Journal Article

Hemoglobin adducts in workers exposed to nitrotoluenes

Christopher R. Jones, Yu-Ying Liu, Ovnair Sepai, Huifang Yan and Gabriele Sabbioni

in Carcinogenesis

Volume 26, issue 1, pages 133-143
Published in print January 2005 | ISSN: 0143-3334
Published online January 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh286
Hemoglobin adducts in workers exposed to nitrotoluenes

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Nitrotoluenes are important intermediates in the chemical industry. 2,6-Dinitrotoluene (26DNT), 2,4-dinitrotoluene (24DNT) and 2-nitrotoluene are carcinogenic in animals and possibly carcinogenic in humans. It is therefore important to develop methods to biomonitor workers exposed to such chemicals. Hemoglobin (Hb) adducts of nitroarenes are established markers of the biological effective dose. We developed a method to measure Hb adducts in biological samples. Hb adducts were measured in rats after a single exposure (0.5 mmol/kg) of 24DNT, 26DNT, 2,4-toluenediamine (24TDA) and 26TDA. Hydrolysis of Hb from rats dosed with 24DNT yields, 4-amino-2-nitrotoluene (4A2NT) (16.3 nmol/g Hb), 24TDA (4.3 nmol/g Hb) and 4-acetylamino-2-aminotoluene (4AA2AT) (0.51 nmol/g Hb). Hydrolysis of Hb from rats dosed with 26DNT yields three amines, 2-amino-6-nitrotoluene (2A6NT) (2.5 nmol/g Hb), 26TDA (1.2 nmol/g Hb) and 2-acetylamino-6-aminotoluene (2AA6AT) (0.17 nmol/g Hb). A similar Hb adduct pattern was found in Chinese workers exposed to nitrotoluenes. With respect to 24DNT, 4A2NT was the predominant adduct, and the amount was ∼24-fold higher than 24TDA. With respect to 26DNT, 2A6NT was the predominant adduct, and the amount was ∼20-fold higher than 26TDA. With respect to the mononitrotoluenes, the Hb adduct of 2NT was present in the highest concentrations. Each worker was examined for adverse health effects linked to exposure to DNT. The health effects were compared with the Hb adduct levels using logistic regression analysis. The odds of suffering from inertia were 3.2 times higher [95% confidence interval (CI) = 1.8–5.8] when the level of 4A2NT Hb adducts increased by one log-unit. Similar odds ratios were observed with somnolence (3.1, CI = 1.4–6.9), nausea (2.4, CI = 1.3–4.3) and dizziness (5.5, CI = 1.3–24.2). These results inferred that quantification of DNT–Hb adducts provided an effective biomarker of toxicity and could be used to estimate the risk associated with a particular exposure to DNT.

Keywords: 2AA4AT, 2-acetylamino-4-aminotoluene; 4AA2AT, 4-acetylamino-2-aminotoluene; 2AA6AT, 2-acetylamino-6-aminotoluene; 2A4NT, 2-amino-4-nitrotoluene; 4A2NT, 4-amino-2-nitrotoluene; 2A6NT, 2-amino-6-nitrotoluene; d, deuterated; DNT, dinitrotoluenes; 26DNT, 2,6-dinitrotoluene; 24DNT, 2,4-dinitrotoluene; EI, electron impact ionization; Hb, hemoglobin; 2MA, 2-methylaniline; 3MA, 3-methylaniline; 4MA, 4-methylaniline; NCI, negative chemical ionization; NT, mononitrotoluenes; 2NT, 2-nitrotoluene; 4NT, 4-nitrotoluene; OR, odds ratio; PFPA, pentafluoropropionic anhydride; t-DNT, technical dinitrotoluene; 24TDA, 2,4-toluenediamine; 26TDA, 2,6-toluenediamine; TNT, trinitrotoluene

Journal Article.  8586 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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