Print Email Facebook Twitter Model studies for evaluating the neurobehavioral effects of complex hydrocarbon solvents. II. Neurobehavioral effects of white spirit in rat and human Title Model studies for evaluating the neurobehavioral effects of complex hydrocarbon solvents. II. Neurobehavioral effects of white spirit in rat and human Author Lammers, J.H.C.M. Emmen, H.H. Muijser, H. Hoogendijk, E.M.G. McKee, R.H. Owen, D.E. Kulig, B.M. TNO Kwaliteit van Leven Publication year 2007 Abstract To evaluate the neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, studies were conducted which involved inhalation exposure of rats and humans to white spirit (WS). The specific objectives of these studies were to evaluate the behavioral effects of exposure to WS in rats and humans and to determine relationships between internal levels of exposure and behavioral effects. In both animals and volunteers, methods for assessment of similar functional effects were used to enable interspecies comparisons. A battery of tests including standardized observational measures, spontaneous motor activity assessments and learned visual discrimination performance was utilized in rat studies to evaluate acute central nervous system (CNS) depression. Groups of rats were exposed to WS at target concentrations of 0, 600, 2400 or 4800 mg/m3, 8 h/day for 3 consecutive days. Blood and brain concentrations of two WS constituents; 1,2,4-trimethylbenzene (TMB) and n-decane (NDEC), were used as biomarkers of internal exposure. In a volunteer study, 12 healthy male subjects were exposed for 4 h to either 57 or 570 mg/m3 WS in two test sessions spaced 7 days apart, and neurobehavioral effects were measured using a computerized neurobehavioral test battery. Blood samples were taken at the end of the exposure period to measure internal concentrations of TMB and NDEC. Results of the behavioral tests in rats indicated WS-induced changes particularly in performance and learned behavior. In humans, some subtle performance deficits were observed, particularly in attention. The behavioral effects were related to concentrations of the WS components in the central nervous system. These studies demonstrated a qualitative similarity in response between rats and humans, adding support to the view that the rodent tests can be used to predict levels of response in humans and to assist in setting occupational exposure levels for hydrocarbon solvents. © 2007 Elsevier Inc. All rights reserved. Subject Toxicology and Applied PharmacologyBehaviorHumanRatSolvent neurotoxicityWhite spirit1,2,4 trimethylbenzenebiological markerdecanehydrocarbonorganic solventstoddard solventunclassified drugadultanimal experimentarticleattentionbehaviorblood samplingcentral nervous system depressioncognitionconditioningcontrolled studycorrelation analysisexposurehumanhuman experimentlearningmalememorymotor activityneuropsychological testneurotoxicitynonhumanobservational studypriority journalqualitative analysisratscoring systemspecies comparisontask performancevisual discriminationAdultAffectAnalysis of VarianceAnimalsAttentionBehavior, AnimalBody WeightDiscrimination (Psychology)HumansHydrocarbonsMaleMental ProcessesModels, AnimalMotor ActivityMotor SkillsNervous SystemNeuropsychological TestsRatsReaction TimeSolventsAnimaliaRattusRodentia To reference this document use: http://resolver.tudelft.nl/uuid:073aefe6-b104-4c22-9500-6fd896202988 DOI https://doi.org/10.1016/j.neuro.2007.03.003 TNO identifier 240077 ISSN 0161-813X Source NeuroToxicology, 28 (4), 736-750 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.