Olfactory mucosal lesions following subcutaneous diethyldithiocarbamate (DDTC)

We found that a single 600 mg/kg subcutaneous dose of the chelating agent diethyldithiocarbamate (DDTC) in rats caused severe damage of the olfactory epithelium. Damage was characterized by degeneration of the receptor cells but sparing of basal cells. This degeneration was characterized centrally (in the olfactory bulb) by 50% shrinkage of glomeruli. Reactive gliosis, as judged by immunoreactivity for glial fibrillary acidic protein, was prominent in the glomeruli at one week. Glomeruli areas had recovered to control values and gliosis in glomeruli had decreased by five weeks after injection. This recovery corresponds to sparing of the regenerative cell of the olfactory epithelium. We hypothesized that DDTC may act by disrupting xenobiotic metabolic pathways requiring divalent cations.