Methyl methacrylate toxicity in rat nasal epithelium: investigation of the time course of lesion development and recovery from short term vapour inhalation.
An investigation of the time course of development and recovery of the nasal lesion induced in rats by inhalation of methyl methacrylate (MMA) was conducted. Groups of 45 female F344 rats (five animals per time point) were exposed whole body for 6 hours per day to 0 (control), 110 or 400 ppm MMA for 1, 2, 5, 10 or 28 consecutive days. Additional animals were retained for a period of 4, 13, 24 or 36 weeks following exposure to assess reversibility of any nasal tissue effects. After inhalation of MMA there was damage to the olfactory epithelium at 110 and 400 ppm. This was apparent following the first day of exposure, but recovery/regeneration was evident during the subsequent days of the exposure phase of the study. The most severely affected section of the nasal passages was that which included the ethmoturbinates. Focal adhesions between the septum and turbinates and between the turbinates themselves were seen in some animals exposed to 400 ppm MMA at time points after 5 days of exposure. There were no lesions in the squamous, transitional or respiratory epithelia and none in control rats. Lesions that developed in rats exposed to 110 ppm MMA subsequently repaired during the exposure period. At 400 ppm, the majority of the olfactory epithelium had returned to normal within 13 weeks of the end of the exposure phase, but minimal respiratory metaplasia remained evident and there were some focal adhesions between the septum and turbinates and between the turbinates themselves.
Hext
P M
PM
Zeneca Central Toxicology Laboratory, Alderley Park, Cheshire SK10 4TJ, Macclesfield, UK
Pinto
P J
PJ
Gaskell
B A
BA
D000280:Administration, Inhalation; D000818:Animals; D004848:Epithelium / Q000187:drug effects; D005260:Female; D008679:Metaplasia / Q000139:chemically induced / Q000473:pathology; D020366:Methylmethacrylate / Q000008:administration & dosage / Q000633:toxicity*; D009297:Nasal Mucosa / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D012038:Regeneration / Q000187:drug effects; D013997:Time Factors; D014420:Turbinates / Q000187:drug effects / Q000473:pathology
D020366:Methylmethacrylate