Repository hosted by TU Delft Library

Home · Contact · About · Disclaimer ·

Behavioural effects and kinetics in brain in response to inhalation of constant or fluctuating toluene concentrations in the rat

Publication files not online:

Author: Lammers, J.H.C.M. · Asperen, J. van · Groot, D. de · Rijcken, W.R.P.
Institution: TNO Kwaliteit van Leven
Source:Environmental Toxicology and Pharmacology, 3, 19, 625-634
Identifier: 238494
doi: doi:10.1016/j.etap.2004.12.028
Keywords: Health Biology · Toxicology and Applied Pharmacology · Motor activity · Peak exposure · Rat · Toluene · Toxicokinetics · Visual discrimination · toluene · animal experiment · animal model · blood level · brain level · concentration response · conference paper · controlled study · exposure · male · motor activity · neurotoxicity · nonhuman · priority journal · rat · toxicokinetics · visual discrimination


The toxicity of exposure by inhalation to organic solvents may not only be related to the total external dose, but also to the pattern of exposure. In this study the impact of the exposure scenario on the behavioural effects of the model solvent toluene in rats was investigated. Rats were exposed for 7.5 h to either a constant concentration or fluctuating concentrations at total external dose levels of 20,000 ppm h and 10,000 ppm h. Different effects on measures of visual discrimination performance were observed in rats exposed to a constant or fluctuating concentrations, and when rats were tested immediately or sometime after the end of exposure to fluctuating concentrations. Motor activity was also differently affected by different exposure scenarios. Physiologically based toxicokinetic (PBTK) modelling was used to predict the toxicokinetics of toluene induced by these different exposure scenarios. The model was calibrated by measuring toluene concentrations in blood and brain during and after exposure. The results show that the acute effects of toluene on behaviour do not depend only on the concentration and duration of exposure, but primarily on the pattern of exposure. © 2005 Elsevier B.V. All rights reserved.