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The objective of our study was to estimate metabolites of pseudocumene in the lung, liver, kidney and urine of rats after single and repeated inhalation exposure. Male Wistar rats were exposed to pseudocumene vapors at nominal concentrations of 25, 100 or 250 ppm in the dynamic inhalation chambers for 6 h or 4 weeks (6h/day; 5 days/week). Following exposure, three metabolites were measured in biologic material after hydrolysis: 3,4-dimethylbenzoic acid (3,4- DMBA), 2,4-dimethylbenzoic acid (2,4-DMBA) and 2,5-dimethylbenzoic acid (2,5-DMBA). The metabolites were analyzed by gas chromatography with a flame ionization detector. The study showed no significant increase in concentrations of the analyzed DMBA metabolites in the liver and lungs of rats exposed to repeated inhalation exposures to pseudocumene as compared to a single exposure. It was found that metabolic transformation of pseudocumene, leading to the production of 3,4- DMBA in the rats kidneys, are more pronounced after repeated inhalation exposure.
The aim of our study was to explore the tissue distribution of 3,5-dimethylbenzene acid (3,5-DMBA) and its excretion with urine of rats and to evaluate toxicokinetics of mesitylene in blood of rats after single and repeated inhalation exposure to mesitylene vapours. Experiments were performed on male outbred IMP:WIST rats. The animals were exposed to mesitylene vapours at the target concentration of 25, 100, and 250 ppm in dynamic inhalation chambers for 6 h at single exposure and for 4 weeks (6 h/day for 5day/week) at repeated exposure. The study revealed in rats, after inhalation exposure to mesitylene, exposure-dependent increases in 3,5-DMBA tissue concentration and urinary excretion as well as enhanced mesitylene concentration in tissues and blood. After termination of exposure, mesitylene was rapidly eliminated from blood of rats. Mesitylene retention reduced in rat lungs after repeated exposure, as compared to a single exposure, was most likely the reason for its lower concentration in lungs and blood. Compared with single exposure, 3,5-DMBA concentration increased in rat lungs after repeated inhalation exposure to mesitylene at 100 and 250 ppm, and in the liver at 250 ppm, which may be associated with the induction of mesitylene-metabolizing enzymes. Mesitylene metabolism in the lungs of the rats after repeated exposure to its low concentrations probably had a significant impact on the increased urinary excretion of 3,5-DMBA.
The vulnerability of the nervous system to toxic insult is particularly high during foetal life and early childhood. Exposures during this period, via maternal blood and/or milk, may result in neurobehavioural disorders, some of which may not become apparent before in adulthood. Methylmercury (MeHg) and polychlorinated biphenyls (PCB) are persistent environmental pollutants and may be present in some food products. Both are neurotoxic. It is suspected that MeHg and PCBs may act synergistically in inducing neurotoxic effects. Some data suggest that catecholaminergic systems, especially the dopaminergic one, are particularly vulnerable to the harmful action of MeHg and PCBs. This study aimed to assess the influence of separate or combined perinatal exposure to MeHg and PCB 153 on brain catecholamine contents in maturity. The subjects were adult (90-94 days of age) rats, progeny of mothers exposed to methylmercury (MeHg, CH₃HgCl) or 2,2’,4,4’,5,5’-hexachlorobiphenyl (PCB 153), or MeHg and PCB 153, from day 7 of gestation to day 21 post partum. MeHg was administered with drinking water at daily doses of 0.5 mg/kg b.w./day. PCB 153 was administered by gavage at daily doses of 5 mg/kg b.w./day. The concentrations of adrenaline (A), noradrenaline (NA), dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were determined by HPLC in homogenates of the following brain regions: olfactory bulb, hippocampus, striatum, occipito-temporal cortex, diencephalon, mesencephalon and cerebellum. The results suggest some exposure-related alterations in amine contents and point to the significant role of gender in their development. In the female MeHg-exposed progeny, the content of NA, DA and DOPAC in the mesencephalon was significanrtly elevated (by 43.1, 68.9 and 65.1%, respectively) while in the male progeny no differences were noted in any region of the brain. On the other hand, in the progeny exposed to PCB 153, some differences, i.e. increased NA concentration in the olfactory bulb (by 59.9%) and hippocampus (by 124.5%) and increased DA (by 75.0%) in the striatum were found in males, whereas in females significant differences were not found. In the case of combined exposure, the data suggest some effects in the female progeny only: a decreased concentration of A in the hippocampus (by 40.9%) but increased in the stratum (by 53.1%) and an increased DA concentration in the mesencephalon (by 78.9%). Summing up, the results confirm that gender may be an important determinant of the rat’s vulnerability to MeHg and PCB153. They provide no evidence, however, of a synergism in the action of these neurotoxicants when given perinatally on the brain catecholaminergic systems in adulthood. A rough analysis of the obtained data allows one to suspect an antagonistic rather than synergistic type of interaction.
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