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COMPARISON OF BIOMARKERS IN WORKERS EXPOSED TO 2,4,6-TRINITROTOLUENE
Citation:
SABBIONI, G., O. SEPAI, H. YAN, H. NORPPA, A. HIRVONEN, Y. ZHENG, H. JARVENTAUS, B. BACK, L. R. BROOKS, S. H. WARREN, D. M. DEMARINI, AND Y. LIU. COMPARISON OF BIOMARKERS IN WORKERS EXPOSED TO 2,4,6-TRINITROTOLUENE. BIOMARKERS. Taylor & Francis, Inc., Philadelphia, PA, 12(1):21-37, (2007).
Impact/Purpose:
to develop methods to biomonitor workers
Description:
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 ammunition factory in China. The external dose (air levels and skin exposure), the internal dose (urine metabolites), the biologically effective dose (hemoglobin adducts, urine mutagenicity), biological effects (chromosomal aberrations and health effects), and individual susceptibilities (genotypes of xenobiotic-metabolizing enzymes) were determined. 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 some controls. The Hb-adduct levels and/or the urinary metabolites did not correlate with the air levels. The urinary mutagenicity determined in a subset of workers (n = 17) correlated with the levels of 4ADNT and 2ADNT in urine. The Hb-adducts correlated moderately with the urine metabolites and strongly with the urine mutagenicity. The genotypes of glutathione transferases (GSTM1, GSTT1, GSTP1) and N-acetyltransferases (NAT1, NAT2) were determined. In general, the genotypes did not significantly influence the adduct levels in the expected manner. The biomarkers correlated with health effects among the workers, including cataracts, splenomegaly, and hepatomegaly. The Hb-adduct 4ADNT was significantly associated with risk of hepatomegaly, splenomegaly and cataract. No statistically significant association was found among urine metabolites, genotypes, and health effects. In conclusion, (i) the air levels did not reflect the internal burden as evidenced by the fact that these levels did not correlate with the biomarkers, (ii) the genotypes did not influence the health effects studied, and (iii) urinary mutagenicity correlated with urinary metabolite levels and Hb-adduct levels. These results show that a set of well-selected biomarkers may be more informative regarding exposure and effect than routinely performed chemical measurements of pollutants in the air or on the skin.