Neurotoxicological Evaluation of Methyl Tertiary‐butyl Ether in Rats

Abstract

Methyl tertiary‐butyl ether (MTBE) is an oxygenate that is added to gasoline to boost octane and enhance combustion, thereby reducing carbon monoxide and hydrocarbon tailpipe emissions. The acute and subchronic neurotoxicity of MTBE were evaluated in rats using a functional observation battery (FOB), measures of motor activity (MA) and a neuropathological evaluation. In the acute study, rats were exposed once to 0, 800, 4000 or 8000 ppm MTBE by inhalation for 6 h and then evaluated three times over a 24‐h period. In the FOB evaluations, treatment‐related effects were seen at the 1‐h session immediately following exposure and were indicative of transient central nervous system (CNS) depression. Effects were most apparent in the high‐dose group (8000 ppm) but were also evident to a lesser extent in the mid‐dose (4000 ppm) group. Labored respiration, ataxia, duck‐walk gait and decreases in muscle tone, hind‐limb grip strength and treadmill performance were the most frequently noted findings. No significant effects were observed in the FOB when testing was conducted at 6 h and 24 h post‐exposure. The pattern of motor activity measured in the different dose groups following exposure was also in keeping with a reversible CNS‐depressant effect of MTBE. In the subchronic study, rats were exposed to 0, 800, 4000 or 8000 ppm MTBE for 6 h a day, 5 days per week, for 13 weeks. No persistent or cumulative effects on neurobehavioral function were found. Body weights and absolute brain weights were reduced in the 8000 ppm group, however there were no differences among groups when brain weight was expressed relative to body weight. No histopathological changes were noted in the brains or peripheral nervous tissues of MTBE‐exposed animals. In summary, MTBE produced signs of acute reversible CNS depression following exposure to 8000 ppm and, to a lesser extent, to 4000 ppm vapor. The no‐observed‐adverse‐effect level for these effects was 800 ppm in the present study. No persistent or cumulative neurotoxic effects were observed following exposure to MTBE at concentrations up to 8000 ppm for 13 weeks. © 1997 by John Wiley & Sons, Ltd.

Impact of gasoline inhalation on some neurobehavioural characteristics of male rats

“…Methyl tertiary butyl ether (MTBE) is an aliphatic ether, a volatile, colorless, and inflammable liquid, currently the most widely used oxygenate as an octane enhancer in gasoline blends. In subchronic and chronic toxicity studies, MTBE appears to have low systemic toxicity; the main findings observed in rats were depressant effects on the CNS, typical of similar ethers [11,12]. Tertiary amyl methyl ether (TAME) causes a significant but transient CNS depression akin to, but slightly more severe than, that resulting from MTBE exposure at the same levels [13].…”

Proposed Occupational Exposure Limits for Non-Carcinogenic Hanford Waste Tank Vapor Chemicals

“…However, ACGIH has assigned a TLV-TWA of 50 ppm (180 mg/m 3 ) for the structural surrogate MTBE (ACGIH 2002a). The TLV-TWA for MTBE is based upon the observance of no adverse symptoms in humans (10 subjects) exposed to up to 50 ppm MTBE (Johanson et al 1995) and a no-observed-adverse-effect level (NOAEL) for repeated inhalation exposure in rats at 800 ppm (Daughtrey et al 1997;Lington et al 1997) and a NOEL of 400 ppm in rats for a two-generation study (Bevan et al 1997).…”

A Review of the Neurotoxicity Risk of Selected Hydrocarbon Fuels

“…Metabolism of MTBE to TBA occurs through a P-450 enzyme system that, in rats, is located both in the olfactory mucosa and liver (Hong et al, 1997). The acute and subchronic neurotoxicity of MTBE was evaluated (Bushy Run Research Center, 1989;Robinson et al, 1990;Daughtrey et al, 1997) in rats using a functional observation battery (FOB), measures of motor activity, and a neuropathological evaluation. In the acute study, rats were exposed once to 0, 800, 4000, or 8000 ppm MTBE by inhalation for 6 h and then evaluated 3 times over a 24-h period.…”