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Hydrolyzable hemoglobin adducts of polyfunctional monocyclic N-substituted arenes as dosimeters of exposure and markers of metabolism

Journal Article · · Environmental Health Perspectives

Hemoglobin adducts of 10 polyfunctional amino- and nitro-substituted benzenes and toluenes were analyzed: 2,4,6-trinitrotoluene, 2,4- and 2,6-dinitrotoluene. 2-amino-4-nitrotoluene, 4-amino-2-nitrotoluene, 2,4- and 2,6-diaminotoluene, 1,3-dinitrobenzene, 1-amino-3-nitrobenzene, and 1,3-diaminobenzene. A single dose (0.5 mmole/kg) of the test compounds was administered to female Wistar rats by gavage, and blood extracted and hemoglobin prepared after 24 hr. One or more cleavage products could be obtained in each case by hydrolyzing hemoglobin (Hb). Hemoglobin binding indices (HBl); binding (mmole/mole Hbl/dose [mmole/kg]) and the ratios of hydrolyzable adducts were determined. The HBl ranged between <0/.02 and 69.0. The results indicate the in vivo formation of several, convalently bound, hydrolyzable hemoglobin adducts. Conclusion on prevailing metabolic pathways can be drawn. Total binding of several compounds seems sufficient for biomonitoring of human blood samples. These chemicals are considered representative for environmental contamination with explosives of this type, and we propose their Hb adducts be used as dosimeters for human exposure to these suspected carcinogens. 8 refs., 2 figs., 2 tabs.

Sponsoring Organization:
USDOE
OSTI ID:
478799
Report Number(s):
CONF-9210376--
Journal Information:
Environmental Health Perspectives, Journal Name: Environmental Health Perspectives Journal Issue: Suppl.6 Vol. 102; ISSN 0091-6765; ISSN EVHPAZ
Country of Publication:
United States
Language:
English