Case report of renal cell carcinoma in automobile manufacturing factory worker due to trichloroethylene exposure in Korea

Patient information

Fifty-two- year-old-male

Chief complaint

Renal cell carcinoma on the left kidney discovered at medical check up.

Present illness

The patient has discovered a cystoma on the left kidney during regular medical check-up in 2003. The size of the cystoma has grown from the original 1.7 cm to 2.7 cm in 2011, therefore, nephrectomy on the left kidney was implemented after CT scan (Fig. 1). Afterwards, through biopsy, the definite diagnosis was renal cell carcinoma. After nephrectomy in 2011, having considered his occupational history to have connection with the renal cell carcinoma, the patient claimed to approve his cancer as occupational disease according to Industrial Accident Compensation Insurance Act.

Fig. 1

CT scan of renal cell carcinoma (Arrow)

Past history

The patient has been diagnosed with type 2 diabetes in 2005, and has received drug treatment until now, and has no outstanding past medical history. The patient has smoked a quarter of a pack of cigarette per day since the age of 26 for about 2 decades and has stopped smoking since 2006. The patient drank three times a month, and each time he drank alcoholic beverage that contains 30 g of alcohol. The patient exercises half an hour a day and has a regular lifestyle. There has been no family history on cancer or other illnesses.

Occupational history

Employed in 1988, the patient was assigned to do abrasive polishing of the crankshaft forging surface until September 1998, and was assigned to do painting from 1998 to present. The abrasive polishing was manual process for several decades and it was fully automated since 1998. When, it was manually done in the past and there was high temperature steam in the process of surface polishing. The workers were not used proper protective equipments at the time. Moreover, the process of scrubbing the product with cleanser after abrasive polishing was also done manually without personal protective equipments. Afterwards, the patient was assigned to painting process since 1998, and was rotated in various processes including pretreatment, intermediate, intermediate inspection, finish coat, final painting inspection, 4 to 6 months for each process. During the process, the patient did spray painting, cleansing the contaminated part using solvent or thinner, sanding, and touch up. The number of vehicles processed a day is approximately 20, and touch up process on 5 to 6 parts on average per car was administered.

Exposure assessment

Examining the chemical materials currently under use, mainly trichloroethylene which was re-evaluated to Group1 since 2012 by IARC to be a risk factor to renal cell carcinoma and cadmium which was classified as Group1. As for 4 part painting (pre-coat, intermediate coat, finish coat and fixed painting part), gear parts and regional sample were gathered. Though we checked the results of work environment monitoring on past trichloroethylene exposure level of 4 part of painting process and crankshaft, auto transmission manufacturing (ATM) process, we couldn’t verify the results since proper measurement was unavailable because, trichloroethylene was not target chemical for work environment measurement. However, as for the 3rd factories, the task of control device manufacturing in vehicle factories, we could verify the measurement results on trichloroethylene and carbon tetrachloride in 1994. After measuring the occupational environment assessment levels on past 3rd factories, trichloroethylene exposure was verified and that process is similar for crankshaft, ATM process. After analyzing samples gathered from work environment assessment, trichloroethylene was not found, whereas cadmium levels were 0.0003 mg/m², 0.0002mg/m³ in painting intermediate level, 0.0001mg/m³ in finish coat level, and not detected in other levels. Other chemicals such as lead, toluene, styrene were extremely minimal or not detected.

The possibility of exposure to trichloroethylene of workers and exposure level

TCE is one of well known carcinogen through interruption of glutathione pathway and the oxidation process. And TCE also known to be a harmful for the metabolism of glutathione by low dose (under 0.1 mmol/ml in serum level) exposure [9]. To assess the possibility and the level of exposure to a worker, documents and data related to the level of exposure have been reviewed. In Korea, Cho conducted a study in 2007 based on the database on 2004 occupational environment survey established by Occupational Safety and Health Research Institute (OSHRI). The study surveyed 392 work environments already using trichloroethylene and 38 work environments newly using trichloroethylene, of which it selected 103 work environments based on the type of occupation, the number of workers and region. The industry which used the most trichloroethylene a month was automobile part manufacturers of motor vehicle and engine assembly industry which used 23,920 L, followed by computer and electronics manufacture industry (19,596 L), assembly metal product manufacture industry (11,990 L). The industry most exposed to trichloroethylene was automobile part manufacture industry which had the maximum exposure concentration of 49.87 ppm close to the exposure standard (50 ppm). The industry most exposed to trichloroethylene was automobile part manufacture industry which had the maximum exposure concentration of 49.87 ppm close to the exposure standard (50 ppm). In case the work was done manually or semiautomatic, 87 % of the workers were exposed to trichloroethylene, and in case the work was done automatically, only 13 % to the trichloroethylene (Table 1) [10]. And also study on the exposure level and meta-analysis of trichloroethylene in Korea. It was concluded that can be seen working past cleaning and degreasing and have been exposed to high concentrations and low concentrations with long duration of trichloroethylene. Especially, some studies, the concentration of trichloroethylene was reported 100 ppm or more [11].

Table 1

Exposure status according to trichloroethylene use in 2006 in Korea

Exposure levels in painting process and ATM process of the workers who worked for measuring the results were less than the detection limit trichloroethylene, which is associated with renal cell carcinoma. To make a conclusion about whether to use trichloroethylene, the results of measurement for the environmental assessment of the past were insufficient. However, industrial hygiene specialists in Board of Committee on Occupational Disease Survey are estimated to be generally trichloroethylene previously worked at the time of the ATM process of the job to be used as a cleaning solution and decided exposure levels similar to the process for review of the articles was determined that when workers are exposed to significant levels of trichloroethylene.

The results of epidemiologic studies

The most important result was a meta-analysis using the 24 series of cohort studies published and case control studies in 2011, the overall relative risk of those exposed to trichloroethylene and those not exposed was 1.27 (95 %CI = 1.13-1.43). The possibility of confounding by smoking is considered low since the odd ratio on lung cancer did not increase [12]. According to recent review about the epidemiologic evidence on the causal relationship between trichloroethylene and renal cell carcinoma, the result of cohort studies were inconsistent, but the results of case–control studies suggested the association [11].

Brüning et al., conducted studies setting 134 patients who received nephrectomy from 1992 to 2000 and 401 patients who received treatments not related kidney in the vicinity as control group. When classifying all the workers associated with cutting and cleansing the metal, which was similar job, as exposed group without environmental inspection on the work environment or definite knowledge of exposure history, the odds ratio was 5.57 (95 %CI = 2.33-13.32). This study also suggested the dose–response relationship between exposure duration and risk for renal cell carcinoma, which, the odds ratio was 3.78 (95 %CI = 1.54-9.28) for less than 10 year exposure duration, 1.80 (95 %CI = 0.67-4.79) for 10 to 20 years, 2.69 (95 %CI = 0.84-8.66) for more than 20 years [13].

In 2006 France, Charbotel et al., utilized trichloroethylene exposure concentration level (ppm) during employment and the length of employment (year) to calculate cumulative exposure level (ppm・year), which is divided into three groups; 1-155 ppm・year as low exposure group (low), 155-355 ppm・year as medium exposure group (medium), more than 335 ppm・year as high exposure group, and in case of having history of being exposed over 15 min to 200 ppm of trichloroethylene concentration level is said to have been peak exposure. The odds ratio according to the level of exposure was 3.34 (95 %CI = 1.27-8.74) in the high exposure group and therefore statistically significant, 1.03 (95 %CI = 0.29-3.70) in medium exposure group, 0.85 (95 %CI = 0.10-7.41) in low exposure group, thus having a dose–response relationship. Especially, the odds ratio of the high exposure group with history of peak exposure was 3.80 (95 %CI = 1.27-11.40) [14].

The recent case–control group studies on trichloroethylene exposure and renal cell carcinoma published by Moore in 2010 also suggested dose–response relationship according to the entire exposure duration, with 13.5 year as cut-off point, in case of exposure under 13.5 years showed 1.89 (95 %CI = 0.84-4.28), in case of exposure over 13.5 years showed 2.25 (95 %CI = 0.95-5.29). The odds ratio in case of exposure under 1080 h was 1.07 (95 %CI = 0.55-2.09) under general classification and 1.22 (95 %CI = 0.48-3.12) under high validity classification. The odds ratio in case of exposure over 1080 h was 2.22 (95 %CI = 1.24-3.99), 2.86(95 %CI = 1.31-6.23) each. After evaluating with cumulative exposure level, in case of below 1.58 ppm・year of cumulative exposure level had the odds ratio of 1.19 (95 %CI = 0.61-2.35) under general classification and 1.77 (95 %CI = 0.64-4.80) under strict classification, and in case of over 1.58 ppm・year had 2.02 (95 %CI = 1.14-3.59) and 2.23 (95 %CI = 1.07-4.64) each [15].

Brusch et al., that one of outstanding points in nephrotoxicity onset of trichloroethylene is that it shows toxicity even with minimal exposure and dose–response relationship is somewhat relatively unclear, and at the onset of tumor, it shows long-term sustainable toxicity by mutagenicity [16].

It can be known that there is a risk factor for renal carcinogenesis both exposure to high concentrations of short duration and long-term exposure low concentration of trichloroethylene as described above. However, industrial hygiene specialists in Board of Committee on Occupational Disease Survey are estimated to be generally trichloroethylene previously worked at the time of the ATM process of the job to be used as a cleaning solution.