Dichlobenil in the fetal and neonatal mouse olfactory mucosa.
The irreversible binding and toxicity of the olfactory toxicant dichlobenil in the mouse perinatal olfactory mucosa were examined by autoradiography and histopathology. In the olfactory mucosa of adult mice the irreversible binding of [14C]dichlobenil-derived radioactivity is confined to the Bowman's glands. The results in this study showed a low irreversible binding of [14C]dichlobenil-derived radioactivity in the fetal olfactory mucosa from day 17 of gestation and a markedly increased binding after birth in accord with the development of the Bowman's glands. No morphological changes were observed in the olfactory mucosa of 1- or 4-day-old neonates given s.c. injections with dichlobenil 12 mg/kg but in 8- or 11-day-old mice given 12 or 25 mg/kg, scattered necrotic Bowman's glands occurred in the dorsomedial olfactory region 24 h after administration. In adult male mice dosed i.p. with dichlobenil a more extensive toxicity in the Bowman's glands was observed. The low toxicity of dichlobenil in the postnatal olfactory mucosa, despite a high irreversible binding at this site, may possibly be related to the cell proliferation in the developing olfactory mucosa leading to replacement of damaged cells.
Eriksson
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C
Department of Pharmacology and Toxicology, Uppsala Biomedical Center, Sweden.
Brittebo
E B
EB
D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D001549:Benzamides / Q000493:pharmacokinetics* / Q000633:toxicity; D005260:Female; D006540:Herbicides / Q000493:pharmacokinetics / Q000633:toxicity; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D009570:Nitriles; D009831:Olfactory Mucosa / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D011247:Pregnancy
D001549:Benzamides; D006540:Herbicides; D009570:Nitriles; C055869:dichlobanil