07N^ 



O 



,CH = N> 



NH 



O 



NITROFURANTOIN 



CAS No. 67-20-9 



C8H6N4O5 



Molecular weight 238.2 



Synonyms: l-(((5-nitro-2-ruranyl)methylene)amino-2,4-imidazolidinedione); 

 l-(5-nitro-2-furfurylideneamino)-hydantoin; A'^-(5-nitro-2-furfurylidene)-l-aminohydantoin; 

 l-((5-nitrofurfurylidene)amino)hydantoin 



Trade names: Benkfuran; Berkfurin; Chemiofuran; Cyantin; Dantafur; Furadantin, Furadantine; 

 Furadantoin; F^uradonin; Furadonine, Furantoin; Furatoin; Furobactina; Ituran; Macrodantin, 

 Nifurantin; NSC 2107; N-Toin; Orafuran; Parafuran; Urizept; USAF EA-2; Welfurin; Zoofurin 



ABSTRACT 



Nitrofurantoin was studied and evaluated because of its widespread use as a drug for treating urinary 

 tract infections in humans, its structural relationship to known carcinogenic 5-nitrofuran com- 

 pounds, and the lack of adequate studies to assess its carcinogenicity Toxicology and carcinogenesis 

 studies of nitrofurantoin were conducted by administering nitrofurantoin (greater than 99% pure) in 

 feed to groups of F344/N rats and B6C3Fi mice of each sex for 14 days, 13 weeks, or 2 years. 



Fourteen-Day and Thirteen-Week Studies: None of the rats (at dietary concentrations up to 20,000 

 ppm) died before the end of the 14-day studies. Rats that received 5,000, 10,000, or 20,000 ppm lost 

 weight. Four of five male and 4/5 female mice that received 10,000 ppm and 1/5 females that received 

 5,000 ppm nitrofurantoin died before the end of the studies. Mice that received 5,000 ppm and male 

 mice that received 10,000 ppm lost weight. 



In the 13-week studies, final mean body weights of rats that received 2,500, 5,000, or 10,000 ppm were 

 10%, 34%, or 47% lower than that of the controls for males and 15%, 31%, or 41% lower for females. 

 Feed consumption by dosed and control rats was generally similar. Degeneration of the germinal epi- 

 thelium of the seminiferous tubules of the testis was observed in male rats that received 2,500 to 

 10,000 ppm nitrofurantoin. Necrosis of the ovarian follicles was observed in 8/10 female rats that re- 

 ceived 10,000 ppm, in 3/10 females that received 5,000 ppm, and in 1/10 that received 2,500 ppm. 



For mice, final mean body weights of the 5,000-ppm groups were 13% lower than that of the controls 

 for males and 15% lower for females. Two of 10 male mice that received 5,000 ppm and 1/10 males 

 that received 300 ppm died before the end of the 13- week studies. Estimated feed consumption was 

 similar for dosed and control groups. Degeneration of the germinal epithelium of the testis was ob- 

 served in males that received 1,300 to 5,000 ppm; necrosis of the ovarian follicles was observed in fe- 

 males that received 5,000 ppm but not in the lower dose groups. Necrosis of the renal tubular epithe- 

 lium was observed in 2/9 males that received 5,000 ppm. 



Based on these results, 2-year studies of nitrofurantoin were conducted by feeding diets containing 0, 

 1,300, or 2,500 ppm nitrofurantoin to groups of 50 male F344/N rats and to groups of 50 male and 



Nitrofurantoin, NTP TR 341 



