Update in progress: Stay tuned!
Suppose that the above graph shows the result of experiments using 10 uM of compound B, 10 uM of compound A, and a mixture of 10 uM of A and 10 uM of B. What does this experiment demonstrate?
- Synergy of A and B
- Additivity of A and B
- Antagonism of A and B
- Don't know
- We are currently examining biologically-based, mathematical models of chemical interactions using kinetic models of receptor-ligand systems. More to come!
- We are working on methods for examining the health effects of mixtures in environmental epidemiology. Dr. Webster was on the organizing committee of a 2015 NIEHS workshop:
- As part of the BU Superfund Research Program, I collaborate with Dr. Jennifer Schlezinger on experimental studies of chemical mixtures.
- Webster TF. Mixtures of endocrine disruptors: How similar must mechanisms be for concentration addition to apply? Toxicology 2013; 313: 129– 133. [accepted 20 January 2013]. doi:10.1016/j.tox.2013.01.009
- Howard GJ, Webster TF. Contrasting Theories of Interaction in Epidemiology and Toxicology. Environ Health Perspect 2013; 121:1–6. [online 26 September 2012]. http://dx.doi.org/10.1289/ehp.1205889
- Howard GJ, Schlezinger JJ, Hahn ME, Webster TF. Generalized Concentration Addition Predicts Joint Effects of Aryl Hydrocarbon Receptor Agonists with Partial Agonists and Competitive Antagonists.Environ Health Perspect. 2010; 118(5):666-672 [Online 22 December 2009]. The full text is freely available doi:10.1289/ehp.0901312.
- Howard GJ, Webster TF. Generalized concentration addition: A method for examining mixtures containing partial agonists. Journal of Theoretical Biology 2009; 259:469–477. [Online 5 April 2009]. Abstract: doi:10.1016/j.jtbi.2009.03.030.
- Howard GJ, Schlezinger JJ, Webster TF. Interactions of TCDD with AhR partial agonists and a competitive antagonist: implications for TEFs. Organohalogen Compounds 2007; 69:1065-1068.
- Schlezinger JJ, Howard GJ, Hurst CH, Emberley JK, Waxman DJ, Webster T, Sherr DH. Environmental and endogenous peroxisome proliferator-activated receptor gamma agonists induce bone marrow B cell growth arrest and apoptosis: interactions between mono(2-ethylhexyl) phthalate, 9-cis-retinoic acid, and 15-deoxy-Delta12,14-prostaglandin J2. J Immunol 2004; 173(5): 3165-77. The full text is freely available here
- Webster, TF. How to add: Perspectives in toxicology & epidemiology. Complex Mixtures and Exposures: Analyzing, Modeling and Predicting Fate and Effects at Multiple Levels of Environmental and Biological Systems. (Woods Hole MA, April 23-24, 2012).
- Webster, TF. Mixtures of endocrine disruptors: how similar must mechanisms be for concentration addition to apply? Society of Toxicology (San Francisco, 11-15 March 2012).
- Webster, TF. Mixtures of endocrine disruptors: how similar must mechanisms be for concentration addition to apply? International Toxicology of Mixtures Conference (Arlington VA, 21-23 October 2011).
- Howard GJ, Schlezinger JJ, Hahn ME, Webster TF. Generalized Concentration Addition (GCA): A method for analyzing mixtures of full and partial agonists. International Toxicology of Mixtures Conference (Arlington VA, 21-23 October 2011).
- Howard GJ, Webster TF. Epidemiologic analysis of concentration-additive mixture data. International Toxicology of Mixtures Conference (Arlington VA, 21-23 October 2011).
- Webster, TF. Chair, Group on Reconciling Epidemiological and Toxicological Approaches to Mixtures. NIEHS Conference on Advancing Research on Mixtures: New Perspectives and Approaches for Predicting Adverse Human Health Effects (Chapel Hill, 26-27 September 2011).
- Howard GJ, Webster TF. Risk difference additivity is an inappropriate test of biological interaction for many combination exposures. International Society for Environmental Epidemiology (Barcelona Spain, 13-16 September 2011).
- Webster, T. Does 2+2=4? It depends what you mean by +. Society for Risk Analysis, New England. USEPA, Boston. 9 February 2011.
- Howard GJ, Schlezinger JJ, Webster TF. Method for assessing interactions of full and partial agonists: Application to AhR ligands. Presented at the SETAC Europe 19th Annual Meeting. 31 May-4 June, 2009, Goteborg, Sweden.
- Howard G, Schlezinger J, Webster TF. Mixtures of AhR Full Agonists, Partial Agonists, and Antagonists: Implications for TEFs. 47th Annual Meeting of the Society of Toxicology. 16-20 March 2008. Seattle, WA.
- Howard GJ, Schlezinger JJ, Webster TF. Interactions of TCDD with AhR partial agonists and a competitive antagonist: implications for TEFs. Presented at the 27th International Symposium on Halogenated Persistent Organic Pollutants (Dioxin 2007), Tokyo, 2-7 September.
- Howard GJ, Schlezinger JJ, Webster TF. Modeling Mixtures of Full and Partial Agonists Using Generalized Concentration Addition. Superfund Basic Research Program 20th Anniversary Meeting. Durham, NC. December 3-5, 2007.
- Howard GJ, Schlezinger JJ, Webster TF. A Generalized Concentration Addition Model Predicts Joint Effects of TCDD and Partial-Agonist PCBs. Presented at the American Chemical Society Annual Meeting, 19-23 August 2007, Boston, MA. ACS 2007
- Howard G, Webster T. Contrasting Theories of Additivity, Synergy, and Antagonism in Epidemiology and Toxicology. Society for Epidemiologic Research. Boston, 19-22 June 2007. American Journal of Epidemiology 2007; 165(11) Suppl: S62.
- Howard GJ, Schlezinger JJ, Webster TF. A Generalized Concentration Addition Model Predicts Interactions of TCDD with Partial-Agonist AhR Ligands. Society of Toxicology Annual Meeting. 25-29 March 2007, Charlotte, NC.
Harry Potter and chemical interaction
- "Golpatt's Third Law states that the antidote for a blended poison will be equal to more than the sum of the antidotes for each of the separate components."--Book VI, pg. 374 [thanks to Greg Howard for pointing this out]