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Dichlobenil in the fetal and neonatal mouse olfactory mucosa
1Department of Pharmacology and Toxicology, Uppsala Biomedical Center, Sweden.
Abstract:
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.
Insights
Dichlobenil irreversibly binds to Bowman
Area of Science:
- Toxicology
- Neuroscience
- Histopathology
Background:
- The olfactory system is crucial for detecting environmental cues.
- Olfactory toxicants can impact sensory perception and health.
- Dichlobenil is an olfactory toxicant whose perinatal effects require investigation.
Purpose of the Study:
- To investigate the irreversible binding and toxicity of dichlobenil in the developing mouse olfactory mucosa.
- To correlate dichlobenil binding patterns with histopathological changes.
- To understand the impact of dichlobenil on olfactory gland development and function.
Main Methods:
- Autoradiography was used to track [14C]dichlobenil-derived radioactivity.
- Histopathology was employed to assess tissue damage and morphological changes.
- Studies were conducted on fetal, neonatal, and adult mice at various developmental stages.
Main Results:
- Irreversible binding of dichlobenil in adult mice was primarily localized to Bowman's glands.
- Binding was low in fetal olfactory mucosa but increased significantly after birth, coinciding with Bowman's gland development.
- Neonates showed minimal toxicity at lower doses, while older pups and adults exhibited necrotic Bowman's glands, particularly at higher doses.
Conclusions:
- Dichlobenil exhibits age-dependent toxicity in the mouse olfactory mucosa, with Bowman's glands being the primary target.
- The developing olfactory mucosa's regenerative capacity, due to cell proliferation, may mitigate dichlobenil toxicity.
- Understanding these mechanisms is vital for assessing risks associated with olfactory toxicants during development.