1. MTD Cronin1, C Yang2,3, A Bassan4, K Arvidson5, I Boyer6, E Fioravanzo4, B Heldreth6, JH Kim7, J Madden1, J Rathman2,8, CH Schwab3, T Yamada9, AP Worth10
COSMOS DB as an International Share Point for Exchanging Safety Evaluation and Toxicity Data, and
Expanding the Known Chemical Space
1 Liverpool John Moores University, Liverpool, UK; 2 Altamira LLC, Columbus OH, USA; 3 Molecular Networks, Erlangen, Germany; 4 Soluzioni Informatiche srl, Vicenza, Italy; 5 Office of Food Safety, US FDA CFSAN, College Park, MD, USA; 6 Cosmetic Ingredient Review, Washington DC, USA;
7 Foundation of Korea Cosmetic Industry Institute, Osan, Korea; 8 Ohio State University, Columbus, OH, USA; 9 National Institute of Technology and Evaluation, Tokyo, Japan; 10 EC Joint Research Centre, IHCP, Ispra, Italy
The funding for COSMOS project was available during 2011-2015 from the European Community's 7th Framework Program (FP7/2007-2013, COSMOS Project grant agreement n°266835) and Cosmetics Europe.
Introduction
COSMOS (www.cosmostox.eu) was one of seven projects within SEURAT-1
cluster, a European research initiative with the long-term goal of achieving
"Safety Evaluation Ultimately Replacing Animal Testing". COSMOS was a unique
collaboration addressing the safety assessment needs of the cosmetics industry,
without the use of animals. The main aim of COSMOS was to develop freely
available tools and workflows to predict the safety to humans following the use of
cosmetic ingredients.
• COSMOS DB v1.0 was released in 2013 to support the activities during the
consortium period ending Dec 2015. The v1.0 final content (SDF and Excel
files) will be available for free download in COSMOS SPACE.
• COSMOS DB v2.0 will continue to be developed, maintained and made
available to public through the COSMOS DataShare Point initiative, creating a
public resource for toxicological data collection and a means to share data
freely with the scientific community.
Summary
• COSMOS DB v2.0 is publicly available (after registration) and maintained
through COSMOS DataShare Point initiative.
• COSMOS DB continues to house qualified data for human health endpoints.
• COSMOS workflow offers building blocks of sources useful for safety
evaluation.
• COSMOS DB v2.0 provides data relevant to international regulation of
cosmetics-related chemicals.
• Direct collaboration / data exchange: CIR (US), HESS (NITE Japan), JRC
(EU), KCII (Korea), US FDA
• Data mining activities of partners: EFSA journals, ECHA (substance
registration) database, SCCS opinions
• More than 80,000 chemical records with more than 40,000 unique structures
• More than 12,000 toxicity studies across 27 endpoints for more than 1,600
compounds
Skin permeability data (planned for COSMOS DB v2.0)
• A total of 470 test substances
• EDETOX (285) and Kent University update (154)
• Addition from COSMOS for cosmetics-related chemicals (108)
US FDA CFSAN OFAS
Food contact substances (over 90
substances)
SCCNFP/SCCP/SCCS Cosmetics and consumer products
Registered Substances Database at ECHA REACH high tonnage chemicals
US EPA ToxRefDB, IRIS Industrial chemicals, agrochemicals, etc.
US National Toxicology Program
Nominated substances for safety concern
potential
EFSA (European Food Safety Agency)
Food/feed-related test substances (opinions
in EFSA journals)
Cosmetics inventory
• Look-up table for cosmetics ingredients and related chemicals in formulations
• Data source includes EU COSING database and US VCRP (voluntary
cosmetic registration program) list from CIR (cosmetics ingredient review)
COSMOS DB v2.0 Content
• Easy-to-use web-based interface for data retrieval
• Formulation of queries from chemistry or toxicity view point
• Chemical names, CAS RN, IDs, full, sub-structure and
similarity searches (read-across)
• Toxicity endpoints, species, strains (or cell lines), routes
of exposure, sites, effects and calls
• Combination of chemistry and toxicity queries for
hypothesis-driven searches
M.T.Cronin@ljmu.ac.uk
chihae.yang@mn-am.com
• Interactive hit lists and
compound information pages
• General information about
studies
• Title, source, reference,
inventory, quality, etc.
• Study comments and
background information
• Study design tables
• Dose level, treatment group and
effects tables
COSMOS Safety Evaluation and TTC Database
Safety evaluation record of
butyl paraben in COSMOS DB
NOAEL summary and QC records
MOS NOAEL
• Point of departure
• NOAEL decisions or BMDL
• Critical study and effects/sites
• Evaluation methods
• Margin of Safety
(SCCNFP/SCCP/SCCS)
• Margin of Exposure (EU EFSA)
• Oral Reference Dose RfD (US
EPA IRIS)
COSMOS Workflow: TTC Database and Decision Tree
* Kroes et. al. Food and Chemical Toxicology, 42 (2004) 65-83
TTC decision tree *
TTC database export
• Provides TTC database export
• COSMOS and Munro database
• Runs TTC decision tree
Toxicity data sources
• US FDA PAFA legacy database
• Food direct and indirect additives, colorants
• oRepeatToxDB (219 test substances)
• HESS (Hazard Evaluation Support System Integrated Platform) database
• NITE Japan provides updates for over 500 test substances
• Data content: NEDO (New Energy and Industrial Technology Development
Organization) and Ministry of Economy, Trade and Industry (METI)
COSMOS DB v2.0 Search & Retrieval
DataShare Point
https://cosmosdb.eu/cosmosdb.v2
COSMOS Share Point
CIR (US)
HESS (Japan)
US FDA
CFSAN
KCII (Korea)
JRC (EU)
LJMU (UK)
Altamira (US)
Molecular Networks
(Germany) S-IN (Italy)
A2476/P602