Science.gov

Sample records for methyl bromide exposure

  1. Severe Illness from Methyl Bromide Exposure at a Condominium Resort--U.S. Virgin Islands, March 2015.

    PubMed

    Kulkarni, Prathit A; Duncan, Mary Anne; Watters, Michelle T; Graziano, Leah T; Vaouli, Elena; Cseh, Larry F; Risher, John F; Orr, Maureen F; Hunte-Ceasar, Tai C; Ellis, Esther M

    2015-07-24

    On March 22, 2015, the Agency for Toxic Substances and Disease Registry (ATSDR) was notified by the U.S. Environmental Protection Agency (EPA) of four cases of suspected acute methyl bromide toxicity among family members vacationing at a condominium resort in the U.S. Virgin Islands. Methyl bromide is a pesticide that has been banned in the United States for use in homes and other residential settings. An investigation conducted by the U.S. Virgin Islands Department of Health (VIDOH), the U.S. Virgin Islands Department of Planning and Natural Resources (DPNR), and EPA confirmed that methyl bromide had been used as a fumigant on March 18 in the building where the family had been residing, 2 days before they were transported to the hospital; three family members had life-threatening illness. On March 25, 2015, a stop-use order for methyl bromide was issued by DPNR to the pest control company that had performed the fumigation. Subsequent investigation revealed that previous fumigation with methyl bromide had occurred on October 20, 2014, at the same condominium resort. In addition to the four ill family members, 37 persons who might have been exposed to methyl bromide as a result of the October 2014 or March 2015 fumigations were identified by VIDOH and ATSDR. Standardized health questionnaires were administered to 16 of the 20 persons for whom contact information was available; six of 16 had symptoms consistent with methyl bromide exposure, including headache and fatigue. Pest control companies should be aware that use of methyl bromide is banned in homes and other residential settings, and clinicians should be aware of the toxicologic syndrome that exposure to methyl bromide can cause.

  2. Illness associated with exposure to methyl bromide-fumigated produce--California, 2010.

    PubMed

    2011-07-15

    Methyl bromide (MeBr) is a toxic gas used to fumigate agricultural fields and some produce. The U.S. Department of Agriculture (USDA) requires MeBr fumigation of grapes imported from Chile to prevent invasion by the Chilean false red mite, Brevipalpus chilensis. In 2010, two workers were exposed intermittently to MeBr over several months as part of their job inspecting produce at a cold-storage facility in Carson, California. Both workers had disabling neurologic symptoms (e.g., ataxia, memory difficulties, and dizziness) and elevated serum bromide concentrations. An environmental investigation revealed the potential for MeBr to accumulate in enclosed areas during the transportation and storage of fumigated grapes. Some MeBr air concentrations measured at a single point in time exceeded current 8-hour exposure limits, suggesting that exposure in confined areas could result in poisoning. Possible measures for facilities managers to consider to reduce postfumigation MeBr exposures include 1) increased aeration time, 2) reduction of packaging that might absorb MeBr or limit aeration, and 3) changes in the stacking of pallets to improve air flow. Facilities should monitor air MeBr levels if they store MeBr-fumigated commodities in enclosed spaces entered by workers. Clinicians should consider occupational and environmental exposures in their differential diagnosis, and workers who might become exposed to fumigants should be informed of the health hazards related to these pesticides.

  3. Neurological manifestation of methyl bromide intoxication.

    PubMed

    Suwanlaong, Kanokrat; Phanthumchinda, Kammant

    2008-03-01

    Methyl bromide is a highly toxic gas with poor olfactory warning properties. It is widely used as insecticidal fumigant for dry foodstuffs and can be toxic to central and peripheral nervous systems. Most neurological manifestations of methyl bromide intoxication occur from inhalation. Acute toxicity characterized by headache, dizziness, abdominal pain, nausea, vomiting and visual disturbances. Tremor, convulsion, unconsciousness and permanent brain damage may occur in severe poisoning. Chronic exposure can cause neuropathy, pyramidal and cerebellar dysfunction, as well as neuropsychiatric disturbances. The first case of methyl bromide intoxication in Thailand has been described. The patient was a 24-year-old man who worked in a warehouse of imported vegetables fumigated with methyl bromide. He presented with unstable gait, vertigo and paresthesia of both feet, for two weeks. He had a history of chronic exposure to methyl bromide for three years. His fourteen co-workers also developed the same symptoms but less in severity. Neurological examination revealed ataxic gait, decreased pain and vibratory sense on both feet, impaired cerebellar signs and hyperactive reflex in all extremities. The serum concentration of methyl bromide was 8.18 mg/dl. Electrophysilogical study was normal. Magnetic resonance imaging of the brain (MRI) revealed bilateral symmetrical lesion of abnormal hypersignal intensity on T2 and fluid-attenuation inversion recovery (FLAIR) sequences at bilateral dentate nuclei of cerebellum and periventricular area of the fourth ventricle. This incident stresses the need for improvement of worker education and safety precautions during all stages of methyl bromide fumigation.

  4. Managing Nematodes without Methyl Bromide

    USDA-ARS?s Scientific Manuscript database

    Methyl bromide is an effective pre-plant soil fumigant used to control nematodes in many high-input, high-value production systems including vegetables, nurseries, ornamentals, tree fruits, strawberries, and grapes. Because methyl bromide has provided a reliable return on investment for nematode c...

  5. Post-exposure treatment with nasal atropine methyl bromide protects against microinstillation inhalation exposure to sarin in guinea pigs

    SciTech Connect

    Che, Magnus M.; Conti, Michele; Boylan, Megan; Sabnekar, Praveena; Rezk, Peter; Sciuto, Alfred M.; Doctor, Bhupendra P.; Nambiar, Madhusoodana P.

    2009-09-15

    We evaluated the protective efficacy of nasal atropine methyl bromide (AMB) which does not cross the blood-brain barrier against sarin inhalation exposure. Age and weight matched male guinea pigs were exposed to 846.5 mg/m{sup 3} sarin using a microinstillation inhalation exposure technique for 4 min. The survival rate at this dose was 20%. Post-exposure treatment with nasal AMB (2.5 mg/kg, 1 min) completely protected against sarin induced toxicity (100% survival). Development of muscular tremors was decreased in animals treated with nasal AMB. Post-exposure treatment with nasal AMB also normalized acute decrease in blood oxygen saturation and heart rate following sarin exposure. Inhibition of blood AChE and BChE activities following sarin exposure was reduced in animals treated with nasal AMB, indicating that survival increases the metabolism of sarin or expression of AChE. The body weight loss of animals exposed to sarin and treated with nasal AMB was similar to saline controls. No differences were observed in lung accessory lobe or tracheal edema following exposure to sarin and subsequent treatment with nasal AMB. Total bronchoalveolar lavage fluid (BALF) protein, a biomarker of lung injury, showed trends similar to saline controls. Surfactant levels post-exposure treatment with nasal AMB returned to normal, similar to saline controls. Alkaline phosphatase levels post-exposure treatment with nasal AMB were decreased. Taken together, these data suggest that nasal AMB blocks the copious airway secretion and peripheral cholinergic effects and protects against lethal inhalation exposure to sarin thus increasing survival.

  6. Post-exposure treatment with nasal atropine methyl bromide protects against microinstillation inhalation exposure to sarin in guinea pigs.

    PubMed

    Che, Magnus M; Conti, Michele; Chanda, Soma; Boylan, Megan; Sabnekar, Praveena; Rezk, Peter; Amari, Ethery; Sciuto, Alfred M; Gordon, Richard K; Doctor, Bhupendra P; Nambiar, Madhusoodana P

    2009-09-15

    We evaluated the protective efficacy of nasal atropine methyl bromide (AMB) which does not cross the blood-brain barrier against sarin inhalation exposure. Age and weight matched male guinea pigs were exposed to 846.5 mg/m(3) sarin using a microinstillation inhalation exposure technique for 4 min. The survival rate at this dose was 20%. Post-exposure treatment with nasal AMB (2.5 mg/kg, 1 min) completely protected against sarin induced toxicity (100% survival). Development of muscular tremors was decreased in animals treated with nasal AMB. Post-exposure treatment with nasal AMB also normalized acute decrease in blood oxygen saturation and heart rate following sarin exposure. Inhibition of blood AChE and BChE activities following sarin exposure was reduced in animals treated with nasal AMB, indicating that survival increases the metabolism of sarin or expression of AChE. The body weight loss of animals exposed to sarin and treated with nasal AMB was similar to saline controls. No differences were observed in lung accessory lobe or tracheal edema following exposure to sarin and subsequent treatment with nasal AMB. Total bronchoalveolar lavage fluid (BALF) protein, a biomarker of lung injury, showed trends similar to saline controls. Surfactant levels post-exposure treatment with nasal AMB returned to normal, similar to saline controls. Alkaline phosphatase levels post-exposure treatment with nasal AMB were decreased. Taken together, these data suggest that nasal AMB blocks the copious airway secretion and peripheral cholinergic effects and protects against lethal inhalation exposure to sarin thus increasing survival.

  7. An Ill Wind: Methyl Bromide Use Near California Schools, 1998.

    ERIC Educational Resources Information Center

    Ross, Zev; Walker, Bill

    A California study investigates the use of the toxic pesticide methyl bromide near the state's public schools, explains why proposed safety rules have failed to protect children and others from exposure, and examines regions at particular exposure risk. Study results show an increasing exposure to methyl bromide near schools already at risk while…

  8. 49 CFR 173.193 - Bromoacetone, methyl bromide, chloropicrin and methyl bromide or methyl chloride mixtures, etc.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... methyl bromide or methyl chloride mixtures, etc. 173.193 Section 173.193 Transportation Other Regulations... bromide, chloropicrin and methyl bromide or methyl chloride mixtures, etc. (a) Bromoacetone must be...) Bromoacetone, methyl bromide, chloropicrin and methyl bromide mixtures, chloropicrin and methyl...

  9. 49 CFR 173.193 - Bromoacetone, methyl bromide, chloropicrin and methyl bromide or methyl chloride mixtures, etc.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... methyl bromide or methyl chloride mixtures, etc. 173.193 Section 173.193 Transportation Other Regulations... bromide, chloropicrin and methyl bromide or methyl chloride mixtures, etc. (a) Bromoacetone must be...) Bromoacetone, methyl bromide, chloropicrin and methyl bromide mixtures, chloropicrin and methyl...

  10. 49 CFR 173.193 - Bromoacetone, methyl bromide, chloropicrin and methyl bromide or methyl chloride mixtures, etc.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... methyl bromide or methyl chloride mixtures, etc. 173.193 Section 173.193 Transportation Other Regulations... bromide, chloropicrin and methyl bromide or methyl chloride mixtures, etc. (a) Bromoacetone must be... Group I performance level. (b) Bromoacetone, methyl bromide, chloropicrin and methyl bromide...

  11. 49 CFR 173.193 - Bromoacetone, methyl bromide, chloropicrin and methyl bromide or methyl chloride mixtures, etc.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... methyl bromide or methyl chloride mixtures, etc. 173.193 Section 173.193 Transportation Other Regulations... bromide, chloropicrin and methyl bromide or methyl chloride mixtures, etc. (a) Bromoacetone must be... Group I performance level. (b) Bromoacetone, methyl bromide, chloropicrin and methyl bromide...

  12. 77 FR 35295 - Methyl Bromide; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-13

    ... AGENCY 40 CFR Part 180 RIN 2070-ZA16 Methyl Bromide; Pesticide Tolerances AGENCY: Environmental... methyl bromide in or on cotton, undelinted seed under the Federal Food, Drug, and Cosmetic Act (FFDCA... to establish a tolerance for residues of methyl bromide, including metabolites and degradates in or...

  13. Dermal absorption of fumigant gases during HAZMAT incident exposure scenarios-Methyl bromide, sulfuryl fluoride, and chloropicrin.

    PubMed

    Gaskin, Sharyn; Heath, Linda; Pisaniello, Dino; Edwards, John W; Logan, Michael; Baxter, Christina

    2017-01-01

    Accidental or intentional releases of toxic gases or vapors are the most common occurrence in hazardous material (HAZMAT) incidents that result in human injuries. The most serious hazard from exposure to gases or vapors is via the respiratory system. Dermal uptake, as a secondary route, is still a concern, most acutely for the unprotected public. There is a limited evidence base describing skin absorption of toxic gases and vapors in HAZMAT exposure scenarios, which are relatively brief compared with traditional test periods for skin absorption studies. We describe research designed to provide experimental data to support decision-making by first responders regarding skin decontamination in HAZMAT-focused exposure scenarios involving toxic gases. We present findings for three common fumigants, methyl bromide, sulfuryl fluoride, and chloropicrin assessed using an Organization for Economic Co-operation and Development in vitro toxicology protocol utilizing human skin and gas/vapor exposures. Results indicate that for atmospheric concentrations that would be lethal via inhalation (LCLo), intact skin provides an excellent barrier to exposures up to 30 min, with little influence of common clothing fabric and high temperature and humidity conditions. The findings may challenge the current HAZMAT dogma requiring mass personal decontamination by strip and shower for short-term exposures to sulfuryl fluoride and chloropicrin gas/vapor.

  14. Methyl bromide users search for science

    SciTech Connect

    Winegar, E.D.

    1995-01-01

    Workers, neighbors and the ozone are protected by regulation from this chemical, but those needing it complain that a solid foundation is lacking for the rules. Although not yet featured on {open_quotes}60 Minutes,{close_quotes} the pesticide methyl bromide is gaining widespread attention because of its central position in debates about worker health and safety, environmental toxics exposure and global ozone depletion.

  15. 49 CFR 173.193 - Bromoacetone, methyl bromide, chloropicrin and methyl bromide or methyl chloride mixtures, etc.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Bromoacetone, methyl bromide, chloropicrin and methyl bromide or methyl chloride mixtures, etc. 173.193 Section 173.193 Transportation Other Regulations... bromide, chloropicrin and methyl bromide or methyl chloride mixtures, etc. (a) Bromoacetone must be...

  16. The neurological effects of methyl bromide intoxication.

    PubMed

    de Souza, Aaron; Narvencar, Kedareshwar P S; Sindhoora, K V

    2013-12-15

    Used primarily as a fumigant or as a substrate in chemical processes, methyl bromide is a highly toxic gas. The gas is usually absorbed by inhalation and effects on the lungs, gastrointestinal tract, skin, and brain are seen. Numerous instances of acute and chronic neurologic injury have been reported: acute poisoning results in seizures, myoclonus, ataxia or cerebral oedema beginning as early as 30 min after exposure while subacute or chronic intoxication presents with diverse slowly progressive neurological and neurobehavioral symptoms. Serum bromide levels may be elevated, but often return rapidly to normal. Electroencephalography may show frontally-predominant slow waves or polyspikes with following slow wave, and MRI reveals characteristic involvement in the dentate nucleus of the cerebellum, the brainstem, and the splenium of the corpus callosum. Symmetric and selective lesions in characteristic sites are observed on imaging and on histopathological examination. These are likely produced by methylation of intracellular lipids, protein and glutathione; production of toxic metabolites; defective neurotransmitter function; and abnormal oxidative phosphorylation. This article reviews the toxic effects of this gas, the pathophysiology and symptoms of its effects on the nervous system, and characteristic findings on MRI; and presents an illustrative case of methyl bromide intoxication due to exposure at a factory producing the compound commercially.

  17. Emission of methyl bromide from biomass burning

    SciTech Connect

    Manoe, S.; Andreae, M.O. )

    1994-03-04

    Bromine is, per atom, far more efficient than chlorine in destroying stratospheric ozone, and methyl bromide is the single largest source of stratospheric bromine. The two main previously known sources of this compound are emissions from the ocean and from the compound's use as an agricultural pesticide. Laboratory biomass combustion experiments showed that methyl bromide was emitted in the smoke from various fuels tested. Methyl bromide was also found in smoke plumes from wildfires in savannas, chaparral, and boreal forest. Global emissions of methyl bromide from biomass burning are estimated to be in the range of 10 to 50 gigagrams per year, which is comparable to the amount produced by ocean emission and pesticide use and represents a major contribution ([approximately]30 percent) to the stratospheric bromine budget.

  18. Methyl Bromide Investigation Expands to Puerto Rico

    EPA Pesticide Factsheets

    (New York, N.Y.) The U.S. Environmental Protection Agency, working with the Virgin Islands government, is investigating the March 2015 incident involving the use of a pesticide containing methyl bromide to fumigate a residence at the Sirenusa apartments on

  19. METHYL BROMIDE ALTERNATIVES FOR CALIFORNIA STRAWBERRY NURSERIES

    USDA-ARS?s Scientific Manuscript database

    The effects of methyl bromide (MB) alternative fumigants on soil pests, plant productivity in nursery and fruiting fields, as well as production costs, were evaluated in California strawberry nurseries by an interdisciplinary team. Our trials followed nursery stock through low and high elevation ph...

  20. 77 FR 20752 - Methyl Bromide; Proposed Pesticide Tolerance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-06

    ... feeding items resulting from fumigation of cottonseed with methyl bromide are covered by existing... produced from cottonseed fumigated with methyl bromide would not contain residues of methyl bromide... pest within the United States. As a feed commodity, imported cottonseed that has been fumigated with...

  1. Actual hazard of methyl bromide fumigation in soil disinfection.

    PubMed Central

    Van Den Oever, R U; Roosels, D; Lahaye, D

    1982-01-01

    Methyl bromide, a highly toxic and ready penetrating fumigant, is widely used against rodents, insects, mites, and a range of pathogenic organisms in soil, compost, and timber. To disinfect soil in greenhouses, methyl bromide is brought under pressure from outside by a vaporiser and blown on to ground under a polyethylene cover. The gas being three times heavier than air easily penetrates the ground. Depending on the local ventilation, a considerable amount of gas evaporates into the surrounding atmosphere, this emission being especially serious during the fumigation procedure and at the removal of the plastic cover. Previously, mechanical injection of methyl bromide on to the ground within closed areas was prohibited, since this technique exposed at least four disinfection workers at a time, who were provided with only a canister respirator, to gas concentrations of over 1000 ppm CH3Br. The present study established that fumigation with methyl bromide also carries risks for the well-protected worker inside, as well as for the one controlling the vaporiser. The concentration during application varies from 30 to 3000 ppm. Concentration in the air declines with time to 4 ppm CH3Br five days after application. Discarding the plastic sheet involves exposure to peak values as high as 200 ppm for a few seconds. On the ninth day after application, milling the soil can expose workers to up to 15 ppm; on the eleventh day no CH3Br concentration in the air could be found. PMID:7066229

  2. [Research advances in methyl bromide in the ocean].

    PubMed

    Du, Hui-na; Xie, Wen-xia; Cui, Yu-qian; Chen, Jian-lei; Ye, Si-yuan

    2014-12-01

    Methyl bromide is an important atmospheric trace gas, which plays significant roles in the global warming and atmospheric chemistry. The ocean plays important and complex roles in the global biogeochemical cycles of methyl bromide, not only the source of atmospheric methyl bromide, but also the sink. Therefore, developing the chemical research of the soluble methyl bromide in the ocean, will not only have a certain guiding significance to the atmospheric ozone layer protection, but also provide a theoretical basis for estimating methyl bromide's contribution to the global environmental change on global scale. This paper reviewed the research advances on methyl bromide in the ocean, from the aspects of the biogeochemical cycle of methyl bromide in the ocean, the analysis and determination method, the concentration distribution, the sea-to-air flux and its sources and sinks in the atmosphere. Some deficiencies in the current studies were put forward, and the directions of the future studies were prospected.

  3. Measurements of atmospheric methyl bromide and bromoform

    SciTech Connect

    Cicerone, R.J.; Heidt, L.E.; Pollock, W.H.

    1988-04-20

    We have measured gaseous methyl bromide (CH/sub 3/Br) and bromoform (CHBr/sub 3/) in air samples that were gathered approximately weekly from five ground-level sites: Point Barrow, Alaska; Mauna Loa Observatory and Cape Kumukahi, Hawaii; Matatula, Samoa; and Kaitorete Spit, New Zealand. Approximately 750 samples have been analyzed for CH/sub 3/Br between January 1985 and October 1987 and 990 samples have been analyzed for CHBr/sub 3/ between early 1984 and September 1987, all by gas chromatography/mass spectroscopy. Methyl bromide concentrations are typically 10--11 parts per trillion (ppt) by volume; there are no clear indications of temporal increases. Bromoform concentrations are typically 2--3 ppt, but large seasonal variations are seen at Point Barrow. copyright American Geophysical Union 1988

  4. Data for methyl bromide decon testing

    EPA Pesticide Factsheets

    Spreadsheets containing data for recovery of spores from different materials. Data on the fumigation parameters are also included.This dataset is associated with the following publication:Wood , J., M. Wendling, W. Richter, A. Lastivka, and L. Mickelsen. Evaluation of the Efficacy of Methyl Bromide in the Decontamination of Building and Interior Materials Contaminated with Bacillus anthracis Spores. APPLIED AND ENVIRONMENTAL MICROBIOLOGY. American Society for Microbiology, Washington, DC, USA, 1-28, (2016).

  5. Methyl bromide volatility measurements from treated fields

    SciTech Connect

    Majewski, M.S.; Woodrow, J.E.; Seiber, J.N. |

    1995-12-31

    Methyl bromide is used as an agricultural soil fumigant and concern is growing over the role it may play in the depletion of stratospheric ozone. Methyl bromide is applied using various techniques and little is known about how much of the applied fumigant volatilizes into the atmosphere after application. The post-application volatilization losses of methyl bromide from two fields using different application practices were measured using an aerodynamic-gradient technique. One field was covered with a high-barrier plastic film tarp during application and the other was left uncovered, but the furrows made by the injection shanks were bedded over. The cumulative volatilization losses from the tarped field were 22% of the nominal application within the first 5 days of the experiment and about 32% of the nominal application within 9 days including the one day after the tarp was removed on day 8. The nontarped field lost 89%of the nominal application by volatilization in 5 days. The error associated, with each flux measurement, as well as variations in daily flux losses with differing sampling period lengths show the degree of variability inherent in this type of study.

  6. Degradation of methyl bromide in anaerobic sediments

    USGS Publications Warehouse

    Oremland, R.S.; Miller, L.G.; Strohmaler, F.E.

    1994-01-01

    Methyl bromide (MeBr) was anaerobically degraded in saltmarsh sediments after reaction with sulfide. The product of this nucleophilic substitution reaction was methanethiol, which underwent further chemical and bacterial reactions to form dimethyl sulfide. These two gases appeared transiently during sediment incubations because they were metabolized by methanogenic and sulfate-reducing bacteria. A second, less significant reaction of MeBr was the exchange with chloride, forming methyl chloride, which was also susceptible to attack by sulfide. Incubation of 14C-labeled methyl iodide as an analogue of MeBr resulted in the formation of 14CH4 and 14CO2 and also indicated that sulfate-reducing bacteria as well as methanogens metabolized the methylated sulfur intermediates. These results suggest that exposed sediments with abundant free sulfide, such as coastal salt-marshes, may constitute a sink for atmospheric MeBr.

  7. Methyl bromide emissions from tarped fields

    SciTech Connect

    Cicerone, R.J.; Williams, J.; Wang, N.Y.

    1995-12-31

    Once in the stratosphere, bromine atoms can destroy ozone effectively. Because of this potential effect, certain organobromine compounds including methyl bromide (MeBr) are being controlled or eliminated by national and international regulations. It would be valuable to determine the fraction of MeBr used in soil fumigations that subsequently enters the atmosphere to better assess the need for, and value of, strong regulations. We have designed and conducted several experiments accompanying field fumigations with MeBr/chloropicrin mixtures. In each of three field-fumigation experiments new Irvine, CA in which the fumigated field was covered immediately with plastic tarping, we have deployed static flux chambers on top of the tarping and measured escape fluxes of MeBr. After tarp removal, the same chambers were replaced on the bare soil to continue the measurements. We have also measured soil bromide contents before and after the fumigation. One experiment yielded an escape fraction of 80 to 87% (with 19% remaining as bromide) while the other two experiments yielded escape fractions of 30 to 35% (with about 70% remaining as bromide). This paper will summarize stratospheric bromine chemistry, describe the field experiments and discuss factors that influence emissions, including soil pH, moisture and organic content and injection technique. We acknowledge TriCal, Inc. for many helpful discussions and for professional field applications of MeBr.

  8. Photodissociation of methyl chloride and methyl bromide in the atmosphere

    NASA Technical Reports Server (NTRS)

    Robbins, D. E.

    1976-01-01

    Methyl chloride (CH3Cl) and methyl bromide (CH3Br) have been suggested to be significant sources of the stratospheric halogens. The breakup of these compounds in the stratosphere by photodissociation or reaction with OH releases halogen atoms which catalytically destroy ozone. Experimental results are presented for ultraviolet photoabsorption cross sections of CH3Cl and CH3Br. Calculations are presented of loss rates for the methyl halides due to photodissociation and reaction with OH and of mixing ratios of these species in the stratosphere.

  9. The Thz Absorption of Methyl Bromide (CH_3BR)

    NASA Astrophysics Data System (ADS)

    Ramos, Marlon; Drouin, Brian J.

    2011-06-01

    The possibility of monitoring Methyl Bromide is of interest for both environmental and health concerns. It has an ozone depletion potential of 0.2% and falls under regulations of the Clean Air Act. Neurological effects from long term exposure may result from its major use as a pesticide. Recent improvements in microwave limb sounding at mm & submm wavelengths have resulted in retrievals of Methyl Chloride from atmospheric spectra. It is conceivable that Methyl Bromide would also be measurable by this technique. In an effort to extend and improve the previous work, the THz spectrum of Methyl Bromide has been measured at JPL. We used an isotopically enriched 13CH_3Br (90%) sample and recorded spectra from 750 - 1200 GHz. Our assignment covers the CH_379Br, CH_381Br, 13CH_379Br and 13CH_381Br isotopologues with J< 66 and K< 17 for the ground vibrational state. We plan to assign vibrational satellites and investigate possible perturbations near K =12 in the ground state.

  10. Methyl bromide fate in fumigated soils

    SciTech Connect

    Anderson, T.A.; Rice, P.J.; Cink, J.H.

    1995-12-31

    Although widespread use of methyl bromide (MeBr) as a sail and structure fumigant has previously been recognized as a potential significant source of atmospheric MeBr, losses have not been well quantified. Our research indicates that, in laboratory studies, MeBr is volatilized rapidly from fumigated soils and that volatility increases with temperature (35{degrees}C > 25{degrees}C and 15{degrees}C) and moisture (0.03 bar and 0.3 bar > 1 bar > 3 bar). Degradation of MeBr in soil, as indicated by production of bromide ion, was also directly related to temperature and moisture. Most of the soil degradation of MeBr in these studies appears to be abiotic based on the observation of toxicity (reduced microbial respiration) in fumigated soils. We also determined the transformation and movement of MeBr in undisturbed soil columns. These studies also indicated that MeBT volatilizes rapidly (> 50% in 48 h) from soil. In addition, MeBr was not detected in the leachate from the soil columns, however, bromide ion was detected at levels above background 48 h after fumigation and peaked at 5 weeks.

  11. Minimizing methyl bromide emissions from soil fumigation

    NASA Astrophysics Data System (ADS)

    Yates, S. R.; Wang, D.; Gan, J.; Ernst, F. F.; Jury, W. A.

    There is great controversy concerning the need to phase out methyl bromide (MeBr) to protect stratospheric ozone. Unlike chlorinated hydrocarbons, MeBr occurs naturally in the atmosphere making it difficult to differentiate the threat to stratospheric ozone depletion from anthropogenic use of MeBr compared to natural sources. New technology has been developed which could nearly eliminate MeBr emissions from soil fumigation, bringing into question the need for a phase out. A field experiment demonstrated that virtually impermeable films (VIF) reduced MeBr emissions to near-zero levels. When compared to soil fumigation using conventional high-density polyethylene film (HDPE), the total global MeBr emission could be reduced from 32 Gg/yr to less than 1 Gg/yr, if VIF were required. In addition, reduced application rates are possible since using VIF reduces wasteful leakage and increases pest-control efficiency. With such low emission rates, and considering the large uncertainty in global estimates of MeBr, it seems that the phase-out of MeBr as a soil fumigant is unjustified.

  12. Methyl Bromide Commodity Fumigation Buffer Zone Lookup Tables

    EPA Pesticide Factsheets

    Product labels for methyl bromide used in commodity and structural fumigation include requirements for buffer zones around treated areas. The information on this page will allow you to find the appropriate buffer zone for your planned application.

  13. 7 CFR 305.6 - Methyl bromide fumigation treatment schedules.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., fumigation with methyl bromide for sapote fruit fly. Regulated citrus fruits originating inside an area quarantined for sapote fruit fly that are to be moved outside the quarantined area may be treated with...

  14. 77 FR 29341 - Protection of Stratospheric Ozone: Request for Methyl Bromide Critical Use Exemption Applications...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-17

    .... Structures and Facilities (Flour Mills, Rice Mills, Pet Food) Applicants must address potential economic... methyl bromide over the last three years; the rate, volume, and target CT of methyl bromide at each... methyl bromide over the last three years; the rate, volume, and target CT of methyl bromide at each...

  15. Residential Proximity to Methyl Bromide Use and Birth Outcomes in an Agricultural Population in California

    PubMed Central

    Gemmill, Alison; Gunier, Robert B.; Bradman, Asa; Eskenazi, Brenda

    2013-01-01

    Background: Methyl bromide, a fungicide often used in strawberry cultivation, is of concern for residents who live near agricultural applications because of its toxicity and potential for drift. Little is known about the effects of methyl bromide exposure during pregnancy. Objective: We investigated the relationship between residential proximity to methyl bromide use and birth outcomes. Methods: Participants were from the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study (n = 442), a longitudinal cohort study examining the health effects of environmental exposures on pregnant women and their children in an agricultural community in northern California. Using data from the California Pesticide Use Reporting system, we employed a geographic information system to estimate the amount of methyl bromide applied within 5 km of a woman’s residence during pregnancy. Multiple linear regression models were used to estimate associations between trimester-specific proximity to use and birth weight, length, head circumference, and gestational age. Results: High methyl bromide use (vs. no use) within 5 km of the home during the second trimester was negatively associated with birth weight (β = –113.1 g; CI: –218.1, –8.1), birth length (β = –0.85 cm; CI: –1.44, –0.27), and head circumference (β = –0.33 cm; CI: –0.67, 0.01). These outcomes were also associated with moderate methyl bromide use during the second trimester. Negative associations with fetal growth parameters were stronger when larger (5 km and 8 km) versus smaller (1 km and 3 km) buffer zones were used to estimate exposure. Conclusions: Residential proximity to methyl bromide use during the second trimester was associated with markers of restricted fetal growth in our study. PMID:23603811

  16. Cherry angiomas associated with exposure to bromides.

    PubMed

    Cohen, A D; Cagnano, E; Vardy, D A

    2001-01-01

    Cherry angiomas are the most common vascular proliferation; however, little is known about the pathogenesis and etiology of these lesions. We present two laboratory technicians who were exposed to brominated compounds for prolonged periods and who developed multiple cherry angiomas on the trunk and extremities. We suggest that the association between exposure to bromides and cherry angiomas should be investigated by a controlled study.

  17. Methyl bromide: effective pest management tool and environmental threat.

    PubMed

    Thomas, W B

    1996-12-01

    Methyl bromide is used extensively on a global basis as a pesticide against nematodes, weeds, insects, fungi, bacteria, and rodents. As a soil fumigant, it is used in significant quantities in the production of strawberry and tomato, as well as other agriculture commodities. Grain, fresh fruit, forestry products, and other materials are fumigated with methyl bromide to control pest infestations during transport and storage. Structures also are treated with this chemical to control wood-destroying insects and rodents. However, methyl bromide has been identified as a significant ozone-depleting substance, resulting in regulatory actions being taken by the U.S. Environmental Protection Agency and the United Nations Environment Program (Montreal Protocol). The science linking methyl bromide to ozone depletion is strong and was reinforced by the 1994 UNEP Montreal Protocol Science Assessment on Ozone Depletion, which states, "Methyl bromide continues to be viewed as a significant ozone-depleting compound." Identifying efficacious and viable alternatives in the near term is critical.

  18. Methyl Bromide: Effective Pest Management Tool and Environmental Threat

    PubMed Central

    Thomas, W. B.

    1996-01-01

    Methyl bromide is used extensively on a global basis as a pesticide against nematodes, weeds, insects, fungi, bacteria, and rodents. As a soil fumigant, it is used in significant quantities in the production of strawberry and tomato, as well as other agriculture commodities. Grain, fresh fruit, forestry products, and other materials are fumigated with methyl bromide to control pest infestations during transport and storage. Structures also are treated with this chemical to control wood-destroying insects and rodents. However, methyl bromide has been identified as a significant ozone-depleting substance, resulting in regulatory actions being taken by the U.S. Environmental Protection Agency and the United Nations Environment Program (Montreal Protocol). The science linking methyl bromide to ozone depletion is strong and was reinforced by the 1994 UNEP Montreal Protocol Science Assessment on Ozone Depletion, which states, "Methyl bromide continues to be viewed as a significant ozone-depleting compound." Identifying efficacious and viable alternatives in the near term is critical. PMID:19277178

  19. Methyl Bromide Fumigation of Pratylenchus brachyurus in Peanut Shells

    PubMed Central

    Minton, N. A.; Gillenwater, H. B.

    1973-01-01

    Five dosages of methyl bromide were used to fumigate peanut (Arachis hypogaea L.) shells and whole pods of peanuts in 1-liter flasks for 24 hr at 25 C. Methyl bromide dosages as low as 24.5 mg/liter killed all Pratylenchus brachyurus (Godfrey) Filip. &Sch. Stech. in peanut shells. Dosages of 44.6 and 50.9 mg/liter killed all but one or two nematodes in shells of whole pods. A 15% reduction in seed germination occurred at the 50.9-mg/liter dosage. PMID:19319321

  20. Prostate cancer and toxicity from critical use exemptions of methyl bromide: Environmental protection helps protect against human health risks

    PubMed Central

    2012-01-01

    Background Although ozone-depleting methyl bromide was destined for phase-out by 2005, it is still widely applied as a consequence of various critical-use-exemptions and mandatory international regulations aiming to restrict the spread of pests and alien species (e.g. in globalized transport and storage). The withdrawal of methyl bromide because of its environmental risk could fortuitously help in the containment of its human toxicity. Methods We performed a systematic review of the literature, including in vitro toxicological and epidemiological studies of occupational and community exposure to the halogenated hydrocarbon pesticide methyl bromide. We focused on toxic (especially chronic) or carcinogenic effects from the use of methyl bromide, on biomonitoring data and reference values. Eligible epidemiological studies were subjected to meta-analysis. Results Out of the 542 peer reviewed publications between 1990-2011, we found only 91 referring to toxicity of methyl bromide and 29 using the term "carcinogenic", "neoplastic" or "mutagenic". Several studies provide new additional data pertaining to the mechanistic aspects of methyl bromide toxicity. Few studies have performed a detailed exposure assessment including biomonitoring. Three evaluated epidemiological studies assessed a possible association between cancer and methyl bromide. Overall, exposure to methyl bromide is associated with an increased risk of prostate cancer OR, 1.21; 95% CI (0,98-1.49), P = 0.076. Two epidemiological studies have analyzed environmental, non-occupational exposure to methyl bromide providing evidence for its health risk to the general public. None of the epidemiological studies addressed its use as a fumigant in freight containers, although recent field and case reports do refer to its toxic effects associated with its use in shipping and storage. Conclusions Both the epidemiological evidence and toxicological data suggest a possible link between methyl bromide exposure and serious

  1. Reactive films for mitigating methyl bromide emissions from fumigated soil

    USDA-ARS?s Scientific Manuscript database

    Emissions of methyl bromide (MeBr) from agricultural fumigation can lead to depletion of the stratospheric ozone layer, and so its use is being phased out. However, as MeBr is still widely used under Critical Use Exemptions, strategies are still required to control such emissions. In this work, nove...

  2. Evaluation of the Efficacy of Methyl Bromide in the ...

    EPA Pesticide Factsheets

    Journal Article The objective of this article is to determine the required conditions for the effective inactivation of Bacillus anthracis (B.a.) spores on materials using methyl bromide (MeBr) and to obtain comparative efficacy data with three avirulent microorganisms, to assess their potential as surrogates for B.a. Ames.

  3. 40 CFR 180.124 - Methyl bromide; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Methyl bromide; tolerances for residues. 180.124 Section 180.124 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances...

  4. 40 CFR 180.124 - Methyl bromide; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Methyl bromide; tolerances for residues. 180.124 Section 180.124 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances...

  5. 40 CFR 180.124 - Methyl bromide; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Methyl bromide; tolerances for residues. 180.124 Section 180.124 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances...

  6. Chemical alternatives to methyl bromide for Florida ornamental production

    USDA-ARS?s Scientific Manuscript database

    This project is a cooperative effort among USDA, ARS and University of Florida researchers, Florida in-ground ornamental producers, and fumigant industry representatives. Funding is provided through the USDA-ARS Area-wide Pest Management Program for Alternatives to Methyl Bromide. The ornamental i...

  7. Evaluation of the Efficacy of Methyl Bromide in the ...

    EPA Pesticide Factsheets

    Journal Article The objective of this article is to determine the required conditions for the effective inactivation of Bacillus anthracis (B.a.) spores on materials using methyl bromide (MeBr) and to obtain comparative efficacy data with three avirulent microorganisms, to assess their potential as surrogates for B.a. Ames.

  8. Depleting methyl bromide residues in soil by reaction with bases

    USDA-ARS?s Scientific Manuscript database

    Despite generally being considered the most effective soil fumigant, methyl bromide (MeBr) use is being phased out because its emissions from soil can lead to stratospheric ozone depletion. However, a large amount is still currently used due to Critical Use Exemptions. As strategies for reducing the...

  9. The Fate of Alternative Soil Funigants to Methyl Bromide

    USDA-ARS?s Scientific Manuscript database

    Soil fumigation is an important agricultural practice for the control of soil-borne pests. Since the phase–out of methyl bromide, due to its role in the depletion of stratospheric ozone, several alternatives such as 1,3-dichloropropene (1,3-D), chloropicrin (CP), and dimethyl disulfide (DMDS) are b...

  10. Bromine in blood, EEG and transaminases in methyl bromide workers.

    PubMed Central

    Verberk, M M; Rooyakkers-Beemster, T; de Vlieger, M; van Vliet, A G

    1979-01-01

    In 33 methyl bromide users, slight electroencephalographic changes (in 10 subjects) and a small increase in serum transaminases were found which could be related to bromine concentration in blood. No relationship was found with subjective symptoms, general neurological examination or the results of serum protein electrophoresis. PMID:444442

  11. Status of Alternatives for Methyl Bromide in the United States

    USDA-ARS?s Scientific Manuscript database

    Methyl bromide is a fumigant used for disinfestation of soils, commodities and structures. Listed as an ozone-depleting chemical international environmental protocols and the U.S. Clean Air Act require that its use be severely restricted. Although use of this fumigant has fallen considerably, the U....

  12. REVIEW OF CONTROL OPTIONS FOR METHYL BROMIDE IN COMMODITY TREATMENT

    EPA Science Inventory

    The report describes recent developments in the control of methyl bromide (MeBr) and discusses technical considerations and requirements for and economic feasibility of recovery. (NOTE: MeBr, fumigant for agricultural commodities, is an ozone depleting chemical. The U.S. EPA has ...

  13. REVIEW OF CONTROL OPTIONS FOR METHYL BROMIDE IN COMMODITY TREATMENT

    EPA Science Inventory

    The report describes recent developments in the control of methyl bromide (MeBr) and discusses technical considerations and requirements for and economic feasibility of recovery. (NOTE: MeBr, fumigant for agricultural commodities, is an ozone depleting chemical. The U.S. EPA has ...

  14. 75 FR 5582 - Methyl Bromide; Amendments to Terminate Uses

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-03

    ... or on alfalfa hay and cottonseed for these product registrations. These are the last products containing the pesticide methyl bromide registered for use on alfalfa hay and cotton seed in the United... post-harvest alfalfa hay and post-harvest cottonseed uses is prohibited after October 31, 2009,...

  15. Methyl bromide phase out could affect future reforestation efforts

    USDA-ARS?s Scientific Manuscript database

    Methyl bromide has long been an integral component in producing healthy tree seedlings in forest nurseries of California, Idaho, Montana, Oregon and Washington. The fumigant was supposed to be completely phased out of use in the United States of America by 2005, but many forest nurseries continue to...

  16. 77 FR 31564 - Notice of Availability of a Treatment Evaluation Document; Methyl Bromide Fumigation of Cottonseed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-29

    ...; Methyl Bromide Fumigation of Cottonseed AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION... add to the Plant Protection and Quarantine Treatment Manual a treatment schedule for methyl bromide... EPA or by any other Federal entity. We have determined a new methyl bromide fumigation treatment...

  17. 77 FR 48153 - Protection of Stratospheric Ozone: Request for Methyl Bromide Critical Use Exemption Applications...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-13

    ... AGENCY Protection of Stratospheric Ozone: Request for Methyl Bromide Critical Use Exemption Applications... Register requesting applications for the Critical Use Exemption from the phaseout of methyl bromide for 2015. On August 3, 2012, EPA received a letter from methyl bromide stakeholders requesting an extension...

  18. 78 FR 36507 - Notice of Availability of a Treatment Evaluation Document; Methyl Bromide Fumigation of Blueberries

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ...; Methyl Bromide Fumigation of Blueberries AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION... schedule for methyl bromide fumigation of blueberries for Mediterranean fruit fly and South American fruit...-i-1-1) requires blueberries to be treated with methyl bromide at 70 F or above using 2 lbs...

  19. 78 FR 32646 - Protection of Stratospheric Ozone: Request for Methyl Bromide Critical Use Exemption Applications...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-31

    ... using for their commodity. Structures and Facilities (flour mills, rice mills, pet food) Published data... the last three years; the rate, volume, and target CT of methyl bromide at each location; volume of... methyl bromide over the last three ] years; the rate, volume, and target CT of methyl bromide at each...

  20. Isotopic Composition of Marine-Derived Methyl Bromide

    NASA Astrophysics Data System (ADS)

    Cottrell, L. D.; Mak, J. E.

    2001-12-01

    Methyl bromide (CH3Br) is the largest source of atmospheric bromine, which catalytically destroys stratospheric ozone 50-60 times more efficiently than chlorine. Despite much attention that has been focused on CH3Br in recent years, it has proven difficult to constrain its global budget. It is of particular interest to compare the magnitude of the anthropogenic source with that of the largest naturally occurring source, which is believed to be marine-derived. One way to estimate the relative strengths of these sources is to use stable carbon isotopes as a tracer. The viability of this approach relies on the distinctiveness of the isotopic composition of each source and, in the case of marine-derived CH3Br, on the extent to which isotopic fracionation occurs during chemical degradation in the water column. Once produced in the water column, CH3Br undergoes ion exchange (CH3Br + Cl- \\rightarrow CH3Cl +Br-) and hydrolysis (CH3Br + H2O \\rightarrow CH3OH +HBr), which changes the isotopic composition of the remaining CH3Br. In this study we measured the fractionation factor (k12/k13) for both ion exchange and hydrolysis of CH3Br in sea water, and then used a simple air-sea exchange model to determine the extent of fractionation that occurs in the water column. Using a range of 20-30 per mil for the isotopic composition of marine biologically produced methyl bromide, the predicted isotopic composition of CH3Br emitted to the atmosphere is significantly enriched and further distinguished from the average anthropogenic signature of -54.4 per mil. An isotopic study may therefore prove to be a useful tool for constraining the methyl bromide budget.

  1. Off-site air monitoring following methyl bromide chamber and building fumigations and evaluation of the ISCST air dispersion model

    SciTech Connect

    Barry, T.; Swgawa, R.; Wofford, P.

    1995-12-31

    The Department of Pesticide Regulation`s preliminary risk characterization of methyl bromide indicated an inadequate margin of safety for several exposure scenarios. Characterization of the air concentrations associated with common methyl bromide use patterns was necessary to determine specific scenarios that result in an unacceptable margin of safety. Field monitoring data were used in conjunction with the Industrial Source Complex, Short Tenn (ISCST) air dispersion model to characterize air concentrations associated with various types of methyl bromide applications. Chamber and building fumigations were monitored and modelled. For each fumigation the emission rates, chamber or building specifications and on-site meteorological data were input into the ISCST model. The model predicted concentrations were compared to measured air concentrations. The concentrations predicted by the ISCST model reflect both the pattern and magnitude of the measured concentrations. Required buffer zones were calculated using the ISCST output.

  2. Budget of Methyl Bromide in the Atmosphere: Isotopic Constraints

    NASA Astrophysics Data System (ADS)

    Bill, M.; Miller, L. G.; Rhew, R. C.; Goldstein, A. H.

    2001-12-01

    Bromine radicals contribute significantly to stratospheric ozone loss through coupled reactions with ClO, HO2, and NO2 radicals. Bromine is approximately 40-100 times more effective, atom for atom, at destroying ozone than chlorine. For instance, Br coupled reactions are responsible for 30 to 50% of the total ozone loss in the polar vortex. The largest source of bromine to the stratosphere is methyl bromide (CH3Br). CH3Br has a concentration in the troposphere of about 10 pptv, a total estimated lifetime of 0.6 to 0.9 years, and has the highest concentration of any long lived organobromine. Unlike chlorofluorocarbons, which are produced entirely by humans, methyl bromide is produced by both anthropogenic and natural processes. We are developing the use of stable isotopes to constrain the budget of CH3Br through quantification of the source signatures and the isotopic fractionations associated with sinks. The largest natural sources appear to be biological production in oceans ( ~35%), biomass burning ( ~13%), and salt marshes ( ~10%). Thus far, the only natural emissions to be isotopically characterized is from salt marsh plants. Carbon isotopic ratios of CH3Br emitted from the salt marsh have a strong diurnal variation from -65\\permil during daytime when emission rates are highest to -12\\permil at night when emissions are ~13% of the daytime rates. The \\delta13C weighted mean of salt marsh emission is -43\\permil CH3Br. Anthropogenically produced CH3Br is used for fumigation of soils, harvested crops and structures, and represents approximately 30% of the total source flux. The fumigation of harvested crops and structures constitutes approximately one third of the anthropogenic source to the atmosphere and, because the release rate of applied CH3Br approaches 100%, it should have a mean isotopic composition equal to industrially manufactured CH3Br, -54.4\\permil. However during soil fumigation, some of the CH3Br is consumed insitu causing isotopic fractionation

  3. Destruction of methyl bromide sorbed to activated carbon by thiosulfate and electrolysis

    USDA-ARS?s Scientific Manuscript database

    Methyl bromide is widely used as a fumigant for post-harvest and quarantine uses at port facilities due to the low treatment times required, but it is vented to the atmosphere after its use. Due to the potential contributions of methyl bromide to stratospheric ozone depletion, technologies for the c...

  4. Solid phase microextraction for active or passive sampling of methyl bromide during fumigations

    USDA-ARS?s Scientific Manuscript database

    The high diffusivity and volatility of methyl bromide make it an ideal compound for Solid Phase Micro Extraction (SPME)-based sampling of air prior to gas-chromatographic quantifications. SPME fibers can be used as active methyl bromide samplers, with high capacities and an equilibrium time of 1-2 m...

  5. Bacterial oxidation of methyl bromide in Mono Lake, California

    USGS Publications Warehouse

    Connell, T.L.; Joye, S.B.; Miller, L.G.; Oremland, R.S.

    1997-01-01

    The oxidation of methyl bromide (MeBr) in the water column of Mono Lake, CA, was studied by measuring the formation of H14CO3 from [14C]MeBr. Potential oxidation was detected throughout the water column, with highest rates occurring in the epilimnion (5-12 m depth). The oxidation of MeBr was eliminated by filter-sterilization, thereby demonstrating the involvement of bacteria. Vertical profiles of MeBr activity differed from those obtained for nitrification and methane oxidation, indicating that MeBr oxidation is not simply a co-oxidation process by either nitrifiers or methanotrophs. Furthermore, specific inhibitors of methane oxidation and/or nitrification (e.g., methyl fluoride, acetylene, allyl sulfide) had no effect upon the rate of MeBr oxidation in live samples. Of a variety of potential electron donors added to Mono Lake water, only trimethylamine resulted in the stimulation of MeBr oxidation. Cumulatively, these results suggest that the oxidation of MeBr in Mono Lake waters is attributable to trimethylamine-degrading methylotrophs. Neither methyl chloride nor methanol inhibited the oxidation of [14C]MeBr in live samples, indicating that these bacteria directly oxidized MeBr rather than the products of MeBr nucleophilic substitution reactions.

  6. Derivation of an occupational exposure limit (OEL) for n-propyl bromide using an improved methodology.

    PubMed

    Rozman, Karl K; Doull, John

    2002-10-01

    n-Propyl bromide is an industrial solvent with increasing production volume due to its use as a replacement for fluorohydrocarbons. Therefore, the number of occupationally exposed workers is growing accordingly. This manuscript presents a thorough evaluation of available animal and human data to derive an occupational exposure limit (OEL) for n-propyl bromide. In addition, structure activity relationship within the homologous series of methyl, ethyl, and n-propyl bromide and an identical spectrum of effects caused by similar doses of 2-propyl bromide are used to increase the confidence of the analysis. The structure activity relationship was entirely consistent for acute and subchronic (neurologic, reproductive, and hematopoietic) toxicities and for mutagenic potency in that CH3Br was more toxic than CH3CH2Br, which in turn was more toxic than CH3CH2CH2Br in every case in all species studied, including humans. Animals appeared to be similarly susceptible as, or slightly more susceptible than, humans to n-propyl bromide's toxicity. An OEL (60-90 ppm) was derived from a limited human study and supported by an across-the-toxic-spectrum comparison of animal and human data for both n-propyl and 2-propyl bromide. A carcinogenic classification was not deemed necessary at the recommended OEL based on very low mutagenic potency and the consistent structure activity relationship across the homologous series of these alkyl bromides.

  7. Error Evaluation of Methyl Bromide Aerodynamic Flux Measurements

    USGS Publications Warehouse

    Majewski, M.S.

    1997-01-01

    Methyl bromide volatilization fluxes were calculated for a tarped and a nontarped field using 2 and 4 hour sampling periods. These field measurements were averaged in 8, 12, and 24 hour increments to simulate longer sampling periods. The daily flux profiles were progressively smoothed and the cumulative volatility losses increased by 20 to 30% with each longer sampling period. Error associated with the original flux measurements was determined from linear regressions of measured wind speed and air concentration as a function of height, and averaged approximately 50%. The high errors resulted from long application times, which resulted in a nonuniform source strength; and variable tarp permeability, which is influenced by temperature, moisture, and thickness. The increase in cumulative volatilization losses that resulted from longer sampling periods were within the experimental error of the flux determination method.

  8. 78 FR 14508 - Notice of Affirmation of Addition of a Treatment Schedule for Methyl Bromide Fumigation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-06

    ... Treatment Schedule for Methyl Bromide Fumigation of Cottonseed AGENCY: Animal and Plant Health Inspection... methyl bromide fumigation of cottonseed for the fungal plant pathogen Fusarium oxysporum f. sp... No. APHIS- 2012-0040), announcing our determination that a new methyl bromide fumigation treatment...

  9. Bioreactors for removing methyl bromide following contained fumigations

    USGS Publications Warehouse

    Miller, L.G.; Baesman, S.M.; Oremland, R.S.

    2003-01-01

    Use of methyl bromide (MeBr) as a quarantine, commodity, or structural fumigant is under scrutiny because its release to the atmosphere contributes to the depletion of stratospheric ozone. A closed-system bioreactor consisting of 0.5 L of a growing culture of a previously described bacterium, strain IMB-1, removed MeBr (> 110 ??mol L-1) from recirculating air. Strain IMB-1 grew slowly to high cell densities in the bioreactor using MeBr as its sole carbon and energy source. Bacterial oxidation of MeBr produced CO2 and hydrobromic acid (HBr), which required continuous neutralization with NaOH for the system to operate effectively. Strain IMB-1 was capable of sustained oxidation of large amounts of MeBr (170 mmol in 46 d). In an open-system bioreactor (10-L fermenter), strain IMB-1 oxidized a continuous supply of MeBr (220 ??mol L-1 in air). Growth was continuous, and 0.5 mol of MeBr was removed from the air supply in 14 d. The specific rate of MeBr oxidation was 7 ?? 10-16 mol cell-1 h-1. Bioreactors such as these can therefore be used to remove large quantities of contaminant MeBr, which opens the possibility of biodegradation as a practical means for its disposal.

  10. Effect of Methyl Bromide on Mycorrhizae and Growth of Sweetgum Seedlings

    Treesearch

    T. H. Filer; E. R. Toole

    1968-01-01

    Fumigation of nursery beds with methyl bromide improved sweetgum, growth by reducing the population of soil-inhabiting pathogens . Although mycorrhizal fungi were reduced, sufficient inoculum survived for rapid mycorrhizal development

  11. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Treatment Longer than 8 Hours

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  12. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Treatment 8 Hours or Less

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  13. Drip application of methyl bromide alternative chemicals for control of soilborne pathogens and weeds.

    PubMed

    Gerik, James S; Hanson, Bradley D

    2011-09-01

    Producers of several high-value crops in California have traditionally used preplant soil fumigation with methyl bromide/chloropicrin combinations. Although methyl bromide has been phased out since 2005, several crop industries, including cut flower producers, have continued methyl bromide use under Critical Use Exemptions, a provision of the Montreal Protocol. This research was conducted to evaluate newer, emerging methyl bromide alternative chemicals. Two field trials were conducted to test several emerging chemicals in combination with metam sodium as replacements for methyl bromide. Emerging chemicals included 2-bromoethanol, dimethyl disulfide, furfural, propylene oxide and sodium azide. Weed and pathogen populations were measured after chemical application, and seed viability was assessed from weed seed previously buried in the plots. In the first trial, the emerging chemicals did not improve pest control compared with metam sodium alone. However, in the second trial, several of these chemicals did improve the pest control performance of metam sodium. The emerging alternative chemicals have the potential to provide better control of soilborne pathogens and weeds when used with metam sodium than metam sodium alone. Registration of these materials could provide California growers with a broader choice of tools compared with the limited methyl bromide alternatives now available. This article is a US Government work and is in the public domain in the USA. Published 2011 by John Wiley & Sons, Ltd.

  14. Bacterial oxidation of methyl bromide in fumigated agricultural soils

    USGS Publications Warehouse

    Miller, L.G.; Connell, T.L.; Guidetti, J.R.; Oremland, R.S.

    1997-01-01

    The oxidation of [14C]methyl bromide ([14C]MeBr) to 14CO2 was measured in field experiments with soils collected from two strawberry plots fumigated with mixtures of MeBr and chloropicrin (CCI3NO2). Although these fumigants are considered potent biocides, we found that the highest rates of MeBr oxidation occurred 1 to 2 days after injection when the fields were tarped, rather than before or several days after injection. No oxidation of MeBr occurred in heat-killed soils, indicating that microbes were the causative agents of the oxidation. Degradation of MeBr by chemical and/or biological processes accounted for 20 to 50% of the loss of MeBr during fumigation, with evasion to the atmosphere inferred to comprise the remainder. In laboratory incubations, complete removal of [14C]MeBr occurred within a few days, with 47 to 67% of the added MeBr oxidized to 14CO2 and the remainder of counts associated with the solid phase. Chloropicrin inhibited the oxidation of MeBr, implying that use of this substance constrains the extent of microbial degradation of MeBr during fumigation. Oxidation was by direct bacterial attack of MeBr and not of methanol, a product of the chemical hydrolysis of MeBr. Neither nitrifying nor methane-oxidizing bacteria were sufficiently active in these soils to account for the observed oxidation of MeBr, nor could the microbial degradation of MeBr be linked to cooxidation with exogenously supplied electron donors. However, repeated addition of MeBr to live soils resulted in higher rates of its removal, suggesting that soil bacteria used MeBr as an electron donor for growth. To support this interpretation, we isolated a gram-negative, aerobic bacterium from these soils which grew with MeBr as a sole source of carbon and energy.

  15. Carbon isotope fractionation of methyl bromide during agricultural soil fumigations

    USGS Publications Warehouse

    Bill, M.; Miller, L.G.; Goldstein, Allen H.

    2002-01-01

    The isotopic composition of methyl bromide (CH3Br) has been suggested to be a potentially useful tracer for constraining the global CH3Br budget. In order to determine the carbon isotopic composition of CH3Br emitted from the most significant anthropogenic application (pre-plant fumigation) we directly measured the ??13C of CH3Br released during commercial fumigation. We also measured the isotopic fractionation associated with degradation in agricultural soil under typical field fumigation conditions. The isotopic composition of CH3Br collected in soil several hours after injection of the fumigant was -44.5??? and this value increased to -20.7??? over the following three days. The mean kinetic isotope effect (KIE) associated with degradation of CH3Br in agricultural soil (12???) was smaller than the reported value for methylotrophic bacterial strain IMB-1, isolated from previously fumigated agricultural soil, but was similar to methylotrophic bacterial strain CC495, isolated from a pristine forest litter zone. Using this fractionation associated with the degradation of CH3Br in agricultural soil and the mean ??13C of the industrially manufactured CH3Br (-54.4???), we calculate that the agricultural soil fumigation source has a carbon isotope signature that ranges from -52.8??? to -42.0???. Roughly 65% of industrially manufactured CH3Br is used for field fumigations. The remaining 35% is used for structural and post-harvest fumigations with a minor amount used during industrial chemical manufacturing. Assuming that the structural and post-harvest fumigation sources of CH3Br are emitted without substantial fractionation, we calculate that the ??13C of anthropogenically emitted CH3Br ranges from -53.2??? to -47.5???.

  16. The fate of alternative soil fumigants to methyl bromide

    NASA Astrophysics Data System (ADS)

    Qin, R.; Gao, S.

    2011-12-01

    Soil fumigation is an important agricultural practice for the control of soil-borne pests. Since the phase-out of methyl bromide, due to its role in the depletion of stratospheric ozone, several alternatives such as 1,3-dichloropropene (1,3-D), chloropicrin (CP), and dimethyl disulfide (DMDS) are being increasingly used. The major processes and factors affecting the fate of these chemicals are evaluated. The high volatility of fumigants leads to high emission loss when no proper containment is used. Recent tarping technology using low permeability films can significantly reduce emissions. Fumigant degradation rate becomes critical to the determination of fumigation rate that affects efficacy and residence time in soil. A series of laboratory incubation experiments were carried out to determine degradation rate of 1,3-D isomers, CP and DMDS in five different soils collected from California and Florida. Fumigant degradation rates depend highly on the amounts of fumigants in soil, chemical characteristics, and soil conditions. Fumigant degradation rate were found to increase for all fumigants as the fumigant amounts in soil decreased. The changes were smaller for 1,3-D isomers compared to CP and DMDS. In soils with the lowest application rate, the degradation rate of fumigants is in the order of CP > DMDS > cis-1,3-D > trans-1,3-D. Soil and environmental factors also affect fumigant degradation rate. These findings suggest that a proper application rate should be determined for specific fumigants in a soil when using low permeability tarp in order to achieve sufficient fumigation efficacy during a certain period of time while minimizing potential surge of emissions after tarp removal and/or long residence time in soil that may cause phytotoxicity or leaching.

  17. Depleting methyl bromide residues in soil by reaction with bases.

    PubMed

    Xuan, Richeng; Ashworth, Daniel J; Luo, Lifang; Wang, Haizhen; Yates, Scott R

    2010-12-01

    Despite generally being considered the most effective soil fumigant, methyl bromide (MeBr) use is being phased out because its emissions from soil can lead to stratospheric ozone depletion. However, a large amount is still currently used due to Critical Use Exemptions. As strategies for reducing the postfumigation emissions of MeBr from soil, Ca(OH)(2), K(2)CO(3), and NH(3) were assessed as means of promoting MeBr degradation. Ammonia aqueous solution (NH(4)OH) was the most effective, because MeBr can be degraded by both hydrolysis and ammonolysis. At 20 °C, the half-lives (t(1/2)) of MeBr were 18.0, 2.5, and 1.3 h in 0.1, 1.0, and 2.0 M NH(4)OH, respectively. In 1.0 M NH(4)OH, increasing the solution temperature to 40 °C reduced the half-life of MeBr to 0.23 h. Ammonia amendment to moist soil also promoted MeBr transformation, and the MeBr degradation rate increased with increasing soil temperature. NH(4)OH (30%, 16 M) very effectively reacted with MeBr that was contained under plastic film. Under Hytibar (a virtually impermeable film, VIF), over 99.5% of the MeBr could be destroyed by 30% NH(4)OH in 8 h at 20 °C. On the basis of these results, good management practices (i.e., VIF plus NH(4)OH) could be developed for continued use of MeBr as a soil fumigant under Critical Use Exemptions, without significant emissions.

  18. Methyl chloride and methyl bromide emissions from baking: an unrecognized anthropogenic source.

    PubMed

    Thornton, Brett F; Horst, Axel; Carrizo, Daniel; Holmstrand, Henry

    2016-05-01

    Methyl chloride and methyl bromide (CH3Cl and CH3Br) are the largest natural sources of chlorine and bromine, respectively, to the stratosphere, where they contribute to ozone depletion. We report the anthropogenic production of CH3Cl and CH3Br during breadbaking, and suggest this production is an abiotic process involving the methyl ester functional groups in pectin and lignin structural polymers of plant cells. Wide variations in baking styles allow only rough estimates of this flux of methyl halides on a global basis. A simple model suggests that CH3Br emissions from breadbaking likely peaked circa 1990 at approximately 200tonnes per year (about 0.3% of industrial production), prior to restrictions on the dough conditioner potassium bromate. In contrast, CH3Cl emissions from breadbaking may be of similar magnitude as acknowledged present-day CH3Cl industrial emissions. Because the mechanisms involve functional groups and compounds widely found in plant materials, this type of methyl halide production may occur in other cooking techniques as well.

  19. Improved light olefin yield from methyl bromide coupling over modified SAPO-34 molecular sieves.

    PubMed

    Zhang, Aihua; Sun, Shouli; Komon, Zachary J A; Osterwalder, Neil; Gadewar, Sagar; Stoimenov, Peter; Auerbach, Daniel J; Stucky, Galen D; McFarland, Eric W

    2011-02-21

    As an alternative to the partial oxidation of methane to synthesis gas followed by methanol synthesis and the subsequent generation of olefins, we have studied the production of light olefins (ethylene and propylene) from the reaction of methyl bromide over various modified microporous silico-aluminophosphate molecular-sieve catalysts with an emphasis on SAPO-34. Some comparisons of methyl halides and methanol as reaction intermediates in their conversion to olefins are presented. Increasing the ratio of Si/Al and incorporation of Co into the catalyst framework improved the methyl bromide yield of light olefins over that obtained using standard SAPO-34.

  20. The ocean in near equilibrium with atmospheric methyl bromide

    NASA Astrophysics Data System (ADS)

    Hu, Lei; Yvon-Lewis, Shari; Liu, Yina; Bianchi, Thomas S.

    2012-09-01

    Saturation-anomaly measurements of methyl bromide (CH3Br) were made in the eastern Pacific (3/30-4/27, 2010) and the eastern Atlantic (10/25-11/26, 2010) to assess the oceanic saturation state as the phaseout of fumigation - non-Quarantine and Pre-Shipment (non-QPS) uses of CH3Br nears completion and atmospheric concentrations continue to decline. These cruises occurred 16 years after the Bromine Latitudinal Air-Sea Transect (BLAST) cruises, which were conducted in the same regions and first established a global oceanic net sink of -12.6 Gg yr-1 for atmospheric CH3Br in 1994. Results from this study suggest saturation anomalies of CH3Br in the surface ocean have become less negative than those observed 16 years ago as the atmospheric burden has declined over the past decade. The global net sea-to-air flux was estimated at 0 to 3 Gg yr-1 in 2010, suggesting that the ocean may become a net small source to atmospheric CH3Br. There are no significant differences between this study and previous studies for measured biological loss rate constants and calculated annual production rates, suggesting that annual production rates and biological degradation rate constants for CH3Br in the surface ocean have likely remained relatively constant over the past 16 years. When including the biological loss rate constants from this study and all previous studies, the mean global biological loss rate constant is constrained to 0.05 ± 0.01 d-1 (at a 95% confidence level). Combining chemical and eddy degradation rate constants, and using an updated gas transfer velocity, we estimate the CH3Br partial atmospheric lifetime with respect to oceanic loss to be 3.1 (2.3 to 5.0) years. Although the new partial atmospheric lifetime is about 1.3 years longer than the best prior estimate, it does not change the overall atmospheric lifetime of CH3Br, 0.8 (0.7-0.9) years.

  1. Bacterial Oxidation of Methyl Bromide in Fumigated Agricultural Soils

    PubMed Central

    Miller, L. G.; Connell, T. L.; Guidetti, J. R.; Oremland, R. S.

    1997-01-01

    The oxidation of [(sup14)C]methyl bromide ([(sup14)C]MeBr) to (sup14)CO(inf2) was measured in field experiments with soils collected from two strawberry plots fumigated with mixtures of MeBr and chloropicrin (CCl(inf3)NO(inf2)). Although these fumigants are considered potent biocides, we found that the highest rates of MeBr oxidation occurred 1 to 2 days after injection when the fields were tarped, rather than before or several days after injection. No oxidation of MeBr occurred in heat-killed soils, indicating that microbes were the causative agents of the oxidation. Degradation of MeBr by chemical and/or biological processes accounted for 20 to 50% of the loss of MeBr during fumigation, with evasion to the atmosphere inferred to comprise the remainder. In laboratory incubations, complete removal of [(sup14)C]MeBr occurred within a few days, with 47 to 67% of the added MeBr oxidized to (sup14)CO(inf2) and the remainder of counts associated with the solid phase. Chloropicrin inhibited the oxidation of MeBr, implying that use of this substance constrains the extent of microbial degradation of MeBr during fumigation. Oxidation was by direct bacterial attack of MeBr and not of methanol, a product of the chemical hydrolysis of MeBr. Neither nitrifying nor methane-oxidizing bacteria were sufficiently active in these soils to account for the observed oxidation of MeBr, nor could the microbial degradation of MeBr be linked to cooxidation with exogenously supplied electron donors. However, repeated addition of MeBr to live soils resulted in higher rates of its removal, suggesting that soil bacteria used MeBr as an electron donor for growth. To support this interpretation, we isolated a gram-negative, aerobic bacterium from these soils which grew with MeBr as a sole source of carbon and energy. PMID:16535728

  2. Comparison of Methyl Bromide and Other Nematicides for Control of Nematodes in Peanut

    PubMed Central

    Rodríguez-Kábana, R.; Robertson, D. G.; King, P. S.

    1987-01-01

    The efficacy of methyl bromide for control ofMeloidogyne arenaria and to increase yields of 'Florunner' peanut (Arachis hypogaea) was studied in a field at the Wiregrass Substation near Headland, Alabama. Methyl bromide was applied in the row at a depth of 35 cm using a subsoiler-bedder 2 weeks before planting at rates of 0, 34, 50, 67, 101, and 118 kg a.i./ha. Methyl bromide treatments of 67 kg a.i./ha or higher resulted in significant (P = 0.05) yield increases similar to those obtained in the same experiment with at-plant applications of aldicarb (2.2 kg a.i./ha), EDB (1.55 ml a.i./m row), or 1,3-D (5.10 ml a.i./m row). The relation between yield (Y) and methyl bromide rate (x) was described (R² = 0.97**) by the exponential function: Y = 2,302.963eb, where b = (- 1.901 - ln x)²/169.482. M. arenaria juvenile populations in soil in mid-August were too low to permit establishment of a relation between application rate of methyl bromide and size of the population. PMID:19290276

  3. Methyl bromide: ocean sources, ocean sinks, and climate sensitivity

    NASA Technical Reports Server (NTRS)

    Anbar, A. D.; Yung, Y. L.; Chavez, F. P.

    1996-01-01

    The oceans play an important role in the geochemical cycle of methyl bromide (CH3Br), the major carrier of O3-destroying bromine to the stratosphere. The quantity of CH3Br produced annually in seawater is comparable to the amount entering the atmosphere each year from natural and anthropogenic sources. The production mechanism is unknown but may be biological. Most of this CH3Br is consumed in situ by hydrolysis or reaction with chloride. The size of the fraction which escapes to the atmosphere is poorly constrained; measurements in seawater and the atmosphere have been used to justify both a large oceanic CH3Br flux to the atmosphere and a small net ocean sink. Since the consumption reactions are extremely temperature-sensitive, small temperature variations have large effects on the CH3Br concentration in seawater, and therefore on the exchange between the atmosphere and the ocean. The net CH3Br flux is also sensitive to variations in the rate of CH3Br production. We have quantified these effects using a simple steady state mass balance model. When CH3Br production rates are linearly scaled with seawater chlorophyll content, this model reproduces the latitudinal variations in marine CH3Br concentrations observed in the east Pacific Ocean by Singh et al. [1983] and by Lobert et al. [1995]. The apparent correlation of CH3Br production with primary production explains the discrepancies between the two observational studies, strengthening recent suggestions that the open ocean is a small net sink for atmospheric CH3Br, rather than a large net source. The Southern Ocean is implicated as a possible large net source of CH3Br to the atmosphere. Since our model indicates that both the direction and magnitude of CH3Br exchange between the atmosphere and ocean are extremely sensitive to temperature and marine productivity, and since the rate of CH3Br production in the oceans is comparable to the rate at which this compound is introduced to the atmosphere, even small

  4. Methyl bromide: ocean sources, ocean sinks, and climate sensitivity

    NASA Technical Reports Server (NTRS)

    Anbar, A. D.; Yung, Y. L.; Chavez, F. P.

    1996-01-01

    The oceans play an important role in the geochemical cycle of methyl bromide (CH3Br), the major carrier of O3-destroying bromine to the stratosphere. The quantity of CH3Br produced annually in seawater is comparable to the amount entering the atmosphere each year from natural and anthropogenic sources. The production mechanism is unknown but may be biological. Most of this CH3Br is consumed in situ by hydrolysis or reaction with chloride. The size of the fraction which escapes to the atmosphere is poorly constrained; measurements in seawater and the atmosphere have been used to justify both a large oceanic CH3Br flux to the atmosphere and a small net ocean sink. Since the consumption reactions are extremely temperature-sensitive, small temperature variations have large effects on the CH3Br concentration in seawater, and therefore on the exchange between the atmosphere and the ocean. The net CH3Br flux is also sensitive to variations in the rate of CH3Br production. We have quantified these effects using a simple steady state mass balance model. When CH3Br production rates are linearly scaled with seawater chlorophyll content, this model reproduces the latitudinal variations in marine CH3Br concentrations observed in the east Pacific Ocean by Singh et al. [1983] and by Lobert et al. [1995]. The apparent correlation of CH3Br production with primary production explains the discrepancies between the two observational studies, strengthening recent suggestions that the open ocean is a small net sink for atmospheric CH3Br, rather than a large net source. The Southern Ocean is implicated as a possible large net source of CH3Br to the atmosphere. Since our model indicates that both the direction and magnitude of CH3Br exchange between the atmosphere and ocean are extremely sensitive to temperature and marine productivity, and since the rate of CH3Br production in the oceans is comparable to the rate at which this compound is introduced to the atmosphere, even small

  5. Methyl bromide: ocean sources, ocean sinks, and climate sensitivity.

    PubMed

    Anbar, A D; Yung, Y L; Chavez, F P

    1996-03-01

    The oceans play an important role in the geochemical cycle of methyl bromide (CH3Br), the major carrier of O3-destroying bromine to the stratosphere. The quantity of CH3Br produced annually in seawater is comparable to the amount entering the atmosphere each year from natural and anthropogenic sources. The production mechanism is unknown but may be biological. Most of this CH3Br is consumed in situ by hydrolysis or reaction with chloride. The size of the fraction which escapes to the atmosphere is poorly constrained; measurements in seawater and the atmosphere have been used to justify both a large oceanic CH3Br flux to the atmosphere and a small net ocean sink. Since the consumption reactions are extremely temperature-sensitive, small temperature variations have large effects on the CH3Br concentration in seawater, and therefore on the exchange between the atmosphere and the ocean. The net CH3Br flux is also sensitive to variations in the rate of CH3Br production. We have quantified these effects using a simple steady state mass balance model. When CH3Br production rates are linearly scaled with seawater chlorophyll content, this model reproduces the latitudinal variations in marine CH3Br concentrations observed in the east Pacific Ocean by Singh et al. [1983] and by Lobert et al. [1995]. The apparent correlation of CH3Br production with primary production explains the discrepancies between the two observational studies, strengthening recent suggestions that the open ocean is a small net sink for atmospheric CH3Br, rather than a large net source. The Southern Ocean is implicated as a possible large net source of CH3Br to the atmosphere. Since our model indicates that both the direction and magnitude of CH3Br exchange between the atmosphere and ocean are extremely sensitive to temperature and marine productivity, and since the rate of CH3Br production in the oceans is comparable to the rate at which this compound is introduced to the atmosphere, even small

  6. Natural methyl bromide and methyl chloride emissions from coastal salt marshes.

    PubMed

    Rhew, R C; Miller, B R; Weiss, R F

    2000-01-20

    Atmospheric methyl bromide (CH3Br) and methyl chloride (CH3Cl), compounds that are involved in stratospheric ozone depletion, originate from both natural and anthropogenic sources. Current estimates of CH3Br and CH3Cl emissions from oceanic sources, terrestrial plants and fungi, biomass burning and anthropogenic inputs do not balance their losses owing to oxidation by hydroxyl radicals, oceanic degradation, and consumption in soils, suggesting that additional natural terrestrial sources may be important. Here we show that CH3Br and CH3Cl are released to the atmosphere from all vegetation zones of two coastal salt marshes. We see very large fluxes of CH3Br and CH3Cl per unit area: up to 42 and 570 micromol m(-2) d(-1), respectively. The fluxes show large diurnal, seasonal and spatial variabilities, but there is a strong correlation between the fluxes of CH3Br and those of CH3Cl, with an average molar flux ratio of roughly 1:20. If our measurements are typical of salt marshes globally, they suggest that such ecosystems, even though they constitute less than 0.1% of the global surface area, may produce roughly 10% of the total fluxes of atmospheric CH3Br and CH3Cl.

  7. Headspace gas chromatographic method for determination of methyl bromide in food ingredients

    SciTech Connect

    DeVries, J.W.; Broge, J.M.; Schroeder, J.P.; Bowers, R.H.; Larson, P.A.; Burns, N.M.

    1985-11-01

    A headspace gas chromatographic (GC) method, which can be automated, has been developed for determination of methyl bromide. This method has been applied to wheat, flour, cocoa, and peanuts. Samples to be analyzed are placed in headspace sample vials, water is added, and the vials are sealed with Teflon-lined septa. After an appropriate equilibration time at 32 degrees C, the samples are analyzed within 10 h. A sample of the headspace is withdrawn and analyzed on a gas chromatograph equipped with an electron capture detector (ECD). Methyl bromide levels were quantitated by comparison of peak area with a standard. The standard was generated by adding a known amount of methyl bromide to a portion of the matrix being analyzed and which was known to be methyl bromide free. The detection limit of the method was 0.4 ppb. The coefficient of variation (CV) was 6.5% for wheat, 8.3% for flour, 3.3% for cocoa, and 11.6% for peanuts.

  8. The history and future of methyl bromide alternatives in the southern United States

    Treesearch

    Tom E. Starkey

    2012-01-01

    This article gives a brief history of the efforts of the Southern Forest Nursery Management Cooperative (SFNMC) in testing methyl bromide (MBr) alternatives for soil fumigation. In the southeastern United States, fumigation with MBr has been the most commonly used method for producing high quality, pest-free forest seedlings in an environment that is conducive for soil...

  9. EVALUATION OF CONTAINMENT AND CONTROL OPTIONS FOR METHYL BROMIDE IN COMMODITY TREATMENT

    EPA Science Inventory

    The report gives results of an investigation of means for methyl bromide (MeBr) recovery, reuse, and destruction to prevent atmospheric emissions if its limited use were still allowed. (NOTE: MeBr is an ozone-depleting chemical scheduled to be phased out by the Clean Air Act by t...

  10. Eradicating European pine shoot moth on ornamental pines with methyl bromide.

    Treesearch

    V.M. Carolin; W.H. Klein; R.M. Thompson

    1962-01-01

    The recent introduction of the European pine shoot moth into this region poses a serious threat to natural pine stands. To combat this threat, quarantines were invoked and eradication programs undertaken. Destruction of infested trees has been used tentatively as an eradication technique. In the meantime, fumigation with methyl bromide was tested over the period of a...

  11. EPA Takes Action Against Illegal Methyl Bromide Use in Puerto Rico

    EPA Pesticide Factsheets

    (New York, N.Y.) As part of its ongoing work to address the illegal use of toxic pesticides containing methyl bromide in the Caribbean, the U.S. Environmental Protection Agency has issued legal complaints against two individuals and a pest control company

  12. 76 FR 34700 - Protection of Stratospheric Ozone: Request for Methyl Bromide Critical Use Exemption Applications...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-14

    ... AGENCY Protection of Stratospheric Ozone: Request for Methyl Bromide Critical Use Exemption Applications... FURTHER INFORMATION CONTACT: General Information: U.S. EPA Stratospheric Ozone Information Hotline, 1-800-296-1996; also http://www.epa.gov/ozone/mbr . Technical Information: Bill Chism, U.S....

  13. Methyl bromide release from activated carbon and the soil/water/carbon interface

    USDA-ARS?s Scientific Manuscript database

    Methyl Bromide (MB) is a major source of stratospheric bromine radical, a known depletor of ozone. The use of ozone-depleting chemicals, including MB, is regulated by the Montreal Protocol. Critical uses of MB are permitted, such as when postharvest fumigation is mandated by an importing country. Fo...

  14. Steam disinfestation as a methyl bromide alternative in California cut flower nurseries

    USDA-ARS?s Scientific Manuscript database

    Steam may be an effective alternative to methyl bromide in cut flower production in California. Advantages of steam include broad spectrum pest control and a zero hour re-entry interval. The principle disadvantage of sheet steaming is cost effectiveness due to current energy prices and application...

  15. Ultraviolet absorption cross-sections of methyl bromide at stratospheric temperatures

    NASA Astrophysics Data System (ADS)

    Gillotay, D.; Simon, P. C.

    1988-04-01

    The absorption cross-sections of methyl bromide (CH3Br) are measured between 180 nm and 260 nm at temperatures of 295 K, 255 K, 227 K, and 209 K. A parametrical formula is proposed to compute the absorption cross-sections for wavelengths between 200 nm and 260 nm and for temperatures between 210 K and 300 K.

  16. Methyl bromide and sulfuryl fluoride effectiveness against red flour beetle life stages

    USDA-ARS?s Scientific Manuscript database

    The efficacy of methyl bromide (MB) and sulfuryl fluoride (SF) for managing all life stages of the red flour beetle, Tribolium castaneum, was investigated in the Hal Ross Flour Mill at Kansas State University. Eggs, young larvae, large larvae, pupae, and adults confined in plastic compartments with ...

  17. Comments on alternatives to methyl bromide for quarantine purposes in forest nurseries

    Treesearch

    David B. South

    2008-01-01

    Viewpoints will vary in regards to the best alternative to methyl bromide (CH3Br) fumigation. In some cases, crop value will determine the best alternative. As the value of the crop increases, the rate (and cost) of the "best" treatment might increase as well. In addition, the recommendation will depend on if the individual has a "...

  18. The use of agricultural by-products to capture methyl bromide following post-harvest fumigation

    USDA-ARS?s Scientific Manuscript database

    Activated carbons were prepared from plum and peach stone as well as almond and walnut shell and comparatively evaluated as sorbents to minimize the atmospheric emission of methyl bromide following postharvest fumigations. A variety of methods were used to make the activated carbons and each is desc...

  19. Removal of methyl bromide in coastal seawater: Chemical and biological rates

    NASA Astrophysics Data System (ADS)

    King, Daniel B.; Saltzman, Eric S.

    1997-08-01

    A stable isotope tracer technique was used to investigate the loss rate of methyl bromide in surface ocean waters. Unfiltered and 0.2 μm-filtered or autoclaved aliquants of Biscayne Bay seawater samples were spiked with 13CH3Br at roughly 10-100 times ambient concentrations (50-800 pM) and incubated for 10-30 hours. The concentration of 13CH3Br was monitored using gas chromatography with isotope dilution mass spectrometry, with CD3Br as the isotope spike. Removal rates in unfiltered aliquants were significantly faster than in the 0.2 μm-filtered or autoclaved aliquants, indicating that some of the loss of methyl bromide was associated with particulate matter. Filtration experiments indicate that the particulate material responsible for methyl bromide loss is between 0.2 and 1.2 μm in diameter, suggesting that bacteria are likely to be responsible. The particulate-related removal of methyl bromide was inhibited by autoclaving, supporting a biological mechanism.

  20. Reduced rates and alternatives to methyl bromide for snapdragon production in Florida

    USDA-ARS?s Scientific Manuscript database

    A field trial was conducted to evaluate soil solarization, Midas™ (iodomethane:chloropicrin 50:50, Arysta LifeScience Corp., Cary, NC) and different rates and formulations of methyl bromide under standard and metalized films for the production of snapdragon (Antirrhinum majus) in Martin County, Flor...

  1. Methods to facilitate the adoption of alternatives to methyl bromide soil fumigation by California strawberry growers

    USDA-ARS?s Scientific Manuscript database

    The goal of this project is to facilitate the adoption of strawberry production systems that do not use methyl bromide (MB). The five year project initially focused on fumigant alternatives to MB. The project has resulted in increased use of barrier films that reduce fumigant emission. The focus s...

  2. Forest nurseries face critical choices with the loss of methyl bromide fumigation

    USDA-ARS?s Scientific Manuscript database

    Forest nurseries in the western United States have relied for decades on methyl bromide for the control of soilborne pathogens such as Cylindrocarpoin, Fusarium, and Pythium species that affect bareroot tree seedling production. However, increased state and federal regulations have led to a substan...

  3. Methyl Bromide Alternatives Area-Wide Pest Management Project - South Atlantic Progress Report

    USDA-ARS?s Scientific Manuscript database

    Protocols and Standard Operational Procedures (SOPs) were developed for collecting environmental and soil edaphic information during and after application of methyl bromide alternatives. Parameters measured included soil moisture, soil bulk density, percent moisture at field capacity (-0.3 bars wat...

  4. EVALUATION OF CONTAINMENT AND CONTROL OPTIONS FOR METHYL BROMIDE IN COMMODITY TREATMENT

    EPA Science Inventory

    The report gives results of an investigation of means for methyl bromide (MeBr) recovery, reuse, and destruction to prevent atmospheric emissions if its limited use were still allowed. (NOTE: MeBr is an ozone-depleting chemical scheduled to be phased out by the Clean Air Act by t...

  5. Evaluation of non-fumigant pesticides as methyl bromide alternatives for managing weeds in vegetables

    USDA-ARS?s Scientific Manuscript database

    The phase out of methyl bromide challenged vegetable growers’ abilities to control weeds in low-density polyethylene (LDPE) mulch production systems. The herbicides halosulfuron, fomesafen, s-metolachlor, and clomazone are needed as part of the pesticide program in LDP vegetable production to contr...

  6. Leisingera methylohalidivorans gen. nov., sp. nov., a marine methylotroph that grows on methyl bromide

    USGS Publications Warehouse

    Schaefer, J.K.; Goodwin, K.D.; McDonald, I.R.; Murrell, J.C.; Oremland, R.S.

    2002-01-01

    A marine methylotroph, designated strain MB2T, was isolated for its ability to grow on methyl bromide as a sole carbon and energy source. Methyl chloride and methyl iodide also supported growth, as did methionine and glycine betaine. A limited amount of growth was observed with dimethyl sulfide. Growth was also noted with unidentified components of the complex media marine broth 2216, yeast extract and Casamino acids. No growth was observed on methylated amines, methanol, formate, acetate, glucose or a variety of other substrates. Growth on methyl bromide and methyl iodide resulted in their oxidation to CO2 with stoichiometric release of bromide and iodide, respectively. Strain MB2T exhibited growth optima at NaCl and Mg2+ concentrations similar to that of seawater. Phylogenetic analysis of the 16S rDNA sequence placed this strain in the ??-Proteobacteria in proximity to the genera Ruegeria and Roseobacter. It is proposed that strain MB2T (= ATCC BAA-92T = DSM 14336T) be designated Leisingera methylohalidivorans gen. nov., sp. nov.

  7. Characterization of methyl bromide and methyl chloride fluxes at temperate freshwater wetlands

    NASA Astrophysics Data System (ADS)

    Hardacre, Catherine J.; Heal, Mathew R.

    2013-01-01

    Methyl bromide (CH3Br) and methyl chloride (CH3Cl) are important natural sources of halogens to the atmosphere. A total of 568 CH3Br and 418 CH3Cl net flux measurements were made for up to 2 years at the same locations within four different wetlands in Scotland. Mean (± 1 standard deviation (SD)) CH3Br and CH3Cl net fluxes across all measurements at each wetland were: Auchencorth Moss, 8 (± 7) and 3560 (± 1260) ng m-2 h-1; Old Castle Farm, 420 (± 70) and 500 (± 260) ng m-2 h-1; Red Moss of Balerno, 500 (± 90) and 140,000 (± 36,000) ng m-2 h-1; and St Margaret's Marsh, 3600 (± 600) and -270 (± 450) ng m-2 h-1. None of the wetlands was a large net sink. Where substantial emissions were observed, these followed seasonal trends, increasing early in the growing season and declining in early autumn. Some diurnal cycles were observed, with emissions greatest during the day, although lower emissions were present at night. None of the measured environmental parameters was a strong "universal" driver for fluxes, which were heterogeneous within and between the wetlands, and larger on average than reported to date; plant species appeared to be the dominant factor, the latter confirmed by vegetation removal experiments. Calluna vulgaris and Phragmites australis emitted particularly large amounts of CH3Br, the former also emitting substantial CH3Cl. While acknowledging the substantial uncertainties in extrapolating globally, observations from this work suggest that wetlands contribute more CH3Br and CH3Cl to the atmosphere than current World Meteorological Organization estimates.

  8. Chemical alternatives for soil fumigation with methyl bromide on tobacco seedbeds in nematode and weed control.

    PubMed

    Kutywayo, V

    2003-01-01

    The proposed phase out of methyl bromide necessitated the evaluation of a number of chemical alternatives to replace it. The recommended rate of application for methyl bromide, 50 g/m2 was evaluated over three years against various rates of 65% 1,3-Dichloropropene mixed with 35% chloropicrin (1,3-D/C-35); a combination of metham sodium and ethylene dibromide (EDB) and 65% 1,3-Dichloropropene (1,3-D) alone. Chloropicrin and 1,3-D have long been registered and used in Zimbabwe as individual chemicals and their combination as a single product had never been tested. 1,3-D/C-35 at 36.9 ml/m2 was as effective as methyl bromide in nematode and weed control and led to similar seed germination and seedling growth rate. A combination of EDB at 21 ml/m2 and metham sodium at 35 ml/m2 was also equally effective. The use of 1,3-D alone at 35 ml/m2 gave unsatisfactory weed control and led to a reduced seedling growth rate. Metham sodium alone at 35 ml/m2 gave comparable weed control, seed germination and seedling growth comparable with methyl bromide. However nematode control evaluated using a gall rating scale was reduced. 1,3-D/C-35 at 36.9 ml/m2 and metham sodium at 35 ml/m2 used in combination with EDB at 21 ml/m2 are therefore, possible replacements for methyl bromide soil fumigation in tobacco seedbeds.

  9. Novel use of aliphatic n-methyl ketones as a fumigant and alternative to methyl bromide for insect control.

    PubMed

    Zhu, Jiwei; Dhammi, Anirudh; van Kretschmar, Jaap B; Vargo, Edward L; Apperson, Charles S; Roe, R Michael

    2017-10-02

    Fumigants like phosphine, methyl bromide and sulfuryl fluoride are highly effective for the control of structural, storage and agricultural arthropod pests. Unfortunately, many of these synthetic compounds are highly toxic to people, many pests have developed resistance to these compounds, and methyl bromide, the "gold standard" for fumigants, was de-registered because of its depletion of the stratospheric ozone layer. Alternative fumigant chemistry is needed. Several plant species produce n-aliphatic methyl ketones to prevent plant herbivory. To examine the use of methyl ketones as a fumigant, structure-mortality studies were conducted using the red imported fire ant, Solenopsis invicta Buren, as a model. A new easy-to-use, inexpensive, and disposable bioassay system was developed for this work. The LC50 s for heptanone, octanone, nonanone and undecanone were 4.27, 5.11, 5.26 and 8.21 μg/cm(3) of ambient air, respectively. Although the former three methyl ketones were more effective than undecanone, subsequent research was conducted with 2-undecanone since this compound already has an US EPA registration as a biopesticide. In dose-response field studies, 12.4 ml of undecanone injected into mounds was the lowest application rate that produced no ant activity in the mound with no re-establishment of ants. Undecanone at reagent grade costs was more cost effective than methyl bromide for fire ants, adult German cockroaches and tobacco budworm eggs, but slightly more expensive for adult flour beetles. The naturally occurring methyl ketone, undecanone, has the potential to be an alternative to current fumigants for a variety of pest applications. This article is protected by copyright. All rights reserved.

  10. Strain IMB-1, a novel bacterium for the removal of methyl bromide in fumigated agricultural soils

    USGS Publications Warehouse

    Connell, Hancock T.L.; Costello, A.M.; Lidstrom, M.E.; Oremland, R.S.

    1998-01-01

    A facultatively methylotrophic bacterium, strain IMB-1, that has been isolated from agricultural soil grows on methyl bromide (MeBr), methyl iodide, methyl chloride, and methylated amines, as well as on glucose, pyruvate, or acetate. Phylogenetic analysis of its 16S rRNA gene sequence indicates that strain IMB-1 classes in the alpha subgroup of the class Proteobacteria and is closely related to members of the genus Rhizobium. The ability of strain IMB-1 to oxidize MeBr to CO2 is constitutive in cells regardless of the growth substrate. Addition of cell suspensions of strain IMB-1 to soils greatly accelerates the oxidation of MeBr, as does pretreatment of soils with low concentrations of methyl iodide. These results suggest that soil treatment strategies can be devised whereby bacteria can effectively consume MeBr during field fumigations, which would diminish or eliminate the outward flux of MeBr to the atmosphere.

  11. Atmospheric chemistry of toxic contaminants 4. Saturated halogenated aliphatics: Methyl bromide, epichlorhydrin, phosgene

    SciTech Connect

    Grosjean, D. )

    1991-01-01

    Mechanisms are outlined for the reactions that contribute to in-situ formation and atmospheric removal of the saturated halogenated aliphatic contaminants methyl bromide, epichlorhydrin, and phosgene. In-situ formation is important only for phosgene and involves the reaction of OH with chloroethenes and other chlorinated hydrocarbons. A ranking of these phosgene precursors is given using data for precursor ambient concentrations and chemical reactivity. The three toxic compounds studied are long-lived in the atmosphere, where removal of phosgene and methyl bromide by chemical reactions is negligibly slow. Epichlorhydrin is removed slowly by reaction with OH, leading to formaldehyde, chloroacetaldehyde, and the chlorinated peroxyacyl nitrate CH{sub 2}ClC(O)OONO{sub 2}.

  12. Evaluation of alternatives to methyl bromide in melon crops in Guatemala.

    PubMed

    Díaz-Pérez, M; Camacho-Ferre, F; Diánez-Martínez, F; De Cara-García, M; Tello-Marquina, J C

    2009-02-01

    The monoculture of melon in Guatemala has caused the massive appearance of plants with an analogous syndrome for the well-known disease commonly called melon collapse, or vine decline, causing significant losses in crops. Methyl bromide is commonly used to sterilize soil prior to planting in Guatemala, but it must be phased out by 2015. The objective of this study was to evaluate the technique of grafting melon onto hybrids of Cucurbita (Cucurbita maxima x Cucurbita moschata), as an alternative to using soil disinfectants (such as Metam sodium, 1,3-dichloropropene, and methyl bromide) for the control of collapse. The results suggested that both soil disinfection and grafting were not necessary in these locations, since there were no statistical differences in terms of yields between the treatments and the untreated control. Furthermore, these results demonstrate that decisions to disinfect the soil must be based on the firm identification of the causal agents, in addition to preliminary assessments of yield losses.

  13. Synthesis of dimethyl aryl acylsulfonium bromides from aryl methyl ketones in a DMSO-HBr system.

    PubMed

    Cao, Zhiling; Shi, Dahua; Qu, Yingying; Tao, Chuanzhou; Liu, Weiwei; Yao, Guowei

    2013-12-16

    A new, simplified method for the synthesis of dimethyl aryl acylsulfonium salts has been developed. A series of dimethyl aryl acylsulfonium bromides were prepared by the reaction of aryl methyl ketones with hydrobromic acid and dimethylsulfoxide (DMSO). This sulfonium salt confirms that bromine production and the bromination reaction take place in the DMSO-HBr oxidation system. What's more, it is also a key intermediate for the synthesis of arylglyoxals.

  14. A CHRONIC INHALATION STUDY OF METHYL BROMIDE TOXICITY IN B6C3F1 MICE. (FINAL REPORT TO THE NATIONAL TOXICOLOGY PROGRAM)

    SciTech Connect

    HABER, S.B.

    1987-06-26

    This report provides a detailed account of a two year chronic inhalation study of methyl bromide toxicity in B6C3Fl mice conducted for the National Toxicology Program. Mice were randomized into three dose groups (10, 33 and 100 ppm methyl bromide) and one control group (0 ppm) per sex and exposed 5 days/week, 6 hours/day, for a total of 103 weeks. Endpoints included body weight; clinical signs and mortality, and at 6, 15 and 24 months of exposure, animals were sacrificed for organ weights, hematology and histopathology. In addition, a subgroup of animals in each dosage group was monitored for neurobehavioral and neuropathological changes. After only 20 weeks of exposure, 48% of the males and 12% of the females in the 100 ppm group had died. Exposures were terminated in that group and the surviving mice were observed for the duration of the study. Exposure of B6C3Fl mice to methyl bromide, even for only 20 weeks, produced significant changes in growth rate, mortality, organ weights and neurobehavioral functioning. These changes occurred in both males and females, but were more pronounced in males.

  15. Replacing methyl bromide in annual strawberry production with glucosinolate-containing green manure crops.

    PubMed

    Lazzeri, Luca; Baruzzi, Gianluca; Malaguti, Lorena; Antoniacci, Loredana

    2003-09-01

    The use of biocidal green manure crops is an agronomic technique for amending soil with fresh organic matter containing volatile compounds active in controlling some soil-borne pests and diseases. Two new selections of the Brassicaceae family were cultivated, incorporated before planting strawberries and tested as an alternative to fumigation with methyl bromide. Two biocidal green manure crops (Brassica juncea L sel ISCI20, Eruca sativa Mill cv Nemat) containing glucosinolate-myrosinase systems, a conventional green manure (barley), untreated soil and a fumigated control were evaluated during two seasons. The effect of these soil management systems on subsequent strawberry performance was evaluated by monitoring yield and plant growth parameters. In both years, biocidal plant green manure treatments led to a fruit yield lower than with methyl bromide, but higher than with conventional green manure or untreated soil. These results confirm the good prospects for biocidal green manures, not only as an environmentally friendly alternative to methyl bromide in conventional agriculture, but also in organic agriculture as an alternative to conventional green manure crops.

  16. Improving food and agriculture productivity and the environment: Canadian initiatives in methyl bromide alternatives and emission control technologies. Revised edition

    SciTech Connect

    Marcotte, M.; Tibelius, C.

    1998-12-31

    Methyl bromide, a fumigant used in the agricultural sector, was listed as an ozone-depleting substance under the Montreal Protocol and is scheduled for phasing out in Canada. This report begins with a review of the joint industry/government approach being taken to plan and manage this phase-out. It then reviews alternative solutions that have been formulated and tested as replacements for the use of methyl bromide in greenhouse cultivation, soil fumigation, strawberry transplant production, tobacco production, grain production, and food processing facilities. Contact names and addresses are provided for those seeking further information. The final sections describe activities in methyl bromide recovery and recycling and list industry and government organizations that have expertise in methyl bromide alternatives.

  17. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, No Stack, More than 8 Hours

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  18. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, No Stack, 8 Hours or Less

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  19. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Horizontal Stacks, 8 Hours or Less

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  20. 1,3-Bis[(6-methyl-2-pyrid-yl)meth-yl]imidazolium bromide.

    PubMed

    Kim, Ga Young; Park, Sang-Kyu; Lee, Dong-Heon; Park, Gyungse

    2009-02-28

    The title compound, C(17)H(19)N(4) (+)·Br(-), is built up from 1,3-bis-[(6-methyl-2-pyridin-yl)meth-yl]imidazolium cations and bromide anions. Each of two 6-methyl-2-pyridyl rings is rotated out of the imidazole plane, making dihedral angles of 79.90 (9) and 86.40 (9)°. The packing is consolidated by aromatic π-π inter-actions between the pyridine rings of neighbouring mol-ecules [centroid-centroid distance = 3.554 (2) Å] and by weak C-H⋯N and C-H⋯Br hydrogen bonds.

  1. High-resolution slice imaging of quantum state-to-state photodissociation of methyl bromide

    SciTech Connect

    Lipciuc, M. Laura; Janssen, Maurice H. M.

    2007-12-14

    The photodissociation of rotationally state-selected methyl bromide is studied in the wavelength region between 213 and 235 nm using slice imaging. A hexapole state selector is used to focus a single (JK=11) rotational quantum state of the parent molecule, and a high speed slice imaging detector measures directly the three-dimensional recoil distribution of the methyl fragment. Experiments were performed on both normal (CH{sub 3}Br) and deuterated (CD{sub 3}Br) parent molecules. The velocity distribution of the methyl fragment shows a rich structure, especially for the CD{sub 3} photofragment, assigned to the formation of vibrationally excited methyl fragments in the {nu}{sub 1} and {nu}{sub 4} vibrational modes. The CH{sub 3} fragment formed with ground state Br({sup 2}P{sub 3/2}) is observed to be rotationally more excited, by some 230-340 cm{sup -1}, compared to the methyl fragment formed with spin-orbit excited Br({sup 2}P{sub 1/2}). Branching ratios and angular distributions are obtained for various methyl product states and they are observed to vary with photodissociation energy. The nonadiabatic transition probability for the {sup 3}Q{sub 0+}{yields}{sup 1}Q{sub 1} transition is calculated from the images and differences between the isotopes are observed. Comparison with previous non-state-selected experiments indicates an enhanced nonadiabatic transition probability for state-selected K=1 methyl bromide parent molecules. From the state-to-state photodissociation experiments the dissociationenergy for both isotopes was determined, D{sub 0}(CH{sub 3}Br)=23 400{+-}133 cm{sup -1} and D{sub 0}(CD{sub 3}Br)=23 827{+-}94 cm{sup -1}.

  2. Methyl-β-Cyclodextrin /Cetyltrimethyl Ammonium Bromide Synergistic Sensitized Fluorescence Method for the Determination of Levofloxacin.

    PubMed

    Ren, Qiuyi; Zhu, Xiashi

    2016-03-01

    A novel method of methyl-β-cyclodextrin (methyl-β-CD) and cetyltrimethyl ammonium bromide (CTAB) synergistic sensitized fluorescence analysis to determine levofloxacin (LVFX) was developed. The results were shown that the fluorescence intensity of LVFX was increased a lot in the system of methyl-β-cyclodextrin-CTAB medium. Under the conditions of λ(ex/em )= 330/507 nm and pH 4.5, the linear range and the detection limit for LVFX were found to be 0.040 ~ 4.0 μg/mL and 0.3 ng/mL, respectively. The mechanism of sensitized fluorescence method was discussed by the solubilization capacity and the microenvironment of medium. The proposed method has been applied for the determination of LVFX in eye drops real samples and human serum with satisfactory recovery.

  3. Enhanced degradation of the volatile fumigant-nematicides 1,3-d and methyl bromide in soil.

    PubMed

    Ou, L T

    1998-03-01

    The use of the gaseous funaigant-nematicide methyl bromide in agriculture is scheduled to be phased out in the year 2001.1,3-Dichloropropene (1,3-D) in combination with chloropicrin and an herbicide is considered to be a viable alternative to methyl bromide for some crops. 1,3-Dichloropropene consists of two isomers, cis- and trans-l,3-D. A number of soil bacteria have been shown to initially degrade 1,3-D or one of its isomers, cis-l,3-D, via hydrolysis. Until recently, the degradation of cis- and trans-l,3-D in soils was considered to exhibit similar kinetics, witla their degradation rates increasing with increases in soil temperature. Enhanced degradation of 1,3-D in soil from a site in Florida with a history of repeated annual applications of 1,3-D was observed in 1994. Biological hydrolysis was involved in the initial degradation of cis- and trans-l,3-D. The two isomers were degraded at different rates, with the trans isomer being degraded more rapidly than the cis isomer. Cis- and trans-l,3-D in soil from the control site were degraded at a similar rate but more slowly than in the enhanced soil. Methyl bromide in soils can be degraded through chemical hydrolysis and methylation to soil organic matter. Some methanotrophic bacteria and ammonia-oxidation bacteria during the oxidation of their primary substrates (methane and ammonia) also have the capacity to cooxidize methyl bromide to formaldehyde and bromide ion. It was recently observed that degradation of methyl bromide was stimulated in methanotrophic soils and in soils treated with ammonium sulfate. Soil methanotrophic bacteria and soil nitrifiers are apparently responsible for cooxidation of methyl bromide in methanotrophic and ammonia treated soils, respectively.

  4. Aerodynamic measurements of methyl bromide volatilization from tarped and nontarped fields

    USGS Publications Warehouse

    Majewski, M.S.; McChesney, M.M.; Woodrow, J.E.; Prueger, J.H.; Seiber, J.N.

    1995-01-01

    Methyl bromide (MeBr) is used extensively in agriculture as a soil fumigant and there is growing concern over the role it may play in the depletion of stratospheric ozone. Methyl bromide is applied using various techniques and very little is known about how much of the applied fumigant volatilizes into the atmosphere after the application. This held study was designed to estimate the post-application methyl bromide volatilization loss rates from two different application practices. The fields were approximately 6 km apart in Monterey County, California, and were treated in conformity with local practices as of 1992. The MeBr was injected at a depth of 25 to 30 cm. One field was covered simultaneously with a high-barrier plastic film tarp during the application, and the other was left uncovered, but the furrows made by the injection shanks were bedded over. Volatilization fluxes were estimated using an aerodynamic-gradient technique immediately following the completion of the application process and continued for 9 d for the tarped held and 6 d for the nontarped field. The cumulative volatilization losses from the tarped field were 22% of the nominal application within the first 5 d of the experiment and about 32% of the nominal application within 9 d including the one day after the tarp was removed on Day 8 after application. In contrast, the nontarped field lost 89% of the nominal application by volatilization in 5 d. The volatilization rate from the tarped field was shown to he significantly lower than the nontarped field at a 95% confidence level.

  5. Aerodynamic measurements of methyl bromide volatilization from tarped and nontarped fields

    SciTech Connect

    Majewski, M.S.; McChesney, M.M.; Woodrow, J.E.; Seiber, J.N.

    1995-07-01

    Methyl bromide (MeBr) is used extensively in agriculture as a soil fumigant and there is growing concern over the role it may play in the depletion of stratospheric ozone. Methyl bromide is applied using various techniques and very little is known about how much of the applied fumigant volatilizes into the atmosphere after the application. This field study was designed to estimate the post-application methyl bromide volatilization loss rates from two different application practices. The fields were approximately 6 km apart in Monterey County, California, and were treated in conformity with local practices as of 1992. The MeBr was injected at a depth of 25 to 30 cm. One field was covered simultaneously with a high-barrier plastic film tarp during the application, and the other was left uncovered, but the furrows made by the injection shanks were bedded over. Volatilization fluxes were estimated using an aerodynamic-gradient technique immediately following the completion of the application process and continued for 9 d for the tarped field and 6 d for the nontarped field. The cumulative volatilization losses from the tarped field were 22% of the nominal application within the first 5 d of the experiment and about 32% of the nominal application within 9 d including the one day after the tarp was removed on Day 8 after application. In contrast, the nontarped field lost 89% of the nominal application by volatilization in 5 d. The volatilization rate from the tarped field was shown to be significantly lower than the nontarped field at a 95% confidence level. 43 refs., 5 figs., 3 tabs.

  6. Thermal and optical studies of some di-methyl-di-alkyl ammonium bromides

    NASA Astrophysics Data System (ADS)

    Witko, Waclaw; Godlewska, Malgorzata; Dynarowicz, Patrycja

    1998-01-01

    Phase situation of homologous series of di-alkyl-di-methyl ammonium bromides represented by the general formula: 2CnN+2C1Br-, with n equals 10, 12, 14, 16, 18, was investigated by means of differential scanning calorimetry and optical microscopy methods in the temperature range 20-180 degrees C. A more complex polymorphism as already reported was detected. All the compounds studied show at least tow anomalies on the DSC curves. The high-temperature phase which appears below the isotropic phase has lancet-like dendritic texture which can be attributed to SmB phase. The enthalpy changes at the transitions were calculated.

  7. Tailoring acidity of HZSM-5 nanoparticles for methyl bromide dehydrobromination by Al and Mg incorporation

    PubMed Central

    2014-01-01

    Three kinds of HZSM-5 nanoparticles with different acidity were tailored by impregnating MgO or varying Si/Al ratios. Both the textural and acidic properties of the as-prepared nanoparticles were characterized by nitrogen adsorption-desorption measurements, X-ray diffraction (XRD), scanning electron microscopy (SEM), ammonia temperature-programmed desorption (NH3-TPD) and Fourier transform infrared spectroscopy (FTIR or Py-FTIR). It was found that the intensity of Lewis acid sites with weak strength was enhanced by impregnating MgO or reducing Al concentration, and such an enhancement could be explained by the formation of Mg(OH)+ or charge unbalance of the MgO framework on the surface of HZSM-5 support. The effect of HZSM-5 nanoparticles' acidity on methyl bromide dehydrobromination as catalyst was evaluated. As the results, MgHZ-360 catalyst with the highest concentration of Lewis acid sites showed excellent stability, which maintained methyl bromide conversion of up 97% in a period of 400 h on stream. Coke characterization by BET measurements and TGA/DTA and GC/MS analysis revealed that polymethylated naphthalenes species were formed outside the channels of the catalyst with higher acid intensity and higher Brønsted acid concentration during the initial period of reaction, while graphitic carbon formed in the channels of catalyst with lower acid intensity and higher Lewis acid concentration during the stable stage. PMID:25328502

  8. Moving away from methyl bromide: political economy of pesticide transition for California strawberries since 2004.

    PubMed

    Mayfield, Erin N; Norman, Catherine Shelley

    2012-09-15

    We examine the progress of the phaseout of the use of the pesticide methyl bromide in the production of California field strawberries. This phaseout is required under the Montreal Protocol and has been contentious in this sector, which receives exemptions from the schedule initially agreed under the treaty, and in international negotiations over the future of the Protocol. We examine the various ex-ante predictions of the impacts on growers, consumers and trade patterns in light of several years of declining allocations under the Critical Use provisions of the Protocol and the 2010 approval of iodomethane for use in California and subsequent 2012 withdrawal of this alternative from the US market. We find that, contrary to ex-ante industry claims, the years of declining methyl bromide use have been years of rising yields, acreage, exports, revenues and market share for California growers, even when faced with a global recession and increased imports from Mexican growers who retain the right to use the chemical under the Protocol. This has implications for the Protocol as a whole and for the remainder of the US phaseout of this chemical in particular. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Evaluation of sorbent materials for the sampling and analysis of phosphine, sulfuryl fluoride and methyl bromide in air.

    PubMed

    Magnusson, R; Rittfeldt, L; Åstot, C

    2015-01-02

    Phosphine (PH3), sulfuryl fluoride (SO2F2) and methyl bromide (CH3Br) are highly toxic chemical substances commonly used for fumigation, i.e., pest control with gaseous pesticides. Residues of fumigation agents constitute a health risk for workers affected, and therefore accurate methods for air sampling and analysis are needed. In this study, three commercial adsorbent tubes; Carbosieve SIII™, Air Toxics™ and Tenax TA™, were evaluated for sampling these highly volatile chemicals in air and their subsequent analysis by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). The breakthrough volume (BTV) of each fumigant was experimentally determined on the different adsorbents at concentrations at or above their permissible exposure limits, using a method based on frontal chromatography of generated fumigant atmospheres. Carbosieve SIII™, a molecular sieve possessing a very high specific area, proved to be a better adsorbent than both Air Toxics™ and Tenax TA™, resulting in at least a 4-fold increase of the BTV50%. BTV50% for Carbosieve SIII™ at 20°C was measured as 4.7L/g, 5.5L/g and 126L/g for phosphine, sulfuryl fluoride and methyl bromide, respectively, implying safe sampling volumes of 1.9L, 2.2L and 50L, respectively, for a commercial tube packed with 800mg Carbosieve SIII™. The temperature dependence of BTV was strong for Carbosieve SIII™, showing a reduction of 3-5%/°C in breakthrough volume within the range -20 to 40°C. Furthermore, although Carbosieve SIII™ reportedly has a higher affinity for water than most other adsorbents, relative humidity had only a moderate influence on the retention capacity of phosphine. Overall, the applicability of Carbosieve SIII™ adsorbent sampling in combination with TD-GC-MS analysis was demonstrated for highly volatile fumigants. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Irradiation as a disinfestation method — update on methyl bromide phase out, regulatory action and emerging opportunities

    NASA Astrophysics Data System (ADS)

    Marcotte, Michelle

    1998-06-01

    Methyl bromide (MeBr), is the most widely used agricultural fumigant in the world for the control of pests and plant diseases. It is used to control pests and diseases in food, agricultural and forestry commodities after harvest, before or during storage or transportation and/or at time of import to control quarantine or storage pests. Knowing MeBr will be phased out has spurred a search for alternative treatments and products, and has placed pressure on regulatory authorities to approve alternatives. Some of methyl bromide use could be replaced with irradiation. Methyl bromide is also used for soil and structural fumigation, and although there is some use of irradiation for packaged soil or greenhouse products, in general, these uses can not be replaced by irradiation. Some radiation processing facilities have either seen increased business to disinfest commodities, or have experienced more inquiries for service. There are many other processes and products competing for this market and irradiation will not win its share of the business without an improved regulatory picture, improved marketing to methyl bromide users and improved information to answer questions from commodity sectors. The United Nations Environment Program — Methyl Bromide Technical Options Committee (MBTOC) provides a venue for the publication or information about the use and availability of irradiation as an alternative to methyl bromide. It provides the technical base to the Montreal Protocol contributing to the setting of phase out dates; this committee is actively researching and assessing all alternatives and needs information about irradiation. The author is a member of the MBTOC committee.

  11. Methylation of cysteine in hemoglobin following exposure to methylating agents

    SciTech Connect

    Bailey, E.; Connors, T.A.; Farmer, P.B.; Gorf, S.M.; Rickard, J.

    1981-06-01

    In addition to reacting with biologically important nucleophilic sites in DNA, alkylating agents also interact with amino acids in proteins. Measurements of the extent of formation of these alkyl amino acids may be used as a means of determining exposure to these compounds. The degree of S-methylation of cysteine in hemoglobin was studied following in vivo exposure of rats to methyl methanesulfonate, dimethylnitrosamine, and 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide. A linear dose-response curve was observed for methyl methanesulfonate over a 100-fold dose range. For dimethylnitrosamine, there was a threshold of doses where no methylation could be detected, and a curved dose-response curve was obtained. At high doses, the degree of methylation of hemoglobin cysteine was 7-fold lower than that with methyl methanesulfonate. In vivo, no alkylation could be observed with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide; however, the existence of naturally occurring S-methylcysteine in the rat hemoglobin may have overshadowed small increases in alkylation arising from exposure to this compound. The natural occurrence of S-methylcysteine was studied in 13 species, and amounts ranging from 5.6 nmol/g globin (hamster) to 481 nmol/g globin (partridge) were observed. The reason for its occurrence is unknown but is under investigation.

  12. A clean start to productive orchards and vineyards: recent research on methyl bromide alternatives for perennial crop nurseries

    USDA-ARS?s Scientific Manuscript database

    Methyl bromide (MB) is an important pest management tool in open field perennial crop nurseries in California for control of many soil borne pests including plant parasitic nematodes, pathogens, and weeds. Because MB is being phased out under the provisions of the Montreal Protocol, alternatives are...

  13. Optimizing postharvest methyl bromide treatments to control spotted wing drosophila, Drosophila suzukii, in sweet cherries from Western USA

    USDA-ARS?s Scientific Manuscript database

    Methyl bromide (MB) chamber fumigations were evaluated for postharvest control of spotted wing drosophila (SWD), Drosophila suzukii (Matsumura) (Diptera: Drosophilidae), in fresh sweet cherry exports from Western USA. Sweet cherries were infested with SWD, incubated to maximize numbers of the most M...

  14. Alternative fumigants to methyl bromide for killing pupae and preventing emergence of apple maggot fly (Diptera:Tephritidae)

    USDA-ARS?s Scientific Manuscript database

    Effects of methyl bromide, ECO2FUME (phosphine gas + CO2), Vapam (sodium methyldithiocarbamate), chloropicrin, Telone II (1, 3 dichloropropene), and chloropicrin + Telone II on killing the pupae and preventing adult emergence of apple maggot fly, Rhagoletis pomonella (Walsh) was determined. In an e...

  15. The history and future of methyl bromide alternatives used in the production of forest seedlings in the southern United States

    Treesearch

    Scott A. Enebak

    2013-01-01

    This paper gives a brief history of the Southern Forest Nursery Management Cooperative’s (SFNMC) efforts in testing methyl bromide (MBr) alternatives for soil fumigation. In the southeastern United States, fumigation with MBr has been the most commonly used method for producing high quality, pest-free forest-tree seedlings in an environment that is conducive for soil-...

  16. 78 FR 68021 - Notice of Affirmation of Addition of a Treatment Schedule for Methyl Bromide Fumigation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-13

    ... Methyl Bromide Fumigation of Blueberries AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION... fumigation of blueberries for Mediterranean fruit fly and South American fruit fly. In a previous notice, we... with the notice. We also determined that the ongoing trade of blueberries would be adversely...

  17. Methyl bromide and the Montreal Protocol: An update on the critical use exemption and quarantine pre-shipment process

    Treesearch

    Scott Enebak

    2007-01-01

    Over the past 50 years, methyl bromide (MBr) has proven to be a consistently reliable pesticide that enhances seedling production and suppresses soilborne pests. It is the industry standard and an essential component of virtually every pest management program in southern forest tree nurseries. Due to the listing of MBr as a ozone depleting substance, the U.S....

  18. Aerosols and contact insecticides as alternatives to methyl bromide in flour mills, food production facilities, and food warehouses

    USDA-ARS?s Scientific Manuscript database

    The fumigant methyl bromide (MB) is being phased out of production and usage to control stored product insects in flour and rice mills, as well as feed and food production plants, in the United States (US) and other developed countries throughout the world. A phase-out schedule has also been establi...

  19. Evaluation of the efficacy of the methyl bromide fumigation schedule against Mexican fruit fly (Diptera: Tephritidae) in citrus fruit

    USDA-ARS?s Scientific Manuscript database

    Methyl bromide fumigation is a major phytosanitary treatment for a wide variety of quarantine pests, including tephritid fruit flies. Mexican fruit fly, Anastrepha ludens (Loew), is a quarantine pest of a number of fruits, including citrus exported from Texas, Mexico and Central American countries....

  20. Effects of reduced-rate methyl bromide applications under conventional and virtually impermeable plastic film in perennial crop field nurseries

    USDA-ARS?s Scientific Manuscript database

    BACKGROUND: Producers of perennial crop nursery stock in California use preplant soil fumigation to meet state phytosanitary requirements. Although methyl bromide (MB) has been phased out in many agricultural industries, it is still the preferred treatment in the perennial nursery industry and is u...

  1. Atmospheric histories of halocarbons from analysis of Antarctic firn air: Methyl bromide, methyl chloride, chloroform, and dichloromethane

    NASA Astrophysics Data System (ADS)

    Trudinger, C. M.; Etheridge, D. M.; Sturrock, G. A.; Fraser, P. J.; Krummel, P. B.; McCulloch, A.

    2004-11-01

    We reconstruct atmospheric levels of methyl bromide (CH3Br), methyl chloride (CH3Cl), chloroform (CHCl3), and dichloromethane (CH2Cl2) back to before 1940 using measurements of air extracted from firn on Law Dome in Antarctica. The firn air at this site has a relatively narrow age spread, giving high time resolution reconstructions. The CH3Br reconstructions confirm previously measured firn records but with more temporal structure. Our CH3Cl reconstruction is slightly different from previous reconstructions, raising some questions about CH3Cl in the firn. Our reconstructions for CHCl3 and CH2Cl2 are the first published records of concentration prior to direct atmospheric measurements. A two-box atmospheric model is used to investigate the budgets of these gases. Much of the variation in CH3Cl can be explained by biomass burning emissions that increase up to 1980 and then are relatively stable apart from some high burning years such as 1997-1998. The CHCl3 firn reconstruction suggests that the anthropogenic source for CHCl3 is greater than previously thought, with human influence on the soil source a possible important contributor here. The CH2Cl2 firn reconstruction is consistent with industrial emission estimates based on audited sales data but suggests that the ocean source of CH2Cl2 is less than previously estimated.

  2. Cytotoxicity, oxidative stress, and apoptosis in HepG2 cells induced by ionic liquid 1-methyl-3-octylimidazolium bromide.

    PubMed

    Li, Xiaoyu; Ma, Junguo; Wang, Jianji

    2015-10-01

    The present study aimed to determine the cytotoxicity of 1-methyl-3-octylimidazolium bromide ([C8mim]Br) on the human hepatocellular carcinoma (HepG2) cells in order to elucidate the biochemical and molecular mechanism of [C8mim]Br-cytotoxicity. For this purpose, cell viability, oxidative stress, apoptosis, caspase activity, and apoptosis-related gene expression in HepG2 cells following [C8mim]Br-exposure were evaluated. The results showed that viability of HepG2 cells was decreased by [C8mim]Br-exposure in a concentration-dependent pattern. Moreover, biochemical assays reveal that [C8mim]Br-exposure can induce apoptosis, cause overproduction of reactive oxygen species (ROS), inhibit superoxide dismutase and catalase, reduce glutathione content, and increase the cellular malondialdehyde level of HepG2 cells. The transcriptions of p53 and bax were markedly up-regulated while bcl-2 was significantly down-regulated in HepG2 cells after [C8mim]Br-exposure, suggesting that p53 and bcl-2 family may be involved in the cytotoxicity and apoptosis of HepG2 cells caused by [C8mim]Br. In addition, we also found that caspase-3, caspase-8, and caspase-9 were significantly activated in HepG2 cells following [C8mim]Br-exposure. Our results suggest that ROS may be a key early signal of [C8mim]Br-induced apoptosis and caspases play a key role in the initiation and execution of apoptosis of HepG2 cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Bacterial and Chemical Degradation of Methyl Bromide and Methyl Chloride in Soils: Too Much of a Good Thing.

    NASA Astrophysics Data System (ADS)

    Miller, L. G.; Baesman, S. M.; Oremland, R. S.

    2005-12-01

    Soils are the second largest sink for atmospheric methyl bromide (CH3Br) and methyl chloride (CH3Cl). The largest sink, reaction with OH in the troposphere, is only two-fold greater. Soils, however, comprise a very thin (1-2 m) zone compared with the troposphere (10-18 km) and are therefore an environment of relatively intense biological activity. Soils influence the composition of the troposphere as well as the flux of ozone-depleting compounds, such as methyl halides, to the stratosphere. Soil bacteria have been shown to degrade tropospheric levels of CH3Br (~10 pptv) and are likely responsible for removing CH3Cl (~550 pptv) from the atmosphere. In fact, the current budgets for atmospheric CH3Br and CH3Cl are imbalanced by as much as 40%, primarily because there are as yet no identified sources to match the bacterial soil sink. The soil microorganisms responsible for degrading CH3Br and CH3Cl at fumigation (%) levels have been identified using stable isotope probing (SIP) and functional gene probing. Not surprisingly, there is a greater diversity of methyl halide degraders present and functioning in soil than has previously been determined using culture techniques. However, the identity of microorganisms responsible for degradation of methyl halides at tropospheric (pptv) levels remains to be determined. Chemical reactions, including hydrolysis and halide exchange, also remove CH3Br but are not as important for CH3Cl. The chemical reactions that operate at low concentrations (e.g. tropospheric levels) also operate at elevated concentrations, such as those achieved during soil fumigation with CH3Br, and we have demonstrated large carbon kinetic isotope effects (KIEs) for these reactions. Similarly, we have reported large carbon KIEs for bacterial degradation of CH3Br and CH3Cl in both soil microcosms and pure cultures of methylotrophic bacteria. The KIEs of these sink reactions are used to constrain the atmospheric budgets and we present the current stable isotope

  4. Destruction of methyl bromide sorbed to activated carbon by thiosulfate or electrolysis.

    PubMed

    Yang, Yu; Li, Yuanqing; Walse, Spencer S; Mitch, William A

    2015-04-07

    Methyl bromide (CH3Br) is widely used as a fumigant for postharvest and quarantine applications for agricultural products at port facilities due to the short treatment period required, but it is vented from fumigation chambers to the atmosphere after its use. Due to the potential contributions of CH3Br to stratospheric ozone depletion, technologies for the capture and degradation of the CH3Br are needed to enable its continued use. Although granular activated carbon (GAC) has been used for CH3Br capture and thiosulfate has been used for destruction of CH3Br in aqueous solution, this research explored techniques for direct destruction of CH3Br sorbed to GAC. Submerging the GAC in an aqueous thiosulfate solution achieved debromination of CH3Br while sorbed to the GAC, but it required molar concentrations of thiosulfate because of the high CH3Br loading and produced substantial concentrations of methyl thiosulfate. Submergence of the GAC in water and use of the GAC as the cathode of an electrolysis unit also debrominated sorbed CH3Br. The reaction appeared to involve a one-electron transfer, producing methyl radicals that incorporated into the GAC. Destruction rates increased with decreasing applied voltage down to ∼-1.2 V vs the standard hydrogen electrode. Cycling experiments conducted at -0.77 V indicated that >80% debromination of CH3Br was achieved over ∼ 30 h with ∼ 100% Coulombic efficiency. Sorptive capacity and degradation efficiency were maintained over at least 3 cycles. Capture of CH3Br fumes from fumigation chambers onto GAC, and electrolytic destruction of the sorbed CH3Br could mitigate the negative impacts of CH3Br usage pending the development of suitable replacement fumigants.

  5. Degradation of methyl bromide by methanotrophic bacteria in cell suspensions and soils

    USGS Publications Warehouse

    Oremland, R.S.; Miller, L.G.; Culbertson, C.W.; Connell, T.L.; Jahnke, L.

    1994-01-01

    Cell suspensions of Methylococcus capsulatus mineralized methyl bromide (MeBr), as evidenced by its removal from the gas phase, the quantitative recovery of Br- in the spent medium, and the production of 14CO2 from [14C]MeBr. Methyl fluoride (MeF) inhibited oxidation of methane as well as that of [14C]MeBr. The rate of MeBr consumption by cells varied inversely with the supply of methane, which suggested a competitive relationship between these two substrates. However, MeBr did not support growth of the methanotroph. In soils exposed to high levels (10,000 ppm) of MeBr, methane oxidation was completely inhibited. At this concentration, MeBr removal rates were equivalent in killed and live controls, which indicated a chemical rather than biological removal reaction. At lower concentrations (1,000 ppm) of MeBr, methanotrophs were active and MeBr consumption rates were 10-fold higher in live controls than in killed controls. Soils exposed to trace levels (10 ppm) of MeBr demonstrated complete consumption within 5 h of incubation, while controls inhibited with MeF or incubated without O2 had 50% lower removal rates. Aerobic soils oxidized [14C]MeBr to 14CO2, and MeF inhibited oxidation by 72%. Field experiments demonstrated slightly lower MeBr removal rates in chambers containing MeF than in chambers lacking MeF. Collectively, these results show that soil methanotrophic bacteria, as well as other microbes, can degrade MeBr present in the environment.

  6. Degradation of methyl bromide by methanotrophic bacteria in cell suspensions and soils.

    PubMed Central

    Oremland, R S; Miller, L G; Culbertson, C W; Connell, T L; Jahnke, L

    1994-01-01

    Cell suspensions of Methylococcus capsulatus mineralized methyl bromide (MeBr), as evidence by its removal from the gas phase, the quantitative recovery of Br- in the spent medium, and the production of 14CO2 from [14C]MeBr. Methyl fluoride fluoride (MeF) inhibited oxidation of methane as well as that of [14C]MeBr. The rate of MeBr consumption by cells varied inversely with the supply of methane, which suggested a competitive relationship between these two substrates. However, MeBr did not support growth of the methanotroph. In soils exposed to high levels (10,000 ppm) of MeBr, methane oxidation was completely inhibited. At this concentration, MeBr removal rates were equivalent in killed and live controls, which indicated a chemical rather than biological removal reaction. At lower concentration (1,000 ppm) of MeBr, methanotrophs were active and MeBr consumption rates were 10-fold higher in live controls than in killed controls. Soils exposed to trace levels (10 ppm) of MeBr demonstrated complete consumption within 5 h of incubation, while controls inhibited with MeF or incubated without O2 had 50% lower removal rates. Aerobic soils oxidized [14C]MeBr to 14CO2, and MeF inhibited oxidation by 72%. Field experiments demonstrated slightly lower MeBr removal rates in chambers containing MeF than in chambers lacking MeF. Collectively, these results show that soil methanotrophic bacteria, as well as other microbes, can degrade MeBr present in the environment. PMID:7986039

  7. An investigation of the atmospheric sources and sinks of Methyl Bromide

    NASA Technical Reports Server (NTRS)

    Singh, Hanwant B.; Kanakidou, M.

    1993-01-01

    Methyl Bromide (CH3Br) is a ubiquitous component of the atmosphere and has been implicated as an important player in the depletion of stratospheric ozone. Atmospheric CH3Br abundances, interhemispheric gradients, oceanic concentrations, man-made emissions, and removal processes have been analyzed and interpreted with the help of a simple box model and a 2D global photochemical model. Its calculated atmospheric lifetime (T) of 1.7-1.9 years, based on reaction with OH radicals, is consistent with a global source of 90-110 Gg (10 exp 9 g)/year. Consequences of a much shorter lifetime of 1.2 years, due to possible deposition/hydrolysis losses, are also considered. Available data are used to estimate a CH3Br source that is 35 percent (20-50 percent) man-made and 65 percent (80-50 percent) natural. Oceans are substantially supersaturated and provide the most important natural source of about 60 (40-80) Gg/year.

  8. Whole-building decontamination of Bacillus anthracis Sterne spores by methyl bromide fumigation.

    PubMed

    Serre, S; Mickelsen, L; Calfee, M W; Wood, J P; Gray, M S; Scheffrahn, R H; Perez, R; Kern, W H; Daniell, N

    2016-01-01

    To evaluate the field inactivation of Bacillus anthracis Sterne spores with methyl bromide (MB) using commercial fumigation techniques. Eighty-seven wood and 87 glass coupons each containing ca. 1 × 10(6) B. anthracis Sterne spores, were placed in 22 locations inside a 1444 m(3) conference building. Four additional 12-coupon sets (six wood, six glass) were removed from the building at 16, 24, 32 and 40 h during fumigation. The building was sealed under two tarpaulins and fumigated with MB at ≥225 g m(-3) mean concentration for 48 h at 28°C and 83% RH. All B. anthracis spores fumigated for more than 16 h were inactivated. A single wood coupon from the 16-h set yielded ca. 2 × 10(3)  CFU. No damage to the building or its contents was observed. MB fumigation is a rapid, economical and effective whole-structure decontamination method for B. anthracis spores. MB fumigation offers a method of whole-structure B. anthracis decontamination without removal of materials, damage to sensitive electronics, costly indoor retrofitting. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  9. A Comprehensive Theoretical Investigation of the Molecular Properties of Methyl Bromide (CH3Br)

    NASA Astrophysics Data System (ADS)

    Yu, Ang-Yang; Efil, Kürşat; Yang, Rui; Hu, Qing-Miao

    2015-12-01

    The properties of the ground and the lowest excited state of methyl bromide (CH3Br) have been studied with and without inclusion of the solvent effects in this work. The geometric parameters, energies, and frequencies of the ground state and the triplet state are calculated by using the MP2(full)/6-311++G** level of theory. The vertical excitation for the singlet state is also investigated. It is found that the theoretical results performed by the TDDFT/B3P86/6-311++G** method are in the best agreement with the experimental results. In addition, the dissociation energy of CH3Br molecule is computed at MP2(full)/6-311++G** level of theory for the gas phase and in water. The ionisation potential (IP), electron affinity (EA), electronegativity (χ), electrophilicity index (ω), hardness (η), softness (S), and chemical potential (μ) values are calculated from HOMO-LUMO energies both in the gas phase and in solvent (water). These theoretical results could serve as a guide for future experimental investigations.

  10. Pirenzepine versus scopolamine methyl bromide in double-contrast barium enema study of large bowel.

    PubMed

    Marraccini, P; Braccini, G; Marrucci, A; Boraschi, P; Bertellotti, L; Testa, R

    1996-01-01

    To evaluate the usefulness of pirenzepine for diagnostic double-contrast barium enema study of the large bowel, pirenzepine and scopolamine methyl bromide (SMB) were compared in a single, blind, randomized trial. Sixty consecutive patients were enrolled in the study. Quantitative analysis of bowel distention was done by measuring the maximum diameter of the transverse colon before and after drug administration. Four independent observers blindly evaluated distention and mucosal coating of the large bowel and global quality of the images. No differences were found in the diagnostic performance between the two drugs. However, pirenzepine induced a slight but significantly larger distention of the large bowel (68 +/- 12 vs. 65 +/- 8 mm, p = 0.02). Heart rate and rhythm during the study were recorded by ECG. SMB induced tachycardia in all patients (from 72 +/- 15 to 98 +/- 24 beats/min, p < 0.01), whereas pirenzepine did not (from 76 +/- 13 to 78 +/- 20, p = NS). After SMB, one-patient exhibited faintness, and some patients complained of visual accommodation defects, dryness of the mouth, and dizziness. Pirenzepine had a diagnostic performance similar to SMB in avoiding adverse effects elicited by SMB.

  11. Laboratory-scale measurements and simulations of effect of application methods on soil methyl bromide emission

    SciTech Connect

    Gan, J.; Yates, S.R.; Spencer, W.F.

    1997-01-01

    Methyl bromide (bromomethane, MeBr), which originates from the oceans, fumigation, and a few other sources, is reportedly contributing to the ozone depletion in the stratosphere. Due to the heavy reliance on this fumigant in the production of many crops, it is of particular importance to accurately quantify the atmospheric input of MeBr arising from agricultural uses, and develop feasible measures to minimize these emissions. In this study, we determined the effect of two important application variables, surface tarp and injection depth, on MeBr transport and transformation in the soil and its emission from the soil surface under controlled conditions. Following 20- and 30-cm injections, covering the soil surface with 1-mil (0.025 mm) high-density polyethylene film resulted in an average of 48% reduction in MeBr emission. Increasing the injection depth from 20 to 60 cm caused a decrease in MeBr emission of 54% under untarped conditions and 40% under tarped conditions. The influence of application methods on MeBr atmospheric emissions should be considered when estimating the contribution of agricultural fumigation to the overall atmospheric MeBr burden on a global scale. The results also indicate that MeBr emission after soil fumigation may be substantially minimized by using surface tarpaulins and deep injections. 34 refs., 5 figs., 1 tab.

  12. An investigation of the atmospheric sources and sinks of methyl bromide

    NASA Astrophysics Data System (ADS)

    Singh, Hanwant B.; Kanakidou, M.

    1993-01-01

    Methyl Bromide (CH3Br) is a ubiquitous component of the atmosphere and has been implicated as an important player in the depletion of stratospheric ozone. Atmospheric CH3Br abundances, interhemispheric gradients, oceanic concentrations, man-made emissions, and removal processes have been analyzed and interpreted with the help of a simple box model and a 2-D global photochemical model. Its calculated atmospheric lifetime (T) of 1.7-1.9 years, based on reaction with OH radicals, is consistent with a global source of 90-110 Gg (109g)/year. Consequences of a much shorter lifetime of 1.2 years, due to possible deposition/hydrolysis losses, are also considered. Available data are used to estimate a CH3Br source that is 35% (20-50%) man-made and 65% (80-50%) natural. Oceans are substantially supersaturated and provide the most important natural source of ≈60 (40-80) Gg/year. Within the oceans 200-300 Gg/year of CH3Br may be produced. Indirect emissions from automobile exhaust and biomass burning can not be well quantified (1-10 Gg/year). A global trend of 0.1-0.2 ppt/year is predicted. Model results show significant vertical and seasonal variations in the atmospheric abundances and interhemispheric gradients of CH3Br. Substantial uncertainties in calibrations, source estimates, and deposition processes are present.

  13. Cardiovascular and antihypertensive actions of 1-methyl-3-keto-4-phenylquinuclidinium bromide.

    PubMed

    Vidrio, H; Hong, E

    1976-01-01

    The sympatholytic and norepinephrine depleting drug 1-methyl-3-keto-4-phenylquinuclidinium bromide (MA540) possessed significant chronic antihypertensive activity in mecamylamine- and renal-hypertensive dogs. The compound was approximately four times more potent than guanethidine in the former model and three times as potent in the latter. MA540 reduced orthostatic blood pressure responses in unanesthetized rabbits, but was approximately ten times less potent than guanethidine. The quinuclidine derivative did not affect cardiac output, heart rate or stroke volume in anesthetized open chest dogs and moderately increased mean blood pressure and total peripheral resistance. It produced diuresis and saluresis in anesthetized dogs, but did not influence water or electrolyte urinary excretion in conscious rats. In the latter test, guanethidine produced antidiuresis and antisaluresis. It was concluded that MA540 is a potent, orally effective antihypertensive agent acting through adrenergic neuron blockade, that it lacks undesirable effects on cardiac and renal functions, and that compared with guanethidine, it is more potent in lowering blood pressure but less so in interfering with orthostatic cardiovascular reflexes.

  14. The Challenge of Research and Extension to Define and Implement Alternatives to Methyl Bromide

    PubMed Central

    Noling, J. W.; Becker, J. O.

    1994-01-01

    Over the past 30 years, methyl bromide (MBr), a broad spectrum fumigant, has been used extensively for soilborne disease and pest control in the production of many fruit, vegetable, turf, and nursery crops. Recently, agricultural emissions of MBr were implicated as a potentially significant contributor to stratospheric ozone depletion. As a precautionary measure for global ozone protection, the U.S. Environmental Protection Agency has enforced federal legislation which mandates a complete phase-out of MBr use within the United States by 1 January 2001. Thus, new cost effective, environmentally compatible strategies for control of nematodes and other soilborne pests and pathogens must be developed and tested in a relatively short time to avoid significant losses in crop productivity. The extent to which certain agricultural industries that are now heavily reliant on MBr are affected will depend on the development of sustainable, integrated tactics to pest control, such as combinations of cultural, chemical, and biological tactics. New muhidisciplinary research and extension programs must be developed to address and overcome major constraints and incompatibilities that have prevented such tactics from being widely adopted. PMID:19279928

  15. Evaluation of the efficacy of the methyl bromide fumigation schedule against Mexican fruit fly (Diptera: Tephritidae) in citrus fruit.

    PubMed

    Hallman, Guy J; Thomas, Donald B

    2011-02-01

    Methyl bromide fumigation is widely used as a phytosanitary treatment. Mexican fruit fly, Anastrepha ludens (Loew) (Diptera: Tephritidae), is a quarantine pest of several fruit, including citrus (Citrus spp.), exported from Texas, Mexico, and Central America. Recently, live larvae have been found with supposedly correctly fumigated citrus fruit. This research investigates the efficacy of the previously approved U.S. Department of Agriculture-Animal and Plant Health Inspection Service treatment schedule: 40 g/m3 methyl bromide at 21-29.4 degrees C for 2 h. Tolerance ofA. ludens to methyl bromide in descending order when fumigated in grapefruit (Citrus X paradisi Macfad.) is third instar > second instar > first instar > egg. Two infestation techniques were compared: insertion into fruit of third instars reared in diet and oviposition by adult A. ludens into fruit and development to the third instar. Inserted larvae were statistically more likely to survive fumigation than oviposited larvae. When fruit were held at ambient temperature, 0.23 +/- 0.12% of larvae were still observed to be moving 4 d postfumigation. Temperatures between 21.9 and 27.2 degrees C were positively related to efficacy measured as larvae moving 24 h after fumigation, pupariation, and adult emergence. Coating grapefruit with Pearl Lustr 2-3 h before fumigation did not significantly affect the proportion of third instars moving 24 h after fumigation, pupariating, or emerging as adults. In conclusion, fumigation with 40 g/m3 methyl bromide for 2 h at fruit temperatures >26.7 degrees C is not found to be inefficacious for A. ludens. Although a few larvae may be found moving >24 h postfumigation, they do not pupariate.

  16. Effect of phytosanitary irradiation and methyl bromide fumigation on the physical, sensory, and microbiological quality of blueberries and sweet cherries.

    PubMed

    Thang, Karen; Au, Kimberlee; Rakovski, Cyril; Prakash, Anuradha

    2016-10-01

    The objective of this study was to determine whether irradiation could serve as a suitable phytosanitary treatment alternative to methyl bromide (MB) fumigation for blueberries and sweet cherry and also to determine the effect of phytosanitary irradiation treatment on survival of Salmonella spp. and Listeria monocytogenes on these fruit. 'Bluecrop' blueberries (Vaccinium corymbosum) and 'Sweetheart' cherries (Prunus avium) were irradiated at 0.4 kGy or fumigated with methyl bromide and evaluated for quality attributes during storage. Irradiation caused an immediate decrease in firmness of both fruit without further significant change during storage. Fumigated fruit, in contrast, softened by 11-14% during storage. Irradiation did not adversely affect blueberry and cherry shelf-life. MB fumigation did not impact blueberry and cherry quality attributes initially; however, fumigated fruit exhibited greater damage and mold growth than the control and irradiated samples during storage. Irradiation at 400 Gy resulted in a ∼1 log CFU g(-1) reduction in Salmonella spp. and Listeria monocytogenes counts, indicating that this treatment cannot significantly enhance safety. This study indicates that irradiation at a target dose of 0.4 kGy for phytosanitary treatment does not negatively impact blueberry and cherry quality and can serve as an alternative to methyl bromide fumigation. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  17. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Open Area Vertical Stacks, 8 Hours or Less, 10 Foot Stack Height

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  18. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Attached Vertical Stacks , 8 Hours or Less, 10 Foot Stack Height

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  19. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Open Area Vertical Stacks, More than 8 Hours, 5 Foot Stack Height

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  20. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Open Area Vertical Stacks, More than 8 Hours, 50 Foot Stack Height

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  1. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Open Area Vertical Stacks , 8 Hours or Less, 5 Foot Stack Height

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  2. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Open Area Vertical Stacks, 8 Hours or Less, 25 Foot Stack Height

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  3. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Open Area Vertical Stacks, More than 8 Hours, 10 Foot Stack Height

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  4. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Open Area Vertical Stacks, 8 Hours or Less, 50 Foot Stack Height

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  5. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Attached Vertical Stacks , 8 Hours or Less, 25 Foot Stack Height

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  6. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Open Area Vertical Stacks, More than 8 Hours, 25 Foot Stack Height

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  7. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Attached Vertical Stacks, More than 8 hours, 25 Foot Stack Height

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  8. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Attached Vertical Stacks, More than 8 hours, 10 Foot Stack Height

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  9. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Attached Vertical Stacks, 8 Hours or Less, 50 Foot Stack Height

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  10. Methyl Bromide Buffer Zone Distances for Commodity and Structural Fumigation: Active Aeration, Attached Vertical Stacks, More than 8 hours, 50 Foot Stack Height

    EPA Pesticide Factsheets

    This document contains buffer zone tables required by certain methyl bromide commodity fumigant product labels that refer to Buffer Zone Lookup Tables located at epa.gov/pesticide-registration/mbcommoditybuffer on the label.

  11. Atmospheric volatilization of methyl bromide, 1,3-dichloropropene, and propargyl bromide through two plastic films: transfer coefficient and temperature effect

    NASA Astrophysics Data System (ADS)

    Wang, D.; Yates, S. R.; Gan, J.; Knuteson, J. A.

    Atmospheric emission of methyl bromide (MeBr) and its potential alternative chemicals such as 1,3-dichloropropene (1,3-D) and propargyl bromide (PrBr) can contribute to air pollution and ozone depletion (for MeBr). One of the main sources of these chemicals is from agricultural soil fumigation. To understand the volatilization dynamics, emission of MeBr, 1,3-D, and PrBr through a polyethylene-based high-barrier film (HBF) and a virtually impermeable film (VIF) was measured using an air flow and sampling system that produced >90% mass balance. The experiment was conducted outdoors and was subjected to ambient daily temperature variations. The HBF film was found to be very permeable to 1,3-D and PrBr, but somewhat less permeable to MeBr. The VIF film was very impermeable to 1,3-D, PrBr, or MeBr. Measured volatilization flux, in general, exhibited strong diurnal variations which were controlled by film temperature. Unlike the HBF film, a time lag (˜12 h) was observed between high-temperatures and high-emission flux values for the VIF film. An impermeable film may be used as an effective means of controlling the atmospheric emission of MeBr and its alternative chemicals.

  12. Manganese Uptake and Distribution in the Brain after Methyl Bromide-Induced Lesions in the Olfactory Epithelia

    PubMed Central

    Thompson, Khristy J.; Molina, Ramon M.; Donaghey, Thomas; Savaliya, Sandeep; Schwob, James E.; Brain, Joseph D.

    2011-01-01

    Manganese (Mn) is an essential nutrient with potential neurotoxic effects. Mn deposited in the nose is apparently transported to the brain through anterograde axonal transport, bypassing the blood-brain barrier. However, the role of the olfactory epithelial cells in Mn transport from the nasal cavity to the blood and brain is not well understood. We utilized the methyl bromide (MeBr) lesion model wherein the olfactory epithelium fully regenerates in a time-dependent and cell type–specific manner over the course of 6–8 weeks postinjury. We instilled 54MnCl2 intranasally at different recovery periods to study the role of specific olfactory epithelial cell types in Mn transport. 54MnCl2 was instilled at 2, 4, 7, 21, and 56 days post-MeBr treatment. 54Mn concentrations in the blood were measured over the first 4-h period and in the brain and other tissues at 7 days postinstillation. Age-matched control rats were similarly studied at 2 and 56 days. Blood and tissue 54Mn levels were reduced initially but returned to control values by day 7 post-MeBr exposure, coinciding with the reestablishment of sustentacular cells. Brain 54Mn levels also decreased but returned to control levels only by 21 days, the period near the completion of neuronal regeneration/bulbar reinnervation. Our data show that Mn transport to the blood and brain temporally correlated with olfactory epithelial regeneration post-MeBr injury. We conclude that (1) sustentacular cells are necessary for Mn transport to the blood and (2) intact axonal projections are required for Mn transport from the nasal cavity to the olfactory bulb and brain. PMID:21177252

  13. Manganese uptake and distribution in the brain after methyl bromide-induced lesions in the olfactory epithelia.

    PubMed

    Thompson, Khristy J; Molina, Ramon M; Donaghey, Thomas; Savaliya, Sandeep; Schwob, James E; Brain, Joseph D

    2011-03-01

    Manganese (Mn) is an essential nutrient with potential neurotoxic effects. Mn deposited in the nose is apparently transported to the brain through anterograde axonal transport, bypassing the blood-brain barrier. However, the role of the olfactory epithelial cells in Mn transport from the nasal cavity to the blood and brain is not well understood. We utilized the methyl bromide (MeBr) lesion model wherein the olfactory epithelium fully regenerates in a time-dependent and cell type-specific manner over the course of 6-8 weeks postinjury. We instilled (54)MnCl(2) intranasally at different recovery periods to study the role of specific olfactory epithelial cell types in Mn transport. (54)MnCl(2) was instilled at 2, 4, 7, 21, and 56 days post-MeBr treatment. (54)Mn concentrations in the blood were measured over the first 4-h period and in the brain and other tissues at 7 days postinstillation. Age-matched control rats were similarly studied at 2 and 56 days. Blood and tissue (54)Mn levels were reduced initially but returned to control values by day 7 post-MeBr exposure, coinciding with the reestablishment of sustentacular cells. Brain (54)Mn levels also decreased but returned to control levels only by 21 days, the period near the completion of neuronal regeneration/bulbar reinnervation. Our data show that Mn transport to the blood and brain temporally correlated with olfactory epithelial regeneration post-MeBr injury. We conclude that (1) sustentacular cells are necessary for Mn transport to the blood and (2) intact axonal projections are required for Mn transport from the nasal cavity to the olfactory bulb and brain.

  14. Methyl bromide emission from fields partially covered with a high-density polyethylene and a virtually impermeable film

    SciTech Connect

    Wang, D.; Yates, S.R.

    1998-09-01

    Recent field studies in the interior valley of southern California have indicated that 56--73% of methyl bromide (MeBr) used in soil fumigation is lost to atmospheric emission when the fields are covered completely with a high-density polyethylene (HDPE) film. The emission can be reduced to less than 5% when a virtually impermeable film or Hytibar is used to cover the fields. This study was conducted to determine MeBr emission from bedded field plots where only the beds were covered with a HDPE or a virtually impermeable plastic film. The results provide an assessment on MeBr emission from field beds partially covered with the HDPE film and the suitability of using a virtually impermeable film for emission reduction. Methyl bromide gas was applied to replicated field beds covered with either a HDPE or the Hytibar film. The films were removed 6 days after MeBr application. Replicated soil cores were taken from different locations of the field beds, 20 days after MeBr application, for the determination of soil bromide ion concentrations. The total amount of MeBr degraded from each plot was calculated from the measured bromide ion concentrations, and the potential emission was determined as the difference between the amount of applied and that of degraded. Results indicated that the potential emission from this bedded system was about 95% for the HDPE treatment and 90% for the Hytibar-covered plots. Regardless of the small improvement with the virtually impermeable film, the experiment clearly indicates that partially covering the field with either a HDPE or a virtually impermeable film would result in unacceptably high emission losses.

  15. Effects of Soil and Water Content on Methyl Bromide Oxidation by the Ammonia-Oxidizing Bacterium Nitrosomonas europaea†

    PubMed Central

    Duddleston, Khrystyne N.; Bottomley, Peter J.; Porter, Angela; Arp, Daniel J.

    2000-01-01

    Little information exists on the potential of NH3-oxidizing bacteria to cooxidize halogenated hydrocarbons in soil. A study was conducted to examine the cooxidation of methyl bromide (MeBr) by an NH3-oxidizing bacterium, Nitrosomonas europaea, under soil conditions. Soil and its water content modified the availability of NH4+ and MeBr and influenced the relative rates of substrate (NH3) and cosubstrate (MeBr) oxidations. These observations highlight the complexity associated with characterizing soil cooxidative activities when soil and water interact to differentially affect substrate and cosubstrate availabilities. PMID:10831449

  16. Direct comparison of 3-centre and 4-centre HBr elimination pathways in methyl-substituted vinyl bromides.

    PubMed

    Pandit, Shubhrangshu; Hornung, Balázs; Orr-Ewing, Andrew J

    2016-10-12

    Elimination of HBr from UV-photoexcited vinyl bromides can occur through both 3-centre and 4-centre transition states (TSs). The competition between these pathways is examined using velocity map imaging of HBr (v = 0-2, J) photofragments. The three vinyl bromides chosen for study have methyl substituents that block either the 3-centre or the 4-centre TS, or leave both pathways open. The kinetic energy distributions extracted from velocity map images of HBr from 193 nm photolysis of the three vinyl bromide compounds are approximately described by a statistical model of energy disposal among the degrees of freedom of the photoproducts, and are attributed to dissociation on the lowest electronic state of the molecule after internal conversion. Dissociation via the 4-centre TS gives greater average kinetic energy release than for the 3-centre TS pathway. The resonance enhanced multi-photon ionization (REMPI) schemes used to detect HBr restrict measurements to J ≤ 7 for v = 2 and J ≤ 15 for v = 0. Within this spectroscopic range, the HBr rotational temperature is colder for the 4-centre than for the 3-centre elimination pathway. Calculations of the intrinsic reaction coordinates and RRKM calculations of HBr elimination rate coefficients provide mechanistic insights into the competition between the pathways.

  17. External and internal exposure of wine growers spraying methyl parathion.

    PubMed

    Muttray, Axel; Bäcker, Gerhard; Jung, Detlev; Hill, Georg; Letzel, Stephan

    2006-04-10

    Organophosphates, used in agriculture, are readily absorbed through the skin. We investigated the relationship between dermal and inhalative methyl parathion exposure and the plasma levels. Twenty-three healthy wine growers sprayed the insecticide for 50 min. Fluorescent brilliant sulfoflavin was added to the spraying fluids and filter papers were fixed on the subjects. The filter papers were used to evaluate the amount of brilliant sulfoflavine on the unprotected skin fluorometrically. Inhalative exposure was measured with personal air sampler. Plasma concentrations of methyl parathion and its metabolite methyl paraoxon were determined with gas chromatography. Cholinesterase activity in serum and erythrocytes was measured before and after exposure. Some wine growers wore protective clothes, none protective gloves. Dermal exposure ranged up to 12,044 microg, inhalative to 22 microg. Maximum plasma concentration of methyl parathion was 12.1 microg/l. Methyl paraoxon was not detectable. Cholinesterase activity did not decrease. Dermal exposure correlated with the methyl parathion plasma level (Spearman's rho=0.72, p<0.001). In conclusion, dermal exposure exceeded inhalative exposure considerably. Measuring dermal deposition with the brilliant sulfoflavin technique may provide a good estimate of the internal load with methyl parathion. Preventive measures should be improved as toxic effects of repeated exposure to low doses of methyl parathion cannot be excluded.

  18. Synthesis, spectral, optical and thermal studies of 1-methyl-2,6-dimethyl-4-hydroxypyridinium chloride monohydrate and bromide monohydrate

    NASA Astrophysics Data System (ADS)

    Dhanuskodi, S.; Manivannan, S.; Philip, J.

    2008-04-01

    Semiorganic 1-methyl-2,6-dimethyl-4-hydroxypyridinium chloride monohydrate (MDMPCl·H 2O) and bromide monohydrate (MDMPBr·H 2O) salts have been synthesized. Single crystals of MDMPCl·H 2O and MDMPBr·H 2O were grown by the slow evaporation method from aqueous solution at constant temperatures 30 and 32 °C respectively. The grown crystals were characterized by elemental analysis, FT-IR and FT-NMR techniques and their molecular structures were elucidated. Thermogravimetric, differential thermal analyses and differential scanning calorimetry reveal the presence of water molecules in the crystal lattices and thermal stabilities. Optical transmittance windows in aqueous solution were found as 300-1100 nm using UV-vis-NIR spectrophotometer.

  19. Evaluation of the combination of dimethyl disulfide and dazomet as an efficient methyl bromide alternative for cucumber production in China.

    PubMed

    Mao, Liangang; Yan, Dongdong; Wang, Qiuxia; Li, Yuan; Ouyang, Canbin; Liu, Pengfei; Shen, Jin; Guo, Meixia; Cao, Aocheng

    2014-05-28

    The combination of dimethyl disulfide (DMDS) and dazomet (DZ) is a potential alternative to methyl bromide (MB) for soil disinfestation. The efficacy of DMDS plus DZ in controlling key soilborne pests was evaluated in a laboratory study and in two commercial cucumber greenhouses. Laboratory studies found that all of the combinations had positive synergistic effects on root-knot nematodes, two key soilborne fungi, and two major weed seeds. Greenhouse trials revealed that the combination of DMDS and DZ (30 + 25 g m(-2)) successfully suppressed Meloidogyne spp. root galling, sharply reduced the colony-forming units of Fusarium spp. and Phytophthora spp. on media, maintained high cucumber yields, and was not significantly different from MB or DMDS alone, but better than DZ alone. All of the chemical treatments provided significantly better results than the nontreated control. The results indicate that the combination of DMDS and DZ is an efficient MB alternative for cucumber production.

  20. PERENNIAL CROP NURSERIES TREATED WITH METHYL BROMIDE AND ALTERNATIVE FUMIGANTS: EFFECTS ON WEED SEED VIABILITY, WEED DENSITIES, AND TIME REQUIRED FOR HAND WEEDING

    USDA-ARS?s Scientific Manuscript database

    Weed control provided by alternative fumigants to methyl bromide (MeBr) needs to be tested in perennial crop nurseries in California because MeBr is being phased out in accordance with the Montreal Protocol, few herbicides are registered for perennial nursery use, and costs of other control measures...

  1. United States Department of Agriculture-Agricultural Research Service research on alternatives to methyl bromide: pre-plant and post-harvest.

    PubMed

    Schneider, Sally M; Rosskopf, Erin N; Leesch, James G; Chellemi, Daniel O; Bull, Carolee T; Mazzola, Mark

    2003-01-01

    Methyl bromide is a widely used fumigant for both pre-plant and post-harvest pest and pathogen control. The Montreal Protocol and the US Clean Air Act mandate a phase-out of the import and manufacture of methyl bromide, beginning in 2001 and culminating with a complete ban, except for quarantine and certain pre-shipment uses and exempted critical uses, in January 2005. In 1995, ARS built on its existing programs in soil-borne plant pathology and post-harvest entomology and plant pathology to initiate a national research program to develop alternatives to methyl bromide. The focus has been on strawberry, pepper, tomato, perennial and nursery cropping systems for pre-plant methyl bromide use and fresh and durable commodities for post-harvest use. Recently the program has been expanded to include research on alternatives for the ornamental and cut flower cropping systems. An overview of the national research program is presented. Results from four specific research trials are presented, ranging from organic to conventional systems. Good progress on short-term alternatives is being made. These will be used as the foundation of integrated management systems which begin with pre-plant management decisions and continue through post-harvest processing.

  2. Development of an activated carbon-based electrode for the capture and rapid electrolytic reductive debromination of methyl bromide from post-harvest fumigations

    USDA-ARS?s Scientific Manuscript database

    Due to concerns surrounding its ozone depletion potential, there is a need for technologies to capture and destroy methyl bromide (CH3Br) emissions from post-harvest fumigations applied to control agricultural pests. Previously we described a system in which CH3Br fumes vented from fumigation chambe...

  3. Activated carbons from end-products of tree nut and tree fruit production as sorbents for removing methyl bromide in ventilation effluent from postharvest chamber fumigation

    USDA-ARS?s Scientific Manuscript database

    End-products of tree nuts and tree fruits grown in California, USA were evaluated for the ability to remove methyl bromide from the ventilation effluent of postharvest chamber fumigations. Activated carbon sorbents from walnut and almond shells as well as peach and prune pits were prepared using dif...

  4. Evaluation of non-fumigant alternatives to methyl bromide for weed control and crop yield in California strawberries (Fragaria ananassa L.)

    USDA-ARS?s Scientific Manuscript database

    In California, USA, agricultural fumigant use regulations hinder the complete transition from methyl bromide (MB) to alternative fumigants. Alternative fumigants such as 1,3-dichloropropene (1,3-D) and chloropicrin (Pic) are being used on approximately half of California conventional strawberry prod...

  5. Postharvest treatment of fresh fruit from California with methyl bromide for postharvest control of light brown apple moth, Epiphyas postvittana (Walker)

    USDA-ARS?s Scientific Manuscript database

    Methyl bromide chamber fumigations were evaluated for postharvest control of light brown apple moth (LBAM), Epiphyas postvittana (Walker), in fresh fruit exports. To simulate external feeding, larvae were contained in gas-permeable cages and distributed throughout loads of peaches, plums, nectarines...

  6. The treatment of fresh fruit from California with methyl bromide for postharvest control of light brown apple moth, Epiphyas postvittana (Walker)

    USDA-ARS?s Scientific Manuscript database

    Methyl bromide chamber fumigations were evaluated for postharvest control of light brown apple moth (LBAM), Epiphyas postvittana (Walker), in fresh fruit exports. To simulate external feeding, larvae were contained in gas-permeable cages and distributed throughout loads of peaches, plums, nectarines...

  7. One-pot preparation of trifluoromethylated homoallylic N-acylhydrazines or α-methylene-γ-lactams from acylhydrazines, trifluoroacetaldehyde methyl hemiacetal, allyl bromide and tin.

    PubMed

    Du, Ganggang; Huang, Danfeng; Wang, Ke-Hu; Chen, Xiaowei; Xu, Yanli; Ma, Junyan; Su, Yingpeng; Fu, Ying; Hu, Yulai

    2016-01-28

    An efficient and convenient one-pot method for the preparation of trifluoromethylated homoallylic N-acylhydrazines or α-methylene-γ-lactams has been described. In this process, allyl bromide and metal tin are used instead of toxic stannanes, and commercially available aqueous trifluoroacetaldehyde methyl hemiacetal was used as a trifluoromethyl source.

  8. The role of adsorption of dodecylethyldimethylammonium bromide and benzyldimethyldodecylammonium bromide surfactants in wetting of polytetrafluoroethylene and poly(methyl methacrylate) surfaces

    NASA Astrophysics Data System (ADS)

    Harkot, Joanna; Jańczuk, Bronisław

    2009-01-01

    The role of adsorption of dodecylethyldimethylammonium bromide (C 12(EDMAB)) and benzyldimethyldodecylammonium bromide (BDDAB) at water-air and polytetrafluoroethylene (PTFE)-water and poly(methyl methacrylate) (PMMA)-water interface, in wetting of PTFE and PMMA surface, was established from the measured values of the contact angle ( θ) of aqueous C 12(EDMAB) and BDDAB solutions in PTFE (PMMA)-solution drop-air system, and from the measured values of the surface tension of aqueous C 12(EDMAB) and BDDAB solutions. Adsorption of C 12(EDMAB) and BDDAB at water-air interface was determined earlier from the Gibbs equation. Adsorption at solid-water interface was deduced from the Lucassen-Reynders equation based on the relationship between adhesion tension ( γLV cos θ) and surface tension ( γLV). The slope of the γLV cos θ- γLV curve was found to be constant and equal to -1, and about -0.3 for PTFE and PMMA surface, respectively (in the case of both surfactant studied: C 12(EDMAB) and BDDAB, and in the whole range of surfactants concentration in solution). It means that the amount of the surfactant adsorbed at the PTFE-water interface, ΓSL, was essentially equal to its amount adsorbed at water-air interface, ΓLV. However, ΓSL at the PMMA-water interface was about three times smaller as compared to that at water-air interface. By extrapolating the linear dependence between γLV cos θ- γLV and dependence between cos θ- γLV and cos θ = 1 we determined the value of the critical surface tension of PTFE and PMMA surface wetting, γc. The obtained values of γc for PTFE surface were equal 23.4 and 23.8 mN/m, 23.1 and 23.2 mN/m for C 12(EDMAB) and BDDAB, respectively and they were higher than the surface tension of PTFE (20.24 mN/m). On the other hand, the obtained values of γc for PMMA surface were equal 31.4 and 30.9 mN/m, 31.7 and 31.3 mN/m for C 12(EDMAB) and BDDAB, respectively and they were smaller than the surface tension of PMMA (39.21 mN/m). Using the

  9. Sources and sinks of methyl bromide and methyl chloride in the tallgrass prairie: Applying a stable isotope tracer technique over highly variable gross fluxes

    NASA Astrophysics Data System (ADS)

    Rhew, Robert C.

    2011-09-01

    Methyl bromide (CH3Br) and methyl chloride (CH3Cl) are important stratospheric ozone depleting compounds, but their natural terrestrial sources and sinks have large uncertainties. Gross fluxes of these compounds were measured during the growing season using a stable isotope tracer technique at a temperate tallgrass prairie in northeastern Kansas, United States. Results show that the tallgrass prairie acts as both a source and sink for CH3Br and CH3Cl, with large emissions associated with Amorpha spp. shrubs and a smaller soil sink than expected. Net flux behavior is not significantly altered by the addition of stable isotope tracers. Four models employed to calculate gross fluxes are largely in agreement with each other except at sites with high CH3Cl emissions, where one model most robustly quantifies gross consumption. Gross production rates may increase at Amorpha sites following simulated rainfall, but gross consumption shows no clear response, suggesting that late season microbial uptake of methyl halides is not strongly influenced by sudden changes in soil moisture.

  10. Bromidotetra-kis-(1H-2-ethyl-5-methyl-imidazole-κN)copper(II) bromide.

    PubMed

    Godlewska, Sylwia; Baranowska, Katarzyna; Socha, Joanna; Dołęga, Anna

    2011-12-01

    The Cu(II) ion in the title compound, [CuBr(C(6)H(10)N(2))(4)]Br, is coordinated in a square-based-pyramidal geometry by the N atoms of four imidazole ligands and a bromide anion in the apical site. Both the Cu(II) and Br(-) atoms lie on a crystallographic fourfold axis. In the crystal, the [CuBr(C(6)H(10)N(2))(4)](+) complex cations are linked to the uncoordinated Br(-) anions (site symmetry [Formula: see text]) by N-H⋯Br hydrogen bonds, generating a three-dimensional network. The ethyl group of the imidazole ligand was modelled as disordered over two orientations with occupancies of 0.620 (8) and 0.380 (8).

  11. Persistent modification of Nav1.9 following chronic exposure to insecticides and pyridostigmine bromide.

    PubMed

    Nutter, Thomas J; Cooper, Brian Y

    2014-06-15

    Many veterans of the 1991 Gulf War (GW) returned from that conflict with a widespread chronic pain affecting deep tissues. Recently, we have shown that a 60day exposure to the insecticides permethrin, chlorpyrifos, and pyridostigmine bromide (NTPB) had little influence on nociceptor action potential forming Nav1.8, but increased Kv7 mediated inhibitory currents 8weeks after treatment. Using the same exposure regimen, we used whole cell patch methods to examine whether the influences of NTPB could be observed on Nav1.9 expressed in muscle and vascular nociceptors. During a 60day exposure to NTPB, rats exhibited lowered muscle pain thresholds and increased rest periods, but these measures subsequently returned to normal levels. Eight and 12weeks after treatments ceased, DRG neurons were excised from the sensory ganglia. Whole cell patch studies revealed little change in voltage dependent activation and deactivation of Nav1.9, but significant increases in the amplitude of Nav1.9 were observed 8weeks after exposure. Cellular studies, at the 8week delay, revealed that NTPB also significantly prolonged action potential duration and afterhyperpolarization (22°C). Acute application of permethrin (10μM) also increased the amplitude of Nav1.9 in skin, muscle and vascular nociceptors. In conclusion, chronic exposure to Gulf War agents produced long term changes in the amplitude of Nav1.9 expressed in muscle and vascular nociceptors. The reported increases in Kv7 amplitude may have been an adaptive response to increased Nav1.9, and effectively suppressed behavioral pain measures in the post treatment period. Factors that alter the balance between Nav1.9 and Kv7 could release spontaneous discharge and produce chronic deep tissue pain.

  12. Methyl Bromide alternatives for vegetable production in Georgia: On-farm trials

    USDA-ARS?s Scientific Manuscript database

    Three fumigant alternatives, methyl iodide plus chloropicirn (MIDAS), dimethyl disulfide plus chloropicrin (DMDS), and Telone II plus chloropicrin plus Vapam (3-Way) have exhibited promising results in small plot trials for the control of pests (weeds, pathogens, nematodes) in plasticulture producti...

  13. Biomarkers of lead exposure and DNA methylation within retrotransposons.

    PubMed

    Wright, Robert O; Schwartz, Joel; Wright, Rosalind J; Bollati, Valentina; Tarantini, Letizia; Park, Sung Kyun; Hu, Howard; Sparrow, David; Vokonas, Pantel; Baccarelli, Andrea

    2010-06-01

    DNA methylation is an epigenetic mark that regulates gene expression. Changes in DNA methylation within white blood cells may result from cumulative exposure to environmental metals such as lead. Bone lead, a marker of cumulative exposure, may therefore better predict DNA methylation than does blood lead. In this study we compared associations between lead biomarkers and DNA methylation. We measured global methylation in participants of the Normative Aging Study (all men) who had archived DNA samples. We measured patella and tibia lead levels by K-X-Ray fluorescence and blood lead by atomic absorption spectrophotometry. DNA samples from blood were used to determine global methylation averages within CpG islands of long interspersed nuclear elements-1 (LINE-1) and Alu retrotransposons. A mixed-effects model using repeated measures of Alu or LINE-1 as the dependent variable and blood/bone lead (tibia or patella in separate models) as the primary exposure marker was fit to the data. Overall mean global methylation (+/- SD) was 26.3 +/- 1.0 as measured by Alu and 76.8 +/- 1.9 as measured by LINE-1. In the mixed-effects model, patella lead levels were inversely associated with LINE-1 (beta = -0.25; p < 0.01) but not Alu (beta = -0.03; p = 0.4). Tibia lead and blood lead did not predict global methylation for either Alu or LINE-1. Patella lead levels predicted reduced global DNA methylation within LINE-1 elements. The association between lead exposure and LINE-1 DNA methylation may have implications for the mechanisms of action of lead on health outcomes, and also suggests that changes in DNA methylation may represent a biomarker of past lead exposure.

  14. Persistent Na+ and K+ channel dysfunctions after chronic exposure to insecticides and pyridostigmine bromide.

    PubMed

    Nutter, T J; Jiang, N; Cooper, Brian Y

    2013-12-01

    Many soldiers that served in the 1991 Gulf War developed widespread chronic pain. Exposure to insecticides and the nerve gas prophylactic pyridostigmine bromide (PB) was identified as risk factors by the Research Advisory Committee on Gulf War Veterans' Illnesses (GWI). We examined whether a 60 day exposure to neurotoxicants/PB (NTPB) produced behavioral, molecular and cellular indices of chronic pain in the rat. Male rats were exposed to chlorpyrifos (120mg/kg; SC), permethrin (2.6mg/kg; topical), and PB (13.0mg/kg; oral) or their respective vehicles (corn oil, ethanol, and water). Permethrin can exert profound influences on voltage activated Na(+) channel proteins; while chlorpyrifos and PB can increase absorption and/or retard metabolism of permethrin as well as inhibit cholinesterases. During and after exposure to these agents, we assessed muscle pressure pain thresholds and activity (distance and rest time). Eight and 12 weeks after treatments ceased, we used whole cell patch electrophysiology to examine the physiology of tissue specific DRG nociceptor channel proteins expressed in muscle and putative vascular nociceptors (voltage dependent, activation, inactivation, and deactivation). Behavioral indices were unchanged after treatment with NTPB. Eight weeks after treatments ended, the peak and average conductance of Kv7 mediated K(+) currents were significantly increased in vascular nociceptors. When a specific Kv7 inhibitor was applied (linopirdine, 10μM) NTPB treated vascular nociceptors emitted significantly more spontaneous APs than vehicle treated neurons. Changes to Kv7 channel physiology were resolved 12 weeks after treatment. The molecular alterations to Kv7 channel proteins and the specific susceptibility of the vascular nociceptor population could be important for the etiology of GWI pain.

  15. Degradation of methyl bromide and methyl chloride in soil microcosms: Use of stable C isotope fractionation and stable isotope probing to identify reactions and the responsible microorganisms

    USGS Publications Warehouse

    Miller, L.G.; Warner, K.L.; Baesman, S.M.; Oremland, R.S.; McDonald, I.R.; Radajewski, S.; Murrell, J.C.

    2004-01-01

    Bacteria in soil microcosm experiments oxidized elevated levels of methyl chloride (MeCl) and methyl bromide (MeBr), the former compound more rapidly than the latter. MeBr was also removed by chemical reactions while MeCl was not. Chemical degradation dominated the early removal of MeBr and accounted for more than half of its total loss. Fractionation of stable carbon isotopes during chemical degradation of MeBr resulted in a kinetic isotope effect (KIE) of 59 ?? 7???. Soil bacterial oxidation dominated the later removal of MeBr and MeCl and was characterized by different KIEs for each compound. The KIE for MeBr oxidation was 69 ?? 9??? and the KIE for MeCl oxidation was 49 ?? 3???. Stable isotope probing revealed that different populations of soil bacteria assimilated added 13C-labeled MeBr and MeCl. The identity of the active MeBr and MeCl degrading bacteria in soil was determined by analysis of 16S rRNA gene sequences amplified from 13C-DNA fractions, which identified a number of sequences from organisms not previously thought to be involved in methyl halide degradation. These included Burkholderia , the major clone type in the 13C-MeBr fraction, and Rhodobacter, Lysobacter and Nocardioides the major clone types in the 13C-MeCl fraction. None of the 16S rRNA gene sequences for methyl halide oxidizing bacteria currently in culture (including Aminobacter strain IMB-1 isolated from fumigated soil) were identified. Functional gene clone types closely related to Aminobacter spp. were identified in libraries containing the sequences for the cmuA gene, which codes for the enzyme known to catalyze the initial step in the oxidation of MeBr and MeCl. The cmuA gene was limited to members of the alpha-Proteobacteria whereas the greater diversity demonstrated by the 16S rRNA gene may indicate that other enzymes catalyze methyl halide oxidation in different groups of bacteria. Copyright ?? 2004 Elsevier Ltd.

  16. Degradation of Methyl Bromide and Methyl Chloride in Soil Microcosms: Use of Stable C Isotope Fractionation and Stable Isotope Probing to Identify Reactions and the Responsible Microorganisms

    NASA Astrophysics Data System (ADS)

    Miller, L. G.; Warner, K. L.; Baesman, S. M.; Oremland, R. S.; McDonald, I. R.; Radajewski, S.; Murrell, J. C.

    2003-12-01

    Methyl bromide (MeBr) and methyl chloride (MeCl) are important atmospheric trace gases that contribute directly to stratospheric ozone depletion. These compounds have natural and anthropogenic sources and sinks in both aquatic and terrestrial environments. Soils comprise the largest known sink for MeBr on the Earth's surface and are also a large sink for MeCl. However, the processes that influence the flux of these compounds from air to soil or soil to air are poorly understood at present. Bacteria in soil microcosm experiments oxidized both MeCl and MeBr, the former compound more rapidly than the latter. MeBr was also removed by chemical reactions while MeCl was not. Chemical degradation of MeBr accounted for more than half of its total loss. We applied new techniques to determine if different bacteria were responsible for degrading MeBr and MeCl. Stable isotope probing revealed that different populations of soil bacteria assimilated added 13C-labeled MeBr and MeCl. Soil bacterial oxidation of MeBr and MeCl was characterized by different kinetic isotope effects (KIEs). The KIE for MeBr oxidation by bacteria was 22 +/- 5 \\permil and the KIE for MeCl oxidation was 56 +/- 3 \\permil, suggesting that different bacteria were responsible for degrading each compound. The identity of the active MeBr and MeCl degrading bacteria in soil was determined by analysis of 16S rDNA sequences amplified from 13C-DNA fractions. The diverse population of active bacteria was reflected by the range of sequences found for the cmuA gene, which codes for the enzyme that catalyzes the initial step in the oxidation of MeBr and MeCl. The diversity and number of different bacteria actively degrading MeBr and MeCl in the soil and the number of bacteria identified that contain the enzyme capable of degrading methyl halides were in contrast to the limited number of methyl halide degrading bacteria that have been isolated thus far from soil and aquatic environments; thus suggesting that the

  17. Evaluation of the Efficacy of Methyl Bromide in the Decontamination of Building and Interior Materials Contaminated with Bacillus anthracis Spores

    PubMed Central

    Wendling, Morgan; Richter, William; Lastivka, Andrew; Mickelsen, Leroy

    2016-01-01

    The primary goal of this study was to determine the conditions required for the effective inactivation of Bacillus anthracis spores on materials by using methyl bromide (MeBr) gas. Another objective was to obtain comparative decontamination efficacy data with three avirulent microorganisms to assess their potential for use as surrogates for B. anthracis Ames. Decontamination tests were conducted with spores of B. anthracis Ames and Geobacillus stearothermophilus, B. anthracis NNR1Δ1, and B. anthracis Sterne inoculated onto six different materials. Experimental variables included temperature, relative humidity (RH), MeBr concentration, and contact time. MeBr was found to be an effective decontaminant under a number of conditions. This study highlights the important role that RH has when fumigation is performed with MeBr. There were no tests in which a ≥6-log10 reduction (LR) of B. anthracis Ames was achieved on all materials when fumigation was done at 45% RH. At 75% RH, an increase in the temperature, the MeBr concentration, or contact time generally improved the efficacy of fumigation with MeBr. This study provides new information for the effective use of MeBr at temperatures and RH levels lower than those that have been recommended previously. The study also provides data to assist with the selection of an avirulent surrogate for B. anthracis Ames spores when additional tests with MeBr are conducted. PMID:26801580

  18. Sorption and desorption characteristics of methyl bromide during and after fumigation of pine (Pinus radiata D. Don) logs.

    PubMed

    Hall, Matthew; Najar-Rodriguez, Adriana; Adlam, Anthony; Hall, Alistair; Brash, Don

    2017-05-01

    The sorption and desorption characteristics of methyl bromide (MB) were determined during and after fumigation of recently harvested pine (Pinus radiata D. Don) logs. The effects of dose (48 or 120 g m(-3) ), degree of bark cover (0, 50 or 100%) and end-grain sealing (sealed or unsealed) on sorption and desorption were determined over time. Sorption of MB was proportional to the dose applied and dependent on the amount of end-grain sealed. After 16 h, an average of 70.7 ± 2.5% of the initial concentration remained in the treated space when end-grains were sealed, whereas only 47.3 ± 2.5% remained when unsealed. During aeration, MB was released from logs, initially ranging from 2.8 to 8.8 g · h m(-3) , depending on the treatment. The rate of desorption quickly decreased during aeration. The surface area of a log is the most important factor influencing MB sorption and desorption rates, with greater surface area resulting in greater (de)sorption rates. Sorption data can now be combined with insect toxicity data to estimate a minimum effective dose of MB for further evaluation, while desorption data can be combined with fumigant plume modelling to assess worker safety. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  19. Ultrafast Transient Absorption Spectroscopy Investigation of Excited-State Dynamics of Methyl Ammonium Lead Bromide Perovskite Nanostructures

    NASA Astrophysics Data System (ADS)

    Jamhawi, Abdelqader; Telfah, Hamzeh; Teunis, Meghan B.; Sardar, Rajesh; Liu, Jinjun

    2017-06-01

    Metal halide perovskites are promising materials for light harvesting. Power conversion efficiency (PCE) of such materials can be improved by tuning the band gap energy and suppressing the trap states. In particular, quantum confinement and shape control of nanostructures are two effective approaches to enhance the photovoltaic properties. Here we report femtosecond transient absorption (TA) spectroscopy studies on the photo-induced dynamics of a series of different nanostructures of methyl ammonium lead bromide (MALB) CH_3NH_3PbBr_3: nanoplatelets (2D), nanowires (1D), nonoparticles (0D), and nanocubes (0D). Experimentally obtained TA spectra are simulated using a global model in both the time and wavelength domains. The fit values of center wavelengths and time constants for various processes demonstrate that dimensional and structural confinement affects not only band structure but also exciton dynamics: Sub-picosecond electron and hole relaxation (in the conduction and valence band, respectively) have been observed, while the exciton recombination process is on the timescale of hundreds of picoseconds. Comparison between TA spectra of different nanostructures suggest that the confinement effect plays a significant role in tuning band gaps and minimizing trap states, which can be utilized to improve the PCE of photovoltaic devices.

  20. Methyl Bromide Alternatives for Control of Root-knot Nematode (Meloidogyne spp.) in Tomato Production in Florida

    PubMed Central

    Desaeger, Johan; Dickson, Donald W.; Locascio, S. J.

    2017-01-01

    The following work was initiated to determine the scope of application methodology and fumigant combinations for increasing efficacy of 1,3-dichloropropene (1,3-D) and metam sodium for management of root-knot nematodes (Meloidogyne spp.) in Florida. A series of five experiments were set up during spring and fall seasons to evaluate the potential of different fumigants, alone or in combination, in polyethylene film tomato production. The most promising chemical alternatives to methyl bromide, in terms of root-knot nematode management, were the combinations 1,3-D-chloropicrin, chloropicrin-proprietary solvent ,and 1,3-D-metam sodium. Sprayed or injected metam sodium generally provided only short-term nematode management and by harvest nematode infection was not different from the nontreated control. Drip-applied metam sodium gave good nematode management under high nematode pressure, but needs further verification to establish (i) the importance of soil moisture and temperature on treatment efficacy and (ii) whether similar management can be obtained with fewer than three drip tubes. Broadcast applications of 1,3-D showed better efficacy as compared to applications on a preformed raised bed. Fumigation did not increase tomato yields in spring when root-knot nematode pressure was low, but during fall all chemical treatments increased yields three to five-fold, as root-knot nematode was a major yield-limiting factor. PMID:28706313

  1. Effects of reduced-rate methyl bromide applications under conventional and virtually impermeable plastic film in perennial crop field nurseries.

    PubMed

    Hanson, Bradley D; Gerik, James S; Schneider, Sally M

    2010-08-01

    Producers of perennial crop nursery stock in California use preplant soil fumigation to meet state phytosanitary requirements. Although methyl bromide (MB) has been phased out in many agricultural industries, it is still the preferred treatment in the perennial nursery industry and is used under Critical Use Exemptions and Quarantine/Preshipment provisions of the Montreal Protocol. The present research was conducted to evaluate reduced-rate MB applications sealed with conventional and low-permeability plastic films compared with the primary alternative material. Reduced rates (100-260 kg ha(-1)) of MB applied in combination with chloropicrin (Pic) and sealed with a low-permeability plastic film provided weed and nematode control similar to the industry standard rate of 392 kg ha(-1) MB:Pic (98:2) sealed with high-density polyethylene (HDPE) film. However, the primary alternative chemical, 1,3-dichloropropene (1,3-D), tended to provide slightly lower pest control even on sites with relatively low plant parasitic nematode, soil-borne pathogen and weed pest pressure. If California regulations change to allow the use of low-permeability films in broadcast fumigant applications, the results of this research suggest that reduced rates of MB in perennial crop nurseries could serve as a bridge strategy until more technically, economically and environmentally acceptable alternatives are developed. Published 2010 by John Wiley & Sons, Ltd.

  2. Antibacterial Activity and Bonding Ability of an Orthodontic Adhesive Containing the Antibacterial Monomer 2-Methacryloxylethyl Hexadecyl Methyl Ammonium Bromide

    PubMed Central

    Yu, Fan; Dong, Yan; Yu, Hao-han; Lin, Ping-ting; Zhang, Ling; Sun, Xiang; Liu, Yan; Xia, Yu-ning; Huang, Li; Chen, Ji-hua

    2017-01-01

    Irreversible white spot lesion (WSL) occurs in up to 50% of patients during orthodontic treatment. Therefore, orthodontic adhesives need to be able to inhibit or reduce bacterial growth in order to prevent or minimize WSL. This study evaluated the antibacterial effect and shear bond strength (SBS) of a resin-based orthodontic adhesive containing the antibacterial monomer 2-methacryloxylethyl hexadecyl methyl ammonium bromide (MAE-HB). MAE-HB was added at three concentrations (1, 3, and 5 wt%) to a commercial orthodontic adhesive Transbond XT, while the blank control comprised unmodified Transbond XT. Their antibacterial effects on Streptococcus mutans were investigated after 0 and 180 days of aging. The SBS of metal brackets bonded to the buccal enamel surface of human premolars was assessed. Compared with the blank control, the MAE-HB-incorporated adhesive exhibited a significant contact inhibitory effect on the growth of S. mutans (P < 0.05), even after 180 days of aging. SBS and adhesive remnant index values revealed that the bonding ability of the experimental adhesive was not significantly adversely affected by the incorporation of MAE-HB at any of the three concentrations. Therefore, orthodontic adhesives with strong and long-lasting bacteriostatic properties can be created through the incorporation of MAE-HB without negatively influencing bonding ability. PMID:28169312

  3. Charging of poly(methyl methacrylate) (PMMA) colloids in cyclohexyl bromide: locking, size dependence, and particle mixtures.

    PubMed

    van der Linden, Marjolein N; Stiefelhagen, Johan C P; Heessels-Gürboğa, Gülşen; van der Hoeven, Jessi E S; Elbers, Nina A; Dijkstra, Marjolein; van Blaaderen, Alfons

    2015-01-13

    We studied suspensions of sterically stabilized poly(methyl methacrylate) (PMMA) particles in the solvent cyclohexyl bromide (CHB; εr = 7.92). We performed microelectrophoresis measurements on suspensions containing a single particle species and on binary mixtures, using confocal microscopy to measure the velocity profiles of the particles. We measured the charge of so-called locked PMMA particles, for which the steric stabilizer, a comb-graft stabilizer of poly(12-hydroxystearic acid) (PHSA) grafted on a backbone of PMMA, was covalently bonded to the particle, and for unlocked particles, for which the stabilizer was adsorbed to the surface of the particle. We observed that locked particles had a significantly higher charge than unlocked particles. We found that the charge increase upon locking was due to chemical coupling of 2-(dimethylamino)ethanol to the PMMA particles, which was used as a catalyst for the locking reaction. For particles of different size we obtained the surface potential and charge from the electrophoretic mobility of the particles. For locked particles we found that the relatively high surface potential (∼ +5.1 kBT/e or +130 mV) was roughly constant for all particle diameters we investigated (1.2 μm < σ < 4.4 μm), and that the particle charge was proportional to the square of the diameter.

  4. Evaluation of the Efficacy of Methyl Bromide in the Decontamination of Building and Interior Materials Contaminated with Bacillus anthracis Spores.

    PubMed

    Wood, Joseph P; Wendling, Morgan; Richter, William; Lastivka, Andrew; Mickelsen, Leroy

    2016-01-22

    The primary goal of this study was to determine the conditions required for the effective inactivation of Bacillus anthracis spores on materials by using methyl bromide (MeBr) gas. Another objective was to obtain comparative decontamination efficacy data with three avirulent microorganisms to assess their potential for use as surrogates for B. anthracis Ames. Decontamination tests were conducted with spores of B. anthracis Ames and Geobacillus stearothermophilus, B. anthracis NNR1Δ1, and B. anthracis Sterne inoculated onto six different materials. Experimental variables included temperature, relative humidity (RH), MeBr concentration, and contact time. MeBr was found to be an effective decontaminant under a number of conditions. This study highlights the important role that RH has when fumigation is performed with MeBr. There were no tests in which a ≥6-log10 reduction (LR) of B. anthracis Ames was achieved on all materials when fumigation was done at 45% RH. At 75% RH, an increase in the temperature, the MeBr concentration, or contact time generally improved the efficacy of fumigation with MeBr. This study provides new information for the effective use of MeBr at temperatures and RH levels lower than those that have been recommended previously. The study also provides data to assist with the selection of an avirulent surrogate for B. anthracis Ames spores when additional tests with MeBr are conducted. Copyright © 2016 Wood et al.

  5. Potential impacts of imposing methyl bromide phaseout on US strawberry growers: a case study of a nomination for a critical use exemption under the Montreal Protocol.

    PubMed

    Norman, Catherine S

    2005-04-01

    The Montreal Protocol on Substances that Deplete the Ozone Layer requires developed countries to phaseout methyl bromide production and non-quarantine uses by 2005 and developing countries to do the same by 2015. Exemptions to phaseout have been significant in slowing the process of abatement; many countries have applied for exemptions for some uses, partly on grounds that phaseout is economically infeasible. Data on the US strawberry market are used to investigate grower costs arising from substitution away from methyl bromide, the impact of trends in and characteristics of the demand for fresh strawberries, and characteristics of trade with countries not yet required to eliminate use of the compound. It appears that actual net costs to growers will be much smaller than the simple increase in production costs cited in the US nomination for exemption.

  6. Octatropine-methyl-bromide and sulglycotide salt in the short-term treatment of active duodenal ulcer. A double blind endoscopic study of 40 outpatients.

    PubMed

    Dobrilla, G; Valentini, M; Bonoldi, M C; Piazzi, L

    1989-01-01

    Forty outpatients with endoscopically confirmed duodenal ulcers were entered in a double blind trial. They were randomly allocated to octatropine-methyl-bromide and sulglycotide salt (GVP) or placebo. The results show that the combination of the two drugs is less efficacious than the two constituent substances taken separately, is not more efficacious than placebo in ulcer healing, and is ineffective with regard to ulcer pain.

  7. Dose-morality and large-scale studies for controlling codling moth (Lepidoptera: Tortricidae) eggs on 'd'Agen' plums by using methyl bromide.

    PubMed

    Leesch, J G; Tebbets, J S; Obenland, D M; Vail, P V; Tebbets, J C

    1999-08-01

    Codling moth, Cydia pomonella (L.), eggs on 'd'Agen' cultivar of plums, Prunus salicina Lindl., were treated with methyl bromide to determine if a quarantine treatment could be developed so that the plums could be exported to Japan from the United States. Small-scale tests consisted of treating codling moth eggs on plums with various doses of methyl bromide at 20 degrees C for 2 h. Small-scale tests showed that 0- to 24-h-old eggs of codling moth on the plums were controlled by doses > 22.5 g/m3. Because testing showed that 48 g/m3 had no adverse effect on the quality of plums, this dose was chosen for large-scale testing to establish the quarantine dose. Large-scale tests consisted of treating plums at 18.5 degrees C for 2 h using methyl bromide at a dose of 48 mg/liter. Large-scale tests showed that the dose of 48 g/m3 killed all 0- to 24-h-old codling moth eggs exposed on plums in packing cartons without affecting the quality of the plums.

  8. Puerto Rico Pesticides Distributors Agree To Come into Compliance with Federal Law and Provide Training To Settle Case Involving Illegal Sale of Methyl Bromide Pesticides In Puerto Rico and the U.S. Virgin Islands

    EPA Pesticide Factsheets

    EPA News Release: Puerto Rico Pesticides Distributors Agree To Come into Compliance with Federal Law and Provide Training To Settle Case Involving Illegal Sale of Methyl Bromide Pesticides In Puerto Rico and the U.S. Virgin Islands

  9. Bacterial oxidation of dibromomethane and methyl bromide in natural waters and enrichment cultures

    USGS Publications Warehouse

    Goodwin, K.D.; Schaefer, J.K.; Oremland, R.S.

    1998-01-01

    Bacterial oxidation of 14CH2Br2 and 14CH3Br was measured in freshwater, estuarine, seawater, and hypersaline-alkaline samples. In general, bacteria from the various sites oxidized similar amounts of 14CH2Br2 and comparatively less 14CH3Br. Bacterial oxidation of 14CH3Br was rapid in freshwater samples compared to bacterial oxidation of 14CH3Br in more saline waters. Freshwater was also the only site in which methyl fluoride-sensitive bacteria (e.g., methanotrophs or nitrifiers) governed brominated methane oxidation. Half-life calculations indicated that bacterial oxidation of CH2Br2 was potentially significant in all of the waters tested. In contrast, only in freshwater was bacterial oxidation of CH3Br as fast as chemical removal. The values calculated for more saline sites suggested that bacterial oxidation of CH3Br was relatively slow compared to chemical and physical loss mechanisms. However, enrichment cultures demonstrated that bacteria in seawater can rapidly oxidize brominated methanes. Two distinct cultures of nonmethanotrophic methylotrophs were recovered; one of these cultures was able to utilize CH2Br2 as a sole carbon source, and the other was able to utilize CH3Br as a sole carbon source.

  10. Identification of Methyl Halide-Utilizing Genes in the Methyl Bromide-Utilizing Bacterial Strain IMB-1 Suggests a High Degree of Conservation of Methyl Halide-Specific Genes in Gram-Negative Bacteria

    USGS Publications Warehouse

    Woodall, C.A.; Warner, K.L.; Oremland, R.S.; Murrell, J.C.; McDonald, I.R.

    2001-01-01

    Strain IMB-1, an aerobic methylotrophic member of the alpha subgroup of the Proteobacteria, can grow with methyl bromide as a sole carbon and energy source. A single cmu gene cluster was identified in IMB-1 that contained six open reading frames: cmuC, cmuA, orf146, paaE, hutI, and partial metF. CmuA from IMB-1 has high sequence homology to the methyltransferase CmuA from Methylobacterium chloromethanicum and Hyphomicrobium chloromethanicum and contains a C-terminal corrinoid-binding motif and an N-terminal methyl-transferase motif. However, cmuB, identified in M. chloromethanicum and H. chloromethanicum, was not detected in IMB-1.

  11. Protection by pyridostigmine bromide of marmoset hemi-diaphragm acetylcholinesterase activity after soman exposure.

    PubMed

    Haigh, Julian R; Adler, Michael; Apland, James P; Deshpande, Sharad S; Barham, Charles B; Desmond, Patrick; Koplovitz, Irwin; Lenz, David E; Gordon, Richard K

    2010-09-06

    Pyridostigmine bromide (PB) was approved by the U.S. Food and Drug Administration (FDA) in 2003 as a pretreatment in humans against the lethal effects of the irreversible nerve agent soman (GD). Organophosphate (OP) chemical warfare agents such as GD exert their toxic effects by inhibiting acetylcholinesterase (AChE) from terminating the action of acetylcholine at postsynaptic sites in cholinergic nerve terminals (including crucial peripheral muscle such as diaphragm). As part of the post-marketing approval of PB, the FDA required (under 21CFR314, the "two animal rule") the study of a non-human primate model (the common marmoset Callithrix jacchus jacchus) to demonstrate increased survival against lethal GD poisoning, and protection of physiological hemi-diaphragm function after PB pretreatment and subsequent GD exposure. Marmosets (male and female) were placed in the following experimental groups: (i) control (saline pretreatment only), (ii) low dose PB (12.5 microg/kg), or (iii) high dose (39.5 microg/kg) PB. Thirty minutes after the PB dose, animals were challenged with either saline (control) or soman (GD, 45 microg/kg), followed 1 min later by atropine (2mg/kg) and 2-PAM (25mg/kg). After a further 16 min, animals were euthanized and the complete diaphragm removed; the right hemi-diaphragm was frozen immediately at -80 degrees C, and the left hemi-diaphragm was placed in a tissue bath for 4h (to allow for decarbamylation to occur), then frozen. AChE activities were determined using the automated WRAIR cholinesterase assay. Blood samples were collected for AChE activities prior to PB, before GD challenge, and after sacrifice. RBC-AChE was inhibited by approximately 18% and 50% at the low and high doses of PB, respectively, compared to control (baseline) activity. In the absence of PB pretreatment, the inhibition of RBC-AChE by GD was 98%. The recovery of hemi-diaphragm AChE activity after the 4h wash period (decarbamylation) was approximately 8% and 17%, at the

  12. Rapid DNA Methylation Changes after Exposure to Traffic Particles

    PubMed Central

    Baccarelli, Andrea; Wright, Robert O.; Bollati, Valentina; Tarantini, Letizia; Litonjua, Augusto A.; Suh, Helen H.; Zanobetti, Antonella; Sparrow, David; Vokonas, Pantel S.; Schwartz, Joel

    2009-01-01

    Rationale: Exposure to particulate air pollution has been related to increased hospitalization and death, particularly from cardiovascular disease. Lower blood DNA methylation content is found in processes related to cardiovascular outcomes, such as oxidative stress, aging, and atherosclerosis. Objectives: We evaluated whether particulate pollution modifies DNA methylation in heavily methylated sequences with high representation throughout the human genome. Methods: We measured DNA methylation of long interspersed nucleotide element (LINE)-1 and Alu repetitive elements by quantitative polymerase chain reaction–pyrosequencing of 1,097 blood samples from 718 elderly participants in the Boston area Normative Aging Study. We used covariate-adjusted mixed models to account for within-subject correlation in repeated measures. We estimated the effects on DNA methylation of ambient particulate pollutants (black carbon, particulate matter with aerodynamic diameter ≤ 2.5 μm [PM2.5], or sulfate) in multiple time windows (4 h to 7 d) before the examination. We estimated standardized regression coefficients (β) expressing the fraction of a standard deviation change in DNA methylation associated with a standard deviation increase in exposure. Measurements and Main Results: Repetitive element DNA methylation varied in association with time-related variables, such as day of the week and season. LINE-1 methylation decreased after recent exposure to higher black carbon (β = −0.11; 95% confidence interval [CI], −0.18 to −0.04; P = 0.002) and PM2.5 (β = −0.13; 95% CI, −0.19 to −0.06; P < 0.001 for the 7-d moving average). In two-pollutant models, only black carbon, a tracer of traffic particles, was significantly associated with LINE-1 methylation (β = −0.09; 95% CI, −0.17 to −0.01; P = 0.03). No association was found with Alu methylation (P > 0.12). Conclusions: We found decreased repeated-element methylation after exposure to traffic particles. Whether

  13. A study of the photodissociation physics of methyl bromide on gallium arsenide(110)

    SciTech Connect

    Schwarz, W.N.

    1992-01-01

    A study of the effects of laser light at various wavelengths, from UV (193 nm) to IR (860 nm), on the reaction of a well characterized ordered GaAs (110) surface with physisorbed CH[sub 3]Br is described. The adsorption of CH[sub 3]Br on the surface is found to be molecular. The amount of coverage is determined by a calibration of exposure versus number of monolayers. Information about the dynamics is obtained by the use of pulsed laser light of 20 ns pulse width combined with time-of-flight (TOF) measurements. The TOF spectra show five distinct features: (1) A direct dissociation peak is observed with UV light of 193 and 248 nm wavelength on samples with coverages >1 ML. For coverages <1 ML this channel is quenched due to resonant electron tunneling. (2) The peak initiated by DEA of hot electrons is fixed in energy at 1.1 eV, independent of the wavelength of the incident light, and has a threshold slightly below 351 nm. This peak is only detectable for coverages >1 ML. (3) The DEA feature due to thermalized electrons appears at different energies for 1 and 2 ML coverage. These energies are not sensitive to the wavelength of the incident laser light, and are located at 0.6 eV for 1 ML and at 0.25 eV for 2 ML. The threshold for this process coincides with the fundamental band gap of GaAs. Both peaks decays as a function of irradiation exposure. The DEA reaction product Br[sup [minus

  14. Crystal structure of 2-bromo-3-di­methyl­amino-N,N,N′,N′,4-penta­methyl-4-(tri­methyl­sil­yloxy)pent-2-eneamidinium bromide

    PubMed Central

    Tiritiris, Ioannis; Kress, Ralf; Kantlehner, Willi

    2015-01-01

    The reaction of the ortho­amide 1,1,1-tris­(di­methyl­amino)-4-methyl-4-(tri­methyl­sil­yloxy)pent-2-yne with bromine in benzene, yields the title salt, C15H33BrN3OSi+·Br−. The C—N bond lengths in the amidinium unit are 1.319 (6) and 1.333 (6) Å, indicating double-bond character, pointing towards charge delocalization within the NCN plane. The C—Br bond length of 1.926 (5) Å is characteristic for a C—Br single bond. Additionally, there is a bromine–bromine inter­action [3.229 (3) Å] present involving the anion and cation. In the crystal, weak C—H⋯Br inter­actions between the methyl H atoms of the cation and the bromide ions are present. PMID:26870498

  15. Atomistic simulations of the solid-liquid transition of 1-ethyl-3-methyl imidazolium bromide ionic liquid

    NASA Astrophysics Data System (ADS)

    Feng, Haijun; Zhou, Jian; Qian, Yu

    2011-10-01

    Achieving melting point around room temperature is important for applications of ionic liquids. In this work, molecular dynamics simulations are carried out to investigate the solid-liquid transition of ionic liquid 1-ethyl-3-methyl imidazolium bromide ([emim]Br) by direct heating, hysteresis, void-nucleation, sandwich, and microcanonical ensemble approaches. Variations of the non-bonded energy, density, diffusion coefficient, and translational order parameter of [emim]Br are analyzed as a function of temperature, and a coexisting solid-liquid system is achieved in the microcanonical ensemble method. The melting points obtained from the first three methods are 547 ± 8 K, 429 ± 8 K, and 370 ± 6 K; while for the sandwich method, the melting points are 403 ± 4 K when merging along the x-axis by anisotropic isothermal-isobaric (NPT) ensemble, 393 ± 4 K when along the y-axis by anisotropic NPT ensemble, and 375 ± 4 K when along the y-axis by isotropic NPT ensemble. For microcanonical ensemble method, when the slabs are merging along different directions (x-axis, y-axis, and z-axis), the melting points are 364 ± 3 K, 365 ± 3 K, and 367 ± 3 K, respectively, the melting points we get by different methods are approximately 55.4%, 21.9%, 5.1%, 14.5%, 11.6%, 6.5%, 3.4%, 3.7%, and 4.3% higher than the experimental value of 352 K. The advantages and disadvantages of each method are discussed. The void-nucleation and microcanonical ensemble methods are most favorable for predicting the solid-liquid transition.

  16. Consumption of tropospheric levels of methyl bromide by C(1) compound-utilizing bacteria and comparison to saturation kinetics.

    PubMed

    Goodwin, K D; Varner, R K; Crill, P M; Oremland, R S

    2001-12-01

    Pure cultures of methylotrophs and methanotrophs are known to oxidize methyl bromide (MeBr); however, their ability to oxidize tropospheric concentrations (parts per trillion by volume [pptv]) has not been tested. Methylotrophs and methanotrophs were able to consume MeBr provided at levels that mimicked the tropospheric mixing ratio of MeBr (12 pptv) at equilibrium with surface waters ( approximately 2 pM). Kinetic investigations using picomolar concentrations of MeBr in a continuously stirred tank reactor (CSTR) were performed using strain IMB-1 and Leisingeria methylohalidivorans strain MB2(T) - terrestrial and marine methylotrophs capable of halorespiration. First-order uptake of MeBr with no indication of threshold was observed for both strains. Strain MB2(T) displayed saturation kinetics in batch experiments using micromolar MeBr concentrations, with an apparent K(s) of 2.4 microM MeBr and a V(max) of 1.6 nmol h(-1) (10(6) cells)(-1). Apparent first-order degradation rate constants measured with the CSTR were consistent with kinetic parameters determined in batch experiments, which used 35- to 1 x 10(7)-fold-higher MeBr concentrations. Ruegeria algicola (a phylogenetic relative of strain MB2(T)), the common heterotrophs Escherichia coli and Bacillus pumilus, and a toluene oxidizer, Pseudomonas mendocina KR1, were also tested. These bacteria showed no significant consumption of 12 pptv MeBr; thus, the ability to consume ambient mixing ratios of MeBr was limited to C(1) compound-oxidizing bacteria in this study. Aerobic C(1) bacteria may provide model organisms for the biological oxidation of tropospheric MeBr in soils and waters.

  17. Quarantine Treatments of Imported Nursery Plants and Exported Cut Flowers by Phosphine Gas (PH3) as Methyl Bromide Alternative.

    PubMed

    Kim, Bong Su; Park, Chung Gyoo; Moon, Young Mi; Sung, Bo Kyung; Ren, Yonglin; Wylie, Stephen J; Lee, Byung Ho

    2016-09-15

    Quarantine treatments by phosphine (PH3) gas have been performed to replace methyl bromide (MeBr) for export cut flowers and imported nursery plant in Korea. In this preliminary study, two dominant insect pests of cut flowers, Tetranychus urticae Koch and Frankliniella occidentalis Pergande, and the dominant insect pest of nursery plants, Planococcus citri Risso, were used to certify optimum concentration and fumigation time, along with evaluation of phytotoxic damages. To validate the results of preliminary tests, quarantine treatments for export cut flowers was performed in a 58-m(3) reefer container. When 14 species of cut flowers were fumigated with 2 g m(-3) PH3 for 24 h (Ct product was 30.9 g h m(-3)) at 5 °C, all pests were effectively controlled and no phytotoxic damage were observed on roses and chrysanthemums. On quarantine trials for imported nursery trees, which was performed at 10 m(3) scale covered with a PVC-tarpaulin tent, 2 g m(-3) of PH3 for 24 h (Ct product was 30.0 g h m(-3)) at 15 °C was enough to kill all pests and no damage was observed on seven species of nursery plants. Phosphine gas shows the promise as MeBr alternative to perishable commodities in terms of efficacy to certain quarantine pest and maintenance of its quality as well as being a more environmentally safe fumigant. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Consumption of Tropospheric Levels of Methyl Bromide by C1 Compound-Utilizing Bacteria and Comparison to Saturation Kinetics

    USGS Publications Warehouse

    Goodwin, K.D.; Varner, R.K.; Crill, P.M.; Oremland, R.S.

    2001-01-01

    Pure cultures of methylotrophs and methanotrophs are known to oxidize methyl bromide (MeBr); however, their ability to oxidize tropospheric concentrations (parts per trillion by volume [pptv]) has not been tested. Methylotrophs and methanotrophs were able to consume MeBr provided at levels that mimicked the tropospheric mixing ratio of MeBr (12 pptv) at equilibrium with surface waters (???2 pM). Kinetic investigations using picomolar concentrations of MeBr in a continuously stirred tank reactor (CSTR) were performed using strain IMB-1 and Leisingeria methylohalidivorans strain MB2T - terrestrial and marine methylotrophs capable of halorespiration. First-order uptake of MeBr with no indication of threshold was observed for both strains. Strain MB2T displayed saturation kinetics in batch experiments using micromolar MeBr concentrations, with an apparent Ks of 2.4 ??M MeBr and a Vmax of 1.6 nmol h-1 (106 cells)-1. Apparent first-order degradation rate constants measured with the CSTR were consistent with kinetic parameters determined in batch experiments, which used 35- to 1 ?? 107-fold-higher MeBr concentrations. Ruegeria algicola (a phylogenetic relative of strain MB2T), the common heterotrophs Escherichia coli and Bacillus pumilus, and a toluene oxidizer, Pseudomonas mendocina KR1, were also tested. These bacteria showed no significant consumption of 12 pptv MeBr; thus, the ability to consume ambient mixing ratios of MeBr was limited to C1 compound-oxidizing bacteria in this study. Aerobic C1 bacteria may provide model organisms for the biological oxidation of tropospheric MeBr in soils and waters.

  19. Octatropine methyl bromide and diazepam combination (Valpinax) in patients with irritable bowel syndrome: a multicentre, randomized, placebo-controlled trial.

    PubMed

    Pace, F; Maurano, A; Ciacci, C; Savarino, V; Attili, A; Iaquinto, G; Magni, E; Porro, G Bianchi

    2010-03-01

    To investigate the efficacy and tolerability of octatropine methyl bromide plus diazepam (Valpinax) in patients with irritable bowel syndrome (IBS). We conducted a randomized, double-blind, multicentre study in 186 patients aged 18-65 years with IBS diagnosed according to Rome II criteria. Following a 2-week washout period, patients received octatropine plus diazepam 40 mg/2.5 mg twice daily or placebo for 6 weeks. The primary efficacy endpoint was response to a weekly question: "did you have satisfactory relief of your abdominal pain and discomfort during the last week?" Other endpoints included abdominal swelling, abdominal pain and discomfort, symptom severity, and the number of bowel movements. A prespecified subgroup analysis was conducted in patients with an abdominal pain and discomfort score > or = 3. The primary efficacy endpoint showed a tendency towards a statistically significant benefit for octatropine plus diazepam over placebo among patients with a baseline abdominal pain and discomfort score of > or = 3 (3 vs. 0 patients; p = 0.059). Octatropine plus diazepam demonstrated significant improvements from baseline in all parameters assessed, but not compared with placebo. Adverse events were reported in 15.1% of patients receiving octatropine plus diazepam. Patients with IBS and an abdominal pain and discomfort score of > or = 3, who may be considered in the active phase of the disease, may derive some benefits from octatropine plus diazepam. This study highlights that Rome II criteria should be considered with particular care in the design of a clinical trial, since it does not consider disease activity level on admission.

  20. Quarantine Treatments of Imported Nursery Plants and Exported Cut Flowers by Phosphine Gas (PH3) as Methyl Bromide Alternative.

    PubMed

    Su Kim, Bong; Park, Chung Gyoo; Mi Moon, Young; Sung, Bo Kyung; Ren, Yonglin; Wylie, Stephen J; Ho Lee, Byung

    2016-12-01

    Quarantine treatments by phosphine (PH3) gas have been performed to replace methyl bromide (MeBr) for export cut flowers and imported nursery plant in Korea. In this preliminary study, two dominant insect pests of cut flowers, Tetranychus urticae Koch and Frankliniella occidentalis Pergande, and the dominant insect pest of nursery plants, Planococcus citri Risso, were used to certify optimum concentration and fumigation time, along with evaluation of phytotoxic damages. To validate the results of preliminary tests, quarantine treatments for export cut flowers was performed in a 58-m(3) reefer container. When 14 species of cut flowers were fumigated with 2 g m(-3) PH3 for 24 h (Ct product was 30.9 g h m(-3)) at 5 °C, all pests were effectively controlled and no phytotoxic damage were observed on roses and chrysanthemums. On quarantine trials for imported nursery trees, which was performed at 10 m(3) scale covered with a PVC-tarpaulin tent, 2 g m(-3) of PH3 for 24 h (Ct product was 30.0 g h m(-3)) at 15 °C was enough to kill all pests and no damage was observed on seven species of nursery plants. Phosphine gas shows the promise as MeBr alternative to perishable commodities in terms of efficacy to certain quarantine pest and maintenance of its quality as well as being a more environmentally safe fumigant. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Laboratory production of bromoform, methylene bromide, and methyl iodide by macroalgae and distribution in nearshore southern California waters

    SciTech Connect

    Manley, S.L. ); Goodwin, K.; North, W.J. )

    1992-12-01

    Production rates of bromoform (CHBr[sub 3]), methylene bromide (CH[sub 2]Br[sub 2]), and methyl iodide (CH[sub 3]I) were measured in the laboratory for 11 species of marine macroalgae. Production rates of the volatile bromomethanes extrapolated to a global scale suggest that marine macroalgae produce 2 [times] 10[sup 11] g Br yr[sup [minus]1] (1 [times] 10[sup 9] mol Br yr[sup [minus]1]), 98% of which is bromoform. Laminarians (kelps) produce 61% of this organic Br. These calculations suggest that marine macroalgae are important in the biogeochemical cycling of Br. Seawater concentrations of CHBr[sub 3], CH[sub 2]Br[sub 2], and CH[sub 3]I were determined from various southern California coastal locales. High concentrations were measured in seawater from the canopy and the bottom of a dense bed of Macrocystis as compared to other sites. Surface seawater concentrations of these halomethanes showed a strong cross-shore gradient with the highest concentration in the kelp canopy and the lowest at 5 km offshore. Seawater adjacent to decaying macroalgae on the bottom of a submarine canyon was not enriched in halomethanes relative to surface water. Water exiting a productive estuary was enriched only with CH[sub 2]Br[sub 2], although two algal species that are abundant there (Ulva and Enteromorpha) showed high laboratory production rates of both CHBr[sub 3] and CH[sub 2]Br[sub 2]. 21 refs., 2 figs., 2 tabs.

  2. Dissociation of internal energy-selected methyl bromide ion revealed from threshold photoelectron-photoion coincidence velocity imaging.

    PubMed

    Tang, Xiaofeng; Zhou, Xiaoguo; Sun, Zhongfa; Liu, Shilin; Liu, Fuyi; Sheng, Liusi; Yan, Bing

    2014-01-28

    Dissociative photoionization of methyl bromide (CH3Br) in an excitation energy range of 10.45-16.90 eV has been investigated by using threshold photoelectron-photoion coincidence (TPEPICO) velocity imaging. The coincident time-of-flight mass spectra indicate that the ground state X(2)E of CH3Br(+) is stable, and both A(2)A1 and B(2)E ionic excited states are fully dissociative to produce the unique fragment ion of CH3 (+). From TPEPICO 3D time-sliced velocity images of CH3 (+) dissociated from specific state-selected CH3Br(+) ion, kinetic energy release distribution (KERD) and angular distribution of CH3 (+) fragment ion are directly obtained. Both spin-orbit states of Br((2)P) atom can be clearly observed in fast dissociation of CH3Br(+)(A(2)A1) ion along C-Br rupture, while a KERD of Maxwell-Boltzmann profile is obtained in dissociation of CH3Br(+)(B(2)E) ion. With the aid of the re-calculated potential energy curves of CH3Br(+) including spin-orbit coupling, dissociation mechanisms of CH3Br(+) ion in A(2)A1 and B(2)E states along C-Br rupture are revealed. For CH3Br(+)(A(2)A1) ion, the CH3 (+) + Br((2)P1/2) channel is occurred via an adiabatic dissociation by vibration, while the Br((2)P3/2) formation is through vibronic coupling to the high vibrational level of X(2)E state followed by rapid dissociation. C-Br bond breaking of CH3Br(+)(B(2)E) ion can occur via slow internal conversion to the excited vibrational level of the lower electronic states and then dissociation.

  3. Associative DNA methylation changes in children with prenatal alcohol exposure.

    PubMed

    Laufer, Benjamin I; Kapalanga, Joachim; Castellani, Christina A; Diehl, Eric J; Yan, Liying; Singh, Shiva M

    2015-01-01

    Prenatal alcohol exposure (PAE) can cause fetal alcohol spectrum disorders (FASD). Previously, we assessed PAE in brain tissue from mouse models, however whether these changes are present in humans remains unknown. In this report, we show some identical changes in DNA methylation in the buccal swabs of six children with FASD using the 450K array. The changes occur in genes related to protocadherins, glutamatergic synapses, and hippo signaling. The results were found to be similar in another heterogeneous replication group of six FASD children. The replicated results suggest that children born with FASD have unique DNA methylation defects that can be influenced by sex and medication exposure. Ultimately, with future clinical development, assessment of DNA methylation from buccal swabs can provide a novel strategy for the diagnosis of FASD.

  4. New Insights into Methyl Bromide Cooxidation by Nitrosomonas europaea Obtained by Experimenting with Moderately Low Density Cell Suspensions†

    PubMed Central

    Duddleston, Khrystyne N.; Bottomley, Peter J.; Porter, Angela J.; Arp, Daniel J.

    2000-01-01

    We examined the rates and sustainability of methyl bromide (MeBr) oxidation in moderately low density cell suspensions (∼6 × 107 cells ml−1) of the NH3-oxidizing bacterium Nitrosomonas europaea. In the presence of 10 mM NH4+ and 0.44, 0.22, and 0.11 mM MeBr, the initial rates of MeBr oxidation were sustained for 12, 12, and 24 h, respectively, despite the fact that only 10% of the NH4+, 18% of the NH4+, and 35% of the NH4+, respectively, were consumed. Although the duration of active MeBr oxidation generally decreased as the MeBr concentration increased, similar amounts of MeBr were oxidized with a large number of the NH4+-MeBr combinations examined (10 to 20 μmol mg [dry weight] of cells−1). Approximately 90% of the NH3-dependent O2 uptake activity and the NO2−-producing activity were lost after N. europaea was exposed to 0.44 mM MeBr for 24 h. After MeBr was removed and the cells were resuspended in fresh growth medium, NO2− production increased exponentially, and 48 to 60 h was required to reach the level of activity observed initially in control cells that were not exposed to MeBr. It is not clear what percentage of the cells were capable of cell division after MeBr oxidation because NO2− accumulated more slowly in the exposed cells than in the unexposed cells despite the fact that the latter were diluted 10-fold to create inocula which exhibited equal initial activities. The decreases in NO2−-producing and MeBr-oxidizing activities could not be attributed directly to NH4+ or NH3 limitation, to a decrease in the pH, to the composition of the incubation medium, or to toxic effects caused by accumulation of the end products of oxidation (NO2− and formaldehyde) in the medium. Additional cooxidation-related studies of N. europaea are needed to identify the mechanism(s) responsible for the MeBr-induced loss of cell activity and/or viability, to determine what percentages of cells damaged by cooxidative activities are culturable, and to determine if

  5. Synthesis of tetraaza bromide macrocyclic and studies of its effect on poly(methyl methacrylate) grafted natural rubber (MG49) - lithium tertrafluoroborate (LiBF4) films

    NASA Astrophysics Data System (ADS)

    Mariam, Siti Nor; Yamin, Bohari M.; Ahmad, Azizan

    2013-11-01

    Good Poly(Methyl Methacrylate) Grafted natural Rubber (MG49) films with homogeneous and smooth surface were obtained in the presence of Lithium Tertrafluoroborate (LiBF4) and 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-7,14-dienium bromide, (Me6N4H4)Br2 as dopants. The conductivity was found to be 3.63×10-6 S/cm an increase by seven fold compare to the undoped MG49.

  6. Synthesis of tetraaza bromide macrocyclic and studies of its effect on poly(methyl methacrylate) grafted natural rubber (MG49) - lithium tertrafluoroborate (LiBF{sub 4}) films

    SciTech Connect

    Mariam, Siti Nor; Yamin, Bohari M.; Ahmad, Azizan

    2013-11-27

    Good Poly(Methyl Methacrylate) Grafted natural Rubber (MG49) films with homogeneous and smooth surface were obtained in the presence of Lithium Tertrafluoroborate (LiBF{sub 4}) and 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-7,14-dienium bromide, (Me{sub 6}N{sub 4}H{sub 4})Br{sub 2} as dopants. The conductivity was found to be 3.63×10{sup −6} S/cm an increase by seven fold compare to the undoped MG49.

  7. Arsenic exposure and DNA methylation among elderly men

    PubMed Central

    Lambrou, Angeliki; Baccarelli, Andrea; Wright, Robert O.; Weisskopf, Marc; Bollati, Valentina; Amarasiriwardena, Chitra; Vokonas, Pantel; Schwartz, Joel

    2012-01-01

    BACKGROUND Arsenic exposure has been linked to epigenetic modifications such as DNA methylation in in vitro and animal studies. This association has also been explored in highly exposed human populations, but studies among populations environmentally exposed to low arsenic levels are lacking. METHODS We evaluated the association between exposure to arsenic, measured in toenails, and blood DNA methylation in Alu and Long Interspersed Nucleotide Element-1 (LINE-1) repetitive elements in elderly men environmentally exposed to low levels of arsenic. We also explored potential effect modification by plasma folate, cobalamin (vitamin B12), and pyridoxine (vitamin B6). The study population was 581 participants from the Normative Aging Study in Boston, of whom 434, 140, and 7 had 1, 2, and 3 visits, respectively, between 1999-2002 and 2006-2007. We used mixed-effects models and included interaction terms to assess potential effect modification by nutritional factors. RESULTS There was a trend of increasing Alu and decreasing LINE-1 DNA methylation as arsenic exposure increased. In subjects with plasma folate below the median (< 14.1 ng/ml), arsenic was positively associated with Alu DNA methylation (β=0.08 [95% confidence interval = 0.03 to 0.13] for one interquartile range [0.06μg/g] increase in arsenic) while a negative association was observed in subjects with plasma folate above the median (β=-0.08 [-0.17 to 0.01]). CONCLUSIONS We found an association between arsenic exposure and DNA methylation in Alu repetitive elements that varied by folate level. This suggests a potential role for nutritional factors in arsenic toxicity. PMID:22833016

  8. Effects of soil type, moisture content, redox potential and methyl bromide fumigation on Kd values of radio-selenium in soil.

    PubMed

    Ashworth, D J; Moore, J; Shaw, G

    2008-07-01

    Understanding the processes that determine the solid-liquid partitioning (K(d) value) of Se is of fundamental importance in assessing the risk associated with the disposal of radio-selenium-containing waste. Using a mini-column (rather than batch) approach, K(d) values for (75)Se were determined over time in relation to soil moisture content (field capacity or saturated), redox potential and methyl bromide fumigation (used to disrupt the soil microbial population) in three contrasting soil types: clay loam, organic and sandy loam. The K(d) values were generally in the range 50-500 L kg(-1), with mean soil K(d) increasing with increasing organic matter content. Saturation with water lowered the measured redox potentials in the soils. However, only in the sandy loam soil did redox potential become negative, and this led to an increase in (75)Se K(d) value in this soil. Comparison of the data with the Eh-pH stability diagram for Se suggested that such strong reduction may have been consistent with the formation of the insoluble Se species, selenide. These findings, coupled with the fact that methyl bromide fumigation had no discernible effect on (75)Se K(d) value in the sandy loam soil, suggest that geochemical, rather than microbial, processes controlled (75)Se partitioning. The inter-relations between soil moisture content, redox potential and Se speciation should be considered in the modelling and assessment of radioactive Se fate and transport in the environment.

  9. Preliminary study of propyl bromide exposure among New Jersey dry cleaners as a result of a pending ban on perchloroethylene.

    PubMed

    Blando, James D; Schill, Donald P; De La Cruz, Mary Pauline; Zhang, Lin; Zhang, Junfeng

    2010-09-01

    Many states are considering, and some states have actively pursued, banning the use of perchloroethylene (PERC) in dry cleaning establishments. Proposed legislation has led many dry cleaners to consider the use of products that contain greater than 90% n-propyl bromide (n-PB; also called 1-bromopropane or 1-BP). Very little information is known about toxicity and exposure to n-PB. Some n-PB-containing products are marketed as nonhazardous and "green" or "organic." This has resulted in some users perceiving the solvent as nontoxic and has resulted in at least one significant poisoning incident in New Jersey. In addition, many dry cleaning operators may not realize that the machine components and settings must be changed when converting from PERC to n-PB containing products. Not performing these modifications may result in overheating and significant leaks in the dry cleaning equipment. A preliminary investigation was conducted of the potential exposures to n-PB and isopropyl bromide (iso-PB; also called 2-bromopropane or 2-BP) among dry cleaners in New Jersey who have converted their machines from PERC to these new solvent products. Personal breathing zone and area samples were collected using the National Institute for Occupational Safety and Health Sampling and Analytical Method 1025, with a slight modification to gas chromatography conditions to facilitate better separation of n-PB from iso-PB. During the preliminary investigation, exposures to n-PB among some workers in two of three shops were measured that were greater than the American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value (TLV) for n-PB. The highest exposure measured among a dry cleaning machine operator was 54 parts per million (ppm) as an 8-hr time-weighted average, which is more than 5 times the ACGIH TLV of 10 ppm. The preliminary investigation also found that the work tasks most likely to result in the highest short-term exposures included the introduction of

  10. Persistent modification of Na{sub v}1.9 following chronic exposure to insecticides and pyridostigmine bromide

    SciTech Connect

    Nutter, Thomas J. Cooper, Brian Y.

    2014-06-15

    Many veterans of the 1991 Gulf War (GW) returned from that conflict with a widespread chronic pain affecting deep tissues. Recently, we have shown that a 60 day exposure to the insecticides permethrin, chlorpyrifos, and pyridostigmine bromide (NTPB) had little influence on nociceptor action potential forming Na{sub v}1.8, but increased K{sub v}7 mediated inhibitory currents 8 weeks after treatment. Using the same exposure regimen, we used whole cell patch methods to examine whether the influences of NTPB could be observed on Na{sub v}1.9 expressed in muscle and vascular nociceptors. During a 60 day exposure to NTPB, rats exhibited lowered muscle pain thresholds and increased rest periods, but these measures subsequently returned to normal levels. Eight and 12 weeks after treatments ceased, DRG neurons were excised from the sensory ganglia. Whole cell patch studies revealed little change in voltage dependent activation and deactivation of Na{sub v}1.9, but significant increases in the amplitude of Na{sub v}1.9 were observed 8 weeks after exposure. Cellular studies, at the 8 week delay, revealed that NTPB also significantly prolonged action potential duration and afterhyperpolarization (22 °C). Acute application of permethrin (10 μM) also increased the amplitude of Na{sub v}1.9 in skin, muscle and vascular nociceptors. In conclusion, chronic exposure to Gulf War agents produced long term changes in the amplitude of Na{sub v}1.9 expressed in muscle and vascular nociceptors. The reported increases in K{sub v}7 amplitude may have been an adaptive response to increased Na{sub v}1.9, and effectively suppressed behavioral pain measures in the post treatment period. Factors that alter the balance between Na{sub v}1.9 and K{sub v}7 could release spontaneous discharge and produce chronic deep tissue pain. - Highlights: • Rats were treated 60 days with permethrin, chlorpyrifos and pyridostigmine bromide. • 8 weeks after treatments, Nav1.9 activation and deactivation were

  11. Protective effect of ipratropium bromide on bronchoconstriction induced by sulfur dioxide exposure during apricot sufurization processes that causes asthma-like syndrome in agricultural environment.

    PubMed

    Yildirim, Zeki; Kilic, Talat; Koksal, Nurhan; Kotuk, Mahir

    2005-05-01

    We previously showed that apricot sulfurization workers are exposed to high concentrations of sulfur dioxide (SO2), resulting in an asthma-like syndrome. The aim of this study was to investigate whether pre-treatment of ipratropium bromide protects bronchoconstriction induced by SO2 exposure during apricot sulfurization processes that causes asthma-like syndrome. Firstly, pulmonary function tests were measured before and immediately after SO2 exposure due to processes of apricot sulfurization in 21 healthy volunteer apricot sulfurization workers who did not use any medication in apricot farms. One week later, same measurements were repeated in the same workers when they were working in same farm but they were administered two puffs of ipratropium bromide (20 microg per dose) before 30 min second SO2 exposure for protection of SO2-induced bronchoconstriction. Occupational SO2 exposure caused significant decrement in forced vital capacity (FVC), forced expiratory volume (FEV1) and forced mid-expiratory flow rate (FEF25-75%) in the worker and these decrements were prevented by ipratropium bromide given 30 min before SO2 exposure. This result suggests that pre-treatment of ipratropium bromide protects SO2-induced bronchoconstriction in healthy worker during apricot sulfurization processes that causes asthma-like syndrome in agricultural environment.

  12. Isomerization of neopentyl chloride and neopentyl bromide by a 1,2-interchange of a halogen atom and a methyl group.

    PubMed

    Lisowski, Carmen E; Duncan, Juliana R; Ranieri, Anthony J; Heard, George L; Setser, D W; Holmes, Bert E

    2010-09-30

    The recombination of chloromethyl and t-butyl radicals at room temperature was used to generate neopentyl chloride molecules with 89 kcal mol(-1) of internal energy. The observed unimolecular reactions, which give 2-methyl-2-butene and 2-methyl-1-butene plus HCl, as products, are explained by a mechanism that involves the interchange of a methyl group and the chlorine atom to yield 2-chloro-2-methylbutane, which subsequently eliminates hydrogen chloride by the usual four-centered mechanism to give the observed products. The interchange isomerization process is the rate-limiting step. Similar experiments were done with CD(2)Cl and C(CH(3))(3) radicals to measure the kinetic-isotope effect to help corroborate the proposed mechanism. Density functional theory was employed at the B3PW91/6-31G(d',p') level to verify the Cl/CH(3) interchange mechanism and to characterize the interchange transition state. These calculations, which provide vibrational frequencies and moments of inertia of the molecule and transition state, were used to evaluate the statistical unimolecular rate constants. Matching the calculated and experimental rate constants, gave 62 ± 2 kcal mol(-1) as the threshold energy for interchange of the Cl atom and a methyl group. The calculated models also were used to reinterpret the thermal unimolecular reactions of neopentyl chloride and neopentyl bromide. The previously assumed Wagner-Meerwein rearrangement mechanism for these reactions can be replaced by a mechanism that involves the interchange of the halogen atom and a methyl group followed by HCl or HBr elimination from 2-chloro-2-methylbutane and 2-bromo-2-methylbutane. Electronic structure calculations also were done to find threshold energies for several related molecules, including 2-chloro-3,3-dimethylbutane, 1-chloro-2-methyl-2-phenylpropane, and 1-chloro-2-methyl-2-vinylpropane, to demonstrate the generality of the interchange reaction involving a methyl, or other hydrocarbon groups, and a

  13. In Brief: Agreement signed for NSF participation in IODP; Asian dust storms' intensity, scale grow; Continued use of methyl bromide allowed

    NASA Astrophysics Data System (ADS)

    Jacobs, Judith; Showstack, Randy

    2004-04-01

    The U.S. National Science Foundation on 30 March signed a cooperative agreement with the Joint Oceanographic Institutions (JOI) in Washington, D.C., to lead U.S. participation in the Integrated Ocean Drilling Program (IODP). Large-scale, destructive dust and sand storms that originate in the dry regions of northern China and Mongolia are plaguing the Korean peninsula, Japan and other parts of northeast Asia nearly five times more frequently than in the 1950s, participants in a meeting sponsored by the U.N. Environment Programme (UNEP) learned on 30 March. Twelve countries have received ``critical use exemptions'' to continue using limited amounts of the pesticide methyl bromide in 2005.

  14. Palladium-catalyzed carbonylative coupling of (2-azaaryl)methyl anion equivalents with (hetero)aryl bromides.

    PubMed

    Jusseau, Xavier; Yin, Hongfei; Lindhardt, Anders T; Skrydstrup, Troels

    2014-11-24

    Conditions for the palladium-catalyzed coupling of (2-pyridyl)acetones with aryl bromides have been developed. Followed by an acid-promoted deacetylation step, the desired 1-(het)aryl-2-(2-pyridyl)ethanones were obtained in good to excellent yields with high functional group tolerance. Test reactions revealed that both the addition of MgCl2 and a specifically positioned heteroatom in the heteroaromatic ring were crucial for product formation indicating the importance of a chelated intermediate in the reaction mechanism. The reaction conditions proved suitable for a number of 5- and 6-membered heteroaromatic starting materials affording all products in good yields. The utility of the obtained 1-(het)aryl-2-(2-pyridyl)ethanones was demonstrated by the straightforward synthesis of several multiaromatic derivatives in only few additional steps. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Reverse osmosis membrane composition, structure and performance modification by bisulphite, iron(III), bromide and chlorite exposure.

    PubMed

    Ferrer, O; Gibert, O; Cortina, J L

    2016-10-15

    Reverse osmosis (RO) membrane exposure to bisulphite, chlorite, bromide and iron(III) was assessed in terms of membrane composition, structure and performance. Membrane composition was determined by Rutherford backscattering spectrometry (RBS) and membrane performance was assessed by water and chloride permeation, using a modified version of the solution-diffusion model. Iron(III) dosage in presence of bisulphite led to an autooxidation of the latter, probably generating free radicals which damaged the membrane. It comprised a significant raise in chloride passage (chloride permeation coefficient increased 5.3-5.1 fold compared to the virgin membrane under the conditions studied) rapidly. No major differences in terms of water permeability and membrane composition were observed. Nevertheless, an increase in the size of the network pores, and a raise in the fraction of aggregate pores of the polyamide (PA) layer were identified, but no amide bond cleavage was observed. These structural changes were therefore, in accordance with the transport properties observed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Co-exposure to pyridostigmine bromide, DEET, and/or permethrin causes sensorimotor deficit and alterations in brain acetylcholinesterase activity.

    PubMed

    Abou-Donia, Mohamed B; Dechkovskaia, Anjelika M; Goldstein, Larry B; Abdel-Rahman, Ali; Bullman, Sarah L; Khan, Wasiuddin A

    2004-02-01

    Military personnel deployed in the Persian Gulf War (PGW) were exposed to a combination of chemicals, including pyridostigmine bromide (PB), DEET, and permethrin. We investigated the dose-response effects of these chemicals, alone or in combination, on the sensorimotor performance and cholinergic system of male Sprague-Dawley rats. Animals were treated with a daily dermal dose of DEET and/or permethrin for 60 days and/or PB (gavage) during the last 15 days. Neurobehavioral performance was assessed on day 60 following the beginning of the treatment with DEET and permethrin. The rats were sacrificed 24 h after the last treatment for biochemical evaluations. PB alone, or in combination with DEET, or DEET and permethrin resulted in deficits in beam-walk score and longer beam-walk times compared to controls. PB alone, or in combination with DEET, permethrin, or DEET and permethrin caused impairment in incline plane performance and forepaw grip strength. PB alone at all doses slightly inhibited plasma butyrylcholinesterase activity, whereas combination of PB with DEET or permethrin increased its activity. Brainstem acetylcholinesterase (AChE) activity significantly increased following treatment with combinations of either DEET or permethrin at all doses, whereas the cerebellum showed a significant increase in AChE activity following treatment with a combination of PB/DEET/permethrin. Co-exposure to PB, DEET, and permethrin resulted in significant inhibition in AChE in midbrain. PB alone or in combination with DEET and permethrin at all doses increased ligand binding for m2 muscarinic acetylcholine receptor in the cortex. In addition, PB and DEET together or a combination of PB, DEET, and permethrin significantly increased ligand binding for nicotinic acetylcholine receptor. These results suggest that exposure to various doses of PB, alone and in combination with DEET and permethrin, leads to sensorimotor deficits and differential alterations of the cholinergic system in

  17. Association between GSTP1 CpG methylation and the early phase of lead exposure.

    PubMed

    Li, Chunping; Yang, Xiaolin; Xu, Ming; Zhang, Jinlong; Sun, Na

    2014-02-01

    GSTP1 is induced by lead, and thus serves as a biomarker of lead exposure. Lead exposure changes DNA methylation status. We attempted to prove that the methylation of the GSTP1 promoter plays an important role in lead toxicity. We conducted a case-control study of 53 workers from a battery plant and 53 age and sex matched healthy volunteers to determine whether the methylation level of the GSTP1 promoter is associated with the risk of lead poisoning. We employed methylation-specific PCR (MSP) in cell models to determine the relationship between the GSTP1 methylation level and lead exposure. We found no association between GSTP1 methylation and lead exposure. The difference in methylation frequencies between the exposure group and the controls was not statistically significant (p = 0.401), and individuals with the methylated GSTP1 gene was not associated with the risk of lead poisoning (adjusted OR = 1.36, 95% CI, 0.22-8.24). This study suggests that GSTP1 methylation is not involved in the early phase of lead toxicity. Further studies should be performed to detect the association between GSTP1 methylation and the risk of lead poisoning in later phases.

  18. Inhalation exposure system used for acute and repeated-dose methyl isocyanate exposures of laboratory animals.

    PubMed

    Adkins, B; O'Connor, R W; Dement, J M

    1987-06-01

    Laboratory animals were exposed by inhalation for 2 hr/day (acute) or 6 hr/day (four consecutive days, repeated dose) to methyl isocyanate (MIC). Exposures were conducted in stainless steel and glass inhalation exposure chambers placed in stainless steel, wire mesh cages. MIC was delivered with nitrogen via stainless steel and Teflon supply lines. Chamber concentrations ranged from 0 to 60 ppm and were monitored continuously with infrared spectrophotometers to 1 ppm and at 2-hr intervals to 20 ppb with a high performance liquid chromatograph equipped with a fluorescence detector. Other operational parameters monitored on a continuous basis included chamber temperature (20-27 degrees C), relative humidity (31-64%), static (transmural) pressure (-0.3 in.), and flow (300-500 L/min). The computer-assistance system interfaced with the inhalation exposure laboratory is described in detail, including the analytical instrumentation calibration system used throughout this investigation.

  19. Adhesion work and wettability of polytetrafluorethylene and poly(methyl methacrylate) by aqueous solutions of cetyltrimethylammonium bromide and Triton X-100 mixture with ethanol.

    PubMed

    Bielawska, Magdalena; Jańczuk, Bronisław; Zdziennicka, Anna

    2013-08-15

    The contact angle measurements of the aqueous solutions of p-(1,1,3,3-tetramethylbutyl)phenoxypoly(ethylene glycol) (TX-100) and cetyltrimethylammonium bromide (CTAB) mixture with ethanol on polytetrafluoroethylene (PTFE) and poly (methyl methacrylate) (PMMA) were carried out in the range of the total concentration of TX-100 and CTAB mixture from 1×10(-6) to 1×10(-3) M and in the whole range of ethanol concentration. In the surfactant mixture, the mole fraction of TX-100 was equal to 0.2; 0.4; 0.6 and 0.8, respectively. From the obtained results, the critical surface tension of PTFE and PMMA wetting and the adhesion work of the solutions to the polymer surface were established. The PMMA surface tension was calculated from the Neumann's equation. It appeared that for the ethanol concentration higher than that corresponding to the association of its molecules, the surface tension of PMMA calculated from the Neumann's equation is close to the critical surface tension of PMMA wetting. It also appeared that it is possible to predict the work of adhesion of the studied solutions to the PMMA surface by using the PMMA surface tension data determined on the basis of the van Oss et al. approach to the interfacial tension and those from the Neumann's equation.

  20. Phasing-out of methyl bromide (CH3Br) and usage of sulfuryl fluoride (SO2F2) for pest control in Europe

    NASA Astrophysics Data System (ADS)

    Reimann, S.; Brunner, D.; Vollmer, M. K.; Henne, S.; Maione, M.; Arduini, I.

    2011-12-01

    Methyl bromide (CH3Br) has been widely used for fumigation in agriculture, in food mills and for transport applications. Due to its high ozone-depleting potential, its use has been banned within the Montreal Protocol and its amendments, except for quarantine/pre-shipment uses. This led to a decline of global atmospheric background concentrations and of world-wide emissions. In Europe, emissions have declined concurrently and a generally good compliance with legislation is suggested based on emission estimates using inverse modelling of continuous measurements from the European high-altitude sites Jungfraujoch (Switzerland) and Monte Cimone (Italy). However, episodic pollution events of CH3Br show a violation of international legislation, as this substance has been banned in Europe from 2007 onwards in agriculture and from 2010 in quarantine/pre-shipment uses. Sulfuryl fluoride (SO2F2) is one of the replacement compounds for CH3Br in food processing structures. SO2F2 does not affect the ozone layer but is a potent greenhouse gas (100-year GWP: 4740) with a lifetime of 36 years. European emissions of SO2F2 are estimated by using measurements at Jungfraujoch. Large pollution events are very sporadic but consistently linked to emissions during long weekends and public holidays, presumably a preferable time to fumi-gate food processing structures.

  1. Evaluation of microwave irradiation for analysis of carbonyl sulfide, carbon disulfide, cyanogen, ethyl formate, methyl bromide, sulfuryl fluoride, propylene oxide, and phosphine in hay.

    PubMed

    Ren, Yonglin; Mahon, Daphne

    2007-01-10

    Fumigant residues in hay were "extracted" by microwave irradiation. Hay, in gastight glass flasks, was placed in a domestic microwave oven, and fumigants were released into the headspace by microwave irradiation. Power settings for maximum release of fumigants were determined for carbonyl sulfide (COS), carbon disulfide (CS(2)), cyanogen (C(2)N(2)), ethyl formate (EF), methyl bromide (CH(3)Br), sulfuryl fluoride (SF), propylene oxide (PPO), and phosphine (PH(3)). Recoveries of fortified samples were >91% for COS, CS(2), CH(3)Br, SF, PPO, and PH(3) and >76% for C(2)N(2) and EF. Completeness of extraction was assessed from the amount of fumigant retained by the microwaved hay. This amount was determined from further microwave irradiation and was always small (<5% of the amount obtained from the initial procedure). Limits of quantification were <0.1 mg/kg for COS, CS(2), C(2)N(2), EF, and PH(3) and <0.5 mg/kg for CH(3)Br, SF, and PPO. These low limits were essentially due to the absence of interference from solvents and no necessity to inject large-volume gas samples. The microwave method is rapid and solvent-free. However, care is required in selecting the appropriate power setting. The safety implications of heating sealed flasks in microwave ovens should be noted.

  2. Development of an Activated Carbon-Based Electrode for the Capture and Rapid Electrolytic Reductive Debromination of Methyl Bromide from Postharvest Fumigations.

    PubMed

    Li, Yuanqing; Liu, Chong; Cui, Yi; Walse, Spencer S; Olver, Ryan; Zilberman, David; Mitch, William A

    2016-10-18

    Due to concerns surrounding its ozone depletion potential, there is a need for technologies to capture and destroy methyl bromide (CH3Br) emissions from postharvest fumigations applied to control agricultural pests. Previously, we described a system in which CH3Br fumes vented from fumigation chambers could be captured by granular activated carbon (GAC). The GAC was converted to a cathode by submergence in a high ionic strength solution and connection to the electrical grid, resulting in reductive debromination of the sorbed CH3Br. The GAC bed was drained and dried for reuse to capture and destroy CH3Br fumes from the next fumigation. However, the loose GAC particles and slow kinetics of this primitive electrode necessitated improvements. Here, we report the development of a cathode containing a thin layer of small GAC particles coating carbon cloth as a current distributor. Combining the high sorption potential of GAC for CH3Br with the conductivity of the carbon cloth current distributor, the cathode significantly lowered the total cell resistance and achieved 96% reductive debromination of CH3Br sorbed at 30% by weight to the GAC within 15 h at -1 V applied potential vs standard hydrogen electrode, a time scale and efficiency suitable for postharvest fumigations. The cathode exhibited stable performance over 50 CH3Br capture and destruction cycles. Initial cost estimates indicate that this technique could treat CH3Br fumes at ∼$5/kg, roughly one-third of the cost of current alternatives.

  3. Lead exposure suppressed ALAD transcription by increasing methylation level of the promoter CpG islands.

    PubMed

    Li, Chunping; Xu, Ming; Wang, Sumeng; Yang, Xiaolin; Zhou, Shourong; Zhang, Jingping; Liu, Qizhan; Sun, Yujie

    2011-05-30

    DNA methylation provides a plausible link between the environment and alterations in gene expression that may lead to disease phenotypes. Lead exposure can change DNA methylation status. Here, we hypothesized that the methylation of the ALAD gene promoter may play an important role in lead toxicity. To determine whether the methylation level of the ALAD promoter is associated with the risk of lead poisoning, we conducted a case-control study of 103 workers from a battery plant and 103 healthy volunteers with matching age and gender distribution. We employed real-time PCR and methylation-specific PCR (MSP) in cell models to determine the relationship between ALAD methylation level and transcription level. We found lead exposure to increase the ALAD gene methylation level and down-regulate ALAD transcription. The difference in methylation frequencies between exposures and controls was statistically significant (p=0.002), and individuals with methylated ALAD gene showed an increased risk of lead poisoning (adjusted OR=3.57, 95% CI, 1.55-8.18). This study suggests that the lead-exposure-induced increases in ALAD methylation may be involved in the mechanism of lead toxicity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  4. Epigenetic marker (LINE-1 promoter) methylation level was associated with occupational lead exposure.

    PubMed

    Li, Chunping; Yang, Xiaolin; Xu, Ming; Zhang, Jinlong; Sun, Na

    2013-05-01

    Occupational and environmental exposures to lead (Pb) are a worldwide concern. DNA methylation plays an important role in the development of Pb toxicity. Here, we try to find out the evidence to prove that the methylation of the LINE-1 promoter may be involved in Pb toxicity. To determine whether the methylation level of the LINE-1 is associated with the risk of Pb poisoning, we first constructed a Pb acetate-treated cell model to detect the association between LINE-1 methylation and Pb exposure. A case-control study involving 53 workers from a battery plant and 57 healthy volunteers with matching age and gender distribution was carried out. We employed methylation-specific real-time PCR to determine the relationship between LINE-1 methylation level and Pb exposure. In the cell model, Pb exposure significantly decreased the level of LINE-1 methylation (p = 0.009). Significant difference in methylation frequencies was found between the exposed and control samples (p < 0.001). We also found a decreasing trend of LINE-1 methylation level with increasing blood Pb level (p < 0.001). Therefore, the LINE-1 promoter methylation might contribute to the risk of Pb poisoning and identified a possible epigenetic biomarker for Pb toxicity, especially in individuals occupationally exposed to Pb.

  5. DOSE-RESPONSE MODELING FOR THE ASSESSMENT OF CUMULATIVE RISK DUE TO EXPOSURE TO N-METHYL CARBAMATE PESTICIDES

    EPA Science Inventory

    The US EPAs N-Methyl Carbamate Cumulative Risk Assessment (NMCRA) assesses the effect on acetylcholine esterase (AChE) activity of exposure to 10 N-methyl carbamate (NMC) pesticides through dietary, drinking water, and residential exposures.

  6. Genome-wide analysis of DNA methylation changes induced by gestational arsenic exposure in liver tumors.

    PubMed

    Suzuki, Takehiro; Yamashita, Satoshi; Ushijima, Toshikazu; Takumi, Shota; Sano, Tomoharu; Michikawa, Takehiro; Nohara, Keiko

    2013-12-01

    Inorganic arsenic is known to be a human carcinogen. Previous studies have reported that DNA methylation changes are involved in arsenic-induced carcinogenesis, therefore, DNA methylation changes that are specific to arsenic-induced tumors would be useful to distinguish tumors induced by arsenic from tumors caused by other factors and to dissect arsenic carcinogenesis. Previous studies have shown that gestational arsenic exposure of C3H mice, which tend to spontaneously develop liver tumors, increases the incidence of tumors in male offspring. In this study we used the same experimental protocol as in those previous studies and searched for DNA regions where methylation status was specifically altered in the liver tumors of arsenic-exposed offspring by using methylated DNA immunoprecipitation-CpG island microarrays. The methylation levels of the DNA regions selected were measured by quantitative methylation-specific PCR and bisulfite sequencing. The results of this study clarified a number of regions where DNA methylation status was altered in the liver tumors in the C3H mice compared to normal liver tissues. Among such regions, we showed that a gene body region of the oncogene Fosb underwent alteration in DNA methylation by gestational arsenic exposure. We also showed that Fosb expression significantly increased corresponding to the DNA methylation level of the gene body in the arsenic-exposed group. These findings suggest that the DNA methylation status can be used to identify tumors increased by gestational arsenic exposure. © 2013 Japanese Cancer Association.

  7. Arsenic Exposure and Epigenetic Alterations: Recent Findings Based on the Illumina 450K DNA Methylation Array.

    PubMed

    Argos, Maria

    2015-06-01

    Arsenic is a major public health concern worldwide. While it is an established carcinogen and associated with a number of other adverse health outcomes, the molecular mechanisms underlying arsenic toxicity are not completely clarified. There is mounting evidence from human studies suggesting that arsenic exposure is associated with epigenetic alterations, including DNA methylation. In this review, we summarize several recent human studies that have evaluated arsenic exposure using the Illumina HumanMethylation 450K BeadChip, which interrogates more than 485,000 methylation sites across the genome. Many of these studies have observed novel regions of the genome associated with arsenic exposure. However, few studies have evaluated the biological and functional relevance of these DNA methylation changes, which are still needed. We emphasize the need for future studies to replicate the identified DNA methylation signals as well as assess whether these markers are associated with risk of arsenic-related diseases.

  8. Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation.

    PubMed

    Breton, Carrie V; Byun, Hyang-Min; Wenten, Made; Pan, Fei; Yang, Allen; Gilliland, Frank D

    2009-09-01

    Prenatal exposure to tobacco smoke increases the risk for diseases later in the child's life that may be mediated through alterations in DNA methylation. To demonstrate that differences in DNA methylation patterns occur in children exposed to tobacco smoke and that variation in detoxification genes may alter these associations. Methylation of DNA repetitive elements, LINE1 and AluYb8, was measured using bisulfite conversion and pyrosequencing in buccal cells of 348 children participating in the Children's Health Study. Gene-specific CpG methylation differences associated with smoke exposure were screened in 272 participants in the Children's Health Study children using an Illumina GoldenGate panel. CpG loci that demonstrated a statistically significant difference in methylation were validated by pyrosequencing. Estimates were standardized across loci using a Z score to enable cross-comparison of results. DNA methylation patterns were associated with in utero exposure to maternal smoking. Exposed children had significantly lower methylation of AluYb8 (beta, -0.31; P = 0.03). Differences in smoking-related effects on LINE1 methylation were observed in children with the common GSTM1 null genotype. Differential methylation of CpG loci in eight genes was identified through the screen. Two genes, AXL and PTPRO, were validated by pyrosequencing and showed significant increases in methylation of 0.37 (P = 0.005) and 0.34 (P = 0.02) in exposed children. The associations with maternal smoking varied by a common GSTP1 haplotype. Life-long effects of in utero exposures may be mediated through alterations in DNA methylation. Variants in detoxification genes may modulate the effects of in utero exposure through epigenetic mechanisms.

  9. Real-World Verification of Methyl Bromide (CH3Br) Phase-Out in Europe and its Partial Replacement with Sulfuryl Fluoride (SO2F2)

    NASA Astrophysics Data System (ADS)

    Reimann, S.; Vollmer, M. K.; Brunner, D.; Henne, S.; Maione, M.; Arduini, I.

    2014-12-01

    In the last decades methyl bromide (CH3Br) has been widely used for pest control in agriculture, during transport and in susceptible environments such as grain elevators, flour mills. Due to its ozone-depleting properties most applications, except for quarantine-preshipment uses, are practically forbidden within the Montreal Protocol and its amendments. This led to a decline of both world-wide emissions and of global background concentrations. In Europe, emissions have declined concurrently, as CH3Br has not been allowed to be used in Europe from 2007 onwards in agriculture and from 2010 in quarantine/preshipment uses. Continuous measurements from the European high-altitude sites Jungfraujoch (Switzerland) and Monte Cimone (Italy) are used to verify this phase-out in different parts of Europe. Pollution events were still detected at these sites until around 2012, potentially indicating forbidden small scale usage of CH3Br in Europe. However, within the last 2 years the abundance and the height of these events have become very small - showing an overall good acceptance of the CH3Br ban in Europe. On the other hand, sulfuryl fluoride (SO2F2) is used as a partial replacement of CH3Br in the fumigation of food processing structures. It shows very distinct, sporadic peak events at the Jungfraujoch measurement site. SO2F2 does not affect the ozone layer but is a potent greenhouse gas (100-year GWP: 4740) with a lifetime of 36 years. European sources of SO2F2 were estimated by using measurements at Jungfraujoch.

  10. Capture of methyl bromide emissions with activated carbon following the fumigation of a small building contaminated with a Bacillus anthracis spore simulant.

    PubMed

    Wood, Joseph P; Clayton, Mathew J; McArthur, Timothy; Serre, Shannon D; Mickelsen, Leroy; Touati, Abderrahmane

    2015-02-01

    A wide-area Bacillus anthracis spore contamination incident will present immense challenges related to decontamination capacity. For this reason, fumigation with methyl bromide (MeBr) has been proposed as a potential remediation option. Although a few bench-scale laboratory studies have been conducted to evaluate activated carbon for the capture of MeBr, these studies were conducted at conditions replicating commodity fumigation using relatively low MeBr concentrations, temperatures, and/or relative humidity (RH) levels. The more rigorous MeBr fumigation requirements to fully inactivate B. anthracis spores are much more of a challenge for an activated carbon system (ACS) to capture MeBr, and warrant their own investigation. Further, while the aforementioned studies have shown activated carbon to be a possible option for the capture of MeBr in gas streams, these tests were conducted at laboratory bench scale, and thus lack operational perspective and data. Thus, we present for the first time the results of a full-scale study to evaluate an ACS employed for the capture of MeBr at conditions that would be used for decontaminating a building structure contaminated with B. anthracis spores. Airflow rate, temperature, RH, and MeBr levels were measured within the ACS during its operation. Despite the relatively high humidity, temperature, and MeBr levels, the MeBr capture efficiency of the ACS was demonstrated to be more than 99%. The concentration of MeBr exhausted from the structure was reduced from 41,000 to 136 ppmv in 3.5 hr, corresponding to an overall atmospheric emission rate of less than 2 kg. The practical adsorption rate of the ACS was determined to be 4.83 kg MeBr/100 kg carbon. The information and data presented here will facilitate future use of this technology when fumigating with MeBr.

  11. Activated carbons from end-products of tree nut and tree fruit production as sorbents for removing methyl bromide in ventilation effluent following postharvest chamber fumigation.

    PubMed

    Hall, Wiley A; Bellamy, David E; Walse, Spencer S

    2015-04-01

    End-products of tree nuts and tree fruits grown in California, USA were evaluated for the ability to remove methyl bromide (MB) from ventilation effluent following postharvest chamber fumigation. Activated carbon sorbents from walnut and almond shells as well as peach and prune pits were prepared using different methods of pyrolysis, activation, and quenching. Each source and preparation was evaluated for yield from starting material (%, m/m) and performance on tests where MB-containing airstreams were directed through a columnar bed of the activated carbon in an experimental apparatus, termed a parallel adsorbent column tester, which was constructed as a scaled-down model of a chamber ventilation system. We report the number of doses needed to first observe the breakthrough of MB downstream of the bed and the capacity of the activated carbon for MB (%, m/m) based on a fractional percentage of MB mass sorbed at breakthrough relative to mass of the bed prior to testing. Results were based on a novel application of solid-phase microextraction with time-weighted averaging sampling of MB concentration in airstreams, which was quantitative across the range of fumigation-relevant conditions and statistically unaffected by relative humidity. Activated carbons from prune pits, prepared either by steam activation or carbon dioxide activation coupled to water quenching, received the greatest number of doses prior to breakthrough and had the highest capacity, approximately 12-14%, outperforming a commercially marketed activated carbon derived from coconut shells. Experimental evidence is presented that links discrepancy in performance to the relative potential for activated carbons to preferentially sorb water vapor relative to MB.

  12. Cyanogen bromide

    Integrated Risk Information System (IRIS)

    Cyanogen bromide ; CASRN 506 - 68 - 3 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic

  13. Vinyl bromide

    Integrated Risk Information System (IRIS)

    Vinyl bromide ; CASRN 593 - 60 - 2 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  14. Rapacuronium bromide.

    PubMed

    Stump, L

    2000-08-01

    Rapacuronium bromide (Raplon; Organon Inc, West Orange, NJ) is a new, fast-onset, short-duration surgical muscle relaxant. While anesthesia providers are learning how to use this new relaxant, PACU nurses must become aware of the potential problems associated with rapacuronium. This article compares and contrasts the effects of succinylcholine and rapacuronium.

  15. Differential Methylation of the Arsenic (III) Methyltransferase Promoter According to Arsenic Exposure

    PubMed Central

    Gribble, Matthew O.; Tang, Wan-yee; Shang, Yan; Pollak, Jonathan; Umans, Jason G.; Francesconi, Kevin A.; Goessler, Walter; Silbergeld, Ellen K.; Guallar, Eliseo; Cole, Shelley A.; Fallin, M. Daniele; Navas-Acien, Ana

    2013-01-01

    Inorganic arsenic is methylated in the body by arsenic (III) methyltransferase. Arsenic methylation is thought to play a role in arsenic-related epigenetic phenomena including aberrant DNA and histone methylation. However, it is unclear whether the promoter of the AS3MT gene, which codes for arsenic (III) methyltransferase, is differentially methylated as a function of arsenic exposure. In this study we evaluated AS3MT promoter methylation according to exposure, assessed by urinary arsenic excretion in a stratified random sample of 48 participants from the Strong Heart Study who had urine arsenic measured at baseline and DNA available from 1989–1991 and 1998–1999. For this study, all data are from the 1989–1991 visit. We measured AS3MT promoter methylation at its 48 CpG loci by bisulphite sequencing. We compared mean % methylation at each CpG locus by arsenic exposure group using linear regression adjusted for study centre, age and sex. A hypomethylated region in the AS3MT promoter was associated with higher arsenic exposure. In vitro, arsenic induced AS3MT promoter hypomethylation and it increased AS3MT expression in human peripheral blood mononuclear cells. These findings may suggest that arsenic exposure influences the epigenetic regulation of a major arsenic metabolism gene. PMID:24154821

  16. Fact Sheet on Measures Required to Protect Workers from Fumigant Exposures

    EPA Pesticide Factsheets

    These safety measures increase protections for fumigant handlers and other agricultural workers and bystanders from exposure to the soil fumigant pesticides chloropicrin, dazomet, metam sodium, metam potassium, and methyl bromide.

  17. In vitro lead exposure changes DNA methylation and expression of IGF2 and PEG1/MEST.

    PubMed

    Nye, Monica D; Hoyo, Cathrine; Murphy, Susan K

    2015-04-01

    Epigenetic processes, such as changes in DNA methylation, likely mediate the link between environmental exposures in utero and altered gene expression. Differentially methylated regions (DMRs) that regulate imprinted genes may be especially vulnerable to environmental exposures since imprinting is established and maintained largely through DNA methylation, resulting in expression from only one parental chromosome. We used the human embryonic kidney cell line, HEK-293, to investigate the effects of exposure to physiologically relevant doses of lead acetate (Pb) on the methylation status of nine imprinted gene DMRs. We assessed mean methylation after seventy-two hours of Pb exposure (0-25 μg/dL) using bisulfite pyrosequencing. The PEG1/MEST and IGF2 DMRs had maximum methylation decreases of 9.6% (20 μg/dL; p<0.005) and 3.8% (25 μg/dL; p<0.005), respectively. Changes at the MEG3 DMRs had a maximum decrease in methylation of 2.9% (MEG3) and 1.8% (MEG3-IG) at 5 μg/dL Pb, but were not statistically significant. The H19, NNAT, PEG3, PLAGL1, and SGCE/PEG10 DMRs showed a less than 0.5% change in methylation, across the dose range used, and were deemed non-responsive to Pb in our model. Pb exposure below reportable/actionable levels increased expression of PEG1/MEST concomitant with decreased methylation. These results suggest that Pb exposure can stably alter the regulatory capacity of multiple imprinted DMRs.

  18. PRKCZ methylation is associated with sunlight exposure in a North American but not a Mediterranean population.

    PubMed

    Aslibekyan, Stella; Dashti, Hassan S; Tanaka, Toshiko; Sha, Jin; Ferrucci, Luigi; Zhi, Degui; Bandinelli, Stefania; Borecki, Ingrid B; Absher, Devin M; Arnett, Donna K; Ordovas, Jose M

    2014-11-01

    Sunlight exposure has been shown to alter DNA methylation patterns across several human cell-types, including T-lymphocytes. Since epigenetic changes establish gene expression profiles, changes in DNA methylation induced by sunlight exposure warrant investigation. The purpose of this study was to assess the effects of sunlight exposure on CD4+ T-cell methylation patterns on an epigenome-wide scale in a North American population of European origin (n=991). In addition, we investigated the genetic contribution to epigenetic variation (methylQTL). We used linear regression to test the associations between methylation scores at 461,281 cytosine-phosphate-guanine (CpG) sites and sunlight exposure, followed by a genome-wide association analysis (methylQTL) to test for associations between methylation at the top CpG locus and common genetic variants, assuming an additive genetic model. We observed an epigenome-wide significant association between sunlight exposure and methylation status at cg26930596 (p=9.2×10(-8)), a CpG site located in protein kinase C zeta (PRKCZ), a gene previously shown to be entrained by light. MethylQTL analysis resulted in significant associations between cg26930596 and two intergenic single nucleotide polymorphisms on chromosome 3, rs4574216 (p=1.5×10(-10)) and rs4405858 (p=1.9×10(-9)). These common genetic variants reside downstream of WWTR1, a transcriptional co-activator of PRKCZ. Associations observed in the North American population, however, did not replicate in an independent Mediterranean cohort. Our preliminary results support the role of sunlight exposure in epigenetic processes, and lay the groundwork for future studies of the molecular link between sunlight and physiologic processes such as tumorigenesis and metabolism.

  19. PRKCZ methylation is associated with sunlight exposure in a North American but not a Mediterranean population

    PubMed Central

    Aslibekyan, Stella; Dashti, Hassan S.; Tanaka, Toshiko; Sha, Jin; Ferrucci, Luigi; Zhi, Degui; Bandinelli, Stefania; Borecki, Ingrid B.; Absher, Devin M.; Arnett, Donna K.; Ordovas, Jose M.

    2015-01-01

    Sunlight exposure has been shown to alter DNA methylation patterns across several human cell-types, including T-lymphocytes. Since epigenetic changes establish gene expression profiles, changes in DNA methylation induced by sunlight exposure warrant investigation. The purpose of this study was to assess the effects of sunlight exposure on CD4+ T-cell methylation patterns on an epigenome-wide scale in a North American population of European origin (n = 991). In addition, we investigated the genetic contribution to epigenetic variation (methylQTL). We used linear regression to test the associations between methylation scores at 461 281 cytosine-phosphate-guanine (CpG) sites and sunlight exposure, followed by a genome-wide association analysis (methylQTL) to test for associations between methylation at the top CpG locus and common genetic variants, assuming an additive genetic model. We observed an epigenome-wide significant association between sunlight exposure and methylation status at cg26930596 (p = 9.2 × 10−8), a CpG site located in protein kinase C zeta (PRKCZ), a gene previously shown to be entrained by light. MethylQTL analysis resulted in significant associations between cg26930596 and two intergenic single nucleotide polymorphisms on chromosome 3, rs4574216 (p = 1.5 × 10−10) and rs4405858 (p = 1.9 × 10−9). These common genetic variants reside downstream of WWTR1, a transcriptional co-activator of PRKCZ. Associations observed in the North American population, however, did not replicate in an independent Mediterranean cohort. Our preliminary results support the role of sunlight exposure in epigenetic processes, and lay the groundwork for future studies of the molecular link between sunlight and physiologic processes such as tumorigenesis and metabolism. PMID:25075435

  20. Endogenous sex hormone exposure and repetitive element DNA methylation in healthy postmenopausal women.

    PubMed

    Boyne, Devon J; Friedenreich, Christine M; McIntyre, John B; Stanczyk, Frank Z; Courneya, Kerry S; King, Will D

    2017-09-19

    Epigenetic mechanisms may help to explain the complex and heterogeneous relation between sex hormones and cancer. Few studies have investigated the effects of sex hormones on epigenetic markers related to cancer risk such as levels of methylation within repetitive DNA elements. Our objective was to describe the association between endogenous sex hormone exposure and levels of LINE-1 and Alu methylation in healthy postmenopausal women. We nested a cross-sectional study within the Alberta Physical Activity and Breast Cancer Prevention Trial (2003-2006). Study participants consisted of healthy postmenopausal women who had never been diagnosed with cancer (n = 289). Sex hormone exposures included serum concentrations of estradiol, estrone, testosterone, androstenedione, and sex hormone-binding globulin. We estimated the participants' lifetime number of menstrual cycles (LNMC) as a proxy for cumulative exposure to ovarian sex hormones. Buffy coat samples were assessed for DNA methylation. Linear regression was used to model the associations of interest and to control for confounding. Both estradiol and estrone had a significant positive dose-response association with LINE-1 methylation. LNMC was associated with both LINE-1 and Alu methylation. Specifically, LNMC had a non-linear "U-shaped" association with LINE-1 methylation regardless of folate intake and a negative linear association with Alu methylation, but only amongst low folate consumers. Androgen exposure was not associated with either outcome. Current and cumulative estrogen exposure was associated with repetitive element DNA methylation in a group of healthy postmenopausal women. LINE-1 and Alu methylation may be epigenetic mechanisms through which estrogen exposure impacts cancer risk.

  1. DIETARY METHYL MERCURY EXPOSURE IN AMERICAN KESTRELS; PILOT STUDY

    EPA Science Inventory

    Anthropogenic mercury emissions have increased atmospheric mercury levels about threefold since the advent of industrial activity. Atmospheric deposition is the primary source of mercury in the environment hence mercury contamination has increased in similar fashion. Methyl mercu...

  2. Developmental effects of methyl benzimidazolecarbamate following exposure during early pregnancy

    EPA Science Inventory

    Methyl 2-benzimidazolecarbamate (MBC) and its parent compound benomyl are used as agricultural fungicides. Both chemicals are embryotoxic if administered during organogenesis, and benomyl is teratogenic. Based on a previous study indicating a lack of maternal effects of MBC follo...

  3. DIETARY METHYL MERCURY EXPOSURE IN AMERICAN KESTRELS; PILOT STUDY

    EPA Science Inventory

    Anthropogenic mercury emissions have increased atmospheric mercury levels about threefold since the advent of industrial activity. Atmospheric deposition is the primary source of mercury in the environment hence mercury contamination has increased in similar fashion. Methyl mercu...

  4. Developmental effects of methyl benzimidazolecarbamate following exposure during early pregnancy

    EPA Science Inventory

    Methyl 2-benzimidazolecarbamate (MBC) and its parent compound benomyl are used as agricultural fungicides. Both chemicals are embryotoxic if administered during organogenesis, and benomyl is teratogenic. Based on a previous study indicating a lack of maternal effects of MBC follo...

  5. Effect of exercise and heat exposure on percutaneous absorption of methyl salicylate.

    PubMed

    Danon, A; Ben-Shimon, S; Ben-Zvi, Z

    1986-01-01

    The effects of exercise, heat exposure or both on the percutaneous absorption of methyl salicylate were studied in 6 healthy volunteers. Exercise was performed to 30% of VO2max, 45 min each hour for 6 h, at ambient temperatures of 22 degrees C or 40 degrees C. Systemic availability was assessed by measurement of plasma salicylate concentrations and cumulative urinary salicyluric acid excretion over an 8-h collection period. The absorption of methyl salicylate was increased to more than 3-times above control in subjects exercising in the heat. It is concluded that exercise and heat exposure, by increasing skin temperature, hydration and blood flow, enhance the percutaneous absorption of methyl salicylate.

  6. USE OF EXPOSURE-RELATED DOSE ESTIMATING MODEL (ERDEM) FOR ASSESSMENT OF AGGREGATE EXPOSURE OF INFANT AND CHILDREN TO N-METHYL CARBAMATE INSECTICIDES

    EPA Science Inventory

    A physiologically based pharmacokinetic (PBPK) model was developed within the Exposure Related Dose Estimating Model (ERDEM) framework to investigate selected exposure inputs related to recognized exposure scenarios of infants and children to N-methyl carbamate pesticides as spec...

  7. USE OF EXPOSURE-RELATED DOSE ESTIMATING MODEL (ERDEM) FOR ASSESSMENT OF AGGREGATE EXPOSURE OF INFANT AND CHILDREN TO N-METHYL CARBAMATE INSECTICIDES

    EPA Science Inventory

    A physiologically based pharmacokinetic (PBPK) model was developed within the Exposure Related Dose Estimating Model (ERDEM) framework to investigate selected exposure inputs related to recognized exposure scenarios of infants and children to N-methyl carbamate pesticides as spec...

  8. Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood.

    PubMed

    Kile, Molly L; Houseman, E Andres; Baccarelli, Andrea A; Quamruzzaman, Quazi; Rahman, Mahmuder; Mostofa, Golam; Cardenas, Andres; Wright, Robert O; Christiani, David C

    2014-05-01

    Prenatal arsenic exposure is associated with increased risk of disease in adulthood. This has led to considerable interest in arsenic's ability to disrupt fetal programming. Many studies report that arsenic exposure alters DNA methylation in whole blood but these studies did not adjust for cell mixture. In this study, we examined the relationship between arsenic in maternal drinking water collected ≤ 16 weeks gestational age and DNA methylation in cord blood (n = 44) adjusting for leukocyte-tagged differentially methylated regions. DNA methylation was quantified using the Infinium HumanMethylation 450 BeadChip array. Recursively partitioned mixture modeling examined the relationship between arsenic and methylation at 473,844 CpG sites. Median arsenic concentration in water was 12 µg/L (range<1- 510 µg/L). Log 10 arsenic was associated with altered DNA methylation across the epigenome (P = 0.002); however, adjusting for leukocyte distributions attenuated this association (P = 0.013). We also observed that arsenic had a strong effect on the distribution of leukocytes in cord blood. In adjusted models, every log 10 increase in maternal drinking water arsenic exposure was estimated to increase CD8+ T cells by 7.4% (P = 0.0004) and decrease in CD4+ T cells by 9.2% (P = 0.0002). These results show that prenatal exposure to arsenic had an exposure-dependent effect on specific T cell subpopulations in cord blood and altered DNA methylation in cord blood. Future research is needed to determine if these small changes in DNA methylation alter gene expression or are associated with adverse health effects.

  9. Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood

    PubMed Central

    Kile, Molly L; Houseman, E Andres; Baccarelli, Andrea A; Quamruzzaman, Quazi; Rahman, Mahmuder; Mostofa, Golam; Cardenas, Andres; Wright, Robert O; Christiani, David C

    2014-01-01

    Prenatal arsenic exposure is associated with increased risk of disease in adulthood. This has led to considerable interest in arsenic’s ability to disrupt fetal programming. Many studies report that arsenic exposure alters DNA methylation in whole blood but these studies did not adjust for cell mixture. In this study, we examined the relationship between arsenic in maternal drinking water collected ≤ 16 weeks gestational age and DNA methylation in cord blood (n = 44) adjusting for leukocyte-tagged differentially methylated regions. DNA methylation was quantified using the Infinium HumanMethylation 450 BeadChip array. Recursively partitioned mixture modeling examined the relationship between arsenic and methylation at 473,844 CpG sites. Median arsenic concentration in water was 12 µg/L (range < 1- 510 µg/L). Log10 arsenic was associated with altered DNA methylation across the epigenome (P = 0.002); however, adjusting for leukocyte distributions attenuated this association (P = 0.013). We also observed that arsenic had a strong effect on the distribution of leukocytes in cord blood. In adjusted models, every log10 increase in maternal drinking water arsenic exposure was estimated to increase CD8+ T cells by 7.4% (P = 0.0004) and decrease in CD4+ T cells by 9.2% (P = 0.0002). These results show that prenatal exposure to arsenic had an exposure-dependent effect on specific T cell subpopulations in cord blood and altered DNA methylation in cord blood. Future research is needed to determine if these small changes in DNA methylation alter gene expression or are associated with adverse health effects. PMID:24525453

  10. Soil Fumigant Labels - Methyl Bromide

    EPA Pesticide Factsheets

    Search soil fumigant pesticide labels by EPA registration number, product name, or company, and follow the link to The Pesticide Product Label System (PPLS) for details. Updated labels include new safety requirements for buffer zones and related measures.

  11. Effects of environmental noise exposure on DNA methylation in the brain and metabolic health.

    PubMed

    Guo, Liqiong; Li, Peng-Hui; Li, Hua; Colicino, Elena; Colicino, Silvia; Wen, Yi; Zhang, Ruiping; Feng, Xiaotian; Barrow, Timothy M; Cayir, Akin; Baccarelli, Andrea A; Byun, Hyang-Min

    2017-02-01

    Environmental noise exposure is associated with adverse effects on human health including hearing loss, heart disease, and changes in stress-related hormone levels. Alteration in DNA methylation in response to environmental exposures is a well-known phenomenon and it is implicated in many human diseases. Understanding how environmental noise exposures affect DNA methylation patterns may help to elucidate the link between noise and adverse effects on health. In this pilot study we examined the effects of environmental noise exposure on DNA methylation of genes related to brain function and investigated whether these changes are related with metabolic health. We exposed four groups of male Wistar rats to moderate intensity noise (70-75dB with 20-4000Hz) at night for three days as short-term exposure, and for three weeks as long-term exposure. Noise exposure was limited to 45dB during the daytime. Control groups were exposed to only 45dB, day and night. We measured DNA methylation in the Bdnf, Comt, Crhr1, Mc2r, and Snca genes in tissue from four brain regions of the rats (hippocampus, frontal lobe, medulla oblongata, and inferior colliculus). Further, we measured blood pressure and body weight after long-term noise exposure. We found that environmental noise exposure is associated with gene-specific DNA methylation changes in specific regions of the brain. Changes in DNA methylation are significantly associated with changes in body weight (between Bdnf DNA methylation and Δ body weight: r=0.59, p=0.018; and between LINE-1 ORF DNA methylation and Δ body weight: =-0.80, p=0.0004). We also observed that noise exposure decreased blood pressure (p=0.038 for SBP, p=0.017 for DBP and p 0. 017 for MAP) and decreased body weight (β=-26g, p=0.008). In conclusion, environmental noise exposures can induce changes in DNA methylation in the brain, which may be associated with adverse effects upon metabolic health through modulation of response to stress-related hormones

  12. Subtle Decreases in DNA Methylation and Gene Expression at the Mouse Igf2 Locus Following Prenatal Alcohol Exposure: Effects of a Methyl-Supplemented Diet

    PubMed Central

    Downing, Chris; Johnson, Thomas E; Larson, Colin; Leakey, Tatiana I; Siegfried, Rachel N; Rafferty, Tonya M; Cooney, Craig A

    2010-01-01

    C57BL/6J (B6) mice are susceptible to in utero growth retardation and a number of morphological malformations following prenatal alcohol exposure, while DBA/2J (D2) mice are relatively resistant. We have previously shown that genomic imprinting may play a role in differential sensitivity between B6 and D2 (Downing and Gilliam 1999). The best characterized mechanism mediating genomic imprinting is differential DNA methylation. In the present study we examined DNA methylation and gene expression, in both embryonic and placental tissue, at the mouse Igf2 locus following in utero ethanol exposure. We also examined the effects of a methyl-supplemented diet on methylation and ethanol teratogenesis. In embryos from susceptible B6 mice, we found small decreases in DNA methylation at four CpG sites in one of the differentially methylated regions of the Igf2 locus; only one of the four sites showed a statistically significant decrease. We observed no significant decreases in methylation in placentae. All Igf2 transcripts showed approximately 1.5 fold decreases following intrauterine alcohol exposure. Placing dams on a methyl-supplemented diet before pregnancy and throughout gestation brought methylation back up to control levels. Methyl-supplementation also resulted in lower prenatal mortality, greater prenatal growth, and decreased digit malformations; it dramatically reduced vertebral malformations. Thus, while prenatal alcohol had only small effects on DNA methylation at the Igf2 locus, placing dams on a methyl-supplemented diet partially ameliorated ethanol teratogenesis. PMID:20705422

  13. Subtle decreases in DNA methylation and gene expression at the mouse Igf2 locus following prenatal alcohol exposure: effects of a methyl-supplemented diet.

    PubMed

    Downing, Chris; Johnson, Thomas E; Larson, Colin; Leakey, Tatiana I; Siegfried, Rachel N; Rafferty, Tonya M; Cooney, Craig A

    2011-02-01

    C57BL/6J (B6) mice are susceptible to in utero growth retardation and a number of morphological malformations following prenatal alcohol exposure, while DBA/2J (D2) mice are relatively resistant. We have previously shown that genomic imprinting may play a role in differential sensitivity between B6 and D2. The best-characterized mechanism mediating genomic imprinting is differential DNA methylation. In the present study we examined DNA methylation and gene expression, in both embryonic and placental tissue, at the mouse Igf2 locus following in utero ethanol exposure. We also examined the effects of a methyl-supplemented diet on methylation and ethanol teratogenesis. In embryos from susceptible B6 mice, we found small decreases in DNA methylation at four CpG sites in one of the differentially methylated regions of the Igf2 locus; only one of the four sites showed a statistically significant decrease. We observed no significant decreases in methylation in placentae. All Igf2 transcripts showed approximately 1.5-fold decreases following intrauterine alcohol exposure. Placing dams on a methyl-supplemented diet before pregnancy and throughout gestation brought methylation back up to control levels. Methyl supplementation also resulted in lower prenatal mortality, greater prenatal growth, and decreased digit malformations; it dramatically reduced vertebral malformations. Thus, although prenatal alcohol had only small effects on DNA methylation at the Igf2 locus, placing dams on a methyl-supplemented diet partially ameliorated ethanol teratogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Exposure to persistent organic pollutants and sperm DNA methylation changes in Arctic and European populations.

    PubMed

    Consales, Claudia; Toft, Gunnar; Leter, Giorgio; Bonde, Jens Peter E; Uccelli, Raffaella; Pacchierotti, Francesca; Eleuteri, Patrizia; Jönsson, Bo A G; Giwercman, Aleksander; Pedersen, Henning S; Struciński, Paweł; Góralczyk, Katarzyna; Zviezdai, Valentyna; Spanò, Marcello

    2016-04-01

    Persistent organic pollutants (POPs), such as PCBs (polychlorinated biphenyls) and DDT [1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane], are environmental contaminants with potential endocrine disrupting activity. DNA methylation levels in peripheral blood lymphocytes have been associated with serum concentrations of POPs in Greenland Inuit and Korean populations. Greenland Inuits are characterized by the highest worldwide POP levels. In this cross-sectional study we evaluated the relationship between serum POP concentrations and DNA methylation levels in sperm of non-occupationally exposed fertile men from Greenland, Warsaw (Poland), and Kharkiv (Ukraine). Serum levels of PCB-153 [1,2,4-trichloro-5-(2,4,5-trichlorophenyl)benzene], as a proxy of the total PCBs body burden, and of p,p'-DDE [1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene], the main metabolite of DDT were measured. Sperm DNA methylation level was assessed globally by flow cytometric (FCM) immunodetection of 5-methyl-cytosines and at specific repetitive DNA sequences (Alu, LINE-1, Satα) by PCR-pyrosequencing after bisulfite conversion. Multivariate linear regression analysis was applied to investigate correlations between serum POP concentrations and DNA methylation. No consistent associations between exposure to POPs and sperm DNA methylation at repetitive DNA sequences were detected. A statistically significant global decrease in methylation was associated with exposure to either POP by FCM analysis. This is the first study to investigate environmental exposure to POPs and DNA methylation levels considering sperm as the target cells. Although POP exposure appears to have a limited negative impact on sperm DNA methylation levels in adult males, the global hypomethylation detected by one of the methods applied suggests that further investigation is warranted.

  15. Global DNA methylation in gonads of adult zebrafish Danio rerio under bisphenol A exposure.

    PubMed

    Liu, Yan; Zhang, Yingying; Tao, Shiyu; Guan, Yongjing; Zhang, Ting; Wang, Zaizhao

    2016-08-01

    Altered DNA methylation is pervasively associated with changes in gene expression and signal transduction after exposure to a wide range of endocrine disrupting chemicals. As a weak estrogenic chemical, bisphenol A (BPA) has been extensively studied for reproductive toxicity. In order to explore the effects of BPA on epigenetic modification in gonads of zebrafish Danio rerio, we measured the global DNA methylation together with the gene expression of DNA methyltransferase (dnmts), glycine N-methyltransferase (gnmt), and ten-eleven translocation (tets) in gonads of D. rerio under BPA exposure by ELISA and quantitative real-time PCR method, respectively. The global level of DNA methylation was significantly decreased in ovaries after exposed to BPA for 7 days, and testes following 35-day exposure. Moreover, the global level of DNA methylation was also significantly reduced in testes after exposed to 15μg/L BPA for 7 days. Besides the alteration of the global level of DNA methylation, varying degrees of transcriptional changes of dnmts, gnmt and tets were detected in gonads of D. rerio under BPA exposure. The present study suggested that BPA might cause the global DNA demethylation in gonads of zebrafish by regulating the transcriptional changes of the DNA methylation/demethylation-associated genes (dnmts, gnmt, and tets). Copyright © 2016. Published by Elsevier Inc.

  16. Prenatal antidepressant exposure associated with CYP2E1 DNA methylation change in neonates

    PubMed Central

    Gurnot, Cécile; Martin-Subero, Ignacio; Mah, Sarah M; Weikum, Whitney; Goodman, Sarah J; Brain, Ursula; Werker, Janet F; Kobor, Michael S; Esteller, Manel; Oberlander, Tim F; Hensch, Takao K

    2015-01-01

    Some but not all neonates are affected by prenatal exposure to serotonin reuptake inhibitor antidepressants (SRI) and maternal mood disturbances. Distinguishing the impact of these 2 exposures is challenging and raises critical questions about whether pharmacological, genetic, or epigenetic factors can explain the spectrum of reported outcomes. Using unbiased DNA methylation array measurements followed by a detailed candidate gene approach, we examined whether prenatal SRI exposure was associated with neonatal DNA methylation changes and whether such changes were associated with differences in birth outcomes. Prenatal SRI exposure was first associated with increased DNA methylation status primarily at CYP2E1(βNon-exposed = 0.06, βSRI-exposed = 0.30, FDR = 0); however, this finding could not be distinguished from the potential impact of prenatal maternal depressed mood. Then, using pyrosequencing of CYP2E1 regulatory regions in an expanded cohort, higher DNA methylation status—both the mean across 16 CpG sites (P < 0.01) and at each specific CpG site (P < 0.05)—was associated with exposure to lower 3rd trimester maternal depressed mood symptoms only in the SRI-exposed neonates, indicating a maternal mood x SRI exposure interaction. In addition, higher DNA methylation levels at CpG2 (P = 0.04), CpG9 (P = 0.04) and CpG10 (P = 0.02), in the interrogated CYP2E1 region, were associated with increased birth weight independently of prenatal maternal mood, SRI drug exposure, or gestational age at birth. Prenatal SRI antidepressant exposure and maternal depressed mood were associated with altered neonatal CYP2E1 DNA methylation status, which, in turn, appeared to be associated with birth weight. PMID:25891251

  17. Lead exposure in pheochromocytoma cells induces persistent changes in amyloid precursor protein gene methylation patterns.

    PubMed

    Li, Yuan-Yuan; Chen, Tian; Wan, Yanjian; Xu, Shun-qing

    2012-08-01

    It has been suggested that lead (Pb) exposure in early life may increase amyloid precursor protein (APP) expression and promote the pathogenesis of Alzheimer's disease in old age. The current study examined whether the DNA methylation patterns of APP gene in rat pheochromocytoma (PC12) cells changed after Pb acetate exposure. Undifferentiated PC12 cells were exposed to three doses of Pb acetate (50, 250, and 500 nM) and one control for 2 days or 1 week. The methylation patterns of APP promoter and global DNA methylation were analyzed. The DNA methyltransferase 1 (DNMT1) expression and the level of amyloid β peptide (Aβ) were also investigated. The results showed that the exposure of the three concentrations of Pb acetate could make the APP promoter hypomethylated. The global DNA methylation level and the expression of DNMT1 were changed in the 500 nM group after 2 days exposure and in the 250 and 500 nM group after 7 days exposure. Thus, Pb may exert neurotoxic effects through mechanisms that alter the global and promoter methylation patterns of APP gene. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012. Copyright © 2010 Wiley Periodicals, Inc.

  18. Physical activity, black carbon exposure, and DNA methylation in the FOXP3 promoter.

    PubMed

    Lovinsky-Desir, Stephanie; Jung, Kyung Hwa; Jezioro, Jacqueline R; Torrone, David Z; de Planell-Saguer, Mariangels; Yan, Beizhan; Perera, Frederica P; Rundle, Andrew G; Perzanowski, Matthew S; Chillrud, Steven N; Miller, Rachel L

    2017-01-01

    Physical activity is associated with improvement in lung function; however, pollution exposure during physical activity can lead to a transient reduction in lung function. This paradoxical relationship may be linked to altered T regulatory (Treg) cell activity, which increases with exercise and suppresses airway inflammation, but decreases in association with exposure to air pollution. To clarify these relationships, we investigated buccal cell DNA methylation of the forkhead box p3 (FOXP3) gene promoter, a proposed biomarker of Treg activity. We hypothesized that active urban children would have lower FOXP3 promoter methylation, associated with better lung function compared to non-active children. We also hypothesized that this relationship would be attenuated by high exposure to the air pollutant black carbon (BC). We performed a cross-sectional study of 135 children ages 9-14 who live in New York City. Activity was measured across 6 days. BC exposure was assessed by personal monitors worn for two 24-h periods, followed by lung function assessment. Buccal swabs were collected for DNA methylation analysis of three regions (six CpG sites) in the FOXP3 promoter. In multivariable regression models, overall, there was no significant relationship between physical activity and FOXP3 promoter methylation (p > 0.05). However, in stratified analyses, among children with higher BC exposure (≥1200 ng/m(3)), physical activity was associated with 2.37% lower methylation in promoter 2 (CpGs -77, -65, and -58) (βestimate = -2.37%, p < 0.01) but not among those with lower BC exposure (βestimate = 0.54%, p > 0.05). Differences across strata were statistically significant (pinteraction = 0.04). Among all children, after controlling for BC concentration, promoter 2 methylation was associated with reduced FEV1/FVC (βestimate = -0.40%, p < 0.01) and reduced FEF25-75% (βestimate = -1.46%, p < 0.01). Physical activity in urban children

  19. Prenatal Arsenic Exposure and DNA Methylation in Maternal and Umbilical Cord Blood Leukocytes

    PubMed Central

    Baccarelli, Andrea; Hoffman, Elaine; Tarantini, Letizia; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Mostofa, Golam; Hsueh, Yu-Mei; Wright, Robert O.; Christiani, David C.

    2012-01-01

    Background: Arsenic is an epigenetic toxicant and could influence fetal developmental programming. Objectives: We evaluated the association between arsenic exposure and DNA methylation in maternal and umbilical cord leukocytes. Methods: Drinking-water and urine samples were collected when women were at ≤ 28 weeks gestation; the samples were analyzed for arsenic using inductively coupled plasma mass spectrometry. DNA methylation at CpG sites in p16 (n = 7) and p53 (n = 4), and in LINE-1 and Alu repetitive elements (3 CpG sites in each), was quantified using pyrosequencing in 113 pairs of maternal and umbilical blood samples. We used general linear models to evaluate the relationship between DNA methylation and tertiles of arsenic exposure. Results: Mean (± SD) drinking-water arsenic concentration was 14.8 ± 36.2 μg/L (range: < 1–230 μg/L). Methylation in LINE-1 increased by 1.36% [95% confidence interval (CI): 0.52, 2.21%] and 1.08% (95% CI: 0.07, 2.10%) in umbilical cord and maternal leukocytes, respectively, in association with the highest versus lowest tertile of total urinary arsenic per gram creatinine. Arsenic exposure was also associated with higher methylation of some of the tested CpG sites in the promoter region of p16 in umbilical cord and maternal leukocytes. No associations were observed for Alu or p53 methylation. Conclusions: Exposure to higher levels of arsenic was positively associated with DNA methylation in LINE-1 repeated elements, and to a lesser degree at CpG sites within the promoter region of the tumor suppressor gene p16. Associations were observed in both maternal and fetal leukocytes. Future research is needed to confirm these results and determine if these small increases in methylation are associated with any health effects. PMID:22466225

  20. Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation.

    PubMed

    Liu, Yunlong; Balaraman, Yokesh; Wang, Guohua; Nephew, Kenneth P; Zhou, Feng C

    2009-10-01

    Alcohol exposure during development can cause variable neurofacial deficit and growth retardation known as fetal alcohol spectrum disorders (FASD). The mechanism underlying FASD is not fully understood. However, alcohol, which is known to affect methyl donor metabolism, may induce aberrant epigenetic changes contributing to FASD. Using a tightly controlled whole-embryo culture, we investigated the effect of alcohol exposure (88mM) at early embryonic neurulation on genome-wide DNA methylation and gene expression in the C57BL/6 mouse. The DNA methylation landscape around promoter CpG islands at early mouse development was analyzed using MeDIP (methylated DNA immunoprecipitation) coupled with microarray (MeDIP-chip). At early neurulation, genes associated with high CpG promoters (HCP) had a lower ratio of methylation but a greater ratio of expression. Alcohol-induced alterations in DNA methylation were observed, particularly in genes on chromosomes 7, 10, and X; remarkably, a >10 fold increase in the number of genes with increased methylation on chromosomes 10 and X was observed in alcohol-exposed embryos with a neural tube defect phenotype compared to embryos without a neural tube defect. Significant changes in methylation were seen in imprinted genes, genes known to play roles in cell cycle, growth, apoptosis, cancer, and in a large number of genes associated with olfaction. Altered methylation was associated with significant (p<0.01) changes in expression for 84 genes. Sequenom EpiTYPER DNA methylation analysis was used for validation of the MeDIP-chip data. Increased methylation of genes known to play a role in metabolism (Cyp4f13) and decreased methylation of genes associated with development (Nlgn3, Elavl2, Sox21 and Sim1), imprinting (Igf2r) and chromatin (Hist1h3d) was confirmed. In a mouse model for FASD, we show for the first time that alcohol exposure during early neurulation can induce aberrant changes in DNA methylation patterns with associated changes in

  1. Prenatal exposure to mixtures of xenoestrogens and repetitive element DNA methylation changes in human placenta

    PubMed Central

    Vilahur, Nadia; Bustamante, Mariona; Byun, Hyang-Min; Fernandez, Mariana F.; Marina, Loreto Santa; Basterrechea, Mikel; Ballester, Ferran; Murcia, Mario; Tardón, Adonina; Fernández-Somoano, Ana; Estivill, Xavier; Olea, Nicolas; Sunyer, Jordi; Baccarelli, Andrea A.

    2014-01-01

    Background Prenatal exposure to endocrine disrupting compounds (EDCs) has previously shown to alter epigenetic marks. Objectives In this work we explore whether prenatal exposure to mixtures of xenoestrogens has the potential to alter the placenta epigenome, by studying DNA methylation in retrotransposons as a surrogate of global DNA methylation. Methods The biomarker Total Effective Xenoestrogen Burden (TEXB) was measured in 192 placentas from participants in the longitudinal INMA Project. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 10 different retrotransposons including 3 different long interspersed nuclear elements (LINEs), 4 short interspersed nuclear elements (SINEs) and 3 human endogenous retrovirus (HERVs). Associations were tested using linear mixed-effects regression models and sex interaction was evaluated. Results A significant sex interaction was observed for AluYb8 (p value for interaction <0.001, significant at Bonferroni corrected p-value threshold of 0.0025). Boys with the highest TEXB-alpha levels of exposure (third tertile) presented on average a decrease of 0.84% in methylation compared to those in the first tertile (p value<0.001), while no significant effects were found in girls (p value= 0.134). Conclusions Our findings suggest that boys may be more susceptible to the effect of exposure to xenoestrogens during prenatal development, producing shifts in DNA methylation of certain sensitive genomic repetitive sequences in a tissue important for fetal growth and development. PMID:24980756

  2. Effects of methyl mercury exposure on the growth of juvenile common loons

    USGS Publications Warehouse

    Kenow, K.P.; Gutreuter, S.; Hines, R.K.; Meyer, M.W.; Fournier, F.; Karasov, W.H.

    2003-01-01

    We conducted a dose-response laboratory study to quantify the level of mercury exposure associated with negative effects on the development of common loon chicks reared in captivity from hatch to 105 days. A dose regimen was implemented that provided exposure levels that bracketed relevant exposure levels of methyl mercury found in loon chicks across North America. We observed no overt signs of mercury toxicosis and detected no significant effect of dietary mercury exposure on growth or food consumption. However, asymptotic mass was lower in chicks that hatched from eggs collected from nests on low pH lakes relative to eggs from neutral pH lakes. Rapid excretion of methyl mercury during feather growth likely provides loon chicks protection from methyl mercury toxicity and may explain the lack of convincing toxicological findings in this study. Lake-source effects suggest that in ovo exposure to methyl mercury or other factors related to lake pH have consequences on chick development.

  3. Determination of methyl-, 2-hydroxyethyl- and 2-cyanoethylmercapturic acids as biomarkers of exposure to alkylating agents in cigarette smoke.

    PubMed

    Scherer, Gerhard; Urban, Michael; Hagedorn, Heinz-Werner; Serafin, Richard; Feng, Shixia; Kapur, Sunil; Muhammad, Raheema; Jin, Yan; Sarkar, Mohamadi; Roethig, Hans-Juergen

    2010-10-01

    Alkylating agents occur in the environment and are formed endogenously. Tobacco smoke contains a variety of alkylating agents or precursors including, among others, N-nitrosodimethylamine (NDMA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), acrylonitrile and ethylene oxide. We developed and validated a method for the simultaneous determination of methylmercapturic acid (MMA, biomarker for methylating agents such as NDMA and NNK), 2-hydroxyethylmercapturic acid (HEMA, biomarker for ethylene oxide) and 2-cyanoethylmercapturic acid (CEMA, biomarker for acrylonitrile) in human urine using deuterated internal standards of each compound. The method involves liquid/liquid extraction of the urine sample, solid phase extraction on anion exchange cartridges, derivatization with pentafluorobenzyl bromide (PFBBr), liquid/liquid extraction of the reaction mixture and LC-MS/MS analysis with positive electrospray ionization. The method was linear in the ranges of 5.00-600, 1.00-50.0 and 1.50-900 ng/ml for MMA, HEMA and CEMA, respectively. The method was applied to two clinical studies in adult smokers of conventional cigarettes who either continued smoking conventional cigarettes, were switched to test cigarettes consisting of either an electrically heated cigarette smoking system (EHCSS) or having a highly activated carbon granule filter that were shown to have reduced exposure to specific smoke constituents, or stopped smoking. Urinary excretion of MMA was found to be unaffected by switching to the test cigarettes or stop smoking. Urinary HEMA excretion decreased by 46 to 54% after switching to test cigarettes and by approximately 74% when stopping smoking. Urinary CEMA excretion decreased by 74-77% when switching to test cigarettes and by approximately 90% when stopping smoking. This validated method for urinary alkylmercapturic acids is suitable to distinguish differences in exposure not only between smokers and nonsmokers but also between smoking of conventional and

  4. Aberrant DNA methylation of some tumor suppressor genes in lung cancers from workers with chromate exposure.

    PubMed

    Ali, Abdellah H K; Kondo, Kazuya; Namura, Toshiaki; Senba, Yoshitaka; Takizawa, Hiromitsu; Nakagawa, Yasushi; Toba, Hiroaki; Kenzaki, Koichiro; Sakiyama, Shoji; Tangoku, Akira

    2011-02-01

    Our previous studies revealed a variety of genetic changes in lung cancers from chromate-exposed workers (chromate lung cancer). In the present study, we examined epigenetic changes in chromate lung cancers. Nested-methylation-specific PCR was employed in studying the methylation of CpG islands in the APC, MGMT, hMLH1 genes in 36 chromate lung cancers and 25 nonchromate lung cancers. Methylation in chromate lung cancers was detected at 86% for APC, 20% for MGMT, and 28% for hMLH1. Whereas, it occurred at lower frequencies in nonchromate lung cancers, particularly in APC (44%) and hMLH1 (0%) genes. Our previous study showed that methylation of p16 gene in chromate lung cancer and nonchromate lung cancer was 33% and 26%, respectively. The mean methylation index (MI), a reflection of the overall methylation status, was significantly higher in chromate lung cancers than nonchromate lung cancers (0.41 vs. 0.21, P=0.001). Methylation of multiple genes (particularly hMLH1, p16, and APC genes) had experienced more than 15 yr of chromate exposure in chromate lung cancer (MI: <15 yr; 0.19, ≥ 15 yr, 0.42). There is a significant correlation of p16 and hMLH1 methylation with the expressional decrease or loss of the corresponding gene products (P=0.037 and 0.024) respectively, and an inverse correlation between APC and MGMT methylation (P = 0.014). This study provides a novel evidence for the chromium carcinogenesis that chromate lung cancer is linked to the progressive methylation of some tumor suppressor genes, which may be related to genomic instability.

  5. Modeling tribal exposures to methyl mercury from fish consumption

    EPA Science Inventory

    Exposure assessment and risk management considerations for tribal fish consumption are different than for the general U.S. population because of higher fish intake from subsistence fishing and/or from unique cultural practices. This research summarizes analyses of available data ...

  6. Modeling tribal exposures to methyl mercury from fish consumption

    EPA Science Inventory

    Exposure assessment and risk management considerations for tribal fish consumption are different than for the general U.S. population because of higher fish intake from subsistence fishing and/or from unique cultural practices. This research summarizes analyses of available data ...

  7. Effects of arsenic exposure on DNA methylation and epigenetic gene regulation.

    PubMed

    Reichard, John F; Puga, Alvaro

    2010-02-01

    Arsenic is a nonmutagenic human carcinogen that induces tumors through unknown mechanisms. A growing body of evidence suggests that its carcinogenicity results from epigenetic changes, particularly in DNA methylation. Changes in gene methylation status, mediated by arsenic, have been proposed to activate oncogene expression or silence tumor suppressor genes, leading to long-term changes in the activity of genes controlling cell transformation. Mostly descriptive, and often contradictory, studies have demonstrated that arsenic exposure is associated with both hypo- and hyper-methylation at various genetic loci in vivo or in vitro. This ambiguity has made it difficult to assess whether the changes induced by arsenic are causally involved in the transformation process or are simply a reflection of the altered physiology of rapidly dividing cancer cells. Here, we discuss the evidence supporting changes in DNA methylation as a cause of arsenic carcinogenesis and highlight the strengths and limitations of these studies, as well as areas where consistencies and inconsistencies exist.

  8. Effects of arsenic exposure on DNA methylation and epigenetic gene regulation

    PubMed Central

    Reichard, John F; Puga, Alvaro

    2010-01-01

    Arsenic is a nonmutagenic human carcinogen that induces tumors through unknown mechanisms. A growing body of evidence suggests that its carcinogenicity results from epigenetic changes, particularly in DNA methylation. Changes in gene methylation status, mediated by arsenic, have been proposed activate oncogene expression or silence tumor suppressor genes, leading to long-term changes in activity of genes controlling cell transformation. Mostly descriptive, and often contradictory, studies have demonstrated that arsenic exposure is associated with both hypo- and hyper-methylation at various genetic loci in vivo or in vitro. This ambiguity has made it difficult to assess whether the changes induced by arsenic are causally involved in the transformation process or are simply a reflection of the altered physiology of rapidly dividing cancer cells. Here, we discuss the evidence supporting changes in DNA methylation as a cause of arsenic carcinogenesis and highlight the strengths and limitations of these studies, as well areas where consistencies and inconsistencies exist. PMID:20514360

  9. Benzopyrene exposure disrupts DNA methylation and growth dynamics in breast cancer cells

    SciTech Connect

    Sadikovic, Bekim; Rodenhiser, David I. . E-mail: drodenhi@uwo.ca

    2006-11-01

    Exposures to environmental carcinogens and unhealthy lifestyle choices increase the incidence of breast cancer. One such compound, benzo(a)pyrene (BaP), leads to covalent DNA modifications and the deregulation of gene expression. To date, these mechanisms of BaP-induced carcinogenesis are poorly understood, particularly in the case of breast cancer. We tested the effects of BaP exposure on cellular growth dynamics and DNA methylation in four breast cancer cell lines since disruptions in DNA methylation lead to deregulated gene expression and the loss of genomic integrity. We observed robust time- and concentration-dependent loss of proliferation, S phase and G2M accumulation and apoptosis in p53 positive MCF-7 and T47-D cells. We observed minimal responses in p53 negative HCC-1086 and MDA MB 231 cells. Furthermore, BaP increased p53 levels in both p53 positive cell lines, as well as p21 levels in MCF-7 cells, an effect that was prevented by the p53-specific inhibitor pifithrin-{alpha}. No changes in global levels of DNA methylation levels induced by BaP were detected by the methyl acceptor assay (MAA) in any cell line, however, methylation profiling by AIMS (amplification of intermethylated sites) analysis showed dynamic, sequence-specific hypo- and hypermethylation events in all cell lines. We also identified BaP-induced hypomethylation events at a number of genomic repeats. Our data confirm the p53-specific disruption of the cell cycle as well as the disruption of DNA methylation as a consequence of BaP treatment, thus reinforcing the link between environmental exposures, DNA methylation and breast cancer.

  10. Response to copper bromide exposure in Vicia sativa L. seeds: analysis of genotoxicity, nucleolar activity and mineral profile.

    PubMed

    Bellani, Lorenza M; Muccifora, Simonetta; Giorgetti, Lucia

    2014-09-01

    Copper bromide (CuBr2) effects on seed germination and plantlet development of Vicia sativa L. are evaluated through mitotic index, chromosome aberrations, nucleolar activity and mineral profile. CuBr2 induces a significant presence of micronuclei, sticky and c-metaphases, anaphase bridges and chromosome breaks. Increased number of nucleoli and scattering of AgNOR proteins from the nucleolus in the nuclear surface at CuBr2 1mM and in the cytoplasm at CuBr2 5mM, goes along with the decrease of root growth. In V. sativa embryo the content of many macro and micronutrients increases up to copper 1mM in agreement with reserve mobilization while at CuBr2 5mM some elements are present in lower amount. We hypothesize that inhibitory effects observed at 5mM are due either to a nutrient shortage or to a direct influence of copper on root cell division, evidenced by low mitotic index, high occurrence of chromosome aberrations and loss of material from the nucleolus.

  11. REFINED PBPK MODEL OF AGGREGATE EXPOSURE TO METHYL TERTIARY-BUTYL ETHER

    EPA Science Inventory

    Aggregate (multiple pathway) exposures to methyl tertiary-butyl ether (MTBE) in air and water occur via dermal, inhalation, and oral routes. Previously, physiologically-based pharmacokinetic (PBPK) models have been used to quantify the kinetic behavior of MTBE and its primary met...

  12. REFINED PBPK MODEL OF AGGREGATE EXPOSURE TO METHYL TERTIARY-BUTYL ETHER

    EPA Science Inventory

    Aggregate (multiple pathway) exposures to methyl tertiary-butyl ether (MTBE) in air and water occur via dermal, inhalation, and oral routes. Previously, physiologically-based pharmacokinetic (PBPK) models have been used to quantify the kinetic behavior of MTBE and its primary met...

  13. Testicular germ-cell apoptosis in stressed rats following combined exposure to pyridostigmine bromide, N,N-diethyl m-toluamide (DEET), and permethrin.

    PubMed

    Abou-Donia, Mohamed B; Suliman, Hagir B; Khan, Wasiuddin A; Abdel-Rahman, Ali A

    2003-01-10

    This study reports and characterizes the testicular apoptosis following daily exposure of male Sprague-Dawley rats to subchronic combined doses of pyridostigmine bromide (PB, 1.3 mg/kg/d in water, oral), a drug used for treatment of myasthenia gravis and prophylactic treatment against nerve agents during the Persian Gulf War; the insect repellent N,N-diethyl m-toluamide (DEET, 40 mg/kg/d in ethanol, dermal); and the insecticide permethrin (0.13 mg/kg in ethanol, dermal), with and without stress for 28 d. Combined exposure to these chemicals was implicated in the development of illnesses including genitourinary disorders among many veterans of the Persian Gulf War. Previous studies from this laboratory have shown that exposure to combination of these chemicals produced greater toxicity compared to single components. Exposure to stress alone did not cause any significant histopathological alterations in the testes. Administration of combination of these chemicals induced apoptosis in rat testicular germ cells, Sertoli cells, and Leydig cells, as well as in the endothelial lining of the blood vessels. Testicular damage was significantly augmented when the animals were further exposed to a combination of chemicals and stress. Histopathological examination of testicular tissue sections showed that apoptosis was confined to the basal germ cells and spermatocytes, indicating suppression of spermatogenesis. Increased apoptosis of testicular cells coincided, in timing and localization, with increased expression of the apoptosis-promoting proteins Bax and p53. Furthermore, significant increase of 3-nitrotyrosine immunostaining in the testis revealed oxidative and/or nitrosation induction of cell death. In conclusion, combined exposure to real-life doses of test compounds caused germ-cell apoptosis that was significantly enhanced by stress.

  14. Prenatal environmental tobacco smoke exposure increases allergic asthma risk with methylation changes in mice.

    PubMed

    Christensen, Sonja; Jaffar, Zeina; Cole, Elizabeth; Porter, Virginia; Ferrini, Maria; Postma, Britten; Pinkerton, Kent E; Yang, Mihi; Kim, Yang Jee; Montrose, Luke; Roberts, Kevan; Holian, Andrij; Cho, Yoon Hee

    2017-07-01

    Allergic asthma remains an inadequately understood disease. In utero exposure to environmental tobacco smoke (ETS) has been identified as an environmental exposure that can increase an individual's asthma risk. To improve our understanding of asthma onset and development, we examined the effect of in utero ETS exposure on allergic disease susceptibility in an asthmatic phenotype using a house dust mite (HDM) allergen-induced murine model. Pregnant C57BL/6 mice were exposed to either filtered air or ETS during gestation, and their offspring were further exposed to HDM at 6-7 weeks old to induce allergic inflammation. Methylation in the promoter regions of allergic inflammation-related genes and genomic DNA was quantified. Exposure to HDM resulted in the onset of allergic lung inflammation, with an increased presence of inflammatory cells, Th2 cytokines (IL-4, IL-5, and IL-13), and airway remodeling. These asthmatic phenotypes were significantly enhanced when the mice had been exposed to in utero ETS. Furthermore, prenatal ETS exposure and subsequent HDM (ETS/HDM)-induced asthmatic phenotypes agree with methylation changes in the selected asthma-related genes, including IL-4, IL-5, IL-13, INF-γ, and FOXP3. Global DNA methylation was significantly lower in ETS/HDM-exposed mice than that of controls, which coincides with the results observed in lung, spleen, and blood DNAs. Prenatal ETS exposure resulted in a severe increase in allergic inflammatory responses after an HDM challenge, with corresponding methylation changes. Prenatal ETS exposure may influence developmental plasticity and result in altered epigenetic programming, leading to an increased susceptibility to asthma. Environ. Mol. Mutagen. 58:423-433, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Pet keeping and tobacco exposure influence CD14 methylation in childhood.

    PubMed

    Munthe-Kaas, Monica Cheng; Bertelsen, Randi J; Torjussen, Tale Maehre; Hjorthaug, Hanne Sagsveen; Undlien, Dag E; Lyle, Robert; Gervin, Kristina; Granum, Berit; Mowinckel, Petter; Carlsen, Kai Håkon; Carlsen, Karin C Lødrup

    2012-12-01

    Several CD14 gene-environment interactions in relation to the development of allergic diseases have been reported, but the underlying biological mechanisms are unclear. We recently showed that CD14 methylation increased during childhood, parallelling a decreased impact of CD14 polymorphisms on soluble CD14 levels. Here, we aim to explore whether environmental stimuli during childhood affects CD14 methylation, thereby providing a biological mechanism through which environment may modulate genetic effect. CD14 methylation levels were quantified in 157 children from the prospective Environment and Childhood Asthma birth cohort at ages 2 and 10. Associations between CD14 methylation levels and house dust levels of endotoxin, β(1,3)-glucans (at 2 yr only), allergens (dog, cat, and house dust mite), pet keeping and tobacco smoke exposure (TSE; questionnaire data) at 2 and 10 yr were explored. Children in homes without pets had larger increases in CD14 methylation through childhood (2-10 yr) compared with children with pets (2.1% increase (p = 0.003) vs. 0.4% decrease (n.s.), global p = 0.04). At 10 yr of age, lower CD14 methylation values were found in children with pets compared with children without pets at both 2 and 10 yr (5.4% vs. 7.5% [p = 0.02]). A similar trend was detected for TSE; children not exposed show larger increases in CD14 methylation, most pronounced in school-age girls exposed vs. not exposed to tobacco (5.5% vs. 7.5% methylation, p = 0.037). Pet keeping and TSE appears to limit increase in CD14 methylation from 2 to 10 yr of age. This may partly explain the diverging CD14 allele associations with allergic diseases detected in different environments. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  16. Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood

    SciTech Connect

    Li, Yue; Xie, Changchun; Murphy, Susan K.; Skaar, David; Nye, Monica; Vidal, Adriana C.; Cecil, Kim M.; Dietrich, Kim N.; Puga, Alvaro; Jirtle, Randy L.; Hoyo, Cathrine

    2015-06-26

    Here, lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk. The objective of this study was to determine whether maternal, postnatal, and early childhood lead exposure can alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth, and development. Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study from birth to 78 months. When participants were adults, we used Sequenom EpiTYPER assays to test peripheral blood DNA to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes. Statistical analyses were conducted using linear regression. Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (β = –0.0014; 95% CI: –0.0023, –0.0005, p = 0.002), stronger in males (β = –0.0024; 95% CI: –0.0038, –0.0009, p = 0.003) than in females (β = –0.0009; 95% CI: –0.0020, 0.0003, p = 0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (β = –0.0013; 95% CI: –0.0023, –0.0003, p = 0.01) DMR methylation, but primarily in females, (β = –0.0017; 95% CI: –0.0029, –0.0006, p = 0.005) rather than in males, (β = –0.0004; 95% CI: –0.0023, 0.0015, p = 0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex (β = 0.0075; 95% CI: 0.0018, 0.0132, p = 0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from 30 to 78 months. Our findings

  17. Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood

    DOE PAGES

    Li, Yue; Xie, Changchun; Murphy, Susan K.; ...

    2015-06-26

    Here, lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk. The objective of this study was to determine whether maternal, postnatal, and early childhood lead exposure can alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth, and development. Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study frommore » birth to 78 months. When participants were adults, we used Sequenom EpiTYPER assays to test peripheral blood DNA to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes. Statistical analyses were conducted using linear regression. Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (β = –0.0014; 95% CI: –0.0023, –0.0005, p = 0.002), stronger in males (β = –0.0024; 95% CI: –0.0038, –0.0009, p = 0.003) than in females (β = –0.0009; 95% CI: –0.0020, 0.0003, p = 0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (β = –0.0013; 95% CI: –0.0023, –0.0003, p = 0.01) DMR methylation, but primarily in females, (β = –0.0017; 95% CI: –0.0029, –0.0006, p = 0.005) rather than in males, (β = –0.0004; 95% CI: –0.0023, 0.0015, p = 0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex (β = 0.0075; 95% CI: 0.0018, 0.0132, p = 0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from 30 to 78 months. Our

  18. Influence of Prenatal Arsenic Exposure and Newborn Sex on Global Methylation of Cord Blood DNA

    PubMed Central

    Pilsner, J. Richard; Hall, Megan N.; Liu, Xinhua; Ilievski, Vesna; Slavkovich, Vesna; Levy, Diane; Factor-Litvak, Pam; Yunus, Mahammad; Rahman, Mahfuzar; Graziano, Joseph H.; Gamble, Mary V.

    2012-01-01

    Background An emerging body of evidence indicates that early-life arsenic (As) exposure may influence the trajectory of health outcomes later in life. However, the mechanisms underlying these observations are unknown. Objective The objective of this study was to investigate the influence of prenatal As exposure on global methylation of cord blood DNA in a study of mother/newborn pairs in Matlab, Bangladesh. Design Maternal and cord blood DNA were available from a convenience sample of 101 mother/newborn pairs. Measures of As exposure included maternal urinary As (uAs), maternal blood As (mbAs) and cord blood As (cbAs). Several measures of global DNA methylation were assessed, including the [3H]-methyl-incorporation assay and three Pyrosequencing assays: Alu, LINE-1 and LUMA. Results In the total sample, increasing quartiles of maternal uAs were associated with an increase in covariate-adjusted means of newborn global DNA methylation as measured by the [3H]-methyl-incorporation assay (quartile 1 (Q1) and Q2 vs. Q4; p = 0.06 and 0.04, respectively). Sex-specific linear regression analyses, while not reaching significance level of 0.05, indicated that the associations between As exposures and Alu, LINE-1 and LUMA were positive among male newborns (N = 58) but negative among female newborns (N = 43); tests for sex differences were borderline significant for the association of cbAs and mbAs with Alu (p = 0.05 and 0.09, respectively) and for the association between maternal uAs and LINE-1 (p = 0.07). Sex-specific correlations between maternal urinary creatinine and newborn methyl-incorporation, Alu and LINE-1 were also evident (p<0.05). Conclusions These results suggest that prenatal As exposure is associated with global DNA methylation in cord blood DNA, possibly in a sex-specific manner. Arsenic-induced epigenetic modifications in utero may potentially influence disease outcomes later in life. Additional studies are needed to confirm these findings

  19. [(1S,2S,3R,4R)-3-Hydr-oxy-4,7,7-tri-methyl-bicyclo-[2.2.1]heptan-2-yl]methyl[(E)-3-(trimethyl-silyl)prop-2-enyl]selen-onium bromide.

    PubMed

    Wang, Hai-Yang; Zhang, Qiang; Li, Yi-Zhi; Gui, Yuan; Huang, Zhi-Zhen

    2008-06-07

    The title compound, a seleno-nium bromide, C(17)H(33)OSeSi(+)·Br(-), was obtained from the reaction of enanti-omerically pure 4,7,7-trimethyl-2-methyl-selanylbicyclo-[2.2.1]heptan-3-ol and (3-bromopropen-yl)trimethyl-silane in acetone. Due to the chiral bicyclic substituent, the crystal structure is not centrosymmetric and has no symmetry plane, with four chiral C atoms in the cation. The asymmetric unit contains one seleno-nium cation and one bromide anion. C-H⋯Br and O-H⋯Br hydrogen bonds link the ions, forming a one-dimensional R-helical chain-like supra-molecular structure.

  20. DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders?

    PubMed Central

    Keil, Kimberly P.; Lein, Pamela J.

    2016-01-01

    There is now compelling evidence that gene by environment interactions are important in the etiology of autism spectrum disorders (ASDs). However, the mechanisms by which environmental factors interact with genetic susceptibilities to confer individual risk for ASD remain a significant knowledge gap in the field. The epigenome, and in particular DNA methylation, is a critical gene expression regulatory mechanism in normal and pathogenic brain development. DNA methylation can be influenced by environmental factors such as diet, hormones, stress, drugs, or exposure to environmental chemicals, suggesting that environmental factors may contribute to adverse neurodevelopmental outcomes of relevance to ASD via effects on DNA methylation in the developing brain. In this review, we describe epidemiological and experimental evidence implicating altered DNA methylation as a potential mechanism by which environmental chemicals confer risk for ASD, using polychlorinated biphenyls (PCBs), lead, and bisphenol A (BPA) as examples. Understanding how environmental chemical exposures influence DNA methylation and how these epigenetic changes modulate the risk and/or severity of ASD will not only provide mechanistic insight regarding gene-environment interactions of relevance to ASD but may also suggest potential intervention strategies for these and potentially other neurodevelopmental disorders. PMID:27158529

  1. Stress and combined exposure to low doses of pyridostigmine bromide, DEET, and permethrin produce neurochemical and neuropathological alterations in cerebral cortex, hippocampus, and cerebellum.

    PubMed

    Abdel-Rahman, A; Abou-Donia, Suzanne; El-Masry, Eman; Shetty, Ashok; Abou-Donia, Mohamed

    2004-01-23

    Exposure to a combination of stress and low doses of the chemicals pyridostigmine bromide (PB), DEET, and permethrin in adult rats, a model of Gulf War exposure, produces blood-brain barrier (BBB) disruption and neuronal cell death in the cingulate cortex, dentate gyrus, thalamus, and hypothalamus. In this study, neuropathological alterations in other areas of the brain where no apparent BBB disruption was observed was studied following such exposure. Animals exposed to both stress and chemical exhibited decreased brain acetylcholinesterase (AChE) activity in the midbrain, brainstem, and cerebellum and decreased m2 muscarinic acetylcholine (ACh) receptor ligand binding in the midbrain and cerebellum. These alterations were associated with significant neuronal cell death, reduced microtubule-associated protein (MAP-2) expression, and increased glial fibrillary acidic protein (GFAP) expression in the cerebral cortex and the hippocampal subfields CA1 and CA3. In the cerebellum, the neurochemical alterations were associated with Purkinje cell loss and increased GFAP immunoreactivity in the white matter. However, animals subjected to either stress or chemicals alone did not show any of these changes in comparison to vehicle-treated controls. Collectively, these results suggest that prolonged exposure to a combination of stress and the chemicals PB, DEET, and permethrin can produce significant damage to the cerebral cortex, hippocampus, and cerebellum, even in the absence of apparent BBB damage. As these areas of the brain are respectively important for the maintenance of motor and sensory functions, learning and memory, and gait and coordination of movements, such alterations could lead to many physiological, pharmacological, and behavioral abnormalities, particularly motor deficits and learning and memory dysfunction.

  2. DNA methylation at stress-related genes is associated with exposure to early life institutionalization.

    PubMed

    Non, Amy L; Hollister, Brittany M; Humphreys, Kathryn L; Childebayeva, Ainash; Esteves, Kyle; Zeanah, Charles H; Fox, Nathan A; Nelson, Charles A; Drury, Stacy S

    2016-09-01

    Differences in DNA methylation have been associated with early life adversity, suggesting that alterations in methylation function as one pathway through which adverse early environments are biologically embedded. This study examined associations between exposure to institutional care, quantified as the proportion of time in institutional care at specified follow-up assessment ages, and DNA methylation status in two stress-related genes: FKBP5 and SLC6A4. We analyzed data from the Bucharest Early Intervention Project, which is a prospective study in which children reared in institutional settings were randomly assigned (mean age 22 months) to either newly created foster care or care as usual (to remain in their current placement) and prospectively followed. A group of children from the same geographic area, with no history of institutionalized caregiving, were also recruited. DNA methylation status was determined in DNA extracted from buccal epithelial cells of children at age 12. An inverse association was identified such that more time spent in institutional care was associated with lower DNA methylation at specific CpG sites within both genes. These results suggest a lasting impact of early severe social deprivation on methylation patterns in these genes, and contribute to a growing literature linking early adversity and epigenetic variation in children. Am J Phys Anthropol 161:84-93, 2016.. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. DNA methylation at stress-related genes is associated with exposure to early life institutionalization

    PubMed Central

    Non, Amy L.; Hollister, Brittany M.; Humphreys, Kathryn L.; Childebayeva, Ainash; Esteves, Kyle; Zeanah, Charles H.; Fox, Nathan A.; Nelson, Charles A.; Drury, Stacy S.

    2017-01-01

    Objectives Differences in DNA methylation have been associated with early life adversity, suggesting that alterations in methylation function as one pathway through which adverse early environments are biologically embedded. This study examined associations between exposure to institutional care, quantified as the percent time in institutional care at specified follow-up assessment ages, and DNA methylation status in two stress-related genes: FKBP5 and SLC6A4. Materials and Methods We analyzed data from the Bucharest Early Intervention Project, which is a prospective study in which children reared in institutional settings were randomly assigned (mean age 22 months) to either newly created foster care or care as usual (to remain in their current placement) and prospectively followed. A group of children from the same geographic area, with no history of institutionalized caregiving, were also recruited. DNA methylation status was determined in DNA extracted from buccal epithelial cells of children at age 12. Results An inverse association was identified such that more time spent in institutional care was associated with lower DNA methylation at specific CpG sites within both genes. Discussion These results suggest a lasting impact of early severe social deprivation on methylation patterns in these genes, and contribute to a growing literature linking early adversity and epigenetic variation in children. PMID:27218411

  4. DNA methylation signatures link prenatal famine exposure to growth and metabolism

    PubMed Central

    Tobi, Elmar W.; Goeman, Jelle J.; Monajemi, Ramin; Gu, Hongcang; Putter, Hein; Zhang, Yanju; Slieker, Roderick C.; Stok, Arthur P.; Thijssen, Peter E.; Müller, Fabian; van Zwet, Erik W.; Bock, Christoph; Meissner, Alexander; Lumey, L. H.; Eline Slagboom, P.; Heijmans, Bastiaan T.

    2014-01-01

    Periconceptional diet may persistently influence DNA methylation levels with phenotypic consequences. However, a comprehensive assessment of the characteristics of prenatal malnutrition-associated differentially methylated regions (P-DMRs) is lacking in humans. Here we report on a genome-scale analysis of differential DNA methylation in whole blood after periconceptional exposure to famine during the Dutch Hunger Winter. We show that P-DMRs preferentially occur at regulatory regions, are characterized by intermediate levels of DNA methylation and map to genes enriched for differential expression during early development. Validation and further exploratory analysis of six P-DMRs highlight the critical role of gestational timing. Interestingly, differential methylation of the P-DMRs extends along pathways related to growth and metabolism. P-DMRs located in INSR and CPT1A have enhancer activity in vitro and differential methylation is associated with birth weight and serum LDL cholesterol. Epigenetic modulation of pathways by prenatal malnutrition may promote an adverse metabolic phenotype in later life. PMID:25424739

  5. Biological effects of short-term, high-concentration exposure to methyl isocyanate. I. Study objectives and inhalation exposure design

    SciTech Connect

    Dodd, D.E.; Frank, F.R.; Fowler, E.H.; Troup, C.M.; Milton, R.M.

    1987-06-01

    Early reports from India indicated that humans were dying within minutes to a few hours from exposure to methyl isocyanate (MIC). Attempts to explain the cause(s) of these rapid mortalities is where Union Carbide Corporation concentrated its post-Bhopal toxicologic investigations. The MIC studies involving rats and guinea pigs focused primarily on the consequences of acute pulmonary damage. All MIC inhalation exposures were acute, of short duration (mainly 15 min), and high in concentration. MIC vapors were statically generated in a double chamber exposure design. Precautionary measures taken during exposures are discussed. Guinea pigs were more susceptible than rats to MIC exposure-related early mortality. A greater than one order of magnitude difference was observed between an MIC concentration that caused no early mortality in rats (3506 ppm) and an MIC concentration that caused partial (6%) early mortality in guinea pigs (225 ppm) for exposures of 10 to 15 min duration. For both species, the most noteworthy clinical signs during exposure were lacrimation, blepharospasm, and mouth breathing. Fifteen minute LC/sub 50/ tests with 14-day postexposure follow-up were conducted, and the LC/sub 50/ (95% confidence limit) values were 171 (114-256) ppm for rats and 112 (61-204) ppm for guinea pigs. Target exposure concentrations for the toxicologic investigations of MIC-induced early mortality were established. A short summary of pertinent results of Union Carbide Corporation's post-Bhopal toxicologic investigations is presented.

  6. Disabling disturbance of olfaction in a dental technician following exposure to methyl methacrylate.

    PubMed

    Braun, D; Wagner, W; Zenner, H-P; Schmahl, F W

    2002-10-01

    It is often difficult to diagnose dysosmia due to occupational olfactotoxic substances. The authors present a case of disabling disturbance of olfaction in a dental technician. This is very likely to have been caused by exposure to methyl methacrylate. From 1988-1992, the dental technician had very extensive and sustained contact with a self-polymerizing acrylic resin based on methyl methacrylate. Her perception of smell was still normal in 1988, but it deteriorated up to 1992. The olfactory disorders have persisted and impede social life and occupational rehabilitation.

  7. Phenanthrene exposure induces cardiac hypertrophy via reducing miR-133a expression by DNA methylation

    PubMed Central

    Huang, Lixing; Xi, Zhihui; Wang, Chonggang; Zhang, Youyu; Yang, Zhibing; Zhang, Shiqi; Chen, Yixin; Zuo, Zhenghong

    2016-01-01

    Growing evidence indicates that there is an emerging link between environmental pollution and cardiac hypertrophy, while the mechanism is unclear. The objective of this study was to examine whether phenanthrene (Phe) could cause cardiac hypertrophy, and elucidate the molecular mechanisms involved. We found that: 1) Phe exposure increased the heart weight and cardiomyocyte size of rats; 2) Phe exposure led to enlarged cell size, and increased protein synthesis in H9C2 cells; 3) Phe exposure induced important markers of cardiac hypertrophy, such as atrial natriuretic peptide, B-type natriuretic peptide, and c-Myc in H9C2 cells and rat hearts; 4) Phe exposure perturbed miR-133a, CdC42 and RhoA, which were key regulators of cardiac hypertrophy, in H9C2 cells and rat hearts; 5) Phe exposure induced DNA methyltransferases (DNMTs) in H9C2 cells and rat hearts; 6) Phe exposure led to methylation of CpG sites within the miR-133a locus and reduced miR-133a expression in H9C2 cells; 7) DNMT inhibition and miR-133a overexpression could both alleviate the enlargement of cell size and perturbation of CdC42 and RhoA caused by Phe exposure. These results indicated that Phe could induce cardiomyocyte hypertrophy in the rat and H9C2 cells. The mechanism might involve reducing miR-133a expression by DNA methylation. PMID:26830171

  8. Effects of combined exposure to pyridostigmine bromide and shaker stress on acoustic startle response, pre-pulse inhibition and open field behavior in mice.

    PubMed

    Dubovicky, M; Paton, S; Morris, M; Mach, M; Lucot, J B

    2007-01-01

    The present study investigated the effect of combined exposure of pyridostigmine bromide (PB) and chronic shaker stress on acoustic startle responses (ASR), pre-pulse inhibition (PPI) and open field behavior of adult C57BL/6J mice. PB (10 mg kg(-1) day(-1) for 7 days) or saline was administered subcutaneously using osmotic Alzet minipumps implanted under the skin on the back of the mice. At the same time, the mice were exposed to 7 days of intermittent shaker stress. They were tested for ASR (100 dB and 120 dB stimuli) and PPI (70 dB + 100 dB and 70 dB + 120 dB) in the acoustic startle monitor system. The mice were assessed during the shaker stress on days 2 and 7 and 7, 14, 21 and 28 days after discontinuation of treatment. Separate groups of mice were tested in the open field in 15 min sessions on days 1, 3 and 6 during shaker stress and PB treatment. Exposure of mice to PB resulted in an exaggerated ASR, reduced PPI and non-significant decrease in locomotor activity. These behavioral changes were apparent only during exposure to PB. Repeated shaker stress did not have any effect on sensorimotor functions or open field behavior of mice. There was no prolonged or delayed effect of PB and/or stress on individual behavioral variables. The study found C57BL/6J mice to be behaviorally sensitive to PB treatment. (c) 2007 John Wiley & Sons, Ltd.

  9. Persistent DNA methylation changes associated with prenatal mercury exposure and cognitive performance during childhood.

    PubMed

    Cardenas, Andres; Rifas-Shiman, Sheryl L; Agha, Golareh; Hivert, Marie-France; Litonjua, Augusto A; DeMeo, Dawn L; Lin, Xihong; Amarasiriwardena, Chitra J; Oken, Emily; Gillman, Matthew W; Baccarelli, Andrea A

    2017-03-21

    Prenatal exposure to mercury, a known neurotoxic metal, is associated with lower cognitive performance during childhood. Disruption of fetal epigenetic programming could explain mercury's neurodevelopmental effects. We screened for epigenome-wide methylation differences associated with maternal prenatal blood mercury levels in 321 cord blood DNA samples and examined the persistence of these alterations during early (n = 75; 2.9-4.9 years) and mid-childhood (n = 291; 6.7-10.5 years). Among males, prenatal mercury levels were associated with lower regional cord blood DNA methylation at the Paraoxonase 1 gene (PON1) that persisted in early childhood and was attenuated in mid-childhood blood. Cord blood methylation at the PON1 locus predicted lower cognitive test scores measured during early childhood. Methylation at the PON1 locus was associated with PON1 expression in an independent set of cord blood samples. The observed persistent epigenetic disruption of the PON1 gene may modulate mercury toxicity in humans and might serve as a biomarker of exposure and disease susceptibility.

  10. Acetylcholinesterase inhibitors as pretreatment before acute exposure to organophosphates: assessment using methyl-paraoxon.

    PubMed

    Lorke, Dietrich E; Hasan, Mohamed Y; Nurulain, Syed M; Shafiullah, Mohamed; Kuča, Kamil; Petroianu, Georg A

    2012-12-01

    Prophylactic administration of reversible acetylcholinesterase (AChE) inhibitors can protect against the lethal effects of organophosphorus compounds (OPCs). The usefulness of pyridostigmine, the only compound approved by the Food and Drug Administration (FDA) for such pretreatment, has been questioned. In search for more efficacious alternatives, we have examined in vivo the efficacy of a group of ten compounds with known anti-AChE activity (pyridostigmine, metoclopramide, tiapride, ranitidine, physostigmine, tacrine, amiloride, methylene blue, 7- methoxytacrine and K-27) to reduce mortality induced by the OPC methyl-paraoxon. AChE inhibitors were given intraperitoneally in equitoxic dosage (25% of LD₀₁) 30 min before OPC exposure. Protection was quantified in rats by determining the relative risk of death (RR) by Cox analysis, with RR=1 for animals given only methyl-paraoxon, but no pretreatment. Only physostigmine (RR=0.39), K-27 (RR=0.40) and tacrine (RR=0.48) significantly (p≤ 0.05) reduced methylparaoxon- induced mortality, when given prophylactically. Pretreatment with pyridostigmine, ranitidine, tiapride, amiloride, metoclopramide and methylene blue did not significantly protect against the lethal effects of methyl-paraoxon. 7-methoxytacrine (7-MEOTA) significantly (p≤ 0.05) increased the relative risk of methyl-paraoxon-induced death (RR=1.31). These results indicate that pretreatment with pyridostigmine cannot be considered a broad-spectrum approach against OPC exposure. K-27 may be a suitable alternative if passage into the brain is contraindicated.

  11. Alterations in DNA methylation and airway hyperreactivity in response to in utero exposure to environmental tobacco smoke

    PubMed Central

    Lee, Joong Won; Jaffar, Zeina; Pinkerton, Kent E.; Porter, Virginia; Postma, Britten; Ferrini, Maria; Holian, Andrij; Roberts, Kevan; Cho, Yoon Hee

    2016-01-01

    Growing evidence indicates that prenatal exposure to maternal smoking is a risk factor for the development of asthma in children. However, the effects of prenatal environmental tobacco smoke (ETS) exposure on the genome and lung immune cells are unclear. This study aims to determine whether in utero ETS exposure alters DNA methylation patterns and increases airway hyperreactivity (AHR) and inflammation. Pregnant C57BL/6 mice were exposed daily to a concentration of 1.0 mg/m3 ETS. AHR was determined in the 6-week-old offspring by measurement of airway resistance. Global and gene promoter methylation levels in lung DNA from offspring were analyzed by luminometric methylation and pyrosequencing assays, respectively. Offspring exposed to ETS showed a marked increase in the number of alveolar macrophages in the bronchoalveolar lavage fluid and level of IL-13 in the airways compared with offspring of filtered-air exposed dams (controls). ETS exposure significantly augmented AHR compared with controls. In the methylation analysis, ETS-exposed offspring had a significantly lower level of global DNA methylation than the controls. We observed a significant increase in IFN-γ, and significant decrease in IL-13 methylation levels in the ETS group compared with controls. Collectively, these data suggest that in utero ETS exposure increases the risk of pulmonary inflammation and AHR through altered DNA methylation, but additional studies are needed to fully determine the causal link between changes in methylation and cytokines levels, as well as AHR. PMID:26525176

  12. Alterations in DNA methylation and airway hyperreactivity in response to in utero exposure to environmental tobacco smoke.

    PubMed

    Lee, Joong Won; Jaffar, Zeina; Pinkerton, Kent E; Porter, Virginia; Postma, Britten; Ferrini, Maria; Holian, Andrij; Roberts, Kevan; Cho, Yoon Hee

    2015-01-01

    Growing evidence indicates that prenatal exposure to maternal smoking is a risk factor for the development of asthma in children. However, the effects of prenatal environmental tobacco smoke (ETS) exposure on the genome and lung immune cells are unclear. This study aims to determine whether in utero ETS exposure alters DNA methylation patterns and increases airway hyperreactivity (AHR) and inflammation. Pregnant C57BL/6 mice were exposed daily to a concentration of 1.0 mg/m(3) ETS. AHR was determined in the 6-week-old offspring by measurement of airway resistance. Global and gene promoter methylation levels in lung DNA from offspring were analyzed by luminometric methylation and pyrosequencing assays, respectively. Offspring exposed to ETS showed a marked increase in the number of alveolar macrophages in the bronchoalveolar lavage fluid and level of IL-13 in the airways compared with offspring of filtered-air exposed dams (controls). ETS exposure significantly augmented AHR compared with controls. In the methylation analysis, ETS-exposed offspring had a significantly lower level of global DNA methylation than the controls. We observed a significant increase in IFN-γ, and significant decrease in IL-13 methylation levels in the ETS group compared with controls. Collectively, these data suggest that in utero ETS exposure increases the risk of pulmonary inflammation and AHR through altered DNA methylation, but additional studies are needed to fully determine the causal link between changes in methylation and cytokines levels, as well as AHR.

  13. Systemic Steroid Exposure Is Associated with Differential Methylation in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Qiu, Weiliang; Baccarelli, Andrea; Carey, Vincent J.; Bacherman, Helene; Rennard, Stephen I.; Agustí, Alvar; Anderson, Wayne H.; Lomas, David A.; DeMeo, Dawn L.

    2012-01-01

    Rationale: Systemic glucocorticoids are used therapeutically to treat a variety of medical conditions. Epigenetic processes such as DNA methylation may reflect exposure to glucocorticoids and may be involved in mediating the responses and side effects associated with these medications. Objectives: To test the hypothesis that differences in DNA methylation are associated with current systemic steroid use. Methods: We obtained DNA methylation data at 27,578 CpG sites in 14,475 genes throughout the genome in two large, independent cohorts: the International COPD Genetics Network (ndiscovery = 1,085) and the Boston Early Onset COPD study (nreplication = 369). Sites were tested for association with current systemic steroid use using generalized linear mixed models. Measurements and Main Results: A total of 511 sites demonstrated significant differential methylation by systemic corticosteroid use in all three of our primary models. Pyrosequencing validation confirmed robust differential methylation at CpG sites annotated to genes such as SLC22A18, LRP3, HIPK3, SCNN1A, FXYD1, IRF7, AZU1, SIT1, GPR97, ABHD16B, and RABGEF1. Functional annotation clustering demonstrated significant enrichment in intrinsic membrane components, hemostasis and coagulation, cellular ion homeostasis, leukocyte and lymphocyte activation and chemotaxis, protein transport, and responses to nutrients. Conclusions: Our analyses suggest that systemic steroid use is associated with site-specific differential methylation throughout the genome. Differentially methylated CpG sites were found in biologically plausible and previously unsuspected pathways; these genes and pathways may be relevant in the development of novel targeted therapies. PMID:23065012

  14. Occupational exposure to methyl methacrylate monomer induces generalised neuropathy in a dental technician.

    PubMed

    Sadoh, D R; Sharief, M K; Howard, R S

    1999-04-24

    A 36-year-old dental technician for 14 years developed paraesthesia and numbness in her legs. Neurophysiological studies revealed absent sensory nerve action potentials (SNAPs) from her lower limbs and normal upper limb SNAPs on presentation. Motor nerve studies were normal. Repeat studies 2 months after leaving her job showed some improvement in the lower limb SNAPs. It is suggested that her symptoms were caused by occupational exposure to methyl methacrylate monomer.

  15. Multigenerational epigenetic inheritance in humans: DNA methylation changes associated with maternal exposure to lead can be transmitted to the grandchildren

    PubMed Central

    Sen, Arko; Heredia, Nicole; Senut, Marie-Claude; Land, Susan; Hollocher, Kurt; Lu, Xiangyi; Dereski, Mary O.; Ruden, Douglas M.

    2015-01-01

    We report that the DNA methylation profile of a child’s neonatal whole blood can be significantly influenced by his or her mother’s neonatal blood lead levels (BLL). We recruited 35 mother-infant pairs in Detroit and measured the whole blood lead (Pb) levels and DNA methylation levels at over 450,000 loci from current blood and neonatal blood from both the mother and the child. We found that mothers with high neonatal BLL correlate with altered DNA methylation at 564 loci in their children’s neonatal blood. Our results suggest that Pb exposure during pregnancy affects the DNA methylation status of the fetal germ cells, which leads to altered DNA methylation in grandchildren’s neonatal dried blood spots. This is the first demonstration that an environmental exposure in pregnant mothers can have an epigenetic effect on the DNA methylation pattern in the grandchildren. PMID:26417717

  16. Bromidotetra­kis­(1H-2-ethyl-5-methyl­imidazole-κN 3)copper(II) bromide

    PubMed Central

    Godlewska, Sylwia; Baranowska, Katarzyna; Socha, Joanna; Dołęga, Anna

    2011-01-01

    The CuII ion in the title compound, [CuBr(C6H10N2)4]Br, is coordinated in a square-based-pyramidal geometry by the N atoms of four imidazole ligands and a bromide anion in the apical site. Both the CuII and Br− atoms lie on a crystallographic fourfold axis. In the crystal, the [CuBr(C6H10N2)4]+ complex cations are linked to the uncoordinated Br− anions (site symmetry ) by N—H⋯Br hydrogen bonds, generating a three-dimensional network. The ethyl group of the imidazole ligand was modelled as disordered over two orientations with occupancies of 0.620 (8) and 0.380 (8). PMID:22199662

  17. Chronic exposure to trichloroethylene increases DNA methylation of the Ifng promoter in CD4(+) T cells.

    PubMed

    Gilbert, Kathleen M; Blossom, Sarah J; Erickson, Stephen W; Broadfoot, Brannon; West, Kirk; Bai, Shasha; Li, Jingyun; Cooney, Craig A

    2016-10-17

    CD4(+) T cells in female MRL+/+ mice exposed to solvent and water pollutant trichloroethylene (TCE) skew toward effector/memory CD4(+) T cells, and demonstrate seemingly non-monotonic alterations in IFN-γ production. In the current study we examined the mechanism for this immunotoxicity using effector/memory and naïve CD4(+) T cells isolated every 6 weeks during a 40 week exposure to TCE (0.5mg/ml in drinking water). A time-dependent effect of TCE exposure on both Ifng gene expression and IFN-γ protein production was observed in effector/memory CD4(+) T cells, with an increase after 22 weeks of exposure and a decrease after 40 weeks of exposure. No such effect of TCE was observed in naïve CD4(+) T cells. A cumulative increase in DNA methylation in the CpG sites of the promoter of the Ifng gene was observed in effector/memory, but not naïve, CD4(+) T cells over time. Also unique to the Ifng promoter was an increase in methylation variance in effector/memory compared to naïve CD4(+) T cells. Taken together, the CpG sites of the Ifng promoter in effector/memory CD4(+) T cells were especially sensitive to the effects of TCE exposure, which may help explain the regulatory effect of the chemical on this gene.

  18. Third trimester phthalate exposure is associated with DNA methylation of growth-related genes in human placenta

    PubMed Central

    Zhao, Yan; Chen, Jiao; Wang, Xiu; Song, Qi; Xu, Hui-Hui; Zhang, Yun-Hui

    2016-01-01

    Strong evidence implicates maternal phthalate exposure during pregnancy in contributing to adverse birth outcomes. Recent research suggests these effects might be mediated through the improper regulation of DNA methylation in offspring tissue. In this study, we examined associations between prenatal phthalate exposure and DNA methylation in human placenta. We recruited 181 mother-newborn pairs (80 fetal growth restriction newborns, 101 normal newborns) in Wenzhou, China and measured third trimester urinary phthalate metabolite concentrations and placental DNA methylation levels of IGF2 and AHRR. We found urinary concentrations of mono (2-ethyl-5- hydroxyhexyl) phthalate (MEHHP), and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) were significantly inversely associated with placental IGF2 DNA methylation. The associations were much more evident in fetal growth restriction (FGR) newborns than those in normal newborns. These findings suggest that changes in placental DNA methylation might be part of the underlying biological pathway between prenatal phthalate exposure and adverse fetal growth. PMID:27653773

  19. Third trimester phthalate exposure is associated with DNA methylation of growth-related genes in human placenta

    NASA Astrophysics Data System (ADS)

    Zhao, Yan; Chen, Jiao; Wang, Xiu; Song, Qi; Xu, Hui-Hui; Zhang, Yun-Hui

    2016-09-01

    Strong evidence implicates maternal phthalate exposure during pregnancy in contributing to adverse birth outcomes. Recent research suggests these effects might be mediated through the improper regulation of DNA methylation in offspring tissue. In this study, we examined associations between prenatal phthalate exposure and DNA methylation in human placenta. We recruited 181 mother-newborn pairs (80 fetal growth restriction newborns, 101 normal newborns) in Wenzhou, China and measured third trimester urinary phthalate metabolite concentrations and placental DNA methylation levels of IGF2 and AHRR. We found urinary concentrations of mono (2-ethyl-5- hydroxyhexyl) phthalate (MEHHP), and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) were significantly inversely associated with placental IGF2 DNA methylation. The associations were much more evident in fetal growth restriction (FGR) newborns than those in normal newborns. These findings suggest that changes in placental DNA methylation might be part of the underlying biological pathway between prenatal phthalate exposure and adverse fetal growth.

  20. Oral administration of pyridostigmine bromide and huperzine A protects human whole blood cholinesterases from ex vivo exposure to soman.

    PubMed

    Gordon, Richard K; Haigh, Julian R; Garcia, Gregory E; Feaster, Shawn R; Riel, Michael A; Lenz, David E; Aisen, Paul S; Doctor, Bhupendra P

    2005-12-15

    Cholinesterases (ChEs) are classified as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) according to their substrate specificity and sensitivity to selected inhibitors. The activities of AChE in red blood cells (RBC-AChE) and BChE in serum can be used as potential biomarkers of suppressed and/or heightened activity in the central and peripheral nervous systems. Exposure to organophosphate (OP) chemical warfare agents (CWAs), pesticides, anesthetics, and a variety of drugs such as cocaine, as well as some neurodegenerative and liver disease states, selectively reduces AChE or BChE activity. In humans, the toxicity of pesticides is well documented. Therefore, blood cholinesterase activity can be exploited as a tool for confirming exposure to these agents and possible treatments. Current assays for measurement of RBC-AChE and serum BChE require several labor-intensive processing steps, suffer from wide statistical variation, and there is no inter-laboratory conversion between methods. These methods, which determine only the serum BChE or RBC-AChE but not both, include the Ellman, radiometric, and deltapH (modified Michel) methods. In contrast, the Walter Reed Army Institute of Research Whole Blood (WRAIR WB, US Patent #6,746,850) cholinesterase assay rapidly determines the activity of both AChE and BChE in unprocessed (uncentrifuged) whole blood, uses a minimally invasive blood sampling technique (e.g., blood from a finger prick), and is semi-automated for high-throughput using the Biomek 2000 robotic system. To date, the WRAIR whole blood assay was used to measure AChE and BChE activities in human blood from volunteers in FDA clinical trials. In the first FDA study, 24 human subjects were given either 30 mg PB orally (n = 19) or placebo (n = 5). Blood samples were obtained pre-dosing and 2.5, 5, 8, and 24 h post-dosing. The samples were analyzed for AChE and BChE activity using the WRAIR WB robotic system, and for PB concentration by HPLC. We found that

  1. A cross-industry assessment of personal exposures to methyl methacrylate.

    PubMed

    Vos, Gordon A; Stephens, John Paul

    2008-01-01

    This study investigated personal exposures to methyl methacrylate (MMA) monomer during monomer production and use within the chemical manufacturing industry. The aim was to include multiple companies and sites to provide information regarding differences and similarities among exposure subgroups within the industry during the time period of 1998-2000. To this end, personal exposure data for MMA monomer from three chemical corporations was combined into a single data set. The data was stratified by sample type (full shift or short term), job classification (monomer production, monomer use, maintenance, distribution, and laboratory operations), company, and facility. Only classifications with three samples or more were included in the final data set, yielding 376 samples for analysis (334 full-shift and 42 short-term samples). Results compare well with previously published data on MMA monomer exposures. Although there was significant variability in several exposure subgroups (particularly among companies and facilities), MMA monomer use in the manufacture of other products resulted in the highest exposure distributions, with lower exposures associated with monomer production, maintenance, and distribution operations. The usefulness of these findings is related to the provision of information for discussion of current needs in the industry regarding data sampling, exposure assessment, and standards development.

  2. Biomonitoring of exposure to N-methyl-2-pyrrolidone in workers of the automobile industry.

    PubMed

    Meier, Swetlana; Schindler, Birgit K; Koslitz, Stephan; Koch, Holger M; Weiss, Tobias; Käfferlein, Heiko U; Brüning, Thomas

    2013-07-01

    N-methyl-2-pyrrolidone (NMP) is an important organic solvent for varnishes in industry. NMP has been previously shown to be a developmental toxicant in rodents. This study reports current exposures to NMP in the spraying department of an automobile plant using biological monitoring. Two specific metabolites, 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methyl-succinimide (2-HMSI), were analyzed in 69 urine samples of 14 workers exposed to NMP and 9 nonexposed controls. Three different working tasks ('loading' and 'cleaning' of the sprayer system and 'wiping/packing' of the sprayed materials) and three sampling times (preshift, postshift, and preshift of the following day) were studied in exposed workers. Median exposures of 5-HNMP and 2-HMSI in postshift urine of exposed workers were 0.91 and 0.52mg g(-1) creatinine, respectively, whereas median levels in controls were below the limit of detection. Decreased levels of 5-HNMP were observed in preshift urine samples on the following day (0.39mg g(-1) creatinine) in exposed workers, while the concentration of 2-HMSI did not change (0.49mg g(-1) creatinine). Highest exposures occurred during sprayer cleaning with a maximum level of 8.31mg g(-1) creatinine of 5-HNMP in postshift urine. In contrast to 'wipers/packers', no decrease in 5-HNMP could be observed in preshift urine samples on day 2 of the 'loaders' and 'cleaners'. Overall, exposure in terms of 5-HNMP postshift and 2-HMSI preshift of the following day were well below the current biological limit values of the European Union (70 and 20mg g(-1) creatinine). Our results provide initial data on NMP exposure in the automobile industry and suggest that the analysis of 5-HNMP in preshift samples also provides essential information, particularly in situations involving direct handling of liquid NMP-containing formulations.

  3. Prenatal exposures and DNA methylation in newborns: a pilot study in Durban, South Africa.

    PubMed

    Goodrich, Jaclyn M; Reddy, Poovendhree; Naidoo, Rajen N; Asharam, Kareshma; Batterman, Stuart; Dolinoy, Dana C

    2016-07-13

    The in utero environment has the potential to influence epigenetic programming and subsequently the health of offspring. Even though pregnant women living in urban Africa are exposed to multiple chemicals and infectious agents that may impact their developing children, the neonatal epigenome has not been studied in these regions. We assessed whether prenatal exposures to air pollution and maternal human immunodeficiency virus (HIV) are associated with changes to DNA methylation throughout the epigenome using a pilot sample from the Mother and Child Environmental (MACE) birth cohort, of which 36% of the mothers are HIV positive. Families living in a high air pollution region (south Durban, n = 11) and a low air pollution region (north Durban, n = 11) with comparable socioeconomic characteristics were selected for analysis. DNA methylation was quantified in cord blood plasma DNA at >430 000 CpG sites using the Infinium HumanMethylation450 BeadChip. Sites associated with living in south Durban or maternal HIV infection (p < 0.001) were more likely to be hypomethylated and located in CpG islands. Top differentially methylated sites by region of Durban were enriched in pathways related to xenobiotic metabolism, oxygen and gas transport, and sensory perception of chemical stimuli when performing gene set enrichment testing with LRpath. Differentially methylated sites by maternal HIV status were enriched in cytochrome P450s, pathways involved in detection of chemical stimuli, metabolic processes, and viral regulation and processing. Given the small sample size of the study, future work examining the impact of prenatal exposures to air pollution, maternal infection, and antiviral treatment on the epigenome and downstream health implications is merited in Sub-Saharan African populations.

  4. Zebrafish embryos as a screen for DNA methylation modifications after compound exposure.

    PubMed

    Bouwmeester, Manon C; Ruiter, Sander; Lommelaars, Tobias; Sippel, Josefine; Hodemaekers, Hennie M; van den Brandhof, Evert-Jan; Pennings, Jeroen L A; Kamstra, Jorke H; Jelinek, Jaroslav; Issa, Jean-Pierre J; Legler, Juliette; van der Ven, Leo T M

    2016-01-15

    Modified epigenetic programming early in life is proposed to underlie the development of an adverse adult phenotype, known as the Developmental Origins of Health and Disease (DOHaD) concept. Several environmental contaminants have been implicated as modifying factors of the developing epigenome. This underlines the need to investigate this newly recognized toxicological risk and systematically screen for the epigenome modifying potential of compounds. In this study, we examined the applicability of the zebrafish embryo as a screening model for DNA methylation modifications. Embryos were exposed from 0 to 72 h post fertilization (hpf) to bisphenol-A (BPA), diethylstilbestrol, 17α-ethynylestradiol, nickel, cadmium, tributyltin, arsenite, perfluoroctanoic acid, valproic acid, flusilazole, 5-azacytidine (5AC) in subtoxic concentrations. Both global and site-specific methylation was examined. Global methylation was only affected by 5AC. Genome wide locus-specific analysis was performed for BPA exposed embryos using Digital Restriction Enzyme Analysis of Methylation (DREAM), which showed minimal wide scale effects on the genome, whereas potential informative markers were not confirmed by pyrosequencing. Site-specific methylation was examined in the promoter regions of three selected genes vasa, vtg1 and cyp19a2, of which vasa (ddx4) was the most responsive. This analysis distinguished estrogenic compounds from metals by direction and sensitivity of the effect compared to embryotoxicity. In conclusion, the zebrafish embryo is a potential screening tool to examine DNA methylation modifications after xenobiotic exposure. The next step is to examine the adult phenotype of exposed embryos and to analyze molecular mechanisms that potentially link epigenetic effects and altered phenotypes, to support the DOHaD hypothesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Ipratropium bromide HFA.

    PubMed

    Wellington, Keri

    2005-01-01

    Ipratropium bromide is a nonselective antagonist of the muscarinic receptors located on airway smooth muscle, and is delivered via a metered-dose inhaler (MDI). Because of the requirement to phase out chlorofluorocarbon (CFC)-propelled MDIs, the ipratropium bromide inhalation aerosol MDI has been redesigned with a hydrofluoroalkane as the propellant (ipratropium bromide HFA). Ipratropium bromide HFA has recently been approved in the US for the maintenance treatment of bronchospasm associated with COPD. Ipratropium bromide HFA 42 microg four times daily (one dose [42 microg] is delivered via two puffs of the inhaler) demonstrated comparable efficacy to that of ipratropium bromide CFC 42 microg four times daily, as measured by spirometric testing, in a large, randomized, double-blind, placebo-controlled, 12-week trial in patients with stable COPD. Similarly, four-times-daily ipratropium bromide HFA 42 microg and ipratropium bromide CFC 42 microg provided a comparable degree of bronchodilation in patients with stable COPD during a 1-year, open-label study primarily designed to assess safety. In both studies, the tolerability profiles of ipratropium bromide HFA and ipratropium bromide CFC were comparable. The most common adverse events were related to respiratory system disorders. During the 1-year study, dry mouth was reported by 1.3% and 0.7% of patients in the ipratropium bromide HFA or ipratropium bromide CFC groups.

  6. Ancestral TCDD exposure promotes epigenetic transgenerational inheritance of imprinted gene Igf2: Methylation status and DNMTs.

    PubMed

    Ma, Jing; Chen, Xi; Liu, Yanan; Xie, Qunhui; Sun, Yawen; Chen, Jingshan; Leng, Ling; Yan, Huan; Zhao, Bin; Tang, Naijun

    2015-12-01

    Ancestral TCDD exposure could induce epigenetic transgenerational phenotypes, which may be mediated in part by imprinted gene inheritance. The aim of our study was to evaluate the transgenerational effects of ancestral TCDD exposure on the imprinted gene insulin-like growth factor-2 (Igf2) in rat somatic tissue. TCDD was administered daily by oral gavage to groups of F0 pregnant SD rats at dose levels of 0 (control), 200 or 800 ng/kg bw during gestation day 8-14. Animal transgenerational model of ancestral exposure to TCDD was carefully built, avoiding sibling inbreeding. Hepatic Igf2 expression of the TCDD male progeny was decreased concomitantly with hepatic damage and increased activities of serum hepatic enzymes both in the F1 and F3 generation. Imprinted Control Region (ICR) of Igf2 manifested a hypermethylated pattern, whereas methylation status in the Differentially Methylated Region 2 (DMR2) showed a hypomethylated manner in the F1 generation. These epigenetic alterations in these two regions maintained similar trends in the F3 generation. Meanwhile, the expressions of DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) changed in a non-monotonic manner both in the F1 and F3 generation. This study provides evidence that ancestral TCDD exposure may promote epigenetic transgenerational alterations of imprinted gene Igf2 in adult somatic tissue.

  7. Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures

    PubMed Central

    Galanter, Joshua M; Gignoux, Christopher R; Oh, Sam S; Torgerson, Dara; Pino-Yanes, Maria; Thakur, Neeta; Eng, Celeste; Hu, Donglei; Huntsman, Scott; Farber, Harold J; Avila, Pedro C; Brigino-Buenaventura, Emerita; LeNoir, Michael A; Meade, Kelly; Serebrisky, Denise; Rodríguez-Cintrón, William; Kumar, Rajesh; Rodríguez-Santana, Jose R; Seibold, Max A; Borrell, Luisa N; Burchard, Esteban G; Zaitlen, Noah

    2017-01-01

    Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs. Genetic ancestry has been suggested as an alternative to this categorization. Herein, we typed over 450,000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who also had high-density genotype data. We found that both self-identified ethnicity and genetically determined ancestry were each significantly associated with methylation levels at 916 and 194 CpGs, respectively, and that shared genomic ancestry accounted for a median of 75.7% (IQR 45.8% to 92%) of the variance in methylation associated with ethnicity. There was a significant enrichment (p=4.2×10-64) of ethnicity-associated sites amongst loci previously associated environmental exposures, particularly maternal smoking during pregnancy. We conclude that differential methylation between ethnic groups is partially explained by the shared genetic ancestry but that environmental factors not captured by ancestry significantly contribute to variation in methylation. DOI: http://dx.doi.org/10.7554/eLife.20532.001 PMID:28044981

  8. Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures.

    PubMed

    Galanter, Joshua M; Gignoux, Christopher R; Oh, Sam S; Torgerson, Dara; Pino-Yanes, Maria; Thakur, Neeta; Eng, Celeste; Hu, Donglei; Huntsman, Scott; Farber, Harold J; Avila, Pedro C; Brigino-Buenaventura, Emerita; LeNoir, Michael A; Meade, Kelly; Serebrisky, Denise; Rodríguez-Cintrón, William; Kumar, Rajesh; Rodríguez-Santana, Jose R; Seibold, Max A; Borrell, Luisa N; Burchard, Esteban G; Zaitlen, Noah

    2017-01-03

    Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs. Genetic ancestry has been suggested as an alternative to this categorization. Herein, we typed over 450,000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who also had high-density genotype data. We found that both self-identified ethnicity and genetically determined ancestry were each significantly associated with methylation levels at 916 and 194 CpGs, respectively, and that shared genomic ancestry accounted for a median of 75.7% (IQR 45.8% to 92%) of the variance in methylation associated with ethnicity. There was a significant enrichment (p=4.2×10(-64)) of ethnicity-associated sites amongst loci previously associated environmental exposures, particularly maternal smoking during pregnancy. We conclude that differential methylation between ethnic groups is partially explained by the shared genetic ancestry but that environmental factors not captured by ancestry significantly contribute to variation in methylation.

  9. Influence of developmental lead exposure on expression of DNA methyltransferases and methyl cytosine-binding proteins in hippocampus.

    PubMed

    Schneider, J S; Kidd, S K; Anderson, D W

    2013-02-13

    Developmental exposure to lead (Pb) has adverse effects on cognitive functioning and behavior that can persist into adulthood. Exposures that occur during fetal or early life periods may produce changes in brain related to physiological re-programming from an epigenetic influence such as altered DNA methylation status. Since DNA methylation is regulated by DNA methyltransferases and methyl cytosine-binding proteins, this study assessed the extent to which developmental Pb exposure might affect expression of these proteins in the hippocampus. Long Evans dams were fed chow with or without added Pb acetate (0, 150, 375, 750 ppm) prior to breeding and remained on the same diet through weaning (perinatal exposure group). Other animals were exposed to the same doses of Pb but exposure started on postnatal day 1 and continued through weaning (early postnatal exposure group). All animals were euthanized on day 55 and hippocampi were removed. Western blot analyses showed significant effects of Pb exposure on DNMT1, DNMT3a, and MeCP2 expression, with effects often seen at the lowest level of exposure and modified by sex and developmental window of Pb exposure. These data suggest potential epigenetic effects of developmental Pb exposure on DNA methylation mediated at least in part through dysregulation of methyltransferases. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  10. DNA methylation is differentially associated with environmental cadmium exposure based on sex and smoking status

    PubMed Central

    Virani, Shama; Rentschler, Katie M.; Nishijo, Muneko; Ruangyuttikarn, Werawan; Swaddiwudhipong, Witaya; Basu, Niladri; Rozek, Laura S.

    2016-01-01

    The adverse health effects of cadmium (Cd) are well known in human populations; however, much of what is known about biological mechanisms of Cd comes from in vitro and animal studies. The adverse health outcomes due to high levels of Cd exposure in the population of Mae Sot, Thailand have been extensively characterized. Here, for the first time, this population is being studied in an epigenetic context. The objective of this study was to characterize the association between DNA methylation markers and Cd exposure, taking into account sex and smoking differences, in an adult population at an increased risk of experiencing adverse health outcomes from high body burden of Cd. One hundred and sixty-nine residents from known exposure areas of Mae Sot, Thailand and one hundred residents from non-exposed areas nearby were surveyed in 2012. Urine and blood samples were collected for measurement of urinary Cd (UCd) and DNA methylation of Cd-related markers (DNMT3B, MGMT, LINE-1, MT2A). UCd levels were 7 times higher in the exposed compared to the unexposed populations (exposed median: 7.4 μg/L, unexposed median: 1.0 μg/L, p <0.001). MGMT hypomethylation was associated with increasing levels of UCd in the total population. Sex-specific associations included MT2A and DNMT3B hypomethylation in women and LINE-1 hypermethylation in men with increasing UCd. Upon subanalysis, these associations separated by smoking status. In summary, environmental Cd exposure is associated with gene-specific DNA methylation in a sex and smoking dependent manner. PMID:26688266

  11. Modulation of microsomal membrane associated detoxication enzymes activity by methyl isocyanate (MIC) exposure

    SciTech Connect

    Mishra, A.; Dwivedi, P.D.; Verma, A.S.; Mishra, J.; Sinha, M.; Dutta, K.K.; Ray, P.K. )

    1991-11-01

    In the industrial disaster at Bhopal, India in 1984 the leakage of 40 tons of methyl isocyanate (MIC) gas from a pesticide plant claimed over 2,500 lives and left an estimated population of 15,000 people suffering from a variety of ailments. MIC induced changes in respiratory functions including bronchial asthma, pulmonary oedema, necrosis of alveoli, hypersensitivity, pneumonities and incapacitated pulmonary functions. Reports have also indicated changes in the respiratory tract of animals as a result of exposure to MIC, the lung being the main target organ attacked by MIC. The authors earlier report of the high dose single exposure toxicity to methyl isocyanate leads to alterations in biotransformation enzymes and their isoenzymic pattern. Recently, a drastic decrease in Na{sup +}, K{sup +}, and Mg{sup ++} ATPase enzyme levels by repeated MIC exposure has been shown. The present study further explores the biochemical basis of MIC intoxication with reference to consecutive dose dependent toxicity in terms of alteration in phase 1 and phase 2 membrane bound detoxication enzymes.

  12. Human Oral Buccal Microbiomes Are Associated with Farmworker Status and Azinphos-Methyl Agricultural Pesticide Exposure

    PubMed Central

    Stanaway, Ian B.; Wallace, James C.; Shojaie, Ali; Griffith, William C.; Hong, Sungwoo; Wilder, Carly S.; Green, Foad H.; Tsai, Jesse; Knight, Misty; Workman, Tomomi; Vigoren, Eric M.; McLean, Jeffrey S.; Thompson, Beti

    2016-01-01

    ABSTRACT In a longitudinal agricultural community cohort sampling of 65 adult farmworkers and 52 adult nonfarmworkers, we investigated agricultural pesticide exposure-associated changes in the oral buccal microbiota. We found a seasonally persistent association between the detected blood concentration of the insecticide azinphos-methyl and the taxonomic composition of the buccal swab oral microbiome. Blood and buccal samples were collected concurrently from individual subjects in two seasons, spring/summer 2005 and winter 2006. Mass spectrometry quantified blood concentrations of the organophosphate insecticide azinphos-methyl. Buccal oral microbiome samples were 16S rRNA gene DNA sequenced, assigned to the bacterial taxonomy, and analyzed after “centered-log-ratio” transformation to handle the compositional nature of the proportional abundances of bacteria per sample. Nonparametric analysis of the transformed microbiome data for individuals with and without azinphos-methyl blood detection showed significant perturbations in seven common bacterial taxa (>0.5% of sample mean read depth), including significant reductions in members of the common oral bacterial genus Streptococcus. Diversity in centered-log-ratio composition between individuals' microbiomes was also investigated using principal-component analysis (PCA) to reveal two primary PCA clusters of microbiome types. The spring/summer “exposed” microbiome cluster with significantly less bacterial diversity was enriched for farmworkers and contained 27 of the 30 individuals who also had azinphos-methyl agricultural pesticide exposure detected in the blood. IMPORTANCE In this study, we show in human subjects that organophosphate pesticide exposure is associated with large-scale significant alterations of the oral buccal microbiota composition, with extinctions of whole taxa suggested in some individuals. The persistence of this association from the spring/summer to the winter also suggests that long

  13. Secondary structural changes in guanidinium hydrochloride denatured mammalian serum albumins and protective effect of small amounts of cationic gemini surfactant pentanediyl-α,ω-bis(cetyldimethylammonium bromide) and methyl-β-cyclodextrin: A spectroscopic study.

    PubMed

    Gull, Nuzhat; Khan, Javed Masood; Ishtikhar, Mohd; Qadeer, Atiyatul; Khan, Rehan Ajmal; Gul, Mudasir; Khan, Rizwan Hasan

    2015-02-01

    In the present study the cationic gemini surfactant assisted refolding of guanidinium hydrochloride (GdCl) denatured mammalian serum albumins viz. sheep serum albumin (SSA), rat serum albumin (RSA) and porcine serum albumin (PSA) using a combination of cationic gemini surfactants, pentanediyl-α,ω-bis(cetyldimethylammonium bromide) (C16H33(CH3)2N(+)-(CH2)5-N(+)(CH3)2C16H33)⋅2Br(-) designated as G5 and methyl-β-cyclodextrin in the artificial chaperone assisted two step method, is attempted. The studies were carried out in an aqueous medium (pH 7.4) using dynamic light scattering (DLS), circular dichroism (CD), and fluorescence spectroscopy. A perusal of DLS data indicates that against the native hydrodynamic radius (Rh) of 4.3nm in SSA, 3.9nm in PSA and 3.5nm in RSA, the Rh of the said proteins, when refolding is attempted by simple dilution, increases to 21.7nm, 36.6nm and 37.2nm, respectively. Hydrodynamic radii very near to the native protein, i.e., 4.0nm, 4.1nm and 4.4nm for RSA, PSA and SSA respectively, is obtained on the sequential addition of G5 and methyl-β-cyclodextrin to the denatured protein. Circular dichroism studies corroborate with the DLS data. The results obtained from the multi-technique approach are ascribed to the presence of two charged head-groups and two hydrocarbon tails in the gemini surfactants resulting in a very strong electrostatic and hydrophobic interactions. Based on the present study it is suggested that the gemini surfactants may be utilized in the protein refolding studies and thus may address one of the most pressing demand of biotechnology industry for the development of efficient and inexpensive folding aides. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure

    PubMed Central

    Gruzieva, Olena; Xu, Cheng-Jian; Breton, Carrie V.; Annesi-Maesano, Isabella; Antó, Josep M.; Auffray, Charles; Ballereau, Stéphane; Bellander, Tom; Bousquet, Jean; Bustamante, Mariona; Charles, Marie-Aline; de Kluizenaar, Yvonne; den Dekker, Herman T.; Duijts, Liesbeth; Felix, Janine F.; Gehring, Ulrike; Guxens, Mònica; Jaddoe, Vincent V.W.; Jankipersadsing, Soesma A.; Merid, Simon Kebede; Kere, Juha; Kumar, Ashish; Lemonnier, Nathanael; Lepeule, Johanna; Nystad, Wenche; Page, Christian Magnus; Panasevich, Sviatlana; Postma, Dirkje; Slama, Rémy; Sunyer, Jordi; Söderhäll, Cilla; Yao, Jin; London, Stephanie J.; Pershagen, Göran; Koppelman, Gerard H.; Melén, Erik

    2016-01-01

    Background: Prenatal exposure to air pollution is considered to be associated with adverse effects on child health. This may partly be mediated by mechanisms related to DNA methylation. Objectives: We investigated associations between exposure to air pollution, using nitrogen dioxide (NO2) as marker, and epigenome-wide cord blood DNA methylation. Methods: We meta-analyzed the associations between NO2 exposure at residential addresses during pregnancy and cord blood DNA methylation (Illumina 450K) in four European and North American studies (n = 1,508) with subsequent look-up analyses in children ages 4 (n = 733) and 8 (n = 786) years. Additionally, we applied a literature-based candidate approach for antioxidant and anti-inflammatory genes. To assess influence of exposure at the transcriptomics level, we related mRNA expression in blood cells to NO2 exposure in 4- (n = 111) and 16-year-olds (n = 239). Results: We found epigenome-wide significant associations [false discovery rate (FDR) p < 0.05] between maternal NO2 exposure during pregnancy and DNA methylation in newborns for 3 CpG sites in mitochondria-related genes: cg12283362 (LONP1), cg24172570 (3.8 kbp upstream of HIBADH), and cg08973675 (SLC25A28). The associations with cg08973675 methylation were also significant in the older children. Further analysis of antioxidant and anti-inflammatory genes revealed differentially methylated CpGs in CAT and TPO in newborns (FDR p < 0.05). NO2 exposure at the time of biosampling in childhood had a significant impact on CAT and TPO expression. Conclusions: NO2 exposure during pregnancy was associated with differential offspring DNA methylation in mitochondria-related genes. Exposure to NO2 was also linked to differential methylation as well as expression of genes involved in antioxidant defense pathways. Citation: Gruzieva O, Xu CJ, Breton CV, Annesi-Maesano I, Antó JM, Auffray C, Ballereau S, Bellander T, Bousquet J, Bustamante M, Charles MA, de Kluizenaar Y, den Dekker

  15. Quality control and statistical modeling for environmental epigenetics: A study on in utero lead exposure and DNA methylation at birth

    PubMed Central

    Goodrich, Jaclyn M; Sánchez, Brisa N; Dolinoy, Dana C; Zhang, Zhenzhen; Hernández-Ávila, Mauricio; Hu, Howard; Peterson, Karen E; Téllez-Rojo, Martha M

    2015-01-01

    DNA methylation data assayed using pyrosequencing techniques are increasingly being used in human cohort studies to investigate associations between epigenetic modifications at candidate genes and exposures to environmental toxicants and to examine environmentally-induced epigenetic alterations as a mechanism underlying observed toxicant-health outcome associations. For instance, in utero lead (Pb) exposure is a neurodevelopmental toxicant of global concern that has also been linked to altered growth in human epidemiological cohorts; a potential mechanism of this association is through alteration of DNA methylation (e.g., at growth-related genes). However, because the associations between toxicants and DNA methylation might be weak, using appropriate quality control and statistical methods is important to increase reliability and power of such studies. Using a simulation study, we compared potential approaches to estimate toxicant-DNA methylation associations that varied by how methylation data were analyzed (repeated measures vs. averaging all CpG sites) and by method to adjust for batch effects (batch controls vs. random effects). We demonstrate that correcting for batch effects using plate controls yields unbiased associations, and that explicitly modeling the CpG site-specific variances and correlations among CpG sites increases statistical power. Using the recommended approaches, we examined the association between DNA methylation (in LINE-1 and growth related genes IGF2, H19 and HSD11B2) and 3 biomarkers of Pb exposure (Pb concentrations in umbilical cord blood, maternal tibia, and maternal patella), among mother-infant pairs of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort (n = 247). Those with 10 μg/g higher patella Pb had, on average, 0.61% higher IGF2 methylation (P = 0.05). Sex-specific trends between Pb and DNA methylation (P < 0.1) were observed among girls including a 0.23% increase in HSD11B2 methylation with 10

  16. Quality control and statistical modeling for environmental epigenetics: a study on in utero lead exposure and DNA methylation at birth.

    PubMed

    Goodrich, Jaclyn M; Sánchez, Brisa N; Dolinoy, Dana C; Zhang, Zhenzhen; Hernández-Ávila, Mauricio; Hu, Howard; Peterson, Karen E; Téllez-Rojo, Martha M

    2015-01-01

    DNA methylation data assayed using pyrosequencing techniques are increasingly being used in human cohort studies to investigate associations between epigenetic modifications at candidate genes and exposures to environmental toxicants and to examine environmentally-induced epigenetic alterations as a mechanism underlying observed toxicant-health outcome associations. For instance, in utero lead (Pb) exposure is a neurodevelopmental toxicant of global concern that has also been linked to altered growth in human epidemiological cohorts; a potential mechanism of this association is through alteration of DNA methylation (e.g., at growth-related genes). However, because the associations between toxicants and DNA methylation might be weak, using appropriate quality control and statistical methods is important to increase reliability and power of such studies. Using a simulation study, we compared potential approaches to estimate toxicant-DNA methylation associations that varied by how methylation data were analyzed (repeated measures vs. averaging all CpG sites) and by method to adjust for batch effects (batch controls vs. random effects). We demonstrate that correcting for batch effects using plate controls yields unbiased associations, and that explicitly modeling the CpG site-specific variances and correlations among CpG sites increases statistical power. Using the recommended approaches, we examined the association between DNA methylation (in LINE-1 and growth related genes IGF2, H19 and HSD11B2) and 3 biomarkers of Pb exposure (Pb concentrations in umbilical cord blood, maternal tibia, and maternal patella), among mother-infant pairs of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort (n = 247). Those with 10 μg/g higher patella Pb had, on average, 0.61% higher IGF2 methylation (P = 0.05). Sex-specific trends between Pb and DNA methylation (P < 0.1) were observed among girls including a 0.23% increase in HSD11B2 methylation with 10

  17. Metabolic programming of MEST DNA methylation by intrauterine exposure to gestational diabetes mellitus.

    PubMed

    El Hajj, Nady; Pliushch, Galyna; Schneider, Eberhard; Dittrich, Marcus; Müller, Tobias; Korenkov, Michael; Aretz, Melanie; Zechner, Ulrich; Lehnen, Harald; Haaf, Thomas

    2013-04-01

    Epigenetic processes are primary candidates when searching for mechanisms that can stably modulate gene expression and metabolic pathways according to early life conditions. To test the effects of gestational diabetes mellitus (GDM) on the epigenome of the next generation, cord blood and placenta tissue were obtained from 88 newborns of mothers with dietetically treated GDM, 98 with insulin-dependent GDM, and 65 without GDM. Bisulfite pyrosequencing was used to compare the methylation levels of seven imprinted genes involved in prenatal and postnatal growth, four genes involved in energy metabolism, one anti-inflammatory gene, one tumor suppressor gene, one pluripotency gene, and two repetitive DNA families. The maternally imprinted MEST gene, the nonimprinted glucocorticoid receptor NR3C1 gene, and interspersed ALU repeats showed significantly decreased methylation levels (4-7 percentage points for MEST, 1-2 for NR3C1, and one for ALUs) in both GDM groups, compared with controls, in both analyzed tissues. Significantly decreased blood MEST methylation (3 percentage points) also was observed in adults with morbid obesity compared with normal-weight controls. Our results support the idea that intrauterine exposure to GDM has long-lasting effects on the epigenome of the offspring. Specifically, epigenetic malprogramming of MEST may contribute to obesity predisposition throughout life.

  18. Impact of early developmental arsenic exposure on promotor CpG-island methylation of genes involved in neuronal plasticity.

    PubMed

    Martínez, Liborio; Jiménez, Verónica; García-Sepúlveda, Christian; Ceballos, Fátima; Delgado, Juan Manuel; Niño-Moreno, Perla; Doniz, Lesly; Saavedra-Alanís, Víctor; Castillo, Claudia G; Santoyo, Martha E; González-Amaro, Roberto; Jiménez-Capdeville, María E

    2011-04-01

    Epigenetic mechanisms are crucial to regulate the expression of different genes required for neuronal plasticity. Neurotoxic substances such as arsenic, which induces cognitive deficits in exposed children before any other manifestation of toxicity, could interfere with the epigenetic modulation of neuronal gene expression required for learning and memory. This study assessed in Wistar rats the effects that developmental arsenic exposure had on DNA methylation patterns in hippocampus and frontal cortex. Animals were exposed to arsenic in drinking water (3 and 36ppm) from gestation until 4 months of age, and DNA methylation in brain cells was determined by flow cytometry, immunohistochemistry and methylation-specific polymerase chain reaction (PCR) of the promoter regions of reelin (RELN) and protein phosphatase 1 (PP1) at 1, 2, 3 and 4 months of age. Immunoreactivity to 5 methyl-cytosine was significantly higher in the cortex and hippocampus of exposed animals compared to controls at 1 month, and DNA hypomethylation was observed the following months in the cortex at high arsenic exposure. Furthermore, we observed a significant increase in the non-methylated form of PP1 gene promoter at 2 and 3 months of age, either in cortex or hippocampus. In order to determine whether this exposure level is associated with memory deficits, a behavioral test was performed at the same age points, revealing progressive and dose-dependent deficits of fear memory. Our results demonstrate alterations of the methylation pattern of genes involved in neuronal plasticity in an animal model of memory deficit associated with arsenic exposure.

  19. DNA methylation levels and long-term trihalomethane exposure in drinking water: an epigenome-wide association study

    PubMed Central

    Salas, Lucas A; Bustamante, Mariona; Gonzalez, Juan R; Gracia-Lavedan, Esther; Moreno, Victor; Kogevinas, Manolis; Villanueva, Cristina M

    2015-01-01

    Trihalomethanes (THM) are undesired disinfection byproducts (DBPs) formed during water treatment. Mice exposed to DBPs showed global DNA hypomethylation and c-myc and c-jun gene-specific hypomethylation, while evidence of epigenetic effects in humans is scarce. We explored the association between lifetime THM exposure and DNA methylation through an epigenome-wide association study. We selected 138 population-based controls from a case-control study of colorectal cancer conducted in Barcelona, Spain, exposed to average lifetime THM levels ≤85 μg/L vs. >85 μg/L (N = 68 and N = 70, respectively). Mean age of participants was 70 years, and 54% were male. Average lifetime THM level in the exposure groups was 64 and 130 µg/L, respectively. DNA was extracted from whole blood and was bisulphite converted to measure DNA methylation levels using the Illumina HumanMethylation450 BeadChip. Data preprocessing was performed using RnBeads. Methylation was compared between exposure groups using empirical Bayes moderated linear regression for CpG sites and Gaussian kernel for CpG regions. ConsensusPathDB was used for gene set enrichment. Statistically significant differences in methylation between exposure groups was found in 140 CpG sites and 30 gene-related regions, after false discovery rate <0.05 and adjustment for age, sex, methylation first principal component, and blood cell proportion. The annotated genes were localized to several cancer pathways. Among them, 29 CpGs had methylation levels associated with THM levels (|Δβ|≥0.05) located in 11 genes associated with cancer in other studies. Our results suggest that THM exposure may affect DNA methylation in genes related to tumors, including colorectal and bladder cancers. Future confirmation studies are required. PMID:26039576

  20. Sex-specific effects of early life cadmium exposure on DNA methylation and implications for birth weight

    PubMed Central

    Kippler, Maria; Engström, Karin; Mlakar, Simona Jurkovic; Bottai, Matteo; Ahmed, Sultan; Hossain, Mohammad Bakhtiar; Raqib, Rubhana; Vahter, Marie; Broberg, Karin

    2013-01-01

    Dietary cadmium exposure was recently found to alter DNA methylation in adults, but data on effects early in life are lacking. Our objective was to evaluate associations between prenatal cadmium exposure, DNA methylation and birth weight. In total 127 mother-child pairs from rural Bangladesh were studied. For comparison, we included 56 children at 4.5 y. Cadmium concentrations in mothers’ blood (gestational week 14) and children’s urine were measured by ICPMS. Global DNA methylation was analyzed by Infinium HumanMethylation450K BeadChip in cord blood and children’s blood. Maternal cadmium exposure was associated with cord blood DNA methylation (p-value < 10–16). The association was markedly sex-specific. In boys, 96% of the top 500 CpG sites showed positive correlations (rS-values > 0.50), whereas most associations in girls were inverse; only 29% were positive (rS > 0.45). In girls we found overrepresentation of methylation changes in genes associated with organ development, morphology and mineralization of bone, whereas changes in boys were found in cell death-related genes. Several individual CpG sites that were positively associated with cadmium were inversely correlated with birth weight, although none statistically significant after correction for multiple comparisons. The associations were, however, fairly robust in multivariable-adjusted linear regression models. We identified CpG sites that were significantly associated with cadmium exposure in both newborns and 4.5-y-old children. In conclusion, cadmium exposure in early life appears to alter DNA methylation differently in girls and boys. This is consistent with previous findings of sex-specific cadmium toxicity. Cadmium-related changes in methylation were also related to lower birth weight. PMID:23644563

  1. Sex-specific effects of early life cadmium exposure on DNA methylation and implications for birth weight.

    PubMed

    Kippler, Maria; Engström, Karin; Mlakar, Simona Jurkovic; Bottai, Matteo; Ahmed, Sultan; Hossain, Mohammad Bakhtiar; Raqib, Rubhana; Vahter, Marie; Broberg, Karin

    2013-05-01

    Dietary cadmium exposure was recently found to alter DNA methylation in adults, but data on effects early in life are lacking. Our objective was to evaluate associations between prenatal cadmium exposure, DNA methylation and birth weight. In total 127 mother-child pairs from rural Bangladesh were studied. For comparison, we included 56 children at 4.5 y. Cadmium concentrations in mothers' blood (gestational week 14) and children's urine were measured by ICPMS. Global DNA methylation was analyzed by Infinium HumanMethylation450K BeadChip in cord blood and children's blood. Maternal cadmium exposure was associated with cord blood DNA methylation (p-value < 10 (-16) ). The association was markedly sex-specific. In boys, 96% of the top 500 CpG sites showed positive correlations (rS-values > 0.50), whereas most associations in girls were inverse; only 29% were positive (rS > 0.45). In girls we found overrepresentation of methylation changes in genes associated with organ development, morphology and mineralization of bone, whereas changes in boys were found in cell death-related genes. Several individual CpG sites that were positively associated with cadmium were inversely correlated with birth weight, although none statistically significant after correction for multiple comparisons. The associations were, however, fairly robust in multivariable-adjusted linear regression models. We identified CpG sites that were significantly associated with cadmium exposure in both newborns and 4.5-y-old children. In conclusion, cadmium exposure in early life appears to alter DNA methylation differently in girls and boys. This is consistent with previous findings of sex-specific cadmium toxicity. Cadmium-related changes in methylation were also related to lower birth weight.

  2. DNA methylation levels and long-term trihalomethane exposure in drinking water: an epigenome-wide association study.

    PubMed

    Salas, Lucas A; Bustamante, Mariona; Gonzalez, Juan R; Gracia-Lavedan, Esther; Moreno, Victor; Kogevinas, Manolis; Villanueva, Cristina M

    2015-01-01

    Trihalomethanes (THM) are undesired disinfection byproducts (DBPs) formed during water treatment. Mice exposed to DBPs showed global DNA hypomethylation and c-myc and c-jun gene-specific hypomethylation, while evidence of epigenetic effects in humans is scarce. We explored the association between lifetime THM exposure and DNA methylation through an epigenome-wide association study. We selected 138 population-based controls from a case-control study of colorectal cancer conducted in Barcelona, Spain, exposed to average lifetime THM levels ≤85 μg/L vs. >85 μg/L (N = 68 and N = 70, respectively). Mean age of participants was 70 years, and 54% were male. Average lifetime THM level in the exposure groups was 64 and 130 µg/L, respectively. DNA was extracted from whole blood and was bisulphite converted to measure DNA methylation levels using the Illumina HumanMethylation450 BeadChip. Data preprocessing was performed using RnBeads. Methylation was compared between exposure groups using empirical Bayes moderated linear regression for CpG sites and Gaussian kernel for CpG regions. ConsensusPathDB was used for gene set enrichment. Statistically significant differences in methylation between exposure groups was found in 140 CpG sites and 30 gene-related regions, after false discovery rate <0.05 and adjustment for age, sex, methylation first principal component, and blood cell proportion. The annotated genes were localized to several cancer pathways. Among them, 29 CpGs had methylation levels associated with THM levels (|Δβ|≥0.05) located in 11 genes associated with cancer in other studies. Our results suggest that THM exposure may affect DNA methylation in genes related to tumors, including colorectal and bladder cancers. Future confirmation studies are required.

  3. Evaluation of sublethal biomarkers in Litopenaeus vannamei on foodborne exposure to methyl parathion.

    PubMed

    Comoglio, L; Amin, O; Roque, A; Betancourt-Lozano, M; Anguas, D; Haro, B M

    2005-09-01

    Sublethal effects of foodborne exposure to methyl parathion (0.62 and 1.31 microg methyl parathion*g(-1) dry weight of food) on juveniles of Litopenaeus vannamei using integrated biochemical (acetylcholinesterase (AChE) and ATPases) and physiological (feeding rate (FR), egestion rate (ER), and hepatosomatic index (HI)) biomarkers were evaluated. The HI was significantly higher in controls than in pesticide treatments. The FR was significantly lower in controls than in pesticide treatments while no significant differences were detected in the ER. AChE activity was significantly higher in controls than in pesticide treatments (control = 0.11 +/- 0.02; solvent control = 0.11 +/- 0.03; 0.62 = 0.07 +/- 0.01; 1.31 = 0.08 +/- 0.02 microM*min(-1)*mgprotein(-1)). The total-ATPase activity was significantly lower in controls than in pesticide treatments (control=77.90+/-12.41; solvent control = 83.69 +/- 22.05; 0.62 = 110.03 +/- 22.17; 1.31 = 121.54 +/- 19.84 microM P(i)*h(-1)*mgprotein(-1)). The Mg(2+)-ATPase activity was significantly higher in treatments than in controls (control = 65.14+/-10.76; solvent control = 75.12 +/- 21.10; 0.62 = 100.53 +/- 20.97; 1.31 = 108.94 +/- 17.26 microM P(i)*h(-1)*mgprotein(-1)). Finally, the results obtained for the Na(+)/K(+)-ATPase activity were significantly higher in control and in 1.31 than in solvent control and in 0.62 (control = 14.06+/-2.63; solvent control=7.30 +/- 4.13; 0.62 = 7.60 +/- 3.81; 1.31 = 13.42 +/- 2.88 microM P(i)*h(-1)*mgprotein(-1)). The results in this study showed that pulse exposures to methyl parathion via food could elicit measurable effects on the marine shrimp L. vannamei, indicating that foodborne exposure can be a reliable toxicological procedure and, if combined with pulse exposures, could also simulate more realistic exposure scenarios.

  4. Effects of Short-term Exposure to Inhalable Particulate Matter on DNA Methylation of Tandem Repeats

    PubMed Central

    Guo, Liqiong; Byun, Hyang-Min; Zhong, Jia; Motta, Valeria; Barupal, Jitendra; Zheng, Yinan; Dou, Chang; Zhang, Feiruo; McCracken, John P.; Diaz, Anaité; Marco, Sanchez-Guerra; Colicino, Silvia; Schwartz, Joel; Wang, Sheng; Hou, Lifang; Baccarelli, Andrea A.

    2015-01-01

    There is compelling evidence that particulate matter (PM) increases lung cancer risk by triggering systemic inflammation, and leukocyte DNA hypomethylation. However, previous investigations focused on repeated element sequences from LINE-1 and Alu families. Tandem repeats, which display a greater propensity to mutate, and are often hypomethylated in cancer patients, have never been investigated in individuals exposed to PM. We measured methylation of three tandem repeats (SATα, NBL2, D4Z4) by polymerase chain reaction–pyrosequencing on blood samples from truck drivers and office workers (60 per group) in Beijing, China. We used lightweight monitors to measure personal PM2.5 (PM with aerodynamic diameter ≤2.5 µm) and elemental carbon (EC, a tracer of PM from vehicular traffic). Ambient PM10 data were obtained from air quality measuring stations. Overall, an interquartile increase in personal PM2.5 and ambient PM10 levels was associated with a significant covariate-adjusted decrease in SATα methylation (−1.35% 5-methyl cytosine [5mC], P = 0.01; and −1.33%5mC; P = 0.01, respectively). Effects from personal PM2.5 and ambient PM10 on SATα methylation were stronger in truck drivers (−2.34%5mC, P = 0.02; −1.44%5mC, P = 0.06) than office workers (−0.95%5mC, P = 0.26; −1.25%5mC, P = 0.12, respectively). Ambient PM10 was negatively correlated with NBL2 methylation in truck drivers (−1.38%5mC, P = 0.03) but not in office workers (1.04%5mC, P = 0.13). Our result suggests that PM exposure is associated with hypomethylation of selected tandem repeats. Measuring tandem-repeat hypomethylation in easy-to-obtain blood specimens might identify individuals with biological effects and potential cancer risk from PM exposure. PMID:24436168

  5. Arsenic exposure from drinking water, arsenic methylation capacity, and carotid intima-media thickness in Bangladesh.

    PubMed

    Chen, Yu; Wu, Fen; Graziano, Joseph H; Parvez, Faruque; Liu, Mengling; Paul, Rina Rani; Shaheen, Ishrat; Sarwar, Golam; Ahmed, Alauddin; Islam, Tariqul; Slavkovich, Vesna; Rundek, Tatjana; Demmer, Ryan T; Desvarieux, Moise; Ahsan, Habibul

    2013-08-01

    We conducted a cross-sectional study to evaluate the interrelationships between past arsenic exposure, biomarkers specific for susceptibility to arsenic exposure, and carotid intima-media thickness (cIMT) in 959 subjects from the Health Effects of Arsenic Longitudinal Study in Bangladesh. We measured cIMT levels on average 7.2 years after baseline during 2010-2011. Arsenic exposure was measured in well water at baseline and in urine samples collected at baseline and during follow-up. Every 1-standard-deviation increase in urinary arsenic (357.9 µg/g creatinine) and well-water arsenic (102.0 µg/L) concentration was related to a 11.7-µm (95% confidence interval (CI): 1.8, 21.6) and 5.1-µm (95% CI: -0.2, 10.3) increase in cIMT, respectively. For every 10% increase in monomethylarsonic acid (MMA) percentage, there was an increase of 12.1 µm (95% CI: 0.4, 23.8) in cIMT. Among participants with a higher urinary MMA percentage, a higher ratio of urinary MMA to inorganic arsenic, and a lower ratio of dimethylarsinic acid to MMA, the association between well-water arsenic and cIMT was stronger. The findings indicate an effect of past long-term arsenic exposure on cIMT, which may be potentiated by suboptimal or incomplete arsenic methylation capacity. Future prospective studies are needed to confirm the association between arsenic methylation capacity and atherosclerosis-related outcomes.

  6. Maternal Exposure to Nitrogen Dioxide, Intake of Methyl Nutrients, and Congenital Heart Defects in Offspring.

    PubMed

    Stingone, Jeanette A; Luben, Thomas J; Carmichael, Suzan L; Aylsworth, Arthur S; Botto, Lorenzo D; Correa, Adolfo; Gilboa, Suzanne M; Langlois, Peter H; Nembhard, Wendy N; Richmond-Bryant, Jennifer; Shaw, Gary M; Olshan, Andrew F

    2017-09-15

    Nutrients that regulate methylation processes may modify susceptibility to the effects of air pollutants. Data from the National Birth Defects Prevention Study (United States, 1997-2006) were used to estimate associations between maternal exposure to nitrogen dioxide (NO2), dietary intake of methyl nutrients, and the odds of congenital heart defects in offspring. NO2 concentrations, a marker of traffic-related air pollution, averaged across postconception weeks 2-8, were assigned to 6,160 nondiabetic mothers of cases and controls using inverse distance-squared weighting of air monitors within 50 km of maternal residences. Intakes of choline, folate, methionine, and vitamins B6 and B12 were assessed using a food frequency questionnaire. Hierarchical regression models, which accounted for similarities across defects, were constructed, and relative excess risks due to interaction were calculated. Relative to women with the lowest NO2 exposure and high methionine intake, women with the highest NO2 exposure and lowest methionine intake had the greatest odds of offspring with a perimembranous ventricular septal defect (odds ratio = 3.23, 95% confidence interval: 1.74, 6.01; relative excess risk due to interaction = 2.15, 95% confidence interval: 0.39, 3.92). Considerable departure from additivity was not observed for other defects. These results provide modest evidence of interaction between nutrition and NO2 exposure during pregnancy. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Arsenic Exposure From Drinking Water, Arsenic Methylation Capacity, and Carotid Intima-Media Thickness in Bangladesh

    PubMed Central

    Chen, Yu; Wu, Fen; Graziano, Joseph H.; Parvez, Faruque; Liu, Mengling; Paul, Rina Rani; Shaheen, Ishrat; Sarwar, Golam; Ahmed, Alauddin; Islam, Tariqul; Slavkovich, Vesna; Rundek, Tatjana; Demmer, Ryan T.; Desvarieux, Moise; Ahsan, Habibul

    2013-01-01

    We conducted a cross-sectional study to evaluate the interrelationships between past arsenic exposure, biomarkers specific for susceptibility to arsenic exposure, and carotid intima-media thickness (cIMT) in 959 subjects from the Health Effects of Arsenic Longitudinal Study in Bangladesh. We measured cIMT levels on average 7.2 years after baseline during 2010–2011. Arsenic exposure was measured in well water at baseline and in urine samples collected at baseline and during follow-up. Every 1-standard-deviation increase in urinary arsenic (357.9 µg/g creatinine) and well-water arsenic (102.0 µg/L) concentration was related to a 11.7-µm (95% confidence interval (CI): 1.8, 21.6) and 5.1-µm (95% CI: −0.2, 10.3) increase in cIMT, respectively. For every 10% increase in monomethylarsonic acid (MMA) percentage, there was an increase of 12.1 µm (95% CI: 0.4, 23.8) in cIMT. Among participants with a higher urinary MMA percentage, a higher ratio of urinary MMA to inorganic arsenic, and a lower ratio of dimethylarsinic acid to MMA, the association between well-water arsenic and cIMT was stronger. The findings indicate an effect of past long-term arsenic exposure on cIMT, which may be potentiated by suboptimal or incomplete arsenic methylation capacity. Future prospective studies are needed to confirm the association between arsenic methylation capacity and atherosclerosis-related outcomes. PMID:23788675

  8. A quantitative analysis of prenatal methyl mercury exposure and cognitive development.

    PubMed

    Cohen, Joshua T; Bellinger, David C; Shaywitz, Bennett A

    2005-11-01

    Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish also contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgements) to quantify the net impact of resulting hypothetical changes in fish consumption across the population. This paper quantifies the impact of prenatal MeHg exposure on cognitive development. Other papers quantify the beneficial impact of prenatal intake of n-3 PUFAs on cognitive function and the extent to which fish consumption protects against coronary heart disease mortality and stroke in adults. This analysis aggregates results from three major prospective epidemiology studies to quantify the association between prenatal MeHg exposure and cognitive development as measured by intelligence quotient (IQ). It finds that prenatal MeHg exposure sufficient to increase the concentration of mercury in maternal hair at parturition by 1 microg/g decreases IQ by 0.7 points. This paper identifies important sources of uncertainty influencing this estimate, concluding that the plausible range of values for this loss is 0 to 1.5 IQ points.

  9. [Pharmacological studies of antispasmodics. III. Antispasmodic activity of 3-(di-2-thienylmethylene)-5-methyl-trans-quino-lizidinium bromide (HRS-902) on smooth muscle organs and its organ selectivity (author's transl)].

    PubMed

    Kubo, S; Morikawa, K; Matsubara, I; Yamazaki, M; Kato, H

    1981-01-01

    Pharmacological activities of HSR-902, a new antispasmodic agent, in gastrointestinal tract, biliary and urinary systems were compared with those of atropine, butylscopolamine bromide, timepidium bromide, prifinium bromide and diphemanil methylsulfate. In isolated smooth muscle organs (stomach, duodenum, ileum, colon, gall bladder and urinary bladder), anti-acetylcholine activities of HSR-902 were the most potent among these agents but its activity in urinary bladder, similar to findings in the cases of atropine and diphemanil methylsulfate, was relatively less potent than that of prifinium bromide, timepidium bromide and butylscopolamine bromide. Regarding the contractions of stomach, jejunum and ileum, which were induced by vagus nerve stimulation or acetylcholine, and on the ileum spontaneous motility, antispasmodic activities of HSR-902 were almost equal to or somewhat more potent than those of atropine, and its activities were more potent than those of prifinium bromide, timepidium bromide, diphemanil methylsulfate and butylscopolamine bromide. On the gall bladder pressure and the counts of perfusion through Oddi's Sphincter, these agents exhibited a similar inhibition and enhancement, respectively. In the case of urinary bladder contractions induced by pelvic nerve stimulation, these agents exhibited a weak inhibition. The inhibitory effect of HSR-902 was relatively less potent than that of other agents except atropine, which had little effect. HSR-902 was similar to atropine in this so-called "atropine-resistance".

  10. Effect on the H19 gene methylation of sperm and organs of offspring after chlorpyrifos-methyl exposure during organogenesis period.

    PubMed

    Shin, Hyo-Sook; Seo, Jong-Hun; Jeong, Sang-Hee; Park, Sung-Won; Park, Young-Il; Son, Seong-Wan; Kang, Hwan-Goo; Kim, Jin Suk

    2015-12-01

    To elucidate the effect on the H19 gene methylation of sperm and organs in offspring by chlorpyrifos-methyl (CPM) exposure during organogenesis period, CPM was administered at doses of 4 (CPM4), 20 (CPM20), and 100 (CPM100) mg/kg bw/day from 7 days post coitum (d.p.c.) to 17 d.p.c. after mating CAST/Ei (♂) and B6 (♀). Anogenital distance (AGD) was measured at postnatal day (PND) 21. Clinical signs, body weights, feed and water consumption, organs weights, serum hormone values, and H19 methylation level of organ and sperm were measured at PND63. Body weights were significantly lower than control until PND6. AGD was significantly decreased in the CPM100 group in males and increased in the CPM20 group in females. The absolute weights of the thymus and epididymis were significantly increased for males in all of CPM treatment groups. In the CPM20 group, absolute weights of liver, kidney, heart, lung, spleen, prostate gland, and testes were significantly increased. Testosterone concentrations in serum were significantly increased by CPM treatment in males. H19 methylation level of liver and thymus showed decreased pattern in a dose-dependent manner in males. The levels of H19 methylation in sperm were 73.76 ± 7.16% (Control), 57.84 ± 12.94% (CPM4), 64.24 ± 3.79% (CPM20), and 64.24 ± 3.79% (CPM100). Conclusively, CPM exposure during organogenesis period can disrupt H19 methylation in sperm, liver, and thymus and disturb the early development of offspring.

  11. Dose-Response Relationship between Inorganic Arsenic Exposure and Lung Cancer among Arseniasis Residents with Low Methylation Capacity.

    PubMed

    Hsu, Kuang-Hung; Tsui, Ke-Hung; Hsu, Ling-I; Chiou, Hung-Yi; Chen, Chien-Jen

    2016-12-22

    Background Exposure to inorganic arsenic (InAs) has been documented as a risk factor for lung cancer. This study examined the association between InAs exposure, its metabolism, and lung cancer occurrence. Methods We followed 1300 residents from an arseniasis area in Taiwan, determined urinary InAs metabolites, and identified 39 lung cancer cases. Cox proportional hazard model was performed. Results The results demonstrated that participants with either the primary methylation index (monomethylarsonic acid [MMA]/InAs) or the secondary methylation index (dimethylarsinic acid[DMA]/MMA) lower than their respective median values were at a higher risk of lung cancer (hazard ratios from 3.41 to 4.66) than those with high methylation capacity. The incidence density of lung cancer increased from 79.9/100000 (year-1) to 467.4/100000 (year-1) for residents with low methylation capacity and from 0 to 158.5/100000 (year-1) for residents with high methylation capacity when the arsenic exposure dose increased from 2-10 ppb to ≥200 ppb, respectively. The analyses revealed a dose-response relationship between lung cancer occurrence and increasing arsenic concentrations in drinking water as well as cumulative arsenic exposure (monotonic trend test; P < .05 and P < .05, respectively) among the residents with low methylation capacity. The relationship between arsenic exposure and lung cancer among high methylaters was not statistically significant. Conclusions Hypomethylation responses to InAs exposure may dose-dependently increase lung cancer occurrence. Impact The high-risk characteristics observed among those exposed should be considered in future preventive medicine and research on arsenic carcinogenesis.

  12. Urinary methyl tert-butyl ether and benzene as biomarkers of exposure to urban traffic.

    PubMed

    Campo, Laura; Cattaneo, Andrea; Consonni, Dario; Scibetta, Licia; Costamagna, Paolo; Cavallo, Domenico M; Bertazzi, Pier Alberto; Fustinoni, Silvia

    2011-02-01

    Methyl tert-butyl ether (MTBE) and benzene are added to gasoline to improve the combustion process and are found in the urban environment as a consequence of vehicular traffic. Herein we evaluate urinary MTBE (MTBE-U) and benzene (BEN-U) as biomarkers of exposure to urban traffic. Milan urban policemen (130 total) were investigated in May, July, October, and December for a total of 171 work shifts. Personal exposure to airborne benzene and carbon monoxide (CO), and atmospheric data, were measured during the work shift, while personal characteristics were collected by a questionnaire. A time/activity diary was completed by each subject during the work shift. Spot urine samples were obtained for the determination of MTBE-U and BEN-U. Median personal exposure to CO and airborne benzene were 3.3 mg/m(3) and 9.6 μg/m(3), respectively; median urinary levels in end-of-shift (ES) samples were 147 ng/L (MTBE-U) and 207 ng/L (BEN-U). The time spent on traffic duty at crossing was about 40% of work time. Multiple linear regression models, taking into account within-subject correlations, were applied to investigate the role of urban pollution, atmospheric conditions, job variables and personal characteristics on the level of biomarkers. MTBE-U was influenced by the month of sampling and positively correlated to the time spent in traffic guarding, CO exposure and atmospheric pressure, while negatively correlated to wind speed (R(2) for total model 0.63, P<0.001). BEN-U was influenced by the month and smoking habit, and positively correlated to urinary creatinine; moreover, an interaction between CO and smoking was found (R(2)=0.62, P<0.001). These results suggest that MTBE-U is a reliable marker for assessing urban traffic exposure, while BEN-U is determined mainly by personal characteristics.

  13. Micelles of the chiral biocompatible surfactant (1R,2S)-dodecyl(2-hydroxy-1-methyl-2-phenylethyl)dimethylammonium bromide (DMEB): molecular dynamics and fragmentation patterns in the gas phase.

    PubMed

    Bongiorno, David; Indelicato, Serena; Ceraulo, Leopoldo; Perricone, Ugo; Calabrese, Valentina; Almerico, Anna Maria; Turco Liveri, Vincenzo; Tutone, Marco

    2017-07-15

    The study of self-assembly processes of surfactant molecules in the gas phase is of great interest for several theoretical and technological reasons related to their possible exploitation as drug carriers, protein shields and cleaning agents in the gas phase. The stability and fragmentation patterns of singly and multiply charged (either positively or negatively) aggregates of the surfactant (1R,2S)-dodecyl(2-hydroxy-1-methyl-2-phenylethyl)dimethyl ammonium bromide (DMEB) in the gas phase have been studied by ion mobility mass spectrometry and tandem mass spectrometry. Molecular dynamics (MD) simulations of positively and negatively singly and multiply charged DMEB aggregates have been performed to obtain structural and energetics information. Finally, in order to ascertain some clues on the DMEB growth mechanism, quantum mechanics calculations were carried out. It has been evidenced that positively and negatively singly charged aggregates at low collision energy decompose preferentially by loss of only one DMEB molecule. Increasing the collision energy, the loss of neutrals becomes increasingly abundant. Multiply charged DMEB aggregates are unstable and decompose forming singly charged monomers or dimers. MD simulations show reverse micelle-like structures with polar heads somewhat segregated into the aggregate interior. Finally, a good correlation between experimental and calculated collisional cross sections (CCS) was found. The fragmentation pathways of DMEB charged species evidenced for singly charged aggregates exhibit features similar to that of other detergent aggregates, but multiply charged aggregates showed a system-specific behavior. QM calculations on the optimized structures (2(1+) , 3(1+) , 1(1-) and 2(1-) ) indicate that the most determinant interactions are due to an OH---Br hydrogen bonding that is also involved in the link between monomeric DMEB units. The MD models gave CCS values in good agreement with experimental ones, evidenced by a less

  14. Chemical kinetic measurements of the effect of trans- and cis-3,3'-Bis[(trimethylammonio)methyl]azobenzene bromide on acetylcholine receptor mediated ion translocation in Electrophorus electricus and Torpedo californica.

    PubMed

    Delcour, A H; Hess, G P

    1986-04-08

    A quench-flow technique was used to study the effect of trans- and cis-3,3'-bis[(trimethylammonio)methyl]azobenzene bromide (trans- and cis-Bis-Q), photoisomerizable ligands, on the acetylcholine receptor in vesicles prepared from the electric organ of Electrophorus electricus and of Torpedo californica. In E. electricus, two rate coefficients of the receptor-mediated translocation of 86Rb+ induced with trans-Bis-Q were measured: JA, the rate coefficient for ion flux, and alpha, the rate coefficient for receptor inactivation (desensitization). Both rate coefficients increase with increasing concentrations of Bis-Q up to 50 microM. At higher concentrations JA decreases in a concentration-dependent manner while alpha remains unchanged. This effect was previously observed with suberyldicholine [Pasquale, E. B., Takeyasu, K., Udgaonkar, J., Cash, D.J., Severski, M.C., & Hess, G. P. (1983) Biochemistry 22, 5967-5973] and with acetylcholine [Takeyasu, K., Udgaonkar, J., & Hess, G. P. (1983) Biochemistry 22, 5973-5978] and was analyzed in terms of a minimum mechanism that accounts for the properties of activation, desensitization, and inhibition of the receptor. Two molecules of trans-Bis-Q must be bound for the channel to open, but at concentrations greater than 50 microM the population of open channels decreases because of the additional binding of one molecule of trans-Bis-Q to a regulatory inhibitory site, independent of the activating sites. cis-Bis-Q does not induce transmembrane ion flux, but it does inhibit the response of the receptor to acetylcholine and induces inactivation (desensitization) in the micromolar range.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Crystal structure of bis(bis{(E)-[(6-{(E)-[(4-fluorobenzyl)imino]methyl}pyridin-2-yl)methylidene](4-fluorophenyl)amine}nickel(II)) tetra-bromide nona-hydrate.

    PubMed

    Basaran, Ismet; Rhaman, Md Mhahabubur; Powell, Douglas R; Hossain, Md Alamgir

    2015-12-01

    In the title complex, [Ni(C21H17F2N3)2]2Br4·9H2O, there are two independent metal complexes per asymmetric unit and two ligands per metal complex. The structural features (bond lengths and angles) of the two complexes are almost identical. In each complex, the nickel(II) ion is coordinated in an octa-hedral environment by six N atoms from two chelating (9E)-N-({6-[(E)-(4-fluoro-benzyl-imino)-meth-yl]pyridin-2-yl}methyl-ene)(4-fluoro-phen-yl)methanammine ligands. The Ni-N bond lengths range from 1.973 (2) to 2.169 (2) Å, while the chelate N-Ni-N angles range from 77.01 (10) to 105.89 (9)°. Additionally, there are four bromide anions and nine solvent water mol-ecules within the asymmetric unit. The water mol-ecules form a hydrogen-bonded network, displaying C-H⋯O, C-H⋯Br, O-H⋯Br, O-H⋯O and O-H⋯F inter-actions into layers parallel to (111). In each unit, the fluoro-phenyl rings of one ligand are stacked with the central ring of the other ligand via π-π inter-actions, with the closest centroid-to-plane distances being 3.445 (5), 3.636 (5), 3.397 (5) and 3.396 (5) Å.

  16. BOTH HYPOMETHYLATION AND HYPERMETHYLATION OF DNA ASSOCIATED WITH ARSENITE EXPOSURE IN CULTURES OF HUMAN CELLS IDENTIFIED BY METHYLATION-SENSITIVE ARBITRARILY-PRIMED PCR

    EPA Science Inventory

    Differentially Methylated DNA Sequences Associated with Exposure to Arsenite in Cultures of Human Cells Identified by Methylation-Sensitive-Primed PCR

    Arsenic, a known human carcinogen, is converted to methylated derivatives by a methyltransferase (Mtase) and its biotra...

  17. Aberrant 5’-CpG Methylation of Cord Blood TNFα Associated with Maternal Exposure to Polybrominated Diphenyl Ethers

    PubMed Central

    Wang, Xiaobin; Tang, Wan-Yee

    2015-01-01

    Growing evidence suggests that maternal exposures to endocrine disrupting chemicals during pregnancy may lead to poor pregnancy outcomes and increased fetal susceptibility to adult diseases. Polybrominated diphenyl ethers (PBDEs), which are ubiquitously used flame-retardants, could leach into the environment; and become persistent organic pollutants via bioaccumulation. In the United States, blood PBDE levels in adults range from 30–100 ng/g- lipid but the alarming health concern revolves around children who have reported blood PBDE levels 3 to 9-fold higher than adults. PBDEs disrupt endocrine, immune, reproductive and nervous systems. However, the mechanism underlying its adverse health effect is not fully understood. Epigenetics is a possible biological mechanism underlying maternal exposure-child health outcomes by regulating gene expression without changes in the DNA sequence. We sought to examine the relationship between maternal exposure to environmental PBDEs and promoter methylation of a proinflammatory gene, tumor necrosis factor alpha (TNFα). We measured the maternal blood PBDE levels and cord blood TNFα promoter methylation levels on 46 paired samples of maternal and cord blood from the Boston Birth Cohort (BBC). We showed that decreased cord blood TNFα methylation associated with high maternal PBDE47 exposure. CpG site-specific methylation showed significantly hypomethylation in the girl whose mother has a high blood PBDE47 level. Consistently, decreased TNFα methylation associated with an increase in TNFα protein level in cord blood. In conclusion, our finding provided evidence that in utero exposure to PBDEs may epigenetically reprogram the offspring’s immunological response through promoter methylation of a proinflammatory gene. PMID:26406892

  18. Changes in Neuronal Dopamine Homeostasis following 1-Methyl-4-phenylpyridinium (MPP+) Exposure*

    PubMed Central

    Choi, Se Joon; Panhelainen, Anne; Schmitz, Yvonne; Larsen, Kristin E.; Kanter, Ellen; Wu, Min; Sulzer, David; Mosharov, Eugene V.

    2015-01-01

    1-Methyl-4-phenylpyridinium (MPP+), the active metabolite of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, selectively kills dopaminergic neurons in vivo and in vitro via a variety of toxic mechanisms, including mitochondrial dysfunction, generation of peroxynitrite, induction of apoptosis, and oxidative stress due to disruption of vesicular dopamine (DA) storage. To investigate the effects of acute MPP+ exposure on neuronal DA homeostasis, we measured stimulation-dependent DA release and non-exocytotic DA efflux from mouse striatal slices and extracellular, intracellular, and cytosolic DA (DAcyt) levels in cultured mouse ventral midbrain neurons. In acute striatal slices, MPP+ exposure gradually decreased stimulation-dependent DA release, followed by massive DA efflux that was dependent on MPP+ concentration, temperature, and DA uptake transporter activity. Similarly, in mouse midbrain neuronal cultures, MPP+ depleted vesicular DA storage accompanied by an elevation of cytosolic and extracellular DA levels. In neuronal cell bodies, increased DAcyt was not due to transmitter leakage from synaptic vesicles but rather to competitive MPP+-dependent inhibition of monoamine oxidase activity. Accordingly, monoamine oxidase blockers pargyline and l-deprenyl had no effect on DAcyt levels in MPP+-treated cells and produced only a moderate effect on the survival of dopaminergic neurons treated with the toxin. In contrast, depletion of intracellular DA by blocking neurotransmitter synthesis resulted in ∼30% reduction of MPP+-mediated toxicity, whereas overexpression of VMAT2 completely rescued dopaminergic neurons. These results demonstrate the utility of comprehensive analysis of DA metabolism using various electrochemical methods and reveal the complexity of the effects of MPP+ on neuronal DA homeostasis and neurotoxicity. PMID:25596531

  19. Changes in neuronal dopamine homeostasis following 1-methyl-4-phenylpyridinium (MPP+) exposure.

    PubMed

    Choi, Se Joon; Panhelainen, Anne; Schmitz, Yvonne; Larsen, Kristin E; Kanter, Ellen; Wu, Min; Sulzer, David; Mosharov, Eugene V

    2015-03-13

    1-Methyl-4-phenylpyridinium (MPP(+)), the active metabolite of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, selectively kills dopaminergic neurons in vivo and in vitro via a variety of toxic mechanisms, including mitochondrial dysfunction, generation of peroxynitrite, induction of apoptosis, and oxidative stress due to disruption of vesicular dopamine (DA) storage. To investigate the effects of acute MPP(+) exposure on neuronal DA homeostasis, we measured stimulation-dependent DA release and non-exocytotic DA efflux from mouse striatal slices and extracellular, intracellular, and cytosolic DA (DAcyt) levels in cultured mouse ventral midbrain neurons. In acute striatal slices, MPP(+) exposure gradually decreased stimulation-dependent DA release, followed by massive DA efflux that was dependent on MPP(+) concentration, temperature, and DA uptake transporter activity. Similarly, in mouse midbrain neuronal cultures, MPP(+) depleted vesicular DA storage accompanied by an elevation of cytosolic and extracellular DA levels. In neuronal cell bodies, increased DAcyt was not due to transmitter leakage from synaptic vesicles but rather to competitive MPP(+)-dependent inhibition of monoamine oxidase activity. Accordingly, monoamine oxidase blockers pargyline and l-deprenyl had no effect on DAcyt levels in MPP(+)-treated cells and produced only a moderate effect on the survival of dopaminergic neurons treated with the toxin. In contrast, depletion of intracellular DA by blocking neurotransmitter synthesis resulted in ∼30% reduction of MPP(+)-mediated toxicity, whereas overexpression of VMAT2 completely rescued dopaminergic neurons. These results demonstrate the utility of comprehensive analysis of DA metabolism using various electrochemical methods and reveal the complexity of the effects of MPP(+) on neuronal DA homeostasis and neurotoxicity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Exposure to methyl tert-butyl ether and benzene among service station attendants and operators.

    PubMed

    Hartle, R

    1993-12-01

    Concerns for atmospheric pollution from auto exhaust have led to the blending of "oxygenates" with motor fuels. The most common oxygenate, methyl tert-butyl ether (MTBE) is currently required within several metropolitan areas (Denver and Phoenix) in the range of 12% of the motor fuel. Amendments to the Clean Air Act may expand this requirement to as many as 44 other areas of the United States in the near future. In consideration of the magnitude of potential uncontrolled exposures from its extensive use and a related concern involving the potential influence of MTBE blending on exposures to other constituents of gasoline (particularly benzene), an evaluation of exposures among service station attendants and operators was undertaken at the request, and in cooperation with, the American Petroleum Institute during the latter part of 1990. For application of the survey results to a broad audience, three categories or types of service stations were identified with regard to MTBE use and exposure potential: a) service stations that do not use MTBE or use it only as an octane enhancer, b) service stations with seasonal requirements to use 12-15% MTBE (the Denver, Colorado, and Phoenix, Arizona, metropolitan areas), and c) service stations equipped with stage II (active) vapor recovery systems (several coastal areas, most notably Southern California). At the two sampled service stations that use only minimal amounts of MTBE (less than 1%), only 1 of 32 personal breathing zone (PBZ) samples from attendants was above the analytical limit of detection, reported at 0.16 ppm. The geometric mean concentration of benzene among this same population (n = 32) was 0.04 ppm.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Effects on specific promoter DNA methylation in zebrafish embryos and larvae following benzo[a]pyrene exposure

    USDA-ARS?s Scientific Manuscript database

    Benzo[a]pyrene (BaP) is an established reproductive and developmental toxicant. BaP exposure in humans and animals has been linked to infertility and multigenerational health consequences. DNA methylation is the most studied epigenetic mechanism that regulates gene expression, and mapping of methyla...

  2. Effects of methyl testosterone exposure on sexual differentiation in medaka, Oryzias latipes

    USGS Publications Warehouse

    Papoulias, D.M.; Noltie, Douglas B.; Tillitt, D.E.

    2000-01-01

    Studies were conducted to characterize effects of a known androgen on sexual differentiation and development of medaka, Oryzias latipes (d-rR strain), at two life stages. Embryos were injected with graded doses of methyl testosterone (MT) prior to epiboly. The occurrence of sex-reversal, and the gonadosomatic index (GSI) were evaluated in adults. Primary germ cells were counted and gonad volumes calculated for larvae to determine if sex-reversal could be detected at an early life stage. Sex-reversal of genetic females to phenotypic males was observed at both life stages. The GSI for phenotypic females was greater than for phenotypic males, while the GSI in XX males was similar to XY males. MT appeared to reduce the GSI of XX females exposed to MT but not sex-reversed. Our results indicate that embryonic exposure to androgens influences sexual development in medaka. Utilizing the d-rR strain of medaka allows detection of an effect as early as 2 weeks after chemical exposure making this a useful tool to screen chemicals for effects on sexual differentiation. Copyright (C) 2000.

  3. Investigation of the oxidative stress condition for occupational exposure to methyl methacrylate.

    PubMed

    Soykut, Buğra; Erdem, Onur; Akay, Cemal; Pişkin, Bülent

    2017-01-01

    The purpose of this study is the evaluation of possible toxicological effects on dental personnel, who are exposed to the production materials of prostheses during their entire working life. In this study, the level of methyl methacrylate (MMA) in ambient air was measured as an indicator of external exposure on the personnel. In order to evaluate the possible toxic effects of oxidative stress, which is thought to play an important role in the formation process of many diseases such as cancer, blood samples of volunteers were examined via the ultraviolet-spectroscopic determination of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase antioxidant enzyme activities, comparing occupationally MMA-exposed ( n = 69) and control ( n = 67) groups. In these groups, malondialdehyde (MDA) and glutathione levels were also determined by the same method. The results showed that SOD activity and MDA and glutathione levels were significantly higher in the exposed group when compared with the control group ( p < 0.001). A significant decrease was determined in the glutathione peroxidase activities of the exposed group ( p < 0.05). No significant difference in CAT activities between the groups has been found. When the results obtained in the study are considered, it is suggested that an adaptive response might be developed by dental technicians against low-level MMA exposure.

  4. A Dose–Response Study of Arsenic Exposure and Global Methylation of Peripheral Blood Mononuclear Cell DNA in Bangladeshi Adults

    PubMed Central

    Niedzwiecki, Megan M.; Hall, Megan N.; Liu, Xinhua; Oka, Julie; Harper, Kristin N.; Slavkovich, Vesna; Ilievski, Vesna; Levy, Diane; van Geen, Alexander; Mey, Jacob L.; Alam, Shafiul; Siddique, Abu B.; Parvez, Faruque; Graziano, Joseph H.

    2013-01-01

    Background: Several studies employing cell culture and animal models have suggested that arsenic (As) exposure induces global DNA hypomethylation. However, As has been associated with global DNA hypermethylation in human study populations. We hypothesized that this discrepancy may reflect a nonlinear relationship between As dose and DNA methylation. Objective: The objective of this study was to examine the dose–response relationship between As and global methylation of peripheral blood mononuclear cell (PBMC) DNA in apparently healthy Bangladeshi adults chronically exposed to a wide range of As concentrations in drinking water. Methods: Global PBMC DNA methylation, plasma folate, blood S-adenosylmethionine (SAM), and concentrations of As in drinking water, blood, and urine were measured in 320 adults. DNA methylation was measured using the [3H]-methyl incorporation assay, which provides disintegration-per-minute (DPM) values that are negatively associated with global DNA methylation. Results: Water, blood, and urinary As were positively correlated with global PBMC DNA methylation (p < 0.05). In multivariable-adjusted models, 1-μg/L increases in water and urinary As were associated with 27.6-unit (95% CI: 6.3, 49.0) and 22.1-unit (95% CI: 0.5, 43.8) decreases in DPM per microgram DNA, respectively. Categorical models indicated that estimated mean levels of PBMC DNA methylation were highest in participants with the highest As exposures. Conclusions: These results suggest that As is positively associated with global methylation of PBMC DNA over a wide range of drinking water As concentrations. Further research is necessary to elucidate underlying mechanisms and physiologic implications. Citation: Niedzwiecki MM, Hall MN, Liu X, Oka J, Harper KN, Slavkovich V, Ilievski V, Levy D, van Geen A, Mey JL, Alam S, Siddique AB, Parvez F, Graziano JH, Gamble MV. 2013. A dose–response study of arsenic exposure and global methylation of peripheral blood mononuclear cell DNA

  5. Prolonged Exposure to Particulate Pollution, Genes Associated with Glutathione Pathways, and DNA Methylation in a Cohort of Older Men

    PubMed Central

    Baccarelli, Andrea; Mittleman, Murray A.; Wright, Robert O.; Sparrow, David; Vokonas, Pantel S.; Tarantini, Letizia; Schwartz, Joel

    2011-01-01

    Background: DNA methylation is a potential pathway linking environmental exposures to disease. Exposure to particulate air pollution has been associated with increased cardiovascular morbidity and mortality, and lower blood DNA methylation has been found in processes related to cardiovascular morbidity. Objective: We hypothesized that prolonged exposure to particulate pollution would be associated with hypomethylation of repetitive DNA elements and that this association would be modified by genes involved in glutathione metabolism and other host characteristics. Methods: DNA methylation of the long interspersed nucleotide element–1 (LINE-1) and the short interspersed nucleotide element Alu were measured by quantitative polymerase chain reaction pyrosequencing in 1,406 blood samples from 706 elderly participants in the Normative Aging Study. We estimated changes in repetitive element DNA methylation associated with ambient particles (particulate matter ≤ 2.5 µm in aerodynamic diameter), black carbon (BC), and sulfates (SO4), with mixed models. We examined multiple exposure windows (1–6 months) before DNA methylation measurement. We investigated whether this association was modified by genotype and phenotype. Results: An interquartile range (IQR) increase in BC over a 90-day period was associated with a decrease of 0.31% 5-methylcytosine (5mC) (95% confidence interval, 0.12–0.50%) in Alu. An IQR increase in SO4 over a 90-day period was associated with a decrease of 0.27% 5mC (0.02–0.52%) in LINE-1. The glutathione S-transferase mu-1–null genotype strengthened the association between BC and Alu hypomethylation. Conclusion: Prolonged exposure to BC and SO4 particles was associated with hypomethylation of two types of repetitive elements. PMID:21385671

  6. Surface and volume properties of dodecylethyldimethylammonium bromide and benzyldimethyldodecylammonium bromide I. Surface properties of dodecylethyldimethylammonium bromide and benzyldimethyldodecylammonium bromide.

    PubMed

    Harkot, Joanna; Jańczuk, Bronisław

    2009-03-15

    Surface tension measurements were carried out for aqueous solutions of two cationic surfactants: dodecylethyldimethylammonium bromide (C(12)(EDMAB)) and benzyldimethyldodecylammonium bromide (BDDAB). Isotherms and thermodynamic adsorption parameters were determined from the surface tension data. Firstly, the surface excess concentration in the adsorbed monolayer and the total concentration of the surfactants were determined, then the standard free energy of adsorption was calculated by different methods. In the calculations, different orientations of the surfactants at the adsorbed monolayer were also taken into account. From the experimental and calculated data it results that the difference in the structure of the two cationic surfactants by changing the methyl group for aryl one in their heads causes an increase of the efficiency and a decrease of the effectiveness of adsorption at water-air interface, and that the standard free energy of adsorption can be predicted from the surface tension of the surfactants assuming the aryl group to be equivalent to 3.5 methylene groups. The experimentally obtained difference between the standard free energy of adsorption of the C(12)(EDMAB) and BDDAB was in good agreement with that theoretically accounted, corresponding to the standard free energy of adsorption of the aryl group. However, the best correlation between the values was obtained when a parallel orientation of the surfactant molecules at the adsorbed monolayer was taken into account.

  7. Maternal E-cigarette Exposure in Mice Alters DNA Methylation and Lung Cytokine Expression in Offspring.

    PubMed

    Chen, Hui; Li, Gerard; Chan, Yik Lung; Chapman, David G; Sukjamnong, Suporn; Nguyen, Tara; Annissa, Tiara; McGrath, Kristine C; Sharma, Pawan; Oliver, Brian G

    2017-09-29

    E-cigarette usage is increasing, especially among the young, with both the general population and physicians perceiving them as a safe alternative to tobacco smoking. Worryingly, e-cigarettes are commonly used by pregnant women. As nicotine is known to adversely affect children in-utero, we hypothesised that nicotine delivered via e-cigarettes would negatively affect lung development. To test this we developed a mouse model of maternal e-vapour (nicotine and nicotine-free) exposure, and investigated the impact on the growth and lung inflammation in both offspring and mothers. Female Balb/c mice were exposed to e-fluid vapour containing nicotine (E-cig18mg/mL, equivalent to 2 cigarettes/treatment, twice daily,) or nicotine free (E-cig0mg/mL) from 6 weeks prior to mating until pups weaned. Male offspring were studied at postnatal day (P) 1, 20 and at 13 weeks. The mothers were studied when the pups weaned. In the mothers' lung, e-cigarette exposure with and without nicotine increased the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α. In adult offspring, TNF-α protein levels were increased in both E-cig18 and E-cig0 groups, whilst IL-1β was suppressed. This was accompanied by global changes in DNA methylation. In this study, we found that e-cigarette exposure during pregnancy adversely affected maternal and offspring lung health. As this occurred with both nicotine free and nicotine containing e-vapour the effects are likely due to by-products of vaporisation rather than nicotine.

  8. Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain

    PubMed Central

    Ngai, Ying Fai; Sulistyoningrum, Dian C.; O'Neill, Ryan; Innis, Sheila M.; Weinberg, Joanne

    2015-01-01

    Prenatal alcohol exposure (PAE) programs the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in HPA dysregulation and hyperresponsiveness to stressors in adulthood. Molecular mechanisms mediating these alterations are not fully understood. Disturbances in one-carbon metabolism, a source of methyl donors for epigenetic processes, contributes to alcoholic liver disease. We assessed whether PAE affects one-carbon metabolism (including Mtr, Mat2a, Mthfr, and Cbs mRNA) and programming of HPA function genes (Nr3c1, Nr3c2, and Slc6a4) in offspring from ethanol-fed (E), pair-fed (PF), and ad libitum-fed control (C) dams. At gestation day 21, plasma total homocysteine and methionine concentrations were higher in E compared with C dams, and E fetuses had higher plasma methionine concentrations and lower whole brain Mtr and Mat2a mRNA compared with C fetuses. In adulthood (55 days), hippocampal Mtr and Cbs mRNA was lower in E compared with C males, whereas Mtr, Mat2a, Mthfr, and Cbs mRNA were higher in E compared with C females. We found lower Nr3c1 mRNA and lower nerve growth factor inducible protein A (NGFI-A) protein in the hippocampus of E compared with PF females, whereas hippocampal Slc6a4 mRNA was higher in E than C males. By contrast, hypothalamic Slc6a4 mRNA was lower in E males and females compared with C offspring. This was accompanied by higher hypothalamic Slc6a4 mean promoter methylation in E compared with PF females. These findings demonstrate that PAE is associated with alterations in one-carbon metabolism and has long-term and region-specific effects on gene expression in the brain. These findings advance our understanding of mechanisms of HPA dysregulation associated with PAE. PMID:26180184

  9. Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain.

    PubMed

    Ngai, Ying Fai; Sulistyoningrum, Dian C; O'Neill, Ryan; Innis, Sheila M; Weinberg, Joanne; Devlin, Angela M

    2015-09-01

    Prenatal alcohol exposure (PAE) programs the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in HPA dysregulation and hyperresponsiveness to stressors in adulthood. Molecular mechanisms mediating these alterations are not fully understood. Disturbances in one-carbon metabolism, a source of methyl donors for epigenetic processes, contributes to alcoholic liver disease. We assessed whether PAE affects one-carbon metabolism (including Mtr, Mat2a, Mthfr, and Cbs mRNA) and programming of HPA function genes (Nr3c1, Nr3c2, and Slc6a4) in offspring from ethanol-fed (E), pair-fed (PF), and ad libitum-fed control (C) dams. At gestation day 21, plasma total homocysteine and methionine concentrations were higher in E compared with C dams, and E fetuses had higher plasma methionine concentrations and lower whole brain Mtr and Mat2a mRNA compared with C fetuses. In adulthood (55 days), hippocampal Mtr and Cbs mRNA was lower in E compared with C males, whereas Mtr, Mat2a, Mthfr, and Cbs mRNA were higher in E compared with C females. We found lower Nr3c1 mRNA and lower nerve growth factor inducible protein A (NGFI-A) protein in the hippocampus of E compared with PF females, whereas hippocampal Slc6a4 mRNA was higher in E than C males. By contrast, hypothalamic Slc6a4 mRNA was lower in E males and females compared with C offspring. This was accompanied by higher hypothalamic Slc6a4 mean promoter methylation in E compared with PF females. These findings demonstrate that PAE is associated with alterations in one-carbon metabolism and has long-term and region-specific effects on gene expression in the brain. These findings advance our understanding of mechanisms of HPA dysregulation associated with PAE.

  10. SLC6A4 methylation as an epigenetic marker of life adversity exposures in humans: A systematic review of literature.

    PubMed

    Provenzi, Livio; Giorda, Roberto; Beri, Silvana; Montirosso, Rosario

    2016-12-01

    The application of epigenetics to the study of behavioral and socio-emotional development in humans has revealed that DNA methylation could be a potential marker of adversity exposure and long-lasting programming of health and disease. The serotonin transporter gene (SLC6A4) is a stress-related gene which has well-documented implications for behavioral and socio-emotional development and which has been shown to be susceptible to transcriptional regulation via epigenetic mechanisms. In the present paper, a systematic review of papers assessing the association among adversity exposures, SLC6A4 methylation and developmental outcomes is reported. Nineteen studies were included. Findings revealed that SLC6A4 methylation has been investigated in humans in association with a number of prenatal and postnatal adverse exposures, encompassing maternal depression during pregnancy, perinatal stress exposure, childhood trauma and abuse, and environmental stress. SLC6A4 is confirmed as a relevant biomarker of early adversity exposures, and epigenetic mechanisms occurring at this gene appear to play a critical role for programming. Nonetheless, specific methodological issues still need to be addressed in future human behavioral epigenetic research.

  11. US EPA, Pesticide Product Label, METHYL BROMIDE ...

    EPA Pesticide Factsheets

    2011-04-21

    ... f\\.Jcl -' p"-)'» OJ\\d -~--~ L..h,.""'I(.~1 tb3~J"'..,J se(t·~~ IN'. 'T'1, Y I () / « f." ... 11"(1 k f- ,''' 7 .-Ir, f.ld,· ... L' -, t .... . t.. I·h) k.. .. , I ') t,/.) 'I)." ...

  12. Embryonic caffeine exposure acts via A1 adenosine receptors to alter adult cardiac function and DNA methylation in mice.

    PubMed

    Buscariollo, Daniela L; Fang, Xiefan; Greenwood, Victoria; Xue, Huiling; Rivkees, Scott A; Wendler, Christopher C

    2014-01-01

    Evidence indicates that disruption of normal prenatal development influences an individual's risk of developing obesity and cardiovascular disease as an adult. Thus, understanding how in utero exposure to chemical agents leads to increased susceptibility to adult diseases is a critical health related issue. Our aim was to determine whether adenosine A1 receptors (A1ARs) mediate the long-term effects of in utero caffeine exposure on cardiac function and whether these long-term effects are the result of changes in DNA methylation patterns in adult hearts. Pregnant A1AR knockout mice were treated with caffeine (20 mg/kg) or vehicle (0.09% NaCl) i.p. at embryonic day 8.5. This caffeine treatment results in serum levels equivalent to the consumption of 2-4 cups of coffee in humans. After dams gave birth, offspring were examined at 8-10 weeks of age. A1AR+/+ offspring treated in utero with caffeine were 10% heavier than vehicle controls. Using echocardiography, we observed altered cardiac function and morphology in adult mice exposed to caffeine in utero. Caffeine treatment decreased cardiac output by 11% and increased left ventricular wall thickness by 29% during diastole. Using DNA methylation arrays, we identified altered DNA methylation patterns in A1AR+/+ caffeine treated hearts, including 7719 differentially methylated regions (DMRs) within the genome and an overall decrease in DNA methylation of 26%. Analysis of genes associated with DMRs revealed that many are associated with cardiac hypertrophy. These data demonstrate that A1ARs mediate in utero caffeine effects on cardiac function and growth and that caffeine exposure leads to changes in DNA methylation.

  13. Embryonic Caffeine Exposure Acts via A1 Adenosine Receptors to Alter Adult Cardiac Function and DNA Methylation in Mice

    PubMed Central

    Greenwood, Victoria; Xue, Huiling; Rivkees, Scott A.; Wendler, Christopher C.

    2014-01-01

    Evidence indicates that disruption of normal prenatal development influences an individual's risk of developing obesity and cardiovascular disease as an adult. Thus, understanding how in utero exposure to chemical agents leads to increased susceptibility to adult diseases is a critical health related issue. Our aim was to determine whether adenosine A1 receptors (A1ARs) mediate the long-term effects of in utero caffeine exposure on cardiac function and whether these long-term effects are the result of changes in DNA methylation patterns in adult hearts. Pregnant A1AR knockout mice were treated with caffeine (20 mg/kg) or vehicle (0.09% NaCl) i.p. at embryonic day 8.5. This caffeine treatment results in serum levels equivalent to the consumption of 2–4 cups of coffee in humans. After dams gave birth, offspring were examined at 8–10 weeks of age. A1AR+/+ offspring treated in utero with caffeine were 10% heavier than vehicle controls. Using echocardiography, we observed altered cardiac function and morphology in adult mice exposed to caffeine in utero. Caffeine treatment decreased cardiac output by 11% and increased left ventricular wall thickness by 29% during diastole. Using DNA methylation arrays, we identified altered DNA methylation patterns in A1AR+/+ caffeine treated hearts, including 7719 differentially methylated regions (DMRs) within the genome and an overall decrease in DNA methylation of 26%. Analysis of genes associated with DMRs revealed that many are associated with cardiac hypertrophy. These data demonstrate that A1ARs mediate in utero caffeine effects on cardiac function and growth and that caffeine exposure leads to changes in DNA methylation. PMID:24475304

  14. Oxidative stress, telomere shortening, and DNA methylation in relation to low-to-moderate occupational exposure to welding fumes.

    PubMed

    Li, Huiqi; Hedmer, Maria; Wojdacz, Tomasz; Hossain, Mohammad Bakhtiar; Lindh, Christian H; Tinnerberg, Håkan; Albin, Maria; Broberg, Karin

    2015-10-01

    Evidence suggests that exposure to welding fumes is a risk factor for lung cancer. We examined relationships between low-to-moderate occupational exposure to particles from welding fumes and cancer-related biomarkers for oxidative stress, changes in telomere length, and alterations in DNA methylation. We enrolled 101 welders and 127 controls (all currently nonsmoking men) from southern Sweden. We performed personal sampling of respirable dust and measured 8-oxodG concentrations in urine using a simplified liquid chromatography tandem mass spectrometry method. Telomere length in peripheral blood was measured by quantitative polymerase chain reaction. Methylation status of 10 tumor suppressor genes was determined by methylation-sensitive high-resolution melting analysis. All analyses were adjusted for age, body mass index, previous smoking, passive smoking, current residence, and wood burning stove/boiler at home. Welders were exposed to respirable dust at 1.2 mg/m(3) (standard deviation, 3.3 mg/m(3); range, 0.1-19.3), whereas control exposures did not exceed 0.1 mg/m(3) (P < 0.001). Welders and controls did not differ in 8-oxodG levels (β = 1.2, P = 0.17) or relative telomere length (β = -0.053, P = 0.083) in adjusted models. Welders showed higher probability of adenomatous polyposis coli (APC) methylation in the unadjusted model (odds ratio = 14, P = 0.014), but this was not significant in the fully adjusted model (P = 0.052). Every working year as a welder was associated with 0.0066 units shorter telomeres (95% confidence interval -0.013 to -0.00053, P = 0.033). Although there were no clear associations between concentrations of respirable dust and the biomarkers, there were modest signs of associations between oxidative stress, telomere alterations, DNA methylation, and occupational exposure to low-to-moderate levels of particles.

  15. Arsenic exposure from drinking water is associated with decreased gene expression and increased DNA methylation in peripheral blood.

    PubMed

    Ameer, Syeda Shegufta; Engström, Karin; Hossain, Mohammad Bakhtiar; Concha, Gabriela; Vahter, Marie; Broberg, Karin

    2017-04-15

    Exposure to inorganic arsenic increases the risk of cancer and non-malignant diseases. Inefficient arsenic metabolism is a marker for susceptibility to arsenic toxicity. Arsenic may alter gene expression, possibly by altering DNA methylation. To elucidate the associations between arsenic exposure, gene expression, and DNA methylation in peripheral blood, and the modifying effects of arsenic metabolism. The study participants, women from the Andes, Argentina, were exposed to arsenic via drinking water. Arsenic exposure was assessed as the sum of arsenic metabolites in urine (U-As), using high performance liquid-chromatography hydride-generation inductively-coupled-plasma-mass-spectrometry, and arsenic metabolism efficiency was assessed by the urinary fractions (%) of the individual metabolites. Genome-wide gene expression (N=80 women) and DNA methylation (N=93; 80 overlapping with gene expression) in peripheral blood were measured using Illumina DirectHyb HumanHT-12 v4.0 and Infinium Human-Methylation 450K BeadChip, respectively. U-As concentrations, ranging 10-1251μg/L, was associated with decreased gene expression: 64% of the top 1000 differentially expressed genes were down-regulated with increasing U-As. U-As was also associated with hypermethylation: 87% of the top 1000CpGs were hypermethylated with increasing U-As. The expression of six genes and six individual CpG sites were significantly associated with increased U-As concentration. Pathway analyses revealed enrichment of genes related to cell death and cancer. The pathways differed somewhat depending on arsenic metabolism efficiency. We found no overlap between arsenic-related gene expression and DNA methylation for individual genes. Increased arsenic exposure was associated with lower gene expression and hypermethylation in peripheral blood, but with no evident overlap. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. LINE-1 methylation in granulocyte DNA and trihalomethane exposure is associated with bladder cancer risk

    PubMed Central

    Salas, Lucas A; Villanueva, Cristina M; Tajuddin, Salman M; Amaral, André F S; Fernandez, Agustín F; Moore, Lee E; Carrato, Alfredo; Tardón, Adonina; Serra, Consol; García-Closas, Reina; Basagaña, Xavier; Rothman, Nathaniel; Silverman, Debra T; Cantor, Kenneth P; Kogevinas, Manolis; Real, Francisco X; Fraga, Mario F; Malats, Núria

    2014-01-01

    DNA methylation changes contribute to bladder carcinogenesis. Trihalomethanes (THM), a class of disinfection by-products, are associated with increased urothelial bladder cancer (UBC) risk. THM exposure in animal models produces DNA hypomethylation. We evaluated the relationship of LINE-1 5-methylcytosine levels (LINE-1%5mC) as outcome of long-term THM exposure among controls and as an effect modifier in the association between THM exposure and UBC risk. We used a case-control study of UBC conducted in Spain. We obtained personal lifetime residential THM levels and measured LINE-1%5mC by pyrosequencing in granulocyte DNA from blood samples in 548 incident cases and 559 hospital controls. Two LINE-1%5mC clusters (above and below 64%) were identified through unsupervised hierarchical cluster analysis. The association between THM levels and LINE-1%5mC was evaluated with β regression analyses and logistic regression was used to estimate odds ratios (OR) adjusting for covariables. LINE-1%5mC change between percentiles 75th and 25th of THM levels was 1.8% (95% confidence interval (CI): 0.1, 3.4%) among controls. THM levels above vs. below the median (26 μg/L) were associated with increased UBC risk, OR = 1.86 (95% CI: 1.25, 2.75), overall and among subjects with low levels of LINE-1%5mC (n = 975), OR = 2.14 (95% CI: 1.39, 3.30), but not associated with UBC risk among subjects’ high levels of LINE-1%5mC (n = 162), interaction P = 0.03. Results suggest a positive association between LINE-1%5mC and THM levels among controls, and LINE-1%5mC status may modify the association between UBC risk and THM exposure. Because reverse causation and chance cannot be ruled out, confirmation studies are warranted. PMID:25482586

  17. LINE-1 methylation in granulocyte DNA and trihalomethane exposure is associated with bladder cancer risk.

    PubMed

    Salas, Lucas A; Villanueva, Cristina M; Tajuddin, Salman M; Amaral, André F S; Fernandez, Agustín F; Moore, Lee E; Carrato, Alfredo; Tardón, Adonina; Serra, Consol; García-Closas, Reina; Basagaña, Xavier; Rothman, Nathaniel; Silverman, Debra T; Cantor, Kenneth P; Kogevinas, Manolis; Real, Francisco X; Fraga, Mario F; Malats, Núria

    2014-11-01

    DNA methylation changes contribute to bladder carcinogenesis. Trihalomethanes (THM), a class of disinfection by-products, are associated with increased urothelial bladder cancer (UBC) risk. THM exposure in animal models produces DNA hypomethylation. We evaluated the relationship of LINE-1 5-methylcytosine levels (LINE-1%5mC) as outcome of long-term THM exposure among controls and as an effect modifier in the association between THM exposure and UBC risk. We used a case-control study of UBC conducted in Spain. We obtained personal lifetime residential THM levels and measured LINE-1%5mC by pyrosequencing in granulocyte DNA from blood samples in 548 incident cases and 559 hospital controls. Two LINE-1%5mC clusters (above and below 64%) were identified through unsupervised hierarchical cluster analysis. The association between THM levels and LINE-1%5mC was evaluated with β regression analyses and logistic regression was used to estimate odds ratios (OR) adjusting for covariables. LINE-1%5mC change between percentiles 75(th) and 25(th) of THM levels was 1.8% (95% confidence interval (CI): 0.1, 3.4%) among controls. THM levels above vs. below the median (26 μg/L) were associated with increased UBC risk, OR = 1.86 (95% CI: 1.25, 2.75), overall and among subjects with low levels of LINE-1%5mC (n = 975), OR = 2.14 (95% CI: 1.39, 3.30), but not associated with UBC risk among subjects' high levels of LINE-1%5mC (n = 162), interaction P = 0.03. Results suggest a positive association between LINE-1%5mC and THM levels among controls, and LINE-1%5mC status may modify the association between UBC risk and THM exposure. Because reverse causation and chance cannot be ruled out, confirmation studies are warranted.

  18. Effects of long-term low-dose cadmium exposure on genomic DNA methylation in human embryo lung fibroblast cells.

    PubMed

    Jiang, Gaofeng; Xu, Lei; Song, Shizhen; Zhu, Changcai; Wu, Qing; Zhang, Ling; Wu, Lei

    2008-02-03

    Cadmium is a toxic transition metal of continuing occupational and environmental concern. As a well-recognized human carcinogen, its carcinogenic mechanisms are still poorly understood. Cadmium has long been considered a non-genotoxic carcinogen and thought to act through epigenetic mechanisms. In the present study, we tested the effects of long-term low-dose cadmium exposure on DNA methylation in human embryo lung fibroblast (HLF) cells. After 2 months of exposure to 0-1.5 micromol/L cadmium, both the level of genomic DNA methylation and the enzyme activity of DNA methyltransferases (DNMTs) were increased in a concentration-related manner. Moreover, our results showed that cadmium exposure up-regulated the mRNA levels of DNMT1, DNMT3a and DNMT3b at higher concentrations. We further tested the growth dynamics of HLF cells, and observed significantly elevated growth rates, decreased cell population of G0/G1-phase and increased cell population of S-phase at 0.9, 1.2, and 1.5 micromol/L concentrations. Our study indicated that long-term low-dose cadmium exposure could disrupt DNA methylation, which may be one of the possible underlying carcinogenic mechanisms of cadmium.

  19. Exposure and response to methyl isocyanate: results of a community based survey in Bhopal.

    PubMed Central

    Andersson, N; Kerr Muir, M; Mehra, V; Salmon, A G

    1988-01-01

    In the two weeks immediately after the Bhopal disaster a community based survey was carried out in a series of eight exposed and two non-exposed clusters of households. The primary concern was the effect of the gas (subsequently identified as methyl isocyanate) on the eyes of the victims but data were also sought on respiratory status and the first symptoms of the exposure. No case of blindness was encountered that could be attributed to the gas. The most frequent symptoms reported were burning of the eyes, coughing, watering of the eyes, and vomiting. Among these, the frequency of cough most closely followed the rate of death in the different clusters. Although much rarer overall, the frequency of reported diarrhoea appeared to bear a stronger relation to death rates. Reports of photophobia and the clinical finding of superficial interpalpebral erosion of the cornea were more frequent where the death rates were lower. This clinical and epidemiological picture is consistent with different effects of the gas at different doses (as estimated from distance from the factory). PMID:3395582

  20. [Study of relationship between arsenic methylation and skin lesion in a population with long-term high arsenic exposure].

    PubMed

    Su, Liqin; Cheng, Yibin; Lin, Shaobin; Wu, Chuanye

    2007-05-01

    To investigate the difference of arsenic metabolism in populations with long-term high arsenic exposure and explore the relationship between arsenic metabolism diversity and skin lesion. 327 residents in an arsenic polluted village were voluntarily enrolled in this study. Questionnaire survey and medical examination were carried out to learn basic information and detect skin lesions. Urinary inorganic and methylated arsenic were speciated by high performance liquid chromatography combined with hydride-generation atomic fluorescence spectrometry. Total arsenic concentration in hair was determined with DDC-Ag method. Hair arsenic content of studied polutions was generally high, but no significant difference were found among the studied four groups. MMA and DMA concentration in urine increased with studied polution age, and were positively related with skin lesion grade. The relative proportion of MMA in serious skin lesion group was significantly higher than in other 3 groups, while DMA/MMA ratio was significantly lower than control and mild group. The relative proportion of MMA was positively related with skin lesion grade, DMA/ MMA ratio was negatively related with skin lesion grade. Males could have higher arsenic cumulation and lower methylation capacity than those of females. The population of above 40 years old may have higher methylation capacity than those of adults below 40yeas old. Smokers and drinkers seemed lower methylation capacity than those of non-smokers and non-drinkers respectively. The methylation of arsenic could affect by several factors, including age gender, smoking and drinking. Arsenic methylation copacity mey be associated with skin lesion induced by arsenic exposure.

  1. Prior exposure to oxidized low-density lipoprotein limits apoptosis in subsequent generations of endothelial cells by altering promoter methylation.

    PubMed

    Mitra, Sona; Khaidakov, Magomed; Lu, Jingjun; Ayyadevara, Srinivas; Szwedo, Jackob; Wang, Xian Wei; Chen, Chien; Khaidakov, Said; Kasula, Srikanth Reddy; Stone, Annjanette; Pogribny, Igor; Mehta, Jawahar L

    2011-08-01

    Oxidized LDL (ox-LDL) plays a critical role in atherogenesis, including apoptosis. As hypercholesterolemia causes epigenetic changes resulting in long-term phenotypic consequences, we hypothesized that repeated and continuous exposure to ox-LDL may alter the pattern of apoptosis in human umbilical vein endothelial cells (HUVECs). We also analyzed global and promoter-specific methylation of apoptosis-related genes. As expected, ox-LDL evoked a dose-dependent increase in apoptosis in the first passage HUVECs that was completely abrogated by lectin-like ox-LDL receptor (LOX-1)-neutralizing antibody. Ox-LDL-induced apoptosis was associated with upregulation of proapoptotic LOX-1, ANXA5, BAX, and CASP3 and inhibition of antiapoptotic BCL2 and cIAP-1 genes accompanied with reciprocal changes in the methylation of promoter regions of these genes. Subsequent passages of cells displayed attenuated apoptotic response to repeat ox-LDL challenge with blunted gene expression and exaggerated methylation of LOX-1, BAX, ANXA5, and CASP3 genes (all P < 0.05 vs. first exposure to ox-LDL). Treatment of cells with LOX-1 antibody before initial ox-LDL treatment prevented both gene-specific promoter methylation and expression changes and reduction of apoptotic response to repeat ox-LDL challenge. Based on these data, we conclude that exposure of HUVECs to ox-LDL induces epigenetic changes leading to resistance to apoptosis in subsequent generations and that this effect may be related to the LOX-1-mediated increase in DNA methylation.

  2. N-methylsuccinimide in plasma and urine as a biomarker of exposure to N-methyl-2-pyrrolidone.

    PubMed

    Jönsson, B A; Akesson, B

    2001-05-01

    N-Methyl-2-pyrrolidone (NMP) is a selective and powerful organic solvent. The aim of this study was to investigate whether the NMP metabolite N-methylsuccinimide (MSI) in plasma and urine can be used as a biomarker of exposure to NMP. Six healthy subjects were exposed to 10, 25, and 50 mg NMP/m3 in an exposure chamber for 8 h. The air levels were monitored by XAD-7 solid sorbent sampling, and analysed by gas chromatography (GC). Plasma and urine were sampled for two days following the exposure, and the levels of MSI were analysed by GC with mass spectrometric detection. The concentration of MSI in plasma and urine rose during the exposure, and reached a peak at about 4 h after the end of the exposure. The concentration then decayed according to a one-compartment model with a half-time of approximately 8 h. About 1% of the inhaled NMP was excreted in urine as MSI. There were very close correlations between the NMP air levels and, on the one hand, the MSI concentrations in plasma collected at the end of exposure (r = 0.98), or the urinary MSI concentration collected during the last 2 h of exposure (r = 0.96), on the other. MSI in plasma or urine is applicable as a biomarker of exposure to NMP. The concentration in plasma and urine mainly reflects the exposure over one day.

  3. A panel study of occupational exposure to fine particulate matter and changes in DNA methylation over a single workday and years worked in boilermaker welders

    PubMed Central

    2013-01-01

    Background Exposure to pollutants including metals and particulate air pollution can alter DNA methylation. Yet little is known about intra-individual changes in DNA methylation over time in relationship to environmental exposures. Therefore, we evaluated the effects of acute- and chronic metal-rich PM2.5 exposures on DNA methylation. Methods Thirty-eight male boilermaker welders participated in a panel study for a total of 54 person days. Whole blood was collected prior to any welding activities (pre-shift) and immediately after the exposure period (post-shift). The percentage of methylated cytosines (%mC) in LINE-1, Alu, and inducible nitric oxide synthase gene (iNOS) were quantified using pyrosequencing. Personal PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 μm) was measured over the work-shift. A questionnaire assessed job history and years worked as a boilermaker. Linear mixed models with repeated measures evaluated associations between DNA methylation, PM2.5 concentration (acute exposure), and years worked as a boilermaker (chronic exposure). Results PM2.5 exposure was associated with increased methylation in the promoter region of the iNOS gene (β = 0.25, SE: 0.11, p-value = 0.04). Additionally, the number of years worked as a boilermaker was associated with increased iNOS methylation (β = 0.03, SE: 0.01, p-value = 0.03). No associations were observed for Alu or LINE-1. Conclusions Acute and chronic exposure to PM2.5 generated from welding activities was associated with a modest change in DNA methylation of the iNOS gene. Future studies are needed to confirm this association and determine if the observed small increase in iNOS methylation are associated with changes in NO production or any adverse health effect. PMID:23758843

  4. Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the DNA Methylation Patterns of Genes Involved in Lipid Metabolism

    NASA Astrophysics Data System (ADS)

    Ke, Zhang-Hong; Pan, Jie-Xue; Jin, Lu-Yang; Xu, Hai-Yan; Yu, Tian-Tian; Ullah, Kamran; Rahman, Tanzil Ur; Ren, Jun; Cheng, Yi; Dong, Xin-Yan; Sheng, Jian-Zhong; Huang, He-Feng

    2016-08-01

    Accumulating evidence suggests a role of bisphenol A (BPA) in metabolic disorders. However, the underlying mechanism is still unclear. Using a mouse BPA exposure model, we investigated the effects of long-term BPA exposure on lipid metabolism and the underlying mechanisms. The male mice exposed to BPA (0.5 μg BPA /kg/day, a human relevant dose) for 10 months exhibited significant hepatic accumulation of triglycerides and cholesterol. The liver cells from the BPA-exposed mice showed significantly increased expression levels of the genes related to lipid synthesis. These liver cells showed decreased DNA methylation levels of Srebf1 and Srebf2, and increased expression levels of Srebf1 and Srebf2 that may upregulate the genes related to lipid synthesis. The expression levels of DNA methyltransferases were decreased in BPA-exposed mouse liver. Hepa1-6 cell line treated with BPA showed decreased expression levels of DNA methyltransferases and increased expression levels of genes involved in lipid synthesis. DNA methyltransferase knockdown in Hepa1-6 led to hypo-methylation and increased expression levels of genes involved in lipid synthesis. Our results suggest that long-term BPA exposure could induce hepatic lipid accumulation, which may be due to the epigenetic reprogramming of the genes involved in lipid metabolism, such as the alterations of DNA methylation patterns.

  5. Functional evidence of persistent airway obstruction in rats following a two-hour inhalation exposure to methyl isocyanate.

    PubMed Central

    Stevens, M A; Fitzgerald, S; Ménache, M G; Costa, D L; Bucher, J R

    1987-01-01

    Pulmonary function was assessed in male, F344 rats 1,2,4,7, and 13 weeks after a single 2-hr exposure to 0, 3, 10, or 30 ppm methyl isocyanate. No significant changes were observed in the rats exposed to 3 ppm through 13 weeks. Diffusing capacity (DLco), quasistatic lung compliance, and homogeneity of ventilation, as determined by multibreath nitrogen washout, were depressed in the rats exposed to 10 and 30 ppm by 1 week after exposure. None of the rats exposed to 30 ppm survived beyond 1 week. By 13 weeks, dramatic increases in lung volumes were observed in the rats exposed to 10 ppm, while DLco and lung compliance were only mildly affected. However, volume-specific DLco and compliance were depressed in the rats exposed to 10 ppm, suggesting that lung hyperinflation or other compensatory means of increasing lung size occurred in response to the methyl isocyanate-induced lung lesion. This group also exhibited increased expiratory times during tidal breathing and severely impaired distribution of ventilated air. Collectively, these results suggest the development and likely progression of a severe, obstructive airway lesion with associated gas trapping, and the existence of a pronounced concentration-response relationship between 3 and 10 ppm methyl isocyanate exposures. PMID:3622448

  6. Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the DNA Methylation Patterns of Genes Involved in Lipid Metabolism

    PubMed Central

    Ke, Zhang-Hong; Pan, Jie-Xue; Jin, Lu-Yang; Xu, Hai-Yan; Yu, Tian-Tian; Ullah, Kamran; Rahman, Tanzil Ur; Ren, Jun; Cheng, Yi; Dong, Xin-Yan; Sheng, Jian-Zhong; Huang, He-Feng

    2016-01-01

    Accumulating evidence suggests a role of bisphenol A (BPA) in metabolic disorders. However, the underlying mechanism is still unclear. Using a mouse BPA exposure model, we investigated the effects of long-term BPA exposure on lipid metabolism and the underlying mechanisms. The male mice exposed to BPA (0.5 μg BPA /kg/day, a human relevant dose) for 10 months exhibited significant hepatic accumulation of triglycerides and cholesterol. The liver cells from the BPA-exposed mice showed significantly increased expression levels of the genes related to lipid synthesis. These liver cells showed decreased DNA methylation levels of Srebf1 and Srebf2, and increased expression levels of Srebf1 and Srebf2 that may upregulate the genes related to lipid synthesis. The expression levels of DNA methyltransferases were decreased in BPA-exposed mouse liver. Hepa1-6 cell line treated with BPA showed decreased expression levels of DNA methyltransferases and increased expression levels of genes involved in lipid synthesis. DNA methyltransferase knockdown in Hepa1-6 led to hypo-methylation and increased expression levels of genes involved in lipid synthesis. Our results suggest that long-term BPA exposure could induce hepatic lipid accumulation, which may be due to the epigenetic reprogramming of the genes involved in lipid metabolism, such as the alterations of DNA methylation patterns. PMID:27502578

  7. Genetic variants, PM2.5 exposure level and global DNA methylation level: A multi-center population-based study in Chinese.

    PubMed

    Liu, Jia; Xie, Kaipeng; Chen, Weihong; Zhu, Meng; Shen, Wei; Yuan, Jing; Cheng, Yang; Geng, Liguo; Wang, Yuzhuo; Li, Zhihua; Zhang, Jiahui; Jin, Guangfu; Dai, Juncheng; Ma, Hongxia; Du, Jiangbo; Wang, Meilin; Zhang, Zhengdong; Hu, Zhibin; Wu, Tangchun; Shen, Hongbing

    2017-03-05

    Global DNA methylation levels can be determined by environmental and genetic factors. There are emerging evidences that methylation status can be modified as exposed to environmental factors such as PM2.5, but the genetic determinants are still largely unknown. To explore whether genetic variants contribute to global DNA methylation levels with consideration of environmental exposures, we systematically evaluated the association between genetic variants and global DNA methylation levels in 301 subjects from three cities in southern, central and northern China with different PM2.5 exposure levels (Zhuhai, Wuhan and Tianjin, respectively). Personal 24-h PM2.5 exposure levels and global DNA methylation levels for each subject were evaluated. Using Illumina Human Exome BeadChip, 241,305 SNVs was genotyped and assessed for their association with global DNA methylation levels. We found that after adjusting for age, gender, PM2.5 exposure level, pack-years of smoking and BMI, 14 SNVs were consistently associated with global DNA methylation levels with pooled P≤1.00×10(-4) after meta-analysis of three cohorts, in which 8 SNVs together with age were independent factors modifying global DNA methylation levels. Joint analysis of these identified SNVs showed a significant allele-dosage association between the number of variants and global DNA methylation levels (P=1.82×10(-23)). In particular, we detected a significant multiplicative interaction between rs4344916 on chromosome 2p22.3 and PM2.5 exposure on global DNA methylation level (P=0.0095). Our findings indicate that genetic variants alone or in combination with PM2.5 play an important role in modifying individual global DNA methylation levels. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. High pesticide exposure events and DNA methylation among pesticide applicators in the agricultural health study.

    PubMed

    Rusiecki, Jennifer A; Beane Freeman, Laura E; Bonner, Matthew R; Alexander, Melannie; Chen, Ligong; Andreotti, Gabriella; Barry, Kathryn H; Moore, Lee E; Byun, Hyang-Min; Kamel, Freya; Alavanja, Michael; Hoppin, Jane A; Baccarelli, Andrea

    2017-01-01

    Pesticide exposure has been associated with acute and chronic adverse health effects. DNA methylation (DNAm) may mediate these effects. We evaluated the association between experiencing unusually high pesticide exposure events (HPEEs) and DNAm among pesticide applicators in the Agricultural Health Study (AHS), a prospective study of applicators from Iowa and North Carolina. DNA was extracted from whole blood from male AHS pesticide applicators (n = 695). Questionnaire data were used to ascertain the occurrence of HPEEs over the participant's lifetime. Pyrosequencing was used to quantify DNAm in CDH1, GSTp1, and MGMT promoters, and in the repetitive element, LINE-1. Linear and robust regression analyses evaluated adjusted associations between HPEE and DNAm. Ever having an HPEE (n = 142; 24%) was associated with elevated DNAm in the GSTp1 promoter at CpG7 (chr11:67,351,134; P < 0.01) and for the mean across the CpGs measured in the GSTp1 promoter (P < 0.01). In stratified analyses, elevated GSTP1 promoter DNAm associated with HPEE was more pronounced among applicators >59 years and those with plasma folate levels ≤16.56 ng/mL (p-interaction <0.01); HPEE was associated with reduced MGMT promoter DNAm at CpG2 (chr10:131,265,803; P = 0.03), CpG3 (chr10:131,265,810; P = 0.05), and the mean across CpGs measured in the MGMT promoter (P = 0.03) among applicators >59 years and reduced LINE-1 DNAm (P = 0.05) among applicators with ≤16.56 ng/mL plasma folate. Non-specific HPEEs may contribute to increased DNAm in GSTp1, and in some groups, reduced DNAm in MGMT and LINE-1. The impacts of these alterations on disease development are unclear, but elevated GSTp1 promoter DNAm and subsequent gene inactivation has been consistently associated with prostate cancer. Environ. Mol. Mutagen. 58:19-29, 2017. © 2016 Wiley Periodicals, Inc.

  9. Lead (Pb) exposure reduces global DNA methylation level by non-competitive inhibition and alteration of dnmt expression.

    PubMed

    Sanchez, Oscar F; Lee, Jinyoung; Yu King Hing, Nathaphon; Kim, Seong-Eun; Freeman, Jennifer L; Yuan, Chongli

    2017-02-22

    Low-dose exposure to lead (Pb) is connected to developmental neurological alterations by inducing molecular changes, such as aberrant gene expression patterns. The attributing molecular mechanism, however, is not well-elucidated. In this study, we revealed epigenetic features and mechanisms that can alter gene expression patterns by identifying changes in DNA methyltransferase (DNMT) activity, expression pattern and DNA methylation level using moelcular studies and a zebrafish animal model. We characterized the effects of Pb on the activities of various DNMTs in vitro and determined the molecular role of Pb in modulating DNMT activity via kinetic experiments. An exposure of 100 or 500 ppb of Pb was found to significantly lower the activity of maintenance DNMTs. The inhibition mechanism can be described using non-competitive Michaelis-Menten kinetics. A zebrafish animal model was then used to assess the biological significance of our findings. An embryonic exposure to 100 or 500 ppb Pb resulted in a significant change in global methylation levels consistent with previous studies using human and rodent model. Our study also suggests that Pb exposure in zebrafish alters the expression patterns of dnmt3 and dnmt4 which are human DNMT3b orthologs. The knowledge from this study suggests that Pb exposure can affect the activity of maintenance DNMTs via non-competitive inhibition, which has not been reported previously. Meanwhile, the expression pattern of de novo methyltransferases can also be altered. Collectively, they result in a reduction in global DNA methylation level in Pb-exposed zebrafish model, which can be compared to findings in human and rodent studies.

  10. Associations of risk factors obesity and occupational airborne exposures with CDKN2A/p16 aberrant DNA methylation in esophageal cancer patients.

    PubMed

    Mohammad Ganji, S; Miotto, E; Callegari, E; Sayehmiri, K; Fereidooni, F; Yazdanbod, M; Rastgar-Jazii, F; Negrini, M

    2010-09-01

    It is known that obesity and occupational airborne exposure such as dust are among risk factors of esophageal cancer development, in particular squamous cell carcinoma (SCC) of esophagus. Here, we tested whether these factors could also affect aberrant DNA methylation. DNAs from 44 fresh tumor tissues and 19 non-tumor adjacent normal tissues, obtained from 44 patients affected by SCC of esophagus (SCCE), were studied for methylation at the CDKN2A/p16 gene promoter by methylation-specific polymerase chain reaction assay. Statistical methods were used to assess association of promoter methylation with biopathological, clinical, and personal information data, including obesity and airborne exposures. Methylation at the CDKN2A/p16 gene promoter was detected in 12 out of 44 tumor samples. None of the non-tumor tissues exhibited the aberrant methylation. Our results confirmed previously described significant association with low tumor stage (P= 0.002); in addition, we found that obesity (P= 0.001) and occupational exposure (P= 0.008) were both significantly associated with CDKN2A/p16 promoter methylation. This study provides evidence that obesity and occupational exposure increase the risk of developing esophageal cancer through an enhancement of CDKN2A/p16 promoter methylation.

  11. Association of Global DNA Methylation and Global DNA Hydroxymethylation with Metals and Other Exposures in Human Blood DNA Samples

    PubMed Central

    Tang, Wan-yee; Shang, Yan; Umans, Jason G.; Francesconi, Kevin A.; Goessler, Walter; Ledesma, Marta; Leon, Montserrat; Laclaustra, Martin; Pollak, Jonathan; Guallar, Eliseo; Cole, Shelley A.; Fallin, M. Dani; Navas-Acien, Ana

    2014-01-01

    Background: The association between human blood DNA global methylation and global hydroxymethylation has not been evaluated in population-based studies. No studies have evaluated environmental determinants of global DNA hydroxymethylation, including exposure to metals. Objective: We evaluated the association between global DNA methylation and global DNA hydroxymethylation in 48 Strong Heart Study participants for which selected metals had been measured in urine at baseline and DNA was available from 1989–1991 (visit 1) and 1998–1999 (visit 3). Methods: We measured the percentage of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in samples using capture and detection antibodies followed by colorimetric quantification. We explored the association of participant characteristics (i.e., age, adiposity, smoking, and metal exposure) with both global DNA methylation and global DNA hydroxymethylation. Results: The Spearman’s correlation coefficient for 5-mC and 5-hmC levels was 0.32 (p = 0.03) at visit 1 and 0.54 (p < 0.001) at visit 3. Trends for both epigenetic modifications were consistent across potential determinants. In cross-sectional analyses, the odds ratios of methylated and hydroxymethylated DNA were 1.56 (95% CI: 0.95, 2.57) and 1.76 (95% CI: 1.07, 2.88), respectively, for the comparison of participants above and below the median percentage of dimethylarsinate. The corresponding odds ratios were 1.64 (95% CI: 1.02, 2.65) and 1.16 (95% CI: 0.70, 1.94), respectively, for the comparison of participants above and below the median cadmium level. Arsenic exposure and metabolism were consistently associated with both epigenetic markers in cross-sectional and prospective analyses. The positive correlation of 5-mC and 5-hmC levels was confirmed in an independent study population. Conclusions: Our findings support that both epigenetic measures are related at the population level. The consistent trends in the associations between these two epigenetic

  12. DNA Methylation-Independent Growth Restriction and Altered Developmental Programming in a Mouse Model of Preconception Male Alcohol Exposure.

    PubMed

    Chang, Richard C; Skiles, William M; Sarah, S Chronister; Wang, Haiqing; Sutton, Gabrielle I; Bedi, Yudhishtar S; Snyder, Matthew; Long, Charles R; Golding, Michael C

    2017-08-17

    The preconception environment is a significant modifier of dysgenesis and the development of environmentally-induced disease. To date, Fetal Alcohol Spectrum Disorders (FASDs) have been exclusively associated with maternal exposures, yet emerging evidence suggests male-inherited alterations in the developmental program of sperm may be relevant to the growth-restriction phenotypes of this condition. Using a mouse model of voluntary consumption, we find chronic preconception male ethanol exposure associates with fetal growth restriction, decreased placental efficiency, abnormalities in cholesterol trafficking, sex-specific alterations in the genetic pathways regulating hepatic fibrosis, and disruptions in the regulation of imprinted genes. Alterations in the DNA methylation profiles of imprinted loci have been identified in clinical studies of alcoholic sperm, suggesting the legacy of paternal drinking may transmit via heritable disruptions in the regulation of imprinted genes. However, the capacity of sperm-inherited changes in DNA methylation to broadly transmit environmentally-induced phenotypes remains unconfirmed. Using bisulphite mutagenesis and second-generation deep sequencing, we find no evidence to suggest that these phenotypes or any of the associated transcriptional changes are linked to alterations in the sperm-inherited DNA methylation profile. These observations are consistent with recent studies examining the male transmission of diet-induced phenotypes and emphasize the importance of epigenetic mechanisms of paternal inheritance beyond DNA methylation. This study challenges the singular importance of maternal alcohol exposures and suggests paternal alcohol abuse is a significant, yet overlooked epidemiological factor complicit in the genesis of alcohol-induced growth defects, and may provide mechanistic insight into the failure of FASD children to thrive postnatally.

  13. Long-term parental methamphetamine exposure of mice influences behavior and hippocampal DNA methylation of the offspring.

    PubMed

    Itzhak, Y; Ergui, I; Young, J I

    2015-02-01

    The high rate of methamphetamine (METH) abuse among young adults and women of childbearing age makes it imperative to determine the long-term effects of METH exposure on the offspring. We hypothesized that parental METH exposure modulates offspring behavior by disrupting epigenetic programming of gene expression in the brain. To simulate the human pattern of drug use, male and female C57Bl/6J mice were exposed to escalating doses of METH or saline from adolescence through adulthood; following mating, females continue to receive drug or saline through gestational day 17. F1 METH male offspring showed enhanced response to cocaine-conditioned reward and hyperlocomotion. Both F1 METH male and female offspring had reduced response to conditioned fear. Cross-fostering experiments have shown that certain behavioral phenotypes were modulated by maternal care of either METH or saline dams. Analysis of offspring hippocampal DNA methylation showed differentially methylated regions as a result of both METH in utero exposure and maternal care. Our results suggest that behavioral phenotypes and epigenotypes of offspring that were exposed to METH in utero are vulnerable to (a) METH exposure during embryonic development, a period when wide epigenetic reprogramming occurs, and (b) postnatal maternal care.

  14. Gene-specific differential DNA methylation and chronic arsenic exposure in an epigenome-wide association study of adults in Bangladesh.

    PubMed

    Argos, Maria; Chen, Lin; Jasmine, Farzana; Tong, Lin; Pierce, Brandon L; Roy, Shantanu; Paul-Brutus, Rachelle; Gamble, Mary V; Harper, Kristin N; Parvez, Faruque; Rahman, Mahfuzar; Rakibuz-Zaman, Muhammad; Slavkovich, Vesna; Baron, John A; Graziano, Joseph H; Kibriya, Muhammad G; Ahsan, Habibul

    2015-01-01

    Inorganic arsenic is one of the most common naturally occurring contaminants found in the environment. Arsenic is associated with a number of health outcomes, with epigenetic modification suggested as a potential mechanism of toxicity. Among a sample of 400 adult participants, we evaluated the association between arsenic exposure, as measured by blood and urinary total arsenic concentrations, and epigenome-wide white blood cell DNA methylation. We used linear regression models to examine the associations between arsenic exposure and methylation at each CpG site, adjusted for sex, age, and batch. Differentially methylated loci were subsequently examined in relation to corresponding gene expression for functional evidence of gene regulation. In adjusted analyses, we observed four differentially methylated CpG sites with urinary total arsenic concentration and three differentially methylated CpG sites with blood arsenic concentration, based on the Bonferroni-corrected significance threshold of p < 1 × 10(-7). Methylation of PLA2G2C (probe cg04605617) was the most significantly associated locus in relation to both urinary (p = 3.40 × 10(-11)) and blood arsenic concentrations (p = 1.48 × 10(-11)). Three additional novel methylation loci-SQSTM1 (cg01225779), SLC4A4 (cg06121226), and IGH (cg13651690)--were also significantly associated with arsenic exposure. Further, there was evidence of methylation-related gene regulation based on gene expression for a subset of differentially methylated loci. We observed significant associations between arsenic exposure and gene-specific differential white blood cell DNA methylation, suggesting that epigenetic modifications may be an important pathway underlying arsenic toxicity. The specific differentially methylated loci identified may inform potential pathways for future interventions.

  15. Hair analysis as a useful procedure for detection of vapour exposure to chemical warfare agents: simulation of sulphur mustard with methyl salicylate.

    PubMed

    Spiandore, Marie; Piram, Anne; Lacoste, Alexandre; Josse, Denis; Doumenq, Pierre

    2014-06-01

    Chemical warfare agents (CWA) are highly toxic compounds which have been produced to kill or hurt people during conflicts or terrorist attacks. Despite the fact that their use is strictly prohibited according to international convention, populations' exposure still recently occurred. Development of markers of exposure to CWA is necessary to distinguish exposed victims from unexposed ones. We present the first study of hair usage as passive sampler to assess contamination by chemicals in vapour form. This work presents more particularly the hair adsorption capacity for methyl salicylate used as a surrogate of the vesicant sulphur mustard. Chemical vapours toxicity through the respiratory route has historically been defined through Haber's law's concentration-time (Ct) product, and vapour exposure of hair to methyl salicylate was conducted with various times or doses of exposure in the range of incapacitating and lethal Ct products corresponding to sulphur mustard. Following exposure, extraction of methyl salicylate from hair was conducted by simple soaking in dichloromethane. Methyl salicylate could be detected on hair for vapour concentration corresponding to about one fifth of the sulphur mustard concentration that would kill 50% of exposed individuals (LCt50). The amount of methyl salicylate recovered from hair increased with time or dose of exposure. It showed a good correlation with the concentration-time product, suggesting that hair could be used like a passive sampler to assess vapour exposure to chemical compounds. It introduces great perspectives concerning the use of hair as a marker of exposure to CWA.

  16. Interfield and intrafield variability of methyl halide emissions from rice paddies

    NASA Astrophysics Data System (ADS)

    Redeker, K. R.; Andrews, J.; Fisher, F.; Sass, R.; Cicerone, R. J.

    2002-12-01

    Methyl halide gases are important sources of atmospheric inorganic halogen radicals. We measured methyl halide emissions from three rice fields over two full growing seasons. Rice paddy emissions of methyl chloride, methyl bromide and methyl iodide are insignificant until field flooding. Rice growth stage determines methyl bromide and methyl iodide emissions while methyl chloride emissions are comparable between planted and unplanted plots. Houston, Texas, and Maxwell, California, field integrated seasonal fluxes of methyl chloride, methyl bromide and methyl iodide are consistent (values range from 2.3 to 3.9, 0.8 to 1.1, and 28.1 to 62.0 mg m-2, respectively) despite differences in multiple field parameters. We also examined field emission variability using 12 chamber placements. Methyl bromide and methyl iodide emissions within homogenous rice paddies require at least three replicates to determine field mean fluxes within 20%, and for methyl chloride emissions, over 10 replications per field are necessary.

  17. Interplay between Cellular Methyl Metabolism and Adaptive Efflux during Oncogenic Transformation from Chronic Arsenic Exposure in Human Cells*S⃞

    PubMed Central

    Coppin, Jean-François; Qu, Wei; Waalkes, Michael P.

    2008-01-01

    After protracted low level arsenic exposure, the normal human prostate epithelial cell line RWPE-1 acquires a malignant phenotype with DNA hypomethylation, indicative of disrupted methyl metabolism, and shows arsenic adaptation involving glutathione overproduction and enhanced arsenic efflux. Thus, the interplay between methyl and glutathione metabolism during this progressive arsenic adaptation was studied. Arsenic-treated cells showed a time-dependent increase in LC50 and a marked increase in homocysteine (Hcy) levels. A marked suppression of S-adenosylmethionine (SAM) levels occurred with decreased methionine adenosyltransferase 2A (converts methionine to SAM) expression and increased negative regulator methionine adenosyltransferase B, suggesting reduced conversion of Hcy to SAM. Consistent with Hcy overproduction, activity and expression of S-adenosylhomocysteine hydrolase (converts S-adenosylhomocysteine to Hcy) were both increased. Expression of cystathionine β-synthase, a key gene in the transsulfuration pathway, and various glutathione production genes were increased, resulting in a 5-fold increase in glutathione. Arsenic efflux increased along with expression of ATP-binding cassette protein C1, which effluxes arsenic as a glutathione conjugate. Evidence of genomic DNA hypomethylation was observed during early arsenic exposure, indicating that the disruption in methyl metabolism had a potential impact related to oncogenesis. Thus, cellular arsenic adaptation is a dynamic, progressive process that involves decreased SAM recycling and concurrent accumulation of Hcy, which is channeled via transsulfuration to increase glutathione and enhance arsenic efflux but may also impact the carcinogenic process. PMID:18487201

  18. Effects of Exposure to Methyl Parathion on Egg Hatchability and Eggshell Chemical Composition in Podocnemis expansa (Testudines, Podocnemididae).

    PubMed

    Valdes, Sady Alexis Chavauty; Vieira, Lucélia Gonçalves; Ferreira, Caio Henrique; dos Santos Mendonça, Juliana; Ribeiro, Priscilla Rosa Queiroz; de Abreu Fernandes, Evandro; Santos, André Luiz Quagliatto

    2015-04-01

    Eggshell evaluation may serve as an indicator of the effect of substances released in the environment, which may change eggshell shape, size, structure, and/or chemical composition. Additionally, exposure may interfere with hatching rates in contaminated eggs. The objective of this study was to better understand how exposure to the insecticide methyl parathion interferes with chemical changes in eggshells of Podocnemis expansa throughout their artificial incubation, as well as with egg hatchability. A total of 343 P. expansa eggs were collected in a natural reproduction area for the species. These eggs were transferred to and artificially incubated in the Wild Animal Teaching and Research Laboratory at Universidade Federal de Uberlândia. On the first day of artificial incubation, 0, 35, 350, and 3500 ppb of methyl parathion were incorporated to the substrate. Eggs were collected every three days for chemical analysis of eggshells. Hatchability was evaluated as the number of hatchlings in each treatment, for the eggs that were not used in the chemical analysis. Student's T-test was used for data on eggshell chemical composition, and the Binomial Test for Two Proportions was used in the hatchability analysis, at a 5% significance level. It was observed that the incorporation of methyl parathion to the substrate on the first day of artificial incubation of P. expansa eggs reduced the levels of total fat in the shells throughout their incubation, besides reducing egg hatchability.

  19. Interfacial chemistry of poly(methyl methacrylate) arising from exposure to vacuum-ultraviolet light and atomic oxygen.

    PubMed

    Yuan, Hanqiu; Killelea, Daniel R; Tepavcevic, Sanja; Kelber, Scott I; Sibener, S J

    2011-04-28

    We herein report on the chemical and physical changes that occur in thin films of poly(methyl methacrylate), PMMA, induced by exposure to high-energy vacuum ultraviolet radiation and a supersonic beam of neutral, ground electronic state O((3)P) atomic oxygen. A combination of in situ quartz crystal microbalance and in situ Fourier-transform infrared reflection-absorption spectroscopy were used to determine the photochemical reaction kinetics and mechanisms during irradiation. The surface morphological changes were measured with atomic force microscopy. The results showed there was no enhancement in the mass loss rate during simultaneous exposure of vacuum ultraviolet (VUV) radiation and atomic oxygen. Rather, the rate of mass loss was impeded when the polymer film was exposed to both reagents. This study elucidates the kinetics of photochemical and oxidative reaction for PMMA, and shows that the synergistic effect involving VUV irradiation and exposure to ground state atomic oxygen depends substantially on the relative fluxes of these reagents.

  20. Chronic neuropsychological and neurological impairment following acute exposure to a solvent mixture of toluene and methyl ethyl ketone (MEK).

    PubMed

    Welch, L; Kirshner, H; Heath, A; Gilliland, R; Broyles, S

    1991-01-01

    A 38 year-old laborer experienced solvent intoxication during each of two spray paintings of a dump truck and other heavy equipment in an enclosed, unventilated garage. The paint base consisted primarily of toluene and methyl ethyl ketone. Nausea, headaches, dizziness, respiratory difficulty and other symptoms began after exposures. Over the next several days he developed impaired concentration, memory loss and cerebellar signs including an intention tremor, gait ataxia and dysarthria. MRI of the brain and EGG early in the work-up were normal, although later MRIs demonstrated fluid collection over the left parietal area. Examination by a toxicologist and neurologist revealed likely toxic encephalopathy with dementia and cerebellar ataxia. Three formal neuropsychological assessments over 2 1/2 years quantified cognitive, motor and behavioral changes. Despite similar findings in chronic exposure to these solvents, lasting sequelae following acute exposure have not been widely reported.

  1. Passive Sampling for Indoor and Outdoor Exposures to Chlorpyrifos, Azinphos-Methyl, and Oxygen Analogs in a Rural Agricultural Community

    PubMed Central

    Gibbs, Jenna L.; Yost, Michael G.; Negrete, Maria; Fenske, Richard A.

    2016-01-01

    oxygen analogs in air and highlight their potential for infiltration of indoor living environments. Citation: Gibbs JL, Yost MG, Negrete M, Fenske RA. 2017. Passive sampling for indoor and outdoor exposures to chlorpyrifos, azinphos-methyl, and oxygen analogs in a rural agricultural community. Environ Health Perspect 125:333–341; http://dx.doi.org/10.1289/EHP425 PMID:27517732

  2. Mercury Bromide Laser Research.

    DTIC Science & Technology

    1981-05-04

    Discharge", Optics Lett., 2(3), (March 1978). 7. R. Burnham, "Discharge Pumped Mercuric Halide Dissociation Lasers", Appl. Phys. Lett., 33: 15 (July 1978...laser and fluorescence signals. Neutral density filters served to prevent saturation of the detector during the laser measurements. F. Laser Output as a...REFERENCES . E. J. Schimitschek and J. E. Celto, " Mercuric Bromide Dissociation Laser in an Electric Discharge," Optics Lett. 2(3), March 1978. This

  3. Model Averaging for Predicting the Exposure to Aflatoxin B1 Using DNA Methylation in White Blood Cells of Infants

    NASA Astrophysics Data System (ADS)

    Rahardiantoro, S.; Sartono, B.; Kurnia, A.

    2017-03-01

    In recent years, DNA methylation has been the special issue to reveal the pattern of a lot of human diseases. Huge amount of data would be the inescapable phenomenon in this case. In addition, some researchers interesting to take some predictions based on these huge data, especially using regression analysis. The classical approach would be failed to take the task. Model averaging by Ando and Li [1] could be an alternative approach to face this problem. This research applied the model averaging to get the best prediction in high dimension of data. In the practice, the case study by Vargas et al [3], data of exposure to aflatoxin B1 (AFB1) and DNA methylation in white blood cells of infants in The Gambia, take the implementation of model averaging. The best ensemble model selected based on the minimum of MAPE, MAE, and MSE of predictions. The result is ensemble model by model averaging with number of predictors in model candidate is 15.

  4. Methylation of the estrogen receptor CpG island in lung tumors is related to the specific type of carcinogen exposure

    SciTech Connect

    Issa, J.P.J.; Baylin, S.B.; Belinsky, S.A. |

    1996-08-15

    Promoter methylation has recently been shown to be an alternative to mutation in inactivating tumor suppressor genes in human neoplasia. Although specific carcinogen exposures have been associated with characteristic mutation patterns in genes, the factors that lead to promoter hypermethylation remain unknown. One gene target for inactivation through promoter methylation is the estrogen receptor (ER). The purpose of this investigation was to determine the methylation status of this gene in lung tumors from smokers and those who never smoked and in rodents exposed to specific environmental carcinogens. Promoter methylation at the ER locus was detected in 4 of 11 tumors from never-smokers (36.4%) and 7 of 35 tumors from smokers (20%, P < 0.001). Lung tumors induced by the tobacco-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone also had a low incidence (16.7%) of ER methylation. In marked contrast, spontaneous and plutonium-induced tumors had a very high (81.8%) incidence of ER methylation. X-ray-induced tumors had an intermediate frequency of ER methylation (38.1%). The presence of ER methylation was associated with absent ER expression in rodent lung cancer cell lines. These results show for the first time that gene-specific promoter methylation can be modulated differentially depending on carcinogen exposure. 39 refs., 4 figs.

  5. Effects of azinphos-methyl exposure on enzymatic and non-enzymatic antioxidant defenses in Biomphalaria glabrata and Lumbriculus variegatus.

    PubMed

    Kristoff, Gisela; Verrengia Guerrero, Noemí R; Cochón, Adriana C

    2008-07-01

    Azinphos-methyl is an organophosphate insecticide used for pest control on a number of food crops in many parts of the world. The oligochaete Lumbriculus variegatus and pigmented and non-pigmented specimens of the gastropod Biomphalaria glabrata are freshwater invertebrates that have been recommended for contamination studies. Recently, it has been shown that L. variegatus worms exhibit a higher cholinesterase (ChE) activity and a greater sensitivity to in vivo ChE inhibition by azinphos-methyl than pigmented B. glabrata snails. The aims of the present study were (1) to investigate if, in addition to its anticholinesterase action, azinphos-methyl has also pro-oxidant activity in L. variegatus and B. glabrata, and (2) to examine if species that are highly susceptible to the neurotoxic effects of organophosphates also suffer a greater degree of oxidative stress. Therefore, total glutathione (t-GSH) levels and activities of cholinesterase (ChE), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glucose 6-phosphate dehydrogenase (G6PDH) were measured in the whole body soft tissue of organisms exposed for 48 and 96 h to a level of azinphos-methyl that produces 50% of inhibition on ChE. Results showed different patterns of antioxidant responses between the gastropods and the oligochaetes, and even between the two phenotypes of gastropods: (1) in exposed L. variegatus t-GSH levels increased and CAT and SOD activities decreased with respect to control organisms, (2) in pigmented gastropods, SOD decreased while CAT transiently diminished, and (3) in non-pigmented gastropods, SOD activity showed a biphasic response. GST and G6PDH were not altered by azinphos-methyl exposure. Of note, t-GSH levels were 4-fold times higher in L. variegatus than in both phenotypes of B. glabrata. This may suggest that GSH could play a more important role in antioxidant defense in L. variegatus than in B. glabrata.

  6. Early life lead exposure causes gender-specific changes in the DNA methylation profile of DNA extracted from dried blood spots

    PubMed Central

    Sen, Arko; Heredia, Nicole; Senut, Marie-Claude; Hess, Matthew; Land, Susan; Qu, Wen; Hollacher, Kurt; Dereski, Mary O; Ruden, Douglas M

    2015-01-01

    Aims In this paper, we tested the hypothesis that early life lead (Pb) exposure associated DNA methylation (5mC) changes are dependent on the sex of the child and can serve as biomarkers for Pb exposure. Methods In this pilot study, we measured the 5mC profiles of DNA extracted from dried blood spots (DBS) in a cohort of 43 children (25 males and 18 females; ages from 3 months to 5 years) from Detroit. Result & Discussion We found that the effect of Pb-exposure on the 5-mC profiles can be separated into three subtypes: affected methylation loci which are conserved irrespective of the sex of the child (conserved); affected methylation loci unique to males (male-specific); and affected methylation loci unique to females (female-specific). PMID:26077427

  7. Postnatal Exposure to Methyl Mercury from Fish Consumption: a Review and New Data from the Seychelles Child Development Study

    PubMed Central

    Myers, Gary J.; Thurston, Sally W.; Pearson, Alexander T.; Davidson, Philip W.; Cox, Christopher; Shamlaye, Conrad F.; Cernichiari, Elsa; Clarkson, Thomas W.

    2009-01-01

    Background Fish is an important source of nutrition worldwide. Fish contain both the neurotoxin methyl mercury (MeHg) and nutrients important for brain development. The developing brain appears to be most sensitive to MeHg toxicity and mothers who consume fish during pregnancy expose their fetus prenatally. Although brain development is most dramatic during fetal life, it continues for years postnatally and additional exposure can occur when a mother breast feeds or the child consumes fish. This raises the possibility that MeHg might influence brain development after birth and thus adversely affect children’s developmental outcomes. We reviewed postnatal MeHg exposure and the associations that have been published to determine the issues associated with it and then carried out a series of analyses involving alternative metrics of postnatal MeHg exposure in the Seychelles Child Development Study (SCDS) Main Cohort. Methods The SCDS is a prospective longitudinal evaluation of prenatal MeHg exposure from fish consumption. The Main Cohort includes 779 subjects on whom recent postnatal exposure data were collected at the 6, 19, 29, 66, and 107 month evaluations. We examined the association of recent postnatal MeHg exposure with multiple 66 and 107-month outcomes and then used three types of alternative postnatal exposure metrics to examine their association with the children’s intelligence quotient (IQ) at 107 months of age. Results Recent postnatal exposure at 107 months of age was adversely associated with four endpoints, three in females only. One alternative postnatal metric was beneficially associated with 9-year IQ in males only. Conclusions We found several associations between postnatal MeHg biomarkers and children’s developmental endpoints. However, as has been the case with prenatal MeHg exposure in the SCDS Main Cohort study, no consistent pattern of associations emerged to support a causal relationship. PMID:19442817

  8. Methamphetamine exposure antagonizes N-methyl-D-aspartate receptor-mediated neurotoxicity in organotypic hippocampal slice cultures.

    PubMed

    Smith, Katherine J; Self, Rachel L; Butler, Tracy R; Mullins, Michael M; Ghayoumi, Layla; Holley, Robert C; Littleton, John M; Prendergast, Mark A

    2007-07-09

    Glutamatergic systems have been increasingly recognized as mediators of methamphetamine's (METH) pharmacological effects though little is known about the means by which METH interacts with glutamate receptors. The present studies examined effects of METH (0.1-100 microM) on [3H]MK-801 binding to membranes prepared from adult rat cortex, hippocampus and cerebellum, as well as the neurotoxicity produced by 24-h exposure to N-methyl-D-aspartate (5-10 microM; NMDA) employing organotypic hippocampal slice cultures of neonatal rat. Co-incubation of [3H]MK-801 with METH (0.1-100 microM) did not reduce dextromethorphan (1 mM)-displaceable ligand binding. Exposure of slice cultures to NMDA for 24-h produced increases in uptake of the non-vital fluorescent marker propidium iodide (PI) of 150-500% above control levels, most notably, in the CA1 region pyramidal cell layer. Co-exposure to METH (>1.0 microM) with NMDA (5 microM) reduced PI uptake by approximately 50% in each subregion, though the CA1 pyramidal cell layer was markedly more sensitive to the protective effects of METH exposure. In contrast, METH exposure did not reduce PI uptake stimulated by 24-h exposure to 10 microM NMDA. Co-exposure to the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid (20 microM) prevented toxicity produced by exposure to 5 or 10 microM NMDA. These findings indicate that the pharmacological effects of short-term METH exposure involve inhibition of NMDA receptor-mediated neuronal signaling, not reflective of direct channel inhibition at an MK-801-sensitive site.

  9. The association between personal sun exposure, serum vitamin D and global methylation in human lymphocytes in a population of healthy adults in South Australia.

    PubMed

    Nair-Shalliker, Visalini; Dhillon, Varinderpal; Clements, Mark; Armstrong, Bruce K; Fenech, Michael

    2014-07-01

    There is a positive association between solar UV exposure and micronucleus frequency in peripheral blood lymphocytes (PBL) and this association may be stronger when serum vitamin D (25(OH)D) levels are insufficient (<50 nmol/L). Micronucleus formation can result from global hypomethylation of DNA repeat sequences. The aim of this analysis was to evaluate the relationship between solar UV exposure and methylation pattern in LINE-1 repetitive elements in PBL DNA and to see if serum 25(OH)D levels modify it. Personal solar UV exposure was estimated from hours of outdoor exposure over 6 weeks recalled at the time of blood collection in 208 male and female participants living in South Australia. Methylation in LINE-1 repetitive elements was assessed in PBL using pyrosequencing. Methylation in LINE-1 decreased with increasing solar UV exposure (% decrease = 0.5% per doubling of sUV; 95%CI: -0.7 to -0.2 p(value) = 0.00003). Although there was no correlation between LINE-1 methylation and micronucleus frequency, there was a 4.3% increase (95%CI: 0.6-8.1 p-value = 0.02) in nucleoplasmic bridges and a 4.3% increase in necrosis (CI: 1.9-6.8 p-value = 0.0005) for every 1% increase in LINE-1 methylation. Serum 25(OH)D was not associated with DNA methylation; or did it modify the association of solar UV with DNA methylation. Exposure to solar UV radiation may reduce DNA methylation in circulating lymphocytes. This association does not appear to be influenced or mediated by vitamin D status. Copyright © 2014. Published by Elsevier B.V.

  10. Oxidative stress, telomere shortening, and DNA methylation in relation to low‐to‐moderate occupational exposure to welding fumes

    PubMed Central

    Li, Huiqi; Hedmer, Maria; Wojdacz, Tomasz; Hossain, Mohammad Bakhtiar; Lindh, Christian H.; Tinnerberg, Håkan; Albin, Maria

    2015-01-01

    Evidence suggests that exposure to welding fumes is a risk factor for lung cancer. We examined relationships between low‐to‐moderate occupational exposure to particles from welding fumes and cancer‐related biomarkers for oxidative stress, changes in telomere length, and alterations in DNA methylation. We enrolled 101 welders and 127 controls (all currently nonsmoking men) from southern Sweden. We performed personal sampling of respirable dust and measured 8‐oxodG concentrations in urine using a simplified liquid chromatography tandem mass spectrometry method. Telomere length in peripheral blood was measured by quantitative polymerase chain reaction. Methylation status of 10 tumor suppressor genes was determined by methylation‐sensitive high‐resolution melting analysis. All analyses were adjusted for age, body mass index, previous smoking, passive smoking, current residence, and wood burning stove/boiler at home. Welders were exposed to respirable dust at 1.2 mg/m3 (standard deviation, 3.3 mg/m3; range, 0.1–19.3), whereas control exposures did not exceed 0.1 mg/m3 (P < 0.001). Welders and controls did not differ in 8‐oxodG levels (β = 1.2, P = 0.17) or relative telomere length (β = −0.053, P = 0.083) in adjusted models. Welders showed higher probability of adenomatous polyposis coli (APC) methylation in the unadjusted model (odds ratio = 14, P = 0.014), but this was not significant in the fully adjusted model (P = 0.052). Every working year as a welder was associated with 0.0066 units shorter telomeres (95% confidence interval −0.013 to −0.00053, P = 0.033). Although there were no clear associations between concentrations of respirable dust and the biomarkers, there were modest signs of associations between oxidative stress, telomere alterations, DNA methylation, and occupational exposure to low‐to‐moderate levels of particles. Environ. Mol. Mutagen. 56:684–693, 2015. © 2015 The Authors

  11. Epigenetic Vestiges of Early Developmental Adversity: Childhood Stress Exposure and DNA Methylation in Adolescence

    PubMed Central

    Essex, Marilyn J.; Boyce, W. Thomas; Hertzman, Clyde; Lam, Lucia L.; Armstrong, Jeffrey M.; Neumann, Sarah M.A.; Kobor, Michael S.

    2011-01-01

    Fifteen-year-old adolescents (N=109) in a longitudinal study of child development were recruited to examine differences in DNA methylation in relation to parent reports of adversity during the adolescents’ infancy and preschool periods. Microarray technology applied to 28,000 cytosine-guanine dinucleotide (CpG) sites within DNA derived from buccal epithelial cells showed differential methylation among adolescents whose parents reported high levels of stress during their children’s early lives. Maternal stressors in infancy and paternal stressors in the preschool years were most strongly predictive of differential methylation, and the patterning of such epigenetic marks varied by children’s gender. To the authors’ knowledge, this is the first report of prospective associations between adversities in early childhood and the epigenetic conformation of adolescents’ genomic DNA. PMID:21883162

  12. Epigenetic vestiges of early developmental adversity: childhood stress exposure and DNA methylation in adolescence.

    PubMed

    Essex, Marilyn J; Boyce, W Thomas; Hertzman, Clyde; Lam, Lucia L; Armstrong, Jeffrey M; Neumann, Sarah M A; Kobor, Michael S

    2013-01-01

    Fifteen-year-old adolescents (N = 109) in a longitudinal study of child development were recruited to examine differences in DNA methylation in relation to parent reports of adversity during the adolescents' infancy and preschool periods. Microarray technology applied to 28,000 cytosine-guanine dinucleotide sites within DNA derived from buccal epithelial cells showed differential methylation among adolescents whose parents reported high levels of stress during their children's early lives. Maternal stressors in infancy and paternal stressors in the preschool years were most strongly predictive of differential methylation, and the patterning of such epigenetic marks varied by children's gender. To the authors' knowledge, this is the first report of prospective associations between adversities in early childhood and the epigenetic conformation of adolescents' genomic DNA. © 2011 The Authors. Child Development © 2011 Society for Research in Child Development, Inc.

  13. Methyl mercury exposure and neurodevelopmental outcomes in the Seychelles Child Development Study Main cohort at age 22 and 24years.

    PubMed

    van Wijngaarden, Edwin; Thurston, Sally W; Myers, Gary J; Harrington, Donald; Cory-Slechta, Deborah A; Strain, J J; Watson, Gene E; Zareba, Grazyna; Love, Tanzy; Henderson, Juliette; Shamlaye, Conrad F; Davidson, Philip W

    All fish contain methyl mercury (MeHg), a known neurotoxicant at adequate dosage. There is still substantial scientific uncertainty about the consequences, if any, of mothers consuming fish with naturally-acquired levels of MeHg contamination. In 1989-1990, we recruited the Main Cohort of the Seychelles Child Development Study to assess the potential developmental effects of prenatal MeHg exposure. We report here on associations with neurodevelopmental outcomes obtained at 22 and 24years of age. Neurodevelopmental tests at 22years included the Boston Naming Test, Cambridge Neuropsychological Test Automated Battery (CANTAB), and the Profile of Mood States. At 24years, we administered the Stroop Word-Color Test, the Barkley Adult ADHD Rating Scale, the Test of Variables of Attention, and the Finger Tapping test. We also administered a healthy behaviors survey at both ages. Primary analyses examined covariate-adjusted associations in multiple linear regression models with prenatal MeHg exposure. In secondary analyses we also examined associations with recent postnatal MeHg exposure. We did not observe adverse associations between prenatal MeHg exposure and any of the measured endpoints. Some measures of attention, executive function, and delayed recall showed improved performance with increasing exposure. Secondary analysis did not show consistent patterns of association with postnatal exposure. Our cohort has been examined at ten different ages over 24years of follow-up. Findings suggest that prenatal and recent postnatal MeHg exposure from ocean fish consumption is not adversely associated with neurobehavioral development at levels that are about ten times higher than typical U.S. exposures. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Health Risk Assessment for Inhalation Exposure to Methyl Tertiary Butyl Ether at Petrol Stations in Southern China

    PubMed Central

    Hu, Dalin; Yang, Jianping; Liu, Yungang; Zhang, Wenjuan; Peng, Xiaowu; Wei, Qinzhi; Yuan, Jianhui; Zhu, Zhiliang

    2016-01-01

    Methyl tertiary butyl ether (MTBE), a well known gasoline additive, is used in China nationwide to enhance the octane number of gasoline and reduce harmful exhaust emissions, yet  little is known regarding the potential health risk associated with occupational exposure to MTBE in petrol stations. In this study, 97 petrol station attendants (PSAs) in southern China were recruited for an assessment of the health risk associated with inhalation exposure to MTBE. The personal exposure levels of MTBE were analyzed by Head Space Solid Phase Microextraction GC/MS, and the demographic characteristics of the PSAs were investigated. Cancer and non-cancer risks were calculated with the methods recommended by the United States Environmental Protection Agency. The results showed that the exposure levels of MTBE in operating workers were much higher than among support staff (p < 0.01) and both were lower than 50 ppm (an occupational threshold limit value). The calculated cancer risks (CRs) at the investigated petrol stations was 0.170 to 0.240 per 106 for operating workers, and 0.026 to 0.049 per 106 for support staff, which are below the typical target range for risk management of 1 × 10−6 to 1 × 10−4; The hazard quotients (HQs) for all subjects were <1. In conclusion, our study indicates that the MTBE exposure of PSAs in southern China is in a low range which does not seem to be a significant health risk. PMID:26861375

  15. Health Risk Assessment for Inhalation Exposure to Methyl Tertiary Butyl Ether at Petrol Stations in Southern China.

    PubMed

    Hu, Dalin; Yang, Jianping; Liu, Yungang; Zhang, Wenjuan; Peng, Xiaowu; Wei, Qinzhi; Yuan, Jianhui; Zhu, Zhiliang

    2016-02-06

    Methyl tertiary butyl ether (MTBE), a well known gasoline additive, is used in China nationwide to enhance the octane number of gasoline and reduce harmful exhaust emissions, yet little is known regarding the potential health risk associated with occupational exposure to MTBE in petrol stations. In this study, 97 petrol station attendants (PSAs) in southern China were recruited for an assessment of the health risk associated with inhalation exposure to MTBE. The personal exposure levels of MTBE were analyzed by Head Space Solid Phase Microextraction GC/MS, and the demographic characteristics of the PSAs were investigated. Cancer and non-cancer risks were calculated with the methods recommended by the United States Environmental Protection Agency. The results showed that the exposure levels of MTBE in operating workers were much higher than among support staff (p < 0.01) and both were lower than 50 ppm (an occupational threshold limit value). The calculated cancer risks (CRs) at the investigated petrol stations was 0.170 to 0.240 per 10⁶ for operating workers, and 0.026 to 0.049 per 10⁶ for support staff, which are below the typical target range for risk management of 1 × 10(-6) to 1 × 10(-4); The hazard quotients (HQs) for all subjects were <1. In conclusion, our study indicates that the MTBE exposure of PSAs in southern China is in a low range which does not seem to be a significant health risk.

  16. Surface Modification of Poly(methyl methacrylate) by Hydrogen-Plasma Exposure and Its Sputtering Characteristics by Ultraviolet Light Irradiation

    NASA Astrophysics Data System (ADS)

    Yoshimura, Satoru; Ikuse, Kazumasa; Sugimoto, Satoshi; Murai, Kensuke; Honjo, Kuniaki; Kiuchi, Masato; Hamaguchi, Satoshi

    2013-09-01

    Surface modification of poly(methyl methacrylate) (PMMA) films by hydrogen-plasma exposure has been studied in the light of sputtering resistance of polymer-based materials in plasma etching processes. Surface measurements of PMMA were performed with X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, and spectroscopic ellipsometry. It has been found that oxygen atoms are preferentially removed from the surface when a PMMA film is subjected to hydrogen-plasma exposure, with the depth of modification being about 40 nm in the case we examined. Hydrogen-plasma exposure is also found to reduce the sputtering yields of PMMA by ultraviolet light irradiation, as in the case of Ar+ ion irradiation [S. Yoshimura et al.: J. Vac. Soc. Jpn. 56 (2013) 129]. The results suggest that PMMA films become hardened and more sputtering resistant due to the formation of a thick (i.e., 40 nm in the case of this study) amorphous carbon layer by hydrogen-plasma exposure. Hydrogen-plasma exposure is thus an effective technique to increase etching resistance of polymer films.

  17. Continuous exposure to the deterrents cis-jasmone and methyl jasmonate does not alter the behavioural responses of Frankliniella occidentalis

    PubMed Central

    Egger, Barbara; Spangl, Bernhard; Koschier, Elisabeth Helene

    2016-01-01

    Behavioural responses of Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), a generalist, cell sap-feeding insect species with piercing-sucking mouthparts, after continuous exposure to two deterrent secondary plant compounds are investigated. We compared in choice assays on bean leaf discs, the settling, feeding, and oviposition preferences of F. occidentalis females that had no experience with the two fatty acid derivatives methyl jasmonate and cis-jasmone before testing (naïve thrips) vs. females that had been exposed to the deterrent compounds before testing (experienced thrips). The thrips were exposed to the deterrents at low or high concentrations for varied time periods and subsequently tested on bean leaf discs treated with the respective deterrent at either a low or a high concentration. Frankliniella occidentalis females avoided settling on the deterrent-treated bean leaf discs for an observation period of 6 h, independent of their previous experience. Our results demonstrate that feeding and oviposition deterrence of the jasmonates to the thrips were not altered by continuous exposure of the thrips to the jasmonates. Habituation was not induced, neither by exposure to the low concentration of the deterrents nor by exposure to the high concentration. These results indicate that the risk of habituation to two volatile deterrent compounds after repeated exposure is not evident in F. occidentalis. This makes the two compounds potential candidates to be integrated in pest management strategies. PMID:26726263

  18. The occurrence of bromide in herbal drugs: is there a need for a Ph. Eur. limit?

    PubMed

    Albert, H; Busch, J; Klier, B; Klötzel, M; Kühn, M; Steinhoff, B

    2013-01-01

    This contribution provides an overview on the current legal requirements regarding limits for bromide and presents data on the actual bromide burden of commonly used herbal drugs. Evaluation of an extensive data base shows that results exceeding the limit of 50 mg/kg are found in specific plants which take up bromide to a high extent from the environment. Thus, positive findings of bromide in herbal drugs do not necessarily serve as a proof for methyl bromide treatment. Taking into account the ADI recommended by EMA and WHO, there are no toxicological concerns with regard to the intake of herbal teas, extracts or comminuted herbal drugs at therapeutic doses. Furthermore, the use of methyl bromide and other fumigants must be documented within the batch documentation. If stated in the batch documentation that no fumigation was carried out, it is not necessary to perform the test on bromide. In cases of a particular suspect and if toxicological concerns exist, additional testing can be performed in accordance with the limits set by Regulation (EC) No. 396/2005. For the above reasons, information obtained by performing the test on bromide is not significant for the assessment of quality. Therefore, it seems no longer necessary to maintain bromide in Ph. Eur. general chapter 2.8.13. Pesticide residues and it is recommended to delete it from Table 2.8.13.-1.

  19. Select Prenatal Environmental Exposures and Subsequent Alterations of Gene-Specific and Repetitive Element DNA Methylation in Fetal Tissues.

    PubMed

    Green, Benjamin B; Marsit, Carmen J

    2015-06-01

    Strong evidence implicates maternal environmental exposures in contributing to adverse outcomes during pregnancy and later in life through the developmental origins of health and disease hypothesis. Recent research suggests these effects are mediated through the improper regulation of DNA methylation in offspring tissues, specifically placental tissue, which plays a critical role in fetal development. This article reviews the relevant literature relating DNA methylation in multiple tissues at or near delivery to several prenatal environmental toxicants and stressors, including cigarette smoke, endocrine disruptors, heavy metals, as well as maternal diet. These human studies expand upon previously reported outcomes in animal model interventions and include effects on both imprinted and non-imprinted genes. We have also noted some of the strengths and limitations in the approaches used, and consider the appropriate interpretation of these findings in terms of their effect size and their relationship to differential gene expression and potential health outcomes. The studies suggest an important role of DNA methylation in mediating the effects of the intrauterine environment on children's health and a need for additional research to better clarify the role of this epigenetic mechanism as well as others.

  20. Intergenerational impact of paternal lifetime exposures to both folic acid deficiency and supplementation on reproductive outcomes and imprinted gene methylation.

    PubMed

    Ly, Lundi; Chan, Donovan; Aarabi, Mahmoud; Landry, Mylène; Behan, Nathalie A; MacFarlane, Amanda J; Trasler, Jacquetta

    2017-07-01

    Do paternal exposures to folic acid deficient (FD), and/or folic acid supplemented (FS) diets, throughout germ cell development adversely affect male germ cells and consequently offspring health outcomes? Male mice exposed over their lifetimes to both FD and FS diets showed decreased sperm counts and altered imprinted gene methylation with evidence of transmission of adverse effects to the offspring, including increased postnatal-preweaning mortality and variability in imprinted gene methylation. There is increasing evidence that disruptions in male germ cell epigenetic reprogramming are associated with offspring abnormalities and intergenerational disease. The fetal period is the critical time of DNA methylation pattern acquisition for developing male germ cells and an adequate supply of methyl donors is required. In addition, DNA methylation patterns continue to be remodeled during postnatal spermatogenesis. Previous studies have shown that lifetime (prenatal and postnatal) folic acid deficiency can alter the sperm epigenome and increase the incidence of fetal morphological abnormalities. Female BALB/c mice (F0) were placed on one of four amino-acid defined diets for 4 weeks before pregnancy and throughout pregnancy and lactation: folic acid control (Ctrl; 2 mg/kg), 7-fold folic acid deficient (7FD; 0.3 mg/kg), 10-fold high FS (10FS, 20 mg/kg) or 20-fold high FS (20FS, 40 mg/kg) diets. F1 males were weaned to their respective prenatal diets to allow for diet exposure during all windows of germline epigenetic reprogramming: the erasure, re-establishment and maintenance phases. F0 females were mated with chow-fed males to produce F1 litters whose germ cells were exposed to the diets throughout embryonic development. F1 males were subsequently mated with chow-fed female mice. Two F2 litters, unexposed to the experimental diets, were generated from each F1 male; one litter was collected at embryonic day (E)18.5 and one delivered and followed postnatally. DNA

  1. Select Prenatal Environmental Exposures and Subsequent Alterations of Gene-Specific and Repetitive Element DNA Methylation in Fetal Tissues

    PubMed Central

    Green, Benjamin B.; Marsit, Carmen J.

    2015-01-01

    Strong evidence implicates maternal environmental exposures in contributing to adverse outcomes during pregnancy and later in life through the developmental origins of health and disease hypothesis. Recent research suggests these effects are mediated through the improper regulation of DNA methylation in offspring tissues, specifically placental tissue, which plays a critical role in fetal development. This article reviews the relevant literature relating DNA methylation in multiple tissues at or near delivery to several prenatal environmental toxicants and stressors, including cigarette smoke, endocrine disruptors, heavy metals, as well as maternal diet. These human studies expand upon previously reported outcomes in animal model interventions and include effects on both imprinted and non-imprinted genes. We have also noted some of the strengths and limitations in the approaches used, and consider the appropriate interpretation of these findings in terms of their effect size and their relationship to differential gene expression and potential health outcomes. The studies suggest an important role of DNA methylation in mediating the effects of the intrauterine environment on children’s health and a need for additional research to better clarify the role of this epigenetic mechanism as well as others. PMID:26231362

  2. PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR HUMAN EXPOSURES TO METHYL TERTIARY-BUTYL ETHER

    EPA Science Inventory

    Humans can be exposed by inhalation, ingestion, or dermal absorption to methyl tertiary-butyl ether (MTBE), an oxygenated fuel additive, from contaminated water sources. The purpose of this research was to develop a physiologically based pharmacokinetic model describing in human...

  3. PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR HUMAN EXPOSURES TO METHYL TERTIARY-BUTYL ETHER

    EPA Science Inventory

    Humans can be exposed by inhalation, ingestion, or dermal absorption to methyl tertiary-butyl ether (MTBE), an oxygenated fuel additive, from contaminated water sources. The purpose of this research was to develop a physiologically based pharmacokinetic model describing in human...

  4. Epigenetic Vestiges of Early Developmental Adversity: Childhood Stress Exposure and DNA Methylation in Adolescence

    ERIC Educational Resources Information Center

    Essex, Marilyn J.; Boyce, W. Thomas; Hertzman, Clyde; Lam, Lucia L.; Armstrong, Jeffrey M.; Neumann, Sarah M. A.; Kobor, Michael S.

    2013-01-01

    Fifteen-year-old adolescents (N = 109) in a longitudinal study of child development were recruited to examine differences in DNA methylation in relation to parent reports of adversity during the adolescents' infancy and preschool periods. Microarray technology applied to 28,000 cytosine-guanine dinucleotide sites within DNA derived from buccal…

  5. Effect of developmental dioxin exposure on methylation and expression of specific imprinted genes in mice.

    PubMed

    Somm, Emmanuel; Stouder, Christelle; Paoloni-Giacobino, Ariane

    2013-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine disruptor affecting the reproductive system in humans. The aim of this study was to evaluate the effects of TCDD administered to pregnant mice at two different doses (2-10 ng/kg/day), on imprinted genes in the male offspring. The degree of methylation and the mRNA expression of Snrpn, Peg3 and Igf2r were analyzed in the sperm, skeletal muscle and liver. TCDD administration (10 ng/kg/day) decreased the sperm count in the male offspring. It did not affect methylation but increased mRNA expression of Snrpn, Peg3, Igf2r and Air ncRNA. In muscle and liver, TCDD (10 ng/kg/day) induced increases in methylation and decreases in mRNA expression of Igf2r. These results show that the robust effects of TCDD on the mRNA expression of Snrpn, Peg3 and Igf2r genes in the sperm and of Igf2r in the muscle and liver are unrelated to changes in methylation in their respective genes.

  6. INHALATION EXPOSURE TO METHYL TERT-BUTYL ETHER (MTBE) AND DIBROMOCHLOROMETHANE (DBCM) USING CONTINUOUS BREATH ANALYSIS

    EPA Science Inventory

    The oxygenate methyl tert-butyl ether (MTBE) has been added to gasoline to help meet national ambient air quality standards in those parts of the U.S. that are non-compliant for carbon monoxide. Although MTBE has provided important health benefits in terms of reduced haza...

  7. Epigenetic Vestiges of Early Developmental Adversity: Childhood Stress Exposure and DNA Methylation in Adolescence

    ERIC Educational Resources Information Center

    Essex, Marilyn J.; Boyce, W. Thomas; Hertzman, Clyde; Lam, Lucia L.; Armstrong, Jeffrey M.; Neumann, Sarah M. A.; Kobor, Michael S.

    2013-01-01

    Fifteen-year-old adolescents (N = 109) in a longitudinal study of child development were recruited to examine differences in DNA methylation in relation to parent reports of adversity during the adolescents' infancy and preschool periods. Microarray technology applied to 28,000 cytosine-guanine dinucleotide sites within DNA derived from buccal…

  8. INHALATION EXPOSURE TO METHYL TERT-BUTYL ETHER (MTBE) AND DIBROMOCHLOROMETHANE (DBCM) USING CONTINUOUS BREATH ANALYSIS

    EPA Science Inventory

    The oxygenate methyl tert-butyl ether (MTBE) has been added to gasoline to help meet national ambient air quality standards in those parts of the U.S. that are non-compliant for carbon monoxide. Although MTBE has provided important health benefits in terms of reduced haza...

  9. DNA methylation signatures triggered by prenatal maternal stress exposure to a natural disaster: Project Ice Storm.

    PubMed

    Cao-Lei, Lei; Massart, Renaud; Suderman, Matthew J; Machnes, Ziv; Elgbeili, Guillaume; Laplante, David P; Szyf, Moshe; King, Suzanne

    2014-01-01

    Prenatal maternal stress (PNMS) predicts a wide variety of behavioral and physical outcomes in the offspring. Although epigenetic processes may be responsible for PNMS effects, human research is hampered by the lack of experimental methods that parallel controlled animal studies. Disasters, however, provide natural experiments that can provide models of prenatal stress. Five months after the 1998 Quebec ice storm we recruited women who had been pregnant during the disaster and assessed their degrees of objective hardship and subjective distress. Thirteen years later, we investigated DNA methylation profiling in T cells obtained from 36 of the children, and compared selected results with those from saliva samples obtained from the same children at age 8. Prenatal maternal objective hardship was correlated with DNA methylation levels in 1675 CGs affiliated with 957 genes predominantly related to immune function; maternal subjective distress was uncorrelated. DNA methylation changes in SCG5 and LTA, both highly correlated with maternal objective stress, were comparable in T cells, peripheral blood mononuclear cells (PBMCs) and saliva cells. These data provide first evidence in humans supporting the conclusion that PNMS results in a lasting, broad, and functionally organized DNA methylation signature in several tissues in offspring. By using a natural disaster model, we can infer that the epigenetic effects found in Project Ice Storm are due to objective levels of hardship experienced by the pregnant woman rather than to her level of sustained distress.

  10. DNA Methylation Signatures Triggered by Prenatal Maternal Stress Exposure to a Natural Disaster: Project Ice Storm

    PubMed Central

    Cao-Lei, Lei; Massart, Renaud; Suderman, Matthew J.; Machnes, Ziv; Elgbeili, Guillaume; Laplante, David P.; Szyf, Moshe; King, Suzanne

    2014-01-01

    Background Prenatal maternal stress (PNMS) predicts a wide variety of behavioral and physical outcomes in the offspring. Although epigenetic processes may be responsible for PNMS effects, human research is hampered by the lack of experimental methods that parallel controlled animal studies. Disasters, however, provide natural experiments that can provide models of prenatal stress. Methods Five months after the 1998 Quebec ice storm we recruited women who had been pregnant during the disaster and assessed their degrees of objective hardship and subjective distress. Thirteen years later, we investigated DNA methylation profiling in T cells obtained from 36 of the children, and compared selected results with those from saliva samples obtained from the same children at age 8. Results Prenatal maternal objective hardship was correlated with DNA methylation levels in 1675 CGs affiliated with 957 genes predominantly related to immune function; maternal subjective distress was uncorrelated. DNA methylation changes in SCG5 and LTA, both highly correlated with maternal objective stress, were comparable in T cells, peripheral blood mononuclear cells (PBMCs) and saliva cells. Conclusions These data provide first evidence in humans supporting the conclusion that PNMS results in a lasting, broad, and functionally organized DNA methylation signature in several tissues in offspring. By using a natural disaster model, we can infer that the epigenetic effects found in Project Ice Storm are due to objective levels of hardship experienced by the pregnant woman rather than to her level of sustained distress. PMID:25238154

  11. Surface and volume properties of dodecylethyldimethylammonium bromide and benzyldimethyldodecylammonium bromide: II. Volumetric properties of dodecylethyldimethylammonium bromide and benzyldimethyldodecylammonium bromide.

    PubMed

    Harkot, Joanna; Jańczuk, Bronisław

    2009-02-15

    Density measurements were carried out for aqueous solutions of two cationic surfactants: dodecylethyldimethylammonium bromide (C(12)(EDMAB)) and benzyldimethyldodecylammonium bromide (BDDAB). On the basis of the obtained results of the measurements the CMC and partial molar volumes of the surfactants studied were also determined. The obtained CMC values were also analyzed with those accounted on the basis of the surface tension data from the previous paper [J. Harkot, B. Jańczuk, J. Colloid Interface Sci. (2008), submitted for publication]. The values of CMC determined from the surface tension and density measurements for C(12)(EDMAB) are equal to 9.9x10(-3) and 1.5x10(-2) M and for BDDAB to 5.25x10(-3) and 5.3x10(-3) M, respectively. These obtained values are very similar. However, in the literature it is difficult to find the CMC values for C(12)(EDMAB) and BDDAB determined by these two methods used by us-especially from the density measurements for BDDAB and surface tension measurements for C(12)(EDMAB). In the case of the apparent molar volumes of C(12)(EDMAB) there is a good agreement between the values obtained by us and those found in the literature. The CMC values for C(12)(EDMAB) and BDDAB were also determined on the basis of their surface tension and free energy of electrostatic interactions between the polar heads of these surfactants and compared with those obtained from the surface tension and density measurements. It was found that the theoretically obtained CMC values were close to those determined from the density and surface tension data for the C(12)(EDMAB) and that the ratios of the CMC values of the surfactants to their concentration at which the water surface tension decreased by about 20 mN/m proved that the presence of the aryl group in the BDDAB head instead of the methyl group caused that its micellization process was more inhibited in relation to its adsorption at air-water interface than that of C(12)(EDMAB).

  12. Gene-Specific Differential DNA Methylation and Chronic Arsenic Exposure in an Epigenome-Wide Association Study of Adults in Bangladesh

    PubMed Central

    Argos, Maria; Chen, Lin; Jasmine, Farzana; Tong, Lin; Pierce, Brandon L.; Roy, Shantanu; Paul-Brutus, Rachelle; Gamble, Mary V.; Harper, Kristin N.; Parvez, Faruque; Rahman, Mahfuzar; Rakibuz-Zaman, Muhammad; Slavkovich, Vesna; Baron, John A.; Graziano, Joseph H.; Kibriya, Muhammad G.

    2014-01-01

    Background: Inorganic arsenic is one of the most common naturally occurring contaminants found in the environment. Arsenic is associated with a number of health outcomes, with epigenetic modification suggested as a potential mechanism of toxicity. Objective: Among a sample of 400 adult participants, we evaluated the association between arsenic exposure, as measured by blood and urinary total arsenic concentrations, and epigenome-wide white blood cell DNA methylation. Methods: We used linear regression models to examine the associations between arsenic exposure and methylation at each CpG site, adjusted for sex, age, and batch. Differentially methylated loci were subsequently examined in relation to corresponding gene expression for functional evidence of gene regulation. Results: In adjusted analyses, we observed four differentially methylated CpG sites with urinary total arsenic concentration and three differentially methylated CpG sites with blood arsenic concentration, based on the Bonferroni-corrected significance threshold of p < 1 × 10–7. Methylation of PLA2G2C (probe cg04605617) was the most significantly associated locus in relation to both urinary (p = 3.40 × 10–11) and blood arsenic concentrations (p = 1.48 × 10–11). Three additional novel methylation loci—SQSTM1 (cg01225779), SLC4A4 (cg06121226), and IGH (cg13651690)—were also significantly associated with arsenic exposure. Further, there was evidence of methylation-related gene regulation based on gene expression for a subset of differentially methylated loci. Conclusions: We observed significant associations between arsenic exposure and gene-specific differential white blood cell DNA methylation, suggesting that epigenetic modifications may be an important pathway underlying arsenic toxicity. The specific differentially methylated loci identified may inform potential pathways for future interventions. Citation: Argos M, Chen L, Jasmine F, Tong L, Pierce BL, Roy S, Paul-Brutus R, Gamble MV

  13. Prenatal Air Pollution Exposures, DNA Methyl Transferase Genotypes, and Associations with Newborn LINE1 and Alu Methylation and Childhood Blood Pressure and Carotid Intima-Media Thickness in the Children’s Health Study

    PubMed Central

    Breton, Carrie V.; Yao, Jin; Millstein, Josh; Gao, Lu; Siegmund, Kimberly D.; Mack, Wendy; Whitfield-Maxwell, Lora; Lurmann, Fred; Hodis, Howard; Avol, Ed; Gilliland, Frank D.

    2016-01-01

    Background: Although exposure to ambient air pollutants increases cardiovascular disease risk in adults little is known about the effects of prenatal exposure. Genetic variation and epigenetic alterations are two mechanisms that may influence the effects of early-life exposures on cardiovascular phenotypes. Objectives: We investigated whether genetic and epigenetic variation modify associations between prenatal air pollution on markers of cardiovascular risk in childhood. Methods: We used linear regression analysis to investigate the associations between prenatal pollutants (PM2.5, PM10, NO2, O3), long interspersed nuclear elements (LINE1) and AluYb8 DNA methylation levels measured in newborn blood spot tests, and carotid intima-media thickness (CIMT) and blood pressure (BP) in 459 participants as part of the Children’s Health Study. Interaction terms were also included to test for effect modification of these associations by genetic variation in methylation reprogramming genes. Results: Prenatal exposure to NO2 in the third trimester of pregnancy was associated with higher systolic BP in 11-year-old children. Prenatal exposure to multiple air pollutants in the first trimester was associated with lower DNA methylation in LINE1, whereas later exposure to O3 was associated with higher LINE1 methylation levels in newborn blood spots. The magnitude of associations with prenatal air pollution varied according to genotype for 11 SNPs within DNA methyltransferase 1 (DNMT1), DNA methyltransferase 3 Beta (DNMT3B), Tet methylcytosine dioxygenase 2 (TET2), and Thymine DNA glycosylase (TDG) genes. Although first-trimester O3 exposure was not associated with CIMT and systolic BP overall, associations within strata of DNMT1 or DNMT3B were observed, and the magnitude and the direction of these associations depended on DNMT1 genotypes. Conclusions: Genetic and epigenetic variation in DNA methylation reprogramming genes and in LINE1 retrotransposons may play important roles in

  14. Prenatal Air Pollution Exposures, DNA Methyl Transferase Genotypes, and Associations with Newborn LINE1 and Alu Methylation and Childhood Blood Pressure and Carotid Intima-Media Thickness in the Children's Health Study.

    PubMed

    Breton, Carrie V; Yao, Jin; Millstein, Josh; Gao, Lu; Siegmund, Kimberly D; Mack, Wendy; Whitfield-Maxwell, Lora; Lurmann, Fred; Hodis, Howard; Avol, Ed; Gilliland, Frank D

    2016-12-01

    Although exposure to ambient air pollutants increases cardiovascular disease risk in adults little is known about the effects of prenatal exposure. Genetic variation and epigenetic alterations are two mechanisms that may influence the effects of early-life exposures on cardiovascular phenotypes. We investigated whether genetic and epigenetic variation modify associations between prenatal air pollution on markers of cardiovascular risk in childhood. We used linear regression analysis to investigate the associations between prenatal pollutants (PM2.5, PM10, NO2, O3), long interspersed nuclear elements (LINE1) and AluYb8 DNA methylation levels measured in newborn blood spot tests, and carotid intima-media thickness (CIMT) and blood pressure (BP) in 459 participants as part of the Children's Health Study. Interaction terms were also included to test for effect modification of these associations by genetic variation in methylation reprogramming genes. Prenatal exposure to NO2 in the third trimester of pregnancy was associated with higher systolic BP in 11-year-old children. Prenatal exposure to multiple air pollutants in the first trimester was associated with lower DNA methylation in LINE1, whereas later exposure to O3 was associated with higher LINE1 methylation levels in newborn blood spots. The magnitude of associations with prenatal air pollution varied according to genotype for 11 SNPs within DNA methyltransferase 1 (DNMT1), DNA methyltransferase 3 Beta (DNMT3B), Tet methylcytosine dioxygenase 2 (TET2), and Thymine DNA glycosylase (TDG) genes. Although first-trimester O3 exposure was not associated with CIMT and systolic BP overall, associations within strata of DNMT1 or DNMT3B were observed, and the magnitude and the direction of these associations depended on DNMT1 genotypes. Genetic and epigenetic variation in DNA methylation reprogramming genes and in LINE1 retrotransposons may play important roles in downstream cardiovascular consequences of prenatal air

  15. Blood Pressure Associated with Arsenic Methylation and Arsenic Metabolism Caused by Chronic Exposure to Arsenic in Tube Well Water.

    PubMed

    Wei, Bing Gan; Ye, Bi Xiong; Yu, Jiang Ping; Yang, Lin Sheng; Li, Hai Rong; Xia, Ya Juan; Wu, Ke Gong

    2017-05-01

    The effects of arsenic exposure from drinking water, arsenic metabolism, and arsenic methylation on blood pressure (BP) were observed in this study. The BP and arsenic species of 560 participants were determined. Logistic regression analysis was applied to estimate the odds ratios of BP associated with arsenic metabolites and arsenic methylation capability. BP was positively associated with cumulative arsenic exposure (CAE). Subjects with abnormal diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) usually had higher urinary iAs (inorganic arsenic), MMA (monomethylated arsenic), DMA (dimethylated arsenic), and TAs (total arsenic) than subjects with normal DBP, SBP, and PP. The iAs%, MMA%, and DMA% differed slightly between subjects with abnormal BP and those with normal BP. The PMI and SMI were slightly higher in subjects with abnormal PP than in those with normal PP. Our findings suggest that higher CAE may elevate BP. Males may have a higher risk of abnormal DBP, whereas females have a higher risk of abnormal SBP and PP. Higher urinary iAs may increase the risk of abnormal BP. Lower PMI may elevate the BP. However, higher SMI may increase the DBP and SBP, and lower SMI may elevate the PP. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  16. Chromatographic detection of 7-methyladenine in urine of rats administered N-methylnitrosourea: a potential marker for monitoring exposure to methylating carcinogens.

    PubMed

    Mandel, H G; Straw, J A; Farmer, P B; Martin, J

    1989-04-01

    Relatively simple and rapid analytical procedures involving two sequential HPLC separations were developed for the isolation of methylated purines in the urine of rats administered radiolabeled methylating carcinogens. Following a dose of [3H]N-methyl-N-nitrosourea (MNU), 7-methyl-adenine (m7Gua) was detected by chromatography as a urinary methylpurine in addition to the expected 7-methylguanine (m7Gua) and 3-methyladenine (m3Ade). When methyl-labeled methionine was given to rats concurrently with MNU, urinary m7Gua was labeled, but no radioactivity was recovered in either of the two methyladenine fractions. The profile of urinary methylated purines following a dose of dimethyl sulfate to the rat was similar. Small amounts of 1-methyladenine (m1Ade) and 3-methylguanine (m3Gua) were also detected in the urine. The excretion of m7Ade derived from the methyl group of the carcinogen rather than from the normal precursor for methylation, implies that this adduct, like m3Ade, may serve as an indicator in urine for exposure to methylating carcinogens.

  17. Rapacuronium bromide (Organon Teknika).

    PubMed

    Plowman, A N

    1999-07-01

    Organon Teknika's rapacuronium bromide (Org-9487), the 16-N-allyl, 17-beta-propionate analog of vecuronium bromide, is in phase III clinical trials in the US and Europe for potential use as an anesthetic. It is a steroidal neuromuscular blocking drug characterized by low potency, rapid rate of block development and short time course of neuromuscular blocking action as compared with other non-depolarizing compounds [170210,221422]. A multicenter, randomized, assessor-blind, placebo-controlled, dose-finding study in patients undergoing tracheal intubation showed that the drug produced a dose dependent neuromuscular block. Doses of 1.5 to 2 mg/kg allowed rapid intubation and short duration of action [273336]. Another study showed that the drug does not cause cardiovascular side-effects [273336]. A meeting was held in Europe on 8 February 1999 to brief company employees on the registration and release of rapacuronium [319211] for which the company anticipates a launch in late 1999 [320706]. Organon estimates that the market value of Org-9487 is between dollar 100 m and dollar 250 m a year, each for Europe and the US [221422].

  18. Effect of Exposure to 900 MHz GSM Mobile Phone Radiofrequency Radiation on Estrogen Receptor Methylation Status in Colon Cells of Male Sprague Dawley Rats

    PubMed Central

    Mokarram, P.; Sheikhi, M.; Mortazavi, S.M.J.; Saeb, S.; Shokrpour, N.

    2017-01-01

    Background: Over the past several years, the rapidly increasing use of mobile phones has raised global concerns about the biological effects of exposure to radiofrequency (RF) radiation. Numerous studies have shown that exposure to electromagnetic fields (EMFs) can be associated with effects on the nervous, endocrine, immune, cardiovascular, hematopoietic and ocular systems. In spite of genetic diversity, the onset and progression of cancer can be controlled by epigenetic mechanisms such as gene promoter methylation. There are extensive studies on the epigenetic changes of the tumor suppressor genes as well as the identification of methylation biomarkers in colorectal cancer. Some studies have revealed that genetic changes can be induced by exposure to RF radiation. However, whether or not RF radiation is capable of inducing epigenetic alteration has not been clarified yet. To date, no study has been conducted on the effect of radiation on epigenetic alterations in colorectal cancer (CRC). Several studies have also shown that methylation of estrogen receptor α (ERα), MYOD, MGMT, SFRP2 and P16 play an important role in CRC. It can be hypothesized that RF exposure can be a reason for the high incidence of CRC in Iran. This study aimed to investigate whether epigenetic pattern of ERα is susceptible to RF radiation and if RF radiation can induce radioadaptive response as epigenetic changes after receiving the challenge dose (γ-ray). Material and Method: 40 male Sprague-Dawley rats were divided into 4 equal groups (Group I: exposure to RF radiation of a GSM cell phone for 4 hours and sacrificed after 24 hours; Group II: RF exposure for 4 hours, exposure to Co-60 gamma radiation (3 Gy) after 24 hours and sacrificed after 72 hrs; Group III: only 3Gy gamma radiation; Group 4: control group). DNA from colon tissues was extracted to evaluate the methylation status by methylation specific PCR. Results: Our finding showed that exposure to GSM cell phone RF radiation was

  19. Effect of Exposure to 900 MHz GSM Mobile Phone Radiofrequency Radiation on Estrogen Receptor Methylation Status in Colon Cells of Male Sprague Dawley Rats.

    PubMed

    Mokarram, P; Sheikhi, M; Mortazavi, S M J; Saeb, S; Shokrpour, N

    2017-03-01

    Over the past several years, the rapidly increasing use of mobile phones has raised global concerns about the biological effects of exposure to radiofrequency (RF) radiation. Numerous studies have shown that exposure to electromagnetic fields (EMFs) can be associated with effects on the nervous, endocrine, immune, cardiovascular, hematopoietic and ocular systems. In spite of genetic diversity, the onset and progression of cancer can be controlled by epigenetic mechanisms such as gene promoter methylation. There are extensive studies on the epigenetic changes of the tumor suppressor genes as well as the identification of methylation biomarkers in colorectal cancer. Some studies have revealed that genetic changes can be induced by exposure to RF radiation. However, whether or not RF radiation is capable of inducing epigenetic alteration has not been clarified yet. To date, no study has been conducted on the effect of radiation on epigenetic alterations in colorectal cancer (CRC). Several studies have also shown that methylation of estrogen receptor α (ERα), MYOD, MGMT, SFRP2 and P16 play an important role in CRC. It can be hypothesized that RF exposure can be a reason for the high incidence of CRC in Iran. This study aimed to investigate whether epigenetic pattern of ERα is susceptible to RF radiation and if RF radiation can induce radioadaptive response as epigenetic changes after receiving the challenge dose (γ-ray). 40 male Sprague-Dawley rats were divided into 4 equal groups (Group I: exposure to RF radiation of a GSM cell phone for 4 hours and sacrificed after 24 hours; Group II: RF exposure for 4 hours, exposure to Co-60 gamma radiation (3 Gy) after 24 hours and sacrificed after 72 hrs; Group III: only 3Gy gamma radiation; Group 4: control group). DNA from colon tissues was extracted to evaluate the methylation status by methylation specific PCR. Our finding showed that exposure to GSM cell phone RF radiation was capable of altering the pattern of ERα gene

  20. In Utero Exposure to Dietary Methyl Nutrients and Breast Cancer Risk in Offspring

    DTIC Science & Technology

    2010-09-01

    and congenital abnormalities (13). For example, folic acid supplementation prevents both the occurrence and recurrence of neural tube defects (2) and...Ames, IA, 2002. 2. Bailey, L.B., G.C. Rampersaud, and G.P.A. Kauwell. 2003. Folic acid supplements and fortification affect the risk for neural tube ...distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Lipotropes (methionine, choline, folate , and vitamin B12) are dietary methyl donors and

  1. Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC)

    PubMed Central

    Richmond, Rebecca C.; Simpkin, Andrew J.; Woodward, Geoff; Gaunt, Tom R.; Lyttleton, Oliver; McArdle, Wendy L.; Ring, Susan M.; Smith, Andrew D.A.C.; Timpson, Nicholas J.; Tilling, Kate; Davey Smith, George; Relton, Caroline L.

    2015-01-01

    Maternal smoking during pregnancy has been found to influence newborn DNA methylation in genes involved in fundamental developmental processes. It is pertinent to understand the degree to which the offspring methylome is sensitive to the intensity and duration of prenatal smoking. An investigation of the persistence of offspring methylation associated with maternal smoking and the relative roles of the intrauterine and postnatal environment is also warranted. In the Avon Longitudinal Study of Parents and Children, we investigated associations between prenatal exposure to maternal smoking and offspring DNA methylation at multiple time points in approximately 800 mother–offspring pairs. In cord blood, methylation at 15 CpG sites in seven gene regions (AHRR, MYO1G, GFI1, CYP1A1, CNTNAP2, KLF13 and ATP9A) was associated with maternal smoking, and a dose-dependent response was observed in relation to smoking duration and intensity. Longitudinal analysis of blood DNA methylation in serial samples at birth, age 7 and 17 years demonstrated that some CpG sites showed reversibility of methylation (GFI1, KLF13 and ATP9A), whereas others showed persistently perturbed patterns (AHRR, MYO1G, CYP1A1 and CNTNAP2). Of those showing persistence, we explored the effect of postnatal smoke exposure and found that the major contribution to altered methylation was attributed to a critical window of in utero exposure. A comparison of paternal and maternal smoking and offspring methylation showed consistently stronger maternal associations, providing further evidence for causal intrauterine mechanisms. These findings emphasize the sensitivity of the methylome to maternal smoking during early development and the long-term impact of such exposure. PMID:25552657

  2. Epigenome-Wide Assessment of DNA Methylation in the Placenta and Arsenic Exposure in the New Hampshire Birth Cohort Study (USA).

    PubMed

    Green, Benjamin B; Karagas, Margaret R; Punshon, Tracy; Jackson, Brian P; Robbins, David J; Houseman, E Andres; Marsit, Carmen J

    2016-08-01

    Arsenic is one of the most commonly encountered environmental toxicants, and research from model systems has suggested that one mode of its toxic activity may be through alterations in DNA methylation. In utero exposure to arsenic can affect fetal, newborn, and infant health, resulting in a range of phenotypic outcomes. This study examined variation in placental DNA methylation and its relationship to arsenic exposure in 343 individuals enrolled in the New Hampshire Birth Cohort Study. Linear regression models using a reference-free correction to account for cellular composition were employed to determine CpG loci affected by arsenic levels. Total arsenic measured in maternal urine during the second trimester was not associated with methylation in the placenta, whereas arsenic levels quantified through maternal toenail collected at birth were associated with methylation at a single CpG locus (p = 4.1 × 10-8). Placenta arsenic levels were associated with 163 differentially methylated loci (false discovery rate < 0.05), with 11 probes within the LYRM2 gene reaching genome-wide significance (p < 10-8). Measurement of LYRM2 mRNA levels indicated that methylation was weakly to moderately correlated with expression (r = 0.15, p < 0.06). In addition, we identified pathways suggesting changes in placental cell subpopulation proportions associated with arsenic exposure. These data demonstrate the potential for arsenic, even at levels commonly experienced in a U.S. population, to have effects on the DNA methylation status of specific genes in the placenta and thus supports a potentially novel mechanism for arsenic to affect long-term children's health. Green BB, Karagas MR, Punshon T, Jackson BP, Robbins DJ, Houseman EA, Marsit CJ. 2016. Epigenome-wide assessment of DNA methylation in the placenta and arsenic exposure in the New Hampshire Birth Cohort Study (USA). Environ Health Perspect 124:1253-1260; http://dx.doi.org/10.1289/ehp.1510437.

  3. Effects of arsenic exposure on DNA methylation in cord blood samples from newborn babies and in a human lymphoblast cell line

    PubMed Central

    2012-01-01

    Background Accumulating evidence indicates that in utero exposure to arsenic is associated with congenital defects and long-term disease consequences including cancers. Recent studies suggest that arsenic carcinogenesis results from epigenetic changes, particularly in DNA methylation. This study aimed to investigate DNA methylation changes as a result of arsenic exposure in utero and in vitro. Methods For the exposure in utero study, a total of seventy-one newborns (fifty-five arsenic-exposed and sixteen unexposed newborns) were recruited. Arsenic concentrations in the drinking water were measured, and exposure in newborns was assessed by measurement of arsenic concentrations in cord blood, nails and hair by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). In the in vitro study, human lymphoblasts were treated with arsenite at 0-100 μM for two, four and eight hours (short-term) and at 0, 0.5 and 1.0 μM for eight-weeks period (long-term). DNA methylation was analyzed in cord blood lymphocytes and lymphoblasts treated with arsenite in vitro. Global DNA methylation was determined as LINE-1 methylation using combined bisulfite restriction analysis (COBRA) and total 5-methyldeoxycytidine (5MedC) content which was determined by HPLC-MS/MS. Methylation of p53 was determined at the promoter region using methylation-specific restriction endonuclease digestion with MspI and HpaII. Results Results showed that arsenic-exposed newborns had significantly higher levels of arsenic in cord blood, fingernails, toenails and hair than those of the unexposed subjects and a slight increase in promoter methylation of p53 in cord blood lymphocytes which significantly correlated with arsenic accumulation in nails (p < 0.05) was observed, while LINE-1 methylation was unchanged. Short-term in vitro arsenite treatment in lymphoblastoid cells clearly demonstrated a significant global hypomethylation, determined as reduction in LINE-1 methylation and total 5-MedC content, and p53

  4. Accounting for Life-Course Exposures in Epigenetic Biomarker Association Studies: Early Life Socioeconomic Position, Candidate Gene DNA Methylation, and Adult Cardiometabolic Risk.

    PubMed

    Huang, Jonathan Y; Gavin, Amelia R; Richardson, Thomas S; Rowhani-Rahbar, Ali; Siscovick, David S; Hochner, Hagit; Friedlander, Yechiel; Enquobahrie, Daniel A

    2016-10-01

    Recent studies suggest that epigenetic programming may mediate the relationship between early life environment, including parental socioeconomic position, and adult cardiometabolic health. However, interpreting associations between early environment and adult DNA methylation may be difficult because of time-dependent confounding by life-course exposures. Among 613 adult women (mean age = 32 years) of the Jerusalem Perinatal Study Family Follow-up (2007-2009), we investigated associations between early life socioeconomic position (paternal occupation and parental education) and mean adult DNA methylation at 5 frequently studied cardiometabolic and stress-response genes (ABCA1, INS-IGF2, LEP, HSD11B2, and NR3C1). We used multivariable linear regression and marginal structural models to estimate associations under 2 causal structures for life-course exposures and timing of methylation measurement. We also examined whether methylation was associated with adult cardiometabolic phenotype. Higher maternal education was consistently associated with higher HSD11B2 methylation (e.g., 0.5%-point higher in 9-12 years vs. ≤8 years, 95% confidence interval: 0.1, 0.8). Higher HSD11B2 methylation was also associated with lower adult weight and total and low-density lipoprotein cholesterol. We found that associations with early life socioeconomic position measures were insensitive to different causal assumption; however, exploratory analysis did not find evidence for a mediating role of methylation in socioeconomic position-cardiometabolic risk associations.

  5. Methyl group balance in brain and liver: role of choline on increased S-adenosyl methionine (SAM) demand by chronic arsenic exposure.

    PubMed

    Ríos, Rosalva; Santoyo, Martha E; Cruz, Daniela; Delgado, Juan Manuel; Zarazúa, Sergio; Jiménez-Capdeville, María E

    2012-11-30

    Arsenic toxicity has been related to its interference with one carbon metabolism, where a high demand of S-adenosylmethionine (SAM) for arsenic methylation as well as a failure of its regeneration would compromise the availability of methyl groups for diverse cellular functions. Since exposed animals show disturbances of methylated products such as methylated arginines, myelin and axon membranes, this work investigates whether alterations of SAM, choline and phosphatidylcholine (PC) in the brain of arsenic exposed rats are associated with myelin alterations and myelin basic protein (MBP) immunoreactivity. Also these metabolites, morphologic and biochemical markers of methyl group alterations were analyzed in the liver, the main site of arsenic methylation. In adult, life-long arsenic exposed rats through drinking water (3 ppm), no changes of SAM, choline and PC concentrations where found in the brain, but SAM and PC were severely decreased in liver accompanied by a significant increase of choline. These results suggest that choline plays an important role as methyl donor in arsenic exposure, which could underlie hepatic affections observed when arsenic exposure is combined with other environmental factors. Also, important myelin and nerve fiber alterations, accompanied by a 75% decrease of MBP immunoreactivity were not associated with a SAM deficit in the brain. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  6. Neuropsychiatric manifestations of bromide ingestion

    PubMed Central

    Battin, David G. J.; Varkey, T. Antony

    1982-01-01

    Two cases of bromide intoxication are reported. Although the serum bromide levels were not particularly high, they were related to typical neurological and psychiatric features of bromism. The authors wish to suggest that the rare syndrome of bromism be considered in the differential diagnosis of obscure or refractory neuro-psychiatric symptomatology. PMID:7134096

  7. Effects of methyl and inorganic mercury exposure on genome homeostasis and mitochondrial function in Caenorhabditis elegans.

    PubMed

    Wyatt, Lauren H; Luz, Anthony L; Cao, Xiou; Maurer, Laura L; Blawas, Ashley M; Aballay, Alejandro; Pan, William K Y; Meyer, Joel N

    2017-04-01

    Mercury toxicity mechanisms have the potential to induce DNA damage and disrupt cellular processes, like mitochondrial function. Proper mitochondrial function is important for cellular bioenergetics and immune signaling and function. Reported impacts of mercury on the nuclear genome (nDNA) are conflicting and inconclusive, and mitochondrial DNA (mtDNA) impacts are relatively unknown. In this study, we assessed genotoxic (mtDNA and nDNA), metabolic, and innate immune impacts of inorganic and organic mercury exposure in Caenorhabditis elegans. Genotoxic outcomes measured included DNA damage, DNA damage repair (nucleotide excision repair, NER; base excision repair, BER), and genomic copy number following MeHg and HgCl2 exposure alone and in combination with known DNA damage-inducing agents ultraviolet C radiation (UVC) and hydrogen peroxide (H2O2), which cause bulky DNA lesions and oxidative DNA damage, respectively. Following exposure to both MeHg and HgCl2, low-level DNA damage (∼0.25 lesions/10kb mtDNA and nDNA) was observed. Unexpectedly, a higher MeHg concentration reduced damage in both genomes compared to controls. However, this observation was likely the result of developmental delay. In co-exposure treatments, both mercury compounds increased initial DNA damage (mtDNA and nDNA) in combination with H2O2 exposure, but had no impact in combination with UVC exposure. Mercury exposure both increased and decreased DNA damage removal via BER. DNA repair after H2O2 exposure in mercury-exposed nematodes resulted in damage levels lower than measured in controls. Impacts to NER were not detected. mtDNA copy number was significantly decreased in the MeHg-UVC and MeHg-H2O2 co-exposure treatments. Mercury exposure had metabolic impacts (steady-state ATP levels) that differed between the compounds; HgCl2 exposure decreased these levels, while MeHg slightly increased levels or had no impact. Both mercury species reduced mRNA levels for immune signaling-related genes, but

  8. Epigenetic modulation upon exposure of lung fibroblasts to TiO2 and ZnO nanoparticles: alterations in DNA methylation

    PubMed Central

    Patil, Nayana A; Gade, WN; Deobagkar, Deepti D

    2016-01-01

    Titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles (NPs) are promising candidates for numerous applications in consumer products. This will lead to increased human exposure, thus posing a threat to human health. Both these types of NPs have been studied for their cell toxicity, immunotoxicity, and genotoxicity. However, effects of these NPs on epigenetic modulations have not been studied. Epigenetics is an important link in the genotype and phenotype modulation and misregulation can often lead to lifestyle diseases. In this study, we have evaluated the DNA methylation-based epigenetic changes upon exposure to various concentrations of NPs. The investigation was designed to evaluate global DNA methylation, estimating the corresponding methyltransferase activity and expression of Dnmt gene using lung fibroblast (MRC5) cell line as lungs are the primary route of entry and target of occupational exposure to TiO2 and ZnO NPs. Enzyme-linked immunosorbent assay-based immunochemical assay revealed dose-related decrease in global DNA methylation and DNA methyltransferase activity. We also found direct correlation between the concentration of NPs, global methylation levels, and expression levels of Dnmt1, 3A, and 3B genes upon exposure. This is the first study to investigate effect of exposure to TiO2 and ZnO on DNA methylation levels in MRC5 cells. Epigenetic processes are known to play an important role in reprogramming and adaptation ability of an organism and can have long-term consequences. We suggest that changes in DNA methylation can serve as good biomarkers for early exposure to NPs since they occur at concentrations well below the sublethal levels. Our results demonstrate a clear epigenetic alteration in response to metal oxide NPs and that this effect was dose-dependent. PMID:27660443

  9. Iron bromide vapor laser

    NASA Astrophysics Data System (ADS)

    Sukhanov, V. B.; Shiyanov, D. V.; Trigub, M. V.; Dimaki, V. A.; Evtushenko, G. S.

    2016-03-01

    We have studied the characteristics of a pulsed gas-discharge laser on iron bromide vapor generating radiation with a wavelength of 452.9 nm at a pulse repetition frequency (PRF) of 5-30 kHz. The maximum output power amounted to 10 mW at a PRF within 5-15 kHz for a voltage of 20-25 kV applied to electrodes of the discharge tube. Addition of HBr to the medium produced leveling of the radial profile of emission. Initial weak lasing at a wavelength of 868.9 nm was observed for the first time, which ceased with buildup of the main 452.9-nm line.

  10. Assessment of global and gene-specific DNA methylation in rat liver and kidney in response to non-genotoxic carcinogen exposure.

    PubMed

    Ozden, Sibel; Turgut Kara, Neslihan; Sezerman, Osman Ugur; Durasi, İlknur Melis; Chen, Tao; Demirel, Goksun; Alpertunga, Buket; Chipman, J Kevin; Mally, Angela

    2015-12-01

    Altered expression of tumor suppressor genes and oncogenes, which is regulated in part at the level of DNA methylation, is an important event involved in non-genotoxic carcinogenesis. This may serve as a marker for early detection of non-genotoxic carcinogens. Therefore, we evaluated the effects of non-genotoxic hepatocarcinogens, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), hexachlorobenzene (HCB), methapyrilene (MPY) and male rat kidney carcinogens, d-limonene, p-dichlorobenzene (DCB), chloroform and ochratoxin A (OTA) on global and CpG island promoter methylation in their respective target tissues in rats. No significant dose-related effects on global DNA hypomethylation were observed in tissues of rats compared to vehicle controls using LC-MS/MS in response to short-term non-genotoxic carcinogen exposure. Initial experiments investigating gene-specific methylation using methylation-specific PCR and bisulfite sequencing, revealed partial methylation of p16 in the liver of rats treated with HCB and TCDD. However, no treatment related effects on the methylation status of Cx32, e-cadherin, VHL, c-myc, Igfbp2, and p15 were observed. We therefore applied genome-wide DNA methylation analysis using methylated DNA immunoprecipitation combined with microarrays to identify alterations in gene-specific methylation. Under the conditions of our study, some genes were differentially methylated in response to MPY and TCDD, whereas d-limonene, DCB and chloroform did not induce any methylation changes. 90-day OTA treatment revealed enrichment of several categories of genes important in protein kinase activity and mTOR cell signaling process which are related to OTA nephrocarcinogenicity. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. DNA methylation changes in whole blood is associated with exposure to the environmental contaminants, mercury, lead, cadmium and bisphenol A, in women undergoing ovarian stimulation for IVF.

    PubMed

    Hanna, Courtney W; Bloom, Michael S; Robinson, Wendy P; Kim, Dongsul; Parsons, Patrick J; vom Saal, Frederick S; Taylor, Julia A; Steuerwald, Amy J; Fujimoto, Victor Y

    2012-05-01

    Changes in DNA methylation may play an important role in the deleterious reproductive effects reported in association with exposure to environmental pollutants. In this pilot study, we identify candidate methylation changes associated with exposure to pollutants in women undergoing in vitro fertilization (IVF). Blood and urine were collected from women on the day of oocyte retrieval. Whole blood was analyzed for mercury and lead, and urine for cadmium using inductively coupled plasma mass spectrometry. Unconjugated bisphenol A (BPA) was analyzed in serum using high-performance liquid chromatography with Coularray detection. Participants were dichotomized as higher or lower exposure groups by median concentrations. Using the Illumina GoldenGate Methylation Cancer Panel I, DNA methylation in whole blood from 43 women was assessed at 1505 CpG sites for association with exposure levels of each pollutant. Candidate CpG sites were identified using a Diff Score >|13| (P< 0.05) and an absolute difference >10% which were confirmed using bisulfite pyrosequencing. Methylation of the GSTM1/5 promoter was increased for women with higher mercury exposure (P= 0.04); however, no correlation was observed (r= 0.17, P= 0.27). Reduced methylation was detected in the COL1A2 promoter in women with higher exposure to lead (P= 0.004), and an inverse correlation was observed (r = - 0.45, P= 0.03). Lower methylation of a promoter CpG site at the TSP50 gene was detected in women with higher BPA exposure (P= 0.005), and again an inverse correlation was identified (r = - 0.51, P= 0.001). Altered DNA methylation at various CpG sites was associated with exposure to mercury, lead or BPA, providing candidates to be investigated using a larger study sample, as the results may reflect an independently associated predictor (e.g. socioeconomic status, diet, genetic variants, altered blood cell composition). Further studies accommodating variations in these factors will be needed to confirm these

  12. Postnatal exposure to trichloroethylene alters glutathione redox homeostasis, methylation potential, and neurotrophin expression in the mouse hippocampus

    PubMed Central

    Blossom, Sarah J.; Melnyk, Stepan; Cooney, Craig A.; Gilbert, Kathleen M.; James, S. Jill

    2012-01-01

    Previous studies have shown that continuous exposure throughout gestation until the juvenile period to environmentally-relevant doses of trichloroethylene (TCE) in the drinking water of MRL+/+ mice promoted adverse behavior associated with glutathione depletion in the cerebellum indicating increased sensitivity to oxidative stress. The purpose of this study was to extend our findings and further characterize the impact of TCE exposure on redox homeostasis and biomarkers of oxidative stress in the hippocampus, a brain region prone to oxidative stress. Instead of a continuous exposure, the mice were exposed to water only or two environmentally relevant doses of TCE in the drinking water postnatally from birth until 6 weeks of age. Biomarkers of plasma metabolites in the transsulfuration pathway and the transmethylation pathway of the methionine cycle were also examined. Gene expression of neurotrophins was examined to investigate a possible relationship between oxidative stress, redox imbalance and neurotrophic factor expression with TCE exposure. Our results show that hippocampi isolated from male mice exposed to TCE showed altered glutathione redox homeostasis indicating a more oxidized state. Also observed was a significant, dose dependent increase in glutathione precursors. Plasma from the TCE treated mice showed alterations in metabolites in the transsulfuration and transmethylation pathways indicating redox imbalance and altered methylation capacity. 3-Nitrotyrosine, a biomarker of protein oxidative stress, was also significantly higher in plasma and hippocampus of TCE-exposed mice compared to controls. In contrast, expression of key neurotrophic factors in the hippocampus (BDNF, NGF, and NT-3) was significantly reduced compared to controls. Our results demonstrate that low-level postnatal and early life TCE exposure modulates neurotrophin gene expression in the mouse hippocampus and may provide a mechanism for TCE-mediated neurotoxicity. PMID:22421312

  13. Biomarker responses and morphological effects in juvenile tilapia Oreochromis mossambicus following sequential exposure to the organophosphate azinphos-methyl.

    PubMed

    Jordaan, Martine S; Reinecke, Sophié A; Reinecke, Adriaan J

    2013-11-15

    Pesticides are contaminants of aquatic environments. Such ecosystems in the Western Cape, South Africa are at risk as most organophosphates are highly toxic to fish and other aquatic organisms. The objective of this experimental study was firstly to determine the acute toxicity of azinphos-methyl (AZP) to juvenile fish (Oreochromis mossambicus) and, secondly, to investigate the effects of repeated exposure of fish to an array of sublethal concentrations on morphological parameters such as growth, condition factor and organ-somatic indices. Food consumption and feeding response time were investigated as ecologically relevant behavioral endpoints which could affect growth, reproduction and survival and subsequently causes impacts at the population and/or community level. Finally, acetylcholinesterase (AChE) was used as biomarker to investigate effects at sub-organismal level following sequential exposure to AZP. The aim was to determine how sequential spraying procedures, using different exposure concentrations and intervals, affected fish as reflected by their responses at different organizational levels. A dose-dependent effect on feeding impairment was observed in the feeding response experiment. The correlation found between growth impairment, feeding activity and AChE inhibition therefore indicates that frequency of exposure can play an important role regarding the severity of impacts to non-target organisms. This study provides evidence that AZP has harmful effects on non-target aquatic organisms, such as fish which can be manifested in the early developmental stages. Sequential exposures showed that dosage and frequency of spraying and spraying interval could exacerbate harmful effects. AChE inhibition and organosomatic indices can be used effectively to measure effects. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Efficacy of scalp hair decontamination following exposure to vapours of sulphur mustard simulants 2-chloroethyl ethyl sulphide and methyl salicylate.

    PubMed

    Spiandore, Marie; Piram, Anne; Lacoste, Alexandre; Prevost, Philippe; Maloni, Pascal; Torre, Franck; Asia, Laurence; Josse, Denis; Doumenq, Pierre

    2017-04-01

    Chemical warfare agents are an actual threat and victims' decontamination is a main concern when mass exposure occurs. Skin decontamination with current protocols has been widely documented, as well as surface decontamination. However, considering hair ability to trap chemicals in vapour phase, we investigated hair decontamination after exposure to sulphur mustard simulants methyl salicylate and 2-chloroethyl ethyl sulphide. Four decontamination protocols were tested on hair, combining showering and emergency decontamination (use of Fuller's earth or Reactive Skin Decontamination Lotion RSDL(®)). Both simulants were recovered from hair after treatment, but contents were significantly reduced (42-85% content allowance). Showering alone was the least efficient protocol. Concerning 2-chloroethyl ethyl sulphide, protocols did not display significant differences in decontamination efficacy. For MeS, use of emergency decontaminants significantly increased showering efficacy (10-20% rise), underlining their usefulness before thorough decontamination. Our results highlighted the need to extensively decontaminate hair after chemical exposure. Residual amounts after decontamination are challenging, as their release from hair could lead to health issues. Copyright © 2016. Published by Elsevier B.V.

  15. Uptake and distribution of /sup 14/C during and following exposure to (/sup 14/C)methyl isocyanate

    SciTech Connect

    Ferguson, J.S.; Kennedy, A.L.; Stock, M.F.; Brown, W.E.; Alarie, Y.

    1988-06-15

    Guinea pigs were exposed to (/sup 14/C)methyl isocyanate (/sup 14/CH/sub 3/-NCO, /sup 14/C MIC) for periods of 1 to 6 hr at concentrations of 0.5 to 15 ppm. Arterial blood samples taken during exposure revealed immediate and rapid uptake of /sup 14/C. Clearance of /sup 14/C was then gradual over a period of 3 days. Similarly /sup 14/C was present in urine and bile immediately following exposure, and clearance paralleled that observed in blood. Guinea pigs fitted with a tracheal cannula and exposed while under anesthesia showed a reduced /sup 14/C uptake in blood indicating that most of the /sup 14/C MIC uptake in normal guinea pigs occurred from retention of this agent in the upper respiratory tract passages. In exposed guinea pigs /sup 14/C was distributed to all examined tissues. In pregnant female mice similarly exposed to /sup 14/C MIC, /sup 14/C was observed in all tissues examined following exposure including the uterus, placenta, and fetus. While the form of /sup 14/C distributed in blood and tissues has not yet been identified, these findings may help to explain the toxicity of MIC or MIC reaction products on organs other than the respiratory tract, as noted by several investigators.

  16. Assessing the combined effect of extremely low-frequency magnetic field exposure and oxidative stress on LINE-1 promoter methylation in human neural cells.

    PubMed

    Giorgi, Gianfranco; Pirazzini, Chiara; Bacalini, Maria Giulia; Giuliani, Cristina; Garagnani, Paolo; Capri, Miriam; Bersani, Ferdinando; Del Re, Brunella

    2017-05-01

    Extremely low frequency magnetic fields (ELF-MF) have been classified as "possibly carcinogenic", but their genotoxic effects are still unclear. Recent findings indicate that epigenetic mechanisms contribute to the genome dysfunction and it is well known that they are affected by environmental factors. To our knowledge, to date the question of whether exposure to ELF-MF can influence epigenetic modifications has been poorly addressed. In this paper, we investigated whether exposure to ELF-MF alone and in combination with oxidative stress (OS) can affect DNA methylation, which is one of the most often studied epigenetic modification. To this end, we analyzed the DNA methylation levels of the 5'untranslated region (5'UTR) of long interspersed nuclear element-1s (LINE-1 or L1), which are commonly used to evaluate the global genome methylation level. Human neural cells (BE(2)C) were exposed for 24 and 48 h to extremely low frequency pulsed magnetic field (PMF; 50 Hz, 1 mT) in combination with OS. The methylation levels of CpGs located in L1 5'UTR region were measured by MassARRAY EpiTYPER. The results indicate that exposures to the single agents PMF and OS induced weak decreases and increases of DNA methylation levels at different CpGs. However, the combined exposure to PMF and OS lead to significant decrease of DNA methylation levels at different CpG sites. Most of the changes were transient, suggesting that cells can restore homeostatic DNA methylation patterns. The results are discussed and future research directions outlined.

  17. The influence of sun exposure on the DNA methylation status of MMP9, miR-137, KRT14 and KRT19 genes in human skin.

    PubMed

    Da Silva Melo, Alanne Rayssa; Barroso, Haline; Uchôa De Araújo, Daniel; Ruidomar Pereira, Francisco; De Oliveira, Naila Francis Paulo

    2015-01-01

    Studies have shown that a variety of environmental factors and habits are associated with epigenetic changes. In addition, various genes are also found to respond to UV radiation. The aim of this study was to investigate the sun exposure influence on the DNA methylation profile on the matrix metalloprotease-9 (MMP9), microRNA 137 (miR-137), cytokeratin 14 (KRT14) and 19 (KRT19) genes of skin cells of subjects with no history of skin diseases. Skin biopsies (5mm) were obtained using a punch technique on sun-exposed (outer forearm) and sun-protected areas (inner arm) from 30 corpses from the Brazilian Service of Death Investigation. Skin types were ranked according to Fitzpatrick's criteria. Genomic DNA was extracted and a DNA methylation analysis was performed using Methylation Specific PCR (MSP) or Methylation-Sensitive Restriction Enzymes (MSRE) of sun-exposed and sun-protected skin areas. No differences were found among the areas (p>0.05; McNemar), with the partially methylated condition found to be a common event in skin for both MMP9 and miR-137 genes and the methylated condition for both KRT14 and KRT19 genes. Additional analysis showed no differences in the methylation status when age, gender and skin type were considered, however, the methylation status of miR-137 gene seems to be gender-related. We conclude that sun exposure does not induce changes in the DNA methylation status in MMP9, miR-137, KRT14 and KRT19 genes.

  18. Sex-Specific Muscular Maturation Responses Following Prenatal Exposure to Methylation-Related Micronutrients in Pigs

    PubMed Central

    Oster, Michael; Trakooljul, Nares; Reyer, Henry; Zeyner, Annette; Muráni, Eduard; Ponsuksili, Siriluck; Wimmers, Klaus

    2017-01-01

    Supplementation of micronutrients involved in DNA methylation, particularly during pregnancy, is recommended because of its impacts on human health, but further evidence is needed regarding the effects of over-supplementation and differences between sexes. Here, a porcine model was used to assess effects of maternal supplementation with one-carbon-cycle compounds during prenatal and postnatal stages on offspring muscle development. Sows received either a standard diet (CON) or a standard diet supplemented with folate, B6, B12, methionine, choline, and zinc (MET) throughout gestation. Myogenesis-, growth-, and nutrient utilization-related transcript expression was assessed using quantitative PCR. Organismal phenotype and gene expression effects differed significantly between males and females. Male MET-offspring showed increased fetal weight during late pregnancy but decreased live weight postnatally, with compensatory transcriptional responses comprising myogenic key drivers (Pax7, MyoD1, myogenin). In contrast, female weights were unaffected by diet, and mRNA abundances corresponded to a phenotype of cellular reorganization via FABP3, FABP4, SPP1 and Insulin-like Growth Factor-signaling. These findings in an animal model suggest that supplementation during pregnancy with methylation-related micronutrients can promote sex-specific myogenic maturation processes related to organismal growth and muscle metabolism. The usage of maternal dietary supplements should be more carefully considered regarding its ability to promote fetal and postnatal health. PMID:28106759

  19. Sex-Specific Muscular Maturation Responses Following Prenatal Exposure to Methylation-Related Micronutrients in Pigs.

    PubMed

    Oster, Michael; Trakooljul, Nares; Reyer, Henry; Zeyner, Annette; Muráni, Eduard; Ponsuksili, Siriluck; Wimmers, Klaus

    2017-01-18

    Supplementation of micronutrients involved in DNA methylation, particularly during pregnancy, is recommended because of its impacts on human health, but further evidence is needed regarding the effects of over-supplementation and differences between sexes. Here, a porcine model was used to assess effects of maternal supplementation with one-carbon-cycle compounds during prenatal and postnatal stages on offspring muscle development. Sows received either a standard diet (CON) or a standard diet supplemented with folate, B6, B12, methionine, choline, and zinc (MET) throughout gestation. Myogenesis-, growth-, and nutrient utilization-related transcript expression was assessed using quantitative PCR. Organismal phenotype and gene expression effects differed significantly between males and females. Male MET-offspring showed increased fetal weight during late pregnancy but decreased live weight postnatally, with compensatory transcriptional responses comprising myogenic key drivers (Pax7, MyoD1, myogenin). In contrast, female weights were unaffected by diet, and mRNA abundances corresponded to a phenotype of cellular reorganization via FABP3, FABP4, SPP1 and Insulin-like Growth Factor-signaling. These findings in an animal model suggest that supplementation during pregnancy with methylation-related micronutrients can promote sex-specific myogenic maturation processes related to organismal growth and muscle metabolism. The usage of maternal dietary supplements should be more carefully considered regarding its ability to promote fetal and postnatal health.

  20. Maternal Arsenic Exposure, Arsenic Methylation Efficiency, and Birth Outcomes in the Biomarkers of Exposure to ARsenic (BEAR) Pregnancy Cohort in Mexico

    PubMed Central

    Laine, Jessica E.; Bailey, Kathryn A.; Rubio-Andrade, Marisela; Olshan, Andrew F.; Smeester, Lisa; Drobná, Zuzana; Herring, Amy H.; Stýblo, Miroslav; García-Vargas, Gonzalo G.

    2014-01-01

    Background: Exposure to inorganic arsenic (iAs) from drinking water is a global public health problem, yet much remains unknown about the extent of exposure in susceptible populations. Objectives: We aimed to establish the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort in Gómez Palacio, Mexico, to better understand the effects of iAs exposure on pregnant women and their children. Methods: Two hundred pregnant women were recruited for this study. Concentrations of iAs in drinking water (DW-iAs) and maternal urinary concentrations of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) were determined. Birth outcomes were analyzed for their relationship to DW-iAs and to the concentrations and proportions of maternal urinary arsenicals. Results: DW-iAs for the study subjects ranged from < 0.5 to 236 μg As/L. More than half of the women (53%) had DW-iAs that exceeded the World Health Organization’s recommended guideline of 10 μg As/L. DW-iAs was significantly associated with the sum of the urinary arsenicals (U-tAs). Maternal urinary concentrations of MMAs were negatively associated with newborn birth weight and gestational age. Maternal urinary concentrations of iAs were associated with lower mean gestational age and newborn length. Conclusions: Biomonitoring results demonstrate that pregnant women in Gómez Palacio are exposed to potentially harmful levels of DW-iAs. The data support a relationship between iAs metabolism in pregnant women and adverse birth outcomes. The results underscore the risks associated with iAs exposure in vulnerable populations. Citation: Laine JE, Bailey KA, Rubio-Andrade M, Olshan AF, Smeester L, Drobná Z, Herring AH, Stýblo M, García-Vargas GG, Fry RC. 2015. Maternal arsenic exposure, arsenic methylation efficiency, and birth outcomes in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Mexico. Environ Health Perspect 123:186–192; http://dx.doi.org/10

  1. Gene transcription profiles, global DNA methylation and potential transgenerational epigenetic effects related to Zn exposure history in Daphnia magna.

    PubMed

    Vandegehuchte, Michiel B; De Coninck, Dieter; Vandenbrouck, Tine; De Coen, Wim M; Janssen, Colin R

    2010-10-01

    A reduced level of DNA methylation has recently been described in both Zn-exposed and non-exposed offspring of Daphnia magna exposed to Zn. The hypothesis examined in this study is that DNA hypomethylation has an effect on gene transcription. A second hypothesis is that accumulative epigenetic effects can affect gene transcription in non-exposed offspring from parents with an exposure history of more than one generation. Transcriptional gene regulation was studied with a cDNA microarray. In the exposed and non-exposed hypomethylated daphnids, a large proportion of common genes were similarly up- or down-regulated, indicating a possible effect of the DNA hypomethylation. Two of these genes can be mechanistically involved in DNA methylation reduction. The similar transcriptional regulation of two and three genes in the F0 and F1 exposed daphnids on one hand and their non-exposed offspring on the other hand, could be the result of a one-generation temporary transgenerational epigenetic effect, which was not accumulative. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  2. Photochemistry of alkyl bromides trapped in water ice films

    NASA Astrophysics Data System (ADS)

    Schrems, O.; Okaikwei, B.; Bluszcz, Th.

    2012-04-01

    Photochemical reactions of atmospheric trace gases taking place at the surface of atmospheric ice particles and in bulk ice are important in stratospheric and tropospheric chemistry but also in polar and alpine snowpack chemistry. Consequently, the understanding of the uptake und incorporation of atmospheric trace gases in water ice as well as their interactions with water molecules is very important for the understanding of processes which occur in ice particles and at the air/ice interface. Reactive atmospheric trace gases trapped in ice are subject of photochemical reactions when irradiated with solar UV radiation. Among such compounds bromine species are highly interesting due to their potential of depleting ozone both in the stratosphere and troposphere. Organic bromine gases can carry bromine to the stratosphere. Methyl bromide (CH3Br) is the largest bromine carrier to the stratosphere. It has both natural and anthropogenic sources. In this contribution we will present the results of our laboratory studies of alkyl bromides (methyl, bromide (CH3Br), dimethyl bromide (CH2Br2), n-propyl bromide (C3H7Br), 1,2-dibromoethane C2H4Br2)), trapped in water ice. We have simulated the UV photochemistry of these brominated alkanes isolated in ice films kept at 16 K and for comparison in solid argon matrices. The photoproducts formed in the ice have been identified by means of FTIR spectroscopy. Reflection absorption infrared spectroscopy (RAIRS) is especially useful to study nascent ice surfaces, kinetics of adsorption/decomposition, and heterogeneous catalysis. Among the observed photoproducts we could identify carbon monoxide and carbon dioxide for each alkyl bromide studied. The photoproduct HBr is dissociated in the bulk ice. Based on the experimental observations possible reaction mechanisms will be discussed.

  3. In utero exposure to maternal smoking is associated with DNA methylation alterations and reduced neuronal content in the developing fetal brain.

    PubMed

    Chatterton, Zac; Hartley, Brigham J; Seok, Man-Ho; Mendelev, Natalia; Chen, Sean; Milekic, Maria; Rosoklija, Gorazd; Stankov, Aleksandar; Trencevsja-Ivanovska, Iskra; Brennand, Kristen; Ge, Yongchao; Dwork, Andrew J; Haghighi, Fatemeh

    2017-01-01

    Intrauterine exposure to maternal smoking is linked to impaired executive function and behavioral problems in the offspring. Maternal smoking is associated with reduced fetal brain growth and smaller volume of cortical gray matter in childhood, indicating that prenatal exposure to tobacco may impact cortical development and manifest as behavioral problems. Cellular development is mediated by changes in epigenetic modifications such as DNA methylation, which can be affected by exposure to tobacco. In this study, we sought to ascertain how maternal smoking during pregnancy affects global DNA methylation profiles of the developing dorsolateral prefrontal cortex (DLPFC) during the second trimester of gestation. When DLPFC methylation profiles (assayed via Illumina, HM450) of smoking-exposed and unexposed fetuses were compared, no differentially methylated regions (DMRs) passed the false discovery correction (FDR ≤ 0.05). However, the most significant DMRs were hypomethylated CpG Islands within the promoter regions of GNA15 and SDHAP3 of smoking-exposed fetuses. Interestingly, the developmental up-regulation of SDHAP3 mRNA was delayed in smoking-exposed fetuses. Interaction analysis between gestational age and smoking exposure identified significant DMRs annotated to SYCE3, C21orf56/LSS, SPAG1 and RNU12/POLDIP3 that passed FDR. Furthermore, utilizing established methods to estimate cell proportions by DNA methylation, we found that exposed DLPFC samples contained a lower proportion of neurons in samples from fetuses exposed to maternal smoking. We also show through in vitro experiments that nicotine impedes the differentiation of neurons independent of cell death. We found evidence that intrauterine smoking exposure alters the developmental patterning of DNA methylation and gene expression and is associated with reduced mature neuronal content, effects that are likely driven by nicotine.

  4. Prenatal exposure to tobacco smoke sex dependently influences methylation and mRNA levels of the Igf axis in lungs of mouse offspring.

    PubMed

    Meyer, K F; Krauss-Etschmann, S; Kooistra, W; Reinders-Luinge, M; Timens, W; Kobzik, L; Plösch, T; Hylkema, M N

    2017-04-01

    Prenatal smoke exposure is a risk factor for abnormal lung development and increased sex-dependent susceptibility for asthma and chronic obstructive pulmonary disease (COPD). Birth cohort studies show genome-wide DNA methylation changes in children from smoking mothers, but evidence for sex-dependent smoke-induced effects is limited. The insulin-like growth factor (IGF) system plays an important role in lung development. We hypothesized that prenatal exposure to smoke induces lasting changes in promoter methylation patterns of Igf1 and Igf1r, thus influencing transcriptional activity and contributing to abnormal lung development. We measured and compared mRNA levels along with promoter methylation of Igf1 and Igf1r and their protein concentrations in lung tissue of 30-day-old mice that had been prenatally exposed to cigarette smoke (PSE) or filtered air (control). Body weight at 30 days after birth was measured as global indicator of normal development. Female PSE mice showed lower mRNA levels of Igf1 and its receptor (Igf1: P = 0.05; Igf1r: P = 0.03). Furthermore, CpG-site-specific methylation changes were detected in Igf1r in a sex-dependent manner and the body weight of female offspring was reduced after prenatal exposure to smoke, while protein concentrations were unaffected. Prenatal exposure to smoke induces a CpG-site-specific loss of Igf1r promoter methylation, which can be associated with body weight. These findings highlight the sex-dependent and potentially detrimental effects of in utero smoke exposure on DNA methylation and Igf1 and Igf1r mRNA levels. The observations support a role for Igf1 and Igf1r in abnormal development. Copyright © 2017 the American Physiological Society.

  5. Maternal phthalate exposure during pregnancy is associated with DNA methylation of LINE-1 and Alu repetitive elements in Mexican-American children.

    PubMed

    Huen, Karen; Calafat, Antonia M; Bradman, Asa; Yousefi, Paul; Eskenazi, Brenda; Holland, Nina

    2016-07-01

    Phthalates are frequently used in personal care products and plasticizers and phthalate exposure is ubiquitous in the US population. Exposure to phthalates during critical periods in utero has been associated with a variety of adverse health outcomes but the biological mechanisms linking these exposures with disease are not well characterized. In this study, we examined the relationship of in utero phthalate exposure with repetitive element DNA methylation, an epigenetic marker of genome instability, in children from the longitudinal birth cohort CHAMACOS. Methylation of Alu and long interspersed nucleotide elements (LINE-1) was determined using pyrosequencing of bisulfite-treated DNA isolated from whole blood samples collected from newborns and 9 year old children (n=355). Concentrations of eleven phthalate metabolites were measured in urine collected from pregnant mothers at 13 and 26 weeks gestation. We found a consistent inverse association between prenatal concentrations of monoethyl phthalate, the most frequently detected urinary metabolite, with cord blood methylation of Alu repeats (β(95%CI): -0.14 (-0.28,0.00) and -0.16 (-0.31, -0.02)) for early and late pregnancy, respectively, and a similar but weaker association with LINE-1 methylation. Additionally, increases in urinary concentrations of di-(2-ethylhexyl) phthalate metabolites during late pregnancy were associated with lower levels of methylation of Alu repeats in 9 year old blood (significant p-values ranged from 0.003 to 0.03). Our findings suggest that prenatal exposure to some phthalates may influence differences in repetitive element methylation, highlighting epigenetics as a plausible biological mechanism through which phthalates may affect health. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Maternal phthalate exposure during pregnancy is associated with DNA methylation of LINE-1 and Alu repetitive elements in Mexican-American children

    PubMed Central

    Huen, Karen; Calafat, Antonia M.; Bradman, Asa; Yousefi, Paul; Eskenazi, Brenda; Holland, Nina

    2016-01-01

    Phthalates are frequently used in personal care products and plasticizers and phthalate exposure is ubiquitous in the US population. Exposure to phthalates during critical periods in utero has been associated with a variety of adverse health outcomes but the biological mechanisms linking these exposures with disease are not well characterized. In this study, we examined the relationship of in utero phthalate exposure with repetitive element DNA methylation, an epigenetic marker of genome instability, in children from the longitudinal birth cohort CHAMACOS. Methylation of Alu and long interspersed nucleotide elements (LINE-1) was determined using pyrosequencing of bisulfite-treated DNA isolated from whole blood samples collected from newborns and 9 year old children (n=355). Concentrations of eleven phthalate metabolites were measured in urine collected from pregnant mothers at 13 and 26 weeks gestation. We found a consistent inverse association between prenatal concentrations of monoethyl phthalate, the most frequently detected urinary metabolite, with cord blood methylation of Alu repeats (β(95%CI):−0.14(−0.28,0.00) and −0.16(−0.31,−0.02)) for early and late pregnancy, respectively, and a similar but weaker association with LINE-1 methylation. Additionally, increases in urinary concentrations of di-(2-ethylhexyl) phthalate metabolites during late pregnancy were associated with lower levels of methylation of Alu repeats in 9 year old blood (significant p-values ranged from 0.003 to 0.03). Our findings suggest that prenatal exposure to some phthalates may influence differences in repetitive element methylation, highlighting epigenetics as a plausible biological mechanism through which phthalates may affect health. PMID:27019040

  7. Exposures to polyvinyl chloride, methyl ketone and other chemicals. The pulmonary and non-pulmonary effect.

    PubMed

    Oleru, U G; Onyekwere, C

    1992-01-01

    As part of the continuing assessment of the health impact of exposures in the emerging industries of Nigeria, a study was conducted to determine the relative impact of exposures encountered in four operations of a shoe factory. The health impact assessment consisted of spirometric lung function evaluations and environmental measurement for polyvinyl chloride (1.6 +/- 5 ppm). The study showed that there were differences among exposure subgroups with respect to pulmonary, neurological and dermal toxicities and that these differences were dictated by the types of exposure encountered. Pulmonary toxicity was most severe in the vinyl chloride-exposed subgroup. Neurological impact was most severe in the leather and methylethyl ketone-exposed subgroup and dermal toxicity most severe in the subgroup exposed to plasticizers and stabilizers. There existed substantial deficits in lung function (forced expiratory volume, forced vital capacity FEV1, FVC) among the subgroups relative to normal, non-industrially exposed Nigerians of similar age and height. The deficits in lung function, particularly in FVC, paralleled the variations in the prevalence of restrictive lung disease, which for the whole study group was 56.5 cases per 1000 person-years. The vinyl chloride-exposed subgroup had the highest prevalence of restrictive lung disease, 92.6 cases per 100 person-years. Step-wise multiple regression suggested that 27% of the deficit in FEV1 was explainable by the number of exposures. The use of person-years as a denominator gives a better estimate of risk than the total number of subjects as it incorporates both the number exposed and the total exposure experience.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Trivalent methylated arsenical-induced phosphatidylserine exposure and apoptosis in platelets may lead to increased thrombus formation

    SciTech Connect

    Bae, Ok-Nam; Lim, Kyung-Min; Chung, Jin-Ho

    2009-09-01

    Trivalent methylated metabolites of arsenic, monomethylarsonous acid (MMA{sup III}) and dimethylarsinous acid (DMA{sup III}), have been found highly reactive and toxic in various cells and in vivo animal models, suggesting their roles in the arsenic-associated toxicity. However, their effects on cardiovascular system including blood cells, one of the most important targets for arsenic toxicity, remain poorly understood. Here we found that MMA{sup III} and DMA{sup III} could induce procoagulant activity and apoptosis in platelets, which play key roles in the development of various cardiovascular diseases (CVDs) through excessive thrombus formation. In freshly isolated human platelets, treatment of MMA{sup III} resulted in phosphatidylserine (PS) exposure, a hallmark of procoagulant activation, accompanied by distinctive apoptotic features including mitochondrial membrane potential disruption, cytochrome c release, and caspase-3 activation. These procoagulant activation and apoptotic features were found to be mediated by the depletion of protein thiol and intracellular ATP, and flippase inhibition by MMA{sup III}, while the intracellular calcium increase or reactive oxygen species generation was not involved. Importantly, increased platelet procoagulant activity by MMA{sup III} resulted in enhanced blood coagulation and excessive thrombus formation in a rat in vivo venous thrombosis model. DMA{sup III} also induced PS-exposure with apoptotic features mediated by protein thiol depletion, which resulted in enhanced thrombin generation. In summary, we believe that this study provides an important evidence for the role of trivalent methylated arsenic metabolites in arsenic-associated CVDs, giving a novel insight into the role of platelet apoptosis in toxicant-induced cardiovascular toxicity.

  9. In vitro exposure of human blood mononuclear cells to active vitamin D does not induce substantial change to DNA methylation on a genome-scale.

    PubMed

    Chavez Valencia, Raul A; Martino, David J; Saffery, Richard; Ellis, Justine A

    2014-05-01

    It is well-established that vitamin D impacts gene regulation via vitamin D response elements (VDREs) across the genome. Recent evidence, primarily at a locus-specific level, suggests that alterations to DNA methylation may also be a relevant mechanism through which vitamin D regulates gene expression. Given the intense interest in vitamin D, particularly as an immune modifier, we sought to examine the impact of vitamin D exposure on the immune cell methylome in vitro. We exposed primary human blood mononuclear cells with up to 100nM calcitriol for up to 120h, and measured genome-scale DNA methylation response using the Illumina Infinium HumanMethylation450 beadchip array. We observed that, while the expression of known vitamin D responsive genes was clearly altered by calcitriol exposure, substantial genome-scale changes to DNA methylation were not induced. Our data suggests that, over the exposure period measured, changes to DNA methylation may not be a predominant mechanism through which vitamin D impacts gene expression in human immune cells. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Long-term ambient particle exposures and blood DNA methylation age: findings from the VA normative aging study

    PubMed Central

    Nwanaji-Enwerem, Jamaji C.; Colicino, Elena; Trevisi, Letizia; Kloog, Itai; Just, Allan C.; Shen, Jincheng; Brennan, Kasey; Dereix, Alexandra; Hou, Lifang; Vokonas, Pantel; Schwartz, Joel; Baccarelli, Andrea A.

    2016-01-01

    Background Ambient particles have been shown to exacerbate measures of biological aging; yet, no studies have examined their relationships with DNA methylation age (DNAm-age), an epigenome-wide DNA methylation based predictor of chronological age. Objective We examined the relationship of DNAm-age with fine particulate matter (PM2.5), a measure of total inhalable particle mass, and black carbon (BC), a measure of particles from vehicular traffic. Methods We used validated spatiotemporal models to generate 1-year PM2.5 and BC exposure levels at the addresses of 589 older men participating in the VA Normative Aging Study with 1–3 visits between 2000 and 2011 (n = 1032 observations). Blood DNAm-age was calculated using 353 CpG sites from the Illumina HumanMethylation450 BeadChip. We estimated associations of PM2.5 and BC with DNAm-age using linear mixed effects models adjusted for age, lifestyle/environmental factors, and aging-related diseases. Results After adjusting for covariates, a 1-µg/m3 increase in PM2.5 (95% CI: 0.30, 0.75, P<0.0001) was significantly associated with a 0.52-year increase in DNAm-age. Adjusted BC models showed similar patterns of association (β = 3.02, 95% CI: 0.48, 5.57, P = 0.02). Only PM2.5 (β = 0.54, 95% CI: 0.24, 0.84, P = 0.0004) remained significantly associated with DNAm-age in two-particle models. Methylation levels from 20 of the 353 CpGs contributing to DNAm-age were significantly associated with PM2.5 levels in our two-particle models. Several of these CpGs mapped to genes implicated in lung pathologies including LZTFL1, PDLIM5, and ATPAF1. Conclusion Our results support an association of long-termambient particle levels with DNAm-age and suggest that DNAm-age is a biomarker of particle-related physiological processes. PMID:27453791

  11. Adolescent alcohol exposure alters lysine demethylase 1 (LSD1) expression and histone methylation in the amygdala during adulthood.

    PubMed

    Kyzar, Evan J; Zhang, Huaibo; Sakharkar, Amul J; Pandey, Subhash C

    2016-05-15

    Alcohol exposure in adolescence is an important risk factor for the development of alcoholism in adulthood. Epigenetic processes are implicated in the persistence of adolescent alcohol exposure-related changes, specifically in the amygdala. We investigated the role of histone methylation mechanisms in the persistent effects of adolescent intermittent ethanol (AIE) exposure in adulthood. Adolescent rats were exposed to 2 g/kg ethanol (2 days on/off) or intermittent n-saline (AIS) during postnatal days (PND) 28-41 and used for behavioral and epigenetic studies. We found that AIE exposure caused a long-lasting decrease in mRNA and protein levels of lysine demethylase 1(Lsd1) and mRNA levels of Lsd1 + 8a (a neuron-specific splice variant) in specific amygdaloid structures compared with AIS-exposed rats when measured at adulthood. Interestingly, AIE increased histone H3 lysine 9 dimethylation (H3K9me2) levels in the central nucleus of the amygdala (CeA) and medial nucleus of the amygdala (MeA) in adulthood without producing any change in H3K4me2 protein levels. Acute ethanol challenge (2 g/kg) in adulthood attenuated anxiety-like behaviors and the decrease in Lsd1 + 8a mRNA levels in the amygdala induced by AIE. AIE caused an increase in H3K9me2 occupancy at the brain-derived neurotrophic factor exon IV promoter in the amygdala that returned to baseline after acute ethanol challenge in adulthood. These results indicate that AIE specifically modulates epizymes involved in H3K9 dimethylation in the amygdala in adulthood, which are possibly responsible for AIE-induced chromatin remodeling and adult psychopathology such as anxiety.

  12. Exposure to methyl tert-butyl ether, benzene, and total hydrocarbons at the Singapore-Malaysia causeway immigration checkpoint

    SciTech Connect

    Tan, C.; Ong, H.Y.; Kok, P.W.

    1996-12-31

    The primary aim of this study was to determine the extent and levels of exposure to volatile organic compounds (VOCs) from automobile emissions in a group of immigration officers at a busy cross-border checkpoint. A majority (80%) of the workers monitored were exposed to benzene at levels between 0.01 and 0.5 ppm, with only 1.2% exceeding the current Occupational Safety and Health Administration occupational exposure limit of 1 ppm. The geometric mean (GM) concentrations of 8-hr time-weighted average exposure were 0.03 ppm, 0.9 ppm, and 2.46 ppm for methyl-tert-butyl ether (MTBE), benzene, and total hydrocarbons (THC), respectively. The highest time-weighted average concentrations measured were 1.05 ppm for MTBE, 2.01 ppm for benzene, and 34 ppm for THC. It was found that motorbikes emitted a more significant amount of pollutants compared with motor cars. On average, officers at the motorcycle booths were exposed to four to five times higher levels of VOCs (GMs of 0.07 ppm, 0.23 ppm, and 4.7 ppm for MTBE, benzene, and THC) than their counterparts at the motor car booths (GMs of 0.01 ppm, 0.05 ppm, and 1.5 ppm). The airborne concentrations of all three pollutants correlated with the flow of vehicle traffic. Close correlations were also noted for the concentrations in ambient air for the three pollutants measured. Benzene and MTBE had a correlation coefficient of 0.97. The overall findings showed that the concentrations of various VOCs were closely related to the traffic density, suggesting that they were from a common source, such as exhaust emissions from the vehicles. The results also indicated that although benzene, MTBE, and THC are known to be volatile, a significant amount could still be detected in the ambient environment, thus contributing to our exposure to these compounds. 4 refs., 6 figs.

  13. Respiratory tract changes in guinea pigs, rats, and mice following a single six-hour exposure to methyl isocyanate vapor

    SciTech Connect

    Fowler, E.H.; Dodd, D.E.

    1987-06-01

    Groups of male and female Fischer 344 rats, B6C3F1 mice, and Hartley guinea pigs were exposed once for 6 hr to mean concentrations of 10.5, 5.4, 2.4, 1.0, or 0 (control) ppm of methyl isocyanate (MIC) vapor. Rats and mice were also exposed to 20.4 ppm of MIC. The majority of deaths occurred during postexposure days 1 through 3. The 6-hr LC/sub 50/ values were 6.1 ppm for rats, 12.2 ppm for mice, and 5.4 ppm for guinea pigs. Notable clinical observations during and immediately following MIC exposure were lacrimation, perinasal/perioral wetness, respiratory difficulty (e.g., mouth breathing), decreased activity, ataxia, and hypothermia. Body weight losses were common in all species following MIC exposures of 2.4 ppm or greater. Microscopic lesions included acute necrosis of the epithelial lining throughout the respiratory tract in animals that died shortly after exposure, coupled with congestion, edema, and inflammation. A microscopic lesion that appeared unique to guinea pigs was bronchiolitis obliterans. Additional microscopic lesions observed in some animals that died or were sacrificed at the end of the study (postexposure day 14) consisted of squamous metaplasia of respiratory epithelium in the nasal cavity, which extended into the larynx, trachea, and in some cases, the bronchi. In addition, epithelial regeneration throughout the tract and submucosal fibroplasia in the trachea, bronchi, and bronchioles were observed, the latter lesion being primarily confined to rodents. Only in guinea pigs were there lesions in the 1.0 ppm group attributed to MIC exposure. In conclusion, guinea pigs were more sensitive to the MIC vapor than were rats, which were in turn more sensitive than mice.

  14. Biological effects of short-term, high-concentration exposure to methyl isocyanate. II. Blood chemistry and hematologic evaluations

    SciTech Connect

    Troup, C.M.; Dodd, D.E.; Fowler, E.H.; Frank, F.R.

    1987-06-01

    Human, rat, and guinea pig packed erythrocytes exposed to 100, 500, or 1000 ppm of methyl isocyanate (MIC) vapor in vitro showed a concentration-related inhibition of cholinesterase (ChE) activity. Rat and guinea pig packed erythrocytes showed an almost complete inhibition of ChE activity at 2000 ppm. In vitro exposures of human and guinea pig blood to 1000 or 2000 ppm of MIC vapor resulted in qualitative alterations in the electrophoretic mobility of hemoglobin (Hb) as measured by citrated agar electrophoresis. In rats and guinea pigs, neither IV injection of liquid MIC nor in vivo exposure to 1000 ppm of MIC by inhalation resulted in any inhibition of erythrocyte ChE activity or alteration in Hb electrophoretic mobility. As a result of these observations, it was concluded that neither ChE inhibition nor structural alteration of Hb were major contributing factors to death resulting from MIC exposure. Rats and guinea pigs receiving IV injections of liquid MIC showed an increase in creatine kinase (CK) levels. This increase could not be attributed to a specific isoenzyme of CK by ion exchange chromatography. Rats exposed to 100, 600, or 1000 ppm of MIC and guinea pigs exposed to 25, 125, or 225 ppm of MIC and bled immediately following a 15-min exposure or at 1, 2, 4, or 16 hr postexposure had the following alterations in blood parameters: (a) an increase in CK, (b) increases in hemoglobin concentration and hematocrit, (c) reticulocytosis (rats only), (d) neutrophilia, (e) a decrease in blood pH and PO/sub 2/, and (f) an increase in blood PCO/sub 2/. These findings indicate the occurrence of generalized hypoxic injury with concomitant pathophysiologic alterations, e.g., increases in hemoglobin and hematocrit concentrations.

  15. Influence of bromide on the performance of the amphipod Hyalella azteca in reconstituted waters

    USGS Publications Warehouse

    Ivey, Chris D.; Ingersoll, Christopher G.

    2016-01-01

    Poor performance of the amphipod Hyalella azteca has been observed in exposures using reconstituted waters. Previous studies have reported success in H. azteca water-only exposures with the addition of relatively high concentrations of bromide. The present study evaluated the influence of lower environmentally representative concentrations of bromide on the response ofH. azteca in 42-d water-only exposures. Improved performance of H. azteca was observed in reconstituted waters with >0.02 mg Br/L.

  16. Environmental arsenic exposure and DNA methylation of the tumor suppressor gene p16 and the DNA repair gene MLH1: effect of arsenic metabolism and genotype.

    PubMed

    Hossain, Mohammad Bakhtiar; Vahter, Marie; Concha, Gabriela; Broberg, Karin

    2012-11-01

    Arsenic is carcinogenic, possibly partly through epigenetic mechanisms. We evaluated the effects of arsenic exposure and metabolism on DNA methylation. Arsenic exposure and methylation efficiency in 202 women in the Argentinean Andes were assessed from concentrations of arsenic metabolites in urine (inorganic arsenic, methylarsonic acid [MMA], and dimethylarsinic acid [DMA]), measured by HPLC-ICPMS. Methylation of CpGs of the tumor suppressor gene p16, the DNA repair gene MLH1, and the repetitive elements LINE1 was measured by PCR pyrosequencing of blood DNA. Genotyping (N = 172) for AS3MT was performed using Sequenom™, and gene expression (N = 90) using Illumina DirectHyb HumanHT-12 v3.0. Median arsenic concentration in urine was 230 μg L(-1) (range 10.1-1251). In linear regression analysis, log(2)-transformed urinary arsenic concentrations were positively associated with methylation of p16 (β = 0.14, P = 0.0028) and MLH1 (β = 0.28, P = 0.0011), but not with LINE1. Arsenic concentrations were of borderline significance negatively correlated with expression of p16 (r(s) = -0.20; P = 0.066)), but not with MLH1. The fraction of inorganic arsenic was positively (β = 0.026; P = 0.010) and DMA was negatively (β = -0.017, P = 0.043) associated with p16 methylation with no effect of MMA. Carriers of the slow-metabolizing AS3MT haplotype were associated with more p16 methylation (P = 0.022). Arsenic exposure was correlated with increased methylation, in blood, of genes encoding enzymes that suppress carcinogenesis, and the arsenic metabolism efficiency modified the degree of epigenetic alterations.

  17. Methyl chloroform

    SciTech Connect

    Wray, T.K.

    1994-04-01

    Methyl chloroform is identified as a Class 1 ozone-depleting substance under Title VI of the CAA Amendments. On Nov. 30, 1993, EPA ordered the phaseout of Class 1 ozone-depleting substances -- chlorofluorocarbons (CFCs), halons, carbon tetrachloride and methyl chloroform -- by Jan. 1, 1996. Methyl chloroform and other Class 1 substances may be used after the dead-line if sources can be found through recycling or existing inventories. Methyl chloroform is listed as a hazardous air pollutant under CAA. It also is a SARA Title III, Sec. 313 compound with a reportable quantity of 1,000 pounds. OSHA and the American Conference of Government Industrial Hygienists have set 350 ppm as the time-weighted average airborne exposure level for methyl chloroform. NIOSH lists its immediately dangerous to life or health'' concentration as 1,000 parts per million. DOT identifies the substance as a hazardous material, Class 6.1 (poison).

  18. Maternal exposure to fluoxetine during gestation and lactation affects the DNA methylation programming of rat's offspring: modulation by folic acid supplementation.

    PubMed

    Toffoli, L V; Rodrigues, G M; Oliveira, J F; Silva, A S; Moreira, E G; Pelosi, G G; Gomes, M V

    2014-05-15

    Fluoxetine is an antidepressant that has been largely used for treatment of depression in pregnancy. In the present study we evaluated the effects of the exposure to fluoxetine during gestation and lactation on DNA methylation of rat brain regions. Female Wistar rats were treated with 5mg/kg of fluoxetine during pregnancy and lactation. In order to assess the effects of fluoxetine in the context of maternal folic acid supplementation we performed an additional combined treatment composed by folic acid (8 mg/kg/day) and fluoxetine (5 mg/kg/day). On the postnatal day 22, male rats were euthanized and hippocampus, cortex, hypothalamus, and periaqueductal gray area were removed. Global DNA methylation was quantified using a high-throughput ELISA-based method. Neurofunctional changes were addressed using validated behavioral tests: hot plate, elevated plus maze and open field. A decrease in the global DNA methylation profile of hippocampus was associated to the exposure to fluoxetine, whereas an increase in methylation was observed in cortex. The combined treatment induced an increase in the methylation of hippocampus indicating the potential of folic acid to modulate this epigenetic alteration. Increase in the latency to the thermal nociceptive response was observed in animals exposed to fluoxetine whereas this effect was abolished in animals from the combined treatment. In summary we demonstrated that exposure to fluoxetine during gestation and lactation affect the DNA methylation of brain and the nociceptive response of rats. Furthermore our data reveal the potential of folic acid to modulate epigenetic and functional changes induced by early exposure to fluoxetine.

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

    PubMed

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

    2006-01-05

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

  20. Neurodevelopment of Amazonian Infants: Antenatal and Postnatal Exposure to Methyl- and Ethylmercury

    PubMed Central

    Dórea, José G.; Marques, Rejane C.; Isejima, Cintya

    2012-01-01

    Neurodevelopment as Gesell development scores (GDSs) in relation to mercury exposure in infants (<6 months of age) of one urban center and two rural villages, respectively, of fisherman and cassiterite miners. Mean total hair-Hg (HHg) concentrations of infants from Itapuã (3.95 ± 1.8 ppm) were statistically (P = 0.0001) d