Neurobehavioural effects and pharmacokinetics of toluene in rats and their relevance to man.
The present study was designed to determine the critical concentrations in blood and brain associated with specific behavioural changes during and after exposure to toluene. The effects of a single four hour exposure to toluene on signalled bar press shock avoidance in rats were tested. Rats exposed to 125, 250, and 500 ppm toluene showed a decline in conditioned avoidance responses at 20 minutes exposure compared with the pre-exposure baseline, although they recovered to almost the same level of performance as that before exposure. Exposure to 1000 ppm toluene for about four hours and 2000 ppm for two hours produced a concentration related increase in incorrect responses, acceleration of the reaction time, and decreases in the effective avoidance response rate. Beginning at 4000 ppm toluene exposure, the response rate increased; thereafter, it gradually decreased and finally slight ataxia was observed. After 4000 ppm exposure, all rats showed signs of excitation such as a pronounced increase in response rate. From analysis of the temporal courses of the blood and brain toluene concentrations during and after each exposure, excitative performance decrements were noticed in rats with blood and brain concentrations about 27 micrograms/ml blood and 32 micrograms/g respectively. Anaesthetic performance decrements were seen when the blood toluene concentration increased to 120 micrograms/ml and that of the brain reached about 160 micrograms/g. According to our results, the effects on the central nervous system are considered to be a function of both the exposure concentration and its duration, which are closely related to the increase of brain and blood toluene concentration.
Kishi
R
R
Department of Public Health, Sapporo Medical College, Japan.
Harabuchi
I
I
Ikeda
T
T
Yokota
H
H
Miyake
H
H
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D014050:Toluene / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics*
D014050:Toluene