There have been no reports concerning the toxic (including neurotoxic) effects of methyl tertiary butyl ether (MTBE) in humans due to occupational exposure. The use of MTBE as a therapeutic agent for dissolving gallstones (12) has provided information regarding the side effects in humans of MTBE administered by infusion. These studies, however, do not provide data relevant to the evaluation of MTBE neurotoxicity.
Studies in animals have not provided evidence of overt neurotoxicity due to MTBE exposure at air concentrations from 100 ppm to 3000 ppm MTBE (13-15). In addition, gross teratogenic effects were not observed in rats and mice at air concentrations from 250 ppm to 2500 ppm MTBE (16-18). A decrease in offspring viability, however, has been reported at air concentrations of 1000 ppm and 2500 ppm (19).
More subtle neurotoxic effects due to MTBE exposure have been reported in two studies sponsored by the Methyl Tertiary Butyl Ether Task Force (20,21). The effects of a single 6-hr exposure to MTBE and exposure for 13 days, 6 hr/day were examined. Both studies used rats and MTBE air concentrations of 8000, 4000, 800, and 0 ppm. Several neurobehavioral effects were reported at all levels of exposure in both studies. The most consistent effects related to MTBE exposure were those on activity. At higher levels of exposure (8000 ppm), a reduction in overall activity, or a sedation effect, was observed. At the lower concentrations tested (4000 and 800 ppm), an increase in overall activity was observed. The authors stated that the increase in overall activity observed at the lower MTBE air concentrations tested (4000 and 800 ppm) "may reflect an exposure-related stimulant effect" (20).
A summary of the neurotoxic effects reported for MTBE is shown in Table 2. To date, studies of occupational exposures of workers to MTBE have not been reported. The two MTBE Task Force studies using rats do provide some dose-response data for MTBE effects in adult animals. These studies do not report a NOAEL of exposure for MTBE. Central nervous system stimulant effects were observed at the lowest dose studied.