Development of kidney tumors in the male F344/N rat after treatment with dimethyl methylphosphonate.
Dimethyl methylphosphonate (DMMP), a chemical that has been used as a flame retardant and as a nerve gas simulant to mimic the physical but not biologic properties of nerve gases, was administered by gavage in corn oil for up to 2 years at doses of 0, 500, or 1000 mg/kg/day to male and female F344/N rats and at doses of 0, 1000, or 2000 mg/kg/day to male and female B6C3F1 mice. Survival in dosed male rats was reduced, due in part to kidney toxicity, and lesions in the kidney included increased severity of spontaneous nephropathy, calcification, hyperplasia of the tubular and transitional epithelium, tubular cell adenocarcinomas, and transitional cell papillomas and carcinomas. Survival in female rats was similar among groups; survival in mice was reduced and this reduced survival decreased the sensitivity for detecting a carcinogenic response. There were no dose-related neoplastic responses in female rats or male or female mice. The spectrum of kidney lesions seen in the male rat given DMMP is similar to that seen after the long-term administration of a variety of other chemicals including unleaded gasoline, hydrocarbon solvents, and 1,4-dichlorobenzene.
Dunnick
J K
JK
National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, North Carolina 27709.
Eustis
S L
SL
Haseman
J K
JK
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000473:pathology; D005260:Female; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009943:Organophosphorus Compounds / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D009943:Organophosphorus Compounds; C031116:dimethyl methylphosphonate