title: Sub-chronic exposure to toluene at 40 ppm alters the monoamine biosynthesis rate in discrete brain areas.
abstract: Effects of long-term exposure to a sub-toxic concentration of toluene (40 ppm, 104 h per week, 16 weeks) have been studied on monoamine biosynthesis rate in rat. The activities of the rate limiting enzymes in catecholamine and 5-hydroxytryptamine biosynthesis tyrosine and tryptophan hydroxylase, respectively, were estimated in vivo by measuring the accumulation of l-dihydroxyphenylalanine and 5-hydroxytryptophan after pharmacological blockade of l-aromatic acid decarboxylases by NSD-1015 (100 mg kg(-1) ip). The sub-chronic exposure to toluene led to a significant and gender dependent alteration in both catecholamine and 5-hydroxytryptamine biosynthesis rate in brainstem catecholaminergic cell groups and hypothalamus. In females exposed to toluene, changes in tryptophan hydroxylation were found in rostral subset of A2C2 (+41%) and in A1C1 (+41%) while a decrease in A5 (-44%) and an increase in A2C2 (+28%) were found in tyrosine hydroxylation. In males, an increase in tryptophane hydroxylation was observed in rostral subset of A2C2 (+35%) while a decrease was observed in ventro-median hypothalamus (-17%). These results suggest that toluene exposure to a dose generally recognized as sub-toxic (40 ppm, no observed adverse effect level) leads to adverse effects on monoaminergic systems. Therefore, the neurotoxicity of toluene should be carefully re-evaluated taking into account not only the exposure level but also the duration.
authors.affiliation: Laboratoire de Physiologie Intégrative Cellulaire et Moléculaire, UMR CNRS 5123, Université Claude Bernard Lyon I, bâtiment 404-Raphaël Dubois, Campus de la Doua, 69 622 Villeurbanne Cedex 08, France. soulage@univ-lyon1.fr
authors.forename: Christophe
authors.initials: C
authors.lastname: Soulage
authors.forename: D
authors.initials: D
authors.lastname: Perrin
authors.forename: P
authors.initials: P
authors.lastname: Berenguer
authors.forename: J M
authors.initials: JM
authors.lastname: Pequignot
mesh_terms: D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D015306:Biogenic Monoamines / Q000096:biosynthesis*; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007980:Levodopa / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014050:Toluene / Q000633:toxicity*; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D015306:Biogenic Monoamines; D014050:Toluene; D007980:Levodopa; D006916:5-Hydroxytryptophan; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase