Chronic inhalation toxicity and carcinogenicity study of methyl bromide in Wistar rats.
The toxicity and carcinogenicity of methyl bromide (MeBr) were studied in male and female Wistar rats exposed by inhalation to 0, 3, 30 or 90 ppm MeBr 6hr/day, 5 days/wk for 29 months. After 13, 52 and 104 wk ten rats/sex/group were killed to provide interim information. Body weights, clinical signs, haematology, biochemistry and gross and microscopic pathology were studied. Mortality was increased by wk 114 in the 90-ppm group. Body weights in males and females of the 90-ppm group were lower than those of the controls throughout the study. Increased incidences of degenerative and hyperplastic changes of the nasal olfactory epithelium were observed in all exposed groups, the incidences being positively correlated with the MeBr concentration; the nasal lesions did not progress appreciably with time. Exposure to 90 ppm MeBr was associated with an increased incidence of lesions in the heart (thrombi, myocardial degeneration), and with hyperkeratosis in the oesophagus and forestomach. Data on site, type and incidence of tumours in the various groups did not indicate carcinogenic activity of MeBr.
Reuzel
P G
PG
TNO-CIVO Toxicology and Nutrition Institute, Zeist, The Netherlands.
Dreef-van der Meulen
H C
HC
Hollanders
V M
VM
Kuper
C F
CF
Feron
V J
VJ
van der Heijden
C A
CA
D000280:Administration, Inhalation; D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects; D006842:Hydrocarbons, Brominated / Q000008:administration & dosage / Q000633:toxicity*; D006965:Hyperplasia; D007668:Kidney / Q000187:drug effects; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D009929:Organ Size / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D013047:Specific Pathogen-Free Organisms
D006842:Hydrocarbons, Brominated; C005218:methyl bromide