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Model studies for evaluating the neurobehavioral effects of complex hydrocarbon solvents II. Neurobehavioral effects of white spirit in rat and human.
Neurotoxicology. 2007 Jul; 28(4):736-50.N

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 4800mg/m(3), 8h/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 4h to either 57 or 570mg/m(3) 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.

Authors+Show Affiliations

TNO Quality of Life, Zeist, The Netherlands. jan.lammers@tno.nlNo 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

Language

eng

PubMed ID

17433444

Citation

Lammers, J H C M., et al. "Model Studies for Evaluating the Neurobehavioral Effects of Complex Hydrocarbon Solvents II. Neurobehavioral Effects of White Spirit in Rat and Human." Neurotoxicology, vol. 28, no. 4, 2007, pp. 736-50.
Lammers JH, Emmen HH, Muijser H, et al. Model studies for evaluating the neurobehavioral effects of complex hydrocarbon solvents II. Neurobehavioral effects of white spirit in rat and human. Neurotoxicology. 2007;28(4):736-50.
Lammers, J. H., Emmen, H. H., Muijser, H., Hoogendijk, E. M., McKee, R. H., Owen, D. E., & Kulig, B. M. (2007). Model studies for evaluating the neurobehavioral effects of complex hydrocarbon solvents II. Neurobehavioral effects of white spirit in rat and human. Neurotoxicology, 28(4), 736-50.
Lammers JH, et al. Model Studies for Evaluating the Neurobehavioral Effects of Complex Hydrocarbon Solvents II. Neurobehavioral Effects of White Spirit in Rat and Human. Neurotoxicology. 2007;28(4):736-50. PubMed PMID: 17433444.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Model studies for evaluating the neurobehavioral effects of complex hydrocarbon solvents II. Neurobehavioral effects of white spirit in rat and human. AU - Lammers,J H C M, AU - Emmen,H H, AU - Muijser,H, AU - Hoogendijk,E M G, AU - McKee,R H, AU - Owen,D E, AU - Kulig,B M, Y1 - 2007/03/15/ PY - 2006/08/25/received PY - 2007/03/07/revised PY - 2007/03/08/accepted PY - 2007/4/17/pubmed PY - 2007/11/1/medline PY - 2007/4/17/entrez SP - 736 EP - 50 JF - Neurotoxicology JO - Neurotoxicology VL - 28 IS - 4 N2 - 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 4800mg/m(3), 8h/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 4h to either 57 or 570mg/m(3) 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. SN - 0161-813X UR - https://www.unboundmedicine.com/medline/citation/17433444/Model_studies_for_evaluating_the_neurobehavioral_effects_of_complex_hydrocarbon_solvents_II__Neurobehavioral_effects_of_white_spirit_in_rat_and_human_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-813X(07)00051-4 DB - PRIME DP - Unbound Medicine ER -