Project IUC AMBIT Workflow read across & category formation

41 Pages·2015·2.15 MB·English

REACH INFORMATION & EXPERIENCE EXCHANGE FORUM IV
19 JUNE 2015
CEFIC LRI Project EEM9.3

Linking LRI AMBIT Chemoinformatic

System with the IUCLID Substance
Dr. Volker Koch, Clariant
CEFIC RIEF IV
CEFIC LRI Project EEM9.3
Database to Support Read across of 19.06.2015
Substance Endpoint data & Category
Public
Formation
2
Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID
Introduction
Public
Dr. Volker Koch, Clariant
CEFIC RIEF IV
CEFIC LRI Project EEM9.3
19.06.2015
3 Confidential, Outline CLN CompTox Project
Dr. Volker Koch, Clariant, CEFIC RIEF IV, CEFIC LRI Project EEM9.3, 19.06.2015
Computational Toxicology (1)
Non-testing approaches are used to fill gaps in Human and
Environmental Safety Assessment (ECETOC, 2012 TR116) :
To avoid animal testing
Reduce resource costs
Bridge the gap of laboratory capacity availability
Methods used for read-across and Category formation
•Read-across - Uses endpoint information for one chemical to predict the
same endpoint for another chemical (also used in Category formation)
•Category formation of Chemicals - A Weight of Evidence approach
using experimental and estimated data from different category members
involving expert knowledge
Read-across and Category formation is supported by in-silico
tools (see ECETOC, 2012, TR 116) using various methodologies like
•QSARs, Expert systems allowing rule-based predictions , Similarity tools etc.
4 Confidential, Outline CLN CompTox Project
Dr. Volker Koch, Clariant, CEFIC RIEF IV, CEFIC LRI Project EEM9.3, 19.06.2015
Computational Toxicology (2)
 MAJOR GOALS OF THE CEFIC LRI PROJECT

 Enhancing the predictive power of in-silico tools like LRI
AMBIT Use of Substance data which are already available in a
company IUCLID Database. In addition CEFIC LRI is checking how
to receive the data from the ECHA Dissemination site for ca. 12000
substances. But other reliable data will be integrated as well

 Support read across and category formation workflows
Avoiding animal tests and enhance the justification for read across
and category formation as requested by authorities.

 Minimize overall testing and resource costs
Using available studies for other substances as well
5 Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID
Dr. Volker Koch, Clariant, CEFIC RIEF IV, CEFIC LRI Project EEM9.3, 19.06.2015
Project overview
Data
AMBIT FUNCTIONS
transfer
Assigning structures
-to constituents, impurities …
Search structures & Data
- exact, similar, substructure
- combined with data search
Read across/category formation
Company IUCLID DB CEFIC LRI AMBIT -Workflows supporting the user
ECHA IUCLID DB Chemoinformatics Prediction tools
As System -Cramer rules, Protein binding etc
Major Data Source Data analysis tools
-Regressions, clustering etc.
Search for data Supporting Data management
possible but Read across -flexible import/export of data
not for structures & Category formation Data exchange
- manual or automated e.g.
webservices
6
Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID
IUCLID
Data handling, Retrieval & Export
Public
Dr. Volker Koch, Clariant
CEFIC RIEF IV
CEFIC LRI Project EEM9.3
19.06.2015
7 Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID
Dr. Volker Koch, Clariant, CEFIC RIEF IV, CEFIC LRI Project EEM9.3, 19.06.2015
IUCLID Database
Name: o-Anisidine
IUCLID Version 4
IUCLID Version 5
CAS No. 90-04-0
Many page scrolls
IUCLID 4 had ca. 850 Database fields IUCLID 5 has > 8500 Database fields
8 Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID
Dr. Volker Koch, Clariant, CEFIC RIEF IV, CEFIC LRI Project EEM9.3, 19.06.2015
IUCLID Substance ID & Composition
 IUCLID Substance ID & Composition
 Every Substance in IUCLID is characterized by at least one composition
A Composition consists of
CONSTITUENTS n>= 1
IMPURITIES n>=0
ADDITIVES n>=0

 A IUCLID substance itself has no chemical structure. Only constituents,
impurities and additives have a structure
 As a IUCLID composition has at least of 1 constituent, at least one structure is
assigned. Most IUCLID substances are related to more than 1 structure
 When the IUCLID composition is transferred, AMBIT assigns
automatically searchable structures to constituents, impurities and
additives (if they are available in the AMBIT structure pool of > 400.000
structures)
9 Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID
Dr. Volker Koch, Clariant, CEFIC RIEF IV, CEFIC LRI Project EEM9.3, 19.06.2015
Data retrieval in IUCLID 5 (1)
 “Manually”
 Query Subst. ID  Select Substance  Select Endpoint  Select EP record
 Scroll to data point of interest
 Using the IUCLID Query Tool
Example: Searching a Substance and a specific endpoint e.g. Biodegradation

Filing of Query blocks required (see next slide)
10 Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID
Dr. Volker Koch, Clariant, CEFIC RIEF IV, CEFIC LRI Project EEM9.3, 19.06.2015
Data retrieval in IUCLID 5 (2)
 The IUCLID Query Tool
The Query tool supports searching for specific data using large and very detailed
input screens (due to the large number of database fields). Less experienced users
may get lost when they try to define a query
Query block for Substance ID Query block for Biodegradation