Session III: Assessing Cumulative Effects of Endocrine Active Substances. Session III: Assessing Cumulative Effects of Endocrine Active Substances. What is cumulative risk and why is it of interest?
Session III: Assessing Cumulative Effects of Endocrine Active Substances
What is cumulative risk and why is it of interest?
What do we know about physiology and pharmacology of the endocrine system that can inform approaches to cumulative risk evaluations?
What’s known about responses to mixtures that can be applied to endocrine active substances?
U.S. EPA, 2003. Framework for Cumulative Risk Assessment. Risk Assessment Forum, Washington. EPA/630/P-02/001F.
Cut & Pasted from: Active Substances
Jerry Heindel Ph/D. NIEHS
EED Gordon Conference June 2008
Allegations of Effects
Concerns for Health Effects from Mixtures
Charlees Active Substances G et al.
Analysis of the interaction of
phytoestrogens and synthetic
chemicals: An in vitro/in vivo
Toxicology and Applied Pharmacology
Volume 218, February 2007, Pages 280-288
Silva E, Rajapakse N, Kortenkamp A, Something from "nothing" - Eight weak estrogenic chemicals combined at concentrations below NOECs produce significant mixture effectsEnviron. Sci. Technol. 36 (8): 1751-1756 APR 15 2002
Operational Definitions Active Substances
Begins with the identification of a group of chemicals – the common mechanism group - induce a common toxic effect by a common mechanism of toxicity
Dose-response analysis on each member to determine its toxic potency for the common toxic effect
For estimating toxic potency – needs to be be conducted on a uniform basis (i.e., same measure of potency, for the same effect, from the same test species/sex using studies of comparable methodology)
Use of dose addition for determining the combined risk
Cumulative Risk: Active SubstancesIs It Relevant for Endocrine Active Substances?