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Model studies for evaluating the acute neurobehavioral effects of complex hydrocarbon solvents. I. Validation of methods with ethanol

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Author: McKee, R.H. · Lammers, J.H.C.M. · Hoogendijk, E.M.G. · Emmen, H.H. · Muijser, H. · Barsotti, D.A. · Owen, D.E. · Kulig, B.M.
Type:article
Date:2006
Institution: TNO Kwaliteit van Leven
Source:NeuroToxicology, 6, 27, 1064-1079
Identifier: 239686
doi: doi:10.1016/j.neuro.2006.05.014
Keywords: Biology · Toxicology and Applied Pharmacology · Acute CNS effects · Behavior · Ethanol · Human · Rat · alcohol · hydrocarbon · solvent · adult · alcohol blood level · alcohol consumption · animal experiment · article · attention · behavior · central nervous system · controlled study · human · human experiment · learning · male · memory · motor activity · neuromuscular function · nonhuman · normal human · observational method · priority journal · psychomotor performance · rat · sensorimotor function · species comparison · statistical significance · toxicokinetics · validation study · visual discrimination · Adult · Affect · Animals · Behavior, Animal · Body Weight · Discrimination (Psychology) · Dose-Response Relationship, Drug · Ethanol · Humans · Learning · Male · Mental Processes · Models, Animal · Motor Activity · Nervous System · Neuropsychological Tests · Psychomotor Performance · Rats · Rats, Wistar · Reproducibility of Results · Solvents · Time Factors · Verbal Behavior · Visual Perception · Animalia

Abstract

As a preliminary step to evaluating the acute neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, joint neurobehavioral/toxicokinetic studies were conducted which involved administering ethanol to rats and volunteers. The specific objectives of the present studies were to evaluate the acute central nervous system (CNS) effects of ethanol in rats and humans and to assess relationships between internal levels of exposure and behavioral effects. A more general objective was to validate a battery of neurobehavioral tests that could be used to carry out comparative studies in both species. Accordingly, a range of tests including standardized observational measures, spontaneous motor activity assessments and learned visual discrimination performance was utilized in rat studies to evaluate acute CNS effects. Groups of rats were given ethanol at levels of approximately 0.5, 1.0 or 2.0 g/kg, with blood level measurements to verify internal doses. In a volunteer study, 12 healthy male subjects were given 0.65 g/kg ethanol, a level approximating the limit for motor vehicle operation in The Netherlands, and neurobehavioral effects were measured prior to and 1 and 3 h after ethanol administration, with a computerized neurobehavioral test battery. Blood and air measurements were made to quantify internal doses. Results of the behavioral tests in rats provided evidence of ethanol-induced changes in neuromuscular, sensori-motor, and activity domains. There were also significant changes in visual discrimination, particularly in the areas of general measures of responding and psychomotor speed. In humans there were small but statistically significant effects on learning and memory, psychomotor skills and attention. However, the effects were subtle and not all parameters within given domains were affected. These studies demonstrated a qualitative similarity in response between rats and humans. © 2006 Elsevier Inc. All rights reserved.