• As part of the BU Superfund Research Program, I collaborate with Dr. Jennifer Schlezinger on experimental studies of chemical mixtures.

• We are currently examining biologically-based, mathematical models of chemical interactions using kinetic models of receptor-ligand systems. More to come!
• As part of the BU Superfund Basic Research Program, I collaborate with Dr. Jennifer Schlezinger on experimental studies of chemical mixtures.

• 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, 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, Hahn ME, Webster TF. Generalized Concentration Addition Predicts Joint Effects of Aryl Hydrocarbon Receptor Agonists with Partial Agonists and Competitive Antagonists.Environ Health Perspect. In press. [Online 22 December 2009]. The full text is freely available doi:10.1289/ehp.0901312.

• 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. Accepted.

• 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 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. 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 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, Goteborg, Sweden, 31 May-4 June, 2009.

• Howard GJ, Webster TF. Generalized concentration addition: A method for examining mixtures containing partial agonists. Journal of Theoretical Biology. [Accepted][Online 5 April 2009]. Abstract: doi:10.1016/j.jtbi.2009.03.030.

• Howard GJ, Webster TF. Generalized concentration addition: A method for examining mixtures containing partial agonists. Journal of Theoretical Biology. [Accepted][Online 5 April 2009].

• Greg Howard and I are currently examining biologically-based, mathematical models of chemical interactions using kinetic models of receptor-ligand systems. More to come!

• Howard GJ, Webster TF. Generalized concentration addition: A method for examining mixtures containing partial agonists. Journal of Theoretical Biology. [Accepted][Online 5 April 2009].

• March 2009: Our new paper is in press at Journal of Theoretical Biology.

• Howard GJ, Webster TF. Generalized concentration addition: A method for examining mixtures containing partial agonists. Journal of Theoretical Biology. [Accepted]

• 20 May 2008: Doctoral student Greg Howard defends his dissertation on Assessing the Combined Effects of Similarly-Acting Agents.

• 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. 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, 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. Organohalogen Compounds 2007; 69:1065-1068.

• 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.

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]

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]

Harry Potter and synergy

• "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]

• Howard GJ, Schlezinger JJ, Webster TF. Interactions of TCDD with AhR partial agonists and a competitive antagonist: implications for TEFs. To be presented at the 27th International Symposium on Halogenated Persistent Organic Pollutants (Dioxin 2007), Tokyo, 2-7 September.

• Howard GJ, Schlezinger JJ, Webster TF. Interactions of TCDD with AhR partial agonists and a competitive antagonist: implications for TEFs. To be presented at the 27th International Symposium on Halogenated Persistent Organic Pollutants (Dioxin 2007), Tokyo, 2-7 September.

• 21 June 2007: Doctoral student Greg Howard wins best poster award at 2007 Society for Epidemiologic Research Conference. See Howard G, Webster T. Contrasting Theories of Additivity, Synergy, and Antagonism in Epidemiology and Toxicology. American Journal of Epidemiology 2007; 165(11) Suppl: S62.

• More News & Awards

• 21 June 2007: Doctoral student Greg Howard wins best poster award at 2007 Society for Epidemiologic Research Conference. See Howard G, Webster T. Contrasting Theories of Additivity, Synergy, and Antagonism in Epidemiology and Toxicology. American Journal of Epidemiology 2007; 165(11) Suppl: S62.

• 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.

• 21 June 2007: Doctoral student Greg Howard wins best poster award at 2007 Society for Epidemiologic Research Conference. See Howard G, Webster T. Contrasting Theories of Additivity, Synergy, and Antagonism in Epidemiology and Toxicology.

• More News & Awards'''

News

• Greg Howard wins best poster award at 2007 Society for Epidemiologic Research Conference. See Howard G, Webster T. Contrasting Theories of Additivity, Synergy, and Antagonism in Epidemiology and Toxicology.

• Greg Howard wins best poster award at 2007 Society for Epidemiologic Research Conference. See Howard G, Webster T. Contrasting Theories of Additivity, Synergy, and Antagonism in Epidemiology and Toxicology.

News Greg Howard wins best poster award at 2007 Society for Epidemiologic Research Conference. See Howard G, Webster T. Contrasting Theories of Additivity, Synergy, and Antagonism in Epidemiology and Toxicology.

• As part of the BU Superfund Basic Research Program, I collaborate with Dr. Jennifer Schlezinger and Dr. Mark Hahn on experimental studies of chemical mixtures.

• Howard GJ, Schlezinger JJ, Webster TF. A Generalized Concentration Addition Model Predicts Joint Effects of TCDD and Partial-Agonist PCBs. To be presented at the American Chemical Society Annual Meeting, 19-23 August 2007, Boston, MA. ACS 2007

• Howard GJ, Schlezinger JJ, Webster TF. A Generalized Concentration Addition Model Predicts Joint Effects of TCDD and Partial-Agonist PCBs. To be presented at the American Chemical Society Annual Meeting, 19-23 August 2007, Boston, MA. ACS 2007

• 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.

News: Greg Howard wins best poster award at 2007 Society for Epidemiologic Research Conference. See Howard G, Webster T. Contrasting Theories of Additivity, Synergy, and Antagonism in Epidemiology and Toxicology.

News: Greg Howard wins best poster award at 2007 Society for Epidemiologic Research Conference. See Howard G, Webster T. Contrasting Theories of Additivity, Synergy, and Antagonism in Epidemiology and Toxicology.

My research:

Publications

Presentations

News: Greg Howard awarded best poster award at 2007 Society for Epidemiologic Research Conference. See Howard G, Webster T. Contrasting Theories of Additivity, Synergy, and Antagonism in Epidemiology and Toxicology.

My research:

Publications

Presentations

News: Greg Howard awarded best poster award at 2007 Society for Epidemiologic Research Conference. See Howard G, Webster T. Contrasting Theories of Additivity, Synergy, and Antagonism in Epidemiology and Toxicology.

• Howard G, Webster T. Contrasting Theories of Additivity, Synergy, and Antagonism in Epidemiology and Toxicology. Society for Epidemiologic Research. Boston, 19-22 June 2007. 

• Howard GJ, Schlezinger JJ, Webster TF. A Generalized Concentration Addition Model Predicts Joint Effects of TCDD and Partial-Agonist PCBs. Society of Toxicology Annual Meeting. 25-29 March 2007, Charlotte, NC.

• Howard GJ, Schlezinger JJ, Webster TF. A Generalized Concentration Addition Model Predicts Joint Effects of TCDD and Partial-Agonist PCBs. 'Society of Toxicology Annual Meeting''. 25-29 March 2007, Charlotte, NC.

Presentations

• Howard GJ, Schlezinger JJ, Webster TF. A Generalized Concentration Addition Model Predicts Joint Effects of TCDD and Partial-Agonist PCBs. Society of Toxicology Annual Meeting. 25-29 March 2007, Charlotte, NC.

(:title Interactions of Chemicals--Research at Boston University School of Public Health:)

and E_i,b are, respectively, the concentrations of A and B that individually lead to effect level i.

and E_i,b are, respectively, the concentrations of A and B that individually lead to effect leveli.

and E_i,b are, respectively, the concentrations of A and B that individually lead to effect level i.

and E_i,b are, respectively, the concentrations of A and B that individually lead to effect level i

where E_i,a and E_i,b are, respectively, the concentrations of A and B that lead individually lead to effect level i

where E_i,a_' and E_i,b_'

and E_i,b

where E_i,a and 'E''_i,b

where ''E_i,a_' and 'E_i,b_'

+ B/E_i,b

concentration addition: A/E_i,a

"concentration addition: A/E''_i,a

"concentration addition: 'A/E'_i,a

f_b[B]

+ f_a[A]

 'fb[B'']

 fa[A]

'f_b[B'']

f_a[A]

independent action: f_ab[A,B] = f_a[A] + f_b[B] - f_a[A]

• 'f_b[B'']

effect summation: f_ab[A,B] = f_a[A]

Three definitions of additivity are typically used:
effect summation: f_ab_'[A,B] = f_a_'[A]

Three definitions of additivity are typically used:

• effect summation: f_ab[A,B]

• effect summation: f_ab[A,B]

effect summation: f_ab[A,B]

effect summation: f_ab[A,B]

Three definitions of additivity are typically used:\\

effect summation: f_ab[A,B]

effect summation: f_ab[A,B]

 effect summation:   fab[A,B]

 effect summation:   fab[A,B] \

 effect summation:   fab[A,B] 

Let's examine these ideas mathematically. We'll define

Three definitions of additivity are typically used:

 effect summation: 

Then effect summation means:

= f_a[A]

=f_a[A]

f_ab[A,B]

f_a[A] + f_b[B]

f_a_'[A] + f_b_'[B]

f_a[A] +

f_a[A] f_b[B]

= f_a_'[A] + f_b_'[B]

Let's examine this idea mathematically. We'll define

Then effect summation means

=f_A[A]

f_A[A]

f_A[A]

%f_A[A]%

f_A[A]

+ f_B[B]

f_a[A]

+ f_b[B]

f_a

[A] + f_b[B]

= f'_a_[A] + f'_b_[B]

[A,B] = f'_a_[A] + f'_b_[B]

Then effect summation means

Let's examine this idea mathematically. We'll define

Then effect summation means

• Doctoral student Greg Howard and I are currently examining biologically-based, mathematical models of chemical interactions using kinetic models of receptor-ligand systems. More to come!

• Doctoral student Greg Howard and I are currently examining biologically-based, mathematical models of chemical interactions using kinetic models of receptor-ligand systems. More to come!

Intrigued?

• Doctoral student Greg Howard and I are currently examining biologically-based, mathematical models of chemical interactions using kinetic models of receptor-ligand systems. More to come!

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?

Intrigued? Read more!

Answer

Interact Answer}Answer? Suppose you answer: "synergy, since the combination of A and B is greater than the individual results summed." Mathematically:

Attach:interactfigure2.tiff Δ

Attach:interactfigure2.tfif Δ

Attach:interactfigure2.tff Δ

The "obvious" answer is "synergy, since the combination of A and B is greater than the individual results summed." Mathematically:

   fAB(A,B)

The "obvious" answer is "synergy, since the combination of A and B is greater than the individual results summed"

The "obvious" answer is "synergy, since the combination of A and B is greater than their individuals results summed"

If you answered "synergy (obviously)" you might be in the majority but you'd be wrong.

If you answered "obviously, synergy" you might be in the majority but you'd be wrong.

Suppose that the above graph shows the result of experiments using 10 uM of compound A, 10 uM of compound B, 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

Suppose that the above graph shows the result of using 10 uM of compound A, 10 uM of compound B, and a mixture of 10 uM of A and 10 uM of B. What does this experiment demonstrate?

My research:

Attach: interact-figure.jpg

Attach interact-figure.jpg

Suppose that the above graph shows the result of using 10 ?M of compound A, 10 ?M of compound B, and a mixture of 10 ?M of A and 10 ?M 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

Suppose t

return to Tom Webster

Attach:figure.mht Δ

• As part of the BU Superfund Basic Research Program, I collaborate with Dr. Jennifer Schlezinger, Dr. Mark Hahn, and doctoral student Greg Howard on experimental studies of chemical mixtures.

• Doctoral student Greg Howard and I are currently examining biologically-based mathematical models of chemical interactions using kinetic models of receptor-ligand systems. More to come!

• Doctoral student Greg Howard and I are currently examining biologically-based mathematical models of chemical interactions using kinetic models of receptor-ligand systems. More to come!
• In the BU Superfund Program, I collaborate with Dr. Jennifer Schlezinger, Dr. Mark Hahn, and doctoral student Greg Howard on experimental studies of chemical mixtures.

• Doctoral student Greg Howard and I are currently examining biologically-based models of chemical interactions using kinetic models of receptor-ligand systems. More to come!

• Doctoral student Greg Howard and I are currently examining biologically-based models of chemical interactions using kinetic models of receptor-ligand interactions. More to come!

Publications

• 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

(:title Interactions of Chemicals:)

return to Tom Webster