Relationship between Methyl Tertiary Butyl Ether Exposure and Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study among Petrol Station Attendants in Southern China.

Methyl tertiary butyl ether (MTBE)-A well known gasoline additive substituting for lead alkyls-causes lipid disorders and liver dysfunctions in animal models. However, whether MTBE exposure is a risk factor for non-alcoholic fatty liver disease (NAFLD) remains uncertain. We evaluate the possible relationship between MTBE exposure and the prevalence of NAFLD among 71 petrol station attendants in southern China. The personal exposure concentrations of MTBE were analyzed by Head Space Solid Phase Microextraction GC/MS. NAFLD was diagnosed by using abdominal ultrasonography according to the guidelines for the diagnosis and treatment of NAFLD suggested by the Chinese Hepatology Association. Demographic and clinical characteristics potentially associated with NAFLD were investigated. Mutivariate logistic regression analysis was applied to measure odds ratios and 95% confidence intervals (CI). The result showed that the total prevalence of NAFLD was 15.49% (11/71) among the study subjects. The average exposure concentrations of MTBE were 292.98 ± 154.90 µg/m³ and 286.64 ± 122.28 µg/m³ in NAFLD and non-NAFLD groups, respectively, and there was no statistically significant difference between them (p > 0.05). After adjusting for age, gender, physical exercise, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), alanine aminotransferase (ALT), white blood cell (WBC), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), the odds ratios were 1.31 (95% CI: 0.85-1.54; p > 0.05), 1.14 (95% CI: 0.81-1.32; p > 0.05), 1.52 (95% CI: 0.93-1.61; p > 0.05) in the groups (including men and women) with exposure concentrations of MTBE of 100-200 µg/m³, 200-300 µg/m³, and ≥300 µg/m³, respectively, as compared to the group (including men and women) ≤100 µg/m³. Our investigation indicates that exposure to MTBE does not seem to be a significant risk factor for the prevalence of NAFLD among petrol station attendants in southern China.

MTBE: recent carcinogenicity studies.

MTBE, a gasoline oxygenate, has contaminated drinking water sources for many years. Carcinogenicity studies conducted in animals in the 1990s raised concerns of potential human health risks. Recent industry-sponsored studies have confirmed the carcinogenic effects of this agent and have identified additional sites of tumor induction (i.e., brain). However, the petroleum industry has attempted to portray these recent findings as demonstrating either no effect or no concern for humans. Our paper briefly summarizes the new findings and puts into perspective the totality of carcinogenic effects and health risks on this environmental chemical.

A fatality from sevoflurane abuse.

A case is presented of a 47-year-old man who died as a result of sevoflurane abuse. Sevoflurane was identified and confirmed by headspace gas chromatography-mass spectrometry. The heart blood sevoflurane concentration was 16 mg/L, and the peripheral blood sevoflurane concentration was 8.0 mg/L. No drugs or other volatile substances were found in the heart blood. The medical examiner ruled that the cause of death was cardiac arrhythmia due to sevoflurane toxicity. Cardiomegaly was listed on Part II of the death certificate. The manner of death was undetermined.

Sevoflurane concentrations in blood, brain, and lung after sevoflurane-induced death.

Sevoflurane concentrations in blood, brain, and lung were measured in an individual apparently dying from sevoflurane inhalation. Sevoflurane is a volatile nonflammable fluorinated methyl isopropyl ether inhaled anesthetic, chemically related to desflurane and isoflurane. The incidence of abuse of sevoflurane is lower than that of other drugs of abuse possibly due to its inaccessibility to the general public and less pleasurable and addicting effects. The dead subject was an anesthetist found prone in bed holding an empty bottle of sevoflurane (Ultane). Serum, urine, and liver were screened for numerous drugs and metabolites using enzyme immunoassays and gas chromatography-mass spectrometry. Analysis did not reveal presence of any drug, including ethanol, other than sevoflurane. Sevoflurane was determined by headspace gas chromatography and revealed concentrations of 15 microg/mL in blood and 130 mg/kg in brain and lung. Autopsy revealed pulmonary edema and frothing in the lung, pathological findings associated with death by sevoflurane or hypoxia. The cause of death was ruled as sevoflurane toxicity and the manner of death as accident.

The distribution of sevoflurane in a sevoflurane induced death.

The distribution of sevoflurane (fluoromethyl 2,2,2,-trifluoro-1-(trifluoromethyl) ethyl ether) in blood, urine, liver, kidney, vitreous humor, and tracheal aspirate is presented from a subject with a sevoflurane induced death. Sevoflurane is a nonflammable general anesthetic administered by inhalation of vaporized liquid. Although general inhalation anesthetics have the potential to be fatal if not properly administered, the incidence of abuse is minute in comparison to other illicit drugs. Currently, there are no citations in the literature defining the body distribution of sevoflurane in a sevoflurane induced death. The decedent was found lying in a bed with an oxygen mask containing a gauze pad secured to his face. Three empty bottles and one partially full bottle of Ultane (sevoflurane) were found with the body in addition to two pill boxes containing a variety of prescription and non-prescription drugs. Serum, urine and gastric contents from the deceased were screened for numerous drugs and metabolites using a combination of thin layer chromatographic, colorimetric and immunoassay techniques. Analysis of biological specimens from the deceased revealed the presence of: amphetamine, caffeine, pseudoephedrine, nicotine, nicotine metabolite, and valproic acid. Sevoflurane concentrations were determined by headspace gas chromatography with flame ionization detection and revealed concentrations of 26.2 microg/mL in the blood, 105 microg/mL in the urine, 31.9 microg/mL in the tracheal aspirate, 86.7 microg/mL in the vitreous humor, 30.8 mg/kg in the liver, and 12.8 mg/kg in the kidney. The decedent had pathologies consistent with respiratory suppression including pulmonary atelectasis, pulmonary edema, and neck vein distention. The official cause of death was respiratory suppression by sevoflurane and the manner of death was unclear.

Visits to physicians after the oxygenation of gasoline in Philadelphia.

During the period between 1992 and 1997, there was an increase in levels of methyl tertiary butyl ether (MTBE) in gasoline in the Philadelphia, Pennsylvania, area. In this study, the authors analyzed billing records from clinical practices that were extensions of the University of Pennsylvania. The authors based their selections on the International Classification of Diseases-9 diagnostic codes, which were determined from (1) previous studies of methyl tertiary butyl ether conducted by the Centers for Disease Control; (2) respiratory symptoms, including asthma and wheezing; and (3) symptoms associated anecdotally with methyl tertiary butyl ether levels in gasoline. The authors normalized all data by the total number of office visits. The incidences of headache, throat irritation, allergic rhinitis, cough, nausea, dizziness, upper respiratory infections, wheezing, otitis media, skin rash, anxiety, insomnia, palpitations, generalized allergy, and malaise were increased during the period studied. Large increases occurred during the winters of 1993-1994 and 1994-1995 (during which there were high levels of MTBE), but not in the preceding summers (during which there were low levels of MTBE). This was especially true for asthma and wheezing. During the summers of 1995, 1996, and 1997, the incidences of the aforementioned symptoms increased greatly.

Interaction between tobacco smoking and occupational exposures in the causation of lung cancer.

The nature of the interaction between smoking and occupational exposure is controversial, in part because of lack of agreement on the definition of interaction and in part because of the scarcity of adequate epidemiologic data. Occupational investigators have assessed interaction primarily as a departure from an additive rather than from a multiplicative model of relative risks (or rate ratios). To determine whether smoking modifies the effect of occupational lung carcinogens, the literature was reviewed for the only four established occupational lung carcinogens for which there are data on smoking: radon daughters, asbestos, arsenic, and chloromethyl ethers. Where possible, departure was assessed from both an additive (synergism) and a multiplicative model (effect modification). Only nine studies were considered to have sufficient sample size and to provide sufficient information on tobacco use and occupational exposure to evaluate interaction. The existing data were contradictory for three of the agents studied: asbestos, radon daughters, and arsenic. Inconclusive or contradictory findings may result from small sample size or lack of comparability of the level of occupational or tobacco exposure. It is noteworthy that, for these four agents, whenever smoking did modify the effect of occupational exposure, the lung cancer rate ratio was greater for nonsmokers (compared to nonexposed nonsmokers) than smokers (compared to nonexposed smokers). However, with the exception of chloromethyl ethers, absolute lung cancer rates were higher for smokers than nonsmokers, regardless of occupational exposure.

Mortality patterns among workers exposed to chloromethyl ethers--a preliminary report.

Chloromethyl methyl ether (CMME) has been used extensively as a crosslinking agent for ion-exchange resins. Commercial grades of CMME are contaminated to the extent of 2-8% with bischloromethyl ether, an alkylating agent which has been shown to be a very potent lung carcinogen in animals. Reports by other investigators in this and other countries have implicated CMME as a lung carcinogen in chemical workers. The purpose of the study reported here was to examine the lung cancer mortality experience with respect to intensity and duration of exposure in six of the seven chemical companies that account for virtually all of the CMME use in the United States. The study included about 1800 workers who were exposed in the period 1948 to 1972 and about 8000 workers not exposed to CMME from the same plants who served as controls. Exposed workers were characterized according to job description and duration of exposure. In several plants the intensity of exposure was numerically graded for each job category with adjustment for temporal changes in the plant processes. Social Security records were used to identify deaths among workers who had left the companies and death certificates have been obtained for virtually all known deaths. The age-adjusted death rate for respiratory cancer in the CMME exposed group as a whole was 2.5 times that in the control group, whereas death rates due to other causes were comparable. There was also a gradation of lung cancer risk according to intensity and duration of exposure and the time elapsed since the onset of exposure.

The prevention by sulphydryl compounds of the toxicity in the cat of 2,6-dimethoxyphenol and its morpholinopropionyl ester.

1 Intravenous (minus)-2,6-dimethoxyphenyl-2-morpholinopropionate hydrochloride (M&B 16,573) produced anaesthesia of short duration in the mouse, rat, rabbit, cat, dog and monkey. In the cat but not in other species, a severe and usually fatal toxic reaction was seen 1-2 h after administration. 2 This toxic reaction but not the anaesthetic properties of M&B 16,573 was prevented by the intravenous administration of cysteine or N-acetylcysteine. Cysteamine or dimercaprol were ineffective. 3 Intravenous administration of 2,6-dimethoxyphenol or 2,6-dimethoxyquinol in the cat produced a response similar to the delayed toxic effects of M&B 16,573 but not preceded by anaesthesia. The toxic effects of these compounds were prevented by cysteine. 4 Intravenous 4-allyl-2,6-dimethoxyphenyl-2-morpholinopropionate hydrochloride produced anaesthesia in the cat without the delayed toxic effects seen after M&B 16,573. 5 The acute toxicity of 2,6-dimethoxyquinol in mice was reduced by the administration of cysteine or N-acetylcysteine. 6 It is postulated that the delayed effects produced by M&B 16,573 in the cat are due to the formation of 2,6-dimethoxyquinol and 2,6-dimethoxybenzoquinone in this species, the toxicity of the latter being reduced by sulphydryl compounds.

PMA deaths in Ontario.

A new street-drug, para-methoxyamphetamine (PMA), recently made its appearance in Ontario. Between March and August 1973 there were nine deaths of young people in this province that were attributed to the drug. PMA appears to have a powerful hallucinogenic effect as well as a marked toxicity to the central nervous system. The clinical picture resembles that observed in cases of acute poisoning by amphetamine and methylenedioxyamphetamine (MDA).