. The overall objective of this research program is to determine the developmental toxicity of in utero methanol exposure in nonhuman primates. The proposed use of methanol as an alternative to gasoline would lead to frequent and widespread exposure of women of childbearing age. The population consists of 2 cohorts of m. fascicularis monkeys whose dams were exposed to methanol during gestation (0, 200, 600, 1800 ppm). Offspring were evaluated from birth to at least 1 year of age, and results indicate that methanol affects recognition memory and motor and/or somatosensory development during infancy. Additional studies proposed for the current application include: 1) comprehensive evaluation of the visual system of exposed and control monkeys; 2) determining whether the effects on recognition memory persist and are identifiable by later tests of related functions; 3) identification of the cause of the puberal growth retardation seen in several females. Tests to evaluate vision will include both Electroretinograms, which test ocular function, and Visual Contrast Sensitivity studies to evaluate the visual cortex. Sources of the infant recognition memory deficits will be examined by use of Tests of Simple and Complex Reaction Time and the Nonmatch-to-Sample List Length Test. In addition, tests for tremor, reaching and grasping will test the possibility that methanol has long-lasting effects on visually-guided reaching. Finally, a battery of hormone assays will be used to evaluate possible sources of puberal growth retardation. These studies will provide a thorough analysis of the developmental effects of methanol in nonhuman primates, and will constitute the only such body of data for application to risk assessment of the consequences of widespread environmental dissemination of methanol.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES006673-07
Application #
6382161
Study Section
Special Emphasis Panel (ZRG4-ALTX-4 (01))
Program Officer
Kirshner, Annette G
Project Start
1994-02-01
Project End
2003-03-31
Budget Start
2001-04-01
Budget End
2003-03-31
Support Year
7
Fiscal Year
2001
Total Cost
$327,651
Indirect Cost
Name
University of Washington
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Burbacher, Thomas M; Shen, Danny D; Lalovic, Bojan et al. (2004) Chronic maternal methanol inhalation in nonhuman primates (Macaca fascicularis): exposure and toxicokinetics prior to and during pregnancy. Neurotoxicol Teratol 26:201-21
Burbacher, Thomas M; Grant, Kimberly S; Shen, Danny D et al. (2004) Chronic maternal methanol inhalation in nonhuman primates (Macaca fascicularis): reproductive performance and birth outcome. Neurotoxicol Teratol 26:639-50