Presentation on theme: "MTBE is an ether that is produced in large amounts in the United States. It is mainly exported to other countries as a fuel additive. MTBE is a concern."— Presentation transcript:
MTBE is an ether that is produced in large amounts in the United States. It is mainly exported to other countries as a fuel additive. MTBE is a concern because it is highly soluble, moves quickly into ground water and stays in the environment for long periods of time. Human and environmental exposures to MTBE are extensive; human health effects are unknown but many studies on animals and microorganisms have been studied. Animals studies have shown shown the carcinogenicity and toxicity of MTBE but more information is needed on the adverse effects on human health. This project will review the available information on the effects of MTBE and the potential effects of MTBE on human health, fate and transport, remediation and regulations. MTBE is used as a solvent and fuel additive that is added to unleaded gasoline to increase the oxygen content and to decrease carbon monoxide emissions. MTBE is a synthetic chemical made from isobutylene and methanol. MTBE is volatile and lipophilic. It is a colorless flammable liquid that has a very high mobility in soil and is resistant to degradation.  The properties of MTBE is a greater problem when it contaminates ground water because it resist biodegradation, moves rapidly through aquifers, and remains at high levels for longer periods of time.  MTBE cancer bioassays have provide evidence of carcinogenicity in experimental animals. Inhalation and oral study in male rats resulted in kidney and testicular tumors, female rats resulted in leukemia and lymphoma. MTBE is not classifiable as to its carcinogenicity to humans because there is no epidemiological evidence. The American Conference of Governmental Industrial Hygienists (ACGIH) classify MTBE as a Confirmed Animal Carcinogen with unknown relevance to Humans. The U.S. Environmental Protection Agency (USEPA) has tentatively classified MTBE as a possible human carcinogen. Methyl tert-butyl ether (MTBE) and its Effects on Humans and Animals Tameka B. Dew, Tony Chung and Antonio F. Machado Dept. of Environmental and Occupational Health, California State University, Northridge The mechanism for MTBE metabolism is important because MTBE and its metabolites may cause renal toxicity, cell proliferation, renal tumors, liver tumors and testicular tumors. Another reason it is important is because the metabolites can be used as a marker for exposure to MTBE. Pathways for the degradation of MTBE is by CYP-450. Kinetic studies have shown that CYP-2A6 has a significant role in the metabolism of MTBE. The main intermediate products in the metabolism of MTBE : ① Tert-butyl alcohol (TBA) ② Formaldehyde ③ Tert-butoxy methanol ④ 2-methyl-2-hydroxy-1-propanol ⑤ 2-hydroxy isobutyric acid ⑥ Acetone ⑦ Acetaldehyde ECOTOXICOLOCIAL EFFECTS OF MTBE SpeciesMTBE Concentration Effects Zebra fish (Danio Rerio)  0.11 and 37 mg/L Increases vitellognin synthesis in males. Lowers fish sperm motility. Bacteria (Streptomyces spp.)  1/800 Minimum Inhibitory Concentration (MIC) Suppresses the growth of Streptomyces. Changes the balance of soil micro flora. Algae  (Navicula pelliculosa, Synechococcus leopoliensis) 2400 mg/LReduces growth and changes algal community composition. LEVELS IN ENVIRONMENT Groundwater (2743 samples) Mean concentration range of MTBE 94.7%< 0.2 μg/l 4.9%0.2 – 20 μg/l 0.4%> 20 μg/l MTBE travels easily in soil through which it migrates quickly to groundwater. It is highly soluble in groundwater and biodegrades very slowly. In surface water MTBE volatilizes easily and as a result it is usually detected at lower concentration than groundwater. The physical and chemical properties of MTBE makes it likely to contaminate public drinking water system. FATE AND TRANSPORT In the United States, almost all MTBE is used as a fuel oxygenate in gasoline.  High concentrations of MTBE in gasoline contaminates soil, surface water, and ground water by point sources of oxygenated gasoline. Inhalation is another MTBE exposure route. ① MTBE enters the environment during all phases of the petroleum fuel cycle (auto emissions, evaporative loss, gasoline stations, vehicle & storage tank releases, pipeline leaks, accidental spills, and refinery releases  ① The release of MTBE into the environment contaminates air, soil and water  ① MTBE is highly soluble so it moves rapidly through soil and into ground water.  ① Contamination of water supply leads to exposure when water is drunk.  1.Granular activated carbon (GAC) is the most popular adsorbent used to remove MTBE from contaminated water and has been proven as a successful MTBE remover.  2.Carbonaceous resins of Ambersorb 563 and 572 has high adsorption capacity for MTBE in water.  3.Zeolite with appropriate pore size as adsorbent removal. 4.Nafion as a solid catalyst for the MTBE removal from aqueous solutions.  5.Removal of MTBE by the PAM-zeolite composite.  6.Native microbial bioremediation.  7.Ultraviolet-Base Ozone and Hydrogen Peroxide.  REGULATION AgencyType of RegulationRegulation LevelsDate of Effective USEPADrinking Water Advisory20-40 ppb12/1997 ATSDRAcute Inhalation Minimal Risk Level Chronic Inhalation Minimal Risk Level Acute Oral Minimal Risk Level Intermediate Oral Minimal Risk Level 2.0 ppm 0.7 ppm 0.4 mg/kg/day 0.3 mg/kg/day 08/1996 ACGIHThreshold Limit Value Time weighed average 100 ppm 8-10hr CaliforniaSecondary MCL EPA complete Ban 5.0 ppb01/07/1999 12/31/2003 Iowa, South Dakota EPA Partial BanNo more than trace amounts (0.5% by vol.) MTBE. 5/11/2000 2/28/2001 Minnesota, Nebraska and Colorado EPA complete ban-2000 There are various health complaints documented following MTBE exposure. In particular residents of Fairburn, Alaska reported symptoms such as headaches, dizziness, nausea and respiratory irritation following an oxygenated fuel program using 15% volume MTBE . Currently, the are no definitive human health effects of MTBE but there are concerns regarding the carcinogenicity, the cytotoxicity and the oxidative stress induced by MTBE in rodents. [8,12] Carcinogenic Effects of MTBE in Rats Cancer bioassay in Srague- Dawley Rats Cancer bioassay in Fischer 344 rats 8 week old rats were gavage with 0, 250 and 1000 mg/kg b.w. of MTBE over 104 weeks until death at 166 weeks.  Results Higher incidence of Leydig interstitial cell tumors of the testes in male rats and increase lymphomas and leukemia in female rats. Fischer 344 rats were exposed to 3000 and 8000 ppm MTBE via inhalation for 24 months.  Result Significantly higher incidence of renal and Leydig cell adenomas were reported in male rats. There are also notable changes to liver, thyroids and adrenals of rodents administered MTBE in published studies. [8,12] MTBE Induces Cytotoxicity and Oxidative Stress on Spermatogenic and Sertoli cells in Male Rats MTBE induces oxidative stress on spermatogenic cells and Sertoli cells of the testis of rodents. Notably, testicular cell membrane are vulnerable to oxidative stress because they are high in polyunsaturated fatty acids that are susceptible to lipid peroxidation.  In addition there was significant increase of the enzyme oxoguanine DNA glycosylase (Ogg1), which repairs DNA impaired by oxidative stress. Suggesting that Sertoli cells of the testis were damaged at the DNA levels following exposure to MTBE.  MTBE impedes testicular cell function and therefore is likely hinder spermatogenesis or may even lead to cell death.  Study on Hsp60, a stress protein in human nasal septa cell To ascertain Hsp60 expression as a biomarker for MTBE exposure, human nasal septum cells were exposed to MTBE concentrations ranging from 0 to 1000μg/l. Notably, the concentrations used in the study correspond to the blood levels measured in residents of US regions that had health complaints following MTBE exposure. Also the levels of MTBE used in study were relevant to those measured in ground water samples.  Results There was a 2-fold increase in the expression of stress protein Hsp60 in human nasal septum cells after MTBE exposure.  The findings of the present study suggest that MTBE induces stress on the human respiratory system.  Many in vitro and in vivo studies have shown the carcinogenicity and toxicity of MTBE. Subacute exposure of MTBE studies have also demonstrated how MTBE has a significant adverse effect on the reproductive system of male Sprague Dawley rats.  Effects observed ① Increase in abnormal sperm ② Irregular and disordered arrangement of the seminiferous epithelium ③ Change in levels of testosterone (T) ④ Change in luteinizing hormone (LH) ⑤ Change in follicle stimulating hormone (FSH) ⑥ Decrease levels of mRNA ⑦ Decrease levels of androgen binding proteins (ABP) MTBE METABOLISM AND METABOLITESABSTRACT INTRODUCTION EFFECTS ON REPRODUCTIVE SYSTEM OF MALE RATS CONCLUSION CHEMICAL STRUCTUREREMEDIATION REFERENCES HEALTH EFFECTS OF MTBE 1. Agency for Toxic Substances and Disease Registry (ATSDR): methyl tert-butyl ether (mtbe) assessed from www.atsdr.gov 2. Ahmed, F. (2001). Toxicology and human health effects following exposure to oxygenated or reformulated gasoline. Toxicology Letters, 123(2), 89-113. 3. Amberg, A., Rosner, E., & Dekant, W. (2001). Toxicokinetics of methyl tert-butyl ether and its metabolites in humans after oral exposure. Toxicological Sciences : An Official Journal of the Society of Toxicology, 61(1), 62-67. 4. Belpoggi, F., Soffritti, M., & Maltoni, C. (1995). Methyl-tertiary-butyl ether (mtbe)--a gasoline additive--causes testicular and lymphohaematopoietic cancers in rats. Toxicology and Industrial Health, 11(2), 119-149. 5. Bird, M.G., Burleigh-Flayer, H.D., Chun, J.S., Douglas, J.F., Kneiss, J.J., Andrews, L.S., 1997. Oncogenicity studies of inhaled methyl tertiary-butyl ether (MTBE) in CD-1 mice and F-344 rats. J. Appl. Toxicol. 17 (Suppl.1),S45–55. 6. Bodenstein, Y., & Duffy, L. (1998). Expression of hsp60, a stress protein, in human nasal septa cells after exposure to mtbe. Environmental Toxicology and Pharmacology, 5(1), 79-83. 7. Bonjar, G. (2004). Potential ecotoxicological implication of methyl tert-butyl ether (mtbe) spills in the environment. Ecotoxicology (London, England), 13(7), 631-635. 8. Borghoff, S., Parkinson, H., & Leavens, T. (2010). Physiologically based pharmacokinetic rat model for methyl tertiary-butyl ether; comparison of selected dose metrics following various mtbe exposure scenarios used for toxicity and carcinogenicity evaluation. Toxicology, 275(1), 79-91. 9. California Environmental Protection Agency (CalEPA): Santa Monica contamination assessed from: calepa.gov 10. Cardinali, F., Blount, B., Schmidt, R., & Morrow, J. (2008). Measurement of fuel oxygenates in tap water using solid-phase microextraction gas chromatography-mass spectrometry. Journal of Chromatographic Science, 46(5) 381-387 11. Environmental Protection Agency (EPA): methyl tert-butyl ether (mtbe) assessed from www.epa.gov 12. de Peyster, A., MacLean, K., Stephens, B., Ahern, L., Westover, C., et al. (2003). Subchronic studies in sprague-dawley rats to investigate mechanisms of mtbe-induced leydig cell cancer. Toxicological Sciences : An Official Journal of the Society of Toxicology, 72(1), 31-42. 13. de Peyster, A., Mihaich, E., Kim, D., Elyea, W., Nemec, M., et al. (2014). Responses of the steroidogenic pathway from exposure to methyl-tert-butyl ether and tert-butanol. Toxicology, 319, 23-37. 14. Fiorenza, S., Suarez, M., & Rifai, H. (2002). Mtbe in groundwater: Status and remediation. Journal of Environmental Engineering, 128(9), 773-781. 15. Hicks, K., Schmidt, R., Nickelsen, M., Boyle, S., Baker, J., et al. (2014). Successful treatment of an mtbe-impacted aquifer using a bioreactor self-colonized by native aquifer bacteria. Biodegradation, 25(1), 41-53. 16. Hung, H., & Lin, T. (2006). Adsorption of mtbe from contaminated water by carbonaceous resins and mordenite zeolite. Journal of Hazardous Materials, 135(1), 210-217. 17. Li, D., Liu, Q., Gong, Y., Huang, Y., & Han, X. (2009). Cytotoxicity and oxidative stress study in cultured rat sertoli cells with methyl tert-butyl ether (mtbe) exposure. Reproductive Toxicology, 27(2), 170-176. 18.Li, D., Yuan, C., Gong, Y., Huang, Y., & Han, X. (2008). The effects of methyl tert-butyl ether (mtbe) on the male rat reproductive system. Food and Chemical Toxicology, 46(7), 2402-2408. 19. Lien, H., & Zhang, W. (2007). Removal of methyl tert-butyl ether (mtbe) with nafion. Journal of Hazardous Materials, 144(1), 194-199. 20. Luttrell, W. (2010). Methyl tert-butyl ether (mtbe). Journal of Chemical Health & Safety, 17(4), 28-29. 21. Moolenaar, R., Hefflin, B., Ashley, D., Middaugh, J., & Etzel, R. (1994). Methyl tertiary butyl ether in human blood after exposure to oxygenated fuel in fairbanks, alaska. Archives of Environmental Health, 49(5), 402-409. 22. Moran, M., Zogorski, J., & Squillace, P. (2005). Mtbe and gasoline hydrocarbons in ground water of the united states. Ground Water, 43(4), 615-627. 23. Moreels, D., Van Cauwenberghe, K., Debaere, B., Rurangwa, E., Vromant, N., et al. (2006). Long-term exposure to environmentally relevant doses of methyl-tert-butyl ether causes significant reproductive dysfunction in the zebrafish (danio rerio). Environmental Toxicology and Chemistry / SETAC, 25(9), 2388-2393. 24. Pankow, J., Korte, N., & Squillace, P. (1997). Review of the environmental behavior and fate of methyl tert-butyl ether. Environmental Toxicology and Chemistry, 16(9), 1836- 1844. 25. Prah, J., Ashley, D., Blount, B., Case, M., Leavens, T., et al. (2004). Dermal, oral, and inhalation pharmacokinetics of methyl tertiary butyl ether (mtbe) in human volunteers. Toxicological Sciences : An Official Journal of the Society of Toxicology, 77(2), 195-205. 26. Rousch, J., & Sommerfeld, M. (1998). Liquid-gas partitioning of the gasoline oxygenate methyl tert-butyl ether (mtbe) under laboratory conditions and its effect on growth of selected algae. Archives of Environmental Contamination and Toxicology, 34(1), 6-11. 27. Shamsipur, M., Miran Beigi, A., Teymouri, M., Poursaberi, T., Mostafavi, S., et al. (2012). Biotransformation of methyl tert-butyl ether by human cytochrome p450 2a6. Biodegradation, 23(2), 311-318. 28. Tawabini, B. (2014). Simultaneous removal of mtbe and benzene from contaminated groundwater using ultraviolet-based ozone and hydrogen peroxide. International Journal of Photoenergy, 2014, 1-7. 29. Zadaka-Amir, D., Nasser, A., Nir, S., & Mishael, Y. (2012). Removal of methyl tertiary-butyl ether (mtbe) from water by polymer-zeolite composites. Microporous and Mesoporous Materials, 151, 216-222. Based on findings of the animal studies and the physiochemical properties of MTBE the EPA should reconsider a safer fuel additive than MTBE. The current EPA drinking water advisory of 20-40 ppb is based on taste and odor is more concerned with the aesthetics of drinking water for consumer consumption. To increase the margin of safety for the public further epidemiology studies should be conducted on MTBE. MTBE contamination of Santa Monica, Ca. Charnock well field In 1995 the city of Santa Monica detected MTBE concentrations that peaked at 610μg/L in their water wells.  It was found that MTBE leaked from underground storage tank at nearby gasoline stations. This resulted in loss of approximately 6 million gallon per day of groundwater supply. Consequently the city of Santa Monica filed a lawsuits against several oil companies and currently there are ongoing remediation.