Dose and time responses models for the incidence of bladder and liver neoplasms in mice fed 2-acetylaminofluorene continuously.

The incidence of bladder and liver neoplasms developed in mice continuously fed 2-acetylaminofluorene (2-AAF) in a multidisciplined study conducted at the National Center for Toxicological Research (NCTR) is represented using a probit model. The estimated incidences are made from time intervals using both sacrificed and dead and moribund mice. A probit log dose model is fit for each type of neoplasm at each time interval where the incidence permits. A probit log time model is fit for each of the neoplastic types for each dose level where the incidence permits. Finally, the response of liver neoplasms to 2-AAF is represented in the dose time plane using a probit plane model. 2-AAF appears to be an early acting bladder carcinogen and a late acting liver carcinogen. The bladders seem to be much more uniform in their response to the carcinogen than the livers and the uniformity of neither response appears to be age dependent. Although the time to appearence of both liver and bladder neoplasms is dose related, the increment in incidence of liver neoplasms with respect to time is not dose related while that of the bladder neoplasms is dose related. The data for bladder neoplasms do not contradict the "no threshold" theory of carcinogenesis while the liver data strongly support it.