Abstract
A retrospective cohort study was carried out in a cardboard factory in Germany to investigate the association between exposure to trichloroethene (TRI) and renal cell cancer. The study group consisted of 169 men who had been exposed to TRI for at least 1 year between 1956 and 1975. The average observation period was 34 years. By the closing day of the study (December 31, 1992) 50 members of the cohort had died, 16 from malignant neoplasms. In 2 out of these 16 cases, kidney cancer was the cause of death, which leads to a standard mortality ratio of 3.28 compared with the local population. Five workers had been diagnosed with kidney cancer: four with renal cell cancers and one with a urothelial cancer of the renal pelvis. The standardized incidence ratio compared with the data of the Danish cancer registry was 7.97 (95% Cl: 2.59–18.59). After the end of the observation period, two additional kidney tumors (one renal cell and one urothelial cancer) were diagnosed in the study group. The control group consisted of 190 unexposed workers in the same plant. By the closing day of the study 52 members of this cohort had died, 16 from malignant neoplasms, but none from kidney cancer. No case of kidney cancer was diagnosed in the control group. The direct comparison of the incidence on renal cell cancer shows a statistically significant increased risk in the cohort of exposed workers. Hence, in all types of analysis the incidence of kidney cancer is statistically elevated among workers exposed to TRI. Our data suggest that exposure to high concentrations of TRI over prolonged periods of time may cause renal tumors in humans. A causal relationship is supported by the identity of tumors produced in rats and a valid mechanistic explanation on the molecular level.
Similar content being viewed by others
References
Asal NR, Risser DR, Kadamani S, Geyer JR, Lee ET, Cherng N (1988b) Risk factors in renal cell carinoma: I. Methodology, demographics, tobacco, beverage use, and obesity. Cancer Detect Prev 11: 359–377
Asal NR, Geyer JR, Risser DR, Lee ET, Kadamani S, Cherng N (1988a) Risk factors in renal cell carcinoma. II. Medical history, occupation, multivariate analysis, and conclusions. Cancer Detect Prev 13: 163–279
Axelson O, Andersson K, Hogstedt C, Holmberg B, Molina G, de Verdier A (1978) A cohort study on trichloroethylene exposure and cancer mortality. J Occup, Med 20: 194–196
Axelson O, Seldén A, Andersson K, Hogstedt C (1994) Updated and expanded Swedish cohort study on trichlorethylene and cancer risk. J Occup Med 36: 556–562
Barret L, Faure J, Guilland B, Chomat D, Didier B, Debru JL (1984) Trichoroethylene occupational exposure: elements for better prevention. Int Arch Occup Environ Health 53: 283–289
Birner G, Vambakas S, Dekant W, Henschler D (1993) Nephrotoxic and genotoxic N-acetyl-S-dichlorovinyl-L-cysteine is a urinary metabolite after occupational 1,1,2-trichloroethene exposure in humans: implications for the risk of trichloroethene exposure. Environ Health Perspect 99: 281–284.
Blair A, Stewart PA, Tolbert PE (1990) Cancer and other causes of death among a cohort of dry cleaners. Br J Ind Med 47: 162–168
Bruckner JV, Davis BD, Blancato JN (1989) Metabolism, toxicity, and carcinogenicity of trichloroethylene. Crit Rev Toxicol 20: 31–50
Coleman M, Douglas A, Hermon C, Peto J (1987) Cohort-study analysis with a Fortran-computer program. Int J Epidemiol 15: 134–137
Coleman MP, Esteve J, Damiecki P, Arslan A, Renard H (1993) Trends in cancer incidence and mortality. IARC Scientific Publications No. 121, Lyon
Conglio WA, Miller K, Mackeever D (1984) The occurrence of volatile organics in drinking water, criteria and standards division. In: Science and Technology Branch Environmental Protection Agency, Washington, D.C.
Dekant W, Metzler M, Henschler D (1986) Identification of S-1,2-dichlorovinyl-N-acetyl-cysteine as a urinary metabolite of trichloroethylene: a possible explanation for its nephrocarcinogenicity in male rats. Biochem Pharmacol 35: 2455–2458
Dekant W, Vamvakas S, Anders MW (1989) Bioactivation of nephrotoxic haloalkenes by glutathione conjugation: formation of toxic and mutagenic intermediates by cysteine conjugated β-lyase. Drug Metab Rev 20: 43–83
Dresen MD, Hoffman F (1986) Volatile organic compounds in groundwater west of LLNL., UCRL-53740.
Finkle WD, McLaughlin JK, Rasgon SA, Yeoh HH, Low JE (1994) Increased risk of renal cell cancer among women using diuretics in the United States. Cancer Causes Control 4: 555–558
Hargarten JJ, Hetrick GH, Fleming AJ (1961) Industrial safety experience with trichloroethylene. Arch Environ Health 3: 103
Henschler D, Eder E, Neudecker T, Metzler M (1977) Carcinogenicity of trichloroethylene: Fact or artifact? Arch Toxicol 37: 233–236
Henschler D, Romen W, Elsässer HM, Reichert D, Eder E, Radwan Z (1980) Carcinogenicity study of trichloroethylene by longterm inhalation in three animal species. Arch Toxicol 43: 237–248
Henschler D, Elsasser H, Romen W, Eder E (1984) Carcinogenicity study of trichloroethylene, with and without epoxide stabilizers, in mice. J Cancer Res Clin Oncol 107: 149–156
Ikeda M, Ohtsuji H, Imamura T, Komoike Y (1972) Urinary excretion of total trichloro-compounds, trichlorethanol, and trichloroacetic acid as a measure of exposure to trichloroethylene and tetrachloroethylene. Br J Ind Med 29: 328–333
Inoue, O, Seiji K, Kawai T, Jin C, Liu Y-T, Chen Z, Cai S-X, Yin S-N, Li G-L, Nakatsuka H, Watanabe T, Ikeda M (1989) Relationship between vapor exposure and metabolite excretion among workers exposed to trichloroethylene. Am J Ind Med 15: 103–110
Kadamani S, Asal NR, Nelson RY (1989) Occupational hydrocarbon exposure and risk of renal cell carcinoma. Am J Ind Med 15: 131–141
Kimmerle G, Eben A (1973) Metabolism, excretion and toxicology of trichloroethylene after inhalation. 1. Experimental exposure on rats. Arch Toxicol 30: 115–126
Kleinbaum D, Kupper L, Morgenstern H (eds) (1982) Epidemiological Research. VNR Company, New York
Kociba RJ, Keyes DG, Jersey GC, Ballard JJ, Dittenber DA, Quast JF, Wade Le, Humiston CG, Schwetz BA (1977) Results of a two year chronic toxicity study with hexachlorobutadiene in rats. Am Ind Hyg Assoc J 38: 589–602
Maltoni C, Lefemine G, Cotti G, Perino G (1988) Long-term carcinogenicity bioassays on trichloroethylene administered by inhalation to Sprague-Dawley rats and Swiss and B6C3F1 mice. Ann NY Aacd Sic 534: 316–342
McCarthy TB, Jones RD (1983) Insutrial gassing poisonings due to trichloroethylene, perchloroethylene, and 1,1,1-trichloroethane, 1961-80. Br J Ind Med 40: 450–455
McCredit M, Stewart JH (1993) Rish factors for kidney cancer in New South Wales.IV. Occupation. Br J Ind Med 50: 349–354
McLaughlin JK, Mandel JS, Blot WJ, Schuman LM, Mehl ES, Fraumeni JFJ (1984) A population-based case-control study of renal cell carcinoma. J Nat Cancer Inst 72: 275–284
McLaughlin JK, Silberman DT, Hsing AW, Ross RK, Schoenberg JB, Yu MC, Stemhagen A, Lynch CF, Blot WJ, Fraumeni JFJ (1992) Cigarette smoking and cancers of the renal pelvis and ureter. Cancer Res 52: 254–257
Müller G, Spassowski M, Henschler D (1972) Trichloroethylene exposure and trichloroethylene metabolities in urine and blood. Arch Toxicol 29: 335–340
Müller M, Birner G, Henschler D, Dekant W (1994) Structures of DNA-adducts normed from haloketenes and halothioketenes: A study to identify possible adducts formed from trichloro-and perchloroethene through bioactivation by glutathione conjugation. IARC Scientific Publication Series 115: 423–428
National Cancer Institue (1976) Bioassay of trichloroethylene for possible carcinogenicity. US Dept of Health, Education, and Welfare, Bethesda, Maryland
National Cancer Institute (1986) Carcinogenesis bioassay of tetrachloroethylene. National Toxicology Program Technical Report 232
National Toxicology Program (1988) Toxicology and carcinogenesis studies of trichloroethylene in four strains of rats (ACl, August, Marshall, Osborne-Mendel) (gavage studies). US Department of Health and Human Serivces TR No. 273
National Toxicology Program (1990) Carcinogenesis studies of trichloroethylene (without) epichlorothydrin in F344/N rats and B6C3F1 mice (gavage studies). US Department of Health and Human Services TR No. 243
Reichert D, Spengler U, Romen W, Henschler D (1984) Carcinogenicity of dischloroacetylene: an inhalation study. Carcinogenesis 5: 1411–1420
Schlehofer B, Heuer C, Niehoff D, Wahrendort J (1993) Occupational and lifestyle risk factors for the etiology of renal cell cancer. J Caner Res Clin Oncol 119: 50
Shindell S, Ulrich S (1985) A cohort study of employees of a manufacturing plant using trichloroethylene, J Occup Med 27: 577–579
Smith AH, Shearn VI, Wood R (1989) Asbestos and kidney cancer: the evidence supports a causal association. Am J Ind Med 16: 159–166
Spirtas R, Stewart PA, Lee JS, Marano DE, Forbes CD, Grauman DJ, Pettigrew HM, Blair A, Hoover RN, Cohen JL (1991) Retrospective cohort mortality study of workers at an aircraft maintenance facility. I Epidemiological results. Br J Ind Med 48: 515–530
Statistisches Bundesamt (1990) Gesundheitswesen: Fachserie 12, Reihe 4, Todesursachen
Stewart PA, Lee JS, Marano DE, Spirtas R, Forbes CD, Blair A (1991) Retrospective cohort mortality study of workers at an aircraft maintenance facility. II. Exposures and their assessment. Br J Ind Med 48: 531–537
Stopps GJ, McLaughlin M (1970) Physiological testing of human subjects exposed to solvent vapors. Am Ind Hyg Accos J 28: 43–50
Stüber K (1931) Gesundheitsschädigungen bei der gewerblichen Verwendung des Trichloräthylens und die Möglichkeiten ihre Verhütung. Arch Gewerbepathol Gewerbehyg 2: 398–456
Tola S, Vilhunen R, Järvinen E, Korkala ML (1980) A cohort study on workers exposed to trichloroethylene. J Occup Med 22: 737–740
Torkelson TR, Rowe VK (1981) Trichloroethylene. Halogenated aliphatic hydrocarbons containing chlorine, bromine and iodine. In: Clayton GD, Clayton FE (eds) Patty’s industrial hygiene and toxicology. Wiley, New York, pp 3553–3560
Ulm K (1993) A simple method to calculate the confidence of a standardized mortality ratio (SMR). Am J Epidemiol 131: 373–375
Vamvakas S, Köster U (1993) The nephrotoxin dichlorovinylcysteine induces expression of the protooncogenes c-fos and c-myc in LLC-PK1 cells — a comparative investigation with growth factors and 12-O-tetradecanoylphorbolacetate. Cell Biol Toxicol 9: 1–13
Vamvakas S, Elfarra AA, Dekant W, Henschler D, Anders MW (1988) Mutagenicity of amino aicd and glutathione S-conjugates in the Ames test. Mutat Res 206: 83–90
Bamvakas S, Dekant W, Henschler D (1989) Assessment of unscheduled DNA synthesis in a cultures line of renal epithelial cells exposed to cysteine S-conjugates of haloalkenes and haloalkanes. Mutat Res 222: 329–335
Vamvakas S, Dekant W, Henschler D (1993) Nephrocarcinogenicity of haloalkenes and alkynes. In: Anders MW, Dekant W Henschler D, Oberleithner H, Silbernagl S (eds) Renal disposition and nephrotoxicity of xenobiotics. Academic Press, San Diego, pp 323–342
Van Duuren BL, Goldschmidt BM, Loewengart G (1979) Carcinogenicity study of halogenated and aliphatic hydrocarbons in mice. J Natl Cancer Inst 63: 1433–1439
Westrick JJ, Mello JW, Thomas RF (1984) The groundwater supply survey. J Am Water Works Assoc 76: 52–56
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Henschler, D., Vamvakas, S., Lammert, M. et al. Increased incidence of renal cell tumors in a cohort of cardboard workers exposed to trichloroethene. Arch Toxicol 69, 291–299 (1995). https://doi.org/10.1007/s002040050173
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s002040050173