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Model studies for evaluating the acute neurobehavioral effects of complex hydrocarbon solvents I. Validation of methods with ethanol.
Neurotoxicology. 2006 Dec; 27(6):1064-79.N

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 2.0g/kg, with blood level measurements to verify internal doses. In a volunteer study, 12 healthy male subjects were given 0.65g/kg ethanol, a level approximating the limit for motor vehicle operation in The Netherlands, and neurobehavioral effects were measured prior to and 1 and 3h 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.

Authors+Show Affiliations

ExxonMobil Biomedical Sciences, Inc., 1545 Route 22 East, P.O. Box 971, Annandale, NJ 08801-0971, USA. richard.h.mckee@exxonmobile.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't
Validation Study

Language

eng

PubMed ID

16831461

Citation

McKee, R H., et al. "Model Studies for Evaluating the Acute Neurobehavioral Effects of Complex Hydrocarbon Solvents I. Validation of Methods With Ethanol." Neurotoxicology, vol. 27, no. 6, 2006, pp. 1064-79.
McKee RH, Lammers JH, Hoogendijk EM, et al. Model studies for evaluating the acute neurobehavioral effects of complex hydrocarbon solvents I. Validation of methods with ethanol. Neurotoxicology. 2006;27(6):1064-79.
McKee, R. H., Lammers, J. H., Hoogendijk, E. M., Emmen, H. H., Muijser, H., Barsotti, D. A., Owen, D. E., & Kulig, B. M. (2006). Model studies for evaluating the acute neurobehavioral effects of complex hydrocarbon solvents I. Validation of methods with ethanol. Neurotoxicology, 27(6), 1064-79.
McKee RH, et al. Model Studies for Evaluating the Acute Neurobehavioral Effects of Complex Hydrocarbon Solvents I. Validation of Methods With Ethanol. Neurotoxicology. 2006;27(6):1064-79. PubMed PMID: 16831461.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Model studies for evaluating the acute neurobehavioral effects of complex hydrocarbon solvents I. Validation of methods with ethanol. AU - McKee,R H, AU - Lammers,J H C M, AU - Hoogendijk,E M G, AU - Emmen,H H, AU - Muijser,H, AU - Barsotti,D A, AU - Owen,D E, AU - Kulig,B M, Y1 - 2006/05/27/ PY - 2006/03/16/received PY - 2006/05/18/revised PY - 2006/05/22/accepted PY - 2006/7/13/pubmed PY - 2007/3/22/medline PY - 2006/7/13/entrez SP - 1064 EP - 79 JF - Neurotoxicology JO - Neurotoxicology VL - 27 IS - 6 N2 - 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 2.0g/kg, with blood level measurements to verify internal doses. In a volunteer study, 12 healthy male subjects were given 0.65g/kg ethanol, a level approximating the limit for motor vehicle operation in The Netherlands, and neurobehavioral effects were measured prior to and 1 and 3h 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. SN - 0161-813X UR - https://www.unboundmedicine.com/medline/citation/16831461/Model_studies_for_evaluating_the_acute_neurobehavioral_effects_of_complex_hydrocarbon_solvents_I__Validation_of_methods_with_ethanol_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-813X(06)00133-1 DB - PRIME DP - Unbound Medicine ER -