Annals of Occupational and Environmental Medicine

A work-relatedness assessment in epidemiological case investigation of occupational cancers: II. Practice: an upper urinary tract cancer in a dyer: Kihun Kim, Hyeoncheol Oh, Jungwon Kim; Ann Occup Environ Med 2020;32:e31. Published online September 1, 2020; DOI: https://doi.org/10.35371/aoem.2020.32.e31

Abstract PDF PubReader ePub: An epidemiological case investigation of occupational cancer is conducted to determine the causation between the cancer and the worker's job. This review describes the overall process of work-relatedness assessment of the epidemiological case investigation through a case of upper urinary tract cancer (UUTC) in benzidine exposed worker in dyeing industry. Medical referrals, occupational history, material safety data sheet, and working environment monitoring submitted by the Korea Workers' Compensation and Welfare Service were reviewed. We further investigated literatures about the cotton dyeing industry, the domestic law and working environment monitoring reports. Benzidine was listed as an International Agency for Research on Cancer risk factor only for bladder cancer among urinary tract cancers, requiring different logical grounds for establishing causation. A literature review was conducted on the metabolic pathways of benzidine to establish biological plausibility. In addition, several papers were investigated that UUTC and bladder cancer share risk factors to extrapolate the epidemiological studies of bladder cancer. Epidemiologic studies of benzidine and bladder cancer were investigated. The worker is a 71-year-old man and performed dyeing and transporting at several dyeing factories for 29 years. The worker was diagnosed with UUTC based on radiologic and histologic results. It was critical to consider that he worked as a dyer for 3 years. The cancer was diagnosed in 2018, with a latent period of approximately 35 years. The worker performed cotton dyeing, and benzidine-based dye was mainly used. The quantitative exposure level of benzidine was reported from non-detection to 397.4 µg/m³. In biological metabolisms, N-acetylhydroxylamine changes DNA structure of urothelium. As a result of reviewing 4 epidemiological studies, the standardized incidence ratio and standardized mortality ratio were significantly high with 3 years of exposure. Work-relatedness was finally assessed as probable based on biological mechanisms and epidemiological evidence. This review will help solutions for work-relatedness assessment processes.

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An Occupational Erythema Multifome Case of a Worker Exposed to Dichlone and 3,3'-Dichlorobenzidine in a Dye Manufacturing Process: Jae Seung Yong, Jung Won Kim, Eun A Kim; Korean Journal of Occupational and Environmental Medicine 2012;24(3):311-318. Published online September 30, 2012; DOI: https://doi.org/10.35371/kjoem.2012.24.3.311

Abstract PDF: BACKGROUND
In Korea, the only case of occupational erythema multiforme was found to be due to Bolivian rosewood, but there has been no case due to occupational chemicals in the manufacturing industry. Here, we report a case of erythema multiforme caused by dichlone and 3,3'-dichlorobenzidine(DCB) in a dye worker.
CASE
REPORT: We report a 43-year-old male worker manifesting erythema multiforme-like skin lesions during the DCB synthesis, The patient's dermatitis was relieved when he avoided the process, and it became aggravated when he restarted his work. Patch and prick tests confirmed positive irritant reactions to two chemicals.
CONCLUSION
This case was diagnosed as erythema multiforme based on clinical manifestations. Symptoms worsened upon exposure to chemicals while avoiding exposure improved symptoms. Skin test results showed that dichlone and 3,3'-dichlorobenzidine induced irritant reactions. We assume that erythema multiforme occurring in workers is an occupational skin disease likely caused by dichlone and 3,3'-dichlorobenzidine.

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The Application of Biological Monitoring and Effects of Ethanol and Phenobarbital on Plasma Protein Adducts Formed in Rats Exposed to Benzidine: Chi Nyon Kim, Se Hoon Lee, Jaehoon Roh; Korean Journal of Occupational and Environmental Medicine 2002;14(4):353-363. Published online December 31, 2002; DOI: https://doi.org/10.35371/kjoem.2002.14.4.353

Abstract PDF: 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.

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Bladder Cancer with Exposure to Benzidine-based Dyes of Dyer: Sung Ah Kim, Jong Woo Lee, Bup Wan Kim, Yong Chul Shin; Korean Journal of Occupational and Environmental Medicine 1999;11(2):304-312. Published online June 30, 1999; DOI: https://doi.org/10.35371/kjoem.1999.11.2.304

Abstract PDF

This is the first report on an occupational bladder cancer in Korea. The ease is 41 years old man who worked as a dyer for 17 years at two dyeing factories, which handled nylon and polyester fabrics in Taegu. He was exposed to many kinds of dyes during weighing, mixing, dissolving and dyeing processes. Among many kinds of acid, disperse and direct dyes that he has been exposed to, several dyes have confirmed to contain benzidine-based dyes, one was o-tolidine-based dye, and one was o-dianisidine-based dye. He visited a hospital due to the gross hematuria and urinary frequency in June, 1998, and he had radical cystectomy with ileal conduit diversion. He had smoked a half-pack of cigarette for 20 years. The main risk factor of bladder cancer is smoking, however, he was relatively a light smoker than usual Korean men. He was exposed to the definite occupational carcinogen even though the level was relatively lower than that of dye manufacturers. His age was younger than the prevalence age of bladder cancer caused by smoking. These evidences support that the dyer' s bladder cancer could be related to the occupational exposure to benzidine-based dyes.

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A work-relatedness assessment in epidemiological case investigation of occupational cancers: II. Practice: an upper urinary tract cancer in a dyer
Kihun Kim, Hyeoncheol Oh, Jungwon Kim
Annals of Occupational and Environmental Medicine.2020;[Epub] CrossRef
Occupational Cancers with Chemical Exposure and their Prevention in Korea: A Literature Review
Kyung-Taek Rim
Asian Pacific Journal of Cancer Prevention.2013; 14(6): 3379. CrossRef
Occupational Reproductive Function Abnormalities and Bladder Cancer in Korea
Jungsun Park, Kyong-Sok Shin, Yangho Kim
Journal of Korean Medical Science.2010; 25(Suppl): S41. CrossRef
Occupational Diseases in Korea
Seong-Kyu Kang, Eun A Kim
Journal of Korean Medical Science.2010; 25(Suppl): S4. CrossRef

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Evaluation of Dermal Measurement for Workers in Benzidine Dihydrochloride and Benzidine Based Dye Manufacturing Factory: Hye Kyeong Yeom, Jae Suk Song, Chi Nyon Kim, Jong Uk Won, Jaehoon Roh; Korean Journal of Occupational and Environmental Medicine 1998;10(1):83-94. Published online February 28, 1998; DOI: https://doi.org/10.35371/kjoem.1998.10.1.83

Abstract PDF

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.

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A work-relatedness assessment in epidemiological case investigation of occupational cancers: II. Practice: an upper urinary tract cancer in a dyer
Kihun Kim, Hyeoncheol Oh, Jungwon Kim
Annals of Occupational and Environmental Medicine.2020;[Epub] CrossRef

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The Metabolism of Benzidine-based Dye Direct Black 38 in the Isolated Perfused Rat Liver: Jong Uk Won, Jaehoon Roh, Chunsung Kim, Younjung Park, Chi Nyun Kim; Korean Journal of Occupational and Environmental Medicine 1996;8(1):59-65. Published online February 29, 1996; DOI: https://doi.org/10.35371/kjoem.1996.8.1.59

Abstract PDF

Direct Black 38, a kind of benzidine-based azo dye, is widely used as a dye for fabric, leather, cotton, cellulosic material, paper, wool, silk, and so on. Benzidine-based azo dyes are proven as a mutagen and linked to bladder cancer. In 1978, Natonal Institute for Occupational Safety and Health recommended that three widely used benzidine-based dyes (Direct Black 38, Direct Blue 6, and Direct Brown 95) should be treated as carcinogens. In this experiment, metabolism of the benzidine-based dye. Direct Black 38 was examined by using an isolated liver perfusion system. To measure the metbolites of Direct Black 38,/ 8.0 micrometer, 30.5 micrometer and 63,3 micrometer of Direct Black 38 was added into the recirculating perfusate of the isolated perfused rat liver. Samples were collected at 0, 10, 20, 30, 60, 90. 120 minute. They were treated with sep-pak and methanol, and the metabohtes were detected and quantified with high performance liquid chromatography (HPLC). Residual non-reactive dye in the perfusate and liver was reduced to benzidine and then analyzed by HPLC. Detected metabolites of ?Direct^-Black 38 were benzidine, N-acetylbenzidine, and N,N'-diacetylbenzidine. The average conentration of benzidine was 0.1 micrometer and this concentration was maintained throughout the experimental period. The average concentration of N-acetylbenzidine was 0.22 micrometer and took the same pattern of benzidine. When 30.5 micrometer of Direct BIact 38 was added to the perfusate, only. N,N'-diacetylbenzidin.e increased slightly with time. From the above results we suggest that only small amount of Dirst Black 38 might be metabolized to benzidine regardless of the s, amount of the Direct Black 38. There are some possible explanations. The liver was damaged during the perparation. And the function of the perfused liver decreased rapidly because adsorbing of dye. The benzidine, acetylbenzidine and diacetylbenzidine metabolized to other metabolites were not detected in this experiment.

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Citations to this article as recorded by

Occupational Cancers with Chemical Exposure and their Prevention in Korea: A Literature Review
Kyung-Taek Rim
Asian Pacific Journal of Cancer Prevention.2013; 14(6): 3379. CrossRef

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Benzidine Exposure Among Benzidine-based Dye Manufacturing Workers: Jae Hoon Roh, Yeon Soon Ahn, Kyoo Sang Kim, Chi Nyon Kim, Hyun Soo Kim; Korean Journal of Occupational and Environmental Medicine 1995;7(2):347-353. Published online October 31, 1995; DOI: https://doi.org/10.35371/kjoem.1995.7.2.347

Abstract PDF

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.

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A work-relatedness assessment in epidemiological case investigation of occupational cancers: II. Practice: an upper urinary tract cancer in a dyer
Kihun Kim, Hyeoncheol Oh, Jungwon Kim
Annals of Occupational and Environmental Medicine.2020;[Epub] CrossRef

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