III. RESULTS: MICE 



Hematopoietic System: Lymphomas in female 

 mice occurred with a significant positive trend 

 by the logistic regression test; the incidence in 

 the high dose group was not significantly 

 greater than that in the controls (Table 26). 



Uterus: Suppurative inflammation was ob- 

 served in 11/50 control mice but in none of the 

 dosed animals. Adenocarcinomas were seen in 

 1/50 low dose and in 1/50 high dose mice. The 

 highest observed incidence of uterine adenomas 

 or adenocarcinomas (combined) in untreated his- 

 torical control female B6C3Fi mice is 1/47; the 

 overall historical incidence is 6/2,010 (0.3%). 



Liver: An Ito cell tumor was observed in 1/50 

 low dose and 1/50 high dose female mice. These 

 tumors consisted of well-differentiated fat cells 

 and varying amounts of collagen-containing 

 mesenchymal tissue. Previously, these tumors 

 have been classified as lipomas or liposarcomas 

 because of their component of fat cells. A lipoma 

 has been diagnosed in 1/2,033 (<0.1%) un- 

 treated historical control female B6C3Fi mice. 

 Hepatocellular adenomas and hepatocellular 

 adenomas or carcinomas (combined) in female 

 mice occurred with significant positive trends by 

 the logistic regression test; the incidences in the 

 dosed groups were not significantly different 

 from those in the controls (Table 27). 



TABLE 26. 



MAUGNANT LYMPHOMAS LN FE.MALE MICE I.\ THE TWO-YEAR FEED STUDY OF 



NITROFURANTOIN (a) 



Control 



1,300 ppm 



2,500 ppm 



Overall Rates 

 Adjusted Rates 

 Terminal Rates 

 Day of First Observation 

 Life Table Tests 

 Logistic Regression Tests 



(a) Historical incidence of lymphomasor leukemia (combined)atstudy laboratory (mean ± SD): 104/448(23% ± 7%); 

 historical incidence in NTP studies: 616/2,041(30% ± 12%) 



TABLE 27. HEPATOCELLULAR TUMORS IN FEMALE MICE IN THE TWO-YEAR FEED STUDY OF 



NITROFURANTOIN 



Control 



1,300 ppm 



2,.500 ppm 



Adenoma 



Overall Rates 

 Adjusted Rates 

 Terminal Rates 

 Day of First Observation 

 Life Table Tests 

 Logistic Regression Tests 



Carcinoma 



Overall Rates 



Adenoma or Carcinoma (a) 

 Overall Rates 

 Adjusted Rates 

 Terminal Rates 

 Day of First Observation 

 Life Table Tests 

 Logistic Regression Tests 



(a) Historical incidence at study laboratory (mean ± SD): 36/447(8% ± 5%); historical incidence in NTP studies: 177/2,033 

 (9% ± 5%) 



Nitrofurantoin, NTP TR 341 



58 



