• Toxicological Research
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• v.31 no.1
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• pp.25-32
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• 2015

The objectives of this study were to investigate the individual characteristics, lifestyle habits, exposure levels, and genetic diversity of xenobiotic-metabolizing enzymes involved in toluene metabolism in Korean and foreign workers exposed to toluene at a manufacturing plant. This study was conducted to determine the effects of culture or ethnicity on toluene metabolism. The results showed that blood and urinary toluene concentrations were dependent on the level of exposure to toluene. We analyzed the correlation between toluene metabolism and genetic diversity in glutathione S-transferase (GST) (M1), GSTT1, and cytochrome p-450 (CYP) $2E1^*5$ as well as lifestyle habits (smoking, drinking, and exercise habits). The results revealed significant correlations between toluene metabolism and GSTM1 and GSTT1 genetic diversity, as well as smoking and exercise.

• Biomedical Science Letters
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• v.7 no.3
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• pp.99-102
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• 2001

Toluene is mainly metabolized in liver by oxidative pathway. Oxigen free radicals occur through the process of toluene metabolism Therefore it causes tissue and cell min by the oxygen free radicals from the metabolism of toluene. Melatonin acts as a highly efficient free radical scavenger that protects cells from damage by oxygen free radicals. To test this hypothesis, toluene hepatotoxicity was induced by an abdominal injection of toluene. To see if the melatonin protects the rat's liver, melatonin was administrated orally, at the time of each toluene injection. Aspartate aminotransferase(AST), alanin aminotransferase(ALT), latic dehydrogenase(LDH) and alkaline phosphatase(ALP) levels in serum were measured to estimate hepatic function. Malondialdehyde(MDA), which gives an indirect index of oxidative injury was also measured. Hippuric acid is the last metabolic Production of toluene was measured by HPLC. There were significantly higher in AST, ALT, LDH, MDA and hippuric acid in toluene group, but there were no significant difference in melatonin group except ALT and hippuric acid. There was significantly lower in ALP level in toluene group, but there was no significant difference melatonin group, suggesting a significant hepatotoxicity due to oxygen free radicals through the process of toluene metabolism Melatonin treatment significantly protected hepatic function and free radical-mediated injury in the liver against toluene-induced changes. Accordingly, this study shows that melatonin is helpful in protecting liver injury by acute toluene intoxication.

• Toxicological Research
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• v.12 no.2
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• pp.243-250
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• 1996

To evaluate an effect of ethanol pretreatment on the toluene metabolism, toluene (50% in olive oil) was given three times at 0.2 ml/100g body weight at the interval of one day to the rats fed with 5% ethanol during two months. The ethanol pretreated rats were not identified particular liver injury by the histopathologic findings. In case of toluene treatment, the ethanol pretreatment to the rats led to more increased concentration of urinary hippuric acid than those treated with only toluene. The ethanol pretreatment to the rats led to the increased activities of hepatic aniline hydroxylase and these enzyme activities were higher both in toluene treated and those pretreated with ethanol, but no differences were found in two groups. Ethanol pretreated rats showed the more increased activities of benzylalcohol dehydrogenase than control group. Moreover, the ethanol pretreatment to the toluene treated rats led to significantly more increased activities of benzylalcohol dehydrogenase compared with those treated with toluene only. Furthermore, the alcohol pretreatment to the toluene treated rats also led to somewhat higher activities of benzaldehyde dehydrogenase than those treated with toluene. In conclusion, these results indicate that the chronic pretreatment of ethanol at not so much liver damage as normal may rather activate the toluene metabolism.

• Preventive Nutrition and Food Science
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• v.5 no.2
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• pp.105-108
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• 2000

To evaluate an effect of oxygen free radical on the toluence metabolism, the rats were fed on a tungstate sup-plemented diet(0.75g of tungstate included in 1kg of standard diet) or a standard diet. To the present xanthine oxidase deficient animal model, toluene(0.15ml/100g of body weight) was injected and then the animals were sacrificed after 24 hrs to determine the toluene metabolizing enzyme activities and toluene metabolite, hippuric acid concentration. The increasing rate of urinary hippuric acid concentration was significantly(p<0.01) higher in tungstate fed animals than in standard diet fed ones. Hepatic cytochrome P_450 contents were significantly higher(p<0.01) in tungstate fed animals than in standard diet fed ones. And tungstate fed animals showed a ten-dency of higher activities of benzylalcohol dehydrogenase while a significantly higher activites of benzaldehyde dehydrogenase (p<0.01) than standard diet fed animals. In conclusion, the more possibly reduced oxygen free radical in toluene-treated rats fed with a tungstate supplemented diet than in those fed with a standard diet would be responsible for the enhancement of toluene metabolism.

• Toxicological Research
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• v.12 no.2
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• pp.237-241
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• 1996

To study an effect of toluene administration on the toluene metabolism in rats liver previously fed a low (casein 7%, LP) or standard (casein 20%, SP) protein diet, toluene (50% in olive oil) was given at 0.2 ml per 100 g body weights once daily during 4 days to the male rats. The content of hepatic cytochrome P-450 was higher in rats fed SP than those fed LP. The hepatic benzylalcohol dehydrogenase activity was higher both in toluene-treated rats and its control group fed SP than those fed LP. The hepatic benzaldehyde dehydrogenase activity was somewhat higher in rats fed SP than those fed LP. In the case of toluene treatment, the increasing rate of hippuric acid contents to the control group were higher in rats SP than those fed LP. In conclusion, it is likely that the metabolic rate of toluene would be higher in rats fed SP than those fed LP.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.7 no.1
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• pp.61-69
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• 1997

To evaluate an effect of pathological liver damage on the toluene metabolism, the rate were induced acute liver damage with 3 times $CCl_4$ injection (0.1 ml of 50 % in olive oil/100 g body wt.) three days. In the present animal molel, the injection of toluene(0.3 ml of 50 % in olive oil) showed the more decreased urine hippuric acid throughout 24 hr in the liver damage induced animals($CCl_4$-pretreated rats) than normal group. The activities of hepatic aniline hydroxylase, benzylalcohol dehydrogenase and benzaldehyde dehydrogenase were significantly decreased in $CCl_4$-pretreated rats than the normal group at 24 hr after injection of toluene. Furthermore, the benzaldehyde dehydrogenase in pooled liver of $CCl_4$-pretreated rats showed similiar $K_m$ value, but showed the more decreased $V_{max}$ value compared with the normal group by the injection of toluene. These results suggest that the rats induced liver damage with $CCl_4$ may reduce the toluene metabolism.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.8 no.2
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• pp.296-305
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• 1998

A study was performed to evaluate an effect of toluene or ethanol pretreatment on the toluene metabolism. A slight liver damage in rats was induced by administration of 0.2 ml of toluene or 0.2 ml of 50% ethanol per 100 g of body weight intraperitoneally every other day for four weeks except the last day before sacrifice. One day before sacrifice, toluene was administered to rats pretreated ethanol or toluene and the control. Rats were sacrificed at the 1st, the 2nd, the 3rd and the 4th week after the first administration of xenobiotics mentioned above. Based on the histopathological findings, liver weight per body weight, serum alanine aminotransferase and hepatic glutathione content, toluene- or ethanol-pretreated groups showed the reversible liver injury. By the treatment of one dose of toluene, the contents of hippuric acid in urine was higher in the group pretreated with toluene or ethanol than control. The contents of cytochrome P-450, benzylalcohol dehydrogenase and benzaldehyde dehydrogenase activities were generally more increased in toluene- or ethanol-pretreated rats than control. $K_m$ values of the benzylalcohol dehydrogenase in pooled liver samples from toluene- and ethanol-pretreated groups were similar each other. $V_{max}$ values of toluene- or ethanol-pretreated group was higher than control. In conclusion, the toluene metabolism is accelerated in rats pretreated with toluene or ethanol.

• Biomedical Science Letters
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• v.5 no.1
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• pp.67-74
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• 1999

To investigate the effect of the circadian variations on the toluene metabolism, 50％ toluene in olive oil (0.2 m1/100 g body weight) was intraperitoneally administered to the rats every other day for 6 days both in the night; 24:00 and the day; 12:00. Each group of animals was sacrificed at 8 hr after last injection of toluene. Hepatic microsomal aniline hydroxylase activity was more increased in control rats of night phase than those of day phase. On the other hand, the activities of hepatic benzylalcohol dehydrogenase in control rats of night phase showed the similiar value with that in those of day phase and in case of toluene treatment, these enzyme activities in rats of night phase were rather more decreased than those of day phase. Furthermore, hepatic benzaldehyde dehydrogenase activities were more or less higher in the control rats of night phase than those of day phase and by toluene treatment, enzyme activities of rats of night phase were somewhat decreased than those of day phase. in vitro, benzylalcohol or benzaldehyde inhibited the activities of benzylalcohol or aldehyde dehydrngenase prepared from the rats liver supematant. There were no differences in urinary hippuric acid contents between the night phase and day phase both in the control and toluene treated group. The increasing rate of liver weight per body weight (％), serum xanthine oxidase activities were higher in rats of night phase than in those of day phase by toluene treatment. In conclusion, these results indicate that the producing rate of benzylalcohol and benzaldehyde from toluene may be higher in rats of night phase than those of day phase.

• Toxicological Research
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• v.14 no.3
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• pp.321-328
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• 1998

This study was performed to evaluate the effect of liver damage on toluene metabolism in rats pretreated with carbon tetachloride. Liver damage in rats was induced by administration of 0.1ml of carbon tetrachloride per 100g of body wight intraperitoneally every day for four weeks except the last day before sacrifice. One day before sacrifice, toluene was administered to the animals instead of carbon tetrachloride. Rats were sacrificed at the 1st, the 2nd, the 3rd and the 4th week after the first administration of carbon tetachloride. Based on the histopathological findings, liver weight and serum alanine aminotransferase, the $CCl_4$-preteated group was found to have gradual severe liver damage. Especially the degree of liver injury became increasingly severe throughout the whole course of the experiment. The contnts of hippuric acid in urine lower in the all groups pretreated with $CCl_4$than that of the control. The contents of hepatic cytochrome P450(CYP), benzylalcohol dehydrogenase and benzaldehyde dehydrogenase activities were decreased in $CCl_4$-pretreated rats than those of the control. The $CCl_4$treated animals showed the gradual decreased activities of these enzyme as injection times elapsed. Km values of the benzylalcohol dehydrogenase in pooled liver samples from $CCl_4$-pretreated or control groups were similar. On the other hand, Vmax values of the $CCl_4$-pretreated group was lower than of the control. Therefore, it can be concluded that reduction of the toluene metabolism in damaged rat liver induced with $CCl_4$was due to the inhibition of CYP content, bezylalcohol and benzaldehyde dehydrogenase activities which related with toluene metabolic enzyme system.

• Journal of Preventive Medicine and Public Health
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• v.21 no.1 s.23
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• pp.152-162
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• 1988

Benzene and toluene, which are widely used aromatic hydrocarbons in workplace, are recently proved to cause health hazards due to their toxic effects. This study investigated the influence of toluene on the urinary excretion of benzene metabolite by administering short term exposure limit(STEL) of these compounds(i.e., 13.8mg/kg of benzene and 108.8 mg/kg of toluene) intraperitoneally into Sprague-Dawley rats. After administration, urinary phenol concentration of rat was measured by gas chromatography for every three hours. Data were analyzed by non-parametric statistical methods using Kruskal-Wallis multi-sample test and Mann-Whitney U test. The following results were obtained : 1. Administration of STEL-benzene increased urinary phenol concentration in lats. 2. Urinary phenol concentration was increased logarithmically according to the dosage of benzene. 3. Excretion of phenol in urine was decreased when benzene and toluene were administered simultaneously compared with administering benzene alone. In summary, these results reveal that administration of STEL of toluene has antagonistic effect of urinary excretion of benzene metabolite in rats.