Hemoglobin adducts, urinary metabolites and health effects in 2,4,6-trinitrotoluene exposed workers
Open Access
- 7 April 2005
- journal article
- research article
- Published by Oxford University Press (OUP) in Carcinogenesis: Integrative Cancer Research
- Vol. 26 (7), 1272-1279
- https://doi.org/10.1093/carcin/bgi078
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, 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.Keywords
This publication has 28 references indexed in Scilit:
- Biomonitoring of arylamines and nitroarenesBiomarkers, 2002
- Increased risk of acute myelogeneous leukemia (AML) and chronic myelogenous leukemia (CML) in a county of Hesse, GermanyInternational Journal of Public Health, 1993
- Electrophilic intermediate in the reaction of glutathione and nitroso arenesJournal of the American Chemical Society, 1992
- In vivo covalent binding of [14C]trinitrotoluene to proteins in the ratChemico-Biological Interactions, 1992
- Mercapturic Acids, Protein Adducts, and DNA Adducts as Biomarkers of Electrophilic ChemicalsCritical Reviews in Toxicology, 1992
- Organic Explosives and Related CompoundsThe Handbook of Environmental Chemistry, 1991
- Gas chromatographic and mass spectrometric determination of nitroaromatics in waterJournal of Chromatography A, 1990
- Structure of the single stable hemoglobin adduct formed by 4-aminobiphenyl in vivoChemical Research in Toxicology, 1988
- Metabolism of Nitroaromatic CompoundsDrug Metabolism Reviews, 1987
- Identification of urinary metabolites of 2,4,6-trinitro-toluene in rats by liquid chromatography-mass spectometryToxicology Letters, 1985