Toxicological Sciences 55, 383-391 (2000)
Copyright © 2000 by the Society of Toxicology
Intranasal Instillation of Aflatoxin B1 in Rats: Bioactivation in the Nasal Mucosa and Neuronal Transport to the Olfactory Bulb
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Box 573, S-751 23 Uppsala, Sweden
Aflatoxin B1 (AFB1) may be present in moldy dust. Inhalation of contaminated dust particles may result in high local exposure of the nasal mucosa. The present study was designed to assess bioactivation and toxicity of AFB1 in the nasal mucosa after intranasal administration of the mycotoxin in rats and also to examine if translocation of the mycotoxin occurs from the nasal mucosa to the brain along olfactory neurons. Female Sprague-Dawley rats were given 3H-AFB1 (0.2, 1 or 20 µg) intranasally and were sacrificed at various intervals (1 h to 20 d). Tissues were examined autoradiographically or histopathologically. Quantitative data were obtained by ß-spectrometry in rats given 3H-AFB1 intranasally or orally (for comparison). The data indicated that intranasal administration of AFB1 resulted in formation of tissue-bound metabolites in sustentacular cells, in some cells of Bowman's glands, and in a population of neuronal cells in the olfactory mucosa, whereas in the respiratory nasal mucosa, there was selective bioactivation of AFB1 in mucous cells. Intranasal instillation of 20 µg AFB1 resulted in disorganized undulating olfactory epithelium, with injured neuronal and sustentacular cells. In the respiratory epithelium, there was selective destruction of mucous cells. ß-Spectrometry and autoradiography with tape-sections of the head of rats given 3H-AFB1 intranasally indicated transport of AFB1 and/or AFB1 metabolites along the axons of the primary olfactory neurons to their terminations in the glomeruli of the olfactory bulb. The data indicate that the materials transported in the olfactory nerves represent AFB1 and/or some of its nonreactive metabolites. It is concluded that application of AFB1 on the nasal mucosa in rats results in high local bioactivation of the mycotoxin in this tissue and translocation of AFB1 and/or its metabolites to the olfactory bulb.
Key Words: aflatoxin B1; intranasal instillation; olfactory mucosa; nasal respiratory mucosa; olfactory bulb; neuronal transport; bioactivation.
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