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

Using a biologically relevant mathematical model, the Michaelis-Menten equation, we examined published data from endocrine active chemicals for evidence of no-threshold dose-response curves. Data were fit to a modified Michaelis-Menten equation which accounted for total background response. Subsequently, the data sets were analyzed using non-linear regression in order to estimate the four parameters of interest (non-hormone controlled background (B-nh), maximum response (R-max) endogenous hormone level (D-0), and the dose at which a half-maximal response was observed (ED50)) and to determine the fit to the fully modified Michaelis-Menten equation. Subsequently, response data were adjusted to account for B-nh and then normalized to R-max while 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. Twenty-six of the data sets fit the modified Michaelis-Menten equation with high multiple correlation coefficients (r>0.90). The normalized data demonstrated a good fit to the modified Michaelis-Menten equation. These results indicate that a variety of biological responses fit the modified Michaelis-Menten equation, which does not have a threshold dose term.