Acute Exposure to Low-Level Methyl Tertiary-Butyl Ether (MTBE): Human Reactions and Pharmacokinetic Response

Cain, William S.; Leaderer, Brian P.; Ginsberg, Gary; Andrews, Larry S.; Cometto‐Muñiz, J. Enrique; Gent, Janneane F.; Buck, Marion G.; Berglund, Larry G.; Mohsenin, Vahid; Monahan, Edward J.; Kjærgaard, Søren K.

doi:10.3109/08958379609005425

Cited by 43 publications

(32 citation statements)

References 26 publications

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“…Presumably a sufficiently long chamber exposure to MTBE would allow the determination of the residence time for the fourth compartment (adipose tissue). Cain et al 37 and Johanson et al 38 have reported results from similar chamber studies. Cain et al exposed four subjects to 6,129 µg/m 3 MTBE for 1 hour, resulting in blood levels rising on average from about 1,000 to 17,000 ng/L.…”

Section: Discussionsupporting

confidence: 56%

Body Burden Measurements and Models to Assess Inhalation Exposure to Methyl Tertiary Butyl Ether (MTBE)

Buckley

Prah

Ashley³

et al. 1997

Journal of the Air & Waste Management Association

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Biomarkers of methyl tertiary butyl ether (MTBE) exposure and the partitioning of inhaled MTBE into the body were investigated in a human chamber study. Two subjects were exposed to an environmentally relevant nominal 5,011 µg/m 3 (1.39 ppm) MTBE for 1 hour, followed by clean-air exposure for 7 hours. Breath and blood were simultaneously sampled, while total urine was collected at prescribed times before, during, and after the exposure. Mass-balance and toxicokinetic analyses were conducted based upon the time series measurement of multiple body-burden endpoints, including MTBE in alveolar breath, and MTBE and tertiary butyl alcohol (TBA) in venous blood and urine.The decay of MTBE in the blood was assessed by fitting the post-exposure data to a 2-or 3-exponential model that yielded residence times (τ) of 2-3 min, 15-50 min, and 3-13 h as measured by alveolar breath, and 5 min, 60 min, and 32 h as evaluated from venous blood measurements. Based on observations of lower than expected blood and breath MTBE during uptake and a decreasing blood-to-breath ratio during the post-exposure decay period, we hypothesize that the respiratory mucous membranes were serving as a reservoir for the retention of MTBE. The decay data suggest that 6-9% of the MTBE intake may be retained by this non-blood reservoir. The compartmental modeling was further used to estimate important parameters that define the uptake of inhaled MTBE. The first of these parameters is f, the fraction of C air exhaled at equilibrium, estimated as 0.60 and 0.46 for the female and male subject, respectively. The second parameter is the blood-tobreath partition coefficient (P) estimated as ~18. The product of these parameters provides an estimate of the blood concentration at equilibrium as 8-11 times the air concentration. Blood TBA lagged MTBE levels and decayed more slowly (τ = 1.5-3 h), providing a more stable indication of longer term integrated exposure. The concentration ranges of MTBE and TBA in urine were similar to that of the blood, ranging from 0.37 to 15 µg/L and 2 to 15 µg/L, respectively. In urine, MTBE and TBA by themselves bore little relationship to the exposure. However, the MTBE:TBA ratio followed the pattern of exposure, with peak values occurring at the end of the exposure (20-and 60-fold greater than pre-exposure values) before decaying back to preexposure levels by the end of the 7-h decay period. Urinary elimination accounted for a very small fraction of total MTBE elimination (<1%). IMPLICATIONSHuman exposure to MTBE has become pervasive due its use as a fuel oxygenate in response to provisions of the Clean Air Act Amendments of 1990. Furthermore, there are concerns that MTBE poses a health hazard. Risk assessment and management provide the means by which MTBE's hazard will be evaluated and managed. The current study reduces the uncertainty in MTBE exposure assessment by measurements and models that define the relationship between exposure to a concentration of MTBE in air and the resulting body burden. Model parameters, inc...

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Section: Discussionsupporting

confidence: 56%

Body Burden Measurements and Models to Assess Inhalation Exposure to Methyl Tertiary Butyl Ether (MTBE)

Buckley

Prah

Ashley³

et al. 1997

Journal of the Air & Waste Management Association

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“…The uptake and elimination of MTBE following inhalation exposure under either controlled conditions or occupational settings have been studied Prah et al, 1995;Cain et al, 1996;Lindstrom and Pleil, 1996;Buckley et al, 1997;Saarinen et al, 1998;Nihle Ân et al, 1998a,b, 1999, Amberg et al, 1999 . Alveolar breath measurement is one method adopted to evaluate the pharmacokinetics of MTBE.…”

Section: Introductionmentioning

confidence: 99%

Toxicokinetics of human exposure to methyl tertiary-butyl ether (MTBE) following short-term controlled exposures

Lee

Möhr

Weisel

2001

J Expo Sci Environ Epidemiol

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Methyl tertiary -butyl ether ( MTBE ) is an oxygenated compound added to gasoline to improve air quality as part of the US Federal Clean Air Act. Due to the increasing and widespread use of MTBE and suspected health effects, a controlled, short -term MTBE inhalation exposure kinetics study was conducted using breath and blood analyses to evaluate the metabolic kinetics of MTBE and its metabolite, tertiary -butyl alcohol ( TBA ) , in the human body. In order to simulate common exposure situations such as gasoline pumping, subjects were exposed to vapors from MTBE in gasoline rather than pure MTBE. Six subjects ( three females, three males ) were exposed to 1.7 ppm of MTBE generated by vaporizing 15 LV% MTBE gasoline mixture for 15 min. The mean percentage of MTBE absorbed was 65.8 5.6% following exposures to MTBE. The mean accumulated percentages expired through inhalation for 1 and 8 h after exposure for all subjects were 40.1% and 69.4%, respectively. The three elimination half -lives of the triphasic exponential breath decay curves for the first compartment was 1 ± 4 min, for the second compartment 9 ± 53 min, and for the third compartment 2 ± 8 h. The half -lives data set for the breath second and blood first compartments suggested that the second breath compartment rather than the first breath compartment is associated with a blood compartment. Possible locations for the very short breath half -life observed are in the lungs or mucous membranes. The third compartment calculated for the blood data represent the vessel poor tissues or adipose tissues. A strong correlation between blood MTBE and breath MTBE was found with mean blood -to -breath ratio of 23.5. The peak blood TBA levels occurred after the MTBE peak concentration and reached the highest levels around 2 ± 4 h after exposures. Following the exposures, immediate increases in MTBE urinary excretion rates were observed with lags in the TBA excretion rate. The TBA concentrations reached their highest levels around 6 ± 8 h, and then gradually returned to background levels around 20 h after exposure. Approximately 0.7 ± 1.5% of the inhaled MTBE dose was excreted as unchange urinary MTBE, and 1 ± 3% was excreted as unconjugated urinary TBA within 24 h after exposure.

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“…Finally, the results of experimental studies in humans in controlled MTBE exposure chambers showed no effects on health (133)(134)(135)(136).…”

Section: Renal Tumorsmentioning

confidence: 99%

Potential Health Effects of Gasoline and Its Constituents: A Review of Current Literature (1990-1997) on Toxicological Data

Caprino¹,

Togna²

1998

Environmental Health Perspectives

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We reviewed toxicological studies, both experimental and epidemiological, that appeared in international literature in the period 1990-1997 and induded both leaded and unleaded gasolines as well as their components and additives. The aim of this overview was to select, arrange, and present references of scientific papers published during the period under consideration and to summarize the data in order to give a comprehensive picture ofthe results of toxicological studies performed in laboratory animals (induding carcinogenic, teratogenic, or embryotoxic activity), mutagenicity and genotoxic aspects in mammalian and bacterial systems, and epidemiological results obtained in humans in relation to gasoline exposure. This paper draws attention to the inherent difficulties in assessing with precision any potential adverse effects on health, that is, the risk of possible damage to man and his environment from gasoline. The difficulty of risk assessment still exists despite the fact that the studies examined are definitely more technically valid than those of earlier years. The uncertainty in overall risk determination from gasoline exposure also derives from the conflicting results of different studies, from the lack of a correct scientific approach in some studies, from the variable characteristics ofthe different gasoline mixtures, and from the difficulties of correcdy handling potentially confounding variables related to lifestyle (e.g., cigarette smoking, drug use) or to preeisting pathological conditions. In this respect, this paper highlights the need for accurately assessing the condusive explanations reported in scientific papers so as to avoid the spread of inaccurate or misleading information on gasoline toxidty in nonscientific papers and in mass-media messages.

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Acute Exposure to Low-Level Methyl Tertiary-Butyl Ether (MTBE): Human Reactions and Pharmacokinetic Response

Cited by 43 publications

References 26 publications

Body Burden Measurements and Models to Assess Inhalation Exposure to Methyl Tertiary Butyl Ether (MTBE)

Body Burden Measurements and Models to Assess Inhalation Exposure to Methyl Tertiary Butyl Ether (MTBE)

Toxicokinetics of human exposure to methyl tertiary-butyl ether (MTBE) following short-term controlled exposures

Potential Health Effects of Gasoline and Its Constituents: A Review of Current Literature (1990-1997) on Toxicological Data

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