III. RESULTS: MICE 



Testis: Aspermatogenesis and degeneration of 

 the germinal epithelium were observed at in- 

 creased incidences in high dose male mice 

 (aspermatogenesis: control, 1/49; low dose, 1/49; 

 high dose, 16/50; degeneration of the germinal 

 epithelium. 0/49; 3/49; 23/50). 



Epididymis: Atypical cells and depletion were 

 observed in high dose male mice (atypical cells: 

 control, 0/50; low dose, 0/49; high dose, 26/50; 

 depletion: 1/50; 1/49; 15/50). 



Kidney: Mineralization of the medulla was ob- 

 served in high dose mice (male: control, 0/50; 

 low dose, 0/50; high dose, 17/50; female: 0/50; 

 0/50; 7/50). Dilatation of the tubules was 

 observed in high dose male mice (male: 0/50; 

 0/50; 14/50; female: 0/50; 1/50; 1/50). 



Adrenal Glands: Cortical spindle cell hyper- 

 plasia was observed at increased incidences in 

 dosed female mice (male: control, 5/50; low dose, 

 3/49; high dose, 4/50; female: 3/50; 41/50; 45/50). 

 A spindle cell (adrenal capsule) adenoma was 

 seen in 1/50 low dose female mice, and a spindle 

 cell (adrenal capsule) carcinoma was seen in 

 1/49 low dose male mice. The historical inci- 

 dences of these tumors are unknown because 

 neither has been entered into the data base as a 

 category separate from adenoma, NOS. Pheo- 

 chromocytomas or malignant pheochromo- 

 cytomas (combined) in male mice occurred with 

 a significant negative trend; the incidences in 

 the dosed groups were significantly lower than 

 that in the controls (Table 28). 



TABLE 28. 



ADRENAL MEDULLARY LESIONS IN MALE MICE IN THE TWO-YEAR FEED STUDY OF 



NITROFURANTOIN 



Control 



1.300 ppm 



2,500 ppm 



Hyperplasia 



Overall Rates 



Pheochromocytoma 



Overall Rates 

 Adjusted Rates 

 Terminal Rates 

 Day of First Observation 

 Life Table Tests 

 Logistic Regression Tests 



Malignant Pheochromocytoma 



Overall Rates 



Pheochromocytoma or Malignant Pheochromocytoma (a) 



Overall Rates 

 Adjusted Rates 

 Terminal Rates 

 Day of First Observation 

 Life Table Tests 

 Logistic Regression Tests 



(a)Historical incidence atstudy laboratory (mean ± SD): 4/437(1% ± 1%); historical incidence in NTP studies: 25/1,962 

 (1% ± 2%) 



59 



Nitrofurantoin, NTP TR 341 



