Carcinogenesis Advance Access originally published online on April 7, 2005
Carcinogenesis 2005 26(7):1272-1279; doi:10.1093/carcin/bgi078
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Carcinogenesis vol.26 no.7 © Oxford University Press 2005; all rights reserved.
Hemoglobin adducts, urinary metabolites and health effects in 2,4,6-trinitrotoluene exposed workers
1 Institute of Environmental and Occupational Toxicology, Casella Postale 108, 6780 Airolo, Switzerland, 2 Walther-Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, 80336 München, Germany, 3 Chinese Academy of Preventive Medicine, Nan Wei Road 29, Beijing 100050, China, 4 Department of Environmental and Occupational Medicine, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, UK and 5 Health Protection Agency, CHAPD-HQ, Chilton OX11 0RQ, UK
* To whom correspondence should be addressed Email: gabriele.sabbioni{at}bluewin.ch
2,4,6-Trinitrotoluene (TNT) is an important occupational and environmental pollutant. In TNT exposed humans, the notable toxic manifestations have included aplastic anemia, toxic hepatitis, cataract, hepatomegaly and liver cancer. Therefore, we developed methods to biomonitor workers exposed to TNT. The workers were employed in a typical ammunition factory in China. The controls were recruited from the same factory. We determined hemoglobin (Hb) adducts and urine metabolites of TNT. Hb-adducts of TNT, 4-amino-2,6-dinitrotoluene (4ADNT) and 2-amino-4,6-dinitrotoluene (2ADNT), and the urine metabolites of TNT, 4ADNT and 2ADNT were found in all the workers and in a few controls. 4ADNT was the main product. Although the levels of 2ADNT correlated well with 4ADNT, 2ADNT was not found in all the samples. Therefore, 4ADNT was the best marker of exposure for Hb-adducts and urine metabolites. The levels of the urine metabolites and Hb-adducts were related to the health status of the workers. The Hb-adduct 4ADNT was statistically significantly associated with risk of hepatomegaly, splenomegaly and cataract. The odds ratio (OR) for cataract, splenomegaly and hepatomegaly were 6.4 [95% confidence interval (CI) = 1.4–29.6], 9.6 (1.1–85.3) and 7.6 (1.3–43.7), respectively. No correlation was found between urine metabolites and health effects. These results were tested for confounding factors like age, workyears, smoker status, smoke years, cigarettes per day and hepatitis B status using stepwise forward logistic regression analysis. In the case of splenomegaly, hepatitis B status is a confounder. In the case of cataract, age is a confounder. The Hb-adduct, 4ADNT, is a good biomarker of exposure and biomarker of biological effect.
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  G. Sabbioni, C. R. Jones, O. Sepai, A. Hirvonen, H. Norppa, H. Jarventaus, H. Glatt, D. Pomplun, H. Yan, L. R. Brooks, et al. Biomarkers of exposure, effect, and susceptibility in workers exposed to nitrotoluenes. Cancer Epidemiol. Biomarkers Prev., March 1, 2006; 15(3): 559 - 566. [Abstract] [Full Text] [PDF]
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