Inhalation toxicity of acetaldehyde in rats. IV. Progression and regression of nasal lesions after discontinuation of exposure.
As part of a long-term inhalation toxicity study with acetaldehyde in rats, progression and regression of nasal lesions were studied in animals exposed to 0, 750, 1500 and 3000/1500 ppm of the test compound for 52 weeks and killed after recovery periods of 26 or 52 weeks. Major compound-related nasal lesions found at the end of the exposure period comprised: (a) thinning of the olfactory epithelium with loss of sensory and sustentacular cells at all concentrations; this condition was accompanied by focal basal cell hyperplasia in low- and mid-concentration animals; (b) hyper- and metaplasia of the respiratory epithelium frequently accompanied by keratinisation and occasionally by proliferations of atypical basal cells in the top-concentration group; and (c) rhinitis in several top-concentration rats. There was strong evidence on the one hand that the hyper- and metaplastic changes found in the respiratory epithelium and the basal cell hyperplasia seen in the olfactory epithelium after 52 weeks of exposure may progress to neoplasms despite discontinuation of the treatment. On the other hand these hyper- and metaplastic changes may regress during the recovery period. Regeneration of the olfactory epithelium was evident in several low- and mid-concentration animals, but not in top-concentration rats. The regenerated epithelium was seen as a layer of stratified undifferentiated epithelium containing small nerve bundles, tiny groups of sensory cells, and groups of epithelial cells resembling acinar cells of the glands of Bowman. Furthermore, replacement of olfactory epithelium by respiratory epithelium was a frequent finding. It was concluded that rat olfactory epithelium severely damaged by acetaldehyde may regenerate, most probably from basal cells, provided the olfactory epithelium has not been fully destroyed.
TNO-CIVO Toxicology and Nutrition Institute, Zeist, The Netherlands.
R A
RA
Woutersen
V J
VJ
Feron
D000079:Acetaldehyde / Q000008:administration & dosage / Q000633:toxicity*; D000280:Administration, Inhalation; D000818:Animals; D004848:Epithelium / Q000187:drug effects; D005260:Female; D006965:Hyperplasia; D008297:Male; D008679:Metaplasia; D009297:Nasal Mucosa / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012038:Regeneration
D000079:Acetaldehyde