Abstract  Methyl tertiary-butyl ether (MTBE), an oxygenating fuel additive, is a common groundwater contaminant and causes male rat renal tumors at high inhalation exposures. MTBE is primarily metabolized to tertiary-butyl alcohol (TBA), which also causes renal tumors in male rats following chronic exposure. The pharmacokinetics of MTBE and TBA in rats has been described previously with a physiologically based pharmacokinetic (PBPK) model for single exposures by oral gavage or inhalation (Borghoff et al., 1996, Fundam. Appl. Toxicol., 30, 264-75). The model has not been used to predict the pharmacokinetics of MTBE and TBA from chronic drinking water, oral gavage, or inhalation exposures, which will be important for extrapolating effects from chronic rodent exposures to humans. The purpose of this work was to compare PBPK model predictions of the pharmacokinetics of MTBE and TBA in rats from drinking water, oral gavage, and inhalation exposure. The scenarios included exposure via drinking water (10-2ml increments) and oral gavage at both 1 and 15000 ppm MTBE vs. 6 h/d inhalation exposure to 400 and 3000 ppm MTBE for 5 days. Water concentrations represented high environmental concentrations (1 ppm) or concentrations resulting in carcinogenic responses in rats following chronic oral exposure (15000 ppm). Inhalation concentrations were the current NOAEL and LOAEL for MTBE. Model predictions of Cmax, Tmax, AUC, and steady state concentrations of MTBE and TBA in blood were compared among the exposure scenarios. The model predicted significant differences in the pharmacokinetics following drinking water exposure versus oral gavage, with inhalation exposure resembling a drinking water exposure scenario. Differences in TBA pharmacokinetics among exposures were mainly due to slow clearance resulting in accumulation over time. The model predictions of the pharmacokinetics of TBA can be used to extrapolate relevant effects among exposure scenarios in rats.

Abstract  This medical thesis reviews recent publications on the screeing and monitoring of workers who are occupationally exposed to C[1]-C[4] monofunctional aliphatic alcohols. Contents: physical and chemical properties of monofunctional alcohols; principal uses and sources of intoxication; metabolism and kinetics; methods of sampling and analysis of the atmosphere and biological media; toxic effects; possible interactions with other toxic agents, potentiation; exposure limits; list of laws and regulations in force in France; action to take in case of acute accidental intoxication; medical surveillance in case of prolonged or repeated exposure.

Abstract  Measurement of the biochemical oxygen demand (BOD) of discharged waste water is required by the authorities in several countries to characterize the concentration of polluting (usually organic) material in the water. It is therefore of importance to Shell and their customers to establish to what extent Shell chemicals are biodegradable and contribute to the BOD of waste water. The BOD may be defined as the quantity of oxygen required for the biological and chemical oxidation of water-borne substances under the conditions of test. In this test a very dilute (usually < 10 mg/1) aqueous solution of a chemical is incubated at 20 °C for 5 days in the presence of a selected biota. Comparison of the oxygen content of the solution at the beginning and at the end of the incubation period provides a measure of the BOD. We carried out our tests according to the method described in the APHA "Standard Methods" No. 219. except tint we added 0.5 mg/l allyl thiourea to prevent nitrification. As the inoculum we applied the efflluent of a municipal sewage treatment plant. In cases where we expected appreciably higher BOD results from an adapted inoculum. We realized adaptation by feeding the bacteria in the original seed With the chemical compound concerned. Our results are presented in the following table expressed as gram oxygen per gram chemical substance. For evaluation of these figures we also calculated the degradation percentage, %TOD. This TOD (theoretical oxygen demand) represents the amount of oxygen needed for complete oxidation of the carbon hydrogen and sulfur to carbon dioxide, water and sulfuric acid. In our TOD calculation we assumed that haIogen atoms were left as halides. -NH2-nitrogen as ammonia and –NO2-nitrogen as nitrate. (In practice oxygen demands higher than 75% of the TOD are not reached because in the test period the bacteria produce new cells and thus not completely mineralize a substrate.)

Abstract  BIOSIS COPYRIGHT: BIOL ABS. The performance of anaerobic hybrid reactors treating an organic solvent-containing synthetic pharmaceutical wastewater was evaluated under various wastewater volumetric loading rates and influent compositional changes. The biodegradation, toxicity and treatability of the target C3 and C4 solvents, tert-butanol, isopropanol, isobutanol, sec-butanol and ethyl acetate, were examined. At a hydraulic retention time (HRT) of 2 days and volumetric loading rates ranging from 3.5 to 4.5 kg COD m-3 day-1, the reactors achieved total and soluble COD removal efficiencies of 97-99% in less than five times the HRT. These removal rates were achieved following the introduction of target solvents not previously supplied to the reactors. However, inadequate removal of tert-butanol resulted in a decrease in the soluble COD removal efficiency to 58%. Bacterial enrichments from the reactor biomass using tert-butanol as the sole substrate proved unsuccessful, confirming that tert-butanol is

Abstract  BIOSIS COPYRIGHT: BIOL ABS. RRM SOIL BACTERIA GASOLINE

Abstract  BIOSIS COPYRIGHT: BIOL ABS. A great deal of research has been directed toward the problem of reduction and control of volatile organic solvents (VOS). The aim of this research was to find a process that is both efficient and low cost. We have been able to use to our advantage the increased interest in biotechnology of the past few years in order to further our research for an environmentally safe aerobic system to degrade VOS emissions from a print shop by using biofiltration technology. Our biofilter is an aerobic system for treating air-borne organic pollutants (in this case: VOS) using the degradation properties of microbial flora. This process consists in diffusing polluted gas across a filter bed into which a microbial cultural has previously been introduced. Peat was the medium of choice for inoculation with microorganisms because of its adsorption/absorption properties, its ability to retain moisture and its buffering capacity. The peat we used was spherical in shape thus it was possible fo

Abstract  Sponsored by Department of Energy, Washington, DC. t bioremediation and risk-management practices are being adapted to the increasing possibility of encountering oxygenates (primarily methyl tert-butyl ether, MTBE, and ethanol) as co-contaminants at the approximately 400,000 leaking underground fuel tank (LUFT) sites nationwide. However, little is known about the effect of oxygenates on microbial populations and the resulting shifts in the microbial ecology and catabolic diversity that may result from the inclusion of oxygenates in reformulated gasoline. Among the possible effects are enrichment of oxygenate degrading bacteria in relation to BTEX (benzene, toluene, ethylbenzene and xylenes)- degrading bacteria, the fortuitous enrichment of bacteria that can degrade both oxygenates and BTEX' compounds, no effect on BTEX-degrading populations, or decreases in populations of certain bacteria as a result of toxicity. This study provided some preliminary information for the development of methods to determine the effect of oxygenates on the microbial community responsible for aerobic BTEX degradation.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. The lignin peroxidase enzyme system of the white-rot fungus, Phanerochaete chrysosporium, was assayed for its capacity to degrade two recalcitrant aliphatic ether compounds, high-molecular-mass polyethylene glycol (PEG 20000) and methyl tert-butyl ether. Ligninolytic cultures of Phanerochaete chrysosporium were spiked with each ether compound and incubated in reaction vessels. Separate incubations were conducted in which the ether compounds were present as sole carbon source. Other parameters, such as varying the methyl tert-butyl ether concentration and veratryl alcohol additions were tested. No significant degradation of either compound was observed under any of the conditions tested. Implications of these results are discussed with respect to the oxidative limitations of the lignin peroxidase enzyme system and structural features of substrate molecules that may be requisite for oxidation by this system.

Abstract  Lipase-displaying whole cells appear to be efficient biocatalysts because of their low preparation costs and simple recycling procedure. The combined utilization of Candida antarctica lipase B (CALB) and Rhizomucor miehei lipase (RML), separately displayed on Pichia pastoris whole cells, to produce biodiesel in co-solvent media was investigated. A response surface methodology incorporating a D-optimal design was employed to obtain the optimum reaction conditions for methyl ester (ME) synthesis. The synergistic effect of the two displayed lipases and the use of tert-butanol and isooctane as the co-solvent media were found to significantly improve the transesterification reaction. Scaled-up reactions using various types of feedstock were carried out in a 0.5-l stirred reactor under optimum conditions, affording ME yields over 90% in 12h. Moreover, the ME yields remained above 85% after 20 repeated batch cycles. In conclusion, this biocatalyst affords a promising route to efficient biodiesel production.

Abstract  Carcinogenicity of ethyl tertiary-butyl ether (ETBE) was examined with inhalation exposure using F344/DuCrlCrlj rats. Groups of 50 male and 50 female rats, 6 week old at commencement, were exposed to ETBE at 0, 500, 1,500 or 5,000 ppm (v/v) in whole-body inhalation chambers for 6 h/day, 5 days/week for 104 weeks. A significant increase in the incidence of hepatocellular adenomas was indicated in males exposed at 5,000 ppm, but not in females at any concentration. In addition, significantly increased incidences of eosinophilic and basophilic cell foci were observed in male rats at 5,000 ppm. Regarding non-neoplastic lesions, rat-specific changes were observed in kidney, with an increase in the severity of chronic progressive nephropathy in both sexes at 5,000 ppm. Increased incidences of urothelial hyperplasia of the pelvis were observed at 1,500 ppm and above, and mineral deposition was apparent in the renal papilla at 5,000 ppm in males. There were no treatment-related histopathological changes observed in any other organs or tissues in either sex. The present 2-year inhalation study demonstrated hepatotumorigenicity of ETBE in male, but not in female rats.

Abstract  A series of novel sulfamides incorporating the dopamine scaffold were synthesized. Reaction of amines and tert-butyl-alcohol/benzyl alcohol in the presence of chlorosulfonyl isocyanate (CSI) afforded sulfamoyl carbamates, which were converted to the title compounds by treatment with trifluoroacetic acid or by palladium-catalyzed hydrogenolysis. Inhibition of six α-carbonic anhydrases (CAs, EC 4.2.1.1), that is, CA I, CA II, CA VA, CA IX, CA XII and CA XIV, and two β-CAs from Candida glabrata (CgCA) and Mycobacterium tuberculosis (Rv3588) with these sulfamides was investigated. All CA isozymes were inhibited in the low micromolar to nanomolar range by the dopamine sulfamide analogues. K(i)s were in the range of 0.061-1.822 μM for CA I, 1.47-2.94 nM for CA II, 2.25-3.34 μM for CA VA, 0.041-0.37 μM for CA IX, 0.021-1.52 μM for CA XII, 0.007-0.219 μM for CA XIV, 0.35-5.31 μM for CgCA and 0.465-4.29 μM for Rv3588. The synthesized sulfamides may lead to inhibitors targeting medicinally relevant CA isoforms with potential applications as antiepileptic, antiobesity antitumor agents or anti-infective.

Abstract  Previous results showed that an indigenously isolated yeast strain of Candida tropicalis was found to produce 12.11 g/L of xylitol under unoptimized conditions in presence of 50 g/L of xylose. In the present study, optimizing the process using one-variable at-a-time resulted in the production of 59.07 g/L of xylitol in 96 h in presence of 100 g/L xylose. Further optimization using response surface methodology led to the production of 65.45 g/L in medium containing 100 g/L xylose, 0.5% yeast extract, 0.03% MgSO(4).7H(2)O and 0.2% KH(2)PO(4), pH-4.5, 30 °C, 200 r/min for 96  h with 4% inoculum level. Addition of 1% methanol in response surface methodology optimized-medium led to the production of 67.12 g/L. Scaling up in 10 L fermentor resulted in productivity of 0.80 g/Lh with yield of 0.68 g/g. Efficient synthesis of xylitol esters was achieved with butyric acid (50.32%) and caproic acid (38.36%) in 4 h using Pseudomonas aeruginosa lipase in t-butanol: tetrahydrofuran (1:1 v/v).

Abstract  Exfoliation of layered materials such as graphite and transition metal dichalcogenides into mono- or few-layers is of significant interest for both the fundamental studies and potential applications. Here we report a systematic investigation of the fundamental factors governing the liquid exfoliation process and the rational design of a cosolvent approach for the exfoliation of layered materials. We show that Young's equation can be used to predict the optimal cosolvent concentration for the effective exfoliation of graphite and molybdenum disulphide in water mixtures with methanol, ethanol, isopropanol and t-butyl alcohol. Moreover, we find that the cosolvent molecular size has an important role in the exfoliation yield, attributed to the larger steric repulsion provided by the larger cosolvent molecules. Our study provides critical insight into the exfoliation of layered materials, and defines a rational strategy for the design of an environmentally friendly pathway to the high yield exfoliation of layered materials.

Abstract  To provide guidance on the selection of proper persulfate processes for the remediation of MTBE contaminated groundwater, MTBE aqueous solutions were treated with three common field persulfate processes including heat activated persulfate, Fe(III)-EDTA activated persulfate and alkaline persulfate, respectively. The results were compared with MTBE oxidation by Fenton's reagent and persulfate alone at 25°C. The impact of the activating conditions on the fate of MTBE and its daughter products was investigated. Heat activation at 40°C offered the most rapid removal of MTBE and its daughter products, while Fe(III)-EDTA activation showed higher efficiency of MTBE removal but low removal efficiency of its daughter products. On the other hand, alkaline persulfate showed slower kinetics for the removal of MTBE and less accumulation of the daughter products. Furthermore, tert-butyl alcohol and acetone were observed as the main purgeable daughter products along with a small amount of tert-butyl formate in persulfate oxidation of MTBE, while tert-butyl formate, tert-butyl alcohol and acetone were the main products in Fenton oxidation. Mechanistic analysis suggests that degradation of MTBE by persulfate most likely happens via non-oxygen demand pathways, different from the dominant oxygen demand degradation pathways observed in Fenton oxidation.

Abstract  Presents individual monographs on the risks to health and the environment associated with 1-butanol, 2-butanol, tert-butanol, and isobutanol. These butanol isomers, which occur naturally as products of fermentation, are also synthesized from petrochemicals and widely used as solvents and intermediates in chemical industries. Human exposure to high concentrations is primarily occupational, while exposure to low concentrations is mainly through foods in which the isomers occur either naturally or as flavouring agents. Although the butanol isomers can be classified as slightly or practically nontoxic, all isomers, in large amounts, have the ability to induce signs of alcoholic intoxication in both animals and man. The most extensive section of each monograph covers data on biological effects observed in experimental animals, in in vitro test systems, and in cases of accidental occupational exposure in man. Particular attention is given to studies useful in assessing effects on the skin, eyes, and respiratory tract of workers exposed to these chemicals.

Abstract  t -Butyl alcohol is widely used in the manufacture of perfumes and a variety of cosmetics. It is also used as a raw material in the production of isobutylene, which may be used to produce methyl tertiary butyl ether, a common gasoline additive, or to produce butyl elastomers used in the production of automobile tires. Male and female F344/N rats and B6C3F1 mice were given t -butyl alcohol (greater than 99% pure) in drinking water for 13 weeks or 2 years. The genetic toxicity of t -butyl alcohol was assessed by testing the ability of the chemical to induce mutations in various strains of Salmonella typhimurium and in L5178Y mouse lymphoma cells, sister chromatid exchanges and chromosomal aberrations in cultured Chinese hamster ovary cells, and by measuring the frequency of micronucleated erythrocytes in mouse peripheral blood. 13-WEEK STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were given 0, 2.5, 5, 10, 20, or 40 mg/mL t -butyl alcohol in drinking water for 13 weeks. All males and six females given 40 mg/mL died during the study. Final mean body weights of 10 and 20 mg/mL males and of 40 mg/mL females were 12%, 17%, or 21% less than those of the corresponding controls, respectively. Serum sorbitol dehydrogenase activities in 10 and 20 mg/mL males were greater than that in the controls after 13 weeks. Serum alanine aminotransferase activity in 40 mg/mL females was greater than that in the controls after 2 weeks and greater in all exposed females after 13 weeks. Urine volumes of 10, 20, and 40 mg/mL males and females decreased, and urine specific gravity values increased. Transitional epithelial hyperplasia and inflammation of the urinary bladder were observed in 20 and 40 mg/mL males and 40 mg/mL females. Absolute and relative liver weights of all exposed groups of females and relative liver weights of 5, 10, and 20 mg/mL males were significantly greater than those of the controls. Absolute and relative kidney weights of all exposed groups of males and females were significantly greater than those of the controls. Incidences of mineralization of the kidney were significantly increased in 10, 20, and 40 mg/mL males. The severity of nephropathy in 2.5, 5, 10, and 20 mg/mL males was significantly greater than that of the controls as was the accumulation of hyaline droplets in the kidney of 5, 10, and 20 mg/mL males. The incidences of nephropathy in 10, 20, and 40 mg/mL females were significantly greater than that of the controls. 13-WEEK STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were given 0, 2.5, 5, 10, 20, or 40 mg/mL t -butyl alcohol in drinking water for 13 weeks. The deaths of two males and one female in the 40 mg/mL group were attributed to exposure to t -butyl alcohol. The final mean body weights of 20 and 40 mg/mL males and 40 mg/mL females were significantly lower than those of the controls. There were no biologically significant differences in hematology parameters of exposed and control groups of mice. Transitional epithelial hyperplasia and inflammation were observed in the urinary bladder of 20 and 40 mg/mL males and 40 mg/mL females. 2-YEAR STUDY IN RATS: Groups of 60 F344/N rats were given 0, 1.25, 2.5, or 5 mg/mL t -butyl alcohol (males) or 0, 2.5, 5, or 10 mg/mL t -butyl alcohol (females) in drinking water for 2 years. These correspond to average daily doses of approximately 90, 200, or 420 mg t -butyl alcohol/kg body weight for males and approximately 180, 330, or 650 mg t -butyl alcohol/kg body weight for females. Ten rats per group were evaluated after 15 months of chemical administration. Survival, Body Weights, and Water Consumption: Survival rates of 5 mg/mL males and 10 mg/mL females were significantly lower than those of the controls. The final mean body weights of exposed groups of males were 15% to 24% lower than that of the controls, and the final mean body weight of 10 mg/mL females was 21% lower than that of the controls. Water consumption by males increased with dose; water consumption by females decreased with dose. Hematology and Urinalysis: At the 15-month inte. Hematology and Urinalysis: At the 15-month interim evaluation, there were no significant differences in hematology parameters in males and females, and there were no significant differences in urinalysis parameters in males. Females given 5 or 10 mg/mL had increased urine specific gravities and decreased urine volumes. Pathology Findings: At the 15-month interim evaluation, relative kidney weights of 2.5 and 5 mg/mL males and absolute and relative kidney weights of 2.5, 5, and 10 mg/mL females were significantly greater than those of the controls. At 2 years, the incidence of mineralization in the kidney increased with dose and that of 5 mg/mL males was significantly greater than that of the controls. In the standard evaluation at the end of the study, the incidences of focal renal tubule hyperplasia and of adenoma were increased in exposed males and a carcinoma was observed in one 5 mg/mL male. Renal tubule hyperplasia occurred in one 10 mg/mL female. An extended evaluation of the kidney identified additional male rats with hyperplasia (control, 11/50; 1.25 mg/mL, 13/50; 2.5 mg/mL, 11/50; 5 mg/mL, 19/50) and renal tubule adenoma (7/50, 8/50, 15/50, 10/50); renal tubule carcinomas were identified in two 1.25 mg/mL males and in one 2.5 mg/mL male. Renal tubule adenoma was identified in one 5 mg/mL male from the 15-month extended evaluation. In the standard and extended evaluations combined, there were dose-related increased incidences of hyperplasia and adenoma. The severity of nephropathy and the incidence and severity of transitional cell hyperplasia of the kidney were increased in exposed male and female rats. Linear foci of mineralization were present in the renal papilla of exposed males. 2-YEAR STUDY IN MICE: Groups of 60 male and 60 female B6C3F1 mice were given 0, 5, 10, or 20 mg/mL t -butyl alcohol in drinking water for 2 years. Exposure levels of 5, 10, or 20 mg/mL delivered average daily doses of approximately 540, 1,040, or 2,070 mg t -butyl alcohol/kg body weight to males and approximately 510, 1,020, or 2,110 mg/kg to females. Survival, Body Weights, and Water Consumption: Survival of 20 mg/mL males was significantly lower than that of the controls. The final mean body weights of exposed groups of males were similar to those of the controls. The mean body weights of females given 20 mg/mL were 10% to 15% lower than those of the controls from week 13 to the end of the study. Water consumption by exposed groups of males and females was similar to that by the controls. Pathology Findings: Incidences of thyroid gland follicular cell hyperplasia were significantly increased in all exposed groups of males and in 10 and 20 mg/mL females. The incidence of follicular cell adenoma or carcinoma (combined) was marginally increased in 10 mg/mL males (0 mg/mL, 1/60; 5 mg/mL, 0/59; 10 mg/mL, 4/59; 20 mg/mL, 2/57). The incidence of follicular cell adenoma was significantly increased in 20 mg/mL females (2/58, 3/60, 2/59, 9/59). The incidences of chronic inflammation and transitional epithelial hyperplasia of the urinary bladder were increased in 20 mg/mL males and to a lesser extent in 20 mg/mL females. GENETIC TOXICOLOGY: t -Butyl alcohol was tested for induction of genetic damage in vitro and in vivo, and all results were negative. In vitro, t -butyl alcohol was negative in Salmonella typhimurium and mouse lymphoma cell mutation tests, and it did not induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells. These in vitro studies were conducted with and without metabolic activation (S9). In vivo, no increase in micronucleated erythrocytes was observed in peripheral blood samples from mice administered t -butyl alcohol in drinking water for 13 weeks. CONCLUSIONS: Under the conditions of these 2-year drinking water studies, there was some evidence of carcinogenic activity of t -butyl alcohol in male F344/N rats based on increased incidences of renal tubule adenoma or carcinoma (combined). There was no evidence of carcinogenic activity in female F344/N rats receiving 2.5, 5, or 10 mg/mL t -butyl alcohol. There was equivocal evidence of carcinogenic activity of t -butyl alcohol in male B6C3F1 mice based on the marginally increased incidences of follicular cell adenoma or carcinoma (combined) of the thyroid gland. There was some evidence of carcinogenic activity of t -butyl alcohol in female B6C3F1 mice based on increased incidences of follicular cell adenoma of the thyroid gland. Exposure to t -butyl alcohol was associated with mineralization and renal tubule hyperplasia in male rats, transitional epithelial hyperplasia and increased severity of nephropathy of the kidney in male and female rats, follicular cell hyperplasia of the thyroid gland in male and female mice, and chronic inflammation and hyperplasia of the urinary bladder in male mice and to a lesser extent in female mice. Synonyms: 2-Methyl-2-propanol, 2-methylpropan-2-ol, TBA, t -butanol, tertiary butyl alcohol, t -butyl hydroxide, trimethyl carbinol, trimethyl methanol

Abstract  In compliance with the Clean Air Act Section 211(b) for fuel and fuel additive registration, the petroleum industry has conducted a series of comparative multi-endpoint studies of evaporative fractions of seven vapor condensates of gasoline (GVC), or gasoline+ether [methyl t- butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE)], or alcohol [ethanol (G/EtOH), t-butyl (G/TBA)] oxygenates. Here we present results from micronucleus (MN) and sister chromatid exchange (SCE) tests. Sprague- Dawley rats (5/sex/group used for both studies) were exposed to target concentrations of 0, 2000, 10000, or 20000mg/m3 of each test material, 6 hr/day, 5d/wk for 4 weeks. Positive control groups (5 rats/sex/group) were used for each study; rats were given cyclophosphamide IP, 24hr prior to sacrifice at doses of 5mg/kg for the SCE study and 40mg/kg for the MN study. At treatment end, blood was collected from the abdominal aorta for the SCE test [cultures established within 24 hr of collection], and femurs removed for the MN test. Femoral bone marrow was prepared and stained using a modified Feulgen method. Approx. 21hr after initiation of culture, cells were exposed to 5ug/ml bromodeoxyuridine (BrdU); colcemid was given at 68hr of culture. Cells were harvested after 72hr in culture and processed for SCE evaluation. No significant increased incidence of micronuclei in polychromatic erythrocytes was observed for any test material. Statistically significant increases in SCE over several doses were observed in rats given GVC alone or G/MTBE; females appeared more sensitive than males. G/TAME induced increased SCE in both sexes at the highest dose only. Although several instances of increased SCE were observed in cultured lymphocytes, gasoline and gasoline/oxygenate blends did not induce cytogenetic effects in bone marrow of exposed animals. Results of these studies will be used for comparative risk assessment of gasoline and gasoline/oxygenate blends.

Abstract  When methyl tertiary-butyl ether (MTBE) in gasoline was first introduced to reduce vehicle exhaust emissions and comply with the Clean Air Act, in the United States, a pattern of complaints emerged characterised by seven "key symptoms." Later, carefully controlled volunteer studies did not confirm the existence of the specific key symptoms, although one study of self-reported sensitive (SRS) people did suggest that a threshold at about 11-15% MTBE in gasoline may exist for SRSs in total symptom scores. Neurobehavioral and psychophysiological studies on volunteers, including SRSs, found no adverse responses associated with MTBE at likely exposure levels. MTBE is well and rapidly absorbed following oral and inhalation exposures. Cmax values for MTBE are achieved almost immediately after oral dosing and within 2 h of continuous inhalation. It is rapidly eliminated, either by exhalation as unchanged MTBE or by urinary excretion of its less volatile metabolites. Metabolism is more rapid humans than in rats, for both MTBE and tert-butyl alcohol (TBA), its more persistent primary metabolite. The other primary metabolite, formaldehyde, is detoxified at a rate very much greater than its formation from MTBE. MTBE has no specific effects on reproduction or development, or on genetic material. Neurological effects were observed only at very high concentrations. In carcinogenicity studies of MTBE, TBA, and methanol (included as an endogenous precursor of formaldehyde, without the presence of TBA), some increases in tumor incidence have been observed, but consistency of outcome was lacking and even some degree of replication was observed in only three cases, none of which had human relevance: alpha(2u)-globulin nephropathy-related renal tubule cell adenoma in male rats; Leydig-cell adenoma in male rats, but not in mice, which provide the better model of the human disease; and B-cell-derived lymphoma/leukemia of doubtful pathogenesis that arose mainly in lungs of orally dosed female rats. In addition, hepatocellular adenomas were significantly higher in female CD-1 mice and thyroid follicular-cell adenomas were increased in female B6C3F1 mice treated with TBA, but these results lack any independent confirmation, which would have been possible from a number of other studies.

Abstract  Through its extensive use as a fuel oxygenate, methyl tert-butyl ether (MTBE) is found nearly ubiquitously throughout the environment. To better understand the environmental fate of MTBE, fugacity models are commonly used. However, models developed by the scientific community and by governmental bodies differ in their predictions of relative MTBE concentrations for relevant environmental compartments and of seasonal concentration variations; further, to date they have not considered the formation of transformation products. In this study, the sensitivity of predicted environmental concentrations of MTBE and its two major degradation products, tert-butyl formate (TBF) and tert-butyl alcohol (TBA), to all types of model input parameters is analyzed in a probabilistic sensitivity analysis. This analysis allowed for an assessment of the most influential parameters for predicting soil, water, and air concentrations and thereby provided insight into why previous modeling studies on MTBE differed. Further, the information from the sensitivity analysis was used to parametrize a multispecies transformation model for predicting European concentration levels of MTBE and, for the first time, TBF and TBA. Water and air concentrations of MTBE predicted with the transformation model were in good agreement with measurements of environmental samples. No studies are available on environmental TBF and TBA levels to compare with model predictions; however, the modeling results indicate that, in the water phase, TBA concentrations may reach appreciable levels. One major uncertainty identified regarding the prediction of TBA levels was the fraction of TBA formed from atmospheric MTBE and TBF.