Cancer of the urinary bladder in highly exposed workers in the production of dinitrotoluenes: a case report

Short Communication


Technical dinitrotoluene (consisting of 2,4- and 2,6-dinitrotoluene isomers) has been widely used as explosives. Both technical isomers are mutagenic in Salmonella typhimurium TA98 strains and carcinogenic in rodents. 2,4-dinitrotoluene shows a dose-dependency of malignant tumors of the kidneys, liver, and mammary glands in rats and mice. In this case report, we discuss a cluster of three cases of urothelial cancer amongst a group of about 60 workers exposed to dinitrotoluenes. The workers were employed in the manufacturing of nitrotoluene explosives in the former German Democratic Republic. The cases occurred within a period of 12 years (1990–2002) leading to a 15.9 fold higher incidence of cancer of the urinary bladder than of the federal state where the chemical factory was located. The observation of the cluster of urothelial cancer in persons highly exposed to nitrotoluenes underlines the putative human carcinogenicity of dinitrotoluenes with the human urothelium as a relevant target tissue.


Explosives Dinitrotoluene Carcinogenicity Urothelial cancer 


  1. Bader M, Göen T, Müller J, Angerer J (1998) Analysis of nitroaromatic compounds in urine by gas chromatography-mass spectrometry for the biological monitoring of explosives. J Chromatogr B Biomed Sci Appl 710:91–99PubMedCrossRefGoogle Scholar
  2. Banerjee H, Hawkins Z, Dutta S, Smoot D (2003) Effects of 2-amino-4,6-dinitrotoluene on p53 tumor suppressor gene expression. Mol Cell Biochem 252:387–389CrossRefPubMedGoogle Scholar
  3. Bartsch H, Malaveille C, Friesen M, Kadlubar FF, Vineis P (1993) Black (air-cured) and blond (flue-cured) tobacco cancer risk. IV: Molecular dosimetry studies implicate aromatic amines as bladder carcinogens. Eur J Cancer 29A:1199–1207CrossRefGoogle Scholar
  4. Bonacker D, Stoiber T, Böhm KJ, Unger E, Degen GH, Thier R, Bolt HM (2004) Chromosomal genotoxicity of nitrobenzene and benzonitrile. Arch Toxicol 78:49–57CrossRefPubMedGoogle Scholar
  5. Brüning T, Chronz C, Thier R, Havelka J, Ko Y, Bolt HM (1999) Occurrence of urinary tract tumors in miners highly exposed to dinitrotoluene. J Occup Environ Med 41:144–149CrossRefPubMedGoogle Scholar
  6. Brüning T, Thier R, Mann H, Melzer H, Bröde P, Dallner G, Bolt HM (2001) Pathological excretion patterns of urinary proteins in miners highly exposed to dinitrotoluene. J Occup Environ Med 43:610–615PubMedCrossRefGoogle Scholar
  7. Brüning T, Thier R, Bolt HM (2002) Nephrotoxicity and nephrocarcinogenicity of dinitrotoluene: new aspects to be considered. Rev Environ Health 17:163–172PubMedGoogle Scholar
  8. Cattley RC, Everitt JI, Gross EA, Moss OR, Hamm TE, Popp JA (1994) Carcinogenicity and toxicity of inhaled nitrobenzene in B6C3F1 mice and F344 and CD rats. Fundam Appl Toxicol 22:328–340CrossRefPubMedGoogle Scholar
  9. Golka K, Prior V, Blaszkewicz M, Bolt HM (2002) The enhanced bladder cancer susceptibility of NAT2 slow acetylators towards aromatic amines: a review considering ethnic differences. Toxicol Lett 128:229–241CrossRefPubMedGoogle Scholar
  10. Holder JW (1999) Nitrobenzene potential human cancer risk based on animal studies. Toxicol Ind Health 15:458–463PubMedGoogle Scholar
  11. Hong CB, Ellis HV, Lee CC, Spinz H, Dacre JC, Glennon JP (1985) Subchronic and chronic toxicity studies of 2,4-dinitrotoluene. Part III. CD-1 mice. J Am Coll Toxicol 4:257–269Google Scholar
  12. Kedderis GL, Dyroff MC, Rickert DE (1984) Hepatic macromolecular covalent binding of the hepatocarcinogen 2,6-dinitrotoluene and its 2,4-isomer in vivo: modulation by the sulfotransferase inhibitors pentachlorophenol and 2,6-dichloro-4-nitrophenol. Carcinogenesis 5:1199–1204PubMedCrossRefGoogle Scholar
  13. Leonard TB, Graichen ME, Popp JA (1987) Dinitrotoluene isomer-specific hepatocarcinogenesis in F344 rats. J Natl Cancer Inst 79:1313–1319PubMedGoogle Scholar
  14. Letzel S, Göen T, Bader M, Angerer J, Kraus T (2003) Exposure to nitroaromatic explosives and health effects during disposal of military waste. Occup Environ Med 60:483–488CrossRefPubMedGoogle Scholar
  15. McGee LM, McCausland A, Plume CA, Marlett NC (1942) Metabolic disturbances in workers exposed to dinitrotoluene. Am J Digest Dis 9:329–332Google Scholar
  16. Rickert DE (1987) Metabolism of nitroaromatic compounds. Drug Metab Rev 18:23–53PubMedCrossRefGoogle Scholar
  17. Rickert DE, Butterworth BE, Popp JA (1984) Dinitrotoluene: acute toxicity, oncogenicity, genotoxicity, and metabolism. Crit Rev Toxicol 13:217–234PubMedCrossRefGoogle Scholar
  18. Robert-Koch Institut (2004) Krebs in Deutschland. 4. überarbeitete, aktualisierte Ausgabe. Arbeitsgemeinschaft bevölkerungsbezogener Krebsregister in Deutschland, SaarbrückenGoogle Scholar
  19. Sayama M, Mori M, Shoji M, Uda S, Kakikawa M, Kondo T, Kodaira KI (1998) Mutagenicity of 2,4- and 2,6-dinitrololuenes and their reduced products in Salmonella typhimurium nitroreductase- and O-acetyltransferase-overproducing Ames test strains. Mutat Res 420:27–32PubMedGoogle Scholar
  20. Talaska G, al-Juburi AZ, Kadlubar FF (1991) Smoking related carcinogen-DNA adducts in biopsy samples of human urinary bladder: identification of N-(deoxyguanosin-8-yl)-4-aminobiphenyl as a major adduct. Proc Natl Acad Sci USA 88:5350–5354PubMedCrossRefGoogle Scholar
  21. Tchounwou PB, Wilson BA, Ishaque AB, Schneider J (2001) Transcriptional activation of stress genes and cytotoxicity in human liver carcinoma cells (HepG2) exposed to 2,4,6-trinitrotoluene, 2,4-dinitrotoluene, and 2,6-dinitrotoluene. Environ Toxicol 16:209–216CrossRefPubMedGoogle Scholar
  22. Turner MJ, Levine RJ, Nyström DD, Crume YS, Rickert DE (1985) Identification and quantification of urinary metabolites of dinitrotoluenes in occupationally exposed humans. Toxicol Appl Pharmacol 80:166–174CrossRefPubMedGoogle Scholar
  23. Zhang C, Daprato RC, Nishino SF, Spain JC, Hughes JB (2001) Remediation of dinitrotoluene contaminated soils from former ammunition plats: soil washing efficiency and effective process monitoring in bioslurry reactors. J Hazard Mater 87:139–154CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Volker Harth
    • 1
  • Hermann M. Bolt
    • 2
  • Thomas Brüning
    • 1
  1. 1.Berufsgenossenschaftliches Forschungsinstitut für Arbeitsmedizin (BGFA)Ruhr-Universität BochumBochumGermany
  2. 2.Institut für Arbeitsphysiologie an der Universität Dortmund (IfADo)DortmundGermany

Personalised recommendations