OBJECTIVES: To evaluate the effects on the formation of benzidine-hemoglobin, and benzidine metabolite-hemoglobin adducts, caused by pretreatment with the known xenobiotic metabolism effectors, ethanol and phenobarbital, in rats administered Direct Black 38 dye. METHODS: The experimental rats were divided into three groups: a control group, an ethanol group and a phenobarbital group. Rats were pretreated with ethanol (1g/kg) or phenobarbital (80mg/kg) 24 hours prior to the oral administration of Direct Black 38 (0.5mmol/kg), with the control group being administered the same amount of distilled water. Blood samples were obtained from the vena cava of 5 rats from each group prior to, and at 30 min, 3 h, 6 h, 9 h, 12 h, 24 h, 48 h, 72 h, 96 h, and 144 h following the oral administration of Direct Black 38. Directly after sampling the blood was separated into hemoglobin and plasma, with the adducts being converted into aromatic amines by basic hydrolysis. Hydrolyzed benzidiene, monoacetylbenzidine and 4-aminobiphenyl were analyzed by reverse-phase liquid chromatography with an electrochemical detector. The quantitative amount of the metabolites was expressed by the hemoglobin binding index (HBI). RESULTS: In the ethanol group, benzidine-, monoacetylben-zidine-, and 4-aminobiphenyl-HBI were increased to a greater extent than those in the control group. These results were attributed to the ethanol inducing N-hydroxylation, which is related to the formation of the hemoglobin adduct. In the phenobarbital group, all the HBIs, with the exception of the benzidine-HBI, were increased to a greater extent than those of the control group. These results were attributed to the phenobarbital inducing N-hydroxylation related to the formation of the hemoglobin adduct. The N-acetylation ratio was only increased with the phenobarbital pretreatment due to the lower benzidine-HBI of the phenobarbital group compared to those of the control and ethanol groups. The N-acetylation ratios for all groups were higher than 1 for the duration of the experimental period. Although the azo reduction was unaffected by the ethanol, it was inhibited by the phenobarbital. The ratio of the benzidine-HBI in the phenobarbital group was lower than those of the ethanol the control groups for the entire experiment. CONCLUSION: Our results indicate that both ethanol and phenobarbital increase the formation of adducts by the induction of N-hydroxylation, but also induced N-acetylation. Phenobarbital decreased the formation of benzidine-HBI due to the decrease of the azo reduction. These results suggest that the effects of ethanol and phenobarbital need to be considered in the biochemical monitoring of Direct Black 38.
Administration, Oral ; Amines ; Animals ; Chromatography, Reverse-Phase ; Ethanol* ; Hydrolysis ; Metabolism ; Phenobarbital* ; Plasma ; Rats* ; Water

This study is performed to evaluate usefulness of dermal measurement of benzidine and benzidine based dye as one of the occupational exposure assessment method for these compounds. We selected one benzidine manufacturing factory and one dye manufacturing factory in Incheon area. Eleven workers were for benzidine manufacturing factory and twenty four for dye. We analyzed relationships among air level, amount on skin and concentration of urinary metabolites for these compounds. Airborne levels of benzidine and dye were measured by NIOSH 5509, 5013 methods. Amount of these compounds on skin was measured with skin wipe method. Concentration of benzidine metabolites in urine was measured by High Performance Liquid Chromatography after alkaline hydrolysis. The amount of benzidine on hand skin was 25.05( - 233.2) ng/ur, and the amount of the neck was 2.01 ( - 11.9) ng/cm2 in the benzidine dihydrochloride manufacturing factory. The amount of benzidine on hand and neck skin has positive correlation with concentration of urinary monoacetyl benzidine (r=0.644, p < 0.05) . The amount of benzidine based dye on hand skin was 55.75( - 457.7) ng/cm2, and the amount of the neck skin was 18( - 284.7) ng/cm in benzidine based dye manufacturing factory The amount of dye on hand and neck skin has positive correlation with concentration of urinary benzidine for dye workers (r=0.467, p < 0.05). When assessing the exposure of workers who deal with benzidine, the amount of benzidine on skin should be measured for an accurate exposure assessment.
Chromatography, Liquid ; Hand ; Hydrolysis ; Incheon ; National Institute for Occupational Safety and Health (U.S.) ; Neck ; Occupational Exposure ; Skin

No abstract available.
Animals ; Carbon* ; Rats*

No abstract available.
Animals ; Carbon* ; Rats*

No abstract available.
Animals ; Ethanol* ; Metabolism* ; Phenobarbital* ; Rats* ; Trichloroethylene*

OBJECTIVES: The effects of ethanol and phenobarbital,which are known to affect metabolism of xenobiotics, on the formation of benzidine-and its metabolites-plasma protein adducts in rats administered benzidine were evaluated. METHODS: The experimental rats were divided into the control,ethanol and phenobar-bital groups. The experimental groups (ethanol and phenobarbital group)were pretreated with ethanol (1g/kg)or phenobarbital (80mg/kg)24 hours prior to the oral administration of benzidine (0.5mmol/kg). Blood samples were obtained from the vena cava from 5 rats in each group; and at 30 min,3 h,6 h,9 h,12 h,24 h,48 h,72 h,96 h,and 144 h after the administration of benzidine using heparin treated syringes.The plasma protein levels were separated immediately after taking blood samples. The adducts were underwent basic hydrolysis to convert them into aromatic amines. The hydrolyzed benzidine, monoacetylbenzidine, and 4-aminobiphenyl were analyzed by reverse-phased liquid chro-matography with an electrochemical detector. The quantitative amount of the metabolites was expressed by the plasma protein binding index(PBI). RESULTS: Similar to the hemoglobin adducts,the levels of the plasma protein adducts of the ethanol and phenobarbital groups (benzidine-, monoacetylbenzidine-, and 4-amino-biphenyl-PBI)were higher than those of the control group. These results are attributable to the fact that ethanol and phenobarbital induced to the plasma protein adduct formation. The N-acetylation ratio in the control group was highest at 72 h with 2.34.In the ethanol group,it was highest at 72 h with a ratio of 2.46 and was highest in the phenobarbital group at 72 h with a ratio of 2.43. The N-acetylation ratio of the plasma protein adducts was relatively lower than that of the hemoglobin adducts.The level of the plasma protein adduct increased more rapidly than the hemoglobin adducts in all experimental groups regardless of the pretreatment,and decreased rapidly after reaching the maximum level. CONCLUSION: The above results indicate that ethanol and phenobarbital increased the level of plasma protein adduct formation. The plasma protein adducts tended to decrease more rapidly than the hemoglobin adducts in the body after benzidine exposure. This results in this study result suggests that the effects of ethanol or phenobarbital need to be considered in the biochemical monitoring,and that the level of the plasma protein adducts be a more proper biomarker than the hemoglobin adducts for assessing the short term exposure to a benzidine and benzidine based dye.
Administration, Oral ; Amines ; Animals ; Environmental Monitoring* ; Ethanol* ; Heparin ; Hydrolysis ; Metabolism ; Phenobarbital* ; Plasma* ; Protein Binding ; Rats* ; Xenobiotics

OBJECTIVES: This study was conducted to provide accurate exposure evaluation of workers in a biologicallymonitored state who were simultaneously exposed to benzene and toluene. For the purpose of this study, an animal experiment was conducted. METHODS: The following concentrations of solvents were administered orally to Sprague-Dawley rats : benzene at 2.26 mg/kg body weight (equivalent concentration to the 2.5 ppm, Threshold Limit Value-ShortTerm Exposure Limit, in the USA) and 9.02 mg/kg body weight (equivalent concentration to the 10 ppm, Threshold Limit Value-TimeWeighted Average in Korea), simultaneously with toluene at 106.42 mg/kg body weight (equivalent concentration to the 100 ppm, Threshold Limit Value-TimeWeighted RESULTS: The following results were obtained from the analysis of reading taken at 3hour intervals of S-phenylmercapturic acid (SPMA) and phenol concentration in urine metabolites of benzene after oral administration for 30 hours. 1. The concentrations of phenol and SPMA in urine were markedly decreased in the initial phase of the mixed group (both benzene and toluene administered group) as compared with the benzeneonly administered group, and the concentrations were slightly elevated. 2. The total excreted amounts of phenol and SPMA in urine decreased in the mixed group compared with the benzene-only group, and these decreases were more remarkable at the benzene administration concentration of 9.02 mg/kg than at 2.26 mg/kg. 3. The urinary excretions of phenol and SPMA were delayed in the case of the mixed group, and the extent of the delay was dependent on the amount of benzene administrat CONCLUSIONS: Benzene metabolism was suppressed by toluene, and hence the excretion of phenol and SPMA as urinary metabolites of benzene was delayed. This result will have applications in the interpretation of results from future biological monitoring of workers exposed to mixed solvents. We should not underestimate the importance of carefully interpreting the results of biological monitoring data when workers are exposed to mixed solvents. We should not underestimate the importance of carefully interpreting the results of biological monitoring data when workers are exposed to mixed benzene and toluene.
Administration, Oral ; Animal Experimentation ; Animals ; Benzene* ; Body Weight ; Environmental Monitoring ; Metabolism ; Phenol* ; Rats* ; Rats, Sprague-Dawley ; Solvents ; Toluene*

To evaluate,the differences of benzidine exposure patterns of the workers in two benzidine-based dye manufacturing factories, the concentration of benzidine: in. air, blood, and urine were measured. The air levels of benzidine dihydrochloride and benzidine-based dye were measured by high performance liquid chromatography with ultraviolet detector. Blood samples were collected at 3 hours after exposure and urine samples were collected at the end of shift. Blood and urine samples were analyzed by high performance liquid chromatography with electrochemical detector. The level of benzidine in reaction process (input, diazotization, and coupling); was 0.381+/-7950 g/m3. The blood benzidine was deteced in 25 workers among 38 in reaction process and their mean levels were 0.0153?0376 ng/mg Hb. The urinary benzidine was detected for 11 workers among 38 workers in the reaction process. The level of benzidine-based dye in drying and packing process was 52.1748+/-4.4111g/m3. The blood benzidine was deteced in 6 workers among 38 in drying and packing process and their mean levels was 0.0062+/-0274 ng/mg Hb. The urinary benzidine was detected for 1 worker among 38 workers exposed to benzidine-based dye. The blood and urinary benzidine were detected in workers exposed to benzidine-based dye. Such results suggested that some part of benzidine-based dye was metaboized to benzidine. Therefore, some regulations for manufacturing and use of the benzidine-based dye are needed to prevent its hazards in industries.
Chromatography, Liquid ; Social Control, Formal

OBJECTIVES: This study was designed to quantify symptoms in the upper extremities and to identify the pain related factors among hospital workers using video display terminals. METHODS: The subject-group consisted of 138 employees working at a hospital using video display terminals. A structured questionnaire was used to estimate the participants' general characteristics, and job contents. Job stress was measured using Karaseks JCQ(Job Content Questionnaire). Pain in the upper extremities was identified according to the NIOSH symptoms survey criteria. Quantification was measured using Kim Chul's method. Pearson's Correlation analysis was used to identify validity in quantification. VAS(visual analog scale) was used to compare with this method. Multiple regression analyses elucidated the relationship between quantified pain and various work factors, such as job stress. Data were analysed with SAS 6.12 program. RESULTS: First, in quantification using Kim Chul's method, the correlation between modified PRS(pain rating score) and VAS was extremely high by 0.60(P<0.01), indicating the high validity of PRS. Second, the groups of high job demand, high job control, and females were related to an increased pain level. CONCLUSIONS: These results suggest that the self pain assessment method, PRS, is valuable and useful in analyzing occupational musculoskeletal symptoms. High demand, job control and gender may influence the levels of pain. Prospective studies about musculoskeletal disorder are required.
Computer Terminals* ; Female ; Humans ; National Institute for Occupational Safety and Health (U.S.) ; Pain Measurement ; Questionnaires ; Upper Extremity*

OBJECTIVES: The study was performed to investigate the changes of urinary thiodiglycolic acid (TDGA) concentration in workers exposed to vinyl chloride monomer (VCM) according to the time of sampling urine. METHODS: The personal exposure to airborne VCM was assessed and urinary TDGA concentration was sampled in 31 workers employed in a VCM and polyvinyl chloride (PVC) manufacturing factory. Urinary TDGA was sampled three times: before the start of the shift after 3 days off (TDGA1), after the end of the first-day shift (TDGA2) and before starting the following day shift after completing the oneday shift (TDGA3). Urinary TDGA in 30 workers who had not been exposed to airborne VCM was sampled after the end of the shift. A gas chromatography/pulsed flame photometric detector (GC/PFPD) was utilized to analyze TDGA concentration in urine after the urine was methylated with trimethylsilyldiazomethane(2.0M in diethyl ether). RESULTS: The creatinine level was 0.179+/-0.271 mg/g in the control workers and 0.218+/-0.443 mg/g in the workers before the start of the shift after 3 days off (TDGA1), showing no significant difference (p=0.7035). Urine samples were compared according to sampling time in order to investigate the change of urinary TDGA concentration in the case of continuous exposure to airborne VCM. In VCM-exposed workers, urinary creatinine concentration was 0.434+/-0.623 mg/g in TDGA2 and 0.767+/-1.056 mg/g in TDGA3, which indicated a gradual but significant increase (p=0.024). In terms of the statistical correlation between airborne VCM and urinary TDGA to evaluate exposure dose per day, of the three urinary TDGA concentrations, TDGA3 showed the highest degree of regression (R(2)=0.4215) with 8h-TWA airborne VCM concentration. CONCLUSION: Based on this result, the excretion half-life of urinary TDGA was assumed to be less than 3 days, because the concentration of urinary TDGA at 3 days after exposure to airborne VCM was decreased to the level of urinary TDGA concentration in the control workers. The concentration of urinary TDGA increased in the case of continuous shift, due to the accumulation of residual metabolites of TDGA. It was considered that TDGA3 can be applied as a useful biological index to evaluate the exposure dose of airborne VCM during one day because TDGA3 showed the highest correlation with the exposure dose of airborne VCM in the previous shift day.
Creatinine ; Half-Life ; Humans ; Polyvinyl Chloride ; Vinyl Chloride*