Pharmacokinetics of Intratracheally-Administered Aflatoxin B1

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Toxicology and Applied Pharmacology







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High concentrations of the carcinogen aflatoxin B1 (AFB1) are commonly found in respirable, airborne grain dusts, and inhaled AFB1 has been shown to be a risk factor for occupational pulmonary carcinogenesis. The fate of AFB1 exposure via the respiratory tract is therefore of interest in an evaluation of potential occupational risk. The pharmacokinetic disposition of intratracheally administered AFB1 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 [3H]AFB1 (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 AFB1 than in those receiving microcrystalline AFB1 (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 AFB1 metabolites AFM1, AFQ1, AFL, and AFP1 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. AFB1 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 AFB1-DNA binding in the microcrystalline group was significantly greater during this time. Thus, particle association of AFB1 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 AFB1 in individuals exposed to grain dusts laden with this carcinogen.


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