Two-year inhalation carcinogenesis studies of methyl methacrylate in rats and mice: inflammation and degeneration of nasal epithelium.
Methyl methacrylate (MMA), a liquid monomer, is used as a chemical intermediate in the manufacture of plexiglass and other acrylic products and as "bone cement" in orthopedic and dental surgery. Toxicology and carcinogenesis inhalation studies of MMA were conducted because of: (1) widespread human exposure; (2) evidence of mutagenicity; and (3) inadequacy of previously conducted long-term oral, dermal, and inhalation studies. Groups of 50 male F344/N rats were exposed to MMA by inhalation at 0, 500, or 1000 ppm, female F344/N rats at 0, 250, or 500 ppm, and male and female B6C3F1 mice at 0, 500, or 1000 ppm, 6 h a day, 5 days a week for 102 weeks. Survival rates of male and female rats and mice exposed to MMA were similar to those of their respective controls. Body weights were reduced in the low and high dose male (3-6% and 5-10%, respectively) and female (5-7% and 8-10%) rats exposed to MMA for more than 80 weeks and in male (7-19% and 6-17%) and female (0-13% and 0-17%) mice for more than 20 weeks. Inhalation exposure of MMA for 102 weeks did not induce any increased incidences of neoplasms in male or female rats or mice. Non-neoplastic lesions in the nasal cavity of MMA-exposed rats and mice were significantly increased and these included inflammation and degeneration of the olfactory epithelium of MMA-exposed male and female rats and inflammation, hyperplasia, cytoplasmic inclusions in the respiratory epithelium, and degeneration of the olfactory epithelium in male and female mice.
Chan
P C
PC
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Eustis
S L
SL
Huff
J E
JE
Haseman
J K
JK
Ragan
H
H
D000280:Administration, Inhalation; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D005260:Female; D008168:Lung / Q000187:drug effects; D008297:Male; D020366:Methylmethacrylate; D008768:Methylmethacrylates / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D009297:Nasal Mucosa / Q000187:drug effects* / Q000473:pathology; D009300:Nasal Septum / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D012220:Rhinitis / Q000139:chemically induced*; D012737:Sex Factors; D013045:Species Specificity
D002273:Carcinogens; D008768:Methylmethacrylates; D020366:Methylmethacrylate