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

R. M. Blair, H. Fang, D. Gaylor, D. M. Sheehan, N. Skakkebæk, M. Ritzén, M. Grumbach, S. Swan, M. Kogevinas, E. Gray

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 (Bnh), maximum response (Rmax), endogenous hormone level (D0), 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 Bnh and then normalized to Rmax, while dose data were adjusted to account for D0 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.

Original languageEnglish
Pages (from-to)S528-S539
JournalAPMIS, Supplement
Volume109
Issue number103
StatePublished - 2001
Externally publishedYes

Keywords

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

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