TABLE i. RESULTS OF REFEREE ANALYSIS OF FORMULATED DIETS IN THE TWO YEAR FEED 



STUDIES OF NITROFURANTOIN 



Date IVIixed 



Target Concentration 

 (ppm) 



Determined Concentration (ppm) 



Study Laboratory (a) 



Referee Laboratory (b) 



02/11/81 

 10/28/81 

 06/02/82 

 11/17/82 



1,300 



«00 



2,500 



1 .300 



1,300 



593 



2,460 



1 ,240 



1 ,270 



640 



2,650 



1 ,290 



(a) Results of duplicate analysis 



(b) Results of triplicate analysis 



FOURTEEN-DAY STUDIES 



Pour- to five-week-old F344/N rats and 4- to 6- 

 week-old B6C3Fi mice were obtained from 

 Charles River Breeding Laboratories. Rats were 

 observed for 21 days and mice for 14 days before 

 being placed on study. Groups of five rats of 

 each sex were fed diets containing 0, 1,300, 

 2,500, 5,000, 10,000, or 20,000 ppm nitrofuran- 

 toin for 14 consecutive days Groups of five mice 

 of each sex were fed diets containing 0, 600, 

 1,300, 2,500, 5,000, or 10,000 ppm. Animals 

 were housed five per cage Feed and water were 

 available ad libitum. Further details of animal 

 maintenance are given in Table 5. 



THIRTEEN-WEEK STUDIES 



Thirteen-week studies were conducted to evalu- 

 ate the cumulative toxic effects of repeated expo- 

 sure to nitrofurantoin and to determine the con- 

 centrations to be used in the 2-year studies. 



Five- to six-week-old F344/N rats and B6C3Fi 

 mice of each sex were obtained from Charles 

 River Breeding Laboratories 18 days before be- 

 ing placed on study. Groups of 10 rats of each 

 sex were fed diets containing 0, 600, 1,300, 

 2,500, 5,000, or 10,000 ppm nitrofurantoin for 13 

 weeks. Groups of 10 mice of each sex were fed 

 diets containing 0, 300, 600, 1,300, 2,500, or 

 5,000 ppm. Animals were housed five per cage 

 Feed and water were available ad libitum. 



Animals were observed two times per day; mori- 

 bund animals were killed. Feed consumption 

 was measured once per week by cage Individual 

 animal weights were recorded once per week. 



At the end of the 13-week studies, survivors 

 were killed. A necropsy was performed on all 

 animals except those excessively autolyzed or 

 cannibalized. Liver weights were determined at 

 necropsy. Groups and tissues examined are 

 listed in Table 5 



TWO-YEAR STUDIES 



Study Design 



Groups of 50 female rats were fed diets contain- 

 ing 0, 600, or 1,300 ppm nitrofurantoin for 103 

 weeks Groups of 50 male rats and 50 mice of 

 each sex were fed diets containing 0, 1,300, or 

 2,500 ppm for 103 weeks. On January 8, 1982, 

 eight cages of control male rats were in- 

 advertently fed diets containing 600 ppm 

 nitrofurantoin. 



Source and Specifications of Animals 



The male and female F344/N rats and B6C3Fi 

 (C57BL/6N, female X C3H/HeN MTV", male) 

 mice used in these studies were produced under 

 strict barrier conditions at Harlan Industries. 

 Breeding stock for the foundation colonies at the 

 production facility originated at the National In- 

 stitutes of Health Repository. Animals shipped 

 for study were progeny of defined microflora- 

 associated parents that were transferred from 

 isolators to barrier-maintained rooms. Rats 

 were shipped to the study laboratory at 4-5 

 weeks of age and mice at 6-7 weeks of age. The 

 animals were quarantined at the study labora- 

 tory for 16 days. Thereafter, a complete necrop- 

 sy was performed on five animals of each sex and 



29 



Nitrofurantoin, NTP TR 341 



