TABLE 5. 



EXPERIMENTAL DESIGN AND MATERIALS AND METHODS IN THE FEED STUDIES OF 



NITROFURANTOIN 



Fourteen-Day Studies 



Thirteen-Week Studies 



Two-Year Studies 



EXPERIMENTAL DESIGN 



Size of Study Groups 



5 males and 5 females of each species 10 males and 10 females of each species 50 males and 50 females uf each species 



Doses 



Rals--0. 1,300,2,500,5.000. 10.000, or Rats--O,fi00. I,:i00, 2,500, 5,000, or 



20,000 ppm nitrofurantoin in feed; 10,000 ppm nitrofurantoin in feed; 



mice 0,600, 1,300, 2,500, 5,000, or mice-O. 300, HOO, 1 ,300, 2,500, or 



10,000 ppm 5,000 ppm 



Date of First Dose 



Rats--2/19/80; mice-3/r2/80 



5/5/80 



Rat.s-male: 0, 1 ,300. or 2„500 ppm nitro- 

 furantoin in feed; female: 0, 600, or 

 1 ,300 ppm; mice -0, 1 ,300, or 2,,5()0 ppm 



Rats-2/26/81; mice -2/19/81 



Date of Last Dose 



RaLs--3/3/80; mice -3/27/80 



8/3/80 



Rats-2/16/83; mice -2/9/83 



Duration of Dosing 



14 consecutive d 



13 wk 



103 wk 



Type and Frequency of Oliservation 



Observed 2 x d; weighed initially Observed 2 X d; weighed 1 X wk 



and 1 X wk thereafter 



Observed 2 X d; weighed initially, 1 x wk 

 for 12 wk (rats) or 13 wk (micel, and then 

 1 X mo; palpated at weighing starting at 

 w k 44 or earlier if masses were noted 



Necropsy and Histologic E.xaniinations 



Necropsy performed on all animals; 

 histologic exams not performed 



Necropsy performed on all animals; 

 the following tissues examined histo- 

 logically for control and high dose 

 groups: adrenal glands, brain, cecum, 

 colon, esophagus, heart, kidneys, 

 liver, lungs and bronchi, mammary 

 gland, mandibular and mesenteric 

 lymph nodes, pancreas, parathyroid 

 glands, pituitary gland, prostate/tesles/ 

 seminal vesicles or ovaries/uterus, 

 regional lymph nodes, salivary glands, 

 skin, small intestine, spleen, sternum 

 including marrow, stomach, thigh 

 muscle, thymus, thyroid gland, 

 trachea, and urinary bladder. Liver 

 weights recorded at necropsy 



Necropsy and histologic exams performed 

 on all animals; the following tissues 

 examined histologically: adrenal glands, 

 brain, cecum, colon, duodenum, esoph- 

 agus, gallbladder (mice), gross lesions, 

 heart, ileum, jejunum, kidneys, larynx, 

 liver, lungs and mainstem bronchi, mam- 

 mary gland, mandibular and mesenteric 

 lymph nodes, nasal cavity and turbinates, 

 pancreas, parathyroid glands, pituitary 

 gland, preputial or clitoral gland, pros- 

 tate/testes/seminal vesicles/epididymis 

 or ovaries/uterus, rectum, regional lymph 

 nodes, salivary glands, skin, spleen, ster- 

 nebrae or femur or vertebrae including 

 marrow, stomach, thymus, thyroid gland, 

 ti.ssue masses, trachea, and urinary 

 bladder 



ANIMALS AND ANIMAL MAINTENANCE 



Strain and Species 



F344/N rats; B6C3Fi mice 



Animal Source 



Rats-Charles River Breeding 

 Laboratories (Portage, MI); 

 mice-Charles River Breeding 

 Laboratories ( Kingston, NY ) 



Study Laboratory 



Southern Research Institute 



F344/N rats; B6C3F, mice 



Charles River Breeding Laboratories 

 (Kingston, NY) 



Southern Research Institute 



F344/N rats; B6C3F, mice 



Harlan Industries (Indianapolis, IN) 



Southern Research Institute 



Method of Animal Identification 



Ear marked with poultry punch 



Ear marked with poultry punch 



Ear marked with poultry punch 



Nitrofurantoin, NTP TR 341 



30 



