A probabilistic statement of the structure activity relationship for environmental risk analysis

In this paper, we define a mode of biological response of an organism to a chemical in terms of a general mathematical model of the response surface. The model describes the combined effects of dose-level exposure and time-duration exposure using 570 96-hr toxicity tests with fathead minnows. The response surface along the dose and time axes for each chemical in these tests were completely defined by two scale factors, one for dose and one for time, and two form factors, one for dose and one for time. The scale factors for dose and time are proportional with the inverse of LC50 and Lt50, respectively. The form factors measure the relative response strategies with respect to dose and time exposures. Only the scale factor for the dose is correlated with the logarithm of the octanol water partition coefficient (log P) and molecular weight (Mw). Additional and independent observations beyond log P and Mw are needed to correlate various modes of chemical action with the form factors. It is shown that narcosis-producing chemicals can be distinguished from other classes of chemicals by the dominance of the response strategy with respect to the dose over time exposures.