally with benzene (110-440 mg/kg), [14C]benzene (220 mg/kg) or trans, trans-muconaldehyde (MUC; 4 mg/kg), a microsomal, hematotoxic metabolite of benzene. Urine, collected over 24 hr, was extracted and analyzed by HPLC with a diode-array detector and by scintillation counting. In addition to trans,trans-muconic acid, previously the only known ring-opened urinary benzene metabolite, a new metabolite, 6-hydroxy-trans,trans-2,4-hexadienoic acid, was detected in urine of mice treated with either benzene or MUC. We identified the new metabolite based on coelution of metabolites and UV spectral comparison with authentic standards in unmethylated and methylated urine extracts. Results presented here are consistent with the intermediacy of MUC in the in vivo metabolism of benzene to ring-opened metabolites. Images p310-a PMID:8275987

  7. trans,trans-Muconic acid, a reliable biological indicator for the detection of individual benzene exposure down to the ppm level.

    PubMed

    Ducos, P; Gaudin, R; Bel, J; Maire, C; Francin, J M; Robert, A; Wild, P

    1992-01-01

    trans,trans-Muconic acid (2,4-hexadienedioic acid) (t,t-MA) is a minor benzene metabolite which can be used as a biological indicator for benzene exposure. The purpose of the study was to evaluate the limits of use of t,t-MA for detection and quantification of occupational exposures to benzene, particularly on an individual scale, phenol being used as the metabolite of reference. A simple and sensitive method previously described by the authors was carried out to analyse t,t-MA in 105 end-of-shift urinary samples from 23 workers exposed to benzene used as an extraction solvent for "concretes" recovery in the perfume industry. Good correlations were found between atmospheric benzene and both metabolites (uncorrected or corrected for creatinine) or between the metabolites themselves, with correlation coefficients from 0.81 to 0.91 (P < 0.0001). Correlation- coefficients were not improved after correction for creatinine. The overall individual benzene exposure range, median, and arithmetic mean were respectively 0.1-75, 4.5, and 9.0 ppm with corresponding t,t-MA excretion of 0.1-47.9, 5.2 and 8.9 mg/l (uncorrected) and phenol excretion of 1.4-298, 30.9, and 42.2 mg/l (uncorrected). In the control group (145 determinations for t,t-MA and 76 for phenol from 79 individuals) the range, median, and arithmetic mean were respectively < 0.04-0.66, 0.08, and 0.13 mg/l (uncorrected t,t-MA) and 1.5-42.0, 9.85 and 11.3 mg/l (uncorrected phenol). t,t-MA was far more specific than phenol and could be easily and practically used to estimate with a given probability the upper or lower corresponding benzene concentrations down to around the ppm level.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. 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.

  9. 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

  10. Investigation into Variation of Endogenous Metabolites in Bone Marrow Cells and Plasma in C3H/He Mice Exposed to Benzene

    PubMed Central

    Sun, Rongli; Zhang, Juan; Yin, Lihong; Pu, Yuepu

    2014-01-01

    Benzene is identified as a carcinogen. Continued exposure of benzene may eventually lead to damage to the bone marrow, accompanied by pancytopenia, aplastic anemia or leukemia. This paper explores the variations of endogenous metabolites to provide possible clues for the molecular mechanism of benzene-induced hematotoxicity. Liquid chromatography coupled with time of flight-mass spectrometry (LC-TOF-MS) and principal component analysis (PCA) was applied to investigate the variation of endogenous metabolites in bone marrow cells and plasma of male C3H/He mice. The mice were injected subcutaneously with benzene (0, 300, 600 mg/day) once daily for seven days. The body weights, relative organ weights, blood parameters and bone marrow smears were also analyzed. The results indicated that benzene caused disturbances in the metabolism of oxidation of fatty acids and essential amino acids (lysine, phenylalanine and tyrosine) in bone marrow cells. Moreover, fatty acid oxidation was also disturbed in plasma and thus might be a common disturbed metabolic pathway induced by benzene in multiple organs. This study aims to investigate the underlying molecular mechanisms involved in benzene hematotoxicity, especially in bone marrow cells. PMID:24658442

  11. 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.

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

    PubMed Central

    Schnatter, A R; Armstrong, T W; Thompson, L S; Nicolich, M J; Katz, A M; Huebner, W W; Pearlman, E D

    1996-01-01

    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 [Schnatter et al., Environ Health Perspect 101 (Suppl 6):85-89 (1993)]. 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. PMID:9118923

  13. 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. PMID:26257031

  14. 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.

  15. 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.

  16. The benzene metabolite para-benzoquinone is genotoxic in human, phorbol-12-acetate-13-myristate induced, peripheral blood mononuclear cells at low concentrations.

    PubMed

    Westphal, Götz Alexander; Bünger, Jürgen; Lichey, Nadine; Taeger, Dirk; Mönnich, Angelika; Hallier, Ernst

    2009-07-01

    Benzene is one of the most prominent occupational and environmental pollutants. The substance is a proven human carcinogen that induces hematologic malignancies in humans, probably at even low doses. Yet knowledge of the mechanisms leading to benzene-induced carcinogenesis is still incomplete. Benzene itself is not genotoxic. The generation of carcinogenic metabolites involves the production of oxidized intermediates such as catechol, hydroquinone and para-benzoquinone (p-BQ) in the liver. Further activation to the ultimate carcinogenic intermediates is most probably catalyzed by myeloperoxidase (MPO). Yet the products of the MPO pathway have not been identified. If an oxidized benzene metabolite such as p-BQ was actually the precursor for the ultimate carcinogenic benzene metabolite and further activation proceeds via MPO mediated reactions, it should be possible to activate p-BQ to a genotoxic compound in vitro. We tested this hypothesis with phorbol-12-acetate-13-myristate (PMA) activated peripheral blood cells exposed to p-BQ, using the cytokinesis-block micronucleus test. Addition of 20-28 ng/ml PMA caused a significant increase of micronuclei at low and non-cytotoxic p-BQ concentrations between 0.04 and 0.2 microg/ml (0.37-1.85 microM). Thus with PMA or p-BQ alone no reproducible elevation of micronuclei was seen up to toxic concentrations. PMA and p-BQ induce micronuclei when administered jointly. Our results add further support to the hypothesis that MPO is a key enzyme in the activation of benzene. PMID:19212761

  17. Effect of repeated benzene inhalation exposures on benzene metabolism, binding to hemoglobin, and induction of micronuclei.

    PubMed

    Sabourin, P J; Sun, J D; MacGregor, J T; Wehr, C M; Birnbaum, L S; Lucier, G; Henderson, R F

    1990-05-01

    Metabolism of benzene is thought to be necessary to produce the toxic effects, including carcinogenicity, associated with benzene exposure. To extrapolate from the results of rodent studies to potential health risks in man, one must know how benzene metabolism is affected by species, dose, dose rate, and repeated versus single exposures. The purpose of our studies was to determine the effect of repeated inhalation exposures on the metabolism of [14C]benzene by rodents. Benzene metabolism was assessed by characterizing and quantitating urinary metabolites, and by quantitating 14C bound to hemoglobin and micronuclei induction. F344/N rats and B6C3F1 mice were exposed, nose-only, to 600 ppm benzene or to air (control) for 6 hr/day, 5 days/week for 3 weeks. On the last day, both benzene-pretreated and control animals were exposed to 600 ppm, 14C-labeled benzene for 6 hr. Individual benzene metabolites in urine collected for 24 hr after the exposure were analyzed. There was a significant decrease in the respiratory rate of mice (but not rats) pretreated with benzene which resulted in lower levels of urinary [14C]benzene metabolites. The analyses indicated that the only effects of benzene pretreatment on the metabolite profile in rat or mouse urine were a slight shift from glucuronidation to sulfation in mice and a shift from sulfation to glucuronidation in rats. Benzene pretreatment also had no effect, in either species, on formation of [14C]benzene-derived hemoglobin adducts. Mice and rats had similar levels of hemoglobin adduct binding, despite the higher metabolism of benzene by mice. This indicates that hemoglobin adduct formation occurs with higher efficiency in rats. After 1 week of exposure to 600 ppm benzene, the frequency of micronucleated, polychromatic erythrocytes (PCEs) in mice was significantly increased. Exposure to the same level of benzene for an additional 2 weeks did not further increase the frequency of micronuclei in PCEs. These results indicate

  18. 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.

  19. 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.

  20. 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.

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

    PubMed Central

    Hutt, A M; Kalf, G F

    1996-01-01

    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 II (topo II) is an essential sulfhydryl (SH)-dependent endonuclease required for replication, recombination, chromosome segregation, and chromosome structure. Topo II cleaves DNA at purine(R)/pyrimidine(Y) repeat sequences that have been shown to be highly recombinogenic in vivo. Certain antineoplastic drugs stabilize topo II-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. BQ interacts wit SH groups of SH-dependent enzymes. Consequently, the aims of this research were to determine whether HQ and BQ are topo II inhibitors. The ability of the compounds to inhibit the activity of topo III was tested using an assay system that depends on the conversion, by homogeneous human topo II, 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 BQ cause a time and concentration (microM)-dependent inhibition of topo II activity. These compounds, which potentially can form adducts with DNA, have no effect on the migration of the supercoiled and open circular forms in the electrophoretic gradient, and BQ-adducted KDNA can be decatenated by topo II. Using a pRYG plasmid DNA with a single RY repeat as a cleavage site, it was determined that BQ does not stimulate the production of linear DNA indicative of an inhibition of topo II religation of strand breaks by stabilization of the covalent topo III-DNA cleavage complex. Rather, BQ most probably inhibits the SH-dependent topo II by binding to

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

    PubMed

    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 II (topo II) is an essential sulfhydryl (SH)-dependent endonuclease required for replication, recombination, chromosome segregation, and chromosome structure. Topo II cleaves DNA at purine(R)/pyrimidine(Y) repeat sequences that have been shown to be highly recombinogenic in vivo. Certain antineoplastic drugs stabilize topo II-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. BQ interacts wit SH groups of SH-dependent enzymes. Consequently, the aims of this research were to determine whether HQ and BQ are topo II inhibitors. The ability of the compounds to inhibit the activity of topo III was tested using an assay system that depends on the conversion, by homogeneous human topo II, 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 BQ cause a time and concentration (microM)-dependent inhibition of topo II activity. These compounds, which potentially can form adducts with DNA, have no effect on the migration of the supercoiled and open circular forms in the electrophoretic gradient, and BQ-adducted KDNA can be decatenated by topo II. Using a pRYG plasmid DNA with a single RY repeat as a cleavage site, it was determined that BQ does not stimulate the production of linear DNA indicative of an inhibition of topo II religation of strand breaks by stabilization of the covalent topo III-DNA cleavage complex. Rather, BQ most probably inhibits the SH-dependent topo II by binding to

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. Effect of CYP2E1 induction by ethanol on the immunotoxicity and genotoxicity of extended low-level benzene exposure.

    PubMed

    Daiker, D H; Shipp, B K; Schoenfeld, H A; Klimpel, G R; Witz, G; Moslen, M T; Ward, J B

    2000-02-11

    Potential additive effects of ethanol consumption, a common life-style factor, and low-level benzene exposure, a ubiquitous environmental pollutant, were investigated. Ethanol is a potent inducer of the cytochrome P-450 2E1 (CYP2E1) enzyme, which bioactivates benzene to metabolites with known genotoxicity and immunotoxicity. A liquid diet containing 4.1% ethanol was used to induce hepatic CYP2E1 activity by 4-fold in female CD-1 mice. Groups of ethanol-treated or pair-fed control mice were exposed to benzene or filtered air in inhalation chambers for 7 h/d, 5 d/wk for 6 or 11 wk. The initial experiment focused on immunotoxicity endpoints based on literature reports that ethanol enhances high-dose benzene effects on spleen, thymus, and bone marrow cellularity and on peripheral red blood cell (RBC) and white blood cell (WBC) counts. No statistically significant alterations were found in spleen lymphocyte cellularity, subtype profile, or function (mitogen-induced proliferation, cytokine production, or natural killer cell lytic activity) after 6 wk of ethanol diet, 0.44 ppm benzene exposure, or both. This observed absence of immunomodulation by ethanol alone, a potential confounding factor, further validates our previously established murine model of sustained CYP2E1 induction by dietary ethanol. Subsequent experiments involved a 10-fold higher benzene level for a longer time of 11 wk and focused on genotoxic endpoints in known target tissues. Bone marrow and spleen cells were evaluated for DNA-protein cross-links, a sensitive transient index of genetic damage, and spleen lymphocytes were monitored for hprt-mutant frequency, a biomarker of cumulative genetic insult. No treatment-associated changes in either genotoxic endpoint were detected in animals exposed to 4.4 ppm benzene for 6 or 11 wk with or without coexposure to ethanol. Thus, our observations suggest an absence of genetic toxicity in CD-1 mice exposed to environmentally relevant levels of benzene with or

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

    PubMed Central

    Irons, R D; Stillman, W S; Colagiovanni, D B; Henry, V A

    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. PMID:1570288

  9. 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.

  10. Genotoxicity of intermittent co-exposure to benzene and toluene in male CD-1 mice.

    PubMed

    Wetmore, Barbara A; Struve, Melanie F; Gao, Pu; Sharma, Sheela; Allison, Neil; Roberts, Kay C; Letinski, Daniel J; Nicolich, Mark J; Bird, Michael G; Dorman, David C

    2008-06-17

    Benzene is an important industrial chemical. At certain levels, benzene has been found to produce aplastic anemia, pancytopenia, myeloblastic anemia and genotoxic effects in humans. Metabolism by cytochrome P450 monooxygenases and myeloperoxidase to hydroquinone, phenol, and other metabolites contributes to benzene toxicity. Other xenobiotic substrates for cytochrome P450 can alter benzene metabolism. At high concentrations, toluene has been shown to inhibit benzene metabolism and benzene-induced toxicities. The present study investigated the genotoxicity of exposure to benzene and toluene at lower and intermittent co-exposures. Mice were exposed via whole-body inhalation for 6h/day for 8 days (over a 15-day time period) to air, 50 ppm benzene, 100 ppm toluene, 50 ppm benzene and 50 ppm toluene, or 50 ppm benzene and 100 ppm toluene. Mice exposed to 50 ppm benzene exhibited an increased frequency (2.4-fold) of micronucleated polychromatic erythrocytes (PCE) and increased levels of urinary metabolites (t,t-muconic acid, hydroquinone, and s-phenylmercapturic acid) vs. air-exposed controls. Benzene co-exposure with 100 ppm toluene resulted in similar urinary metabolite levels but a 3.7-fold increase in frequency of micronucleated PCE. Benzene co-exposure with 50 ppm toluene resulted in a similar elevation of micronuclei frequency as with 100 ppm toluene which did not differ significantly from 50 ppm benzene exposure alone. Both co-exposures - 50 ppm benzene with 50 or 100 ppm toluene - resulted in significantly elevated CYP2E1 activities that did not occur following benzene or toluene exposure alone. Whole blood glutathione (GSH) levels were similarly decreased following exposure to 50 ppm benzene and/or 100 ppm toluene, while co-exposure to 50 ppm benzene and 100 ppm toluene significantly decreased GSSG levels and increased the GSH/GSSG ratio. The higher frequency of micronucleated PCE following benzene and toluene co-exposure when compared with mice exposed to

  11. 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

  12. Biochemical toxicity of benzene.

    PubMed

    Rana, S V S; Verma, Yeshvandra

    2005-04-01

    Human exposure to benzene in work environment is a global occupational health problem. After inhalation or absorption, benzene targets organs viz. liver, kidney, lung, heart and brain etc. It is metabolized mainly in the liver by cytochrome P450 multifunctional oxygenase system. Benzene causes haematotoxicity through its phenolic metabolites that act in concert to produce DNA strand breaks, chromosomal damage, sister chromatid exchange, inhibition of topoisomerase II and damage to mitotic spindle. The carcinogenic and myelotoxic effects of benzene are associated with free radical formation either as benzene metabolites or lipid peroxidation products. Benzene oxide and phenol have been considered as proheptons. Liver microsomes play an important role in biotransformation of benzene whereas in kidney, it produces degenerative intracellular changes. Cohort studies made in different countries suggest that benzene induces multiple myeloma in petrochemical workers. Though extensive studies have been performed on its toxicity, endocrinal disruption caused by benzene remains poorly known. Transgenic cytochrome P450 IIE1 mice may help in understanding further toxic manifestations of benzene.

  13. 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

  14. Phthalate metabolite levels and menopausal hot flashes in midlife women.

    PubMed

    Ziv-Gal, Ayelet; Gallicchio, Lisa; Chiang, Catheryne; Ther, Sara N; Miller, Susan R; Zacur, Howard A; Dills, Russell L; Flaws, Jodi A

    2016-04-01

    During the menopausal transition, a woman's reproductive capacity declines, her hormone milieu changes, and her risk of hot flashes increases. Exposure to phthalates, which can be found in personal care products, can also result in altered reproductive function. Here, we investigated the associations between phthalate metabolite levels and midlife hot flashes. Eligible women (45-54 years of age) provided detailed information on hot flashes history and donated urine samples (n=195). Urinary phthalate metabolite levels were measured by HPLC-MS/MS. A higher total sum of phthalate metabolites commonly found in personal care products was associated with an increased risk of ever experiencing hot flashes (odds ratio (OR)=1.45; 95% confidence interval (CI)=1.07-1.96), hot flashes in the past 30days (OR=1.43; 95%CI=1.04-1.96), and more frequent hot flashes (OR=1.47; 95%CI=1.06-2.05). These data suggest that some phthalate exposures from personal care products are associated with menopausal hot flashes in women.

  15. 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

  16. Urinary phthalate metabolite concentrations and blood glucose levels during pregnancy

    PubMed Central

    Robledo, Candace A.; Peck, Jennifer D.; Stoner, Julie; Calafat, Antonia M.; Carabin, Hélène; Cowan, Linda; Goodman, Jean R.

    2016-01-01

    Purpose To examine associations between phthalate metabolite urinary concentrations during early pregnancy and blood glucose levels obtained at the time of screening for gestational diabetes mellitus (GDM). Methods Upon initiation of prenatal care, women with a mean gestational age of 12.8 weeks were recruited for a study of environmental chemical exposures (n = 110) and provided a spot urinary specimen. Blood glucose concentrations (mg/dl) were obtained from the electronic medical record for those patients who did not experience a pregnancy loss and did not transfer care to another facility prior to glucose screening (n = 72). Urinary concentrations of nine phthalate metabolites and creatinine were measured at the US Centers for Disease Control and Prevention. Associations between tertiles of phthalate metabolites concentrations and blood glucose levels were estimated using linear regression. Results Compared to pregnant women in the lowest concentration tertile, women with the highest urinary concentrations (≥3rd tertile) of mono-iso-butyl phthalate (tertile: ≥15.3 μg/l, β = −18.3, 95% CI: −35.4, −1.2) and monobenzyl phthalate (tertile: ≥30.3 μg/l, β = −17.3, 95% CI: −34.1, −0.4) had lower blood glucose levels at the time of GDM screening after adjustment for urinary creatinine and demographic covariates. Conclusion Because maternal glucose levels increase during pregnancy to provide adequate nutrition for fetal growth and development, these findings may have implications for fetal health. However, given the limitations of our study, findings should be interpreted cautiously. PMID:25726127

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. [A method for measuring urinary concentrations of benzene. Its use in monitoring of subjects exposed to low levels].

    PubMed

    Fiorentino, M L; Ghittori, S; Pezzagno, G

    1990-01-01

    Benzene is a widely diffuse solvent (atmosphere, cigarette smoke, some foods); in the industrial environment benzene is currently present at concentrations of ppm. A valid method of biological monitoring that is easy to perform is needed for assessing occupational and non-occupational exposures. A new method has been developed to evaluate low concentrations of benzene in urine samples by means of a "dynamic" headspace (50 ml of urine in a 120 ml vial). The urine is saturated with anhydrous Na2SO4 in order to support the entrance of benzene in the air over the urine. The solvent is stripped from the urine surface and concentrated on an adsorbent substrate (Carbotrap 100 tube) by means of a suction pump (150 ml/min). A simultaneous intake of filtered air through a charcoal tube allows wash-up of the headspace. Benzene is thermically desorbed and injected in a column (Thermal tube desorber-Supelco; 370 degrees C thermal flash; borosilicate capillary glass column SPB-1 60 m length, 0.75 mm I.D., 1 micron film thickness; G.C. Dani 8580-FID). The detection limit of the method is about 50 ng/l and the variation coefficient is 4.7%. The method was checked on urine samples of 5 non-smokers and 5 smokers: mean values of 135 and 944 ng/l respectively were obtained. A further analysis on urine samples of 60 smokers revealed a significant relationship (p less than 0.001) between urinary benzene concentrations and C0 alveolar concentrations (r = 0.626). A close relationship between benzene exposure levels and urinary concentrations was found in a group of workers exposed to low environmental benzene concentrations (mean value 1200 micrograms/m3) (r = 0.763).

  3. 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. PMID:12507175

  4. Can NO(2) be used to indicate ambient and personal levels of benzene and 1,3-butadiene in air?

    PubMed

    Modig, Lars; Sunesson, Anna-Lena; Levin, Jan-Olof; Sundgren, Margit; Hagenbjörk-Gustafsson, Annika; Forsberg, Bertil

    2004-12-01

    The aim of this study was to investigate the relation between two toxic volatile organic compounds, 1,3-butadiene and benzene, and a commonly used indicator of vehicle exhaust fumes, NO(2). This was to see if NO(2) can be used to indicate personal exposure to carcinogenic substances or at least estimate ambient levels measured at a stationary point. During the winter of 2001, 40 randomly selected persons living in the City of Umea (in the north of Sweden) were recruited to the study. Personal measurements of 1,3-butadiene, benzene and NO(2) were performed for one week, and were repeated for 20 of the 40 participants. Additional information was gathered using a diary kept by each participant. During the same time period weekly stationary measurements were performed at one urban background station and one street station in the city centre. The results from the personal measurements showed a negligible association of NO(2) with 1,3-butadiene (r= 0.06) as well as with benzene (r= 0.10), while the correlation coefficient between 1,3-butadiene and benzene was high and significant (r= 0.67). In contrast to the personal measurements, the stationary measurements showed strong relations between 1,3-butadiene, benzene and NO(2) both within and in-between the street and urban background station. This study supports NO(2) as a potential indicator for 1,3-butadiene and benzene levels in streets or urban background air, while the weak relations found for the personal measurements do not support the use of NO(2) as an indicator for personal 1,3-butadiene and benzene exposure. PMID:15568043

  5. 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

  6. 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

  7. Biomarkers of human exposure to benzene

    SciTech Connect

    Bechtold, W.E.; Henderson, R.F. )

    1993-01-01

    Three biomarkers for benzene exposure were developed. The first biomarker, muconic acid in urine, results from the ring opening of a benzene metabolite. A gas chromatography/mass spectroscopy (GC/MS) assay was developed to measure urinary muconic acid, and the analyte in urine samples from workers occupationally exposed to benzene was determined. Workers exposed to benzene concentrations as low as 4.4 ppm over an 8-h day showed higher urinary muconic acid concentrations than did any control individual (p < .005). The second biomarker, S-phenylcysteine (SPC) in hemoglobin (Hb), results from the addition of benzene oxide to a cysteine sulfhydryl group. A GC/MS assay was developed to measure SPC in the blood of F344/N rats and B67C3F mice exposed to benzene by inhalation. The cysteine moiety on rat Hb is at a more accessible site than on Hb of mice or humans, and rats showed considerably higher levels of SPC than did mice. As yet, we have been unable to detect SPC in the globin of humans occupationally exposed to benzene. The third biomarker is SPC in albumin. In humans occupationally exposed to average concentrations of 0, 4.4, 8.4, and 23.1 ppm benzene, 8 h/d, 5 d/wk, SPC increased in the exposed groups linearly, giving a statistically significant slope (p < .001) of 0.044 [+-] 0.008 pmol/mg albumin/ppm. The assay for SPC is arduous and often imprecise; assuming these difficulties can be overcome, muconic acid in urine and SPC in albumin may be useful for accurately determining benzene exposure. 25 refs., 4 figs., 1 tab.

  8. Genetic Influences on Metabolite Levels: A Comparison across Metabolomic Platforms.

    PubMed

    Yet, Idil; Menni, Cristina; Shin, So-Youn; Mangino, Massimo; Soranzo, Nicole; Adamski, Jerzy; Suhre, Karsten; Spector, Tim D; Kastenmüller, Gabi; Bell, Jordana T

    2016-01-01

    Metabolomic profiling is a powerful approach to characterize human metabolism and help understand common disease risk. Although multiple high-throughput technologies have been developed to assay the human metabolome, no technique is capable of capturing the entire human metabolism. Large-scale metabolomics data are being generated in multiple cohorts, but the datasets are typically profiled using different metabolomics platforms. Here, we compared analyses across two of the most frequently used metabolomic platforms, Biocrates and Metabolon, with the aim of assessing how complimentary metabolite profiles are across platforms. We profiled serum samples from 1,001 twins using both targeted (Biocrates, n = 160 metabolites) and non-targeted (Metabolon, n = 488 metabolites) mass spectrometry platforms. We compared metabolite distributions and performed genome-wide association analyses to identify shared genetic influences on metabolites across platforms. Comparison of 43 metabolites named for the same compound on both platforms indicated strong positive correlations, with few exceptions. Genome-wide association scans with high-throughput metabolic profiles were performed for each dataset and identified genetic variants at 7 loci associated with 16 unique metabolites on both platforms. The 16 metabolites showed consistent genetic associations and appear to be robustly measured across platforms. These included both metabolites named for the same compound across platforms as well as unique metabolites, of which 2 (nonanoylcarnitine (C9) [Biocrates]/Unknown metabolite X-13431 [Metabolon] and PC aa C28:1 [Biocrates]/1-stearoylglycerol [Metabolon]) are likely to represent the same or related biochemical entities. The results demonstrate the complementary nature of both platforms, and can be informative for future studies of comparative and integrative metabolomics analyses in samples profiled on different platforms. PMID:27073872

  9. 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.

  10. 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...

  11. Occupational exposures associated with petroleum-derived products containing trace levels of benzene.

    PubMed

    Williams, Pamela R D; Panko, Julie M; Unice, Ken; Brown, Jay L; Paustenbach, Dennis J

    2008-09-01

    Benzene may be present as a trace impurity or residual component of mixed petroleum products due to refining processes. In this article, the authors review the historical benzene content of various petroleum-derived products and characterize the airborne concentrations of benzene associated with the typical handling or use of these products in the United States, based on indoor exposure modeling and industrial hygiene air monitoring data collected since the late 1970s. Analysis showed that products that normally contained less than 0.1% v/v benzene, such as paints and paint solvents, printing solvents and inks, cutting and honing oils, adhesives, mineral spirits and degreasers, and jet fuel typically have yielded time-weighted average (TWA) airborne concentrations of benzene in the breathing zone and surrounding air ranging on average from <0.01 to 0.3 ppm. Except for a limited number of studies where the benzene content of the product was not confirmed to be <0.1% v/v, airborne benzene concentrations were also less than current occupational exposure limits (e.g., threshold limit value of 0.5 ppm and permissible exposure limit of 1.0 ppm) based on exceedance fraction calculations. Exposure modeling using Monte Carlo techniques also predicted 8-hr TWA near field airborne benzene concentrations ranging from 0.002 to 0.4 ppm under three hypothetical solvent use scenarios involving mineral spirits. The overall weight-of-evidence indicates that the vast majority of products manufactured in the United States after about 1978 contained <0.1% v/v benzene, and 8-hr TWA airborne concentrations of benzene in the workplace during the use of these products would not have been expected to exceed 0.5 ppm under most product use scenarios. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: a document containing exposure modeling scenarios and

  12. Benzene metabolism in rodents at doses relevant to human exposure from urban air.

    PubMed

    Turteltaub, Kenneth W; Mani, Chitra

    2003-02-01

    Benzene is both an environmental pollutant and a component of cigarette smoke, gasoline, and automotive emissions. Although occupational exposure to benzene has been shown to cause blood disorders and cancer in humans, the potential health effects resulting from exposure to low levels of benzene are not known. The goals of this project were to determine how well benzene is metabolized and to assess its binding to macromolecules in rodents at doses more closely mimicking human environmental exposure. To determine whether genotoxic metabolites of benzene are produced at environmental exposure levels. various doses of 14C-benzene were given intraperitoneally to male B6C3F1 mice at doses from 5 ng/kg to 500 mg/kg body weight. Samples of urine, plasma, liver, and bone marrow were taken at selected times up to 48 hours after exposure. Individual benzene metabolites in the samples were measured by accelerator mass spectrometry (AMS*). Metabolites were quantified by determining the area under the curve (AUC) for 24 to 48 hours. The major metabolites found in urine were an unidentified radiolabeled metabolite. phenyl sulfate, phenyl glucuronide. and muconic acid (an indicator of muconaldehyde formation). The major metabolites found in plasma, liver, and bone marrow samples were muconic acid and hydroquinone. Only liver showed a dose response for hydroquinone and muconic acid. The kinetics of both DNA and protein adduct formation were assessed over 48 hours at a 14C-benzene dose of 5 microg/kg body weight. A dose-response study was then conducted using 14C-benzene doses from 5 ng/kg to 500 mg/kg body weight in B6C3F1 mice. Adduct levels were determined by AMS in liver and bone marrow. DNA and protein adducts in liver reached maximum levels 30 minutes after benzene administration, whereas those in bone marrow reached maximum levels after six hours. Both protein and DNA adduct AUCs were greater in bone marrow than in liver. Dose-response assessments at both 1 and 12 hours

  13. 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

  14. Hematotoxicity and concentration-dependent conjugation of phenol in mice following inhalation exposure to benzene.

    PubMed

    Wells, M S; Nerland, D E

    1991-04-01

    Benzene is metabolized to one or more hematotoxic species. Saturation of benzene metabolism could limit the production of toxic species. Saturation of phase II enzymes involved in the conjugation of the phenolic metabolites of benzene also could affect the hematotoxicity of benzene. To investigate the latter possibility, we exposed male Swiss mice, via the inhalation route, to various concentrations of benzene for 6 h per day for 5 days. Following termination of the final exposure the mice were killed and the levels of phenylsulfate and phenylglucuronide in the blood determined. Spleen weights were recorded and the number of white blood cells counted. At low benzene exposure concentrations phenylsulfate is the major conjugated form of phenol in the blood. At high exposure concentrations, phenylglucuronide is the predominant species. The reductions in spleen weight and white blood cell numbers correlated with the concentration of phenylsulfate in the blood, but are most probably not causally related.

  15. 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.

  16. A calibrated human PBPK model for benzene inhalation with urinary bladder and bone marrow compartments.

    PubMed

    Knutsen, Jeffrey S; Kerger, Brent D; Finley, Brent; Paustenbach, Dennis J

    2013-07-01

    A physiologically-based pharmacokinetic (PBPK) model of benzene inhalation based on a recent mouse model was adapted to include bone marrow (target organ) and urinary bladder compartments. Empirical data on human liver microsomal protein levels and linked CYP2E1 activities were incorporated into the model, and metabolite-specific conversion rate parameters were estimated by fitting to human biomonitoring data and adjusting for background levels of urinary metabolites. Human studies of benzene levels in blood and breath, and phenol levels in urine were used to validate the rate of human conversion of benzene to benzene oxide, and urinary benzene metabolites from Chinese benzene worker populations provided model validation for rates of human conversion of benzene to muconic acid (MA) and phenylmercapturic acid (PMA), phenol (PH), catechol (CA), hydroquinone (HQ), and benzenetriol (BT). The calibrated human model reveals that while liver microsomal protein and CYP2E1 activities are lower on average in humans compared to mice, the mouse also shows far lower rates of benzene conversion to MA and PMA, and far higher conversion of benzene to BO/PH, and of BO/PH to CA, HQ, and BT. The model also differed substantially from existing human PBPK models with respect to several metabolic rate parameters of importance to interpreting benzene metabolism and health risks in human populations associated with bone marrow doses. The model provides a new methodological paradigm focused on integrating linked human liver metabolism data and calibration using biomonitoring data, thus allowing for model uncertainty analysis and more rigorous validation.

  17. The mutagenic effects of low level sub-acute inhalation exposure to benzene in CD-1 mice.

    PubMed

    Ward, J B; Ammenheuser, M M; Ramanujam, V M; Morris, D L; Whorton, E B; Legator, M S

    1992-07-01

    Benzene is a widely used chemical and common environmental contaminant. It is carcinogenic in man and animals and is genotoxic in mice, rats, and occupationally exposed humans at doses above one part per million. In order to evaluate the genotoxic effects of prolonged exposures to very low concentrations of benzene, we exposed CD-1 mice to benzene by inhalation for 22 h per day, seven days per week for six weeks at 40, 100 and 1000 parts per billion (ppb). Additional groups were exposed to purified air or were housed in standard plastic cages. The effects of in vivo exposure to benzene were evaluated by using an autoradiographic assay to determine the frequency of mutants which represent mutations at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in spleen lymphocytes. At the end of the six weeks exposure period lymphocytes were recovered from the spleens of the mice and cryopreserved prior to assay. Mutant cells were selected on the basis of their ability to incorporate tritiated thymidine in the presence of 6-thioguanine. The weighted mean variant (mutant) frequencies (Vf) of female mice (three per group) were 7.2 x 10(-6) at 0 ppb; 29.2 x 10(-6) at 40 ppb; 62.5 x 10(-6) at 100 ppb and 25.0 x 10(-6) at 1000 ppb. The Vf of unexposed mice housed in standard cages was 13.2 x 10(-6). In male mice the same pattern of response was observed, but the increases in Vf in response to benzene were not as great. In both sexes of mice, the increases at 40 and 100 ppb were significantly greater than at 0 ppb (P less than 0.05). The increase in Vf with exposure to 100 ppb and the decline at 1000 ppb parallel the results observed for chromosome damage in spleen lymphocytes from the same animals (Au et al., Mutation Res., 260 (1991) 219-224). These results indicate that sub-chronic exposure to benzene at levels below the current Occupational Safety and Health Administration Permitted Exposure Limit may induce gene mutations in lymphocytes in mice.

  18. 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

  19. 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

  20. van der Waals rovibration levels and the high resolution spectrum of the argon-benzene dimer

    NASA Astrophysics Data System (ADS)

    van der Avoird, Ad

    1993-04-01

    The van der Waals vibrations of Ar-benzene are calculated from two different intermolecular potentials, which are analytic fits to the same ab initio potential. The rovibrational Hamiltonian was derived earlier; the wave functions of the large amplitude vibrations are expanded in products of harmonic oscillator functions. The rotational structure of each van der Waals state is obtained from perturbation theory, as well as from variational calculations of the complete rovibrational states for J=0, 1, and 2. The degenerate bending modes and combinations have a large vibrational angular momentum; for their rotational structure it is important to include all first, second, and higher order rovibrational (Coriolis) coupling. The calculated vibrational frequencies, the information about rovibrational coupling, and the PI(C6v) selection rules for van der Waals transitions, in combination with the vibronic 601 transition on the benzene monomer, lead to a partially new assignment of the three van der Waals sidebands observed in high resolution UV spectra.

  1. 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.

  2. 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

  3. Trends of PCB, hexachlorobenzene, and. beta. -benzene hexachloride levels in the adipose tissue of the U. S. population

    SciTech Connect

    Robinson, P.E.; Remmers, J. ); Mack, G.A. ); Levy, R. ); Mohadjer, L. )

    1990-12-01

    Results are presented on the levels of selected toxic chemicals in the adipose tissue of the U.S. population. Estimates of baseline levels and time trends are presented for the chemicals {beta}-benzene hexachloride ({beta}-BHC), hexachlorobenzene, and polychlorinated biphenyls (PCBs). The statistical analyses are based on chemical data obtained from analysis of tissue specimens collected from a nationally representative sample of autopsied cadavers and surgical patients by EPA's National Human Adipose Tissue Survey during the period 1970 through 1983. The results show that while nearly the entire U.S. population has detectable levels of these chemicals, the actual concentration levels of {beta}-BHC and PCBs are steadily decreasing and the levels of HCB are remaining fairly constant. Comparisons of levels across demographic subpopulations show that there are some differences in concentration levels across geographic regions, age groups, and race groups.

  4. Gut Microbial Fatty Acid Metabolites Reduce Triacylglycerol Levels in Hepatocytes.

    PubMed

    Nanthirudjanar, Tharnath; Furumoto, Hidehiro; Zheng, Jiawen; Kim, Young-Il; Goto, Tsuyoshi; Takahashi, Nobuyuki; Kawada, Teruo; Park, Si-Bum; Hirata, Akiko; Kitamura, Nahoko; Kishino, Shigenobu; Ogawa, Jun; Hirata, Takashi; Sugawara, Tatsuya

    2015-11-01

    Hydroxy and oxo fatty acids were recently found to be produced as intermediates during gut microbial fatty acid metabolism. Lactobacillus plantarum produces these fatty acids from unsaturated fatty acids such as linoleic acid. In this study, we investigated the effects of these gut microbial fatty acid metabolites on the lipogenesis in liver cells. We screened their effect on sterol regulatory element binding protein-1c (SREBP-1c) expression in HepG2 cells treated with a synthetic liver X receptor α (LXRα) agonist (T0901317). The results showed that 10-hydroxy-12(Z)-octadecenoic acid (18:1) (HYA), 10-hydroxy-6(Z),12(Z)-octadecadienoic acid (18:2) (γHYA), 10-oxo-12(Z)-18:1 (KetoA), and 10-oxo-6(Z),12(Z)-18:2 (γKetoA) significantly decreased SREBP-1c mRNA expression induced by T0901317. These fatty acids also downregulated the mRNA expression of lipogenic genes by suppressing LXRα activity and inhibiting SREBP-1 maturation. Oral administration of KetoA, which effectively reduced triacylglycerol accumulation and acetyl-CoA carboxylase 2 (ACC2) expression in HepG2 cells, for 2 weeks significantly decreased Srebp-1c, Scd-1, and Acc2 expression in the liver of mice fed a high-sucrose diet. Our findings suggest that the hypolipidemic effect of the fatty acid metabolites produced by L. plantarum can be exploited in the treatment of cardiovascular diseases or dyslipidemia. PMID:26399511

  5. 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

  6. Exposure of hematopoietic stem cells to benzene or 1,4-benzoquinone induces gender-specific gene expression.

    PubMed

    Faiola, Brenda; Fuller, Elizabeth S; Wong, Victoria A; Pluta, Linda; Abernethy, Diane J; Rose, Jason; Recio, Leslie

    2004-01-01

    Chronic exposure to benzene results in progressive decline of hematopoietic function and may lead to the onset of various disorders, including aplastic anemia, myelodysplastic syndrome, and leukemia. Damage to macromolecules resulting from benzene metabolites and misrepair of DNA lesions may lead to changes in hematopoietic stem cells (HSCs) that give rise to leukemic clones. We have shown previously that male mice exposed to benzene by inhalation were significantly more susceptible to benzene-induced toxicities than females. Because HSCs are targets for benzene-induced cytotoxicity and genotoxicity, we investigated DNA damage responses in HSC from both genders of 129/SvJ mice after exposure to 1,4-benzoquinone (BQ) in vitro or benzene in vivo. 1,4-BQ is a highly reactive metabolite of benzene that can cause cellular damage by forming protein and DNA adducts and producing reactive oxygen species. HSCs cultured in the presence of 1,4-BQ for 24 hours showed a gender-independent, dose-dependent cytotoxic response. RNA isolated from 1,4-BQ-treated HSCs and HSCs from mice exposed to 100 ppm benzene by inhalation showed altered expression of apoptosis, DNA repair, cell cycle, and growth control genes compared with unexposed HSCs. Rad51, xpc, and mdm-2 transcript levels were increased in male but not female HSCs exposed to 1,4-BQ. Males exposed to benzene exhibited higher mRNA levels for xpc, ku80, ccng, and wig1. These gene expression differences may partially explain the gender disparity in benzene susceptibility. HSC culture systems such as the one used here will be useful for testing the hematotoxicity of various substances, including other benzene metabolites.

  7. Phase II metabolism of benzene.

    PubMed Central

    Schrenk, D; Orzechowski, A; Schwarz, L R; Snyder, R; Burchell, B; Ingelman-Sundberg, M; Bock, K W

    1996-01-01

    The hepatic metabolism of benzene is thought to be a prerequisite for its bony marrow toxicity. However, the complete pattern of benzene metabolites formed in the liver and their role in bone marrow toxicity are not fully understood. Therefore, benzene metabolism was studied in isolated rodent hepatocytes. Rat hepatocytes released benzene-1,2-dihydrodiol, hydroquinone (HQ), catechol (CT), phenol (PH), trans-trans-muconic acid, and a number of phase II metabolites such as PH sulfate and PH glucuronide. Pretreatment of animals with 3-methylcholantrene (3-MC) markedly increased PH glucuronide formation while PH sulfate formation was decreased. Likewise, V79 cells transfected with the 3-MC-inducible rat UGT1.6 cDNA showed a considerable rate of PH and HQ glucuronidation. In addition to inducing glucuronidation of phenols, 3-MC treatment (reported to protect rats from the myelotoxicity of benzene) resulted in a decrease of hepatic CYP2E1. In contrast, pretreatment of rats with the CYP2E1-inducer isopropanol strongly enhanced benzene metabolism and the formation of phenolic metabolites. Mouse hepatocytes formed much higher amounts of HQ than rat hepatocytes and considerable amounts of 1,2,4-trihydroxybenzene (THB) sulfate and HQ sulfate. In conclusion, the protective effect of 3-MC in rats is probably due to a shift from the labile PH sulfate to the more stable PH glucuronide, and to a decrease in hepatic CYP2E1. The higher susceptibility of mice toward benzene may be related to the high rate of formation of the myelotoxic metabolite HQ and the semistable phase II metabolites HQ sulfate and THB sulfate. Images Figure 4. PMID:9118891

  8. Facts about Benzene

    MedlinePlus

    ... of benzene from tobacco smoke, gas stations, motor vehicle exhaust, and industrial emissions. Indoor air generally contains ... to anemia. Also, it can damage the immune system by changing blood levels of antibodies and causing ...

  9. 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.

  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. PMID:23222815

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

    PubMed Central

    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. PMID:27058040

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

    PubMed Central

    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; Slagboom, P. Eline; 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.

    2016-01-01

    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. PMID:26068415

  14. 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

  15. 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.

  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. Do optimally ripe blackberries contain the highest levels of metabolites?

    PubMed

    Mikulic-Petkovsek, Maja; Koron, Darinka; Zorenc, Zala; Veberic, Robert

    2017-01-15

    Five blackberry cultivars were selected for the study ('Chester Thornless', 'Cacanska Bestrna', 'Loch Ness', 'Smoothstem' and 'Thornfree') and harvested at three different maturity stages (under-, optimal- and over-ripe). Optimally ripe and over-ripe blackberries contained significantly higher levels of total sugars compared to under-ripe fruit. 'Loch Ness' cultivar was characterized by 2.2-2.6-fold higher levels of total sugars than other cultivars and consequently, the highest sugar/acids ratio. 'Chester Thornless' stands out as the cultivar with the highest level of vitamin C in under-ripe (125.87mgkg(-1)) and optimally mature fruit (127.66mgkg(-1)). Maturity stage significantly affected the accumulation of phenolic compounds. The content of total anthocyanins increased for 43% at optimal maturity stage and cinnamic acid derivatives for 57% compared to under-ripe fruit. Over-ripe blackberries were distinguished by the highest content of total phenolics (1251-2115mg GAE kg(-1) FW) and greatest FRAP values (25.9-43.2mM TE kg(-1) FW). PMID:27542448

  19. 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

  20. 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.

  1. Aryl hydrocarbon receptor mediates benzene-induced hematotoxicity.

    PubMed

    Yoon, Byung-Il; Hirabayashi, Yoko; Kawasaki, Yasushi; Kodama, Yukio; Kaneko, Toyozo; Kanno, Jun; Kim, Dae-Yong; Fujii-Kuriyama, Yoshiaki; Inoue, Tohru

    2002-11-01

    Benzene can induce hematotoxicity and leukemia in humans and mice. Since a review of the literature shows that the CYP2E1 knockout mouse is not known to possess any benzene toxicity, the metabolism of benzene by CYP2E1 in the liver is regarded to be prerequisite for its cytotoxicity and genotoxicity, although the mechanism is not fully understood yet. Because it was found some years ago that benzene was also a substrate for CYP1A1, we investigated the involvement of the aryl hydrocarbon receptor (AhR) in benzene hematotoxicity using AhR wild-type (AhR(+/+)), heterozygous (AhR(+/-)), and homozygous (AhR(-/-)) male mice. Interestingly, following a 2-week inhalation of 300 ppm benzene (a potent dose for leukemogenicity), no hematotoxicity was induced in AhR(-/-) mice. Further, there were no changes in cellularity of peripheral blood and bone marrow (BM), nor in levels of granulocyte-macrophage colony-forming units in BM. This lack of hematotoxicity was associated with the lack of p21 overexpression, which was regularly seen in the wild-type mice following benzene inhalation. Combined treatment with two major benzene metabolites, phenol and hydroquinone, induced hemopoietic toxicity, although it was not known whether this happened due to a surprising lack of expression of CYP2E1 by AhR knockout, or due to a lack of other AhR-mediated CYP enzymes, including 1A1 (i.e., a possible alternative pathway of benzene metabolism). The former possibility, evaluated in the present study, failed to show a significant relationship between AhR and the expression of CYP2E1. Furthermore, a subsequent evaluation of AhR expression after benzene inhalation tended to show higher but less significant expression in the liver, and none in the BM, compared with sham control. Although this study failed to identify the more likely of the above-mentioned two possibilities, the study using AhR knockout mice on benzene inhalation presents the unique possibility that the benzene toxicity may be

  2. 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. PMID:26411479

  3. 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.

  4. 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 ...

  5. 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.

  6. Levels of dialkylphosphate metabolites in urine among general U.S. population.

    PubMed

    Jain, Ram B

    2016-04-01

    Data from National Health and Nutrition Examination Survey for years 2003-2008 were used to study the factors that affect urinary levels of dialkylphosphate (DAP) metabolites in urine. Separate regression models were fitted for children aged 6-11 years, adolescents aged 12-19 years, and adults aged ≥20 years. Specifically, DAP metabolites that were analyzed were: dimethylphosphate (DMP), diethylphosphate (DEP), dimethylthiophosphate (DMTP), and diethylthiophosphate (DETP). Males had statistically significantly lower adjusted levels than females for DMP for adolescents, for DEP for adults, for DMTP for both adolescents and adults, and for DETP for both children and adults. Nonsmokers had statistically significantly higher adjusted levels than smokers for DMTP for adolescents and for DMP and DMTP for adults. Exposure to second hand smoke at home was associated with relatively higher levels of DMP among children (p=0.01) but the reverse was found to be true for DMTP (p<0.01) among adolescents as well as adults (p=0.02). Children had higher levels of DMTP than both adolescents and adults (p<0.01) and higher levels of DETP than adolescents (p=0.02). Age was found to be negatively associated with the levels of DMTP (p=0.01) among children and positively associated (p<0.01) with the levels of all four metabolites among adults. PMID:26970058

  7. 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.

  8. 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.

  9. Polysubstance and Alcohol Dependence: Unique Abnormalities of Magnetic Resonance-Derived Brain Metabolite Levels

    PubMed Central

    Abé, Christoph; Mon, Anderson; Durazzo, Timothy C.; Pennington, David L.; Schmidt, Thomas P.; Meyerhoff, Dieter J.

    2012-01-01

    BACKGROUND Although comorbid substance misuse is common in alcohol dependence, and polysubstance abusers (PSU) represent the largest group of individuals seeking treatment for drug abuse today, we know little about potential brain abnormalities in this population. Brain magnetic resonance spectroscopy studies of mono-substance use disorders (e.g., alcohol or cocaine) reveal abnormal levels of cortical metabolites (reflecting neuronal integrity, cell membrane turnover/synthesis, cellular bioenergetics, gliosis) and altered concentrations of glutamate and γ-aminobutyric acid (GABA). The concurrent misuse of several substances may have unique and different effects on brain biology and function compared to any mono-substance misuse. METHODS High field brain magnetic resonance spectroscopy at 4 Tesla and neurocognitive testing were performed at one month of abstinence in 40 alcohol dependent individuals (ALC), 28 alcohol dependent PSU and 16 drug-free controls. Absolute metabolite concentrations were calculated in anterior cingulate (ACC), parieto-occipital (POC) and dorsolateral prefrontal cortices (DLPFC). RESULTS Compared to ALC, PSU demonstrated significant metabolic abnormalities in the DLPFC and strong trends to lower GABA in the ACC. Metabolite levels in ALC and light drinking controls were statistically equivalent. Within PSU, lower DLPFC GABA levels related to greater cocaine consumption. Several cortical metabolite concentrations were associated with cognitive performance. CONCLUSIONS While metabolite concentrations in ALC at one month of abstinence were largely normal, PSU showed persistent and functionally significant metabolic abnormalities, primarily in the DLPFC. Our results point to specific metabolic deficits as biomarkers in polysubstance misuse and as targets for pharmacological and behavioral PSU-specific treatment. PMID:23122599

  10. Sleep deprivation in the rat: XVIII. Regional brain levels of monoamines and their metabolites.

    PubMed

    Bergmann, B M; Seiden, L S; Landis, C A; Gilliland, M A; Rechtschaffen, A

    1994-10-01

    Several theories have linked sleep with change in monoamine activity. However, the use of sleep deprivation to show that changes in sleep generate changes in monoamines (directly or through feedback) has produced inconsistent results. To explore whether longer sleep deprivation, better documented sleep loss, more complete controls or regional brain analyses would produce clear sleep loss-induced change, eight rats were subjected to total sleep deprivation (TSD) by the disk-over-water method for 11-20 days and were guillotined along with yoked control (TSC) and home-cage control (HCC) rats. Brains were removed and dissected to obtain the caudate, frontal cortex, hippocampus, hypothalamus, midbrain and hindbrain (pons-medulla). Tissue sections were analyzed for concentrations of serotonin (5HT), its metabolite 5-hydroxyindoleacetic acid (5HIAA), dopamine (DA), its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), and either norepinephrine or, in the caudate section, the DA metabolite homovanillic acid. The ratios DOPAC/DA and 5HIAA/5HT, which under some conditions are indicators of turnover, were also calculated. Because sleep deprivation time varied across sets of TSD, TSC and HCC rats and not all eight sets were analyzed simultaneously, a repeated-measures ANOVA was performed within sets with HCC, TSC and TSD considered as successive levels of sleep deprivation treatment. In no case did TSD rats have significantly higher or lower values of amines, metabolites or ratios than both HCC and TSC rats. The most common outlying values were for TSC rats. Thus, these results failed to demonstrate sleep loss-induced regional changes in levels of major brain monoamines or their metabolites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7531362

  11. 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.

  12. 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.

  13. 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.

  14. 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. PMID:27466017

  15. 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.

  16. 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...

  17. 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

  18. CSF levels of receptor-active endorphins in schizophrenic patients: correlations with symptomatology and monoamine metabolites.

    PubMed

    Lindström, L H; Besev, G; Gunne, L M; Terenius, L

    1986-10-01

    Cerebrospinal fluid (CSF) levels of an opioid receptor-active, chromatographically separated endorphin fraction (Fraction I) were measured in 45 schizophrenic patients and 18 healthy volunteers. Significantly increased levels of Fraction I differentiated the patient group from controls, with no difference being found between newly admitted untreated and chronic previously neuroleptic-treated subjects. Fraction I levels did not correlate with age, weight, height, duration of illness, total time hospitalized, or age when symptoms first appeared. No differences were found between patients with or without a family history of schizophrenia. Fraction I levels were negatively correlated with "hallucinations" and "indecision" on the Comprehensive Psychopathological Rating Scale. Increased levels of Fraction I were associated with low levels of the dopamine metabolite homovanillic acid in drug-free schizophrenics. This relationship was not present after neuroleptic treatment or in healthy controls. No relationship was found between Fraction I and the serotonin metabolite 5-hydroxyindoleacetic acid. Neuroleptic treatment did not significantly change Fraction I levels; when only patients above the control range were considered, however, a significant decrease was observed. The data support our previous hypothesis of an increased opioid activity in schizophrenia and further indicate a concomitant dysfunction of brain endorphin and dopamine activity in schizophrenic patients.

  19. 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.

  20. 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.

  1. 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. PMID:26519048

  2. 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.

  3. 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.

  4. Studies on the mechanism of benzene toxicity.

    PubMed Central

    Snyder, R; Dimitriadis, E; Guy, R; Hu, P; Cooper, K; Bauer, H; Witz, G; Goldstein, B D

    1989-01-01

    Using the 59Fe uptake method of Lee et al. it was shown that erythropoiesis in female mice was inhibited following IP administration of benzene, hydroquinone, p-benzoquinone, and muconaldehyde. Toluene protected against the effects of benzene. Coadministration of phenol plus either hydroquinone or catechol resulted in greatly increased toxicity. The combination of metabolites most effective in reducing iron uptake was hydroquinone plus muconaldehyde. We have also shown that treating animals with benzene leads to the formation of adducts of bone marrow DNA as measured by the 32P-postlabeling technique. PMID:2792049

  5. Chromosome aberrations in lymphocytes of mice after sub-acute low-level inhalation exposure to benzene.

    PubMed

    Au, W W; Ramanujam, V M; Ward, J B; Legator, M S

    1991-06-01

    Male and female CD-1 mice were exposed to near ambient air concentrations of benzene by inhalation for 22 h per day, 7 days per week for 6 weeks. The concentrations were 0, 40, 100 and 1000 ppb. Significant increases in chromosome aberrations in spleen lymphocytes were observed in exposed compared with control mice except in the high-dose group (p less than 0.05 for female mice in 2 experiments and for male mice in 1 experiment; p less than 0.15 for male mice in the second experiment). A lack of increase in aberrations among mice of the high-dose group may be due to an induction of detoxifying enzymes as observed by us in a previous study (Au et al., 1988b). We also found that the female mice were more sensitive to the clastogenic activity of benzene than male mice under our experimental conditions. Our study serves to emphasize the need to conduct subchronic, low-dose in vivo genotoxicity studies using exposure conditions similar to those of humans, for evaluation of potential hazards. Our data suggest that the current occupational exposure concentrations for benzene (less than 1000 ppb) may still be hazardous to humans.

  6. Percutaneous penetration of benzene and benzene contained in solvents used in the rubber industry

    SciTech Connect

    Maibach, H.I.; Anjo, D.M.

    1981-09-01

    Penetration of benzene through the skin of the rhesus monkey was determined using /sup 14/C-benzene, and quantitating the labelled metabolites in urine. The modes of application and amounts of benzene that penetrated the skin (indicated in parentheses) are as follows: (1) a single, direct cutaneous application of liquid benzene (0.172 +/- 0.139%); (2) a single application of benzene-containing (0.36%) solvent (0.0805 +/- 0.0306%); (3) multiple washes with full-strength benzene (0.848 +/- 0.0806%); (4) multiple washes with the benzene-containing (0.35%) solvent (0.431 +/- 0.258%); (5) removal of the stratum corneum followed by application of full-strength benzene (0.09 +/- 0.627%); and (6) application of benzene to the palmar surface (0.651 +/- 0.482%). Until more complete human data becomes available, benzene penetration in the monkey may be used to estimate penetration in man, both for industrial hygiene purposes and general toxicological use.

  7. 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).

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. Acanthamoeba castellanii metabolites increase the intracellular calcium level and cause cytotoxicity in wish cells.

    PubMed

    Mattana, A; Bennardini, F; Usai, S; Fiori, P L; Franconi, F; Cappuccinelli, P

    1997-08-01

    Previous studies have shown that trophozoites of the pathogenic free-living amoeba Acanthamoeba castellanii rapidly lyse a variety of cells in vitro. However, the role played by cytolitic molecules that may participate in Acanthamoebal cytopathogenicity has yet to be completely elucidated. The aim of this work was to study whether soluble molecules released by A. castellanii trophozoites could induce cytopathic effect in human epithelial cells in vitro. The results obtained indicate that A. castellanii trophozoites constitutively elaborate and release soluble factors that immediately elicit a cytosolic free-calcium increase in target cells. This phenomenon is induced by low molecular weight amoebic metabolites and depends on a transmembrane influx of extracellular calcium. Morphological changes, cytoskeletal damage, cell death and cytolysis followed the elevation of cytosolic free-calcium levels. Calcium ions are very important for cell homeostasis, in fact, they control the functions of a variety of cellular responses, including secretion, cell proliferation and apoptosis. Our results suggest that the substained elevation of the cytosolic free-calcium in response to A. castellanii metabolites might play a fundamental role in target cell damage during Acanthamoeba infections. PMID:9245619

  13. Brain met-enkephalin immunostaining after subacute and subchronic exposure to benzene

    SciTech Connect

    Gandarias, J.M. de; Echevarria, E.; Martinez-Millan, L.; Casis, L.; Martinez-Garcia, F.

    1994-01-01

    Benzene is used in a wide variety of domestic and occupational activities, and due to its lipophilic nature, it accumulates in lipid-rich tissues like the brain. In this sense, neurotoxic action has long been associated with organic solvent exposure and it has been shown that benzene, injected in a single dose or during a prolongued administration, modifies the content of dopamine, noradrenaline, serotonin and its main metabolite 5-hydroxy indolacetic acid, in several brain regions of the rat, then revealing a stimulating action on brain monoamine synthesis and turnover. However, information concerning neurotoxic action of benzene exposure in vivo on peptidergic neuromodulatory systems is still lacking. Nevertheless, it has been recently described that subacute benzene exposure in rats generates regional changes in brain aminopeptidase activity. These proteolytic enzymes have been widely associated with metabolic control of neuropeptides and it has been suggested that they could play a role in benzene neurotoxic mechanism by hypothetically changing regional neuropeptide levels. This being the case, we focused on analyzing met-enkephalin immunostaining in different brain regions of the rat after subacute and subchronic administration of benzene. 12 refs., 3 figs.

  14. Pomegranate Juice and Extracts Provide Similar Levels of Plasma and Urinary Ellagitannin Metabolites in Human Subjects

    PubMed Central

    Zhang, Yanjun; McKeever, Rodney; Henning, Susanne M.; Lee, Ru-po; Suchard, Marc A.; Li, Zhaoping; Chen, Steve; Thames, Gail; Zerlin, Alona; Nguyen, Martha; Wang, David; Dreher, Mark; Heber, David

    2008-01-01

    Abstract Pomegranate juice (PJ), a rich source of polyphenols including ellagitannins, has attracted much attention due to its reported health benefits. This has resulted in the consumption of liquid and powder pomegranate extracts as alternatives to PJ. Therefore establishing the bioavailability of polyphenols from these extract preparations is necessary. Sixteen healthy volunteers sequentially consumed, with a 1-week washout period between treatments, PJ (8 ounces, Wonderful fruit variety), a pomegranate polyphenol liquid extract (POMxl, 8 ounces), and a pomegranate polyphenol powder extract (POMxp, 1,000 mg). The three interventions provided 857, 776, and 755 mg of polyphenols as gallic acid equivalents, respectively. Plasma bioavailability, judged based on ellagic acid levels over a 6-hour period, did not show statistical differences in area under the curve for the three interventions: 0.14 ± 0.05, 0.11 ± 0.03, and 0.11 ± 0.04 μmol · hour/L for PJ, POMxl, and POMxp, respectively. The time of maximum concentration was delayed for POMxp (2.58 ± 0.42 hours) compared to PJ (0.65 ± 0.23 hours) and POMxl (0.94 ± 0.06 hours). Urolithin-A glucuronide, a urinary metabolite of ellagic acid, was not significantly different with the three interventions, reaching levels of approximately 1,000 ng/mL. This study demonstrates that ellagitannin metabolites, delivered from pomegranate fruits, as PJ, POMxl, and POMxp, reach equivalent levels with a delay in time of maximum concentration of POMxp compared to PJ and POMxl. PMID:18598186

  15. Human urinary/seminal phthalates or their metabolite levels and semen quality: A meta-analysis.

    PubMed

    Cai, Hongquan; Zheng, Weiwei; Zheng, Pai; Wang, Shu; Tan, Hui; He, Gengsheng; Qu, Weidong

    2015-10-01

    Health concerns surrounding human exposure to phthalates include diminished semen quality. Epidemiological findings remain inconsistent. We have performed a quality appraisal and meta-analysis to quantitatively summarize evidence for associations between phthalate exposures and human semen quality. Pubmed and Web of Science were searched for pertinent studies through October 2014. Cited references were reviewed to identify secondary studies. Studies that reported quantitative estimates of the association between phthalates or their metabolite levels in humans and semen quality were eligible. Random effects models were used to calculate pooled effects estimates. Overall, 20 studies met our inclusion criteria. Subsequently, 14 studies were included in the meta-analysis. Urinary monobutyl phthalate (MBP) and monobenzyl phthalate (MBzP) were associated with reduced sperm concentration (MBP [7.4-25.3 µg/L], pooled odds ratio [OR]=2.60, 95% confidence interval [CI]=1.32-5.15; MBzP [14.0-540.2 µg/L], pooled OR=2.23, 95% CI=1.16-4.30). Both MBP (24.6-14,459.0 µg/L) and MEHP (3.1-208.1 µg/L) were inversely associated with straight line velocity (VSL; MBP, pooled β=-2.51, 95% CI=-4.44, -0.59; MEHP, pooled β=-1.06, 95% CI=-1.99, -0.12). An IQR increase in MBzP and MEP levels (MBzP, IQR=11.35 µg/L; MEP, IQR=449.4 µg/L) was associated with an increase in comet extent (CE; MBzP, pooled β=3.57, 95% CI=0.89-6.25; MEP, pooled β=4.22, 95% CI=1.66-6.77). No associations were observed between monomethyl phthalate and any semen parameters. Our meta-analysis strengthens the evidence that specific phthalates or their metabolite levels may affect semen quality.

  16. Correlation between environmental and biological monitoring of exposure to benzene in petrochemical industry operators.

    PubMed

    Carrieri, Mariella; Tranfo, Giovanna; Pigini, Daniela; Paci, Enrico; Salamon, Fabiola; Scapellato, Maria L; Fracasso, Maria E; Manno, Maurizio; Bartolucci, Giovanni B

    2010-01-15

    The present work was aimed to study in petrochemical industry operators the correlation, if any, between environmental exposure to low levels of benzene and two biological exposure indexes in end-shift urine, i.e. trans, trans-muconic acid (t,t-MA) and S-phenylmercapturic acid (SPMA). Exposure to benzene was assessed in 133 male subjects employed in outdoor operations in a petrochemical plant, using personal passive-diffusive air samplers worn at the breathing zone; adsorbed benzene was determined by GC-FID analysis. S-PMA was determined by a new HPLCMS/MS method, after (quantitative) acidic hydrolysis of the cysteine conjugate precursor. t,t-MA was measured by an HPLC-UV method. Smoking habits were assessed by means of a self-administered questionnaire. Both environmental and biological monitoring data showed that benzene exposure of petrochemical industry operators was low (mean values were 0.014ppm, 101mug/g creat, and 2.8mug/g creat, for benzene, t,t-MA, and S-PMA, respectively) if compared with the ACGIH limits. Cigarette smoking was confirmed to be a strong confounding factor for the urinary excretion of both metabolites: statistically significant increases of t,t-MA and S-PMA levels were recorded in smokers when compared to non-smokers (p<0.0001). The best correlation found was that between exposure to benzene and S-PMA levels, particularly in non-smokers. This was partly due to the hydrolysis of the S-PMA precursor N-acetyl-S-(1,2-dihydro-2-hydroxyphenyl)-l-cysteine, a crucial step of the new analytical method used, which indeed reduced the variability of the results by means of an improved standardization of this critical preanalytical factor. A weaker correlation was found between exposure to benzene and t,t-MA, possibly explained by the fact that the latter is also a metabolite of sorbic acid, a common diet component. In summary, even at such low levels of exposure, urinary metabolites proved to be a useful tool for assessing individual occupational

  17. Effects of Dietary Protein Levels for Gestating Gilts on Reproductive Performance, Blood Metabolites and Milk Composition

    PubMed Central

    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. PMID:25049930

  18. Feasibility of hair sampling to assess levels of organophosphate metabolites in rural areas of Sri Lanka

    PubMed Central

    Knipe, D.W.; Jayasumana, C.; Siribaddana, S.; Priyadarshana, C.; Pearson, M.; Gunnell, D.; Metcalfe, C.; Tzatzarakis, M.N.; Tsatsakis, A.M.

    2016-01-01

    Measuring chronic pesticide exposure is important in order to investigate the associated health effects. Traditional biological samples (blood/urine) are difficult to collect, store and transport in large epidemiological studies in settings such as rural Asia. We assessed the acceptability of collecting hair samples from a rural Sri Lankan population and found that this method of data collection was feasible. We also assessed the level of non-specific metabolites (DAPS) of organophosphate pesticides in the hair samples. The median concentration (pg/mg) of each DAP was: diethyl phosphate: 83.3 (IQI 56.0, 209.4); diethyl thiophosphate: 34.7 (IQI 13.8, 147.9); diethyl dithiophosphate: 34.5 (IQI 23.4, 55.2); and dimethyl phosphate: 3 (IQI 3, 109.7). Total diethylphosphates were recovered in >80% of samples and were positively correlated with self-reported pesticide exposure. PMID:26894816

  19. 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.

  20. Feasibility of hair sampling to assess levels of organophosphate metabolites in rural areas of Sri Lanka.

    PubMed

    Knipe, D W; Jayasumana, C; Siribaddana, S; Priyadarshana, C; Pearson, M; Gunnell, D; Metcalfe, C; Tzatzarakis, M N; Tsatsakis, A M

    2016-05-01

    Measuring chronic pesticide exposure is important in order to investigate the associated health effects. Traditional biological samples (blood/urine) are difficult to collect, store and transport in large epidemiological studies in settings such as rural Asia. We assessed the acceptability of collecting hair samples from a rural Sri Lankan population and found that this method of data collection was feasible. We also assessed the level of non-specific metabolites (DAPS) of organophosphate pesticides in the hair samples. The median concentration (pg/mg) of each DAP was: diethyl phosphate: 83.3 (IQI 56.0, 209.4); diethyl thiophosphate: 34.7 (IQI 13.8, 147.9); diethyl dithiophosphate: 34.5 (IQI 23.4, 55.2); and dimethyl phosphate: 3 (IQI 3, 109.7). Total diethylphosphates were recovered in >80% of samples and were positively correlated with self-reported pesticide exposure.

  1. 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.

  2. Electroanalytical approaches to understanding benzene metabolism.

    PubMed

    Lunte, S M; Lunte, C E

    1990-01-01

    Electrochemical techniques are ideally suited to the study of the metabolism of aromatic xenobiotics because the metabolites are frequently easier to oxidize than the parent compounds. In many cases, the trace metabolites have the lowest oxidation potentials and hence electrochemical methods have the greatest selectivity for these compounds. The sensitivity of dual-electrode liquid chromatography-electrochemistry for the detection and identification of trace metabolites was demonstrated by the detection of the secondary metabolite, hydroquinone, in a microsomal incubation containing benzene and ascorbic acid. The use of an electrochemical detector in a series configuration provides increased selectivity for chemically reversible metabolites such as hydroquinone. Electrochemical methods can also be used to generate metabolites. The products of the electrochemical oxidation of phenol and biphenol are compared with those generated in a peroxidase incubation.

  3. 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.

  4. 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.

  5. 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. PMID:19748114

  6. 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

  7. CSF levels of the histamine metabolite tele-methylhistamine are only slightly decreased in Alzheimer's disease.

    PubMed

    Motawaj, Mouhammad; Peoc'h, Katell; Callebert, Jacques; Arrang, Jean-Michel

    2010-01-01

    Neuropathological studies have reported a strong neurofibrillary degeneration of the tuberomamillary nucleus, the region of origin of histamine neurons, in Alzheimer's disease (AD). Histaminergic neurons enhance cognition and memory, suggesting that their degeneration may contribute to the cognitive decline of AD. Besides neurons, the brain histaminergic system comprises mast cells and microglia that can also produce histamine. The level of activity of this histaminergic system in AD remained unknown. In the present study, we have measured the levels of the main histamine metabolite in brain, tele-methylhistamine (t-MeHA), an index of histaminergic system activity, in the cerebrospinal fluid (CSF) of 97 non-AD (controls) and 91 AD patients, males or females. t-MeHA levels in CSF of controls tended to be higher, although non-significantly, in females than in males. t-MeHA levels of controls and AD significantly increased with age (1.66 ± 0.13, 2.04 ± 0.12, and 2.76 ± 0.12 pmol/ml at 40, 60 and 80 years, respectively). In spite of the strong degeneration of histamine neurons in the disease, t-MeHA levels in CSF were only slightly decreased in AD compared to controls (2.14 ± 0.10 vs 2.76 ± 0.13 pmol/ml, -22%, p < 0.01). This decrease was similar whatever the age, and was slightly higher in females than in males. The increase observed with age, and the limited magnitude of the decrease in AD even at late stages may result from the compensatory activation of spared neurons, as well as the neuroinflammation-induced activation of microglia occurring in senescence and AD.

  8. Fruit and vegetable intake and urinary levels of prostaglandin E₂ metabolite in postmenopausal women.

    PubMed

    Kim, Sangmi; Rimando, Joseph; Sandler, Dale P

    2015-01-01

    Prostaglandin E2 (PGE2) is an inflammatory mediator that plays key roles in promoting tumor development and progression. Urinary concentration of a major PGE2 metabolite (PGE-M) has been recently proposed as a promising cancer biomarker. Using dietary intake data from 600 postmenopausal women aged 50-74 years, we examined cross-sectional relationships between fruit and vegetable intake and urinary levels of PGE-M, determined using liquid chromatography/tandem mass spectrometry. After multivariable adjustment, increasing consumption of fruits, but not vegetables, was associated with reduced levels of urinary PGE-M (P for linear trend = 0.02), with geometric means of 5.8 [95% confidence interval (CI): 5.2-6.6] in the lowest quintile versus 4.8 (95% CI: 4.3-5.4) in the highest quintile (Q5) of fruit consumption. A better quality diet, indicated by higher scores on the Healthy Eating Index, was also associated with decreased PGE-M (P for linear trend <0.01). The lack of association with vegetable intake may be related to variation in antioxidant capacities of the major dietary sources of fruits and vegetables for the study participants. Our findings suggest that urinary PGE-M may be modifiable by a healthy diet that follows current national dietary guideline. Further studies are warranted to assess potential utility of urinary PGE-M in assessing cancer prevention efficacy.

  9. Benzene pollution from gasoline usage.

    PubMed

    Foo, S C

    1991-04-01

    Local gasolines contain benzene ranging from 1.8 to 3.7% and their use can lead to significant exposure to benzene. Gasoline station attendants were found to be exposed to short-term exposure levels (STEL) of 0.064-179 ppm. Their 8-h time-weighted averaged (TWA) exposure ranged from 0.028 to 0.71 ppm. For motorcar service mechanics, TWA exposure levels ranged from 0.014 to 1.7 ppm. The exposure of drivers of gasoline delivery tankers ranged from 0.08 to 2.37 ppm for personal TWA exposure over the whole workshift. For local people not occupationally exposed to gasoline or other benzene-containing volatile chemicals, exposure from the ambient environment ranged from 0.0023 to 0.027 ppm. Gasoline usage also contributed to the contamination of surface water with benzene. Benzene levels in water samples taken from drains leading from gasoline stations were between 1.1 and 40.4 micrograms l-1.

  10. Biomonitoring of benzene and 1,3-butadiene exposure and early biological effects in traffic policemen.

    PubMed

    Arayasiri, Manaswee; Mahidol, Chulabhorn; Navasumrit, Panida; Autrup, Herman; Ruchirawat, Mathuros

    2010-09-15

    The objective of this study was to determine benzene and 1,3-butadiene exposure through ambient air and personal air monitoring, as well as through biomarkers of exposure, and to evaluate the potential health risk of exposure through the use of biomarkers of early biological effects in central Bangkok traffic policemen. Ambient air concentrations of benzene and 1,3-butadiene at the roadsides were significantly higher than in police offices used as control sites (p<0.001). Traffic policemen had a significantly higher exposure to benzene (median 38.62 microg/m(3)) and 1,3-butadiene (median 3.08 microg/m(3)) than office policemen (median 6.17 microg/m(3) for benzene and 0.37 microg/m(3) for 1,3-butadiene) (p<0.001). Biomarkers of benzene exposure, blood benzene, and urinary metabolite, trans, trans-muconic acid were significantly higher in traffic policemen than office policemen (p<0.001). No significant difference between traffic and office policemen was found in urinary benzene metabolite, S-phenyl mercapturic acid, or in urinary 1,3-butadiene metabolite, monohydroxy-butenyl mercapturic acid. Biomarkers of early biological effects, 8-hydroxy-2'-deoxyguanosine in leukocytes (8-OHdG), DNA-strand breaks, and DNA-repair capacity, measured as an increase in gamma ray-induced chromosome aberrations were significantly higher in traffic policemen than controls (p<0.001 for 8-OHdG, p<0.01 for tail length, p<0.001 for olive tail moment, p<0.05 for dicentrics and p<0.01 for deletions). Multiple regression model including individual exposure, biomarkers of exposure, ages and years of work as independent variables showed that only the levels of individual 1,3-butadiene exposure were significantly associated with 8-OHdG and olive tail moment at p<0.0001 indicating more influence of 1,3-butadiene on DNA damage. These results indicated that traffic policemen, who are exposed to benzene and 1,3-butadiene at the roadside in central Bangkok, are potentially at a higher risk for

  11. 10 CFR 26.163 - Cutoff levels for drugs and drug metabolites.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Cocaine metabolite 2 150 Opiates: Morphine 2000 Codeine 2000 6-acetylmorphine 3 10 Phencyclidine (PCP) 25... benzoylecgonine. 3 Test for 6-AM when the confirmatory test shows a morphine concentration exceeding 2,000...

  12. 10 CFR 26.163 - Cutoff levels for drugs and drug metabolites.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Cocaine metabolite 2 150 Opiates: Morphine 2000 Codeine 2000 6-acetylmorphine 3 10 Phencyclidine (PCP) 25... benzoylecgonine. 3 Test for 6-AM when the confirmatory test shows a morphine concentration exceeding 2,000...

  13. 10 CFR 26.163 - Cutoff levels for drugs and drug metabolites.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Cocaine metabolite 2 150 Opiates: Morphine 2000 Codeine 2000 6-acetylmorphine 3 10 Phencyclidine (PCP) 25... benzoylecgonine. 3 Test for 6-AM when the confirmatory test shows a morphine concentration exceeding 2,000...

  14. 10 CFR 26.163 - Cutoff levels for drugs and drug metabolites.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Cocaine metabolite 2 150 Opiates: Morphine 2000 Codeine 2000 6-acetylmorphine 3 10 Phencyclidine (PCP) 25... benzoylecgonine. 3 Test for 6-AM when the confirmatory test shows a morphine concentration exceeding 2,000...

  15. 10 CFR 26.163 - Cutoff levels for drugs and drug metabolites.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Cocaine metabolite 2 150 Opiates: Morphine 2000 Codeine 2000 6-acetylmorphine 3 10 Phencyclidine (PCP) 25... benzoylecgonine. 3 Test for 6-AM when the confirmatory test shows a morphine concentration exceeding 2,000...

  16. 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.

  17. Carcinogenic effects of benzene: Cesare Maltoni's contributions.

    PubMed

    Mehlman, Myron A

    2002-12-01

    Cesare Maltoni's contributions to understanding, identifying, and characterizing widely used commercial chemicals in experimental animals are among the most important methods developed in the history of toxicology and serve to protect working men and women, the general population, and our environment from hazardous substances. Maltoni developed experimental methods that have reached the "platinum standard" for protection of public health. Benzene was among the 400 or more chemicals that Maltoni and his associates tested for carcinogenicity. In 1976, Maltoni reported that benzene is a potent experimental carcinogen. Maltoni's experiments clearly demonstrated that benzene is carcinogenic in Sprague-Dawley rats, Wistar rats, Swiss mice, and RF/J mice when administered by inhalation or ingestion. Benzene caused carcinomas of the Zymbal gland, oral cavity, nasal cavities; cancers of the skin, forestomach, mammary glands, and lungs; angiosarcomas and hepatomas of the liver; and hemolymphoreticular cancers. Thus, benzene was shown to be a multipotential carcinogen that produced cancers in several species of animals by various routes of administration. On November 2, 1977, Chemical Week reported that Maltoni provided a "bombshell" when he demonstrated the "first direct link" between benzene and cancer. In this paper, I shall summarize early experiments and human studies and reports; Maltoni's experimental contribution to understanding the carcinogenicity of benzene in humans and animals; earlier knowledge concerning benzene toxicity; and benzene standards and permissible exposure levels.

  18. Effects of feeding two levels of propionibacteria to dairy cows on plasma hormones and metabolites.

    PubMed

    Aleman, Mayte M; Stein, Dan R; Allen, Dustin T; Perry, Emily; Lehloenya, Keneuoe V; Rehberger, Thomas G; Mertz, Keith J; Jones, David A; Spicer, Leon J

    2007-05-01

    To determine the effect of feeding propionibacteria on metabolic indicators during lactation, multiparous and primiparous Holstein cows were fed one of three dietary treatments in a 2 x 3 factorial design from 2 weeks prepartum to 30 weeks post partum: (1) Control (primiparous n=5, multiparous n=8) fed a total mixed ration (TMR); (2) high-dose group (primiparous n=6, multiparous n=5) fed TMR plus 6 x 10 (11) cfu/head daily (high-dose P169) of propionibacterium strain P169; or (3) low-dose group (primiparous n=8, multiparous n=6) fed TMR plus 6 x 10(10) cfu/head daily (low-dose P169) of P169. Blood samples were collected weekly and analysed for plasma concentrations of glucose, insulin, insulin-like growth factor-I (IGF-I), leptin, nonesterified fatty acids (NEFA) and cholesterol. Between weeks 25 and 30, all groups received bovine somatotropin (bST) every 2 weeks. Low-dose P169 multiparous cows had lower (P<0.05) plasma insulin and glucose concentrations than high-dose P169 multiparous cows, whereas high-dose P169 primiparous cows had lower glucose but greater insulin concentartions than low-dose P169 primiparous cows (P<0.05). Plasma insulinratioglucose molar ratios were 13-18% lower (P<0.05) in low-dose P169 cows than in control or high-dose P169 cows. Plasma IGF-I, NEFA and leptin levels did not differ among diet groups between weeks 1 and 25. Low-dose P169 multiparous cows had 25% greater plasma cholesterol levels than high-dose P169 and control multiparous cows, but cholesterol levels in primiparous cows did not differ. During bST treatment, high-dose P169 multiparous cows and low-dose P169 primiparous cows had lower IGF-I levels than their respective controls and, regardless of parity, high-dose P169 cows had greater NEFA than control cows. Although supplemental feeding of P169 altered plasma hormones and metabolites, the particular effects were dependent on dose of P169 and parity of cows.

  19. 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.

    PubMed Central

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

    1996-01-01

    Chronic exposure of humans of benzene affects hematopoietic stem and progenitor cells and leads to aplastic anemia. The stromal macrophage, a target of benzene toxicity, secretes interleukin-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 to 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 cytokines and deficient IL-1 alpha production subsequent to the inhibition of calpain by p-benzoquinone and the prevention of pre-IL-1 processing. Images Figure 2. Figure 3. Figure 6. Figure 7. Figure 8. PMID:9118901

  20. 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.

  1. Occurrence of fungal metabolites--fumonisins at the ng/L level in aqueous environmental samples.

    PubMed

    Waśkiewicz, Agnieszka; Bocianowski, Jan; Perczak, Adam; Goliński, Piotr

    2015-08-15

    The B-series fumonisins (FBs) are some of the most prevalent mycotoxins produced as a secondary metabolite by Fusarium species growing on cereals. For decades they have been studied extensively in food and feed products, but there is no information about their occurrence in the aquatic environment or about how these mycotoxins are transported to the surface water and the groundwater. The aim of this study was to clarify the causes of fumonisin occurrence in aquatic ecosystems by examining the relation between mycotoxin contamination of crops and their levels in the aquatic environment. Water samples were collected from drainage ditches and wells or watercourses located in agricultural areas in the Wielkopolska region, Poland. Our research conducted on an annual basis showed the seasonal variability of fumonisin B1 concentration in the analyzed water samples, with the highest concentration in the post-harvest season (September to October) at 48.2 ng L(-1), and the lowest in winter and spring at 21.9 ng L(-1). Fumonisins B2 and B3 in water samples were not detected. Cereal samples were collected in the harvest season from each agricultural area close to tested water bodies. Mycotoxins were present in all cereal samples at concentrations from 43.3 to 1055.9 ng g(-1). Our results confirm that fumonisins are transported to aquatic systems by rainwater through soil. On the basis of available literature, this is the first report concerning the presence of fumonisin B1 in different aquatic environments. To date their ecotoxicological effects are largely unknown and require further investigation.

  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. PMID:20346362

  3. 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

  4. Phthalate metabolites in obese individuals undergoing weight loss: Urinary levels and estimation of the phthalates daily intake.

    PubMed

    Dirtu, Alin C; Geens, Tinne; Dirinck, Eveline; Malarvannan, Govindan; Neels, Hugo; Van Gaal, Luc; Jorens, Philippe G; Covaci, Adrian

    2013-09-01

    Human exposure to chemicals commonly encountered in our environment, like phthalates, is routinely assessed through urinary measurement of their metabolites. A particular attention is given to the specific population groups, such as obese, for which the dietary intake of environmental chemicals is higher. To evaluate the exposure to phthalates, nine phthalate metabolites (PMs) were analyzed in urine collected from obese individuals and a control population. Obese individuals lost weight through either bariatric surgery or a conservative weight loss program with dietary and lifestyle counseling. Urine samples were also collected from the obese individuals after 3, 6 and 12months of weight loss. Individual daily intakes of the corresponding phthalate diesters were estimated based on the urinary PM concentrations. A high variability was recorded for the levels of each PM in both obese and control urine samples showing the exposure to high levels of PMs in specific subgroups. The most important PM metabolite as percentage contribution to the total PM levels was mono-ethyl phthalate followed by the metabolites of di-butyl phthalate and di 2-ethyl-hexyl phthalate (DEHP). No differences in the PM levels and profiles between obese entering the program and controls were observed. Although paralleled by a significant decrease of their weight, an increase in the urinary PM levels after 3 to 6months loss was seen. Constant figures for the estimated phthalates daily intake were observed over the studied period, suggesting that besides food consumption, other human exposure sources to phthalates (e.g. air, dust) might be also important. The weight loss treatment method followed by obese individuals influenced the correlations between PM levels, suggesting a change of the intake sources with time. Except for few gender differences recorded between the urinary DEHP metabolites correlations, no other differences were observed for the urinary PM levels as a function of age, body

  5. 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.

  6. 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...

  7. Benzene dosimetry in experimental animals: relevance for risk assessment.

    PubMed

    Henderson, R F; Sabourin, P J; Medinsky, M A; Birnbaum, L S; Lucier, G L

    1992-01-01

    The findings of the studies summarized in this report provide some understanding of the possible role of dosimetry in the different response of the rats and mice to benzene in the long-term bioassay studies. The more sensitive species, the mice, definitely has a higher capacity to metabolize benzene and to metabolize it to more of the putative toxic metabolites than do rats. A major finding of these studies is that in three different animal species, from mice to monkeys, the metabolic pathways leading to production of the putative toxic metabolites appear to be low-capacity, high-affinity pathways that are saturated at relatively low-exposure concentrations. This does not prove, but suggests, that the same may be true in humans. If the total formation of the putative toxic metabolites is predictive of the toxicity of benzene, then the animal studies suggest that calculations of the risk associated with low dose exposures based on the results of animal studies conducted at high doses would underestimate the toxicity of benzene. The current report concerns only dosimetry. Another problem in assessing the risk to humans from benzene exposure is the fact that the animal models do not respond to benzene in the same way as humans. The major concern for humans exposed to benzene, based on epidemiology studies, is the risk of developing acute myelogenous leukemia (Rinksy, 1987). The cancers developed by the rodents on the long-term bioassay studies were at other sites (liver, lung, Zymbal's gland, lymph tissue, ovaries, and mammary gland). There is as yet no good animal model for benzene-induced leukemia. However, it has been suggested that benzene may also increase the incidence of Hodgkin's disease, malignant lymphoma, multiple myeloma and lung cancer in humans, although a statistical basis for this is lacking (Askoy, 1985). It is not unreasonable to assume that whatever form of cancer is induced, the induction is most likely through the reactive metabolites produced

  8. 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.

  9. A physiological model for simulation of benzene metabolism by rats and mice.

    PubMed

    Medinsky, M A; Sabourin, P J; Lucier, G; Birnbaum, L S; Henderson, R F

    1989-06-15

    Studies conducted by the National Toxicology Program on the chronic toxicity of benzene indicated that B6C3F1 mice are more sensitive to the toxic effects of benzene than are F344 rats. A physiological model was developed to describe the uptake and metabolism of benzene in rats and mice and to determine if the observed differences in toxic effects could be explained by differences in the pathways for metabolism of benzene or by differences in uptake of benzene. Major pathways for elimination of benzene included metabolism to hydroquinone glucuronide or hydroquinone sulfate, phenyl glucuronide or phenyl sulfate, muconic acid, and prephenyl mercapturic acid or phenyl mercapturic acid. Model simulations for total benzene metabolized and for profiles of benzene metabolites were conducted for oral or inhalation exposure and compared to data for urinary excretion of benzene metabolites after exposure of rats and mice to [14C]- or [3H]-benzene by inhalation or gavage. Results for total amount of benzene metabolized, expressed per kilogram body weight, indicated that for inhalation exposure concentrations up to 1000 ppm, mice metabolized at least two to three times as much benzene as did rats. Simulations of oral exposure to benzene resulted in more benzene metabolized per kilogram body weight by rats at oral exposures of greater than 50 mg/kg. Patterns of metabolites formed after either route of exposure were very different for F344/N rats and B6C3F1 mice. Rats primarily formed the detoxification metabolite, phenyl sulfate. Mice formed hydroquinone glucuronide and muconic acid in addition to phenyl sulfate. Hydroquinone and muconic acid are associated with pathways leading to the formation of the putative toxic metabolites of benzene. Metabolic rate parameters, Vmax and Km, were very different for hydroquinone conjugate and muconic acid formation compared to formation of phenyl conjugates and phenyl mercapturic acids. Putative toxication pathways could be characterized as

  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. CEST-MRI detects metabolite levels altered by breast cancer cell aggressiveness and chemotherapy response.

    PubMed

    Chan, Kannie W Y; Jiang, Lu; Cheng, Menglin; Wijnen, Jannie P; Liu, Guanshu; Huang, Peng; van Zijl, Peter C M; McMahon, Michael T; Glunde, Kristine

    2016-06-01

    Chemical exchange saturation transfer (CEST) is an MRI contrast mechanism that detects the exchange of protons from distinct hydroxyl, amine, and amide groups to tissue water through the transfer of signal loss, with repeated exchange enhancing their effective signal. We applied CEST to detect systematically 15 common cellular metabolites in a panel of differentially aggressive human breast cancer cell lines. The highest CEST contrast was generated by creatine, myo-inositol, glutamate, and glycerophosphocholine, whose cellular concentrations decreased with increasing breast cancer aggressiveness. These decreased metabolite concentrations resulted in turn in a decreased CEST profile with increasing breast cancer aggressiveness in water-soluble extracts of breast cell lines. Treatment of both breast cancer cell lines with the chemotherapy drug doxorubicin resulted in increased metabolic CEST profiles, which correlated with significant increases in creatine, phosphocreatine, and glycerophosphocholine. CEST can detect breast cancer aggressiveness and response to chemotherapy in water-soluble extracts of breast cell lines. The presented results help shed light on possible contributions from CEST-active metabolites to the CEST contrast produced by breast cancers. The metabolic CEST profile may improve detection sensitivity over conventional MRS, and may have the potential to assess breast cancer aggressiveness and response to chemotherapy non-invasively using MRI if specialized metabolic CEST profile detection can be realized in vivo. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27100284

  13. 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.

  14. 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.

  15. 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.

  16. Disruption of Adenosine-5′-Phosphosulfate Kinase in Arabidopsis Reduces Levels of Sulfated Secondary Metabolites[W

    PubMed Central

    Mugford, Sarah G.; Yoshimoto, Naoko; Reichelt, Michael; Wirtz, Markus; Hill, Lionel; Mugford, Sam T.; Nakazato, Yoshimi; Noji, Masaaki; Takahashi, Hideki; Kramell, Robert; Gigolashvili, Tamara; Flügge, Ulf-Ingo; Wasternack, Claus; Gershenzon, Jonathan; Hell, Rüdiger; Saito, Kazuki; Kopriva, Stanislav

    2009-01-01

    Plants can metabolize sulfate by two pathways, which branch at the level of adenosine 5′-phosphosulfate (APS). APS can be reduced to sulfide and incorporated into Cys in the primary sulfate assimilation pathway or phosphorylated by APS kinase to 3′-phosphoadenosine 5′-phosphosulfate, which is the activated sulfate form for sulfation reactions. To assess to what extent APS kinase regulates accumulation of sulfated compounds, we analyzed the corresponding gene family in Arabidopsis thaliana. Analysis of T-DNA insertion knockout lines for each of the four isoforms did not reveal any phenotypical alterations. However, when all six combinations of double mutants were compared, the apk1 apk2 plants were significantly smaller than wild-type plants. The levels of glucosinolates, a major class of sulfated secondary metabolites, and the sulfated 12-hydroxyjasmonate were reduced approximately fivefold in apk1 apk2 plants. Although auxin levels were increased in the apk1 apk2 mutants, as is the case for most plants with compromised glucosinolate synthesis, typical high auxin phenotypes were not observed. The reduction in glucosinolates resulted in increased transcript levels for genes involved in glucosinolate biosynthesis and accumulation of desulfated precursors. It also led to great alterations in sulfur metabolism: the levels of sulfate and thiols increased in the apk1 apk2 plants. The data indicate that the APK1 and APK2 isoforms of APS kinase play a major role in the synthesis of secondary sulfated metabolites and are required for normal growth rates. PMID:19304933

  17. Delivery of benzene to Alcaligenes xylosoxidans by solid polymers in a two-phase partitioning bioreactor.

    PubMed

    Daugulis, Andrew J; Amsden, Brian G; Bochanysz, Justina; Kayssi, Ahmed

    2003-07-01

    Toxic levels of benzene were decreased to sub-inhibitory levels in a bioreactor via absorption by polymer beads or cylinders (poly(ethylene-co-vinyl acetate) or poly(styrene-co-butadiene)). After inoculation with Alcaligenes xylosoxidans, the remaining benzene in the aqueous phase as well as the benzene taken up by the polymers was degraded to completion. The capacity of these polymers for benzene, and benzene diffusivity within the polymers were also determined.

  18. Influence of genetic polymorphism on t,t-MA/S-PMA ratio in 301 benzene exposed subjects.

    PubMed

    Carbonari, Damiano; Proietto, Annarita; Fioretti, Marzia; Tranfo, Giovanna; Paci, Enrico; Papacchini, Maddalena; Mansi, Antonella

    2014-12-01

    This study investigated the effect of polymorphic genes GSTT1, GSTM1, GSTA1, EHPX1, NQO1, CYP2E1, CYP1A and MPO on the urinary concentrations and ratio (R) of the benzene metabolites trans,trans-muconic acid (t,t-MA) and S-phenyl mercapturic acid (S-PMA) in 301 oil refinery workers. The metabolites' concentrations are lower and R is higher (100.66) in non-smokers (n=184) than in smokers (n=117, R=36.54). Non-smokers have lower S-PMA and a higher R in GSTT1 null genotypes than in positive, and a higher S-PMA and a lower R in GSTA1 wild type genotypes. In smokers the GSTT1 null genotype effect on both S-PMA and R is confirmed, and is also shown in GSTM1 null, but not in GSTA1 wild type genotypes. GSTT1 null polymorphism reduces the conjugation rate of benzene epoxide with GSH, and to a lesser extent also GSTTA1 mutant, GSTM1 null and NQO1 mutant genotypes. The activity of one GST is compensated by another in GSTM1 and GSTA1 defective subjects, but not in GSTT1 null genotypes, whose average S-PMA excretion is about 50% with respect to the positive ones, for the same benzene exposure. R showed to be a more sensitive marker for these effects than the metabolite levels.

  19. DNA methylation changes associated with cancer risk factors and blood levels of vitamin metabolites in a prospective study.

    PubMed

    Vineis, Paolo; Chuang, Shu-Chun; Vaissière, Thomas; Cuenin, Cyrille; Ricceri, Fulvio; Johansson, Mattias; Ueland, Per; Brennan, Paul; Herceg, Zdenko

    2011-02-01

    Aberrant DNA methylation is a major epigenetic mechanism of gene silencing in a wide range of human cancers. Previous studies on DNA methylation typically used paired tumor and normal-appearing surrounding tissues from cancer-bearing individuals. However, genomic DNA isolated from surrogate tissues such as blood cells represents an attractive material that can be exploited in the discovery of biomarkers of exposure and tumorigenesis. Here we examined the association between lung cancer and DNA methylation patterns in a panel of candidate genes. We also investigated whether blood levels of vitamin metabolites modify DNA methylation levels in blood cells. To this end, we quantitatively determined DNA methylation levels in blood cells of nested cases and controls from a prospective study with well defined dietary habits and lifestyles. Multiple CpG sites in five genes (CDKN2A/p16, RASSF1A, GSTP1, MTHFR, and MGMT) that are frequent targets of hypermethylation in a variety of human malignancies were included in the analysis. While no clear association between DNA methylation patterns and the case/control status was found, with the exception of RASSF1A hypermethylation, methylation level changed according to serum levels of 1-carbon metabolites and vitamins B. Overall, folate was associated with increased methylation levels of RASSF1A and MTHFR and methionine was associated with decreased methylation levels of RASSF1A. The associations with folate were more pronounced among never smokers while the associations with methionine were more evident among ever-smokers. These results are consistent with the notion that blood levels of 1-carbon metabolism markers and dietary/lifestyle factors may modify DNA methylation levels in blood cells and that blood cells can be exploited for the discovery of epigenetic biomarkers of exposures, providing proof-of-principle on the use of blood samples in the context of prospective studies.

  20. Refiners have several options for reducing gasoline benzene

    SciTech Connect

    Goelzer, A.R.; Hernandez-Robinson, A. ); Ram, S. ); Chin, A.A. ); Harandi, M.N.; Smith, C.M. )

    1993-09-13

    Although the linkage between gasoline benzene content and evaporative, running, and tailpipe emission is not yet defined, the U.S. 1990 Clean Air Act Amendments mandate a benzene content of less than 1.0 vol% in reformulated gasolines. Likewise, the California Air Resources Board plans to restrict benzene to less than about 0.8 vol %. Mobil Research and Development Corp. and Badger Co. Inc. have developed several alternatives for reducing benzene levels in gasoline. Where benzene extraction is viable and maximum catalytic reformer hydrogen is needed, the companies' cumene and ethylbenzene processes are desirable. Mobil's benzene reduction process can be an alternative to benzene hydrosaturation. All of these processes utilize low-value offgas from the fluid catalytic cracking (FCC) unit.

  1. Low occupational exposure to benzene in a petrochemical plant: modulating effect of genetic polymorphisms and smoking habit on the urinary t,t-MA/SPMA ratio.

    PubMed

    Mansi, Antonella; Bruni, Roberta; Capone, Pasquale; Paci, Enrico; Pigini, Daniela; Simeoni, Carla; Gnerre, Rossella; Papacchini, Maddalena; Tranfo, Giovanna

    2012-08-13

    The identification of reliable biomarkers is critical for the assessment of occupational exposure of benzene: S-phenylmercapturic acid (SPMA) and trans,trans-muconic acid (t,t-MA) are the most currently used. t,t-MA is an open-ring metabolite, but it is also a metabolite of the food preservative sorbic acid, while SPMA is formed by conjugation with glutathione, and several studies suggested that the genetic polymorphism of glutathione S-transferases modulates its production. This study compared the ability of these metabolites to assess the benzene exposure in a big group of petrochemical workers. Furthermore, investigated how genetic polymorphism of glutathione S-transferase theta 1 (GSTT1), glutathione S-transferase mu 1 (GSTM1), glutathione S-transferase pi 1 (GSTP1) and smoking habits, may influence their excretion. Results showed that occupational exposure to benzene was negligible compared to that from smoking and confirmed the modulating effect of the genetic polymorphism of GSTT1 on the urinary excretion of SPMA, but not of t, t-MA, even at very low levels of benzene exposure. The same effect was found for GSTM1, but only for smokers. The t,t-MA/SPMA ratio was not a constant value and resulted to be higher than the corresponding Biological Exposure Index (BEI) ratio, which is currently equal to 20. Higher values of metabolite have been associated with the GSTT1 or GSTM1 null genotype and these are responsible for increase health risk. We suggest that this ratio could be used as a marker of individual susceptibility for subjects with benzene exposure.

  2. Muscle glycogen levels and blood metabolites in reindeer (Rangifer tarandus tarandus L.) after transport and lairage.

    PubMed

    Wiklund, E; Andersson, A; Malmfors, G; Lundström, K

    1996-01-01

    A total of 66 reindeer cows and calves were included in a study on the effects of supplementary feeding, transport and lairage on muscle glycogen content, ultimate pH and blood metabolite values. Thirty reindeer (10 not transported, 20 transported 800 km) received no supplementary feed (groups A-C), another 30 animals (10 not transported, 20 transported 1000 km) were given a supplementary reindeer feed mixture 2 months prior to slaughter (groups D-F) and six animals, which had been part of a feeding experiment, were fed for 5 months and slaughtered at the research unit. Glycogen determinations and pH measurements were made in m. longissimus, m. biceps femoris and m. triceps brachii. Blood samples were collected at slaughter and muscle samples were taken 30 min after slaughter. Ultimate pH was measured 30 hr post mortem. The glycogen content in the muscles of groups A-C was very low (100-200 mmol/kg). In groups D-G, the glycogen content was equivalent to normal beef muscle values (300-500 mmol/kg). The values of the blood metabolites urea and creatinine, both of which could indicate protein catabolism caused by stress, were significantly (p < 0.05) higher in animals not having received supplemental feed (groups A-C). Alkaline phosphatase values were significantly (p < 0.05) higher in supplemental fed animals (groups D-G), indicating that their nutritional status was good. Total protein values were significantly (p < 0.05) higher in groups A, D, E and F compared to the other groups. Lorry transport did not significantly (p > 0.05) reduce the muscle glycogen content. Lairage (groups C and F) showed no negative effect on the parameters examined. These results suggest that the animals' physical condition and nutritional status have a considerable effect on their ability to tolerate various stress factors, such as lorry transport and lairage. PMID:22060679

  3. 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.

  4. Benzene release. status report

    SciTech Connect

    Dworjanyn, L.O.; Rappe, K.G.; Gauglitz, P.A.

    1997-11-04

    Scoping benzene release measurements were conducted on 4 wt percent KTPB `DEMO` formulation slurry using a round, flat bottomed 100-mL flask containing 75 mL slurry. The slurry was agitated with a magnetic stirrer bar to keep the surface refreshed without creating a vortex. Benzene release measurements were made by purging the vapor space at a constant rate and analyzing for benzene by gas chromatography with automatic data acquisition. Some of the data have been rounded or simplified in view of the scoping nature of this study.

  5. Benzene exposure: An overview of monitoring methods and their findings

    PubMed Central

    Weisel, Clifford P.

    2014-01-01

    Benzene has been measured throughout the environment and is commonly emitted in several industrial and transportation settings leading to widespread environmental and occupational exposures. Inhalation is the most common exposure route but benzene rapidly penetrates the skin and can contaminant water and food resulting in dermal and ingestion exposures. While less toxic solvents have been substituted for benzene, it still is a component of petroleum products, including gasoline, and is a trace impurity in industrial products resulting in continued sub to low ppm occupational exposures, though higher exposures exist in small, uncontrolled workshops in developing countries. Emissions from gasoline/petrochemical industry are its main sources to the ambient air, but a person’s total inhalation exposure can be elevated from emissions from cigarettes, consumer products and gasoline powered engines/tools stored in garages attached to homes. Air samples are collected in canisters or on adsorbent with subsequent quantification by gas chromatography. Ambient air concentrations vary from sub-ppb range, low ppb, and tens of ppb in rural/suburban, urban, and source impacted areas, respectively. Short-term environmental exposures of ppm occur during vehicle fueling. Indoor air concentrations of tens of ppb occur in microenvironments containing indoor sources. Occupational and environmental exposures have declined where regulations limit benzene in gasoline (<1%) and cigarette smoking has been banned from public and work places. Similar controls should be implemented worldwide to reduce benzene exposure. Biomarkers of benzene used to estimate exposure and risk include: benzene in breath, blood and urine; its urinary metabolites: phenol, t,t-muconic acid (t,tMA) and S-phenylmercapturic acid (sPMA); and blood protein adducts. The biomarker studies suggest benzene environmental exposures are in the sub to low ppb range though non-benzene sources for urinary metabolites

  6. 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, ...

  7. 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).

  8. 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.

  9. Urinary levels of eight phthalate metabolites and bisphenol A in mother-child pairs from two Spanish locations.

    PubMed

    Cutanda, Francisco; Koch, Holger M; Esteban, Marta; Sánchez, Jinny; Angerer, Jürgen; Castaño, Argelia

    2015-01-01

    Exposure to some phthalate diesters and bisphenol A in the general population is a cause of increasing concern because of their potential adverse effects on the reproductive and endocrine systems and their broad presence in foodstuff and consumer products. The aims of this work are to assess patterns of exposure to phthalates and bisphenol A in a pilot sample of Spanish mothers and their children, and to provide basic information to address priorities in future Spanish surveys/research. Urinary levels of eight phthalate metabolites and bisphenol A have been measured in samples from 120 mother-child pairs in one rural and one urban location in central Spain, recruited as part of the European project DEMOCOPHES. More than 96% of the participants were exposed to all the compounds studied here with generally higher levels in children than their mothers. The sum of secondary DEHP metabolites gave a GM of 33.3μg/g creatinine (95% CI 30.2-36.6) for mothers and 63.0μg/g creatinine (95% CI 56.8-69.8) for children. Mono-ethyl phthalate (MEP) was the metabolite with the highest levels, with geometric means (GM) of 150.8μg/g creatinine (95% CI 124.0-183.5) for mothers and 198.9μg/g creatinine (95% CI 165.2-239.6) for children. Bisphenol A urinary levels were relatively low with geometric means of 2.0μg/g (95% CI 1.6-2.4) for mothers and 2.01μg/g (95% CI 1.7-2.4) for children. Personal care products like body lotions and fragrances showed associations with MEHP, MEP, MnBP and cx-MiNP and canteen food with MBzP and bisphenol A. Exposure of mothers and their children are correlated, except for MEP. As phthalates and bisphenol A are non-persistent chemicals, a daily, intermittent exposure of the population is taking place.

  10. 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

  11. 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.

  12. Season of Sampling and Season of Birth Influence Serotonin Metabolite Levels in Human Cerebrospinal Fluid

    PubMed Central

    Luykx, Jurjen J.; Bakker, Steven C.; Lentjes, Eef; Boks, Marco P. M.; van Geloven, Nan; Eijkemans, Marinus J. C.; Janson, Esther; Strengman, Eric; de Lepper, Anne M.; Westenberg, Herman; Klopper, Kai E.; Hoorn, Hendrik J.; Gelissen, Harry P. M. M.; Jordan, Julian; Tolenaar, Noortje M.; van Dongen, Eric P. A.; Michel, Bregt; Abramovic, Lucija; Horvath, Steve; Kappen, Teus; Bruins, Peter; Keijzers, Peter; Borgdorff, Paul; Ophoff, Roel A.; Kahn, René S.

    2012-01-01

    Background Animal studies have revealed seasonal patterns in cerebrospinal fluid (CSF) monoamine (MA) turnover. In humans, no study had systematically assessed seasonal patterns in CSF MA turnover in a large set of healthy adults. Methodology/Principal Findings Standardized amounts of CSF were prospectively collected from 223 healthy individuals undergoing spinal anesthesia for minor surgical procedures. The metabolites of serotonin (5-hydroxyindoleacetic acid, 5-HIAA), dopamine (homovanillic acid, HVA) and norepinephrine (3-methoxy-4-hydroxyphenylglycol, MPHG) were measured using high performance liquid chromatography (HPLC). Concentration measurements by sampling and birth dates were modeled using a non-linear quantile cosine function and locally weighted scatterplot smoothing (LOESS, span = 0.75). The cosine model showed a unimodal season of sampling 5-HIAA zenith in April and a nadir in October (p-value of the amplitude of the cosine = 0.00050), with predicted maximum (PCmax) and minimum (PCmin) concentrations of 173 and 108 nmol/L, respectively, implying a 60% increase from trough to peak. Season of birth showed a unimodal 5-HIAA zenith in May and a nadir in November (p = 0.00339; PCmax = 172 and PCmin = 126). The non-parametric LOESS showed a similar pattern to the cosine in both season of sampling and season of birth models, validating the cosine model. A final model including both sampling and birth months demonstrated that both sampling and birth seasons were independent predictors of 5-HIAA concentrations. Conclusion In subjects without mental illness, 5-HT turnover shows circannual variation by season of sampling as well as season of birth, with peaks in spring and troughs in fall. PMID:22312427

  13. 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.

  14. Benzene and leukemia. An epidemiologic risk assessment

    SciTech Connect

    Rinsky, R.A.; Smith, A.B.; Hornung, R.; Filloon, T.G.; Young, R.J.; Okun, A.H.; Landrigan, P.J.

    1987-04-23

    To assess quantitatively the association between benzene exposure and leukemia, we examined the mortality rate of a cohort with occupational exposure to benzene. Cumulative exposure for each cohort member was estimated from historical air-sampling data and, when no sampling data existed, from interpolation on the basis of existing data. The overall standardized mortality ratio (a measure of relative risk multiplied by 100) for leukemia was 337 (95 percent confidence interval, 154 to 641), and that for multiple myeloma was 409 (95 percent confidence interval, 110 to 1047). With stratification according to levels of cumulative exposure, the standardized mortality ratios for leukemia increased from 109 to 322, 1186, and 6637 with increases in cumulative benzene exposure from less than 40 parts per million-years (ppm-years), to 40 to 199, 200 to 399, and 400 or more, respectively. A cumulative benzene exposure of 400 ppm-years is equivalent to a mean annual exposure of 10 ppm over a 40-year working lifetime; 10 ppm is the currently enforceable standard in the United States for occupational exposure to benzene. To examine the shape of the exposure-response relation, we performed a conditional logistic-regression analysis, in which 10 controls were matched to each cohort member with leukemia. From this model, it can be calculated that protection from benzene-induced leukemia would increase exponentially with any reduction in the permissible exposure limit.

  15. 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...

  16. 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.

  17. Liquid chromatography-tandem mass spectrometric analysis of ten estrogen metabolites at sub-picogram levels in breast cancer women.

    PubMed

    Khedr, Alaa; Alahdal, Abdulrahman M

    2016-09-15

    The measurement of estrogens at sub-picogram levels is essential for research on breast cancer and postmenopausal plasma. Heretofore, these concentration levels have rarely been achieved. However, it is possible through derivatization but still represent problems for monitoring catechol estrogens and 16α-hydroxyestrone (16α-OH-E1). Estrogens possess poor ionization efficiency in MS/MS, which results in insufficient sensitivity for analyzing samples at trace concentrations. The method presented here was used to extract ten estrogen metabolites (EMs) with a derivatization step involving a new adduct. The electrospray ionization (ESI) MS/MS sensitivity for the EMs was enhanced by derivatization with 3-bromomethyl-propyphenazone (BMP). The lower limits of quantification (LLOQ) of the EMs were 12-100 femtogram on-column, equivalent to 0.3-3.6pg/mL plasma, and the limits of detection (LOD) were 0.1-0.8pg/mL plasma. The percentage coefficient of variation (CV%) at the LLOQ was <20 for all investigated EMs. Ionization suppression was minimized by reacting the excess reagent, BMP, with methanol. The method was successfully applied for the determination of ten EMs in the plasma of fifty healthy postmenopausal and fifty ductal breast cancer women aged 47-65 years old. 16α-OH-E1 and three catechol estrogen metabolites, 4-OH-E1, 2-OH-E2 and 4-OH-E2, were successfully measured in the plasma of healthy and breast cancer women. The methyl-propyphenazone-EM derivatives exhibited better sensitivity in ESI-MS (7.5-fold) compared to the commonly used dansylation procedure. PMID:27497156

  18. Attenuation of aqueous benzene in soils under saturated flow conditions.

    PubMed

    Kim, S-B; Kim, D-J; Yun, S-T

    2006-01-01

    The fate of aqueous benzene in subsurface was investigated in this study, focusing on the role of sorption and biodegradation on the benzene attenuation under dynamic flow conditions. Two sets of column tests were conducted in Plexiglass flow cells packed uniformly with sandy aquifer materials. The first set of the experiment was conducted with a step-type injection of benzene with different powder activated carbon (PAC) contents: (1) PAC = 0 %; (2) PAC = 0.5 %; (3) PAC = 2.0%. The second set was performed as a pulse-type with different test conditions: (4) benzene; (5) benzene and bacteria (Pseudomonas aeruginosa); (6) benzene and bacteria (P. aeruginosa) with hydrogen peroxide. In addition, numerical experiments were performed to examine the role of sorption processes on the benzene attenuation. In the step mode experiments, the KCl breakthrough curves (BTCs) reached the input concentration while the benzene BTCs were considerably lower than those of KCl with slight retardation for all cases, indicating that both reversible/retardation and irreversible sorption occurred. The pulse type tests showed that attenuation of benzene increased in the presence of bacteria due to biodegradation. The benzene attenuation by microbial degradation increased furthermore in the presence of hydrogen peroxide owing to sufficient supply of dissolved oxygen in soil column. Numerical experiments demonstrated that retardation could not contribute to the attenuation of benzene in soils but could only extend its breakthrough time. Experimental results indicated that aqueous benzene could be attenuated by irreversible sorption and biodegradation during transport through the subsurface. Additionally, the attenuation of aqueous benzene is closely related to organic carbon content and oxygen level existing in contaminated aquifers.

  19. Nutritionally related blood metabolites and performance of finishing pigs fed on graded levels of dietary fibre.

    PubMed

    Bakare, Archibold Garikayi; Ndou, Saymore Petros; Madzimure, James; Chimonyo, Michael

    2016-06-01

    The objective of the study was to determine effect of feeding fibrous diets on performance and biochemical profiles of finishing pigs. A total of 84 clinically healthy male pigs were used in the experiment. Body weight of the pigs at the beginning of the experiment was 85 ± 10.1 kg. Maize cob (MC), sunflower hulls (SH), lucerne hay (LH) and dried citrus pulp (PU) were incorporated in a basal diet for finishing pigs at different inclusion levels of 0, 80, 160, 240, 320 and 400 g/kg. Effects of week of feeding, fibre source and inclusion level of fibre were significant (P < 0.05). Pigs consumed more LH compared to MC, SH and PU. Average daily gain was high for pigs consuming diets with inclusion levels of 0, 80, 160 and 240 g/kg and low for pigs consuming 320 and 400 g/kg inclusion level of fibre in a diet. There was an increase in serum total concentration (TP) with an increase in PU, MC and LH in pig diets (P < 0.05). Creatine kinase (CK) concentrations decreased as levels of PU, LH and MC increased (P < 0.05). Increasing inclusion level of LH and SH in pig diets resulted in an increase in glycated haemoglobin concentration (P < 0.05). It can be concluded that level of PU, LH, MC and SH in diets of finishing pigs negatively influences average daily feed intake, average daily gain and biochemical profiles. PMID:26984596

  20. 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

  1. 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

  2. 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

  3. Vitamin B12 deficiency & levels of metabolites in an apparently normal urban south Indian elderly population

    PubMed Central

    Shobha, Vineeta; Tarey, Subhash D.; Singh, Ramya G.; Shetty, Priya; Unni, Uma S.; Srinivasan, Krishnamachari; Kurpad, Anura V.

    2011-01-01

    Background & objectives: There is no published literature on the extent of vitamin B12 deficiency in elderly Indians as determined by plasma vitamin B12 levels and methylmalonic acid (MMA) levels. Vitamin B12 deficiency is expected to be higher in elderly Indians due to vegetarianism, varied socio-economic strata and high prevalence of Helicobacter pylori infection. We therefore, studied the dietary habits of south Indian urban elderly population and measured vitamin B12, MMA red cell folate and homocysteine (Hcy) levels. Methods: Healthy elderly urban subjects (175, >60 yr) were recruited. Detailed history, physical examination and neurological assessment were carried out. Food Frequency Questionnaire (FFQ) for dietary analysis for daily intake of calories, vitamin B12, folate and detailed psychological assessment for cognitive functions was carried out. Blood samples were analyzed for routine haematology and biochemistry, vitamin B12, red cell folate, MMA and Hcy. Results: The mean age of the study population was 66.3 yr. Median values for daily dietary intake of vitamin B12 and folate were 2.4 and 349.2 μg/day respectively. Sixty two (35%) participants consumed multivitamin supplements. Plasma vitamin B12 level and the dietary intake of vitamin B12 was significantly correlated (P=0.157). Plasma vitamin B12 and Hcy were inversely correlated (P= -0.509). Red cell folate was inversely correlated with Hcy (P= -0.550). Significant negative correlation was observed between plasma vitamin B12 and MMA in the entire study population (P= -0.220). Subjects consuming vitamin supplements (n=62) had significantly higher plasma vitamin B12 levels, lower MMA levels and lower Hcy levels. There was no significant correlation between plasma vitamin B12, MMA, Hcy and red cell folate and any of the 10 cognitive tests including Hindi Mental Status Examination (HMSE). Interpretation & conclusions: Our study is indicative of higher vitamin B12 (2.4 μg/day) intakes in urban south

  4. The electronic structure and molecular symmetry of pure benzene and benzene coadsorbed with CO on Ni(111)

    NASA Astrophysics Data System (ADS)

    Huber, W.; Steinrück, H.-P.; Pache, T.; Menzel, D.

    1989-07-01

    Benzene adsorption on Ni(111) was studied by ARUPS using linearly polarized synchrotron radiation at various benzene coverages and for benzene coadsorbed with CO. Overall the electronic structure of chemisorbed benzene is found to be very similar for the different benzene coverages and in the presence of coadsorbed CO: only small shifts in the electronic binding energies are observed which are attributed to electrostatic initial state changes. Using dipole selection rules the orientation of the adsorbed benzene molecules is determined to be parallel to the surface for all layers investigated. The molecular symmetry is reduced to C 3v in all cases. The photon energy dependence of the photoionization cross section shows a pronounced resonance of the 2e 1u level at a photon energy of 25 eV ( Ekin ≈ 13 eV); the corresponding electron emission is centered along the surface normal. This resonance is attributed to a shape resonance into an a 1 final state.

  5. Activation of bone marrow phagocytes following benzene treatment of mice.

    PubMed Central

    Laskin, D L; MacEachern, L; Snyder, R

    1989-01-01

    Techniques in flow cytometry/cell sorting were used to characterize the effects of benzene and its metabolites on subpopulations of bone marrow cells. Treatment of male Balb/c mice with benzene (880 mg/kg) or a combination of its metabolites, hydroquinone and phenol (50 mg/kg), resulted in a 30 to 40% decrease in bone marrow cellularity. Flow cytometric analysis revealed two subpopulations of bone marrow cells that could be distinguished by their size and density or granularity. The larger, more dense subpopulation was found to consist predominantly of macrophages and granulocytes as determined by monoclonal antibody binding and by cell sorting. Benzene treatment had no selective cytotoxic effects on subpopulations of bone marrow cells. To determine if benzene treatment activated bone marrow phagocytes, we quantified production of hydrogen peroxide by these cells using the fluorescent indicator dye, 2',7'-dichlorofluorescein diacetate. We found that macrophages and granulocytes from bone marrow of treated mice produced 50% more hydrogen peroxide in response to the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate than did cells from control animals. It is hypothesized that phagocyte activation and production of cytotoxic reactive oxygen intermediates may contribute to hematotoxicity induced by benzene. PMID:2676504

  6. Urinary excretion of unmetabolized benzene as an indicator of benzene exposure.

    PubMed

    Ghittori, S; Fiorentino, M L; Maestri, L; Cordioli, G; Imbriani, M

    1993-03-01

    Benzene concentrations in urine samples (Cu, ng/L) from 110 workers exposed to benzene in chemical plants and gasoline pumps were determined by injecting urine supernate into a gas chromatograph. The urine was saturated with anhydrous N2SO4 to facilitate the passage of benzene in the air over the urine. The solvent was stripped from the urine surface and concentrated on an adsorbent substrate (Carbotrap tube) by means of a suction pump (flow rate 150 ml/m). Wash-up of the head space was achieved by simultaneous intake of filtered air through charcoal. Benzene was thermically desorbed and injected in a column (thermal tube disorder, Supelco; 370 degrees C thermal flash; borosilicate capillary glass column SPB-1, 60 m length, 0.75 mm ID, 1 microns film thickness; GC Dani 8580-FID). Benzene concentrations in the urine from 40 non-exposed subjects (20 smokers > 20 cigarette/d and 20 nonsmokers) were also determined [median value of 790 ng/L (10.17 nmol/L) and 131 ng/L (1.70 nmol/L), respectively]. The 8-h time-weighted exposure intensity (Cl, micrograms/m3) of individual workers was monitored by means of charcoal tubes. The median value for exposure to benzene was 736 micrograms/m3 (9.42 mumol/m3) [geometric standard deviation (GSD) = 2.99; range 64 micrograms/m3 (0.82 mumol/m3) to 13,387 micrograms/m3) (171.30 mumol/m3)]. The following linear correlation was found between benzene concentrations in urine (Cu, ng/L) and benzene concentrations in the breathing zone (Cl, micrograms/m3): log(Cu) = 0.645 x log(Cl) + 1.399 r = .559, n = 110, p < .0001 With exclusion of workers who smoked from the study, the correlation between air benzene concentration and benzene measured in urine was: log(Cu) = 0.872 x log(Cl) + 0.6 r = .763, n = 63, p < .0001 The study results indicate that the urinary level of benzene is an indicator of occupational exposure to benzene.

  7. 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.

  8. 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.

  9. Juvenile development, ecdysteroids and hemolymph level of metabolites in the spider Brachypelma albopilosum (Theraphosidae).

    PubMed

    Trabalon, Marie; Blais, Catherine

    2012-04-01

    In the present work, juvenile development and physiological state of mygalomorph Brachypelma albopilosum were investigated by means of individual rearing under controlled conditions. Males required 4-5 years for development from first juvenile instar to adulthood, passing through 8 to 12 juvenile molts. Females developed to adults in 5-6 years with a variable juvenile molt number from 9 to 13. The development and growth of males and females took place in a similar way until the last juvenile molt leading to subadults. Ecdysteroids, total lipid, cholesterol, and protein concentrations increased along with the different development instars in both males and females. After the last juvenile molt, spiders presented morphological and biochemical sex differences. Subadult and adulthood males were smaller in size and weight than females; hemolymph levels of ecdysteroids, total lipids, cholesterol, and glucose were higher in males. These physiological and biochemical differences can be correlated to the different sexual development between males and females. PMID:22311802

  10. Actions of mammalian insulin on a Neurospora variant: effects on intracellular metabolite levels as monitored by P-31 NMR spectroscopy

    SciTech Connect

    Greenfield, N.J.; McKenzie, M.A.; Jordan, F.; Takahashi, M.; Lenard, J.

    1986-05-01

    Fourier transform P-31 NMR spectroscopy (81 MHz) was used to investigate the biochemical nature of insulin action upon the cell wall-deficient slime mutant of Neurospora crassa. Spectra of oxygenated, living cells (ca.10/sup 9//ml.) in late logarithmic-early stationary phase of growth were accumulated for approximately 20 min. (350-450 pulses). Pronounced differences were seen in the metabolite levels of cells cultured for 18-21 hours in the presence of insulin (100 nM) as compared to cells cultured in its absence. Differences in the insulin-grown cells included higher levels of sugar phosphates, inorganic (cytoplasmic) phosphate, NAD+/NADH and UDP-glucose (UDPG) compared to control cells, in which UDP-N-acetylglucosamine (UDPNAG) was the prominent sugar nucleotide. When 100 mM glucose was administered with insulin immediately prior to measurement, short term effects were seen. There were significant increases of sugar phosphates, inorganic phosphate, NAD+/NADH, phosphodiesters and UDPG relative to the case of glucose addition alone. These results are wholly consistent with the known influence of insulin upon mammalian metabolism: stimulation of glucose uptake, phosphorylation and oxidation, phosphatide synthesis and Pi uptake.

  11. 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. PMID:26904662

  12. 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

  13. 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.

  14. Regional Metabolite Levels and Turnover in the Awake Rat Brain under the Influence of Nicotine

    PubMed Central

    Wang, Jie; Jiang, Lihong; Jiang, Yifeng; Ma, Xiaoxian; Graeme, F. Mason

    2010-01-01

    As one of the most widespread drugs of abuse, nicotine has long been known to impact the brain, particularly with respect to addiction. However, the regional effects of nicotine on the concentrations and kinetics of amino acid neurotransmitters and some energetically related neurochemicals have been little studied. In this investigation, acute effects of nicotine were measured by 1H-observed/13C-edited nuclear magnetic resonance spectroscopy method in extracts obtained from nicotine-naïve, freely moving rats given 0.7 mg/kg nicotine or saline, with [1-13C] glucose to track metabolism. Nicotine was observed to exert significant effects on the concentrations of N-acetylaspartate (NAA), and γ-aminobutyric acid (GABA), particularly in the striatum. Nicotine decreased brain glucose oxidation, glutamate-glutamine neurotransmitter cycling, and GABA synthesis regionally, including in the parietal and occipital cortices and the striatum. The olfactory bulb showed kinetics that differed markedly from those observed in the rest of the brain. Independently of nicotine, the concentration of glutamate was found to be correlated significantly with levels of NAA and GABA, suggesting a potential interplay of energetics and excitatory and inhibitory neurotransmission. In summary, the study revealed that the neurochemicals were most affected in the cortex and striatum of the rat brain after acute nicotine treatment. PMID:20345764

  15. Relationship between disease activity and serum levels of vitamin D metabolites and parathyroid hormone in ankylosing spondylitis.

    PubMed

    Lange, U; Jung, O; Teichmann, J; Neeck, G

    2001-12-01

    Vertebral fractures due to osteoporosis are a common but frequently unrecognized complication of ankylosing spondylitis (AS) and various factors may contribute to the development of osteoporosis in AS. It is known that inflammatory activity in rheumatic disease (i.e., proinflammatory cytokines) itself plays a possible role in the pathophysiology of bone loss. 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) seems to be another possible candidate for mediatory function in regulating both the inflammatory process and bone turnover. The aim of this study was to evaluate the relation between disease activity, bone turnover and calciotropic hormones. In 70 patients with established AS and an age- and sex-matched control group, the relation between disease activity (erythrocyte sedimentation rate, C-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index), and serum levels of vitamin D metabolites, parathyroid hormone (PTH), bone alkaline phosphatase (bAP) and urinary pyridinium cross-links were determined. Serum levels of 1,25(OH)2D3 (p<0.01) and PTH (p<0.01) were negatively correlated with disease activity, the excretion of urinary pyridinium crosslinks showed a positive correlation with disease activity (p<0.01), and 1,25(OH)2D3 and PTH were positively correlated with bAP (p<0.01). These results indicate that high disease activity in AS is associated with an alteration in vitamin D metabolism and increased bone resorption. Furthermore, the decreased levels of 1,25(OH)2D3 may contribute to a negative calcium balance and inhibition of bone formation. Our results suggest further research is necessary to determine whether low levels of 1,25(OH)2D3 as an endogenous immune modulator suppressing activated T cells and cell proliferation may accelerate the inflammation process in AS. PMID:11846329

  16. Metabolite Levels in the Brain Reward Pathway Discriminate Those Who Remain Abstinent From Those Who Resume Hazardous Alcohol Consumption After Treatment for Alcohol Dependence*

    PubMed Central

    Durazzo, Timothy C.; Pathak, Varsha; Gazdzinski, Stefan; Mon, Anderson; Meyerhoff, Dieter J.

    2010-01-01

    Objective: This study compared baseline metabolite levels in components of the brain reward system among individuals who remained abstinent and those who resumed hazardous alcohol consumption after treatment for alcohol dependence. Method: Fifty-one treatment-seeking alcohol-dependent individuals (abstinent for approximately 7 days [SD = 3]) and 26 light-drinking nonsmoking controls completed 1.5-T proton magnetic resonance spectroscopic imaging, yielding regional concentrations of N-acetylaspartate, choline-containing compounds, creatine-containing compounds, and myoinositol. Metabolite levels were obtained in the following component of the brain reward system: dorsolateral prefrontal cortex, anterior cingulate cortex, insula, superior corona radiata, and cerebellar vermis. Alcohol-dependent participants were followed over a 12-month period after baseline study (i.e., at 7 days of abstinence [SD = 3]) and were classified as abstainers (no alcohol consumption; n = 18) and resumers (any alcohol consumption; n = 33) at follow-up. Baseline metabolite levels in abstainers and resumers and light-drinking nonsmoking controls were compared in the above regions of interest. Results: Resumers demonstrated significantly lower baseline N-acetylaspartate concentrations than light-drinking nonsmoking controls and abstainers in all regions of interest. Resumers also exhibited lower creatine-containing-compound concentrations than abstainers in the dorsolateral prefrontal cortex, superior corona radiata, and cerebellar vermis. Abstainers did not differ from light-drinking nonsmoking controls on baseline metabolite concentrations in any region of interest. Conclusions: The significantly decreased N-acetylaspartate and creatine-containing-compound concentrations in resumers suggest compromised neuronal integrity and abnormalities in cellular bioenergetics in major neocortical components and white-matter interconnectivity of the brain reward pathway. The lack of metabolite

  17. 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.

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

    PubMed

    Morgan, Marsha K; Sobus, Jon R; Barr, Dana Boyd; Croghan, Carry W; Chen, Fu-Lin; Walker, Richard; Alston, Lillian; Andersen, Erik; Clifton, Matthew S

    2016-01-01

    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 design and sampling methodology for the Pilot Study to Estimate Human Exposures to Pyrethroids using an Exposure Reconstruction Approach (Ex-R study). Two major objectives were to quantify the concentrations of several pyrethroid metabolites in bedtime, first morning void (FMV), and 24-h urine samples as concentration (wet weight), specific-gravity (SG) corrected, creatinine (CR) corrected, and excretion rate values for 50 Ex-R adults over a six-week monitoring period and to determine if these correction approaches for urine dilution reduced the variability of the biomarker levels. The Ex-R study was conducted at the United States Environmental Protection Agency's Human Studies Facility in Chapel Hill, North Carolina USA and at participants' homes within a 40-mile radius of this facility. Recruitment of participants and field activities occurred between October 2009 and May 2011. Participants, ages 19-50 years old, provided daily food, activity, and pesticide-use diaries and collected their own urine samples (bedtime, FMV, and 24-h) during weeks 1, 2, and 6 of a six-week monitoring period. A total of 2503 urine samples were collected from the study participants. These samples were analyzed for the pyrethroid metabolites 3-phenoxybenzoic acid (3-PBA), cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane carboxylic acid (cis/trans-DCCA), and 2-methyl-3-phenylbenzoic acid (MPA) using high performance liquid chromatography/tandem mass spectrometry. Only 3-PBA was frequently detected (>50%) in the adult urine samples. Median urinary 3-PBA levels were 0.88 ng/mL, 0.96 ng/mL-SG, 1.04 ng/mg, and 1.04 ng/min for concentration, SG-corrected, CR-corrected, and excretion rate values, respectively

  19. p53-dependent gene profiling for reactive oxygen species after benzene inhalation: special reference to genes associated with cell cycle regulation.

    PubMed

    Hirabayashi, Yoko

    2005-05-30

    Benzene toxicity has long been thought to be due to its metabolites including reactive oxygen species (ROS). However, the major toxicological effect of benzene in wild-type mice carrying normal alleles of the p53 gene appears to be the significant perturbation of cell cycle regulation, possibly via an indirect signaling pathway. Other prominent genotoxic cellular damage can occur in the absence of cell cycle arrest in p53 gene deficiency. The suppression of cell cycle is clearly detected using a tool for stem-cell-specific cell cycle observation by the BU-UV method. Cells (including hemopoietic progenitor cells) in S-phase are labeled in vivo with bromodeoxyuridine (BrdU) and then exposed to near-ultraviolet (UV) light to kill cells that incorporated BrdU. The target fraction, the S-phase, is then evaluated on the basis of decreased numbers of hemopoietic colonies formed in assays such as for granulomacrophage colony-forming units (CFU-GM). Benzene toxicity was found to be more prominent in the primitive stem-cell compartment, as first suggested more than 20 years ago. Interestingly, when one examines the stem-cell-specific steady-state gene expression profiling, several key genes associated with benzene exposure are specifically identified, including CYP2E1. Benzene toxicity was found to be mediated by aryl hydrocarbon receptor (AhR) at an expression level; thus, the effect of benzene can be detected in nature at lower levels in the stem-cell compartment than expected. Alterations in gene expression profiles compared with those in steady-state gene expression profiles in the stem-cell compartment may elucidate the mechanism underlying benzene toxicity. Functional gene expressions after benzene exposure are not always detected, because their phenotypic expressions are often masked by the balance of expression of genes participating in various pathways of homeostasis, for example, p53. Thus, the actual expressions of the above-mentioned cell cycle-related genes may

  20. Modulation of the immune response to Listeria monocytogenes by benzene inhalation.

    PubMed

    Rosenthal, G J; Snyder, C A

    1985-09-30

    Benzene is a potent bone marrow toxicant. While all blood cell types are targets for benzene poisoning, lymphocytes are particularly sensitive. The immunotoxic consequences of benzene or its metabolites have been demonstrated in a number of in vitro studies; however, little data exist regarding the effects of benzene on host resistance to infectious agents. This investigation examined the effects of benzene on murine resistance to an infectious agent, Listeria monocytogenes. Four concentrations of benzene were employed, 10, 30, 100, and 300 ppm. To determine recovery from the effects of benzene, two exposure regimens were employed: 5 days prior to infection (preexposure), or 5 days prior to and 7 days during infection (continuous exposure). Appropriate air controls were maintained. Splenic bacterial counts and immune responsive cell populations were determined from mice killed at Days 1, 4, and 7 of infection. Preexposure to benzene produced increased bacterial numbers at Day 4 of the infection only at the highest benzene concentration (300 ppm). In contrast, continuous exposure produced increased bacterial numbers at Day 4 of infection at all but the lowest benzene concentration (10 ppm). Bacteria counts were not increased in any benzene-treated group at Day 1 or Day 7 of infection. The increased bacterial numbers at Day 4 suggest an effect on cell-mediated immune responses. Both T and B lymphocytes were particularly sensitive to benzene exhibiting reductions at all concentrations greater than or equal to 30 ppm for both exposure regimens. Esterase-positive cells, however, were relatively resistant to benzenes effects. The results point to a benzene-induced delay in the immune response to L. monocytogenes.

  1. Anaerobic benzene biodegradation by a pure bacterial culture of Bacillus cereus under nitrate reducing conditions.

    PubMed

    Dou, Junfeng; Ding, Aizhong; Liu, Xiang; Du, Yongchao; Deng, Dong; Wang, Jinsheng

    2010-01-01

    A pure culture using benzene as sole carbon and energy sources was isolated by screening procedure from gasoline contaminated soil. The analysis of the 16S rDNA gene sequence, morpholpgical and physiological characteristics showed that the isolated strain was a member of genus Bacillus cereus. The biodegradation performance of benzene by B. cereus was evaluated, and the results showed that benzene could be efficiently biodegraded when the initial benzene concentration was below 150 mg/L. The metabolites of anaerobic nitrate-dependent benzene oxidation by strain B. cereus were identified as phenol and benzoate. The results of substrate interaction between binary combinations for benzene, phenol and benzoate showed that the simultaneous presence of benzene stimulated the degradation of benzoate, whereas the addition of benzene inhibited the degradation of phenol. Benzene degradation by B. cereus was enhanced by the addition of phenol and benzoate, the enhanced effects were more pronounced at higher concentration. To our knowledge, this is the first report that the isolated bacterial culture of B. cereus can efficiently degraded benzene under nitrate reducing conditions.

  2. 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. PMID:22797934

  3. Changes in Primary and Secondary Metabolite Levels in Response to Gene Targeting-Mediated Site-Directed Mutagenesis of the Anthranilate Synthase Gene in Rice

    PubMed Central

    Saika, Hiroaki; Oikawa, Akira; Nakabayashi, Ryo; Matsuda, Fumio; Saito, Kazuki; Toki, Seiichi

    2012-01-01

    Gene targeting (GT) via homologous recombination allows precise modification of a target gene of interest. In a previous study, we successfully used GT to produce rice plants accumulating high levels of free tryptophan (Trp) in mature seeds and young leaves via targeted modification of a gene encoding anthranilate synthase—a key enzyme of Trp biosynthesis. Here, we performed metabolome analysis in the leaves and mature seeds of GT plants. Of 72 metabolites detected in both organs, a total of 13, including Trp, involved in amino acid metabolism, accumulated to levels >1.5-fold higher than controls in both leaves and mature seeds of GT plants. Surprisingly, the contents of certain metabolites valuable for both humans and livestock, such as γ-aminobutyric acid and vitamin B, were significantly increased in mature seeds of GT plants. Moreover, untargeted analysis using LC-MS revealed that secondary metabolites, including an indole alkaloid, 2-[2-hydroxy-3-β-D-glucopyranosyloxy-1-(1H-indol-3-yl)propyl] tryptophan, also accumulate to higher levels in GT plants. Some of these metabolite changes in plants produced via GT are similar to those observed in plants over expressing mutated genes, thus demonstrating that in vivo protein engineering via GT can be an effective approach to metabolic engineering in crops. PMID:24957777

  4. Molecular dynamics simulations of the effects of salts on the aggregation properties of benzene in water.

    SciTech Connect

    Smith, P. E.

    2003-07-16

    The specific aims of the project were: to provide an atomic level description of the interactions between benzene, water and ions in solutions. To determine the degree of association between two benzene molecules in aqueous and salt solutions. To investigate the structure and dynamics of the interface between benzene and water or salt solution.

  5. 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.

  6. Hesperetin and its sulfate and glucuronide metabolites inhibit TNF-α induced human aortic endothelial cell migration and decrease plasminogen activator inhibitor-1 (PAI-1) levels.

    PubMed

    Giménez-Bastida, Juan Antonio; González-Sarrías, Antonio; Vallejo, Fernando; Espín, Juan Carlos; Tomás-Barberán, Francisco A

    2016-01-01

    Epidemiological, clinical and preclinical studies have reported the protection offered by citrus consumption, mainly orange, against cardiovascular diseases, which is primarily mediated by the antiatherogenic and vasculoprotective effects of the flavanone hesperetin-7-O-rutinoside (hesperidin). However, flavanone aglycones or glycosides are not present in the bloodstream but their derived phase-II metabolites could be the actual bioactive molecules. To date, only a few studies have explored the effects of circulating hesperetin-derived metabolites (glucuronides and sulfates) on endothelial cells. Herein, we describe for the first time the effects of hesperetin 3'-O-glucuronide, hesperetin 7-O-glucuronide, hesperetin 3'-O-sulfate, hesperetin 7-O-sulfate and hesperetin on human aortic endothelial cell (HAEC) migration upon pro-inflammatory stimuli as an essential step to angiogenesis. Hesperetin and its derived metabolites, at physiologically relevant concentrations (1-10 μM), significantly attenuated cell migration in the presence of the pro-inflammatory cytokine TNF-α (50 ng mL(-1)), which was accompanied and perhaps mediated by a significant decrease in the levels of the thrombogenic plasminogen activator inhibitor-1 (PAI-1). However, hesperetin metabolites did not counteract the TNF-α-induced production of pro-inflammatory interleukin-6 (IL-6) and IL-8. We also study here for the first time, the metabolism of hesperetin and its derived metabolites by HAEC with and without a pro-inflammatory stimulus. All these results reinforce the concept according to which circulating phase-II hesperetin metabolites are critical molecules contributing to the cardioprotective effects upon consumption of citrus fruits such as orange.

  7. Plasmodium falciparum spermidine synthase inhibition results in unique perturbation-specific effects observed on transcript, protein and metabolite levels

    PubMed Central

    2010-01-01

    also observed. Most notably, uridine phosphorylase, adenosine deaminase, lysine decarboxylase (LDC) and S-adenosylmethionine synthetase were differentially expressed at the transcript and/or protein level. Several genes in associated metabolic pathways (purine metabolism and various methyltransferases) were also affected. The specific nature of the perturbation was additionally reflected by changes in polyamine metabolite levels. Conclusions This study details the malaria parasite's response to PfSpdSyn inhibition on the transcriptomic, proteomic and metabolic levels. The results corroborate and significantly expand previous functional genomics studies relating to polyamine depletion in this parasite. Moreover, they confirm the role of transcriptional regulation in P. falciparum, particularly in this pathway. The findings promote this essential pathway as a target for antimalarial chemotherapeutic intervention strategies. PMID:20385001

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

    PubMed

    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.

  9. 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

  10. Binding of a 3,3', 4,4'-tetrachlorobiphenyl (CB-77) metabolite to fetal transthyretin and effects on fetal thyroid hormone levels in mice.

    PubMed

    Darnerud, P O; Morse, D; Klasson-Wehler, E; Brouwer, A

    1996-01-01

    The present study was conducted in order to study the effect of the PCB congener 3,3', 4,4'-tetrachlorobiphenyl (CB-77) on fetal thyroxin homeostasis in the mouse, and to examine a possible underlying mechanism behind the effect. C57BL mice were treated with 14C-labelled or unlabelled CB-77 (1 or 10 mg/kg body wt.) on day 13 of gestation, and control animals were treated with corn oil. The experiment was terminated at 4 days after exposure. Maternal and fetal plasma and livers, and whole fetuses for homogenate preparation, were collected and analysed for total radioactivity, in vitro binding of 125I-thyroxin to plasma transthyretin (TTR; a thyroxin-transporting protein), and free and total thyroxin (FT4, TT4) levels. Maternal plasma, fetal plasma and homogenates were also analyzed for presence of CB-77 and metabolites. Results showed a dose-dependent uptake of radioactivity in plasma and liver, fetal plasma 14C-levels being about five-times higher in 10 mg/kg dosed animals as after 1 mg/kg. Fetal; plasma levels of total radioactivity were four- to nine-times above maternal levels and corresponded to only one compound, the metabolite 4-OH-3,3', 4',5-tetrachlorobiphenyl (4-OH-tCB). 4-OH-tCB was the major metabolite also in whole fetuses, with only small amounts of the parent compound (approximately 15% of the 4-OH-tCB) and traces (approximately 6%) of two other metabolites, 2-OH-3,3, 4,4'-tetrachlorobiphenyl and 5-OH-3,3', 4,4'-tetrachlorobiphenyl. Polyacrylamide gel electrophoresis confirmed that the 14C-radioactivity in fetal plasma was bound to TTR, and revealed that in vitro binding of 125I-T4 to fetal TTR was reduced to 50% of control values in treated animals (10 mg/kg body wt.). Fetal plasma FT4 and TT4 levels were significantly decreased (64 and 55% of control fetuses) after 10 mg/kg treatment. In conclusion, exposure of pregnant mice to CB-77 results in the accumulation of the metabolite 4-OH-tCB in fetal mouse plasma. The metabolite binds to TTR and is

  11. Corticosterone stress response and plasma metabolite levels during breeding and molt in a free-living migratory songbird, the wood thrush (Hylocichla mustelina).

    PubMed

    Done, Tyler; Gow, Elizabeth A; Stutchbury, Bridget J M

    2011-04-01

    Many birds face energetic trade-offs between different life history stages, such as reproductive effort, feather molt and the non-breeding period. Little is known about how physiological measures of condition (corticosterone, plasma metabolites) in free-living birds change from nesting stages to the post-breeding molt period or whether this is influenced by prior reproductive effort. We evaluated whether corticosterone (CORT) and plasma metabolite levels vary with date, nest stage and sex in a free-living migratory songbird, the wood thrush (Hylocichla mustelina). We also tested whether (1) baseline CORT levels early in the season were predictive of subsequent reproductive success and (2) whether prior reproductive effort influenced CORT levels and blood metabolites during molt. Baseline CORT levels decreased with date during both the incubation stage and nestling stage, but did not vary significantly across stage of breeding season. Stress-induced CORT declined with date during incubation and varied significantly across breeding stage, with lower levels during feather molt. Profiles of the metabolites of β-hydroxybutyrate, glycerol, and triglyceride did not vary significantly with date or breeding stage. Only triglycerides varied significantly with sex, with females having higher levels than males. Reproductive output was highly variable (0-10 fledglings per season) but baseline CORT levels in females during the first incubation period of the season was not related to subsequent reproductive output. Prior reproductive effort, measured as the cumulative number of young hatched during the breeding season, was positively related to stress-induced CORT during molt. High reproductive effort in wood thrush appears to have physiological carry-over effects into the molt period which could potentially affect rate of molt and preparation for fall migration.

  12. Acute high dose exposure to benzene in shipyard workers

    SciTech Connect

    Midzenski, M.A.; McDiarmid, M.A.; Rothman, N.; Kolodner, K. )

    1992-01-01

    Fifteen degassers were acutely exposed over several days to high concentrations (> 60 ppm) of benzene during removal of residual fuel (degassing) from shipboard fuel tanks. Medical surveillance evaluation mandated by the Occupational Safety and Health Administration's (OSHA) Benzene Standard initially revealed 11 workers (73%) reporting neurotoxic symptoms while degassing. Workers with more than 2 days (16 hours) of acute exposure were significantly more likely to report dizziness and nausea than those with 2 or fewer days of acute exposure. Repeated laboratory analyses performed over a 4-month period after the acute exposure revealed at least one hematologic abnormality consistent with benzene exposure in 9 (60%) of these degassers. One year later, 6 workers (40%) had persistent abnormalities; an additional worker with normal hematologic parameters at the time of our initial evaluation subsequently developed an abnormality consistent with benzene exposure. Numerous large granular lymphocytes were observed on 6 (40%) of the peripheral blood smears. Despite these laboratory findings, there were no significant associations between the presence of hematologic abnormalities and either the number of hours of acute benzene exposure or the duration of employment as a degasser. Volatilization of benzene from the residual fuel was the suspected source of benzene in the headspace of tanks. Confined space exposure to petroleum products may be exposing workers to benzene at levels above the OSHA Short-Term Exposure Limit (STEL). This situation warrants further study.

  13. 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. PMID:25960203

  14. 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.

  15. Chemoenzymatic synthesis of monocyclic arene oxides and arene hydrates from substituted benzene substrates.

    PubMed

    Boyd, Derek R; Sharma, Narain D; Ljubez, Vera; McGeehin, Peter K M; Stevenson, Paul J; Blain, Marine; Allen, Christopher C R

    2013-05-14

    Enantiopure cis-dihydrodiol bacterial metabolites of substituted benzene substrates were used as precursors, in a chemoenzymatic synthesis of the corresponding benzene oxides and of a substituted oxepine, via dihydrobenzene oxide intermediates. A rapid total racemization of the substituted benzene 2,3-oxides was found to have occurred, via their oxepine valence tautomers, in accord with predictions and theoretical calculations. Reduction of a substituted arene oxide to yield a racemic arene hydrate was observed. Arene hydrates have also been synthesised, in enantiopure form, from the corresponding dihydroarene oxide or trans-bromoacetate precursors. Biotransformation of one arene hydrate enantiomer resulted in a toluene-dioxygenase catalysed cis-dihydroxylation to yield a benzene cis-triol metabolite.

  16. 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.

  17. Early Liver and Kidney Dysfunction Associated with Occupational Exposure to Sub-Threshold Limit Value Levels of Benzene, Toluene, and Xylenes in Unleaded Petrol

    PubMed Central

    Neghab, Masoud; Hosseinzadeh, Kiamars; Hassanzadeh, Jafar

    2015-01-01

    Background Unleaded petrol contains significant amounts of monocyclic aromatic hydrocarbons such as benzene, toluene, and xylenes (BTX). Toxic responses following occupational exposure to unleaded petrol have been evaluated only in limited studies. The main purpose of this study was to ascertain whether (or not) exposure to unleaded petrol, under normal working conditions, is associated with any hepatotoxic or nephrotoxic response. Methods This was a cross-sectional study in which 200 employees of Shiraz petrol stations with current exposure to unleaded petrol, as well as 200 unexposed employees, were investigated. Atmospheric concentrations of BTX were measured using standard methods. Additionally, urine and fasting blood samples were taken from individuals for urinalysis and routine biochemical tests of kidney and liver function. Results The geometric means of airborne concentrations of BTX were found to be 0.8 mg m−3, 1.4 mg m−3, and 2.8 mg m−3, respectively. Additionally, means of direct bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea and plasma creatinine were significantly higher in exposed individuals than in unexposed employees. Conversely, serum albumin, total protein, and serum concentrations of calcium and sodium were significantly lower in petrol station workers than in their unexposed counterparts. Conclusion The average exposure of petrol station workers to BTX did not exceed the current threshold limit values (TLVs) for these chemicals. However, evidence of subtle, subclinical and prepathologic early liver and kidney dysfunction was evident in exposed individuals. PMID:26929843

  18. 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

  19. 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

  20. The effect of the lunar cycle on fecal cortisol metabolite levels and foraging ecology of nocturnally and diurnally active spiny mice.

    PubMed

    Gutman, Roee; Dayan, Tamar; Levy, Ofir; Schubert, Iris; Kronfeld-Schor, Noga

    2011-01-01

    We studied stress hormones and foraging of nocturnal Acomys cahirinus and diurnal A. russatus in field populations as well as in two field enclosures populated by both species and two field enclosures with individuals of A. russatus alone. When alone, A. russatus individuals become also nocturnally active. We asked whether nocturnally active A. russatus will respond to moon phase and whether this response will be obtained also in diurnally active individuals. We studied giving-up densities (GUDs) in artificial foraging patches and fecal cortisol metabolite levels. Both species exhibited elevated fecal cortisol metabolite levels and foraged to higher GUDs in full moon nights; thus A. russatus retains physiological response and behavioral patterns that correlate with full moon conditions, as can be expected in nocturnal rodents, in spite of its diurnal activity. The endocrinological and behavioral response of this diurnal species to moon phase reflects its evolutionary heritage.

  1. The Effect of the Lunar Cycle on Fecal Cortisol Metabolite Levels and Foraging Ecology of Nocturnally and Diurnally Active Spiny Mice

    PubMed Central

    Dayan, Tamar; Kronfeld-Schor, Noga

    2011-01-01

    We studied stress hormones and foraging of nocturnal Acomys cahirinus and diurnal A. russatus in field populations as well as in two field enclosures populated by both species and two field enclosures with individuals of A. russatus alone. When alone, A. russatus individuals become also nocturnally active. We asked whether nocturnally active A. russatus will respond to moon phase and whether this response will be obtained also in diurnally active individuals. We studied giving-up densities (GUDs) in artificial foraging patches and fecal cortisol metabolite levels. Both species exhibited elevated fecal cortisol metabolite levels and foraged to higher GUDs in full moon nights; thus A. russatus retains physiological response and behavioral patterns that correlate with full moon conditions, as can be expected in nocturnal rodents, in spite of its diurnal activity. The endocrinological and behavioral response of this diurnal species to moon phase reflects its evolutionary heritage. PMID:21829733

  2. 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 ...

  3. 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.

  4. Benzene upgrading reformer integration

    SciTech Connect

    Harandi, M.N.; Owen, H.

    1990-08-21

    This patent describes a continuous process for providing an integrated product recovery system for a primary catalytic hydrocarbon reforming reactor and a secondary catalytic olefins oligomerization-alkylation reactor. It comprises: withdrawing reformer effluent from primary reformer reactor; separating in a primary separation zone the reformer effluent into a primary overhead stream comprising noncondensible light paraffins and a primary bottoms stream comprising C{sub 6} to C{sub 8} aromatic hydrocarbons; withdrawing oligomerization effluent from secondary oligomerization-alkylation reactor; separating in a secondary separation zone the oligomerization effluent into a secondary overhead stream; adding the primary bottoms stream and the secondary bottoms stream to the fractionation column; withdrawing from the top of the fractionation column a stream comprising C{sub 4} {minus} hydrocarbons; withdrawing from the bottom of the fractionation column a stream comprising C{sub 5} + hydrocarbons; adding the C{sub 5} + hydrocarbon stream to the reboiler unit; withdrawing from the reboiler unit a vapor stream comprising benzene and a liquid stream comprising C{sub 5} + hydrocarbons boiling in the gasoline range; adding at least a portion of the vapor stream comprising benzene to the secondary catalytic olefins oligomerization-alkylation reactor; and adding a light olefins feedstream.

  5. 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.

  6. Effects of Styrene-metabolizing Enzyme Polymorphisms and Lifestyle Behaviors on Blood Styrene and Urinary Metabolite Levels in Workers Chronically Exposed to Styrene

    PubMed Central

    2015-01-01

    The aim of this study was to investigate whether genetic polymorphisms of CYP2E1, GSTM1, and GSTT1 and lifestyle habits (smoking, drinking, and exercise) modulate the levels of urinary styrene metabolites such as mandelic acid (MA) and phenylglyoxylic acid (PGA) after occupational exposure to styrene. We recruited 79 male workers who had received chronic exposure in styrene fiberglass-reinforced plastic manufacturing factories. We found that serum albumin was significantly correlated with blood styrene/ambient styrene (BS/AS), urinary styrene (US)/AS, and US/BS ratios as well as urinary metabolites, that total protein correlated with US/MA and US/PGA ratios, and that low density lipoprotein (LDL)-cholesterol significantly correlated with US/BS, US/MA, and US/PGA ratios. Multiple logistic regression analyses using styrene-metabolizing enzyme genotypes and lifestyle habits as dependent variables and blood and urine styrene concentrations and urine styrene metabolite levels as independent variables revealed that CYP2E1*5 was associated with the MA/US ratio and GSTM1 with US/BS, that a smoking habit was associated with US/AS and MA/US ratios and MA and PGA levels, and that regular exercise was correlated with PGA/US. In conclusion, the results suggested that genetic polymorphisms of styrene-metabolizing enzymes, lifestyle behaviors, and albumin and LDL-cholesterol serving as homeostasis factors together are involved in styrene metabolism. PMID:26877838

  7. Effects of Styrene-metabolizing Enzyme Polymorphisms and Lifestyle Behaviors on Blood Styrene and Urinary Metabolite Levels in Workers Chronically Exposed to Styrene.

    PubMed

    Kim, Ki-Woong

    2015-12-01

    The aim of this study was to investigate whether genetic polymorphisms of CYP2E1, GSTM1, and GSTT1 and lifestyle habits (smoking, drinking, and exercise) modulate the levels of urinary styrene metabolites such as mandelic acid (MA) and phenylglyoxylic acid (PGA) after occupational exposure to styrene. We recruited 79 male workers who had received chronic exposure in styrene fiberglass-reinforced plastic manufacturing factories. We found that serum albumin was significantly correlated with blood styrene/ambient styrene (BS/AS), urinary styrene (US)/AS, and US/BS ratios as well as urinary metabolites, that total protein correlated with US/MA and US/PGA ratios, and that low density lipoprotein (LDL)-cholesterol significantly correlated with US/BS, US/MA, and US/PGA ratios. Multiple logistic regression analyses using styrene-metabolizing enzyme genotypes and lifestyle habits as dependent variables and blood and urine styrene concentrations and urine styrene metabolite levels as independent variables revealed that CYP2E1*5 was associated with the MA/US ratio and GSTM1 with US/BS, that a smoking habit was associated with US/AS and MA/US ratios and MA and PGA levels, and that regular exercise was correlated with PGA/US. In conclusion, the results suggested that genetic polymorphisms of styrene-metabolizing enzymes, lifestyle behaviors, and albumin and LDL-cholesterol serving as homeostasis factors together are involved in styrene metabolism. PMID:26877838

  8. Reduction of benzene metabolism and toxicity in mice that lack CYP2E1 expression.

    PubMed

    Valentine, J L; Lee, S S; Seaton, M J; Asgharian, B; Farris, G; Corton, J C; Gonzalez, F J; Medinsky, M A

    1996-11-01

    Transgenic CYP2E1 knockout mice (cyp2e1-/-) were used to investigate the involvement of CYP2E1 in the in vivo metabolism of benzene and in the development of benzene-induced toxicity. After benzene exposure, absence of CYP2E1 protein was confirmed by Western blot analysis of mouse liver samples. For the metabolism studies, male cyp2e1-/- and wild-type control mice were exposed to 200 ppm benzene, along with a radiolabeled tracer dose of [14C]benzene (1.0 Ci/mol) by nose-only inhalation for 6 hr. Total urinary radioactivity and all radiolabeled individual metabolites were reduced in urine of cyp2e1-/- mice compared to wild-type controls during the 48-hr period after benzene exposure. In addition, a significantly greater percentage of total urinary radioactivity could be accounted for as phenylsulfate conjugates in cyp2e1-/- mice compared to wild-type mice, indicating the importance of CYP2E1 in oxidation of phenol following benzene exposure in normal mice. For the toxicity studies, male cyp2e1-/-, wild-type, and B6C3F1 mice were exposed by whole-body inhalation to 0 ppm (control) or 200 ppm benzene, 6 hr/day for 5 days. On Day 5, blood, bone marrow, thymus, and spleen were removed for evaluation of micronuclei frequencies and tissue cellularities. No benzene-induced cytotoxicity or genotoxicity was observed in cyp2e1-/- mice. In contrast, benzene exposure resulted in severe genotoxicity and cytotoxicity in both wild-type and B6C3F1 mice. These studies conclusively demonstrate that CYP2E1 is the major determinant of in vivo benzene metabolism and benzene-induced myelotoxicity in mice.

  9. 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.

  10. 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

  11. 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.

  12. 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. PMID:24579243

  13. 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.

  14. Analysis of transcript and metabolite levels in Italian rice (Oryza sativa L.) cultivars subjected to osmotic stress or benzothiadiazole treatment.

    PubMed

    Baldoni, Elena; Mattana, Monica; Locatelli, Franca; Consonni, Roberto; Cagliani, Laura R; Picchi, Valentina; Abbruscato, Pamela; Genga, Annamaria

    2013-09-01

    One of the major objectives of rice (Oryza sativa L.) breeding programs is the development of new varieties with higher tolerance/resistance to both abiotic and biotic stresses. In this study, Italian rice cultivars were subjected to osmotic stress or benzothiadiazole (BTH) treatments. An analysis of the expression of selected genes known to be involved in the stress response and (1)H nuclear magnetic resonance ((1)H NMR) metabolic profiling were combined with multivariate statistical analyses to elucidate potential correlations between gene expression or metabolite content and observed tolerant/resistant phenotypes. We observed that the expression of three chosen genes (two WRKY genes and one peroxidase encoding gene) differed between susceptible and resistant cultivars in response to BTH treatments. Moreover, the analysis of metabolite content, in particular in the osmotic stress experiment, enabled discrimination between selected cultivars based on differences in the accumulation of some primary metabolites, primarily sugars. This research highlights the potential usefulness of this approach to characterise rice varieties based on transcriptional or metabolic changes due to adverse environmental conditions.

  15. 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.

  16. 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.

  17. 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.

  18. Associations between five-factor model of the Positive and Negative Syndrome Scale and plasma levels of monoamine metabolite in patients with schizophrenia.

    PubMed

    Watanabe, Kenya; Miura, Itaru; Kanno-Nozaki, Keiko; Horikoshi, Sho; Mashiko, Hirobumi; Niwa, Shin-Ichi; Yabe, Hirooki

    2015-12-15

    The five-factor model of the Positive and Negative Syndrome Scale (PANSS) for schizophrenia symptoms is the most common multiple-factor model used in analyses; its use may improve evaluation of symptoms in schizophrenia patients. Plasma monoamine metabolite levels are possible indicators of clinical symptoms or response to antipsychotics in schizophrenia. We investigated the association between five-factor model components and plasma monoamine metabolites levels to explore the model's biological basis. Plasma levels of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were measured using high-performance liquid chromatography in 65 Japanese patients with schizophrenia. Significant negative correlation between plasma 5-HIAA levels and the depression/anxiety component was found. Furthermore, significant positive correlation was found between plasma MHPG levels and the excitement component. Plasma HVA levels were not correlated with any five-factor model component. These results suggest that the five-factor model of the PANSS may have a biological basis, and may be useful for elucidating the psychopathology of schizophrenia. Assessment using the five-factor model may enable understanding of monoaminergic dysfunction, possibly allowing more appropriate medication selection. Further studies of a larger number of first-episode schizophrenia patients are needed to confirm and extend these results.

  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. 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

  1. Law and regulation of benzene.

    PubMed Central

    Feitshans, I L

    1989-01-01

    OSHA has created final benzene regulations after extensive rulemakings on two occasions, 1978 and 1987. These standards have been the subject of extensive litigation for nearly 20 years. This article examines in detail the conceptual underpinnings of the Benzene Case, (which was decided by the U.S. Supreme Court in 1980) in light of U.S. administrative law precedents that have set limits upon administrative discretion under the test for "substantial evidence" and the "hard look doctrine." This article also addresses recent developments in the wake of the Benzene Case and their implications for benzene regulations following the "significant risk" doctrine in that case. This article briefly describes other national, regional, and international laws governing the use of benzene. This article concludes that the revisions of the benzene regulation and subsequent rulemaking provide substantial evidence of scientific underpinnings for regulatory action and that laws from other nations reflect an international consensus that occupational exposure to benzene is a proper subject of regulation. Such regulations and policies are therefore likely to withstand scrutiny and remain enforceable as widely accepted norms. PMID:2792048

  2. Oxidative DNA damage and influence of genetic polymorphisms among urban and rural schoolchildren exposed to benzene.

    PubMed

    Buthbumrung, Nantaporn; Mahidol, Chulabhorn; Navasumrit, Panida; Promvijit, Jeerawan; Hunsonti, Potchanee; Autrup, Herman; Ruchirawat, Mathuros

    2008-04-15

    Traffic related urban air pollution is a major environmental health problem in many large cities. Children living in urban areas are exposed to benzene and other toxic pollutants simultaneously on a regular basis. Assessment of benzene exposure and oxidative DNA damage in schoolchildren in Bangkok compared with the rural schoolchildren was studied through the use of biomarkers. Benzene levels in ambient air at the roadside adjacent to Bangkok schools was 3.95-fold greater than that of rural school areas. Personal exposure to benzene in Bangkok schoolchildren was 3.04-fold higher than that in the rural schoolchildren. Blood benzene, urinary benzene and urinary muconic acid (MA) levels were significantly higher in the Bangkok schoolchildren. A significantly higher level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in leukocytes and in urine was found in Bangkok children than in the rural children. There was a significant correlation between individual benzene exposure level and blood benzene (rs=0.193, P<0.05), urinary benzene (rs=0.298, P<0.05), urinary MA (rs=0.348, P<0.01), and 8-OHdG in leukocyte (rs=0.130, P<0.05). In addition, a significant correlation between urinary MA and 8-OHdG in leukocytes (rs=0.241, P<0.05) was also found. Polymorphisms of various xenobiotic metabolizing genes responsible for susceptibility to benzene toxicity have been studied; however only the GSTM1 genotypes had a significant effect on urinary MA excretion. Our data indicates that children living in the areas of high traffic density are exposed to a higher level of benzene than those living in rural areas. Exposure to higher level of benzene in urban children may contribute to oxidative DNA damage, suggesting an increased health risk from traffic benzene emission.

  3. 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

  4. Effects of a high-caloric diet and physical exercise on brain metabolite levels: a combined proton MRS and histologic study

    PubMed Central

    Auer, Matthias K; Sack, Markus; Lenz, Jenny N; Jakovcevski, Mira; Biedermann, Sarah V; Falfán-Melgoza, Claudia; Deussing, Jan; Steinle, Jörg; Bielohuby, Maximilian; Bidlingmaier, Martin; Pfister, Frederik; Stalla, Günter K; Ende, Gabriele; Weber-Fahr, Wolfgang; Fuss, Johannes; Gass, Peter

    2015-01-01

    Excessive intake of high-caloric diets as well as subsequent development of obesity and diabetes mellitus may exert a wide range of unfavorable effects on the central nervous system (CNS). It has been suggested that one mechanism in this context is the promotion of neuroinflammation. The potentially harmful effects of such diets were suggested to be mitigated by physical exercise. Here, we conducted a study investigating the effects of physical exercise in a cafeteria-diet mouse model on CNS metabolites by means of in vivo proton magnetic resonance spectroscopy (1HMRS). In addition postmortem histologic and real-time (RT)-PCR analyses for inflammatory markers were performed. Cafeteria diet induced obesity and hyperglycemia, which was only partially moderated by exercise. It also induced several changes in CNS metabolites such as reduced hippocampal glutamate (Glu), choline-containing compounds (tCho) and N-acetylaspartate (NAA)+N-acetyl-aspartyl-glutamic acid (NAAG) (tNAA) levels, whereas opposite effects were seen for running. No association of these effects with markers of central inflammation could be observed. These findings suggest that while voluntary wheel running alone is insufficient to prevent the unfavorable peripheral sequelae of the diet, it counteracted many changes in brain metabolites. The observed effects seem to be independent of neuroinflammation. PMID:25564238

  5. Effects of a high-caloric diet and physical exercise on brain metabolite levels: a combined proton MRS and histologic study.

    PubMed

    Auer, Matthias K; Sack, Markus; Lenz, Jenny N; Jakovcevski, Mira; Biedermann, Sarah V; Falfán-Melgoza, Claudia; Deussing, Jan; Steinle, Jörg; Bielohuby, Maximilian; Bidlingmaier, Martin; Pfister, Frederik; Stalla, Günter K; Ende, Gabriele; Weber-Fahr, Wolfgang; Fuss, Johannes; Gass, Peter

    2015-03-31

    Excessive intake of high-caloric diets as well as subsequent development of obesity and diabetes mellitus may exert a wide range of unfavorable effects on the central nervous system (CNS). It has been suggested that one mechanism in this context is the promotion of neuroinflammation. The potentially harmful effects of such diets were suggested to be mitigated by physical exercise. Here, we conducted a study investigating the effects of physical exercise in a cafeteria-diet mouse model on CNS metabolites by means of in vivo proton magnetic resonance spectroscopy ((1)HMRS). In addition postmortem histologic and real-time (RT)-PCR analyses for inflammatory markers were performed. Cafeteria diet induced obesity and hyperglycemia, which was only partially moderated by exercise. It also induced several changes in CNS metabolites such as reduced hippocampal glutamate (Glu), choline-containing compounds (tCho) and N-acetylaspartate (NAA)+N-acetyl-aspartyl-glutamic acid (NAAG) (tNAA) levels, whereas opposite effects were seen for running. No association of these effects with markers of central inflammation could be observed. These findings suggest that while voluntary wheel running alone is insufficient to prevent the unfavorable peripheral sequelae of the diet, it counteracted many changes in brain metabolites. The observed effects seem to be independent of neuroinflammation.

  6. A high-throughput approach to identify genomic variants of bacterial metabolite producers at the single-cell level

    PubMed Central

    2012-01-01

    We present a novel method for visualizing intracellular metabolite concentrations within single cells of Escherichia coli and Corynebacterium glutamicum that expedites the screening process of producers. It is based on transcription factors and we used it to isolate new L-lysine producing mutants of C. glutamicum from a large library of mutagenized cells using fluorescence-activated cell sorting (FACS). This high-throughput method fills the gap between existing high-throughput methods for mutant generation and genome analysis. The technology has diverse applications in the analysis of producer populations and screening of mutant libraries that carry mutations in plasmids or genomes. PMID:22640862

  7. 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.

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

    PubMed

    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

  11. 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

  12. 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.

  13. 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

  14. 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

    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

  15. 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.

  16. 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.

  17. 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.

  18. A proposed role played by benzene itself in the induction of acute cytopenia: inhibition of DNA synthesis.

    PubMed

    Lee, E W; Garner, C D; Johnson, J T

    1988-04-01

    A single intraperitoneal dose of benzene (880 mg/kg) in mice inhibited DNA synthesis of bone marrow cells within one hour postinjection. However, there was no inhibitory effect on the synthesis of heme and protein at that dosage. Dose-dependent inhibition of DNA synthesis by benzene was observed over the range of 440 to 1760 mg/kg, supporting the idea that cytopenia which was observed by others following multiple doses of benzene (e.g., 440 or 880 mg/kg) might be due to the inhibitory effect of benzene on DNA synthesis. In our studies, benzene concentrations above 81 micrograms/g wet bone marrow resulted in inhibition of DNA synthesis, regardless of whether it was given ip or by inhalation. The effect of benzene itself, rather than its toxic metabolites, on DNA synthesis was further seen in experiments using a bone marrow cell culture system and cell-free DNA synthetic system. Experimental results demonstrated that benzene alone was capable of inhibiting the DNA synthesis of bone marrow cells and that the reduced DNA synthesis resulted from the inhibitory effect of benzene on DNA polymerase alpha, the enzyme that catalyzes the last step of the DNA synthetic pathway. Thus, benzene itself could play a significant role in inducing myelotoxicity in the case of acute or subacute toxicity by exerting its inhibitory effect on DNA synthesis.

  19. 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

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

    PubMed

    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

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

    PubMed

    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.

  2. Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000.

    PubMed Central

    Silva, Manori J; Barr, Dana B; Reidy, John A; Malek, Nicole A; Hodge, Carolyn C; Caudill, Samuel P; Brock, John W; Needham, Larry L; Calafat, Antonia M

    2004-01-01

    We measured the urinary monoester metabolites of seven commonly used phthalates in approximately 2,540 samples collected from participants of the National Health and Nutrition Examination Survey (NHANES), 1999-2000, who were greater than or equal to 6 years of age. We found detectable levels of metabolites monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono-(2-ethylhexyl) phthalate (MEHP) in > 75% of the samples, suggesting widespread exposure in the United States to diethyl phthalate, dibutyl phthalate or diisobutylphthalate, benzylbutyl phthalate, and di-(2-ethylhexyl) phthalate, respectively. We infrequently detected monoisononyl phthalate, mono-cyclohexyl phthalate, and mono-n-octyl phthalate, suggesting that human exposures to di-isononyl phthalate, dioctylphthalate, and dicyclohexyl phthalate, respectively, are lower than those listed above, or the pathways, routes of exposure, or pharmacokinetic factors such as absorption, distribution, metabolism, and elimination are different. Non-Hispanic blacks had significantly higher concentrations of MEP than did Mexican Americans and non-Hispanic whites. Compared with adolescents and adults, children had significantly higher levels of MBP, MBzP, and MEHP but had significantly lower concentrations of MEP. Females had significantly higher concentrations of MEP and MBzP than did males, but similar MEHP levels. Of particular interest, females of all ages had significantly higher concentrations of the reproductive toxicant MBP than did males of all ages; however, women of reproductive age (i.e., 20-39 years of age) had concentrations similar to adolescent girls and women 40 years of age. These population data on exposure to phthalates will serve an important role in public health by helping to set research priorities and by establishing a nationally representative baseline of exposure with which population levels can be compared. PMID:14998749

  3. Association Between Variants in Arsenic (+3 Oxidation State) Methyltranserase (AS3MT) and Urinary Metabolites of Inorganic Arsenic: Role of Exposure Level.

    PubMed

    Xu, Xiaofan; Drobná, Zuzana; Voruganti, V Saroja; Barron, Keri; González-Horta, Carmen; Sánchez-Ramírez, Blanca; Ballinas-Casarrubias, Lourdes; Cerón, Roberto Hernández; Morales, Damián Viniegra; Terrazas, Francisco A Baeza; Ishida, María C; Gutiérrez-Torres, Daniela S; Saunders, R Jesse; Crandell, Jamie; Fry, Rebecca C; Loomis, Dana; García-Vargas, Gonzalo G; Del Razo, Luz M; Stýblo, Miroslav; Mendez, Michelle A

    2016-09-01

    Variants in AS3MT, the gene encoding arsenic (+3 oxidation state) methyltranserase, have been shown to influence patterns of inorganic arsenic (iAs) metabolism. Several studies have suggested that capacity to metabolize iAs may vary depending on levels of iAs exposure. However, it is not known whether the influence of variants in AS3MT on iAs metabolism also vary by level of exposure. We investigated, in a population of Mexican adults exposed to drinking water As, whether associations between 7 candidate variants in AS3MT and urinary iAs metabolites were consistent with prior studies, and whether these associations varied depending on the level of exposure. Overall, associations between urinary iAs metabolites and AS3MT variants were consistent with the literature. Referent genotypes, defined as the genotype previously associated with a higher percentage of urinary dimethylated As (DMAs%), were associated with significant increases in the DMAs% and ratio of DMAs to monomethylated As (MAs), and significant reductions in MAs% and iAs%. For 3 variants, associations between genotypes and iAs metabolism were significantly stronger among subjects exposed to water As >50 versus ≤50 ppb (water As X genotype interaction P < .05). In contrast, for 1 variant (rs17881215), associations were significantly stronger at exposures ≤50 ppb. Results suggest that iAs exposure may influence the extent to which several AS3MT variants affect iAs metabolism. The variants most strongly associated with iAs metabolism-and perhaps with susceptibility to iAs-associated disease-may vary in settings with exposure level. PMID:27370415

  4. Contribution of tobacco smoke to environmental benzene exposure in Germany

    SciTech Connect

    Scherer, G.; Ruppert, T.; Daube, H.

    1995-12-31

    The concentrations of environmental tobacco smoke (ETS) constituents including benzene were measured in the living rooms of 10 nonsmoking households and 20 households with at least one smoker situated in the city and suburbs of Munich. In the city, the median benzene levels during the evening, when all household members were at home, were 8.1 and 10.4 {mu}g/m{sup 3} in nonsmoking and smoking homes, respectively. The corresponding levels of 3.5 and 4.6 {mu}g/m{sup 3} were considerably lower in the suburbs. Median time-integrated 1-week benzene concentrations in the city were 10.6 {mu}g/m{sup 3} in nonsmoking homes and 13.1 {mu}g/m{sup 3} in smoking homes. In the suburbs, the corresponding values were 3.2 and 5.6 {mu}g/m{sup 3}. No difference was found between smoking and nonsmoking households located either in the city or in the suburbs. There was no statistically significant difference between benzene exposure of non-smokers in smoking and nonsmoking homes. Nonsmokers living in nonsmoking households in the city had significantly higher exposure to benzene compared to their counterparts living in the suburban. Nonsmokers from all households with smokers were significantly more exposed to benzene than nonsmokers living in the nonsmoking households (personal samplers: 13.2 vs. 7.0 {mu}g/m{sup 3}, p < 0.05; benzene in exhalate: 2.6 vs. 1.8 {mu}g/m{sup 3}, p < 0.01; trans-muconic acid excretion in urine: 73 vs. 62 {mu}g/g creatinine), but the contribution of ETS to the total benzene exposure was relatively low compared to that from other sources. Analysis of variance showed that at most 15% of the benzene exposure of nonsmokers living in smoking homes was attributable to ETS. For nonsmokers living in nonsmoking households benzene exposure from ETS was insignificant.

  5. Modeling theta-theta Interactions with the Effective Fragment Potential Method: The Benzene Dimer and Substituents

    SciTech Connect

    Toni Smithl; Lyudmila V. Slipchenko; Mark S. Gordon

    2008-02-27

    This study compares the results of the general effective fragment potential (EFP2) method to the results of a previous combined coupled cluster with single, double, and perturbative triple excitations [CCSD(T)] and symmetry-adapted perturbation theory (SAPT) study [Sinnokrot and Sherrill, J. Am. Chem. Soc., 2004, 126, 7690] on substituent effects in {pi}-{pi} interactions. EFP2 is found to accurately model the binding energies of the benzene-benzene, benzene-phenol, benzene-toluene, benzene-fluorobenzene, and benzene-benzonitrile dimers, as compared with high-level methods [Sinnokrot and Sherrill, J. Am. Chem. Soc., 2004, 126, 7690], but at a fraction of the computational cost of CCSD(T). In addition, an EFP-based Monte Carlo/simulated annealing study was undertaken to examine the potential energy surface of the substituted dimers.

  6. The Solubility of Phenylborate Compounds in Benzene

    SciTech Connect

    Eibling, R.E.

    1998-04-01

    The original goal of this scoping study was to determine if the solubility of sodium and potassium tetraphenylborates in benzene was sufficiently large to justify designing and performing kinetic studies on a benzene-phase catalytic reaction.

  7. Relation of dissociative phenomena to levels of cerebrospinal fluid monoamine metabolites and beta-endorphin in patients with eating disorders: a pilot study.

    PubMed

    Demitrack, M A; Putnam, F W; Rubinow, D R; Pigott, T A; Altemus, M; Krahn, D D; Gold, P W

    1993-10-01

    Dissociation is made manifest by a failure to integrate thoughts, feelings, memories, and actions into a unified sense of consciousness. Although dissociation is presumed to be a special state of consciousness manifested by state-dependent memory and physiology, the psychobiology of dissociation is poorly understood. In this study, we examined cerebrospinal fluid levels of the major monoamine metabolites and beta-endorphin in patients with eating disorders (11 with anorexia nervosa, 16 with bulimia nervosa), while they were acutely ill. Dissociative capacity was measured using the Dissociative Experiences Scale (DES). We provide evidence that neurochemical changes in dopaminergic, serotonergic, and opioid systems may be associated with the clinical expression of dissociation in patients with eating disorders during the acute phase of their illness. These preliminary results are compatible with previous studies of neurochemical disturbances in the eating disorders and suggest that future work in dissociation should specifically include examination of these neurobiologic systems.

  8. 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.

  9. 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. PMID:23743798

  10. 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.

  11. 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

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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

  3. 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.

  4. Effects of feeding level of milk replacer on body growth, plasma metabolite and insulin concentrations, and visceral organ growth of suckling calves.

    PubMed

    Kamiya, Mitsuru; Matsuzaki, Masatoshi; Orito, Hideki; Kamiya, Yuko; Nakamura, Yoshi-nori; Tsuneishi, Eisaku

    2009-12-01

    The objective was to evaluate effects of feeding level of milk replacer on body growth, plasma metabolite and insulin concentrations, and allometric growth of visceral organs in suckling calves. Holstein bull calves (n = 8; 3-4 days of age) were fed either a low amount (average 0.63 kgDM/day, LM) or high amount (average 1.15 kgDM/day, HM) of high protein milk replacer until they were slaughtered at 6 weeks of age. Body weight (BW) at 4, 5, and 6 weeks of age, feed intake, average daily gain, and feed efficiency were higher in the HM than LM calves. The HM group had higher plasma glucose at 3 and 4 weeks of age and insulin levels after the age of 4 weeks compared with LM calves whereas no effect was detected on plasma nonesterified fatty acid or urea nitrogen concentrations. The HM calves had greater empty body weight (EBW), viscera-free BW and most of the organs dissected than LM calves. Relative weights (% of EBW) of liver, spleen, kidneys, and internal fat were higher, whereas head and large intestine was lower in HM than LM calves. The results suggest that increased milk feeding levels would accelerate the growth of the body and specific organs.

  5. 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

  6. 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

  7. 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.

  8. Elevated levels of urinary prostaglandin e metabolite indicate a poor prognosis in ever smoker head and neck squamous cell carcinoma patients.

    PubMed

    Kekatpure, Vikram D; Boyle, Jay O; Zhou, Xi Kathy; Duffield-Lillico, Anna J; Gross, Neil D; Lee, Nancy Y; Subbaramaiah, Kotha; Morrow, Jason D; Milne, Ginger; Lippman, Scott M; Dannenberg, Andrew J

    2009-11-01

    Cyclooxygenase (COX)-derived prostaglandin E(2) (PGE(2)) plays a role in the development and progression of several tumor types including head and neck squamous cell carcinoma (HNSCC). Measurements of urinary PGE metabolite (PGE-M) can be used as an index of systemic PGE(2) production. In ever smokers, increased levels of urinary PGE-M reflect increased COX-2 activity. In this study, we determined whether baseline levels of urinary PGE-M were prognostic for ever smoker HNSCC patients. A retrospective chart review of ever smoker HNSCC patients treated with curative intent was done. Fifteen of 31 evaluable patients developed progressive disease (recurrence or a second primary tumor) after a median follow-up of 38 months. There were no statistically significant differences between patients with (n = 15) or without disease progression (n = 16) with regard to stage, site, treatment received, smoking status, and aspirin use during follow-up. Median urinary PGE-M levels were significantly higher in HNSCC patients with disease progression (21.7 ng/mg creatinine) compared with patients without (13.35 ng/mg creatinine; P = 0.03). Importantly, patients with high baseline levels of urinary PGE-M had a significantly greater risk of disease progression (hazard ratio, 4.76, 95% CI, 1.31-17.30; P < 0.01) and death (hazard ratio, 9.54; 95% CI, 1.17-77.7; P = 0.01) than patients with low baseline levels of urinary PGE-M. These differences were most evident among patients with early-stage disease. Taken together, our findings suggest that high baseline levels of urinary PGE-M indicate a poor prognosis in HNSCC patients. Possibly, HNSCC patients with high COX-2 activity manifested by elevated urinary PGE-M will benefit from treatment with a COX-2 inhibitor. PMID:19843689

  9. Bacterial dehalorespiration with chlorinated benzenes.

    PubMed

    Adrian, L; Szewzyk, U; Wecke, J; Görisch, H

    2000-11-30

    Chlorobenzenes are toxic, highly persistent and ubiquitously distributed environmental contaminants that accumulate in the food chain. The only known microbial transformation of 1,2,3,5-tetrachlorobenzene (TeCB) and higher chlorinated benzenes is the reductive dechlorination to lower chlorinated benzenes under anaerobic conditions observed with mixed bacterial cultures. The lower chlorinated benzenes can subsequently be mineralized by aerobic bacteria. Here we describe the isolation of the oxygen-sensitive strain CBDB1, a pure culture capable of reductive dechlorination of chlorobenzenes. Strain CBDB1 is a highly specialized bacterium that stoichiometrically dechlorinates 1,2,3-trichlorobenzene (TCB), 1,2,4-TCB, 1,2,3,4-TeCB, 1,2,3,5-TeCB and 1,2,4,5-TeCB to dichlorobenzenes or 1,3,5-TCB. The presence of chlorobenzene as an electron acceptor and hydrogen as an electron donor is essential for growth, and indicates that strain CBDB1 meets its energy needs by a dehalorespiratory process. According to their 16S rRNA gene sequences, strain CBDB1, Dehalococcoides ethenogenes and several uncultivated bacteria form a new bacterial cluster, of which strain CBDB1 is the first, so far, to thrive on a purely synthetic medium.

  10. Bioremediation of chlorinated benzene compounds

    SciTech Connect

    Peck, P.C.; Rhodes, S.H.; Guerin, T.F.

    1995-12-31

    In early 1994, investigations at a pharmaceutical manufacturing site revealed extensive areas of soil contaminated with chlorinated benzenes. The soil was a heavy clay and contained chlorobenzene (CB), 1,2-dichlorobenzene (referred to in this paper as DCB), and small amounts of 1,3- and 1,4-dichlorobenzene and other solvents. The soil was bioremediated in a pilot-scale treatment using an ex situ process with various inorganic and organic amendments. Approximately 90% of the DCB mass present in the soil was removed over a period of 2 to 3 weeks. Up to 100-fold increases in both total heterotrophs and specific degraders were observed. Residual concentrations of chlorinated benzenes were generally below detection limits. Adding organic matter did not appear to significantly enhance the treatment efficiency. Mass balance calculations applied to the treatment indicated that less than 5% of the chlorinated benzenes were removed by volatilization. Evidence was obtained that approximately 90% of the DCB was removed by biodegradation in these pilot-scale trials. Laboratory shake flask trials were conducted which confirmed that the soils in the pilot-scale treatment contained microorganisms capable of mineralizing CB and DCB.

  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. 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. PMID:26824528

  13. 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

  14. Assessment of human exposure to benzene through foods from the Belgian market.

    PubMed

    Medeiros Vinci, Raquel; Jacxsens, Liesbeth; Van Loco, Joris; Matsiko, Eric; Lachat, Carl; de Schaetzen, Thibault; Canfyn, Michael; Van Overmeire, Ilse; Kolsteren, Patrick; De Meulenaer, Bruno

    2012-08-01

    Benzene is a volatile organic compound known to be carcinogenic to humans (Group 1) and may be present in food. In the present study, 455 food samples from the Belgian market were analyzed for benzene contents and some possible sources of its occurrence in the foodstuffs were evaluated. Benzene was found above the level of detection in 58% of analyzed samples with the highest contents found in processed foods such as smoked and canned fish, and foods which contained these as ingredients (up to 76.21 μg kg(-1)). Unprocessed foods such as raw meat, fish, and eggs contained much lower concentrations of benzene. Using the benzene concentrations in food, a quantitative dietary exposure assessment of benzene intake was conducted on a national representative sample of the Belgian population over 15 years of age. The mean benzene intake for all foods was 0.020 μg kg bw d(-1) according to a probabilistic analysis. These values are below the minimum risk level for oral chronic exposure to benzene (0.5 μg kg bw d(-1)). PMID:22483726

  15. Effects of benzene inhalation on lymphocyte subpopulations and immune response in mice.

    PubMed

    Aoyama, K

    1986-08-01

    To clarify the immunotoxicity of benzene, the effects of benzene inhalation on T and B lymphocytes and immune responses in mice were examined. BALB/c male mice were exposed to 50 or 200 ppm benzene vapor, 6 hr/day for 7 or 14 consecutive days. T and B lymphocytes, in blood and spleen, were detected by the cytotoxicity assay with anti-Thy-1.2 monoclonal antibody and the membrane immunofluorescence test with anti-immunoglobulin antibody, respectively. Humoral immune response to sheep red blood cells was determined by the hemolytic plaque-forming cell assay. Cell-mediated immune response was measured by contact sensitivity (CS) to picryl chloride. The activity of suppressor cells was evaluated in spleen by the suppressive effect on passive transfer of CS. The ratio and absolute number of T and B lymphocytes in blood and spleen were depressed after a 7-day exposure at 50 ppm benzene. The depression of B lymphocytes was dose dependent and more intense than that of T lymphocytes. The ability to form antibodies was suppressed by benzene at all exposure levels, but the CS response was resistant to benzene inhalation and rather enhanced at 200 ppm exposure for 14 days. The activity of suppressor cells could not be detected at this dose level. These data show that benzene inhalation effects on humoral and cell-mediated immune responses are a result of the selective toxicity of benzene to B lymphocytes and suppressor T cells.

  16. Benzene emission from the actual car fleet in relation to petrol composition in Denmark

    NASA Astrophysics Data System (ADS)

    Palmgren, Finn; Hansen, Asger B.; Berkowicz, Ruwim; Skov, Henrik

    The present study covers an investigation of the trends in air pollution levels of benzene in Danish cities and their relationship with the benzene content in petrol. Petrol samples from the two refineries in Denmark as well as sold petrol from some representative Danish petrol stations were analysed. The benzene content in Danish petrol was reduced from 3.5% for 95 octane prior to 1995 to approx. 2% in 1995 and further to 1 % in 1998. Air quality measurements of aromatic VOC are available from two Danish cities; Copenhagen since 1994 and Odense since 1997. Measurements of benzene, CO and NO x from these two locations were analysed using the Operational Street Pollution Model (OSPM) and trends in the actual emissions of these pollutants were determined. It is shown that the decrease in both the concentration levels and in the emissions was significantly larger for benzene than for CO and NO x. The decreasing trends of NO x and CO could be explained by the increasing fraction of petrol-fuelled vehicles with three way catalysts (TWC). The much steeper decreasing trend for benzene can most likely be attributed to a combination of the effect of the increasing share of the TWC vehicles and a simultaneous reduction of benzene content in Danish petrol. The reduction of benzene concentrations and emissions is observed despite that the total amount of aromatics in petrol has increased slightly in the same period.

  17. Assessment of human exposure to benzene through foods from the Belgian market.

    PubMed

    Medeiros Vinci, Raquel; Jacxsens, Liesbeth; Van Loco, Joris; Matsiko, Eric; Lachat, Carl; de Schaetzen, Thibault; Canfyn, Michael; Van Overmeire, Ilse; Kolsteren, Patrick; De Meulenaer, Bruno

    2012-08-01

    Benzene is a volatile organic compound known to be carcinogenic to humans (Group 1) and may be present in food. In the present study, 455 food samples from the Belgian market were analyzed for benzene contents and some possible sources of its occurrence in the foodstuffs were evaluated. Benzene was found above the level of detection in 58% of analyzed samples with the highest contents found in processed foods such as smoked and canned fish, and foods which contained these as ingredients (up to 76.21 μg kg(-1)). Unprocessed foods such as raw meat, fish, and eggs contained much lower concentrations of benzene. Using the benzene concentrations in food, a quantitative dietary exposure assessment of benzene intake was conducted on a national representative sample of the Belgian population over 15 years of age. The mean benzene intake for all foods was 0.020 μg kg bw d(-1) according to a probabilistic analysis. These values are below the minimum risk level for oral chronic exposure to benzene (0.5 μg kg bw d(-1)).

  18. Male mice deficient in microsomal epoxide hydrolase are not susceptible to benzene-induced toxicity.

    PubMed

    Bauer, Alison K; Faiola, Brenda; Abernethy, Diane J; Marchan, Rosemarie; Pluta, Linda J; Wong, Victoria A; Gonzalez, Frank J; Butterworth, Byron E; Borghoff, Susan J; Everitt, Jeffrey I; Recio, Leslie

    2003-04-01

    Enzymes involved in benzene metabolism are likely genetic determinants of benzene-induced toxicity. Polymorphisms in human microsomal epoxide hydrolase (mEH) are associated with an increased risk of developing leukemia, specifically those associated with benzene. This study was designed to investigate the importance of mEH in benzene-induced toxicity. Male and female mEH-deficient (mEH-/-) mice and background mice (129/Sv) were exposed to inhaled benzene (0, 10, 50, or 100 ppm) 5 days/week, 6 h/day, for a two-week duration. Total white blood cell counts and bone marrow cell counts were used to assess hematotoxicity and myelotoxicity. Micronucleated peripheral blood cells were counted to assess genotoxicity, and the p21 mRNA level in bone marrow cells was used as a determinant of the p53-regulated DNA damage response. Male mEH-/- mice did not have any significant hematotoxicity or myelotoxicity at the highest benzene exposure compared to the male 129/Sv mice. Significant hematotoxicity or myelotoxicity did not occur in the female mEH-/- or 129/Sv mice. Male mEH-/- mice were also unresponsive to benzene-induced genotoxicity compared to a significant induction in the male 129/Sv mice. The female mEH-/- and 129/Sv mice were virtually unresponsive to benzene-induced genotoxicity. While p21 mRNA expression was highly induced in male 129/Sv mice after exposure to 100-ppm benzene, no significant alteration was observed in male mEH-/- mice. Likewise, p21 mRNA expression in female mEH-/- mice was not significantly induced upon benzene exposure whereas a significant induction was observed in female 129/Sv mice. Thus mEH appears to be critical in benzene-induced toxicity in male, but not female, mice.

  19. 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.

  20. 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

  1. 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

  2. Effect of precalving and postcalving dietary energy level on performance and blood metabolite concentrations of dairy cows throughout lactation.

    PubMed

    Law, R A; Young, F J; Patterson, D C; Kilpatrick, D J; Wylie, A R G; Ingvarsten, K L; Hameleers, A; McCoy, M A; Mayne, C S; Ferris, C

    2011-02-01

    The effects of the level of energy intake (high E and low E) offered before and after calving on body condition score at calving, production performance, and energy status in the first 250 d of lactation were evaluated in a 2 × 2 factorial design experiment involving 80 Holstein-Friesian dairy animals (40 primiparous and 40 multiparous). From d 80 until d 21 precalving, primiparous animals were offered either high or low pasture allowances. Thereafter, these animals were housed and had ad libitum access to a high energy density diet (high E) or restricted access [6 kg of dry matter (DM) per d] to a low energy density diet (low E), respectively, until calving. From d 100 until d 42 precalving, multiparous animals were offered either ad libitum or restricted (10 kg of DM/d) access to a late lactation diet, and thereafter, had ad libitum access to a high E diet or restricted access (7 kg of DM complete diet/d) to a low E diet, respectively, until calving. The forage to concentrate (F:C) ratios (DM basis) of these high E and low E diets [d 42 (d 21 in primiparous animals) until calving] were 64:36 and 83:17, respectively. Cows offered high E and low E precalving diets were allocated to either a high E or low E postcalving diet [F:C ratio (DM basis) of 30:70 and 70:30, respectively] and remained on these diets until d 250 of lactation. Multiparous animals offered a high E diet precalving had a significantly higher body condition score at calving than those offered the low E diet precalving. This effect was not evident in primiparous animals. Precalving diet had no significant effect on plasma nonesterified fatty acid concentrations during the last 3 wk precalving in primi- or multiparous animals. Primiparous animals offered a high E diet precalving had significantly higher postcalving plasma concentrations of nonesterified fatty acid, suggesting greater mobilization of body reserves. Primi- and multiparous animals offered a high E diet postcalving had a significantly

  3. Biliary excretion of foreign compounds. Benzene and its derivatives in the rat

    PubMed Central

    Abou-El-Makarem, M. M.; Millburn, P.; Smith, R. L.; Williams, R. T.

    1967-01-01

    1. The extent of the excretion in the bile of the rat of benzene and 21 of its simple derivatives was studied. 2. Some 16 compounds of molecular weight less than 200, and including neutral molecules (benzene and toluene), aromatic acids, aromatic amines and phenols, were injected in solution intraperitoneally into biliary-cannulated rats. Metabolites in the bile were identified and estimated. The extent of biliary excretion of these compounds was low, i.e. 0–10% of the dose in 24hr., and most appeared in the bile mainly as conjugates. 3. The biliary excretion of six conjugates of molecular weight less than 300, including three glycine conjugates, one sulphate conjugate, one glucuronic acid conjugate and two acetyl derivatives, was low (less than 3% of the dose). 4. It is concluded that simple benzene derivatives of molecular weight less than about 300 are poorly excreted in rat bile. PMID:16742555

  4. 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

  5. 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

  6. 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

  7. The effect of angiotensin II microinjection into the bed nucleus of the stria terminalis on serum lipid peroxidation and nitric oxide metabolite levels

    PubMed Central

    Kafami, Marzieh

    2016-01-01

    Background: Overactivity of renin-angiotensin system is involved in the pathophysiology of renal and cardiovascular diseases. It is suggested that endothelial cells can release nitric oxide (NO) and reactive oxygen species in response to angiotensin II (Ang II). Angiotensin type 1 (AT1) receptor of Ang II has been found in the bed nucleus of the stria terminalis (BST). BST is involved in autonomic function. This study was performed to find the role of central Ang II in serum lipid peroxidation product and in releasing NO into circulation. Materials and Methods: Twenty-one catheterized rats were placed in stereotaxic instrument. A hole was drilled above BST. In the control group, saline 0.9% (100 nl) was microinjected into the BST. In the second group, Ang II (100 μM, 100–150 nl) was microinjected into the BST. In the third group losartan (an AT1 antagonist) was microinjected (100 μM, 200 nl) before Ang II into the BST. Systolic blood pressure was recorded. The NO metabolite (nitrite) and malondialdehyde (MDA) were measured in the rat's serum. Results: The data indicated that microinjection of Ang II into the BST produced a pressor response (P < 0.0001). It also increased MDA and nitrite levels of the serum significantly (P < 0.001, P < 0.0001). Pretreatment with losartan before Ang II microinjection attenuated serum's levels of MDA and nitrite (P < 0.001, P < 0.0001). Conclusion: Our findings suggest that central effect of Ang II on blood pressure is accompanied with increased levels of MDA and nitrite in the circulation. PMID:27376045

  8. 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

  9. 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.

  10. 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. PMID:18618286

  11. 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

  12. 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

  13. 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.

  14. 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. PMID:26735038

  15. High benzene concentrations can favour Gram-positive bacteria in groundwaters from a contaminated aquifer.

    PubMed

    Fahy, Anne; Ball, Andrew S; Lethbridge, Gordon; McGenity, Terry J; Timmis, Kenneth N

    2008-09-01

    Exposure to pollution exerts strong selective pressure on microbial communities, which may affect their potential to adapt to current or future environmental challenges. In this microcosm study, we used DNA fingerprinting based on 16S rRNA genes to document the impact of high concentrations of benzene on two bacterial communities from a benzene-contaminated aquifer situated below a petrochemical plant (SIReN, UK). The two groundwaters harboured distinct aerobic benzene-degrading communities able to metabolize benzene to below detection levels (1 microg L(-1)). A benzene concentration of 100 mg L(-1) caused a major shift from Betaproteobacteria to Actinobacteria, in particular Arthrobacter spp. A similar shift from Betaproteobacteria to Arthrobacter spp. and Rhodococcus erythropolis was observed in minimal medium (MM) inoculated with a third groundwater. These Gram-positive-dominated communities were able to grow on benzene at concentrations up to 600 mg L(-1) in groundwater and up to 1000 mg L(-1) in MM, concentrations that cause significant solvent stress to cellular systems. Therefore, Gram-positive bacteria were better competitors than Gram-negative organisms under experimental conditions of high benzene loads, which suggests that solvent-tolerant Gram-positive bacteria can play a role in the natural attenuation of benzene or the remediation of contaminated sites.

  16. S-phenylcysteine in albumin as a benzene biomarker

    SciTech Connect

    Bechtold, W.E.; Strunk, M.R.

    1996-12-01

    Biological markers of internal dose are useful for improving the extrapolation of health effects from exposures to high levels of toxic air pollutants in animals to low, ambient exposures in humans. Previous results from our laboratory have shown that benzene is metabolized by humans to form the adduct S-phenylcysteine (SPC). Levels of SPC measured in humans occupationally exposed to benzene were increased linearly relative to exposure concentrations ranging from 0 to 23.1 ppm for 8 hr/day, 5 days/week. However, the method of measurement used was laborious, prone to imprecision and interferences, and insufficiently sensitive for the low-dose exposures anticipated in the United States (100 ppb>). An improved chemical method was necessary before SPC adducts in albumin could be used as a benzene biomarker. A simple, sensitive method to measure SPC adducts is being developed and is based on the cleavage of the cysteine sulfhydryl from blood proteins treated with Raney nickel (RN) in deuterium oxide. The product of the reaction with SPC is monodeuterobenzene. SPC treated with RN released monodeuterobenzene in a concentration-dependent fashion. SPC was measured by RN treatment of globin from rats repeatedly exposed by inhalation to 600 ppm benzene. SPC levels measured using the RN approach were 690 {+-} 390 pmol SPC/mg Hb (mean {+-} % difference, n = 2), as opposed to 290 {+-} 45 pmol SPC/mg Hb (mean {+-} SEM, n = 3) as measured by our previous method. This method may facilitate the cost-effective, routine analysis of SPC in large populations of people exposed to ambient levels of benzene. 4 refs., 3 figs.

  17. Increased leukemia-associated gene expression in benzene-exposed workers.

    PubMed

    Li, Keqiu; Jing, Yaqing; Yang, Caihong; Liu, Shasha; Zhao, Yuxia; He, Xiaobo; Li, Fei; Han, Jiayi; Li, Guang

    2014-07-04

    Long-term exposure to benzene causes several adverse health effects, including an increased risk of acute myeloid leukemia. This study was to identify genetic alternations involved in pathogenesis of leukemia in benzene-exposed workers without clinical symptoms of leukemia. This study included 33 shoe-factory workers exposed to benzene at levels from 1 ppm to 10 ppm. These workers were divided into 3 groups based on the benzene exposure time, 1- < 7, 7- < 12, and 12- < 24 years. 17 individuals without benzene exposure history were recruited as controls. Cytogenetic analysis using Affymetrix Cytogenetics Array found copy-number variations (CNVs) in several chromosomes of benzene-exposed workers. Expression of targeted genes in these altered chromosomes, NOTCH1 and BSG, which play roles in leukemia pathogenesis, was further examined using real-time PCR. The NOTCH1 mRNA level was significantly increased in all 3 groups of workers, and the NOTCH1 mRNA level in the 12- < 24 years group was significantly higher than that in 1- < 7 and 7- < 12 years groups. Compared to the controls, the BSG mRNA level was significantly increased in 7- < 12 and 12- < 24 years groups, but not in the 1- < 7 years group. These results suggest that CNVs and leukemia-related gene expression might play roles in leukemia development in benzene-exposed workers.

  18. Superfund fact sheet: Benzene. Fact sheet

    SciTech Connect

    Not Available

    1992-09-01

    The fact sheet describes benzene, a chemical that can be found in a variety of products, including petroleum products (e.g. gasoline), some household cleaners, and some glues and adhesives. Explanations of how people are exposed to benzene and how benzene can enter the body and may affect human health are given. The fact sheet is one in a series providing reference information about Superfund issues and is intended for readers with no formal scientific training.

  19. 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)

  20. Acute cytogenetic effect of benzene on rat bone marrow cells in vivo and the effect of inducers or inhibitors of drug-metabolizing enzymes.

    PubMed

    Fujie, K; Ito, Y; Maeda, S

    1992-12-01

    Acute cytogenetic effects of benzene in LE rat bone marrow cells in vivo were studied. Chromosome aberrations (CA) induced by benzene consisted mainly of gaps and breaks. Cells with exchanges were rarely observed. The incidence of benzene-induced CA was at its maximum level 12 h after the p.o. or i.p. administration of benzene, dependent on the dose of benzene administered, and higher in male rats than in female rats. However, the sex difference was not observed in the repeated inhalation experiment. Chromosome damage was higher with the p.o. than the i.p. administration. LE rats were more sensitive than Wistar and SD rats to the clastogenic action of benzene. Phenobarbital and Sudan III are well known as inducers of drug-metabolizing enzymes. The peak percentage of benzene-induced CA in the rats pretreated with phenobarbital was observed 6 h after the benzene injection, and it occurred at a higher level than in the rats given only benzene. On the other hand, Sudan III pretreatment suppressed benzene-induced CA at all periods after the benzene injection. SKF-525A (a cytochrome P-450 inhibitor) and cyclohexene oxide (an epoxide hydrase inhibitor) pretreatment also suppressed benzene-induced CA.

  1. Evidence for strain-specific differences in benzene toxicity as a function of host target cell susceptibility.

    PubMed

    Neun, D J; Penn, A; Snyder, C A

    1992-01-01

    It has long been recognized that benzene exposure produces disparate toxic responses among different species or even among different strains within the same species. There is ample evidence that species- or strain-dependent differences in metabolic activity correlate with the disparate responses to benzene. However, bone marrow cells (the putative targets of benzene toxicity) may also exhibit species- or strain-dependent differences in susceptibility to the toxic effects of benzene. To investigate this hypothesis, two sets of companion experiments were performed. First, two strains of mice, Swiss Webster (SW) and C57B1/6J (C57), were exposed to 300 ppm benzene via inhalation and the effects of the exposures were determined on bone marrow cellularity and the development of bone marrow CFU-e (Colony Forming Unit-erythroid, an early red cell progenitor). Second, bone marrow cells from the same strains were exposed in vitro to five known benzene metabolites (1,4 benzoquinone, catechol, hydroquinone, muconic acid, and phenol) individually and in binary combinations. Benzene exposure, in vivo, reduced bone marrow cellularity and the development of CFU-e in both strains; however, reductions in both these endpoints were more severe in the SW strain. When bone marrow cells from the two strains were exposed in vitro to the five benzene metabolites individually, benzoquinone, hydroquinone, and catechol reduced the numbers of CFU-e in both strains in dose-dependent responses, phenol weakly reduced the numbers of the C57 CFU-e only and in a non-dose-dependent manner, and muconic acid was without effect on cells from either strain.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. 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.

  3. The harmonic frequencies of benzene

    NASA Astrophysics Data System (ADS)

    Handy, Nicholas C.; Maslen, Paul E.; Amos, Roger D.; Andrews, Jamie S.; Murray, Christopher W.; Laming, Gregory J.

    1992-09-01

    We report calculations for the harmonic frequencies of C 6H 6 and C 6D 6. Our most sophisticated quantum chemistry values are obtained with the MP2 method and a TZ2P+f basis set (288 basis functions), which are the largest such calculations reported on benzene to date. Using the SCF density, we also calculate the frequencies using the exchange and correlation expressions of density functional theory. We compare our calculated harmonic frequencies with those deduced from experiment by Goodman, Ozkabak and Thakur. The density functional frequencies appear to be more reliable predictions than the MP2 frequencies and they are obtained at significantly less cost.

  4. 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.

  5. MEASUREMENT OF BENZENE OXIDE IN THE BLOOD OF RATS FOLLOWING ADMINISTRATION OF BENZENE

    EPA Science Inventory

    Although it is generally assumed that metabolism of benzene proceeds through an initial step involving oxidation to benzene oxide (BO) by CYP450 in the liver, the production of BO has never been unambiguously confirmed in animals dosed with benzene. Furthermore, prevailing hypo...

  6. Gas phase acidity of substituted benzenes

    NASA Astrophysics Data System (ADS)

    Bouchoux, Guy

    2011-04-01

    Deprotonation thermochemistry of benzene derivatives C 6H 5X (X = H, F, Cl, OH, NH 2, CN, CHO, NO 2, CH 3, C 2H 5, CHCH 2, CCH) has been examined at the G3B3 level of theory. For X = F, Cl, CN, CHO and NO 2, the most favorable deprotonation site is the ortho position of the phenyl ring. This regio-specificity is directly related to the field/inductive effect of the substituent. G3B3 gas phase acidities, Δ acidH° and Δ acidG°, compare within less than 4 kJ mol -1 with experimental data. A noticeable exception is nitrobenzene for which tabulated acidity appear to be underestimated by ca. 120 kJ mol -1.

  7. Levels of metabolites of organophosphate pesticides, phthalates, and bisphenol A in pooled urine specimens from pregnant women participating in the Norwegian Mother and Child Cohort Study (MoBa).

    PubMed

    Ye, Xibiao; Pierik, Frank H; Angerer, Jürgen; Meltzer, Helle Margrete; Jaddoe, Vincent W V; Tiemeier, Henning; Hoppin, Jane A; Longnecker, Matthew P

    2009-09-01

    Concerns about reproductive and developmental health risks of exposure to organophosphate (OP) pesticides, phthalates, and bisphenol A (BPA) among the general population are increasing. Six dialkyl phosphate (DAP) metabolites, 3,5,6-trichloro-2-pyridinol (TCPy), BPA, and fourteen phthalate metabolites were measured in 10 pooled urine samples representing 110 pregnant women who participated in the Norwegian Mother and Child Birth Cohort (MoBa) study in 2004. Daily intakes were estimated from urinary data and compared with reference doses (RfDs) and daily tolerable intakes (TDIs). The MoBa women had a higher mean BPA concentration (4.50 microg/L) than the pregnant women in the Generation R Study (Generation R) in the Netherlands and the National Health and Nutrition Examination Survey (NHANES) in the United States. The mean concentration of total DAP metabolites (24.20 microg/L) in MoBa women was higher than that in NHANES women but lower than that in Generation R women. The diethyl phthalate metabolite mono-ethyl phthalate (MEP) was the dominant phthalate metabolite in all three studies, with the mean concentrations of greater than 300 microg/L. The MoBa and Generation R women had higher mean concentrations of mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP) than the NHANES women. The estimated average daily intakes of BPA, chlorpyrifos/chlorpyrifos-methyl and phthalates in MoBa (and the other two studies) were below the RfDs and TDIs. The higher levels of metabolites in the MoBa participants may have been from intake via pesticide residues in food (organophosphates), consumption of canned food, especially fish/seafood (BPA), and use of personal care products (selected phthalates).

  8. Gas chromatography with pulsed flame photometric detection multiresidue method for organophosphate pesticide and metabolite residues at the parts-per-billion level in representatives commodities of fruits and vegetable crop groups.

    PubMed

    Podhorniak, L V; Negron, J F; Griffith, F D

    2001-01-01

    A gas chromatographic method with a pulsed flame photometric detector (P-FPD) is presented for the analysis of 28 parent organophosphate (OP) pesticides and their OP metabolites. A total of 57 organophosphates were analyzed in 10 representative fruit and vegetable crop groups. The method is based on a judicious selection of known procedures from FDA sources such as the Pesticide Analytical Manual and Laboratory Information Bulletins, combined in a manner to recover the OPs and their metabolite(s) at the part-per-billion (ppb) level. The method uses an acetone extraction with either miniaturized Hydromatrix column partitioning or alternately a miniaturized methylene dichloride liquid-liquid partitioning, followed by solid-phase extraction (SPE) cleanup with graphitized carbon black (GCB) and PSA cartridges. Determination of residues is by programmed temperature capillary column gas chromatography fitted with a P-FPD set in the phosphorus mode. The method is designed so that a set of samples can be prepared in 1 working day for overnight instrumental analysis. The recovery data indicates that a daily column-cutting procedure used in combination with the SPE extract cleanup effectively reduces matrix enhancement at the ppb level for many organophosphates. The OPs most susceptible to elevated recoveries around or greater than 150%, based on peak area calculations, were trichlorfon, phosmet, and the metabolites of dimethoate, fenamiphos, fenthion, and phorate. PMID:11417651

  9. Chemical of current interest--benzene.

    PubMed

    Marcus, W L

    1987-03-01

    Benzene is one of the world's major commodity chemicals. It is derived from petroleum and coal and is used both as a solvent and as a starting material in chemical syntheses. The numerous industrial uses of benzene over the last century need not be recounted here, but the most recent addition to the list of uses of benzene is as a component in a mixture of aromatic compounds added to gasoline for the purpose of replacing lead compounds as anti-knock ingredients. The best known and longest recognized toxic effect of benzene is the depression of bone marrow function seen in occupationally exposed individuals. These people have been found to display anemia, leucopenia, and/or thrombocytopenia. When pancytopenia, i.e., the simultaneous depression of all three cell types, occurs and is accompanied by bone marrow necrosis, the syndrome is called aplastic anemia. In addition to observing this decrease in humans and relating it to benzene exposure, it has been possible to establish animal models which mimic the human disease. The result has been considerable scientific investigation into the mechanism of benzene toxicity. Although the association between benzene exposure and aplastic anemia has been recognized and accepted throughout most of this century, it is only recently that leukemia, particularly of the acute myelogenous type, has been related to benzene. The acceptance of benzene as an etiological agent in aplastic anemia in large measure derives from our ability to reproduce the disease in most animals treated with sufficiently high doses of benzene over the necessary time period. Unfortunately, despite extensive efforts in several laboratories, it has not been possible to establish a reproducible, reliable model for the study of benzene-induced leukemia. The recent demonstration that several animals exposed to benzene either by inhalation or in the drinking water during studies by Drs. B. Goldstein and C. Maltoni suggests that such a model may be forthcoming

  10. 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

  11. Major sources of benzene exposure

    SciTech Connect

    Wallace, L.A. )

    1989-07-01

    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.

  12. 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.

  13. Major sources of benzene exposure.

    PubMed

    Wallace, L A

    1989-07-01

    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.

  14. Biological monitoring of benzene exposure for process operators during ordinary activity in the upstream petroleum industry.

    PubMed

    Bråtveit, Magne; Kirkeleit, Jorunn; Hollund, Bjørg Eli; Moen, Bente E

    2007-07-01

    This study characterized the exposure of crude oil process operators to benzene and related aromatics during ordinary activity and investigated whether the operators take up benzene at this level of exposure. We performed the study on a fixed, integrated oil and gas production facility on Norway's continental shelf. The study population included 12 operators and 9 referents. We measured personal exposure to benzene, toluene, ethylbenzene and xylene during three consecutive 12-h work shifts using organic vapour passive dosimeter badges. We sampled blood and urine before departure to the production facility (pre-shift), immediately after the work shift on Day 13 of the work period (post-shift) and immediately before the following work shift (pre-next shift). We also measured the exposure to hydrocarbons during short-term tasks by active sampling using Tenax tubes. The arithmetic mean exposure over the 3 days was 0.042 ppm for benzene (range <0.001-0.69 ppm), 0.05 ppm for toluene, 0.02 ppm for ethylbenzene and 0.03 ppm for xylene. Full-shift personal exposure was significantly higher when the process operators performed flotation work during the shift versus other tasks. Work in the flotation area was associated with short-term (6-15 min) arithmetic mean exposure to benzene of 1.06 ppm (range 0.09-2.33 ppm). The concentrations of benzene in blood and urine did not differ between operators and referents at any time point. When we adjusted for current smoking in regression analysis, benzene exposure was significantly associated with the post-shift concentration of benzene in blood (P = 0.01) and urine (P = 0.03), respectively. Although these operators perform tasks with relatively high short-term exposure to benzene, the full-shift mean exposure is low during ordinary activity. Some evidence indicates benzene uptake within this range of exposure.

  15. 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. PMID:26930323

  16. Benzene and human health: A historical review and appraisal of associations with various diseases.

    PubMed

    Galbraith, David; Gross, Sherilyn A; Paustenbach, Dennis

    2010-11-01

    Over the last century, benzene has been a well-studied chemical, with some acute and chronic exposures being directly associated with observed hematologic effects in humans and animals. Chronic heavy exposures to benzene have also been associated with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) in humans. Other disease processes have also been studied, but have generally not been supported by epidemiologic studies of workers using benzene in the workplace. Within occupational cohorts with large populations and very low airborne benzene exposures (less than 0.1–1.0 ppm), it can be difficult to separate background disease incidence from those occurring due to occupational exposures. In the last few decades, some scientists and physicians have suggested that chronic exposures to various airborne concentrations of benzene may increase the risk of developing non-Hodgkin's lymphoma (NHL) (Savitz and Andrews, 1997, Am J Ind Med 31:287–295; Smith et al., 2007, Cancer Epidemiol Biomarkers Prev 16:385–391), multiple myeloma (MM) (Goldstein, 1990, Ann NY Acad Sci 609:225–230; Infante, 2006, Ann NY Acad Sci 1076:90–109), and various other hematopoietic disorders. We present a state-of-the-science review of the medical and regulatory aspects regarding the hazards of occupational exposure to benzene. We also review the available scientific and medical evidence relating to benzene and the risk of developing various disorders following specific levels of exposure. Our evaluation indicates that the only malignant hematopoietic disease that has been clearly linked to benzene exposure is AML. Information from the recent "Benzene 2009," a symposium of international experts focusing on the health effects and mechanisms of toxicity of benzene, hosted by the Technical University of Munich, has been incorporated and referenced.

  17. 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.

  18. The use of biomonitoring data in exposure and human health risk assessment: benzene case study.

    PubMed

    Arnold, Scott M; Angerer, Juergen; Boogaard, Peter J; Hughes, Michael F; O'Lone, Raegan B; Robison, Steven H; Schnatter, A Robert

    2013-02-01

    Abstract 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/m(3)), but greater than blood or urine concentrations relating to the air concentration at the 1 × 10(-5) excess cancer risk (2.9 µg/m(3)). 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.

  19. 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

  20. 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...

  1. 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...

  2. 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...

  3. 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....

  4. 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...

  5. 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...

  6. 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....

  7. 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....

  8. 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...

  9. 29 CFR 1910.1028 - Benzene.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... safety data sheet (MSDS) which addresses benzene and complies with 29 CFR 1910.1200. (ii) Employers who... the requirements of 29 CFR 1910.1200(h) (1) and (2), and shall include specific information on benzene... and unloading operations, except for the provisions of 29 CFR 1910.1200 as incorporated into...

  10. 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...

  11. 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...

  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. 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...

  14. 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....

  15. 29 CFR 1910.1028 - Benzene.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... safety data sheet (MSDS) which addresses benzene and complies with 29 CFR 1910.1200. (ii) Employers who... the requirements of 29 CFR 1910.1200(h) (1) and (2), and shall include specific information on benzene... and unloading operations, except for the provisions of 29 CFR 1910.1200 as incorporated into...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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....

  2. Degradation of benzene in the environment

    SciTech Connect

    Korte, F.; Klein, W.

    1982-01-01

    A test system for measurement of benzene and other aromatic compounds using a carbon 14 label is described. The biodegradability test of ecotoxicological profile analysis is performed in a closed system, thus allowing the investigation of volatile compounds. Results show that benzene is readily biodegradable. (JMT)

  3. Effects of Elevated CO2 on Levels of Primary Metabolites and Transcripts of Genes Encoding Respiratory Enzymes and Their Diurnal Patterns in Arabidopsis thaliana: Possible Relationships with Respiratory Rates

    PubMed Central

    Watanabe, Chihiro K.; Sato, Shigeru; Yanagisawa, Shuichi; Uesono, Yukifumi; Terashima, Ichiro; Noguchi, Ko

    2014-01-01

    Elevated CO2 affects plant growth and photosynthesis, which results in changes in plant respiration. However, the mechanisms underlying the responses of plant respiration to elevated CO2 are poorly understood. In this study, we measured diurnal changes in the transcript levels of genes encoding respiratory enzymes, the maximal activities of the enzymes and primary metabolite levels in shoots of Arabidopsis thaliana grown under moderate or elevated CO2 conditions (390 or 780 parts per million by volume CO2, respectively). We examined the relationships between these changes and respiratory rates. Under elevated CO2, the transcript levels of several genes encoding respiratory enzymes increased at the end of the light period, but these increases did not result in changes in the maximal activities of the corresponding enzymes. The levels of some primary metabolites such as starch and sugar phosphates increased under elevated CO2, particularly at the end of the light period. The O2 uptake rate at the end of the dark period was higher under elevated CO2 than under moderate CO2, but higher under moderate CO2 than under elevated CO2 at the end of the light period. These results indicate that the changes in O2 uptake rates are not directly related to changes in maximal enzyme activities and primary metabolite levels. Instead, elevated CO2 may affect anabolic processes that consume respiratory ATP, thereby affecting O2 uptake rates. PMID:24319073

  4. Differences in the pathways for metabolism of benzene in rats and mice simulated by a physiological model.

    PubMed

    Medinsky, M A; Sabourin, P J; Henderson, R F; Lucier, G; Birnbaum, L S

    1989-07-01

    Studies conducted by the National Toxicology Program on the chronic toxicity of benzene indicated that B6C3F1 mice were more sensitive to the carcinogenic effects of benzene than were F344 rats. A physiological model was developed to describe the uptake and metabolism of benzene in rats and mice. Our objective was to determine if differences in toxic effects could be explained by differences in pathways for benzene metabolism or by differences in total uptake of benzene. Compartments incorporated into the model included liver, fat, a poorly perfused tissue group, a richly perfused tissue group, an alveolar or lung compartment and blood. Metabolism of benzene was assumed to take place only in the liver and to proceed by four major competing pathways. These included formation of hydroquinone conjugates (HQC), formation of phenyl conjugates (PHC), ring-breakage and formation of muconic acid (MUC), and conjugation with glutathione with subsequent mercapturic acid (PMA) formation. Values for parameters such as alveolar ventilation, cardiac output, organ volumes, blood flow, partition coefficients, and metabolic rate constants were taken from the literature. Model simulations confirmed that during and after 6-hr inhalation exposures mice metabolized more benzene on a mumole per kilogram body weight basis than did rats. After oral exposure, rats metabolized more benzene than mice at doses above 50 mg/kg because of the more rapid absorption and exhalation of benzene by mice. Model simulations for PHC and PMA, generally considered to be detoxification metabolites, were similar in shape and dose-response to those for total metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. 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

  6. Association between intrafollicular concentration of benzene and outcome of controlled ovarian stimulation in IVF/ICSI cycles: a pilot study

    PubMed Central

    2014-01-01

    Background Several studies have shown that exposure to benzene is associated to menstrual disorders, miscarriages and other disorders of the reproductive system. We performed an observational prospective pilot study to evaluate if levels of benzene in follicular fluid were correlated with response to controlled ovarian stimulation. Method Thirty-four normogonadotrophic women undergoing IVF were enrolled. Intra-follicular benzene levels were evaluated by chromatography/mass spectrometry. Based on median benzene level, we divided the study population in two groups: Group A with a “low” intra-follicular benzene concentration (n = 19, benzene <0.54 ng/mL) and Group B with a “high” intra-follicular benzene concentration (n = 15, benzene ≥ 0.54 ng/mL). The ovarian response to gonadotrophins and the outcome of IVF were analyzed in the two groups. Results The two groups did not differ in terms of demographic or anthropometric characteristics. Group B had significantly higher basal FSH levels, lower estradiol peak concentration, and fewer oocytes retrieved and embryos transferred (p < 0.05). Number of gonadotrophin vials, length of controlled ovarian stimulation and ongoing pregnancy rate were similar in the two groups. Conclusion In conclusion, ovarian response to endogenous and exogenous gonadotrophins appeared to be influenced by intra-follicular benzene levels. PMID:24991235

  7. 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. PMID:24821439

  8. 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...

  9. 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

  10. Mitochondrial DNA copy number and hnRNP A2/B1 protein: biomarkers for direct exposure of benzene.

    PubMed

    Eom, Ha-Young; Kim, Hye-Ran; Kim, Hwan-Young; Han, Dong-Kyun; Baek, Hee-Jo; Lee, Jae-Hyuk; Moon, Jai Dong; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook; Kook, Hoon; Shin, Myung-Geun

    2011-12-01

    The present study was performed to identify biomarkers for exposure of benzene in blood cells and hematopoietic tissues. Peripheral mononuclear cells, hematopoietic stem cells, and leukemia cell lines were cultured in RPMI 1640 media with the addition of 0, 1, and 10 mM of benzene. Hydrogen peroxide was measured using an enzyme immunoassay. Mitochondrial mass, membrane potential, and mitochondrial DNA (mtDNA) copy number were measured using MitoTracker Green/Red probes, and real-time polymerase chain reaction. In addition, two-dimensional gel electrophoresis and mass spectrometry matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) technology were performed to identify protein markers. The mitochondrial contents and membrane potentials were dramatically increased after three weeks of direct benzene exposure. The hydrogen peroxide level increased significantly after two weeks of treatment with benzene (4.4 ± 1.9 µM/mg protein) compared to the non-benzene treatment group (1.2 ± 1.0; p = 0.001). The mtDNA copy number gradually increased after exposure to benzene. Numerous protein markers showed significant aberrant expression after exposure to benzene. Among them, the heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 was markedly decreased after exposure to benzene. Thus, increased mitochondrial mass, mtDNA copy number, and the hnRNP A2/B1 protein were biomarkers for benzene-related toxicity and hematotoxicity.

  11. Reduction of benzene toxicity by toluene.

    PubMed

    Plappert, U; Barthel, E; Seidel, H J

    1994-01-01

    BDF1 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.

  12. 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.

  13. 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.

  14. 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

  15. Benzene: a secondary pollutant formed in the three-way catalyst.

    PubMed

    Bruehlmann, Stefan; Forss, Anna-Maria; Steffen, Dominik; Heeb, Norbert V

    2005-01-01

    Benzene emissions from a relevant proportion of today's gasoline-driven passenger cars and light-duty vehicles can increase by up to 2 orders of magnitude when driving at high engine load (e.g., on highways). Under such conditions, post-catalyst benzene levels exceeded those found pre-catalyst. As a consequence, formation of benzene in the catalyst was postulated. To further reduce ambient air concentrations of benzene,these critical operating conditions must be carefully avoided. Here, we report in detail to what extent and at what operating conditions catalyst-induced benzene and toluene formation can occur. For that purpose, a EURO-1 passenger car (1.8 L, model year 1995)fulfilling the valid regulations, equipped with a new, two-layered, Pd-CeO2-Al2O3/Rh-ZrO2-Al2O3 three-way catalyst was operated at steady state on a chassis dynamometer at 100, 125, and 150 km/h at variable air to fuel ratios. Pre- and post-catalyst exhaust gas concentrations of benzene, toluene, C2-, and C3-benzenes were monitored at a time resolution of 0.5 Hz by means of chemical ionization mass spectrometry. A net benzene formation window, ranging from pre-catalyst exhaust gas temperatures of 600-730 degrees C and lambda-values of 0.83-0.95, with a pronounced minimum at 0.87, was observed. Dealkylation reactions of aromatic hydrocarbons are assumed to be the major pathway leading to benzene. PMID:15667114

  16. The nature of chromosomal aberrations detected in humans exposed to benzene.

    PubMed

    Zhang, Luoping; Eastmond, David A; Smith, Martyn T

    2002-01-01

    Benzene is an established cause of human leukemia that is thought to act by producing chromosomal aberrations and altered in cell differentiation. In several recent studies increased levels of chromosomal aberrations in peripheral blood lymphocytes were correlated with a heightened risk of cancer, especially hematological malignancies. Thus, chromosomal aberrations may be a predictor of future leukemia risk. Previous studies exploring whether benzene exposure induces chromosomal aberrations have yielded mostly positive results. However, it remains unclear whether the chromosomal aberrations induced by benzene occur in a distinct pattern. Here, we thoroughly review the major chromosome studies published to date in benzene-exposed workers, benzene-poisoned and preleukemia patients, and leukemia cases associated with benzene expose. Although three cytogenetic markers (chromosomal aberrations, sister chromatid exchanges, and micronuclei) are commonly examined, our primary focus is on studies of chromosomal aberrations, because only this marker has so far been correlated with increased cancer risk. This review surveys the published literature, analyzes the study results, and discusses the characteristics of effects reported. In most studies of currently exposed workers, increases in chromosomal aberrations were observed. However, due to the relatively small number of affected individuals and variability in the reported aberrations, firm conclusions cannot be made about the involvement of specific chromosomes or chromosome regions. Further, in leukemia cases associated with benzene exposure, there is no evidence of a unique pattern of benzene-induced chromosomal aberrations in humans. Leukemia cases associated with benzene exposure are, however, more likely to contain clonal chromosome aberrations then those arising de novo in the general population.

  17. Variations in Prkdc and susceptibility to benzene-induced toxicity in mice.

    PubMed

    Faiola, Brenda; Bauer, Alison K; Fuller, Elizabeth S; Wong, Victoria A; Pluta, Linda J; Abernethy, Diane J; Mangum, James B; Everitt, Jeffrey I; Recio, Leslie

    2003-10-01

    Benzene, a carcinogen that induces chromosomal breaks, is strongly associated with leukemias in humans. Possible genetic determinants of benzene susceptibility include proteins involved in repair of benzene-induced DNA damage. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), encoded by Prkdc, is one such protein. DNA-PKcs is involved in the nonhomologous end-joining (NHEJ) pathway of DNA double-strand break (DSB) repair. Here we compared the toxic effects of benzene on mice (C57BL/6 and 129/Sv) homozygous for the wild-type Prkdc allele and mice (129/SvJ) homozygous for a Prkdc functional polymorphism that leads to diminished DNA-PK activity and enhanced apoptosis in response to radiation-induced damage. Male and female mice were exposed to 0, 10, 50, or 100 ppm benzene for 6 h/d, 5 d/week for 2 weeks. Male mice were more susceptible to benzene toxicity compared with females. Hematotoxicity was evident in all male mice but was not seen in female mice. We observed similar, large increases in both micronucleated erythrocyte populations in all male mice. Female mice had smaller but significant increases in micronucleated cells. The p53-dependent response was induced in all strains and genders of mice following benzene exposure, as indicated by an increase in p21 mRNA levels in bone marrow that frequently corresponded with cell cycle arrest in G2/M. Prkdc does not appear to be a significant genetic susceptibility factor for acute benzene toxicity. Moreover, the role of NHEJ, mediated by DNA-PK, in restoring genomic integrity following benzene-induced DSB remains equivocal.

  18. 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.

  19. 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)].

  20. MR spectroscopy and diffusion tensor imaging of the brain in congenital muscular dystrophy with merosin deficiency: metabolite level decreases, fractional anisotropy decreases, and apparent diffusion coefficient increases in the white matter.

    PubMed

    Sijens, P E; Fock, J M; Meiners, L C; Potze, J H; Irwan, R; Oudkerk, M

    2007-06-01

    Brain magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) in one patient with merosin-deficient congenital muscular dystrophy (MDCMD) revealed significant metabolite (choline, creatine, N-acetyl aspartate) level reductions, fractional anisotropy (FA) reduction and increased apparent diffusion coefficient (ADC) in the white matter (p<0.01, all). In the gray matter, the MRS properties did not differ significantly from those in controls. The ADC and FA, however, differed significantly as in the white matter, although the differences were less pronounced. This is the first quantitative MR study of the brain in a patient with MDCMD, which revealed that the concentrations of all MRS measured metabolites were decreased only in the white matter. This observation, combined with the DTI observed ADC increases and FA decrease, indicated a presence of vasogenic edema in the white matter.

  1. 46 CFR 197.565 - Notifying personnel of benzene hazards.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... appendices A and B of this subpart or a MSDS on benzene meeting the requirements of 29 CFR 1910.1200(g) is... 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....

  2. 46 CFR 197.565 - Notifying personnel of benzene hazards.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... appendices A and B of this subpart or a MSDS on benzene meeting the requirements of 29 CFR 1910.1200(g) is... 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....

  3. 46 CFR 197.565 - Notifying personnel of benzene hazards.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... appendices A and B of this subpart or a MSDS on benzene meeting the requirements of 29 CFR 1910.1200(g) is... 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....

  4. 46 CFR 197.565 - Notifying personnel of benzene hazards.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... appendices A and B of this subpart or a MSDS on benzene meeting the requirements of 29 CFR 1910.1200(g) is... 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....

  5. 46 CFR 197.565 - Notifying personnel of benzene hazards.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... appendices A and B of this subpart or a MSDS on benzene meeting the requirements of 29 CFR 1910.1200(g) is... 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....

  6. Tyrosine aminotransferase activity in the benzene intoxicated rat

    SciTech Connect

    Bong, M.; Michalska, A.; Laskowska-Klita, T.; Szymczyk, T.

    1985-01-01

    The toxic effect of hydrocarbon solvents on hepatic metabolism manifests itself by changes in the enzymatic pattern of blood serum. Changes in the activity of phosphatases as well as leucine aminopeptidase, glutamine aminotransferase, sorbitol dehydrogenase and ..gamma..-glutamyltransferase were observed in rats intoxicated with different fractions of benzene. Therefore it seemed reasonable to investigate the effect of benzene fraction of petroleum on cellular metabolism. The results of the present work concern the activity of tyrosine aminotransferase, the enzyme involved in catabolism of aromatic amino acid which is known to be under both hormonal and stress dependent control. Changes in tyrosine aminotransferase activity effect the level of tyrosine oxidation as well as the metabolic conversion of this amino acid into tyramine, tyroxin, adrenaline and noradrenaline.

  7. 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(+).

  8. EPR study of Gallium atoms in benzene

    SciTech Connect

    Howard, J.A.; Joly, H.A.; Mile, B.; Sutcliffe, R. )

    1991-09-05

    An EPR study of a Ga atom matrix isolated in benzene at 77 K has revealed the presence of a paramagnetic species with the magnetic parameters {alpha}{sub zz}(69) = 256 MHz, {alpha}{sub xx}(69) = 270 MHz, {alpha}{sub yy}(69) = 284 MHz, {alpha}{sub zz}(71) = 325 MHz, {alpha}{sub xx}(71) = 343 MHz, {alpha}{sub yy}(71) = 361 Mhz, g{sub zz} = 1.9970, g{approximately}{sub xx} = 1.9750, and g{sub yy} = 1.9350. These parameters are consistent with a trapped atom or a weak Ga-benzene complex that has had the degeneracy of the Ga p orbitals lifted by interaction with the benzene matrix. This contrasts with Al in benzene which gives a mononuclear monoligand complex, Al(C{sub 6}H{sub 6}), with quite strong bonding between the metal atom and the ligand.

  9. 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.

  10. Electromers of the benzene dimer radical cation.

    PubMed

    Błoch-Mechkour, Anna; Bally, Thomas

    2015-04-28

    The well-studied benzene dimer radical cation, which is prototypical for this class of species, has been reinvestigated computationally. Thereby it turned out that both the σ-hemibonded and the half-shifted sandwich structures of the benzene dimer cation, which had been independently proposed, represent stationary points on the B2PLYP-D potential energy surfaces. However, these structures belong to distinct electronic states, both of which are associated with potential surfaces that are very flat with regard to rotation of the two benzene rings in an opposite sense relative to each other. The surfaces of these two "electromers" of the benzene dimer cation are separated by only 3-4 kcal mol(-1) and do not intersect along the rotation coordinate, which represents a rather unique electronic structure situation. When moving on either of the two surfaces the title complex is an extremely fluxional species, in spite of its being bound by over 20 kcal mol(-1).

  11. Photoionization spectrum of liquid benzene

    SciTech Connect

    Saik, V. O.; Lipsky, S. )

    1994-11-17

    The photocurrent from neat liquid benzene has been studied for excitation energies from threshold to 10.3 eV and for externally applied electric fields from 1 to 50 kV/cm. Using a power law fit to the energy dependence of the threshold current, an onset of [epsilon][sub t] = 7.65 [+-] 0.1 eV has been obtained. The field dependence was fit to an exponential radial probability density for thermalized ion-pair separation distances with an average separation distance of [r] = 23 [+-] 2 A at an excitation energy, [epsilon] of 8.86 eV (1.2 eV above threshold). Photocurrent was too weak to establish a dependence of [r] on excitation energy. The quantum yield for photocurrent at 8.86 eV was determined by comparison with the photocurrent from TMPD in 2,2,4-trimethylpentane (isooctane) to be 6.5 [times] 10[sup [minus]4] at zero field. From this, the intrinsic molecular ionization probability at [epsilon] = 8.86 eV was determined to be 0.6 [+-] 0.3. 30 refs., 5 figs.

  12. Benzene-derived carbon nanothreads

    NASA Astrophysics Data System (ADS)

    Fitzgibbons, Thomas C.; Guthrie, Malcolm; Xu, En-Shi; Crespi, Vincent H.; Davidowski, Stephen K.; Cody, George D.; Alem, Nasim; Badding, John V.

    2015-01-01

    Low-dimensional carbon nanomaterials such as fullerenes, nanotubes, graphene and diamondoids have extraordinary physical and chemical properties. Compression-induced polymerization of aromatic molecules could provide a viable synthetic route to ordered carbon nanomaterials, but despite almost a century of study this approach has produced only amorphous products. Here we report recovery to ambient pressure of macroscopic quantities of a crystalline one- dimensional sp3 carbon nanomaterial formed by high-pressure solid-state reaction of benzene. X-ray and neutron diffraction, Raman spectroscopy, solid-state NMR, transmission electron microscopy and first-principles calculations reveal close- packed bundles of subnanometre-diameter sp3-bonded carbon threads capped with hydrogen, crystalline in two dimensions and short-range ordered in the third. These nanothreads promise extraordinary properties such as strength and stiffness higher than that of sp2 carbon nanotubes or conven tional high-strength polymers. They may be the first member of a new class of ordered sp3 nanomaterials synthesized by kinetic control of high-pressure solid-state reactions.

  13. Benzene-derived carbon nanothreads.

    PubMed

    Fitzgibbons, Thomas C; Guthrie, Malcolm; Xu, En-shi; Crespi, Vincent H; Davidowski, Stephen K; Cody, George D; Alem, Nasim; Badding, John V

    2015-01-01

    Low-dimensional carbon nanomaterials such as fullerenes, nanotubes, graphene and diamondoids have extraordinary physical and chemical properties. Compression-induced polymerization of aromatic molecules could provide a viable synthetic route to ordered carbon nanomaterials, but despite almost a century of study this approach has produced only amorphous products. Here we report recovery to ambient pressure of macroscopic quantities of a crystalline one- dimensional sp(3) carbon nanomaterial formed by high-pressure solid-state reaction of benzene. X-ray and neutron diffraction, Raman spectroscopy, solid-state NMR, transmission electron microscopy and first-principles calculations reveal close- packed bundles of subnanometre-diameter sp(3)-bonded carbon threads capped with hydrogen, crystalline in two dimensions and short-range ordered in the third. These nanothreads promise extraordinary properties such as strength and stiffness higher than that of sp(2) carbon nanotubes or conventional high-strength polymers. They may be the first member of a new class of ordered sp(3) nanomaterials synthesized by kinetic control of high-pressure solid-state reactions.

  14. 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.

  15. Meeting benzene regulations through new desalting applications

    SciTech Connect

    Schantz, S.; Garcia, J.; Mourer, J.

    1995-09-01

    In the past, the industry has studied the impact of changing desalting variables on total oil undercarry. With the advent of the NESHAP regulations, benzene measurement is performed on a scheduled basis but not observed as desalting variables are changed and optimized. Benzene is normally present in crude at concentrations ranging from 0.1 to 0.6 ppm, and it is extremely soluble in water: up to 1,800 mg/l at standard temperature and pressure. The NESHAP benzene standard has created a strong interest in real-time experiments to clarify the factors that affect benzene concentrations in desalter effluent water. The work reported on in this paper attempts to answer the following questions: can the benzene concentration in desalter wastewater be determined reliably in real time so that desalter operational parameters can be tuned to minimize this concentration; how do changes in four key desalter variables--temperature, chemical dosage, wash water rate, and mix-valve pressure differential, affect benzene concentration in the effluent water?

  16. Benzene dynamics and biodegradation in alluvial aquifers affected by river fluctuations.

    PubMed

    Batlle-Aguilar, J; Morasch, B; Hunkeler, D; Brouyère, S

    2014-01-01

    The spatial distribution and temporal dynamics of a benzene plume in an alluvial aquifer strongly affected by river fluctuations was studied. Benzene concentrations, aquifer geochemistry datasets, past river morphology, and benzene degradation rates estimated in situ using stable carbon isotope enrichment were analyzed in concert with aquifer heterogeneity and river fluctuations. Geochemistry data demonstrated that benzene biodegradation was on-going under sulfate reducing conditions. Long-term monitoring of hydraulic heads and characterization of the alluvial aquifer formed the basis of a detailed modeled image of aquifer heterogeneity. Hydraulic conductivity was found to strongly correlate with benzene degradation, indicating that low hydraulic conductivity areas are capable of sustaining benzene anaerobic biodegradation provided the electron acceptor (SO4 (2-) ) does not become rate limiting. Modeling results demonstrated that the groundwater flux direction is reversed on annual basis when the river level rises up to 2 m, thereby forcing the infiltration of oxygenated surface water into the aquifer. The mobilization state of metal trace elements such as Zn, Cd, and As present in the aquifer predominantly depended on the strong potential gradient within the plume. However, infiltration of oxygenated water was found to trigger a change from strongly reducing to oxic conditions near the river, causing mobilization of previously immobile metal species and vice versa. MNA appears to be an appropriate remediation strategy in this type of dynamic environment provided that aquifer characterization and targeted monitoring of redox conditions are adequate and electron acceptors remain available until concentrations of toxic compounds reduce to acceptable levels.

  17. Lymphohaematopoietic malignancies and quantitative estimates of exposure to benzene in Canadian petroleum distribution workers.

    PubMed Central

    Schnatter, A R; Armstrong, T W; Nicolich, M J; Thompson, F S; Katz, A M; Huebner, W W; Pearlman, E D

    1996-01-01

    OBJECTIVE: To evaluate the relation between mortality from lymphohaematopoietic cancer and long term, low level exposures to benzene among male petroleum distribution workers. METHODS: This nested case control study identified all fatal cases of lymphohaematopoietic cancer among a previously studied cohort. Of the 29 cases, 14 had leukaemia, seven multiple myeloma, and eight non-Hodgkin's lymphoma. A four to one matching ratio was used to select a stratified sample of controls from the same cohort, controlling for year of birth and time at risk. Industrial hygienists estimated workplace exposures for benzene and total hydrocarbons, without knowledge of case or control status, for combinations of job, location, and era represented in all work histories. Average daily benzene concentrations ranged from 0.01 to 6.2 parts per million (ppm) for all jobs. Company medical records were used to abstract information on other potential confounders such as cigarette smoking, although the data were incomplete. Odds ratios (ORs) were calculated with conditional logistic regression techniques for several exposure variables. RESULTS: Risks of leukaemia, non-Hodgkin's lymphoma, and multiple myeloma were not associated with increasing cumulative exposure to benzene or total hydrocarbons. For leukaemia, the logistic regression model predicted an OR of 1.002 (P < 0.77) for each ppm-y of exposure to benzene. Duration of exposure to benzene was more closely associated with risk of leukaemia than other exposure variables. It was not possible to completely control for other risk factors, although there was suggestive evidence that smoking and a family history of cancer may have played a part in the risk of leukaemia. CONCLUSION: This study did not show a relation between lymphohaematopoietic cancer and long term, low level exposures to benzene. The power of the study to detect low-such as twofold-risks was limited. Thus, further study on exposures to benzene in this concentration range

  18. 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.

  19. 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. PMID:26784149

  20. 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

    2015-08-01

    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. PMID:26158391

  1. 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

    2015-08-01

    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.

  2. 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.

  3. 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.

  4. Chemistry of muconaldehydes of possible relevance to the toxicology of benzene

    SciTech Connect

    Bleasdale, C.; Kennedy, G.; MacGregor, J.O.

    1996-12-01

    (ZZ)-Muconaidehyde reacted with primary amines to give N-substituted-2-(2{prime}-oxoethyl)-pyrroles, which were reduced to 4substituted-2-(2{prime}-hydroxyethyl)-pyrroles by sodium borohydride. The pyrrole-forming reaction is exhibited by valine and its methyl ester, and is being developed with terminal valine in hemoglobin as a means of dose monitoring (ZZ)-muconaldehyde, a putative metabolite of benzene. Reactions in aqueous solution between (ZZ)-muconaldehyde and adenosine, deoxyadenosine, guanosine, or deoxyguanosine leading to pyrrole-containing adducts are described. The elucidation of the structures of the adducts was assisted by the study of reactions between (ZZ)-muconaldehyde and both nucleoside derivatives and a model compound for guanosine. Reactions of (ZZ)-muconaldehyde are complicated by its isomerization to (EZ)- and (EE)-muconaldehyde. The kinetics of this process have been studied in benzene, acetonitrile, and dimethylsulfoxide. 17 refs., 1 tab.

  5. Green tea attenuates benzene-induced oxidative stress in pump workers.

    PubMed

    Emara, Ashraf M; El-Bahrawy, Hoda

    2008-01-01

    Workers exposed to benzene frequently suffer from toxicities of the bone marrow as well as the central nervous, immune, and reproductive systems. This toxicity most likely is a result of the oxidative metabolism of benzene to reactive products. As green tea possesses antioxidant effects, the objective of this study was to examine any amelioration of benzene-induced oxidative stress in pump workers drinking 6 cups (150 ml/cup) of freshly prepared tea daily. Sixty male non-smoking subjects, divided into four groups: no benzene exposure/no green tea; no exposure/tea; exposure/no tea; and, exposure/tea, were monitored after a 6 mo period. On the final day of the study, urine samples were collected for analyses of benzene, trans-trans muconic acid, and phenol. Blood was also collected at this time; plasma was assayed for total antioxidant activity, malondialdehyde (MDA), and glutathione (GSH) while erythrocytes were analyzed for activity of antioxidant enzymes glutathione peroxidase (GSHPX), superoxide dismutase (SOD), and catalase. The results demonstrated that urinary levels of benzene, trans-trans muconic acid, and phenol were elevated in all pump workers, and that this elevation was mitigated by consumption of green tea. The benzene exposures also led to significant reductions in plasma GSH levels and erythrocyte antioxidant enzyme activities; these effects were abrogated (to near-control levels) by the tea. Interestingly, among control subjects, tea ingestion itself caused significant increases in both GSHPX and catalase activities. Unlike with the other plasma parameters, while the benzene exposures also significantly increased plasma MDA levels and decreased total antioxidant activity, tea ingestion did not cause a near-total reversion to control values; the effects on these two endpoints were more like those noted with the urine parameters (mitigation, not abrogation). These studies demonstrate that drinking green tea during benzene exposure can reduce several

  6. 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

  7. Subcellular-level resolution MALDI-MS imaging of maize leaf metabolites by MALDI-linear ion trap-Orbitrap mass spectrometer.

    PubMed

    Korte, Andrew R; Yandeau-Nelson, Marna D; Nikolau, Basil J; Lee, Young Jin

    2015-03-01

    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. Here, 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. 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. 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.; 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. 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

  9. 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.

  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

    2008-04-01

    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. Adsorptive treatment of shale-tar benzene

    SciTech Connect

    Alekseeva, R.V.; Kharitonova, L.K.

    1984-01-01

    This article describes the use of adsorbents to remove thiophene from benzene. A nickel-substituted type X zeolite has been developed as a thiophene-selective adsorbent. Unsaturates were removed from the benzene by using A-4M microbead adsorbent. The optimal treating conditions were selected in pilot-unit tests at a pressure p=2 MPa, using a mathematically designed experiment. The A-4M adsorbent can be used repeatedly, with a service life of 6 months. The clarified benzene was treated at room temperature, passing the benzene at a velocity of 0.3 cm/min through a bed of NiCaX, which adsorbs unsaturated hydrocarbons along with the thiophene. The final stage in the treatment is the removal of saturated hydrocarbons from the benzene on commercial CaA zeolite in the vapor phase at 100/sup 0/C with a feed velocity of 0.3 cm/min. The hydrocarbons were desorbed from the void spaces of the zeolite with n-pentane, subsequently removing the desorbent by conventional fractionation.

  12. Quantification of Secondary Metabolites.

    PubMed

    2016-01-01

    Plants are a rich source of secondary metabolites that have medicinal and aromatic properties. Secondary metabolites such as alkaloids, iridoids and phenolics generally produced by plants for their defence mechanisms have been implicated in the therapeutic properties of most medicinal plants. Hence, quantification of these metabolites will aid to discover new and effective drugs from plant sources and also to scientifically validate the existing traditional practices. Quantification of large group of phytochemicals such as phenolics and flavonoids is quantified in this context.

  13. Benzene and lead exposure assessment among occupational bus drivers in Bangkok traffic.

    PubMed

    Muttamara, S; Leong, Shing Tet; Arayasiri, M

    2004-01-01

    Four environmental and biological monitoring sites were strategically established to evaluate benzene and lead exposure assessment at various traffic zones of Bangkok Metropolitan Region(BMR). Biological measurement of 48 non air-conditioned, male bus drivers was carried to study the relationship between individual exposure levels and exposure biomarkers. The study group was further subdivided into four age groups(16-25, 26-35, 36-45 and 46-55 years old) to monitor the age-related exposure effects. A total of 12 unexposed persons were deliberately chosen as the control group. Measurement of unmetobolized benzene in blood and analysis of urinary tt-Muconic acid urine and urinary creatinine are recommended as biomarkers of benzene exposure. Measurement of lead in blood and urine is also recommended for the biological monitoring of lead exposure. During the monitoring period, benzene and lead levels at Yaowarat Road was C6H6: 42.46 +/- 3.88 microg/m3 , Pb: 0.29 +/- 0.03 microg/m3 and decreased to C6H6: 33.5 +/- 1.35 microg/m3, Pb: 0.13 +/- 0.01 microg/m3 at Phahonyothin Road. Significant difference was established between the nonsmoking exposed group and nonsmoking control group for blood benzene concentrations (P < 0.001, two-tailed, Mann-Whiteney U test). Strong correlations were also found between trans-trans-Muconic acid concentrations in post shift samples and atmospheric benzene concentrations. Similarly, good correlation between all of biomarkers and lead level in air is established from automobile emissions. The analysis revealed that among the occupational population in the urban sites, the driver groups were found to have the highest risk of benzene and lead exposures derived from automobile emission. PMID:14971454

  14. Occurrence of benzene as a heat-induced contaminant of carrot juice for babies in a general survey of beverages.

    PubMed

    Lachenmeier, Dirk W; Reusch, Helmut; Sproll, Constanze; Schoeberl, Kerstin; Kuballa, Thomas

    2008-10-01

    A survey of benzene contamination of 451 beverage samples, using headspace sampling combined with gas chromatography and mass spectrometry (HS-GC/MS) with a quantification limit of 0.13 microg l(-1), was conducted. Artefactual benzene formation during headspace sampling was excluded by gentle heating at 50 degrees C only and adjustment of sample pH to 10. The incidence of benzene contamination in soft drinks, beverages for babies, alcopops and beer-mixed drinks was relatively low, with average concentrations below the EU drinking-water limit of 1 microg l(-1). Significantly higher concentrations were only found in carrot juice, with the highest levels in carrot juice specifically intended for infants. About 94% of 33 carrot juice for infants had detectable benzene levels, with an average concentration of 1.86 +/- 1.05 microg l(-1). Benzene contamination of beverages was significantly correlated to iron and copper concentrations, which act as catalyst in benzene formation. The formation of benzene in carrot juice was predominantly caused by a heat-induced mechanism, which explains the higher levels in infant carrot juices that are subject to higher heat-treatment to exclude microbiological contamination. PMID:18608484

  15. Personal benzene vapor detection device. Final report

    SciTech Connect

    Glatkowski, P.; Druy, M.

    1992-07-01

    A badge was developed as a personal vapor detector to record the cumulative exposure of an individual to benzene vapor. The badge consisted of an optical fiber, small sections of which were coated with a membrane specific for the adsorption of benzene vapor. Membranes made of polyethylene and nylon, and filled with zeolite were applied to a silver halide fiber. Following exposure, the fiber was subjected to Fourier Transform Infrared (FTIR) spectrometry. The coating successfully retained the benzene vapor for several days. A concentration of 100,000 parts per million (ppm) could be detected. Concentrations of dichlorobenzene of 80,000ppm were also detected. Unique absorbance peaks were used to distinguish the two compounds. It was possible to reuse the sensor. However, the desired detectability range of 1 to 100ppm was not met.

  16. Health effects of benzene exposure among children following a flaring incident at the British Petroleum Refinery in Texas City.

    PubMed

    D'Andrea, Mark A; Reddy, G Kesava

    2014-02-01

    Human exposure to benzene is associated with multiple adverse health effects leading to hematological malignancies. The objective of this retrospective study was to evaluate the health consequences of benzene exposure in children following a flaring incident at the British petroleum (BP) refinery in Texas City, Texas. The study included children aged <17 years who had been exposed and unexposed to benzene. Using medical charts, clinical data including white blood cell (WBC) counts, platelets counts, hemoglobin, hematocrit, blood urea nitrogen (BUN), creatinine, alkaline phosphatase (ALP), aspartate amino transferase (AST), alanine amino transferase (ALT), and somatic symptom complaints by the children exposed to benzene were reviewed and analyzed. A total of 312 subjects (benzene exposed, n = 157 and unexposed, n = 155) were included. Hematologic analysis showed that WBC counts were significantly decreased in benzene-exposed children compared with the unexposed children (6.8 ± 2.1 versus 7.3 ± 1.7, P = .022). Conversely, platelet (X 10(3) per μL) counts were increased significantly in the benzene-exposed group compared with the unexposed group (278.4 ± 59.9 versus 261.6 ± 51.7, P = .005). Similarly, benzene-exposed children had significantly higher levels of ALP (183.7± 95.6 versus 165 ± 70.3 IU/L, P = .04), AST (23.6 ± 15.3 versus 20.5 ± 5.5 IU/L, P = .015), and ALT (19.2 ± 7.8 versus 16.9 ± 6.9 IU/L, P = .005) compared with the unexposed children. Together, the results of the study reveal that children exposed to benzene experienced significantly altered blood profiles, liver enzymes, and somatic symptoms indicating that children exposed to benzene are at a higher risk of developing hepatic or blood related disorders.

  17. Gas phase nitrosation of substituted benzenes

    NASA Astrophysics Data System (ADS)

    Dechamps, Noémie; Gerbaux, Pascal; Flammang, Robert; Bouchoux, Guy; Nam, Pham-Cam; Nguyen, Minh-Tho

    2004-03-01

    Using a combination of tandem mass spectrometric experiments (ion-molecule reactions, collisional activation, neutralization-reionization, MS/MS/MS) and theoretical calculations, protonated substituted benzenes are demonstrated to readily react with neutral t-butyl nitrite by the formation of stable complexes linking ionized nitric oxide to the benzene derivatives. The overall process is proposed to involve the concomitant elimination of neutral 2-methyl-2-propanol. Proton-bound dimers are proposed to intervene as the key-intermediates in these reactions, which also competitively produce protonated t-butyl nitrite. All the experiments were performed in a single hybrid tandem mass spectrometer of sector-quadrupole-sector configuration.

  18. 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.

  19. 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).

  20. 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.

  1. 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

  2. Effect of carbon and hydrogen isotopic substitutions on the thermal diffusion of benzene

    SciTech Connect

    Rutherford, W.M.

    1989-01-01

    Measurements of the thermal diffusion factor of the benzene/carbon 13 substituted benzene pair and of the benzene/deuterated benzene pair are reported. The results show some interesting effects of mass distribution. (AIP)

  3. Solubilities of Toluene, Benzene and TCE in High-Biomass Systems

    SciTech Connect

    Barton, John W.; Vodraska, Christopher D; Flanary, Sandie A.; Davison, Brian H

    2008-01-01

    We report measurements of solubility limits for benzene, toluene, and TCE in systems that contain varying levels of biomass up to 0.13 g/mL. The solubility limit increased from 20 to 48 mM when biomass (in the form of yeast) was added to aqueous batch systems containing benzene. The toluene solubility limit increased from 4.9 to greater than 20 mM. For TCE, the solubility increased from 8 mM to more than 1000 mM. Solubility for TCE was most heavily impacted by biomass levels, changing by two orders of magnitude.

  4. 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.

  5. Analysis of plasma microRNA expression profiles in a Chinese population occupationally exposed to benzene and in a population with chronic benzene poisoning

    PubMed Central

    Liu, Yang; Chen, Xianwen; Bian, Qian; Shi, Yuan; Liu, Qingdong; Ding, Lu; Zhang, Hengdong

    2016-01-01

    Background Circulating microRNA (miRNA) has attractive interests as a non-invasive biomarker of physiological and pathological conditions. Our study aimed to investigate the potential effects of chronic benzene poisoning (CBP) and benzene exposure on miRNA expression, and identify CBP-related miRNAs. Methods In the discovery stage, we used a microarray assay to detect the miRNA expression profiles among pooled plasma samples from ten CBP patients, ten healthy benzene-exposed individuals and ten non-benzene exposed individuals. Subsequently, we conducted an expanded validation of six candidate miRNAs in 27 CBP patients- low blood counts, 54 healthy benzene-exposed individuals and 54 non-exposed individuals. Moreover, we predicted the biological functions of putative target genes using a Gene Ontology (GO) function enrichment analysis and KEGG pathway analysis. Results In the discovery stage, compared with non-exposures, 36 and 12 miRNAs demonstrated at least a 1.0-fold differential expression in the CBP patients and the benzene exposures, respectively. And compared with benzene exposures, 58 miRNAs demonstrated at least a 1.0-fold differential expression in the CBP patients. In the expanded validation stage, compared with non-exposures as well as exposures, miR-24-3p and miR-221-3p were significantly up-regulated (1.99- and 2.06-fold for miR-24-3p, 2.19- and 3.93-fold for miR-221-3p, P<0.01) while miR-122-5p and miR-638 were significantly down-regulated (−3.45- and −2.60-fold for miR-122-5p, −1.82- and −3.20-fold for miR-638, P<0.001) in the CBP patients; compared with non-exposures, the plasma level of miR-638 was significantly up-regulated (1.38-fold, P<0.01) while the plasma levels miR-122-5p and miR-221-3p were significantly down-regulated (−0.85- and −1.74-fold, P<0.01) in the exposures, which were consistent with the results of microarray analysis. Conclusions The four indicated plasma miRNAs may be biomarkers of indicating responses to benzene

  6. Evaluation of genotoxic effects of benzene and its derivatives in workers of gas stations.

    PubMed

    Trevisan, Patrícia; da Silva, Juliane Nascimento; da Silva, Alessandra Pawelec; Rosa, Rafael Fabiano Machado; Paskulin, Giorgio Adriano; Thiesen, Flávia Valladão; de Oliveira, Ceres Andréia Vieira; Zen, Paulo Ricardo Gazzola

    2014-04-01

    The search for reliable biomarkers of human exposure to benzene and its derivatives is still subject of research. Many of the proposed biomarkers have limitations ranging from the low sensitivity to the wide variability of results. Thus, the aim of our study was to assess the frequencies of chromosomal abnormalities (CA) and sister chromatid exchanges (SCE) in workers of gas stations, with (cases, n = 19) and without (local controls, n = 6) risk of exposure to benzene and its derivatives, comparing them with the results from the general population (external controls, n = 38). The blood dosages of benzene, toluene, and xylenes were measured in all participants. Blood solvent levels were compared with the findings obtained in cytogenetic evaluation and a research protocol which included data of the workplace, lifestyle, and health of the individuals. We did not detect the presence of benzene and its derivatives and did not find chromosomal damage that may be associated with the gas station activity in cases. Moreover, although we found an association of increased SCE and the working time in the local controls, the values found for SCE are within normal limits. Thus, our evaluation of SCE and CA reflected the levels of benzene and its derivatives observed in the blood. We believe, therefore, that SCE and CA may actually constitute possible tests for the evaluation of these exposures. However, we believe that further studies, including individuals at risk, are important to confirm this assertion.

  7. 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.

  8. 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. PMID:25218254

  9. 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

  10. Behavioral changes in mice following benzene inhalation.

    PubMed

    Evans, H L; Dempster, A M; Snyder, C A

    1981-01-01

    Although benzene is an important occupational health hazard and a carcinogen, the possibility that behavioral changes may forewarn of the later-occurring hematological changes has not been investigated. A time-sampling protocol was used to quantify the occurrence of 7 categories of behavior in the homecage following daily 6-hr exposures to two strains of adult mice (CD1 and C57BL/6J). The behavioral categories were stereotypic behavior, sleeping, resting, eating, grooming, locomotion, and fighting. The inhalation exposures were designed to reflect occupational exposure. Dynamic vapor exposure techniques in standard inhalation chambers were employed. Exposure to 300 or 900 ppm benzene increased the occurrence of eating and grooming and reduced the number of mice that were sleeping or resting. The responses to benzene of both the CD1 and the C57 strains were similar. The positive findings with benzene inhalation indicate the utility of behavioral investigations into the toxicology of inhaled organic solvents. The methods described herein illustrate an objective observation of animal behavior that is capable of documenting toxicity and of guiding detailed follow-up studies aimed at mechanism of action.

  11. IRIS TOXICOLOGICAL REVIEW OF BENZENE (NONCANCER EFFECTS)

    EPA Science Inventory

    Benzene, also known as benzol, is widely used as an industrial solvent, as an intermediate in chemical syntheses, and as a component of gasoline; hence, the potential for human exposure is great. The emphasis of this document is a discussion of the noncancer adverse healt...

  12. Formation of benzene in the interstellar medium.

    PubMed

    Jones, Brant M; Zhang, Fangtong; Kaiser, Ralf I; Jamal, Adeel; Mebel, Alexander M; Cordiner, Martin A; Charnley, Steven B

    2011-01-11

    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 (C(6)H(6)) can be synthesized via the barrierless, exoergic reaction of the ethynyl radical and 1,3-butadiene, C(2)H + H(2)CCHCHCH(2) → C(6)H(6) + 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.

  13. Electroencephalographic findings in workers exposed to benzene.

    PubMed

    Kellerová, V

    1985-01-01

    Preventive EEG examination was carried out in 40 workers significantly exposed to benzene. The EEG findings were compared with those of a control group of 48 healthy persons, a group of 110 workers significantly exposed to toluene and xylene and a group of 236 workers exposed to vinyl chloride. The individuals exposed to benzene exhibited 22.5% of abnormal and 45% threshold findings, the abnormalities being episodic, diffuse or a combination of the two. The effect of benzene entailed a frequent (32.5%) occurrence of a characteristic frequency lability. Sleep phenomena were found in a total of 60% cases (37.5% cases reached stage 1 B3 while 15% reached stage 2 according to Roth [14]). The rapid onset of deeper sleep stages (in 30% cases) is considered typical for benzene exposure. The photic driving response often had an extended frequency range (a total of 61.1%, to beta frequencies only in 30.55%, to both beta and theta frequencies also in 30.55% of cases). The different EEG features characteristic of the neurotoxic action of various types of organic solvents make possible a more efficient diagnostics of the effects of these chemicals on the CNS. PMID:4086812

  14. 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...

  15. 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...

  16. 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.

  17. 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...

  18. 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...

  19. 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...

  20. 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,...

  1. 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...

  2. 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...

  3. 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...

  4. 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,...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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,...

  10. 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,...

  11. 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...

  12. 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,...

  13. 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...

  14. 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...

  15. 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...

  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 721.1210 - 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...

  18. 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...

  19. 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...

  20. 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).

  1. Quantification of Secondary Metabolites.

    PubMed

    2016-01-01

    Plants are a rich source of secondary metabolites that have medicinal and aromatic properties. Secondary metabolites such as alkaloids, iridoids and phenolics generally produced by plants for their defence mechanisms have been implicated in the therapeutic properties of most medicinal plants. Hence, quantification of these metabolites will aid to discover new and effective drugs from plant sources and also to scientifically validate the existing traditional practices. Quantification of large group of phytochemicals such as phenolics and flavonoids is quantified in this context. PMID:26939265

  2. Differences in rates of benzene metabolism correlate with observed genotoxicity.

    PubMed

    Kenyon, E M; Kraichely, R E; Hudson, K T; Medinsky, M A

    1996-01-01

    Benzene (BZ) requires oxidative metabolism via cytochrome P450 2E1 (CYP 2E1) to exert its hematotoxic and genotoxic effects. Male mice are two- to threefold more sensitive to the genotoxic effects of BZ as measured by micronuclei induction and sister chromatid exchanges. The purpose of our study was to investigate sex-related differences in the metabolism of BZ, phenol (PHE) and hydroquinone (HQ) in order to understand the metabolic basis for sex-dependent differences in BZ genotoxic susceptibility in mice. Rates of BZ oxidation were quantitated using closed chamber gas uptake studies with male and female B6C3F1 mice exposed to initial low (400-500 ppm), intermediate (1200-1300 ppm), and high (2600-2800 ppm) BZ concentrations. Acetone-pretreated and diethyldithiocarbamate-pretreated male mice were also studied to determine the extent to which induction and inhibition of CYP 2E1, respectively, would alter in vivo BZ oxidation rates. Elimination of PHE and HQ from blood was also compared in male and female mice to complement previously reported data on sex-related differences in urinary excretion of conjugated metabolites following iv administration of PHE. Based on PBPK model analysis, the optimized rate of metabolism (Vmax) of BZ was almost twofold higher in male mice (14.0 mumol/hr-kg) than in female mice (7.9 mumol/hr-kg); both male and female mice gas-uptake data were well fit with a KM of 3.0 microM. Pretreatment of male mice with 1% acetone in drinking water for 8 days to specifically induce CYP 2E1 enhanced the rate of BZ oxidation by approximately fivefold (Vmax = 75 mumol/hr-kg), while diethyldithiocarbamate pretreatment (320 mg/kg ip 30 min prior to uptake study) completely inhibited BZ oxidation (Vmax = 0 mumol/hr-kg). Thus, both pretreatment regimens are potentially useful investigative tools to study the metabolic basis for benzene toxicity. Elimination of PHE from blood was significantly faster in male mice, while elimination of HQ did not differ

  3. [Effect of metals, benzene, pesticides and ethylene oxide on the haematopoietic system].

    PubMed

    Pyszel, Angelika; Wróbel, Tomasz; Szuba, Andrzej; Andrzejak, Ryszard

    2005-01-01

    The hematopoietic system, due to intensive cells proliferation, is very sensitive to toxic substances. Many chemicals, includi