The objective of the study is to determine the following aspects of the exposure-dose-response relationship for inhaled methanol: 1) Fetal Neurotoxicity, as defined by alterations in the behavioral development of Macaca fascicularis offspring exposed in utero to methanol; 2) maternal reproductive toxicity, as defined by decreased conceptions and/or live birth deliveries in methanol exposed M. fascicularis females; and 3) maternal pharmacokinetic changes related to pregnancy, as defined by changes in the blood clearance and/or distribution kinetics of methanol in exposed non human primate females. The proposed study will assess maternal methanol pharmacokinetics at three levels of methanol inhalation exposure, 2O0ppm, 600ppm, and 1,800ppm (and a control). The effects of methanol exposure on female reproductive functions will be studied by mating each female, for up to 3 matings, with a non exposed male. The primary focus of the proposed study is the assessment of the effects of in utero methanol exposure on the neurobehavioral development of the infant. Methanol-exposed and control offspring will be tested from birth to 1 year of age on a series of behavioral assessments, largely adapted from studies of human infants. Assessments of early reflex development, visual acuity, recognition memory, object permanence, social behavior and spatial and non spatial memory will be used. The proposed study follows the design of an ongoing investigation of methanol reproductive and developmental effects in primates supported by the Health Effects Institute (HEI). This ongoing investigation was begun in response to the need for data regarding the effects of chronic methanol inhalation exposure brought on by the increased use of methanol as a motor fuel. Because of the costs associated with this project, however, a second source of funds is required to complete the investigation as originally designed. The results of the study will indicate whether chronic, low-level exposure to methanol prior to and during pregnancy affects female reproductive functions and subsequent offspring neurobehavioral development. Since the fetus and infant are known to be one of the most sensitive subgroups to many neurotoxic substances that readily pass through the placenta, this evaluation should provide extremely important data regarding the risks of environmental and/or occupational exposure to methanol resulting from increased use of methanol as a motor fuel.
| 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 |
