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© 1990 Oxford University Press

research-article

Benzene Hemoglobin Adducts in Mice and Rats: Characterization of Formation and Physiological Modeling1

JAMES D. SUN2, MICHELE A. MEDINSKY, LINDA S. BIRNBAUM*, GEORGE LUCIER* and ROGENE F. HENDERSON

Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute P.O. Box 5890, Albuquerque, New Mexico 87185; *National Institute of Environmental Health Science, Research Triangle Park North Carolina 27709

Received January 22, 1990; accepted April 27, 1990

Benzene Hemoglobin Adducts in Mice and Rats: Characterization of Formation and Physiological Modeling. SUN, J. D., MEDINSKY, M. A., BIRNBAUM, L. S., LUCIER, G., AND HENDERSON, R. F. (1990). Fundam. Appl. Toxicol 15, 468–475. Benzene is a myelotoxin and a human leukemogen. Humans are exposed to this compound, both occupationally and environmentally. This study was conducted to determine whether formation of benzene-derived adducts with blood hemoglobin (Hb) can be used as a biomarker of exposure to benzene. B6C3F1 mice and F344/N rats were given 0.1 to 10,000 µmol [14C]benzene/kg body wt, orally. Twenty-four hours later, animals were euthanized, and globin was isolated from blood samples. The globin was analyzed by liquid scintillation spectrometry for the presence of [14C]benzene-de-rived adducts. Hb adduct formation was linear with respect to dose for amounts of up to 500 µmol [14C]benzene/kg body wt, for both rodent species. Within this linear dose-response range, mice formed adducts from [14C]benzene approximately 3.5 times less efficiently [0.022 ± 0.010 (pmol adducts/mg globin)/(µmol/kg body wt dose)] than did rats [0.076 ± 0.014 (pmol adducts)/ µmol/kg body wt dose)]. Benzene-derived Hb adducts also accumulated linearly when mice and rats were given up to three daily doses of 500 µmol [14C]benzene/kg body wt. These data were used to develop a physiological model for benzene-derived Hb adduct formation. Both first-order and saturable pathways for adduct formation were incorporated. The results showed that the model simulated the levels of Hb adducts in both mice and rats after oral exposures to benzene and predicted the levels of Hb adducts present after inhalation exposure. These studies suggest that Hb adducts might be useful biomarkers for human exposures to benzene.


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