title: Four weeks' inhalation exposure of Long Evans rats to 4-tert-butyltoluene: effect on evoked potentials, behaviour, and brain neurochemistry.
abstract: Long-lasting central nervous system (CNS) neurotoxicity of 4-tert-butyltoluene (TBT) has been investigated using electrophysiology, behaviour, and neurochemistry 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 somatosensory evoked potentials were not affected by TBT. In Auditory Brain Stem Response there was no shift in hearing threshold, but the amplitude of the first wave was increased in both exposed groups at high stimulus levels. Three to four months after the end of exposure, behavioural studies in Morris water 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 regional and subcellular (synaptosomal) neurochemical investigations of the brain. TBT reduced the NA concentration in whole brain minus cerebellum. Synaptosomal choline acetyltransferase activity increased and acetylcholinesterase activity was unchanged suggesting increased synaptosomal ability for acetylcholine synthesis. The relative and total yield of synaptosomal protein was reduced suggesting reduced density and total number of synapses in situ, respectively. We hypothesise that a reduced yield of synaptosomal protein reflects a more general effect of organic solvent exposure on the software 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 serotonergic, and these long-lasting effects may cause or reflect TBT-compromised CNS function.
authors.affiliation: Institute of Food Safety and Toxicology, Danish Veterinary and Food Administration, Søborg. hrl@fdir.dk
authors.forename: H R
authors.initials: HR
authors.lastname: Lam
authors.forename: O
authors.initials: O
authors.lastname: Ladefoged
authors.forename: G
authors.initials: G
authors.lastname: Ostergaard
authors.forename: U
authors.initials: U
authors.lastname: Hass
authors.forename: S P
authors.initials: SP
authors.lastname: Lund
authors.forename: L
authors.initials: L
authors.lastname: Simonsen
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000280:Administration, Inhalation; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D005082:Physical Exertion / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology; D014050:Toluene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D018377:Neurotransmitter Agents; D014050:Toluene; C027647:4-tert-butyltoluene; D007770:L-Lactate Dehydrogenase; D000110:Acetylcholinesterase