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.

It is important to identify the causal relationship between occupational exposure and the disease in the area of compensation because most cancers have long latent period. This review presents the principles that should be considered when evaluating the work-relatedness. We reviewed reports on occupational cancers published by the International Agency for Research on Cancer, American Conference of Governmental Industrial Hygienists, National Toxicology Program, Environmental Protection Agency, European Union, which are the world's most prestigious organizations. In addition, we reviewed relevant papers and books published in Korea. The process is conducted in the order of cancer diagnosis, exposure assessment for carcinogens, and work-relatedness assessment. The probability of causation is determined stochastically rather than deterministically. There is no absolute standard for accreditation criteria and results may vary according to expert opinions and in each country or organization. Revealing the causal relationship of occupational cancers is a difficult process owing to inconsistency in relevant epidemiological studies, lack of well-established biological mechanisms, loss of objective occupational historical data, and other complexity of individual cases. Causation is unclear in many cases. Nevertheless, the data should be reviewed in detail for each case suspected of work-related cancers, and an assessment should be made through valid and plausible logic and literature evidences.

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