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Workshop on Modeling Reactive Toxicity, Logan, UT, March 23-24, 2010

Utah STate University Campus

3rd Workshop on Reactive Toxicity University Inn and Conference Center Utah State University March 23-24, 2010

Predicting the hazards of reactive chemicals is a major uncertainty in safety assessment because of inadequate models for chemical reactivity, itself.  Two IQF retreats in Knoxville explored the role of reactive toxicity in predictive toxicology and published a conceptual framework for improving QSAR models for chemical reactivity.  That framework outlined a series of systematic databases for model compounds which mimic reactive sites in biological systems.  T.W Schultz et al. created the first of the databases for glutathione reactivity, and the data are used to predict a variety of assessment endpoints such as skin and lung sensitization, aquatic toxicity and cellular assays.  The Logan retreat by invitation only will review progress and discuss options for the next database.

Workshop Goals

The International QSAR Foundation has invited a number of international experts from the European Union, Canada, and the USA to a retreat at Utah State University in Logan, Utah to evaluate the use of model nucleophiles as an organizing principle for predicting the many adverse effects of reactive chemicals. Predicting the effects of chemicals involves the prediction of molecular interactions with biological systems as well as the biological consequences of those interactions.  Reactive chemicals form covalent bonds with macromolecules which increases the potency of chemicals as well as the spectrum of long-term effects.  Chemicals that selectively bind to thiol groups in proteins commonly impact the immune system which is observed as skin and lung sensitization as well as delayed organ failure.  Our framework suggests that if the reaction rates of chemicals toward model nucleophiles such as glutathione and lysine can be predicted, the reaction rates will correlate with endpoints used to assess skin sensitization, inhalation toxicity, hepatocyte toxicity and aquatic toxicity.

Last Updated (Saturday, 13 February 2010 08:05)

 

Agenda

Monday May 22
19h00 Group Dinner - Hamiltons Steak & Seafood, 2427 North Main – shuttle departs from hotel at 18h30

Tuesday March 23
08h30 Welcome & Introductions - Bill Doucette
08h45 Review of Purpose and Agenda - Gil Veith
09h00 Reactive Toxicity: Progress Report on Filling the Gap - Gil Veith
10h30 Coffee
10h45 GSH Reactivity: an in chemico method and overview of its database - Terry Schultz
11h30 Model improvement in the Skin Sensitization Consortium - Mike Comber

12h15 Catered Lunch
13h00 Current status of reactivity models in aquatic toxicity – Mark Cronin
13h45 Current status of reactivity models in inhalation toxicity – Kendall Wallace
14h30 Estimating reactivity from structure using the OECD (Q)SAR Application Toolbox – Terry Schultz

15h15 Break
15h30 Molecular mechanisms of hepatocyte cytotoxicity and reactivity of α,β- unsaturated carbonyls , quinones versus alkanals - Peter O’Brien
16h15 Charge to the group for selecting model nucleophiles – Gil Veith
19h00 Group Dinner - Le Nonne Ristorante - 129 North 100 East - – shuttle departs from hotel at 18h30

Wednesday March 24
08h45 Summary of Day 1- Gil Veith
09h00 Utilization of cysteine and lysine peptides for screening reactivity of skin sensitizers - Frank Gerberick
09h45 Cysteine vs lysine reactivity: a biological significance - Jean-Pierre Lepoittevin
10h30 Coffee

10h45 Reactions of aldehydes with proteins and cellular targets. - Jon Doorn
11h30 Opportunities for measuring amine reactivity under LINK – Mark Cronin
12h00 Catered Lunch
Transportation to airport as needed


13h00 2-Pyridone as a model for hard nucleophile reactivity - Gil Veith
13h30 Analytical Capabilities of Utah State University – Bill Doucette
14h00 Gaps in Current Models and Correlations - Group Discussion
15h00 Refreshments

15h30 Discussion of Next Steps in Database Development
Dinner on your own (keep receipts)

Thursday March 25
09h00 The Thursday morning session will prepare a summary of the discussions, is open to all interested participants, but not intended to delay your flights home. Participants with possible afternoon connections may leave Wednesday as needed. Those with morning flights will have Thursday airport transportation as needed.
12h00 Adjourn

Last Updated (Wednesday, 09 June 2010 11:29)

 

Presentations

Tuesday March 23
Reactive Toxicity: Progress Report on Filling the Gap Gil Veith ppt
GSH Reactivity: an in chemico method and overview of its database Terry Schultz ppt
Model improvement in the Skin Sensitization Consortium Mike Comber ppt
Current status of reactivity models in aquatic toxicity Kendall Wallace ppt
Current status of reactivity models in inhalation toxicity Mark Cronin ppt
Estimating reactivity from structure using the OECD (Q)SAR Application Toolbox Terry Schultz ppt
Wednesday March 24
Utilization of cysteine and lysine roulette en ligne peptides for screening reactivity of skin sensitizers Frank Gerberick ppt
Reactions of aldehydes with proteins and cellular targets Jon Doorn pptx
Opportunities for measuring amine reactivity under LINK Mark Cronin ppt
2-Pyridone as a model for hard nucleophile reactivity Gil Veith ppt
Analytical Capabilities of Utah State University Bill Doucette ppt

Last Updated (Monday, 14 June 2010 09:29)