Application of a biologically-based RFD estimation method to tetrachlorodibenzo-p-dioxin (TCDD) mediated immune suppression and enzyme induction.
The current methods for a reference dose (RfD) determination can be enhanced through the use of biologically-based dose response analysis. Methods developed here utilizes information from tetrachlorodibenzo-p-dioxin (TCDD) to focus on noncancer endpoints, specifically TCDD mediated immune system alterations and enzyme induction. Dose-response analysis, using the Sigmoid-Emax (EMAX) function, is applied to multiple studies to determine consistency of response. Through the use of multiple studies and statistical comparison of parameter estimates, it was demonstrated that the slope estimates across studies were very consistent. This adds confidence to the subsequent effect dose estimates. This study also compares traditional methods of risk assessment such as the NOAEL/safety factor to a modified benchmark dose approach which is introduced here. Confidence in the estimation of an effect dose (ED10) was improved through the use of multiple datasets. This is key to adding confidence to the benchmark dose estimates. In addition, the Sigmoid-Emax function when applied to dose-response data using nonlinear regression analysis provides a significantly improved fit to data increasing confidence in parameter estimates which subsequently improve effect dose estimates.
McGrath
L F
LF
New Jersey Graduate Program in Public Health, UMDNJ-Robert Wood Johnson Medical School, Piscataway 08854-5632, USA.
Georgopoulos
P
P
Gallo
M A
MA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects*; D005260:Female; D000882:Haplorhini; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D051379:Mice; D019055:No-Observed-Adverse-Effect Level; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage* / Q000633:toxicity*; D018570:Risk Assessment; D012449:Safety; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D000072317:Polychlorinated Dibenzodioxins