National Toxicology Program

The National Toxicology Program (NTP) workshop, "Animal Models for the NTP Rodent Cancer Bioassay: Strains & Stocks -- Should We Switch?" was the first in a series of workshops associated with the NTP Roadmap to critically evaluate the NTP testing program and determine whether any refinements or new strategies were needed. One of the workshop's objectives was to determine whether the NTP F344 rat model continued to be appropriate to identify substances that may pose a carcinogenic hazard for humans. In addition to problems inherent in the F344 strain (mononuclear cell leukemia, testicular tumors) the NTP F344 rats had a number of other health related concerns, including infertility, sporadic seizures, spontaneous chylothorax, and absence of the mandibular lymph nodes. Furthermore, the F344 rat was not recommended by various regulatory agencies for use in reproductive and developmental toxicity studies. Participants at the workshop strongly advised the NTP to discontinue use of the then current F344 rat model and suggested three options: 1) re-establish the F344/N from another source, 2) create an F1 hybrid such as the F344/Brown Norway cross (FBNF1); or 3) consider using an alternative strain or stock such as the outbred Wistar Han. Initially a commercial source of the F344 was used, but after much research and deliberation, the NTP has made a decision to switch to the outbred Wistar Han rat.

The Wistar Han rat was selected because of its hardiness, overall low incidence of spontaneous background tumors, long survivability, moderate size, and robust reproductive characteristics. It is considered a good model for chronic inhalation studies because of its infrequent sporadic incidence of mononuclear cell leukemia, which often complicates identification of pulmonary and liver pathology. The Wistar Han is also considered an appropriate model for dosed feed, dosed water, and gavage administration studies in which dosing begins as young adults or in utero. In an effort to harmonize model use across NTP studies, the Wistar Han rat will be the principal rat model used in NTP studies unless otherwise specified based on study requirements. NTP studies include the rodent toxicity and carcinogenicity bioassay and prechronic toxicity studies, ADME and toxicokinetic studies, reproductive and developmental toxicity studies, immunotoxicity studies and toxicogenomic assays.