PMID: 7846314Dec 1, 1994Paper

Reproducibility of the dose-response curve of steroid-induced cleft palate in mice

Risk Analysis : an Official Publication of the Society for Risk Analysis
S C FreniG E Moore

Abstract

Pregnant CD-1 mice were exposed to cortisone acetate at doses ranging from 20 to 100 mg/kg/day on days 10-13 by oral and intramuscular routes. Multiple replicate assays were conducted under identical conditions to assess the reproducibility of the dose-response curve for cleft palate. The data were fitted to the probit, logistic, multistage or Armitage-Doll, and Weibull dose-response model separately for each route of exposure. The curves were then tested for parallel slopes (probit and logistic models) or coincidence of model parameters (multistage and Weibull models). The 19 replicate experiments had a wide range of slope estimates, wider for the oral than for the intramuscular experiments. For all models and both routes of exposure the null hypothesis of equality of slopes was rejected at a significant level of p < 0.001. For the intramuscular group of replicates, rejection of slope equality could in part be explained by not maintaining a standard dosing regime. The rejection of equivalence of dose-response curves from replicate studies showed that it is difficult to reproduce dose-response data of a single study within the limits defined by the dose-response model. This has important consequences for quantitative risk asses...Continue Reading

References

Aug 1, 1992·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·J F HolsonJ F Young
Oct 1, 1991·The Cleft Palate-craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association·S C Freni, W F Zapisek
Sep 15, 1987·Toxicology and Applied Pharmacology·L S BirnbaumR E Morrissey
Feb 9, 1973·Annals of the New York Academy of Sciences·J C Shannon, R G Creech
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Related Concepts

Cortone acetate
Cleft Palate, Isolated
Adreson
Dose-Response Relationship, Drug
Two-Parameter Models
Likelihood Functions
Logistic Regression
Benefit-Risk Assessment

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