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Epidemiologic Notes and Reports Testicular Cancer in Leather Workers -- Fulton County, New York

Between 1982 and 1984, three cases of testicular cancer were diagnosed in workers at a leather tannery in Fulton County, New York (1). The occurrence of this cluster of cases in association with exposure to suspected etiologic agents prompted an investigation by representatives of the Amalgamated Clothing and Textile Workers Union, the Mount Sinai School of Medicine, the New York State Department of Health, and the National Institute for Occupational Safety and Health (NIOSH). The investigation included medical assessment of the three index patients, an environmental assessment of the tannery, and epidemiologic studies of the tannery workforce. Medical and Occupational Assessment of Index Patients

The first case occurred in 1982, when embryonal cell carcinoma was diagnosed in a 31-year-old worker who had begun work in leather tanning 13 years earlier. A second case of combined seminoma and embryonal carcinoma was diagnosed in 1984 in a 36-year-old worker who had begun work in this industry 19 years earlier. The third case of embryonal cell carcinoma was also diagnosed in 1984 in a 25-year-old worker who had worked in tanning for 8 years. All three employees had worked together on the finishing line during the night shift at the index tannery from approximately January 1978 to June 1979. The workers had become aware of each other's illnesses in the course of their medical care and subsequently brought the cluster of cases to the attention of investigators. Environmental Exposure Assessment

The index tannery, in operation since the late 1800s, completes the tanning process for partially processed hides received from domestic and international sources, then finishes the hides by applying dyes and other surface coatings. In the finishing process, hides on a series of conveyors pass under banks of nozzles that spray the hides with coating materials consisting of numerous solvents and pigments. The finish is then dried by gas-fired heaters, and the hides are subsequently dried in a room-sized oven. Hides are transferred to and from conveyors manually. The three index patients worked alongside the first process conveyor directly beyond the spray nozzles; they smoothed the coating materials onto the leather surface with hand-held felt applicators.

NIOSH reviewed descriptions of the tanning process and collected air and bulk samples in the finishing room of the tannery where the three index patients had been employed. The sampling detected a wide range of hydrocarbons, ketones, metals, and alcohols. The compounds detected in the highest concentrations included several glycol ethers known to be testicular toxins (noncarcinogenic agents that cause testicular dysfunction in animals): 2-ethoxyethanol, 0.3-0.5 ppm (Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) 200 ppm*); 2-ethoxyethyl acetate, 0.2-1.5 ppm (OSHA PEL 100 ppm*); and 2-butoxyethanol, 0.5-10.9 ppm (OSHA PEL 50 ppm*) (2). However, no documented testicular carcinogens were found in the samples.

In addition to air and bulk sampling, the investigation included observation of the current process, review of Material Safety Data Sheets** for previously used materials, and descriptions of past work practices and engineering controls. This procedure determined that the solvent dimethylformamide (DMF) had been used in the finishing line process until recently. The company had discontinued using materials containing DMF because the initial investigators of the cluster had reported potentially substantial exposures to DMF for finishing line workers and had identified reports of other clusters of testicular cancer in association with exposures to DMF (1). DMF was not detected by NIOSH in any air or bulk samples taken at the time of this investigation. Epidemiologic Studies

Case-Referent Study. Many leather-processing operations use the same chemicals, and Fulton County is the focus of this industry in New York. To determine whether there was evidence for an association of testicular cancer with work in the leather industry (and, by extension, with chemical exposures common to that industry), Fulton County was used as the population base for a case-referent study. A case-patient was defined as "any male resident between age 20 and 54 in Fulton County who developed testicular cancer between January 1974 and March 1987." Cases were identified by review of the New York State Cancer Registry. Information on all three index cases was found in this registry, and seven additional cases of testicular cancer were identified. The registry was also used to select a control group, consisting of 129 men of similar age who lived in Fulton County and who developed any other type of cancer between 1974 and March 1987. Usual occupation and industry at the time of diagnosis (as provided by the reporting physician) for both case-patients and controls were determined from registry records and were characterized as being leather- or nonleather-related (according to whether the registry information included "leather" or related terms).

Five of the 10 case-patients and 17 of the 129 controls (for whom occupation could be determined) had been employed in leather-related occupations (odds ratio of 5.8 (95% CI 1.5-22.0)). Follow-up interviews were conducted with nine of these 10 persons with testicular cancer; one person was not interviewed. The occupational histories derived from cancer registry files for the five case-patients with leather- related occupations were confirmed by direct interview. Three of those interviewed had no occupational experience in the leather industry. These interviews also identified a sixth person with testicular cancer who had worked on a leather-finishing line and as a textile dyer, although this information was not included in the above statistical analysis.

Cohort Incidence Study. Because the three index patients all worked on the finishing line at the tannery, a cohort study was conducted of the tannery workforce to determine whether the occurrence of these cases represented an unexpectedly high rate of testicular cancer. Company-provided records identified 80 persons who had worked in the finishing department of the Fulton County tannery at any time between 1975 and 1987. Data on age and first year of employment were used to calculate person-years at risk. The expected number of cases of testicular cancer for this population was determined by multiplying the age- and calendar-year-specific incidence rates for New York State (excluding New York City) (compiled from registry data for 1976-1985) by the person-years at risk. Three cases in this population represent a standardized incidence ratio (observed cases/expected cases) of 40.5 (95% CI 8.1--118.4) (3), which indicates an elevated risk for testicular cancer among finishing line workers. Reported by: E Frumin, M Brathwaite, W Towne, Amalgamated Clothing and Textile Workers Union; SM Levin, MD, DB Baker, MD, SV Monaghan, PJ Landrigan, MD, Div of Environmental and Occupational Medicine, Dept of Community Medicine, Mt. Sinai School of Medicine, New York City; EG Marshal, PhD, JM Melius, MD, MA London, MS, New York State Dept of Health. Industrywide Studies Br, Div of Surveillance, Hazard Evaluations, and Field Studies, National Institute for Occupational Safety and Health, CDC.

Editorial Note

Editorial Note: Public health agencies are often requested to investigate small clusters of disease among groups of workers. In this report, the detection of a cluster of malignancies prompted a series of investigations and resulted in a response by the New York State Department of Health that was based on prudent public health practice. This investigation illustrates problems commonly encountered in cluster studies: the small number of workers involved and the nature of the potential exposures made it difficult to interpret the results of the investigations and to reach unequivocal conclusions (4). Despite these limitations, however, a public health response to the situation was required.

The epidemiologic studies in Fulton County suggested an association of testicular cancer with employment in tanneries. Although these studies did not identify a definite causative exposure, two previous clusters of testicular cancer (5) have been linked to occupational exposure to DMF, a substance that had been widely used in the index tannery and other tanneries. Animal studies also have shown certain glycol ethers to be testicular toxins but have not shown carcinogenicity (2).

Epidemiologic evidence for an association of DMF with testicular cancer is inconsistent. In 1986, a study of three cases of testicular cancer in workers employed in the repair and overhaul of F-4 jet aircraft found that these workers had been exposed to several heavy metals, including cadmium, and to several solvents, including DMF (5). Follow-up investigation at two similar facilities revealed four cases at a second F-4 aircraft repair facility where DMF was used but no cases at a facility where F-15 aircraft were refurbished without DMF use (5). In contrast, an epidemiologic study of an industrial cohort exposed to DMF in the manufacture of synthetic fibers detected no excess of testicular cancer (6).

Several animal studies have not demonstrated that DMF is mutagenic (7,8) or carcinogenic (9,10), although a malignant testicular tumor was found in one of 18 rats exposed to DMF by intraperitoneal injection (11). Further study is needed to assess DMF more fully for carcinogenic and mutagenic potential. DMF is currently in test status in the long-term bioassay program conducted by the National Toxicology Program. OSHA now regulates DMF at a PEL of 10 ppm (and recommends avoidance of dermal exposure) because of its hepatotoxicity. Based on available process descriptions, exposures to DMF in the index tannery and in aircraft repair facilities (5) were probably higher than 10 ppm. Because of concerns generated by the cases reported here, the tannery replaced the DMF-containing dyes with other finishing materials that do not contain DMF. Similar facilities in Fulton County are taking or considering similar action. These actions are consistent with prudent public health practice given the accumulating information on health risks associated with DMF. Because MF is readily absorbed through the skin, proper work practices and use of protective clothing should be emphasized in programs when other solvents cannot be substituted. Workers should be advised of the chemical composition of solvents to which they are exposed and made aware of possible health hazards.

Approximately 94,000 U.S. workers are potentially exposed to DMF (NIOSH, unpublished data). The risk of testicular cancer in DMF-exposed populations and other tannery workers, and the occupational exposure to DMF and other solvents in other clusters of testicular cancer, requires further evaluation with epidemiologic and toxicologic methods. The New York State Department of Health supports the decision of the index tannery and others in the region to eliminate the use of DMF and urges the improvement of work processes to reduce exposures to all hazardous chemical substances. The department also recommends that tannery workers consult their physicians for medical examinations. NIOSH concurs with the state health department's action.

References

  1. Levin SM, Baker DB, Landrigan PJ, et al. Testicular cancer in leather tanners exposed to dimethylformamide (Letter). Lancet 1987;2:1153. 2.National Institute for Occupational Safety and Health. Current intelligence bulletin #39: the glycol ethers, with particular reference to 2-methoxyethanol and 2-ethoxyethanol--evidence of adverse reproductive effects. Cincinnati: US Department of Health and Human Services, Public Health Service, 1983; DHHS publication no. (NIOSH)83-112. 3.Rothman KJ, Boice JD Jr. Epidemiologic analysis with a programmable calculator. 2nd ed. Boston, Massachusetts: Epidemiology Resources, 1982. 4.Schulte PA, Ehrenberg RL, Singal M. Investigation of occupational cancer clusters: theory and practice. Am J Public Health 1987;77:52-6. 5.Ducatman AM, Conwill DE, Crawl J. Germ cell tumors of the testicle among aircraft repairmen. J Urol 1986;136:834-6. 6.Chen JL, Fayerweather WE, Pell S. Cancer incidence of workers exposed to dimethylformamide and/or acrylonitrile. J Occup Med 1988;30:813-8. 7.Antoine JL, Arany J, Leonard A, Henrotte J, Jenar-Dubuisson G, Decat G. Lack of mutagenic activity of dimethylformamide. Toxicology 1983;26:207-12. 8.McGregor DB. Tier II mutagenic screening of 13 NIOSH priority compounds: individual compound report no. 33: N,N-dimethylformamide. Musselburgh, Scotland: Inveresk Research International Limited, 1981:1-189. 9.Herrold KM. Aflatoxin induced lesions in Syrian hamsters. Br J Cancer 1969;23:655-60. 10.Carnaghan RB. Hepatic tumours and other chronic liver changes in rats following a single oral administration of aflatoxin. Br J Cancer 1967;21:811-4. 11.Kommineni C. Pathologic studies of aflatoxin fractions and dimethylformamide in MRC (Medical Research Council) rats. Diss Abstr Int B Sci Eng 1973;34/01-B:291. *With "skin notation," indicating the potential for significant skin absorption. **The Material Safety Data Sheet is a source of information on the ingredients and toxicity of a material or chemical product. It is provided by the supplier or manufacturer and is required, under OSHA regulations, to be made available to any employee exposed to the material.



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