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 Pharmacology
Behavior
Human
Rat
Solvent neurotoxicity
White spirit
1,2,4 trimethylbenzene
biological marker
decane
hydrocarbon
organic solvent
stoddard solvent
unclassified drug
adult
animal experiment
article
attention
behavior
blood sampling
central nervous system depression
cognition
conditioning
controlled study
correlation analysis
exposure
human
human experiment
learning
male
memory
motor activity
neuropsychological test
neurotoxicity
nonhuman
observational study
priority journal
qualitative analysis
rat
scoring system
species comparison
task performance
visual discrimination
Adult
Affect
Analysis of Variance
Animals
Attention
Behavior, Animal
Body Weight
Discrimination (Psychology)
Humans
Hydrocarbons
Male
Mental Processes
Models, Animal
Motor Activity
Motor Skills
Nervous System
Neuropsychological Tests
Rats
Reaction Time
Solvents
Animalia
Rattus
Rodentia
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