Benzene hemoglobin adducts in mice and rats: Characterization of formation and physiological modeling

Journal Article · Mon Oct 01 00:00:00 EDT 1990 · Fundamental and Applied Toxicology; (USA)

DOI:https://doi.org/10.1016/0272-0590(90)90033-G· OSTI ID:5982584

Sun, J D; Medinsky, M A; Birnbaum, L S; Lucier, G; Henderson, R F ^[1]

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1. Inhalation Toxicology Research Institute, Albuquerque, NM (USA)

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 mumol (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-derived adducts. Hb adduct formation was linear with respect to dose for amounts of up to 500 mumol (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)/(mumol/kg body wt dose)) than did rats (0.076 +/- 0.014 (pmol adducts)/(mumol/kg body wt dose)). Benzene-derived Hb adducts also accumulated linearly when mice and rats were given up to three daily doses of 500 mumol (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.

• OSTI ID: 5982584
• Journal Information: Fundamental and Applied Toxicology; (USA), Journal Name: Fundamental and Applied Toxicology; (USA) Vol. 15:3; ISSN FAATD; ISSN 0272-0590
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ANIMALS
AROMATICS
BENZENE
BIOLOGICAL MARKERS
BIOLOGICAL MODELS
BIOLOGICAL PATHWAYS
BIOLOGICAL VARIABILITY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CARCINOGENESIS
DNA ADDUCTS
DOSE-RESPONSE RELATIONSHIPS
GENETIC VARIABILITY
GLOBINS
HEMOGLOBIN
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LEUKEMOGENESIS
MAMMALS
MICE
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATHOGENESIS
PIGMENTS
PORPHYRINS
PROTEINS
RATS
RODENTS
TRACER TECHNIQUES
VERTEBRATES