Four weeks' inhalation exposure of Long Evans rats to 4-tert-butyltoluene:Effect on evoked potentials, behaviour and brain neurochemistry

Long-lasting central nervous system (CNS) neurotoxicity of 4-tert-butyltolu ene (TBT) has been investigated using electrophysiology, behaviour, and neu rochemistry in Long Evans rats exposed by inhalation to 0, 20, or 40 p.p.m. TBT 6 hr/day, 7 days/week for 4 weeks. Flash evoked potentials and somatos ensory evoked potentials were not affected by TBT In Auditory Brain Stem Re sponse there was no shift in hearing threshold, but the amplitude of the fi rst wave was increased in both exposed groups at high stimulus levels. Thre e to four months after the end of exposure, behavioural studies in Morris w ater maze and eight-arm maze failed to demonstrate any TBT induced effects. Exposure was followed by a 5 months exposure-free period prior to gross re gional and subcellular (synaptosomal) neurochemical investigations of the b rain. TBT reduced the NA concentration in whole brain minus cerebellum. Syn aptosomal choline acetyltransferase activity increased and acetylcholineste rase activity was unchanged suggesting increased synaptosomal ability for a cetylcholine synthesis. The relative and total yield of synaptosomal protei n was reduced suggesting reduced density and total number of synapses in si tu, respectively. We hypothesise that a reduced yield of synaptosomal prote in reflects a more general effect of organic solvent exposure on the softwa re of the brain. The synaptosomal concentration per mg synaptosomal protein and the total amount of 5-hydroxytryptamine were not affected whereas the total amount of synaptosomal noradrenaline decreased. The concentration and the total amount of synaptosomal dopamine decreased. The noradrenergic and dopaminergic parts of CNS may be more vulnerable to TBT than the serotoner gic, and these long-lasting effects may cause or reflect TBT-compromised CN S function.