Using the NTP database to assess the value of rodent carcinogenicity studies for determining human cancer risk

The large database of carcinogenicity results generated by the National Toxicology Program (NTP) provides a unique opportunity to critically evaluate important scientific issues such as (1) the frequency of positive outcomes, (2) the interspecies correlation in carcinogenic response between rats and mice, (3) the correlation between body weight and tumor incidence, (4) estimates of the false-positive and false-negative rates, and (5) the frequency of decreasing tumor incidences. Such database evaluations enable us to better understand the value and limitations of rodent carcinogenicity studies for determining human cancer risk. However, as the NTP database becomes increasingly accessible to the general scientific community, there is also increased opportunity for misuse of the database. This article reexamines and updates previous database evaluations, presents four scientific principles that should be employed by anyone attempting to use this database, and illustrates how failure to apply these principles can lead to misleading results.