Pharmacokinetics of intratracheally administered aflatoxin B1
| Autor: | Dennis W Wilson, Roger A. Coulombe, J. M. Huie, R. W. Ball, Raghubir P. Sharma |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Male
Aflatoxin medicine.medical_specialty Aflatoxin B1 Bronchi Absorption (skin) Toxicology Models Biological Absorption chemistry.chemical_compound fluids and secretions Pharmacokinetics Aflatoxins Internal medicine medicine Toxicokinetics Animals Tissue Distribution Mycotoxin Lung Carcinogen Pharmacology Dust Rats Inbred Strains DNA respiratory tract diseases Rats Trachea medicine.anatomical_structure Endocrinology chemistry Carcinogens Crystallization Respiratory tract |
| Zdroj: | Toxicology and applied pharmacology. 109(2) |
| ISSN: | 0041-008X |
| Popis: | High concentrations of the carcinogen aflatoxin B 1 (AFB 1 ) are commonly found in respirable, airborne grain dusts, and inhaled AFB 1 has been shown to be a risk factor for occupational pulmonary carcinogenesis. The fate of AFB 1 exposure via the respiratory tract is therefore of interest in an evaluation of potential occupational risk. The pharmacokinetic disposition of intratracheally administered AFB 1 was studied in male Sprague-Dawley rats. Blood and tissues were sampled at selected intervals for 3 weeks following administration of a single dose of grain dust-adsorbed or microcrystalline [ 3 H]AFB 1 (6 μCi; 300 μg/kg). The blood concentration-time profiles from both groups best approximated a two-compartment open model with first-order absorption. The first-order absorption rate constant was significantly less in the animals given dust-adsorbed AFB 1 than in those receiving microcrystalline AFB 1 (0.0083 vs 0.1060 min −1 , respectively), although the first-order elimination rate constants for both groups were nearly identical (0.00928 and 0.00921 hr −1 , respectively). Blood concentrations of the AFB 1 metabolites AFM 1 , AFQ 1 , AFL, and AFP 1 showed little differences among the two groups. The tissue concentrations of aflatoxins for the microcrystalline group were significantly greater at 3 hr in all tissues examined except for the trachea and lung in which those for the dust-adsorbed group were greater. At 3 days and 3 weeks, no significant differences between exposure groups were seen in any tissue except fat, where the amount of aflatoxins was greater for the dust-adsorbed group. AFB 1 binding to DNA was significantly greater in the trachea and lung of the dust-adsorbed group compared to that in the microcrystalline group at 3 hr, whereas in the liver the AFB 1 -DNA binding in the microcrystalline group was significantly greater during this time. Thus, particle association of AFB 1 increased the respiratory tract retention of this compound at early time intervals, which might be a factor in the reputed carcinogenic action of this compound in the respiratory tract. These findings may be useful as part of a comprehensive study to evaluate the disposition of AFB 1 in individuals exposed to grain dusts laden with this carcinogen. |
| Databáze: | OpenAIRE |
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