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Carcinogenesis Advance Access published online on April 7, 2005
Carcinogenesis, doi:10.1093/carcin/bgi078
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oupjournals.org
Received December 21, 2004
Revised March 17, 2005
Accepted March 22, 2005

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Hemoglobin adducts, urinary metabolites, and health effects in 2,4,6-trinitrotoluene exposed workers

Gabriele Sabbioni 1*, Yu-Ying Liu 2, Huifang Yan 2, and Ovnair Sepai 3

1 Institute of Environmental and Occupational Toxicology, Casella Postale 108, 6780 Airolo, Switzerland; Walther-Straub-Institut fuer Pharmakologie und Toxikologie, Ludwig-Maximilians-Universitaet Muenchen, 80336 Muenchen
2 Chinese Academy of Preventive Medicine, Nan Wei Road 29, Beijing, P.R. China 100050
3 Department of Environmental and Occupational Medicine, The Medical School, University of Newcastle upon Tyne, Newcastle Upon Tyne, UK; Health Protection Agency, CHAPD-HQ, Chilton Oxon, OX11 0RQ, UK

* To whom correspondence should be addressed.
Gabriele Sabbioni, E-mail: gabriele.sabbioni{at}bluewin.ch


  Abstract

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, cataracts, hepatomegaly, and liver cancer. Therefore, we developed methods to biomonitor workers exposed to TNT. The workers were employed in a typical military TNT-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 workers and in a few controls. 4ADNT was the main product. The levels of 2ADNT correlate well with 4ADNT, but 2ADNT was not found in all 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 6.5 (95% confidence interval (CI) =1.4-29.6), 9.9 (1.1-90.0), and 7.6 (1.2-43.7), respectively. No relation 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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