2-week inhalation study of N-monomethylformamide in rats.
N-Monomethylformamide (MMF) is a chemical intermediate with potential for inhalation exposure in humans. Human exposures to MMF have occurred in cancer chemotherapy but have been limited due to liver damage. To assess the toxicity of MMF, groups of 15 male rats each were exposed by nose-only inhalation, 6 hr/day, 5 days/week, for 2 weeks to either 0 (control), 50, 130, or 400 ppm MMF. Five rats per group were killed following the 10th exposure, five were killed after a 14-day postexposure recovery period, and five rats were used to determine urinary MMF excretion. Parameters investigated were clinical observations and body weights, clinical pathology, and gross and microscopic pathology including organ weights. Liver damage occurred in rats exposed to either 130 or 400 ppm. This was detected both by increases in serum enzyme activity indicative of liver injury and by microscopic changes in the liver. The changes were more severe in the 400-ppm rats and were partially reversible. Other organs were not adversely affected by inhalation of MMF. The amount of MMF excreted in the urine was dependent on the exposure concentration and MMF was present 14 days postexposure at the higher exposure levels. The no-observed-effect level under the conditions of this experiment was 50 ppm.
Kennedy
G L
GL
E. I. du Pont de Nemours & Company, Inc., Haskell Laboratory for Toxicology and Industrial Medicine, Newark, Delaware 19714.
Ferenz
R L
RL
Burgess
B A
BA
Stula
E F
EF
D000280:Administration, Inhalation; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005559:Formamides / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D014556:Urine / Q000032:analysis
D000970:Antineoplastic Agents; D005559:Formamides; D002784:Cholesterol; C002950:methylformamide