APPENDIX I. AUDIT SUMMARY 



The experimental data, documents, and pathology specimens for the 2-year toxicology and carcino- 

 genesis studies of nitrofurantoin in rats and mice were audited for accuracy, consistency, complete- 

 ness, and compliance with Good Laboratory Practice regulations of the Food and Drug Administra- 

 tion (fully implemented by the National Toxicology Program (NTP) beginning October 1, 1981). The 

 animal studies were conducted for the NTP by Southern Research Institute (Birmingham, AL) under 

 a subcontract with Tracor Jitco, Inc., until May 31, 1982, and then under contract with the National 

 Institute of Environmental Health Sciences (NIEHS). Animal exposure to the chemical in feed began 

 in February 1981. The retrospective audit was conducted for the NIEHS at the NTP Archives in June 

 1986 by Dynamac Corporation,. J. C. Bhandari, D.V.M., Ph.D., Principal Investigator. The other indi- 

 viduals who conducted the audit are listed in the full audit report, which is on file at the NIEHS. The 

 audit included a review of: 



1. AH records concerning animal receipt, quarantine, randomization, and disposition prior to 

 study start. 



2. Body weight, feed consumption, and clinical observation data for a random 10% sample of the 

 study animals. 



3. All inlife records, including protocol, correspondence, environmental conditions, palpable 

 masses, mortality, animal identification, and correlation of final inlife observation of masses, 

 date of death, and disposition with necropsy records. 



4. All chemistry records. 



5. All postmortem records for individual animals concerning identification, disposition codes, 

 condition codes, correlations between gross observations and microscopic diagnoses, and tis- 

 sue accountability. 



6. All wet tissue bags for inventory and wet tissues from a random 10% sample of the study ani- 

 mals, plus other relevant cases, to verify animal identification and examine for untrimmed 

 potential lesions 



7. Blocks and slides of tissues from control and high dose groups of study animals to examine for 

 proper match and inventory. 



8. Comparison of individual animal data tables. 



9. Draft (4/87) of the NTP Technical Report on the 2-year studies of nitrofurantoin. 



Inlife procedures and events were documented adequately by the archival records with the exception 

 of analytical data for chemical/vehicle samples in the animal room and bulk chemical reanalysis 

 within 30 days prior to initiation of the study. The relatively few audit findings from review of the in- 

 life records were miscellaneous and minor; for example, four mice (one control male, two control fe- 

 males, and one high dose female) were coded as moribund kill in clinical records and were coded as 

 found dead in necropsy records. No corresponding necropsy descriptions of masses were found for five 

 rats; these discrepancies were resolved by examination of the wet tissues. Animal disposition for one 

 control male rat (animal no. 10) and one high dose male mouse (animal no. 7) was found to be recorded 

 in error in EISRPTOl . Because the resulting changes in the statistical analyses did not infiuence in- 

 terpretation of the studies, these changes were not incorporated into the Technical Report. 



Inspection of wet tissues for individual animal identifiers showed that 42/48 rats and 31/34 mice were 

 identified correctly by their residual tissues. All animals that were cross-checked were correctly 

 identified, with the exception of one control male rat with a torn ear that prevented further verifica- 

 tion. The audit identified five untrimmed potential lesions in the wet tissues of 48 rats examined and 

 three untrimmed potential lesions in 34 mice examined. These lesions were in nontarget tissues and 

 were examined by NTP pathologists. The correlation between gross observation and microscopic di- 

 agnoses was very good (only one noncorrelation in rats and three in mice). Full details of these and 

 other audit findings are presented in the audit report. In conclusion, the study records at the NTP 

 Archives support the data and results presented in the NTP Technical Report. 



Nitrofurantoin, NTP TR 341 218 



