Print Email Facebook Twitter Model studies for evaluating the acute neurobehavioral effects of complex hydrocarbon solvents. I. Validation of methods with ethanol Title Model studies for evaluating the acute neurobehavioral effects of complex hydrocarbon solvents. I. Validation of methods with ethanol 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. TNO Kwaliteit van Leven Publication year 2006 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. Subject BiologyToxicology and Applied PharmacologyAcute CNS effectsBehaviorEthanolHumanRatalcoholhydrocarbonsolventadultalcohol blood levelalcohol consumptionanimal experimentarticleattentionbehaviorcentral nervous systemcontrolled studyhumanhuman experimentlearningmalememorymotor activityneuromuscular functionnonhumannormal humanobservational methodpriority journalpsychomotor performanceratsensorimotor functionspecies comparisonstatistical significancetoxicokineticsvalidation studyvisual discriminationAdultAffectAnimalsBehavior, AnimalBody WeightDiscrimination (Psychology)Dose-Response Relationship, DrugEthanolHumansLearningMaleMental ProcessesModels, AnimalMotor ActivityNervous SystemNeuropsychological TestsPsychomotor PerformanceRatsRats, WistarReproducibility of ResultsSolventsTime FactorsVerbal BehaviorVisual PerceptionAnimalia To reference this document use: http://resolver.tudelft.nl/uuid:991b0d07-4acb-45b2-a7a9-ecef36aaa862 DOI https://doi.org/10.1016/j.neuro.2006.05.014 TNO identifier 239686 ISSN 0161-813X Source NeuroToxicology, 27 (6), 1064-1079 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.