Kidney and urinary bladder lesions in F344/N rats and B6C3F1 mice after 13 weeks of 2,2-bis(bromomethyl)-1,3-propanediol administration.
Thirteen-week toxicity studies of the flame retardant 2,2-bis(bromomethyl)-1,3-propanediol (BMP; dibromoneopentyl glycol; FR-1138; CAS No. 329690-0) were conducted in male and female F344/N rats and B6C3F1 mice. The chemical was administered by oral gavage in corn oil 5 days per week for 13 weeks to rats at doses of 0, 50, 100, 200, 400, and 800 mg/kg and to mice at doses of 0, 25, 50, 100, 200, and 400 mg/kg, or in the feed for 13 weeks at concentrations of 0, 1250, 2500, 5000, 10,000, and 20,000 ppm for rats and at 0, 625, 1250, 2500, 5000, and 10,000 ppm for mice. There was a dose-related decrease in body weight gain in rats and mice after chemical administration. Mortality attributed to toxicity of BMP was seen in the gavage study in 2/10 high-dose (800 mg/kg) male rats and 3/10 high-dose (400 mg/kg) male mice no dose-related mortality occurred in the feed study. Minimal degeneration in the renal papilla was seen in male rats at 800 mg/kg in the gavage study and at doses of 5000 ppm or more in the feed study. This was also present in one female rat at the 20,000 ppm dose. In male mice renal papillary necrosis occurred at 400 mg/kg after dosing by the gavage route and at 2500, 5000, and 10,000 ppm in the dosed-feed study. In female mice papillary necrosis occurred only at the 10,000 ppm dose in the feed study. Tubular cell regeneration of the renal cortex was also present in mice at the same dose levels at which the papillary necrosis was observed. Transitional cell hypeplasia of the urinary bladder was seen in male rats at 400 and 800 mg/kg and in both sexes of mice at 200 and 400 mg/kg. Hyperplasia of the urinary bladder was also seen when BMP was administered in the feed at doses of 20,000 ppm to male rats; at doses of 2500, 5000, and 10,000 ppm to male mice; and at doses of 5000 and 10,000 ppm to female mice. The kidney and urinary bladder are target organs when BMP is administered by gavage or the dosed-feed route; mice were more sensitive than rats for the development of kidney and bladder lesions. Male rats and mice were more sensitive than females for the development of renal papillary degeneration or necrosis.
Elwell
M R
MR
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Dunnick
J K
JK
Brown
H R
HR
Montgomery
C A
CA
D000818:Animals; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005411:Flame Retardants / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009336:Necrosis / Q000139:chemically induced; D011409:Propylene Glycols / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D001745:Urinary Bladder Diseases / Q000139:chemically induced*
D005411:Flame Retardants; D011409:Propylene Glycols; C060080:2,2-bis(bromomethyl)-1,3-propanediol