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Neurobehavioural evaluation and kinetics of inhalation of constant or fluctuating toluene concentrations in human volunteers

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Author: Lammers, J.H.C.M. · Meuling, W.J.A. · Muijser, H. · Freidig, A.P. · Bessems, J.G.M.
Institution: TNO Kwaliteit van Leven
Source:Environmental Toxicology and Pharmacology, 3, 20, 431-442
Identifier: 238803
doi: doi:10.1016/j.etap.2005.05.003
Keywords: Health · Toxicology and Applied Pharmacology · Human · Neurobehaviour · PBTK modelling · Peak exposure · Toluene · Toxicokinetics · ortho cresol · toluene · adolescent · article · attention · blood analysis · brain level · central nervous system function · controlled study · exposure · human · male · memory · mood · motor performance · neurologic examination · normal human · perception · priority journal · qualitative analysis · urinalysis · Animalia


The health risks of inhalation exposure to volatile organic solvents may not only depend on the total external dose, but also on the pattern of exposure. It has been suggested that exposure to regularly occurring peak concentrations may have a stronger impact on the brain than constant exposure at the same average level. Recent animal experimental studies conducted in our laboratory using relatively high concentrations of toluene have shown different effects on discrimination performance and motor activity during and after exposure, depending on the exposure scenario. Relevance of these findings for man was evaluated in a volunteer study in which 11 healthy men (age 20-49 years) were exposed by inhalation for 4 h to either a constant concentration of 40 ppm toluene or to three 30-min exposure peaks at 110 ppm during this 4 h period. Selected tests from the Neurobehavioural Evaluation System (NES) were performed repeatedly during and after exposure. Blood concentrations of toluene as well as urinary o-cresol excretion were measured at relevant time points. The results show that toluene concentration in blood increased during constant exposure and fluctuated during occupationally relevant peak exposures. Presumably, brain concentrations showed similar qualitative patterns. No clear changes were observed on neurobehavioural measures of motor performance, attention, perceptual coding and memory, or on measures of mood and affect. The exposure conditions do not seem to induce significant acute changes in central nervous system function similar to those observed at much higher concentrations in animals, although a statistical correlation was found between one motor performance test (Finger Tapping Test with alternating hands) and blood toluene concentrations. Urinary o-cresol excretion appeared to be significantly higher during the first 2 h after exposure. © 2005 Elsevier B.V. All rights reserved.