## Abstract

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 (ED_{50})) 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 ED_{50}. 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.

Original language | English |
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Pages (from-to) | S528-S539 |

Journal | APMIS, Supplement |

Volume | 109 |

Issue number | 103 |

State | Published - 2001 |

Externally published | Yes |

## Keywords

- Dose-response
- Endocrine disruptor
- Endogenous dose
- Michaelis-Menten
- Non-hormone controlled background
- Risk assessment
- Threshold