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Title: Study of the neuroligical effects of low-level methanol in normal subjects and subjects with susceptibility to folate deficiency

Principal Investigator / Author(s): Becker, Charles

Contractor: UC San Francisco

Contract Number: a033-172

Research Program Area: Health & Exposure

Topic Areas: Health Effects of Air Pollution, Vulnerable Populations


Methanol powered vehicles are being introduced in the United States as a solution to air pollution. Very little is known about methanol as an air pollutant and about the effects of low level exposure on neurobehavioral functioning. Folic acid plays an important role in for-mate metabolism and may influence the concentrations of this toxic metabolite of methanol. The objective of this study is to provide information about whether or not acute exposure to methanol at the current industrial threshold limit value of 200 parts per million (PPM) for four hours would have adverse effects on human neurobehavioral, neurophysiological and visual performances. Twenty six healthy subjects (male: n = 15, female: n = 11; age: 26-51 years) were exposed in a chamber for four hours to methanol vapor (200 PPM, 260 mg/m3) or to water vapor. The subjects served as their own controls in a double-blind design. Mother six subjects from two possible foliate deficient groups were also examined. The following endpoints were tested before, during or / and after exposure to methanol and water vapors: blood and urine formate and methanol levels; auditory-event-related potentials: visual performance: and behavioral tests. In an analysis of the results in the normal population, no important effects due to methanol exposure were found for the neurobehavioral and visual tests. However, possible effects were observed when outcomes were adjusted for factors possibly contributing to between-subject variability. For example, methanol effects were observed on P-300 auditory evoked potential amplitudes when adjusted for several variables, but particularly smoking and alcohol consumption. Exposure to methanol at 200 PPM during the study increased the concentration of methanol in serum and the amount of methanol excreted in urine. No statistically significant differences in serum for-mate concentration were found between the exposure and control conditions at any time point or for area under the curve. Additionally, most of the test results from the foliate-susceptible subjects did not demonstrate any notable deviation from the normal population of the study. One susceptible individual, while in a foliate deficient state, accumulated formate after exposure. In summary, while methanol concentrations reflected the exposure condition, no important neurobehavioral differences were found in the normal and susceptible populations after exposure to 200 PPM methanol for four hours. Because the study was not designed to examine the influence of age, gender, foliate status, smoking and alcohol consumption, other more powerful and appropriately designed studies will be required to clearly demonstrate methanol effects relating to any of these factors.


For questions regarding this research project, including available data and progress status, contact: Research Division staff at (916) 445-0753

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