Post on 22-Jul-2020
• 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 2012-2015
• NOAEL values were adjusted by uncertainty factors,
e.g., duration.
Toxicity Profiles of Cosmetics Data
• 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).
Introduction and Objectives
C Yang1,2, DP Hristozov1, A Tarkhov2, T Kleinöder2, I Boyer3, MTD Cronin4, E Fioravanzo5, JH Kim6, B Heldreth3, A
Mostrag-Szlichtyng1, JF Rathman1, A Richarz4, CH Schwab2, V Vitcheva1,2, AP Worth7
COSMOS DB as an international share point for exchanging regulatory and
toxicity data of cosmetics ingredients and related substances
chihae@altamira-llc.com
The funding from the European Community’s 7th Framework Program (FP7/2007-2013) 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.
COSMOS DB houses the building blocks of
sources useful for safety evaluation
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
1 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 Systems
Toxicology, Ispra, Italy
www.cosmostox.eu
Building Blocks of COSMOS Share Point
• 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)
Safety Evaluation Database
COSMOS DB v2.0
• Process (arrows): Red = automatic; Black dotted = manual harvesting• TTC database stores the full history of NOAEL decisions and rationales.
Compilation Process:
COSMOS DB – Safety Evaluation and TTC
Study Inclusion Criteria
Summary
SCCNFP/ SCCP/ SCCS
US FDA
CFSAN
CIR (US)KCII (Korea)
COSMOS
Share PointPublic data sharing
Public data sharing
Users
HESS (Japan)
Data update by COSMOS Share Point
EFSA
COSMOS TTC Database
Rat
LiverKidneyGIReproductiveEndocrineSpleen
• 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
Analysis of NOAEL Distribution
TTC databases and decision tree
Select decision tree
Skin permeability data
• A total of 470 test substances: EDETOX (285),
Kent University update (154), Cosmetics addition
by COSMOS partners (108)
US FDA CFSAN OFASFood contact substances (over 90
substances)
SCCNFP/SCCP/SCCS Cosmetics and consumer products
Registered Substances Database
at ECHA
REACH high tonnage chemicals
US EPA ToxREFDB, IRISIndustrial chemicals, agrochemicals,
etc.
US National Toxicology ProgramNominated substances for safety
concern potential
EFSA (European Food Safety
Agency)
Food/feed related test substances
(opinions in EFSA journals)
Toxicity data sources
• US FDA PAFA legacy database
‒ Food direct and indirect additives, Colorants
• oRepeatTox DB
JRC (EU)
• 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)
Species/Duration Target organs
Safety evaluation record of butyl
paraben in COSMOS DB
NOAEL summary and QC records
COSMOS DB
- provides TTC
database export
- runs TTC decision
trees*
Export TTC database
* Kroes et. al. 2004 Food and Chemical
Toxicology 42 (2004) 65–83
PCPC†
33393,512 INCI names*(3,713 CAS)
19,390 INCI names* (9,275 CAS)
CosIng
Cosmetics inventory
A look-up table for cosmetics ingredients and related chemicals
used in formulations
† 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. 20036-4702. The v1.0
and 2.0 counts therefore will be different.
*INCI: International Nomenclature for Cosmetics Ingredients
MOS NOAEL