Threshold analysis of selected dose-response data for endocrine active chemicals

Using a biologically relevant mathematical model, the Michaelis-Menten equa tion, we examined published data from endocrine active chemicals for eviden ce of no-threshold dose-response curves. Data were fit to a modified Michae lis-Menten equation which accounted for total background response. Subseque ntly, the data sets were analyzed using non-linear regression in order to e stimate the four parameters of interest (non-hormone controlled background (B-nh), maximum response (R-max), endogenous hormone level (D-0), and the d ose at which a half-maximal response was observed (ED50)) and to determine the fit to the fully modified Michaelis-Menten equation. Subsequently, resp onse data were adjusted to account for B-nh and then normalized to R-max, w hile dose data were adjusted to account for D-0 and then normalized to the ED50. This data set was combined into a single, composite data set and fit to the fully modified Michaelis-Menten equation. We examined 31 data sets ( 24 endpoints) from studies on 9 different chemical/hormone treatments. Twen ty-six of the data sets fit the modified Michaelis-Menten equation with hig h multiple correlation coefficients (r>0.90). The normalized data demonstra ted a good fit to the modified Michaelis-Menten equation. These results ind icate that a variety of biological responses fit the modified Michaelis-Men ten equation, which does not have a threshold dose term.