Pathology requirements for rodent two-year studies. I. A review of current procedures.

In the early 1970s the National Cancer Institute (NCI) initiated an animal bioassay program to determine if chemicals, to which the public are exposed, are hazardous by nature of their ability to induce cancer in animals. Experience with such tests led to the development of program guidelines in 1976. The pathology portion of this protocol included the histopathologic examination of a minimum of 25 organs/tissues from every animal on study. Since 1976 additional tissues have been added so that the current National Toxicology Program (NTP) protocol includes the histopathologic examination of 42-44 sections of 31-33 tissues from each animal. Thus an average of 25,000-26,000 sections are evaluated on a typical 600 animal (300 rats and 300 mice) study. A review of 277 NCI/NTP chemical bioassays which used this protocol revealed that this extensive list appears to be in excess of what is required to answer the question of whether a given chemical causes cancer in the test species. In addition, this protocol may be flawed in its ability to detect non-neoplastic chemically related disease.