Assessment of offspring development and behavior following gestational exposure to inhaled methanol in the rat. 1995

M E Stanton, and K M Crofton, and L E Gray, and C J Gordon, and W K Boyes, and M L Mole, and D B Peele, and P J Bushnell
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.

The prospect of widespread human exposure associated with its use as an alternative fuel has sparked concern about the toxic potential of inhaled methanol (MeOH). Previous studies have revealed congenital malformations in rats following inhaled MeOH (Nelson et al. (1985). Fundam. Appl. Toxicol. 5, 727-736) but these studies did not include postnatal behavioral assessment. In the present study, pregnant Long-Evans rats were placed in exposure chambers containing 15,000 ppm MeOH or air for 7 hr/day on Gestational Days (GD) 7-19. The total alveolar dose of methanol was estimated at about 6.1 g/kg/day, for a total dose of about 42.7 g/kg for the entire study. Maternal body weights were recorded daily and blood methanol concentrations were determined at the end of exposure on GD 7, 10, 14, and 18. Following birth (Postnatal Day 0 [PND 0]), a number of tests were performed at various points in development, including: offspring mortality and body wt (PND 1,3), motor activity (PND 13-21, 30, 60), olfactory learning (PND 18), behavioral thermoregulation (PND 20-21), T-maze learning (PND 23-24), acoustic startle response (PND 24, 60), reflex modification audiometry (PND 60), pubertal landmarks (PND 31-56), passive avoidance (PND 72), and visual-evoked potentials (PND 160). Maternal blood MeOH levels, measured from samples taken within 15 min after removal from the exposure chamber, declined from about 3.8 mg/ml on the first day of exposure to 3.1 mg/ml on the 12th day of exposure. MeOH transiently reduced maternal body wt (4-7%) on GD 8-10, and offspring BW (5%) on PND 1. No other test revealed significant effects of MeOH. Prenatal exposure to high levels of inhaled MeOH appears to have little effect on this broad battery of tests beyond PND 1 in the rat.

UI MeSH Term Description Entries
D007858 Learning Relatively permanent change in behavior that is the result of past experience or practice. The concept includes the acquisition of knowledge. Phenomenography
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D009422 Nervous System Diseases Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle. Neurologic Disorders,Nervous System Disorders,Neurological Disorders,Disease, Nervous System,Diseases, Nervous System,Disorder, Nervous System,Disorder, Neurologic,Disorder, Neurological,Disorders, Nervous System,Disorders, Neurologic,Disorders, Neurological,Nervous System Disease,Nervous System Disorder,Neurologic Disorder,Neurological Disorder
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011297 Prenatal Exposure Delayed Effects The consequences of exposing the FETUS in utero to certain factors, such as NUTRITION PHYSIOLOGICAL PHENOMENA; PHYSIOLOGICAL STRESS; DRUGS; RADIATION; and other physical or chemical factors. These consequences are observed later in the offspring after BIRTH. Delayed Effects, Prenatal Exposure,Late Effects, Prenatal Exposure
D001833 Body Temperature Regulation The processes of heating and cooling that an organism uses to control its temperature. Heat Loss,Thermoregulation,Regulation, Body Temperature,Temperature Regulation, Body,Body Temperature Regulations,Heat Losses,Loss, Heat,Losses, Heat,Regulations, Body Temperature,Temperature Regulations, Body,Thermoregulations
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D005074 Evoked Potentials, Visual The electric response evoked in the cerebral cortex by visual stimulation or stimulation of the visual pathways. Visual Evoked Response,Evoked Potential, Visual,Evoked Response, Visual,Evoked Responses, Visual,Potential, Visual Evoked,Potentials, Visual Evoked,Response, Visual Evoked,Responses, Visual Evoked,Visual Evoked Potential,Visual Evoked Potentials,Visual Evoked Responses
D005260 Female Females
D006128 Growth Gradual increase in the number, the size, and the complexity of cells of an individual. Growth generally results in increase in ORGAN WEIGHT; BODY WEIGHT; and BODY HEIGHT.

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