Method of analysis of monotone dose-response probabilities after long-term exposure to a toxicant

A nonparametric hazard-function (HP) method for generating monotonically increasing incidence vs dose curves after long-term exposure to a toxic agent (e.g. radiation or chemical carcinogens) is described in detail in this paper. Here, incidence refers to the response-probability estimate that is adjusted for competing risks. The maximum likelihood principle was used to arrive at an appropriate point estimate of the cumulative hazard function (i.e. the negative natural logarithm of the proportion of the nonresponders) and the response probability for an array of doses that depends on the data set to be analyzed. The resultant point estimates can be used to develop or select an appropriate model for risk vs dose assessment. As an example of the application of the HF method, data for liver neoplasms caused by long-term exposure of mice to 2-acetylaminofluorene and data for radiation pneumonitis and pulmonary fibrosis caused by long-term exposure of dogs to ionizing radiation are analyzed.