General Concepts in QSAR for Using the  QSAR Application Toolbox <br />
Part IIiForming Chemical Categories<br />
What do we mean by a chemical category?<br />A chemical category is a group of chemicals with attributes in common:<br />S...
Annex IX of REACH <br />Substances whose physicochemical, toxicological and ecotoxicological properties are likely to be s...
Source:  OECD Manual for Investigation of High Production Volume (HPV) Chemicals. OECD Paris. <br />OECD Definition of Cat...
Forming Chemical Categories<br />Chemical categories are being grouped based on attributes important to toxicological beha...
General Concepts in QSAR for Using the  QSAR Application Toolbox <br />
Part IVQSAR and the OECD Toolbox<br />Integrating Methods for Convenience, Consistency and Documentation <br />
Why Do We Need the QSAR Toolbox?<br />Defining category boundaries requires the calculation of complex attributes of chemi...
QSAR Application Toolbox<br />Filling data gaps using available test data<br />and principles of predictive toxicology<br ...
General Objectives:<br />-ENV/JM(2006)47<br />QSAR Application Toolbox<br />Improve accessibility of (Q)SAR methods and da...
Typical queries with the  QSAR Application Toolbox<br />Is the chemical included in regulatory inventories or existing che...
Typical queries with the  QSAR Application Toolbox<br />Explore a chemical list for possible analogues using predefined, m...
QSAR Toolbox Workflow<br />The first version of the QSAR Toolbox is designed to <br />facilitate the work of hazard assess...
Logical sequence of Using Toolbox components<br />Chemical<br />Input<br />Chemical<br />Profiling<br />Category<br />Defi...
Logical sequence of Using Toolbox components<br />Chemical<br />Input<br />Chemical<br />Profiling<br />Category<br />Defi...
CAS#
SMILES/InChi
Draw Chemical Structure
Select from User List/Inventory</li></ul>B. Group of chemicals<br /><ul><li>User List
Inventory
Specialized Databases</li></li></ul><li>Logical sequence of Using Toolbox components<br />Chemical<br />Input<br />Chemica...
Predefined
Upcoming SlideShare
Loading in …5
×

General Concepts in QSAR for Using the QSAR Application Toolbox Part 3

3,366 views

Published on

Published in: Education, Technology, Business
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
3,366
On SlideShare
0
From Embeds
0
Number of Embeds
1,590
Actions
Shares
0
Downloads
39
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide

General Concepts in QSAR for Using the QSAR Application Toolbox Part 3

  1. 1. General Concepts in QSAR for Using the QSAR Application Toolbox <br />
  2. 2. Part IIiForming Chemical Categories<br />
  3. 3. What do we mean by a chemical category?<br />A chemical category is a group of chemicals with attributes in common:<br />Structure e.g., common substructure or electronic properties<br />Property e.g., similar physicochemical, topological, geometrical, or surface properties<br />Behavior e.g., toxicological response underpinned by common toxicity mechanisms <br />Function e.g., preservatives, solvents, detergents, fragrances, lubricants , heat transfer, etc.<br />
  4. 4. Annex IX of REACH <br />Substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or “category” of substances. <br />Application of the group concept requires that physicochemical properties, human health effects and environmental effects or environmental fate may be predicted from data for a reference substance within the group by interpolation to other substances in the group (read-across approach). This avoids the need to test every substance for every endpoint.<br />
  5. 5. Source: OECD Manual for Investigation of High Production Volume (HPV) Chemicals. OECD Paris. <br />OECD Definition of Category<br />A chemical category is a group of chemicals whose physicochemical and toxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity <br />These structural similarities may create a predictable pattern in any or all of the following parameters: physicochemical properties, environmental fate and environmental effects, and human health effects<br />
  6. 6. Forming Chemical Categories<br />Chemical categories are being grouped based on attributes important to toxicological behavior<br />Literature and other data sources are used to organize available data for common assessment endpoints<br />Read-across and trend analysis are used to extrapolate the data from tested chemicals to untested chemicals <br />In many cases, the analysis of trends (our examples in this lecture) is used to designate the boundaries for similarity in each of the categories<br />
  7. 7. General Concepts in QSAR for Using the QSAR Application Toolbox <br />
  8. 8. Part IVQSAR and the OECD Toolbox<br />Integrating Methods for Convenience, Consistency and Documentation <br />
  9. 9. Why Do We Need the QSAR Toolbox?<br />Defining category boundaries requires the calculation of complex attributes of chemicals to determine which attributes best explain available data<br />In many cases, metabolic simulators are needed to provide metabolic maps and active metabolites <br />To do trend analysis, hundreds of available data must be compiled and flexibly analyzed for trends<br />
  10. 10. QSAR Application Toolbox<br />Filling data gaps using available test data<br />and principles of predictive toxicology<br />Developed for OECD and ECHA by the Laboratory of<br /> Mathematical Chemistry, Bourgas, Bulgaria<br />Professor Ovanes Mekenyan, Head<br />
  11. 11.
  12. 12. General Objectives:<br />-ENV/JM(2006)47<br />QSAR Application Toolbox<br />Improve accessibility of (Q)SAR methods and databases<br />Facilitate selection of chemical analogues and categories<br />Integrate metabolism/mechanisms with categories and QSAR<br />Assist in the estimation of missing values for chemicals<br />
  13. 13. Typical queries with the QSAR Application Toolbox<br />Is the chemical included in regulatory inventories or existing chemical categories?<br />Has the chemical already been assessed by other agencies/organizations?<br />Would you like to search for available data on assessment endpoints for each chemical?<br />
  14. 14. Typical queries with the QSAR Application Toolbox<br />Explore a chemical list for possible analogues using predefined, mechanistic, empiric and custom-built categorization schemes?<br />Group chemicals based on common chemical/toxic mechanism and/or metabolism?<br />Design a data matrix of a chemical category?<br />
  15. 15. QSAR Toolbox Workflow<br />The first version of the QSAR Toolbox is designed to <br />facilitate the work of hazard assessors in filling data gaps <br />for untested chemicals through the use of chemical categories<br />
  16. 16. Logical sequence of Using Toolbox components<br />Chemical<br />Input<br />Chemical<br />Profiling<br />Category<br />Definition<br />Filling<br />Data <br />Gaps<br />Report<br />Hazard<br />Endpoints<br />
  17. 17. Logical sequence of Using Toolbox components<br />Chemical<br />Input<br />Chemical<br />Profiling<br />Category<br />Definition<br />Filling<br />Data<br />Gaps<br />Report<br />Hazard<br />Endpoints<br />User Alternatives for Chemical ID:<br />A. Single target chemical<br /><ul><li>Name
  18. 18. CAS#
  19. 19. SMILES/InChi
  20. 20. Draw Chemical Structure
  21. 21. Select from User List/Inventory</li></ul>B. Group of chemicals<br /><ul><li>User List
  22. 22. Inventory
  23. 23. Specialized Databases</li></li></ul><li>Logical sequence of Using Toolbox components<br />Chemical<br />Input<br />Chemical<br />Profiling<br />Category<br />Definition<br />Filling<br />Data<br />Gaps<br />Report<br />Hazard<br />Endpoints<br />General characterization schemes:<br /><ul><li>Substance information
  24. 24. Predefined
  25. 25. Mechanistic
  26. 26. Empirical
  27. 27. Custom
  28. 28. Metabolism</li></li></ul><li>Logical sequence of Using Toolbox components<br />Chemical<br />Input<br />Chemical<br />Profiling<br />Category<br />Definition<br />Filling<br />Data<br />Gaps<br />Report<br />Hazard<br />Endpoints<br />Compiling Endpoint Data (SIDS plus)<br /><ul><li>Aquatic Toxicity (complete AQUIRE)
  29. 29. Ecotoxicology (complete ECOTOX)
  30. 30. Bioaccumulation
  31. 31. Mutagenicity
  32. 32. Skin Sensitization
  33. 33. Carcinogenicity
  34. 34. Rodent Repeat Dose
  35. 35. Documented QSAR Estimates</li></li></ul><li>Chemical<br />Input<br />Chemical<br />Profiling<br />Category<br />Definition<br />Filling<br />Data<br />Gaps<br />Report<br />Hazard<br /> Endpoints<br />Forming and Pruning Categories:<br /><ul><li>Predefined
  36. 36. Mechanistic
  37. 37. Empirical
  38. 38. Custom
  39. 39. Metabolism</li></li></ul><li>Logical sequence of Using Toolbox components<br />Chemical<br />Input<br />Chemical<br />Profiling<br />Category<br />Definition<br />Filling<br />Data<br />Gaps<br />Report<br />Hazard<br />Endpoints<br />Forming and Pruning Categories:<br /><ul><li>Predefined
  40. 40. OECD categorization
  41. 41. US EPA categorization
  42. 42. Inventory affiliation
  43. 43. Database affiliation
  44. 44. Substance type</li></li></ul><li>Logical sequence of Using Toolbox components<br />Chemical<br />Input<br />Chemical<br />Profiling<br />Category<br />Definition<br />Filling<br />Data<br /> Gaps<br />Report<br />Hazard<br />Endpoints<br />Accepted Approaches<br /><ul><li>Read-across
  45. 45. Trend analysis
  46. 46. QSAR models</li></li></ul><li>Logical sequence of Using Toolbox components<br />Chemical<br />Input<br />Chemical<br />Profiling<br />Category<br />Definition<br />Filling<br />Data<br />Gaps<br />Report<br />Hazard<br />Endpoints<br />Report the results:<br /><ul><li>Estimate Reporting Formats (QMRF)
  47. 47. IUCLID 5 Harmonized Templates
  48. 48. SIDS Data Dossiers
  49. 49. Complete Session History
  50. 50. User-Defined Reports</li></li></ul><li>Summary <br />Explore a chemical list for possible analogues using predefined, mechanistic, empiric and custom-built categorization schemes?<br />Group chemicals based on common chemical/toxic mechanism and/or metabolism?<br />Design a data matrix of a chemical category?<br />

×