The Laboratory of Mathematical Chemistry (LMC) was established 30 years ago, in Burgas, Bulgaria, within the University ‘Prof. Dr. Asen Zlatarov’. Nowadays, the Laboratory is one of the most influential molecular modelling labs worldwide.

1. 1
Ovanes Mekenyan
Laboratory of Mathematical Chemistry
University “Prof. As. Zlatarov”, Bourgas, Bulgaria
London, November, 2014

2. 2
“Assen Zlatarov”
UNIVERSITY
BURGAS

3. 3
The best town for living in Bulgaria for 2013-14

4. The need of alternative testing strategies avoiding animal use
4
Timeline
Enormous annual use of experimental animals worldwide
Regulatory Acceptance
in vivo

5. The need of alternative testing strategies avoiding animal use
5
Timeline
Enormous annual use of experimental animals worldwide
United States, 2010
>100 million
Canada, 2009
>3.3 million
Regulatory Acceptance
in vivo
United Kingdom, 2012
>4.1 million
peta.org

6. The need of alternative testing strategies avoiding animal use
6
Development of highly reliable in vitro test
Timeline
in vivo in vitro
Regulatory Acceptance

7. The need of alternative testing strategies avoiding animal use
7
Computational In silico testing
Timeline
in vivo in vitro in silico
Regulatory Acceptance

8. 8
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

9. QSAR and read-across methods used for submissions to the ECHA
9
for existing substances at or above 1000 tpa*
(2011 ECHA report)
QSAR Read across 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
NICEATM2
USA
ECVAM1
EU
1European Center for the Validation of Alternative Methods
2NTP Interagency Center for the Evaluation of Alternative Toxicological Methods/Interagency Coordinating Committee on the
Validation of Alternative Methods
3Japanese Center for the Validation of Alternative Methods
4Korean Center for the Validation of Alternative Methods
JaCVAM3
Japan
KoCVAM4
Korea
Health Canada
They shared common activities on utilization of alternative to Animal testing
by cooperation in a single organization:
International Cooperation on Alternative Test Methods
(ICATM)

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Global Scientific centers for alternative testing strategies
NICEATM2
USA
ECVAM1
EU
1European Center for the Validation of Alternative Methods
2NTP Interagency Center for the Evaluation of Alternative Toxicological Methods/Interagency Coordinating Committee on the
Validation of Alternative Methods
3Japanese Center for the Validation of Alternative Methods
4Korean Center for the Validation of Alternative Methods
JaCVAM3
Japan
KoCVAM4
Korea
Health 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

13. 13
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 models
on 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 vitro
rat 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
Skin
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
Biodegradation
Identifying stable degradants

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Major scientific achievements of LMC
Global systems for hazard assessment
•OECD QSAR TOOLBOX
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

20. Category concept and read-across
Software for grouping chemicals into categories
and filling gaps in (eco)toxicity data needed for assessing the hazards of chemicals
TOXIC?
ICG50=?
TOXICITY (IGC50)
logKow
No data

21. Category concept and read-across
Software for grouping chemicals into categories
and filling gaps in (eco)toxicity data needed for assessing the hazards of chemicals
TOXICITY (IGC50)
logKow
Collecting Analogs - Aldehydes “Schiff base formers”
Predicted ICG50 – 1.52x102 mg/L
Aldehyde – “Schiff base former”

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Major scientific achievements of LMC
Global systems for hazard assessment
HESS SYSTEM - JAPAN
Hazard Evaluation Support System Integrated Platform
Supported by the New Energy and Industrial Technology
Development Organization
JAPAN
DEVELOPED by

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Major scientific achievements of LMC
Global systems for hazard assessment
HESS SYSTEM - JAPAN
Hazard Evaluation Support System Integrated Platform
For predicting repeated dose toxicity
Supported by the New Energy and Industrial Technology
Development Organization
JAPAN
DEVELOPED by

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Major scientific achievements of LMC
Simulating metabolism
Predicting fate and hazard accounting for metabolism
LMC products

25. Simulation of metabolism
Human Health – Skin metabolism
Phase II reactions
Protein conjugate
Reactive species

26. Simulation of metabolism
Human Health – Liver S9
Cl
Cl
O
Cl
OH
Cl
O
Mutagenic metabolite

27. Simulation of metabolism
Biodegradation
CH2
O
O
O OH
CH2 OH
OH
CH2
HO
O OH
O
Stable degradant

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Major scientific achievements of LMC
Trainings on QSAR Toolbox and OASIS models
ECHA

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Trainings on QSAR Toolbox and OASIS models
Tokyo
Major scientific achievements of LMC

30. Sydney
30
Major scientific achievements of LMC
Trainings on QSAR Toolbox and OASIS models

31. Canberra
31
Major scientific achievements of LMC
Trainings on QSAR Toolbox and OASIS models

32. Madrid
32
Major scientific achievements of LMC
Trainings on QSAR Toolbox and OASIS models

33. Major scientific achievements of LMC
Barcelona
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Trainings on QSAR Toolbox and OASIS models

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Bern
Major scientific achievements of LMC
Trainings on QSAR Toolbox and OASIS models

35. Ottawa
35
Major scientific achievements of LMC
Trainings on QSAR Toolbox and OASIS models

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Major scientific achievements of LMC
Trainings on QSAR Toolbox and OASIS models
Oxford

37. Regulatory agencies – major partners of LMC

38. Industrial companies – major partners of LMC

39. Laboratory of Mathematical Chemistry
Let’s Take a Break
We’ll Back in 5 Mins
“Assen Zlatarov”
UNIVERSITY
Bourgas
BULGARIA

40. Laboratory of Mathematical Chemistry
“Assen Zlatarov”
UNIVERSITY
Bourgas
BULGARIA

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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.