New functionalities in Toolbox 2.0

1. Multi-document application 2. QA of chemical structures 3. Working on 2D or 2.5D mode INPUT

1.New profiles added: Toxic hazard classification by Cramer (two versions) Acute aquatic toxicity by Verhaar Mutagenicity/Carcinogenicity alerts by Benigni/Bossa Micronucleus alerts by Benigni/Bossa Oncologic Primary classification Organic functional groups (four versions) US EPA New chemical categories – updated ECOSAR - updated Eye/Skin Irritation/Corrosion PROFILING

1.New profiles added 2. All ToxTree profiles were recoded in TB2 3.New organization of the profilers PROFILING

Groups of profilers Predefined General Mechanistic Endpoint Specific Empiric Custom 5 PROFILING

4. Improved transparency of the category description 5. Possibility to correlate profile/profile and profile/endpoint PROFILING

1. Endpoint tree New SIDS data tree developed New Biological library with taxonomy introduced Tree hierarchy could be set manually 7 ENDPOINT

1. SIDS tree New SIDS data tree developed New Biological library with taxonomy introduced Tree hierarchy could be set manually 2. Databases and Inventories New and updated databases and inventories Update of list of Endpoints Categorical and numerical data available Conversion of data in different scale Data could be defined in range Gathering data for all tautomers of a chemical Filtering Endpoint tree – to get easier to the target endpoint 8 ENDPOINT

# NAME # of Chemicals Chemical ID available Number of DATA # of Endpoints ENDPOINTS CAS2DName 1Aquatic ECETOC EC50,LOEC,MATC,NOEC 2Aquatic Japan MoE EC50,LC50,LOEC,NOEC 3Aquatic OASIS EC50,I50,IC50,IGC50,LC50,LD50,MRC50,pT 4Aquatic US-EPA ECOTOX BAF,BCF,BMCXX,ECXX,EDXX,ERXX,ETXX,ICXX,LCXX,LDXX,LE TC,LOEL,LOER,LRXX,LTXX,MATC,MATR,NOEC,NOEL,N OER,NR-LETH,NR-ZERO,T1/2 5Bioaccumulation Canada BCF 6Bioaccumulation fish CEFIC LRI BCF 7Biodegradation OASIS BOD 8Biota-Sediment Accumulation Factor BSAF 9Carcinogenic Potency DataBase CPDP TD50 10Carcinogenicity&Mutagenicity ISSCAN Gene mutation,Histopathology: neoplastic,TD50 11ERBA OASIS Relative ERBA 12Eye Irritation ECETOC MMAS 13Genotoxicity OASIS Chromosome aberration,Gene mutation 14kMdatabase kM 15Micronucleus ISSMIC142 1Chromosome aberration 16Micronucleus OASIS557 1Chromosome aberration 17Phys-chem EPISUITE Experimental: Boiling point, Нenry's Law constant, Log BCF, Log Koa, Log Kos, Log P, Melting point, NO3 rate constant, OH rate constant, Ozone rate constant, Vapor Pressure, Water solubility, log kM Half-Life, pKa 18Repeat Dose Toxicity NEDO LOEL,NOEL 19Repeated dose toxicity Fraunhofer ITEM LOEL,oLOEL,oNOEL 20Skin Irritation RIVM Primary Irritation Index 21Skin Sensitisation ECETOC RESPIRATORY SENSITISATION,SKIN SENSITISATION 22Skin Sensitisation OASIS Skin sensitization 23Terrestrial US-EPA ECOTOX BAF,BCF,BMCXX,ECXX,EDXX,ERXX,ETXX,ICXX,LCXX,LDXX,LE TC,LOEL,LOER,LRXX,LTXX,MATC,MATR,NOEC,NOEL,N OER,NR-LETH,NR-ZERO,T1/2 24Toxicity Japan MHLW Gene mutation,LD50 25ToxRefDB LOEL Currently available Databases, APRIL 12, 2010

10 #Databases Unique RealationCAS/2D 1EINECS HQ EINECS LQ HPVC OECD DSSTox REACH ECB ECHA PR Canada DSL US HPV Challenge Program METI Japan TSCA Currently available Inventories, April 12,

11 Summary of available databases and inventories New databases Repeat Dose Toxicity NEDO Repeated dose toxicity Fraunhofer ITEM Carcinogenic Potency DataBase CPDP Biota-Sediment Accumulation Factor kMdatabase Micronucleus OASIS Micronucleus ISSMIC ToxRefDB Updated databases Aquatic US-EPA ECOTOX Terrestrial US-EPA ECOTOX Phys-chem EPISUITE Genotoxicity OASIS Skin Sensitisation OASIS New Inventories DSSTox REACH ECB ECHA PR Updated Inventories EINECS HQ EINECS LQ HPVC OECD CategoryDatabasesInventories New83 Update53 Old124 All

1. SIDS tree New SIDS data tree developed New Biological library with taxonomy introduced Tree hierarchy could be set manually 2. Databases and Inventories New and updated databases and inventories Update of list of Endpoints Categorical and numerical data available Conversion of data in different scale Data could be defined in range Gathering data for all tautomers of a chemical Filtering Endpoint tree – to get easier to the target endpoint 3. Docking to IUCLID 5 and Catalog Data exchange via XML files Data exchange via WebServices 12 ENDPOINT

1.Goal: To use simultaneously data form different categorical and ratio scales 2.Solution: Defining an expandable libraries of: Scale definitions – description of a scale. Each data point can be associated with only one scale. Scale conversions – rules for conversion of a data point associated with a scale to a different scale Scale conversions information could be saved/reloaded 13 Use of categorical and ratio data in different scales ENDPOINT

1. Possibility to combine two categories 2. Categorization in “strict” mode 3. Create categories by using TB2 derived SAR models CATEGORIZATION

15 1. Read-across based on data in nominal or ordinal scale 2. Graphical visualization of data in nominal or ordinal scale 3. Median and mode are added as a measures of central tendency of data (along with min/max) 4. Filtering (subcategorization) by Meta data –such as test organism, etc. Molecular descriptor ranges QA of chemicals structures – QA(CAS-2D) FILLING DATA GAP

1.The layout of three standard reports Prediction reporting format – TPRF as a single file Model reporting format - QMRF as XML Category reporting format (CCRF) 2.User selected part of the Data matrix will be reported in TPRF 3.User interface for creating/designing custom reports 4.User interface for editing of reports’ data REPORTING

1. Auto-Update functionality 2. Client-Server version 3. Undo-Redo throughout the system IT Items