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.