1. COSMOS DB as an international share point for exchanging regulatory and toxicity data of cosmetics ingredients and related substances
C Yang1,2, DP Hristozov1, A Tarkhov2, T Kleinöder2, I Boyer3, MTD Cronin4, E Fioravanzo5, JH Kim6, B Heldreth3, A Mostrag-Szylichtyng1, JF Rathman1, A Richarz4, CH Schwab2, V Vitcheva1,2, AP Worth7
3 Altamira LLC, Columbus OH, USA; 2Molecular Networks, Erlangen, Germany; 3Cosmetic Ingredient Review, Washington DC, USA; 4Liverpool John Moores University, England; 5Soluzioni Informatiche srl, Vicenza, Italy; 6Korean Cosmetics Institute of Industries, Seoul Korea; 7EC Joint Research Centre, IHCP Systemes Toxicology, Ispra, Italy
Introduction and Objectives
Building Blocks of COSMOS Share Point
Safety Evaluation Database
As one of the practical alternatives to repeated dose toxicity testing, COSMOS consortium has established databases and in silico tools. To enable the pragmatic methods, the COSMOS database has been expanded to include safety evaluation data as well as the TTC (threshold of toxicological concern) databases.
Objectives
Expand the COSMSO DB data model to include safety evaluation data as well as TTC database
Provide workflow tools to run TTC trees
Lay foundation to interface with institutions with cosmetics related issues
Point of departure
NOAEL (or BMDL) decisions
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 DB houses the building blocks of sources useful for safety evaluation
KCII (Korea)
CIR (US)
HESS (Japan)
JRC (EU)
Public data sharing
US FDA CFSAN
COSMOS Share Point
COSMOS TTC Database
Public data sharing
Users
SCCNFP/ SCCP/ SCCS
EFSA
Data update by COSMOS Share Point
COSMOS DB v2.0
Compilation Process:
COSMOS DB – Safety Evaluation and TTC
Safety evaluation record of butyl paraben in COSMOS DB
Cosmetics inventory
A look-up table for cosmetics ingredients and related chemicals used in formulations
MOS
NOAEL
CosIng
PCPC†
3,512 INCI names*
(3,713 CAS)
19,390 INCI names*
(9,275 CAS)
3339
*INCI: International Nomenclature for Cosmetics Ingredients
† In v2.0 the US list (voluntary cosmetic registration program) is provided by CIR (cosmetic ingredient review). The current v1.0 counts are from “Compilation of Ingredients Used in Cosmetics in the United States“, 1st Edition, JE Bailey, Ed. The Personal Care Products Council, Washington D.C The v1.0 and 2.0 counts therefore will be different.
NOAEL summary and QC records
Toxicity data sources
US FDA PAFA legacy database
Food direct and indirect additives, Colorants
oRepeatTox DB
Process (arrows): Red = automatic; Black dotted = manual harvesting
TTC database stores the full history of NOAEL decisions and rationales.
TTC databases and decision tree
Study Inclusion Criteria
COSMOS DB
- provides TTC database export
- runs TTC decision trees*
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)
Selected lowest NOAELs from reliable studies
Effects considered for NOAEL/LOAEL
Non-neoplastic systemic effects
Developmental effects included if critical
Toxicologically significant, human relevant endpoints when mechanism is known
Data record reliability confirmed by database QC
Study results reliability confirmed by NOAEL review sessions on the high impact portion of the database
The lowest 10% and records varying greatly across the data sources
Studies for 150 chemicals reviewed by ILSI experts during
NOAEL values were adjusted by uncertainty factors, e.g., duration.
Select decision tree
Export TTC database
Skin permeability data
A total of 470 test substances: EDETOX (285), Kent University update (154), Cosmetics addition by COSMOS partners (108)
* Kroes et. al Food and Chemical Toxicology 42 (2004) 65–83
Summary
Toxicity Profiles of Cosmetics Data
Analysis of NOAEL Distribution
COSMOS Database has expanded the data model to include skin permeability, safety evaluation, and TTC databases.
The safety evaluation database now includes all updated Margin of Safety data from SCCNFP/SCCP/SCCS. It also includes RfP, MOE, ADI available from other regulatory bodies.
COSMOS TTC database established and can export the full dataset as well as combination of the current Munro database.
COSMOS DB workflow includes TTC database export as well as TTC Decision Tree (Kroes 2004)* and the Oral-to-dermal exposure tiered workflow (ILSI EG2).
Species/Duration
Target organs
Liver
Kidney GI
Reproductive
Endocrine
Spleen
Rat
A total of 793 compounds in cosmetics inventory was associated with 1150 unique in vivo studies
Other short-term and special toxicology studies are not included.
Rat is the single most tested species and liver is the top target organ
Most common pathological findings include steatosis phenotypes.
Subchronic studies have the lowest average NOAEL values
Cosmetics alone have higher thresholds in general than Munro.
The thresholds for Munro (Class I = 3.0; Class II = 0.91; Class III = 0.15 mg/kg-bw/day) are not affected much by the inclusion of additional 360 cosmetics-related chemicals. (ILSI EG1)
The funding from the European Community’s 7th Framework Program (FP7/ ) COSMOS Project (grant agreement n°266835) and Cosmetics Europe, and support from EPAA are gratefully acknowledged. We also thank ILSI Europe and the expert groups 1 and 2 in support of COSMOS project.