Ovanes Mekenyan - Lush Prize Conference 2014
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1 London, November, 2014 Ovanes Mekenyan Laboratory of Mathematical Chemistry University “Prof. As. Zlatarov ”, Bourgas , Bulgaria
Transcript of Ovanes Mekenyan - Lush Prize Conference 2014
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London, November, 2014
Ovanes MekenyanLaboratory of Mathematical Chemistry
University “Prof. As. Zlatarov”, Bourgas, Bulgaria
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BURGAS
“Assen Zlatarov”UNIVERSITY
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The best town for living in Bulgaria for 2013-14
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The need of alternative testing strategies avoiding animal use
Timeline
Regulatory Acceptance
in vivo
Enormous annual use of experimental animals worldwide
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The need of alternative testing strategies avoiding animal use
Timeline
Regulatory Acceptance
in vivo
United States, 2010
>100 million
Canada, 2009
>3.3 million
United Kingdom, 2012
>4.1 million
peta.org
Enormous annual use of experimental animals worldwide
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The need of alternative testing strategies avoiding animal use
Timeline
Regulatory Acceptance
in vitroin vivo
Development of highly reliable in vitro test
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The need of alternative testing strategies avoiding animal use
Computational In silico testing
Timeline
Regulatory Acceptance
in vitroin vivo in silico
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Global regulations for chemical risk assessment
REACH -Registration, Evaluation, Authorisation and Restriction of Chemicals
ChAMP - The Chemical Assessment and Management Program
CSCL - Japanese Chemical Substances Control Law
Chemicals Management Plan
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QSAR and read-across methods used for submissions to the ECHA for existing substances at or above 1000 tpa*
(2011 ECHA report)
Read acrossQSAR env = environmental endpoint; hh = human health endpoint
*H. Spielmann et al. ATLA 39, 481–493, 2011
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Global Scientific centers for alternative testing strategies
2NTP Interagency Center for the Evaluation of Alternative Toxicological Methods/Interagency Coordinating Committee on the Validation of Alternative Methods3Japanese Center for the Validation of Alternative Methods
1European Center for the Validation of Alternative Methods
4Korean Center for the Validation of Alternative Methods
NICEATM2
USAECVAM1
EUJaCVAM3
JapanKoCVAM4
KoreaHealth Canada
They shared common activities on utilization of alternative to Animal testingby cooperation in a single organization:
International Cooperation on Alternative Test Methods(ICATM)
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Global Scientific centers for alternative testing strategies
2NTP Interagency Center for the Evaluation of Alternative Toxicological Methods/Interagency Coordinating Committee on the Validation of Alternative Methods3Japanese Center for the Validation of Alternative Methods
1European Center for the Validation of Alternative Methods
4Korean Center for the Validation of Alternative Methods
NICEATM2
USAECVAM1
EUJaCVAM3
JapanKoCVAM4
KoreaHealth Canada
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Scientific areas of LMC
•Applying molecular modeling for predicting toxicity of chemicals
Analyzing chemical structures
Explaining interaction mechanisms
Developing models
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Scientific areas of LMC
•Applying molecular modeling for predicting toxicity of chemicals
•Building information technologies for implementation of the models
Analyzing chemical structures
Explaining interaction mechanisms
Developing models
Integrating modelson software platforms
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Scientific areas of LMC
•Applying molecular modeling for predicting toxicity of chemicals
•Building information technology for implementation of the models
•Metabolism simulation
In silico simulation of metabolism
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Scientific areas of LMC
•Applying molecular modeling for predicting toxicity of chemicals
•Developing information technology for implementation of the models
•Metabolism simulation
In silico simulation of metabolism
in vivo/ in vitrorat metabolism
Predicting metabolic activation of chemicals
Identifying toxic metabolites
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Scientific areas of LMC
•Applying molecular modeling for predicting toxicity of chemicals
•Developing information technology for implementation of the models
•Metabolism simulation
In silico simulation of metabolism
Skinmetabolism
Predicting metabolic activation of chemicals
Identifying toxic metabolites
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Scientific areas of LMC
•Applying molecular modeling for predicting toxicity of chemicals
•Developing information technology for implementation of the models
•Metabolism simulation
In silico simulation of metabolism
Biodegradation
Identifying stable degradants
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Major scientific achievements of LMC
•OECD QSAR TOOLBOX
Global systems for hazard assessment
Freeware system developed with the scientific and financial assistance of:
and
DEVELOPED by
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Download statistics of QSAR Toolbox by registered users worldwide
Software for grouping chemicals into categories and filling gaps in (eco)toxicity data needed for assessing the hazards of chemicals
Category concept and read-across
TOXIC?ICG50=?
TOX
ICIT
Y (I
GC
50
)
logKow
No data
Software for grouping chemicals into categories and filling gaps in (eco)toxicity data needed for assessing the hazards of chemicals
Category concept and read-acrossTO
XIC
ITY
(IG
C5
0)
logKow
Aldehyde – “Schiff base former”
Collecting Analogs - Aldehydes “Schiff base formers”
Predicted ICG50 – 1.52x102 mg/L
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Major scientific achievements of LMC
Global systems for hazard assessment
Hazard Evaluation Support System Integrated Platform
Supported by the New Energy and Industrial Technology Development Organization
JAPAN
HESS SYSTEM - JAPAN
DEVELOPED by
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Major scientific achievements of LMC
Global systems for hazard assessment
Hazard Evaluation Support System Integrated PlatformFor predicting repeated dose toxicity
Supported by the New Energy and Industrial Technology Development Organization
JAPAN
HESS SYSTEM - JAPAN
DEVELOPED by
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Major scientific achievements of LMC
Simulating metabolism
Predicting fate and hazard accounting for metabolism
LMC products
Simulation of metabolism
Human Health – Skin metabolism
Protein conjugate
Phase II reactions
Reactive species
Simulation of metabolism
Human Health – Liver S9
Cl
Cl
O
Cl
OH
Cl
O
Mutagenic metabolite
Simulation of metabolism
Biodegradation
CH2
O
O
O OH
CH2 OH
OH
CH2
HO
O OH
O
Stable degradant
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Trainings on QSAR Toolbox and OASIS models
Major scientific achievements of LMC
ECHA
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Trainings on QSAR Toolbox and OASIS models
Tokyo
Major scientific achievements of LMC
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Sydney
Trainings on QSAR Toolbox and OASIS models
Major scientific achievements of LMC
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Canberra
Trainings on QSAR Toolbox and OASIS models
Major scientific achievements of LMC
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Madrid
Trainings on QSAR Toolbox and OASIS models
Major scientific achievements of LMC
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Barcelona
Trainings on QSAR Toolbox and OASIS models
Major scientific achievements of LMC
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Bern
Trainings on QSAR Toolbox and OASIS models
Major scientific achievements of LMC
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Ottawa
Trainings on QSAR Toolbox and OASIS models
Major scientific achievements of LMC
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Trainings on QSAR Toolbox and OASIS models
Major scientific achievements of LMC
Oxford
Regulatory agencies – major partners of LMC
Industrial companies – major partners of LMC
Let’s Take a Break We’ll Back in 5 Mins
“Assen Zlatarov”UNIVERSITY
BourgasBULGARIA
Laboratory of Mathematical Chemistry
“Assen Zlatarov”UNIVERSITY
BourgasBULGARIA
Laboratory of Mathematical Chemistry
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Instead of conclusion
Ones I`ve got a phone call from an old lady begging me to cure the tumor of her cat…
at that moment I understood that even with QSAR I am helping to save animals.
