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- Neurotoxic Effects of Gasoline and Gasoline Constituents

The effects associated with the intentional use of gasoline as an intoxicant (gasoline sniffing) are commonly neurologic in nature and include ataxia, tremor, and an acute or subacute encephalopathic syndrome [see Fortenberry for a review (1)].

Occupational exposure to gasoline has been associated with numerous signs of neurotoxicity. Significant effects on intellectual capacity, psychomotor and visuomotor function, immediate and delayed memory, and an increased proportionate mortality ratio (PMR) due to mental and psychoneurotic conditions have been reported for gasoline service station workers (2,3). Symptoms such as headache, fatigue, loss of memory, and giddiness have also been reported (4). Neurological effects (dizziness, headache) have been reported in laboratory studies of human volunteers exposed to gasoline vapor. These effects were observed at a concentration of 2600 ppm but not at concentrations of 1000 ppm and below (5,6).

In animals, acute exposure of dogs to high concentrations of gasoline have been associated with neurologic effects at 10,000 ppm and death at 25,000 ppm (7). A preliminary study of rats exposed to 1500 ppm gasoline for 6 hr/day, 5 days/week for up to 18 months demonstrated more extensive axonal dystrophy and degeneration in the distal gracile tract of the spinal cord as well as abnormalities of anterior horn cells (8). Chronic exposure, 6 hr/ day for 5 days/week for 90 days, of rats and monkeys to 400 ppm and 1500 ppm gasoline, however, did not produce overt neurotoxicity or changes in visual evoked responses (9). In another study, rats and mice exposed to 50, 275, or 1500 ppm gasoline for 6 hr/day, 5 days/week for up to 113 weeks also failed to show signs of overt neurotoxicity (10). A study of the effects of exposure to unleaded gasoline on the hyp,othalamo-pituitary-thyroid-adrenal system in rats has indicated a significant increase in serum corticosterone and adrenal catecholamines and a decrease in hypothalamic noradrenaline. These effects were observed only after 60 days of exposure to > 600 ppm unleaded gasoline in air for 8 hr/day, 5 days/week. Effects were not observed after 1, 3, 7, 14, or 30 days of exposure (11). A summary of the neurotoxic effects reported for gasoline is shown in Table 1. Thus far, studies of human exposures to gasoline have provided little data regarding the actual level of gasoline exposure. Although some exposure data are available for the studies using animal models, the small number of studies and the use of different dosing schedules and neurotoxic end points make a doseresponse analysis for the various end points reported very difficult. At this time, sufficient data are not available to support calculating a no-observed-adverse-effect level (NOAEL) for the neurotoxic effects of chronic low-level gasoline exposure.

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