INTERNATIONAL COOPERATION ON COSMETIC REGULATION
REPORT TEMPLATE
REPORT FOR INTERNATIONAL COOPERATION ON COSMETIC REGULATION Principles of Cosmetic Product Safety Assessment
Report is:1
⌧  Prepared For ICCR                      ICCR Report                          ICCR Guidance Author:
Authors: Daisuke Araki (1), Dan Bagley (2), John Bailey (3), Rolf Fautz (4), Gulnara Gabidullina (5), Kazuko Ito (6), Linda Loretz (3), Beta Montemayor (7), Pushpa Rao (8), Hitoshi Sasa (9), Takahiko Suwa (10), Florian Schellauf (11)
Affiliations:
(1) Kanebo Cosmetics, 3-28, Kotobukicho 5-chome, Odawara, Kanagawa 250-0002, Japan.
(2) Colgate Palmolive, 909 River Road, PO Box 1343, 08855-1343 Piscataway, USA
(3) Personal Care Products Council, 1101 17th Street, NW, Suite 300, 20036-4702 Washington DC, USA
(4) Kao/Kanebo, Pfungstaedter Strasse 92-100, 64297 Darmstadt, Germany
(5) Procter and Gamble, Rusham Park, Whitehall Lane, TW20 9WN, Egham, UK
(6) JCIA, Toranomon 45MT Building, 1-5 Toranomon-5chome, 105-0001Minato-ku, Japan
(7) CCTFA, 420 Britannia Road East, Suite 102, L4Z 3L5, Mississauga ON, Canada
(8) Energizer
(9) Shiseido, 2-12-1Fukuura, Kanazawa-ku, Yokohama, Japan
(10) Shiseido, 2-2-1 Hayabuchi Tsuzuki, 224-8558 Yokohama, Japan
(11) COLIPA, Avenue Herrmann Debroux 15A, 1160 Auderghem, Brussels, Belgium.
Date of Preparation:May 25, 2011Status: Final – for adoption
1 Documents submitted to ICCR by industry working groups or other interested parties may have “for ICCR” in their title, e.g. “Report Prepared for ICCR”.  Only documents that are endorsed by ICCR Steering Committee or that produced by the Steering Committee or an ICCR WG are to be titled “ICCR Guidance”, “ICCR Report”, etc.
TABLE OF CONTENTS
TABLE OF CONTENTS    2
1. PURPOSE    3
2. SCOPE    3
DEFINITIONS
3
AND
3. ACRONYMS
4. RESPONSIBILITIES    3
5. DISCUSSION    3
5.1 General Principles
5.2 Considerations with regard to animal testing
5.3 Role of the person responsible for safety assessment
5.4 Reasoning of the safety assessment
5.5 Selection of the appropriate toxicological endpoint(s)
5.6 Weight of evidence approach
5.7 Considerations for products for specific target populations
5.8 Safety Assessment Conclusion
APPENDICES
Appendix 1: Regulatory definitions of a cosmetic product7 Appendix 2: Weight
approach  8 evidence
of
1. PURPOSE
The purpose of the ICCR Document on Principles of Cosmetic Product Safety Assessment is to provide a general framework for use in different jurisdictions in the development of safety substantiation principles for cosmetic products. The use of this framework will help to promote development of approaches and supporting principles that will be consistent and, to the fullest extent possible, aligned across jurisdictionsIt is recommended that this document be used in the overall development of approaches to cosmetic ingredient and product safety substantiation necessary to meet the legal and regulatory requirements in different countries/regions
2. SCOPE
This document describes the ICCR consensus on cosmetic product safety assessment principles and provides a core document which may be complemented with further safety-related ICCR documents o
n specific issues.
The definitions of a cosmetic product in the various jurisdictions are provided in annex I.
It does not replace the need for in-depth training and experience for a person performing a safety assessment or conducting in-market control nor does it provide a list of specific toxicological endpoints or study protocols.
DEFINITIONS
AND
3. ACRONYMS
ICCR International Cooperation on Cosmetic Regulation
4. RESPONSIBILITIES
The document has been prepared for ICCR by an industry working group comprised of safety and regulatory experts from the four ICCR jurisdictions.
5. DISCUSSION
5.1 General Principles
Cosmetic products are formulations comprised of specific combinations of substances or mixtures2. In general, it is possible to assess their safety by considering and examining the relevant toxicological endpoints of their ingredients, and the likely local and systemic consumer exposure to the product.
The following general safety assessment principles are applied:
2 For easier readability, these are referred to as ‘ingredients’ in the remainder of the document, although this latter term may also have specific, narrower regulatory meaning  in relation to some regional specific regulatory requirements.
o The safety assessment of cosmetic ingredients is not a standardized procedure, but should be performed on a case-by-case basis using best science. In particular, checklist approaches and decisions based on hazard alone are considered inappropriate and not adequate to thoroughly assess safety.
o The safety assessment of cosmetic ingredients involves a systematic stepwise approach that starts f
rom conservative assumptions and includes refined approaches, as required and/or appropriate.
o The safety assessments should utilize the most up to date approaches available while taking into account current legal/regulatory requirements3.
o The assessment should utilize the entire scope of information available to reach science-based decisions using a weight-of-evidence approach.
o Local and systemic human exposure is of the greatest importance for the safety assessment of cosmetic ingredients; the route, the magnitude and nature of human exposure are the key drivers for the definition of the package of safety data needed. All relevant endpoints need to be addressed but not necessarily with specific study data. (“Data need is exposure-driven”).
o The exposure assessment should cover the normal and reasonably foreseeable use of products.
When appropriate, specific consideration has to be given to vulnerable sub-groups of a user population.
o All relevant existing data should be evaluated before new animal testing is undertaken. New safety testing may be warranted when the existing information is not adequate to support the safety of an ingr
edient or when new potential safety issues arise4.
o The availability of adequate information on the toxicity of the ingredients should in all cases prevent the requirement to study systemic toxicity of the finished product or repetition of already existing studies.
A safety assessment process includes:
o Ingredient characterization through relevant physico-chemical data, purity and profile of impurities, and chemical structure of constituent ingredients comprising a product.
o Assessment of all relevant toxicological hazard information. Data on closely related structural analogues, and structure-activity modeling data, may be considered.
o Considerations with regard to the stability of ingredients and product formulation as well as their microbiological status.
o Exposure assessment including an understanding of how the product is used: the amount, frequency, and duration of intended use; and target users.
o Calculation of safety or exposure margins (as appropriate), using the relevant dose metric for the endpoint considered.
o Post Market Surveillance to support continued product safety.
3 Examples for available safety assessment guidance:
•The SCCS's Notes of Guidance for the Testing of Cosmetic Ingredients and their Safety Evaluation, 7th Revision ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_s_004.pdf •CTFA Safety Evaluation Guidelines (2007)
•Nohynek GJ, Antignac E, Re T, Toutain H. Toxicol Appl Pharmacol. 2010 Mar 1;243(2):239-59
4 Animal testing for cosmetic purposes is not allowed in the EU.
5.2 Considerations with regard to animal testing
buchiData for assessing the safety of finished products have traditionally been obtained from animal tests either on the ingredients or the final formulation or both. The cosmetic industry has been at the forefront of research into the development of non-animal alternative methods for more than 25 years, and is committed to continuing this work to eventually eliminate animal testing as soon as possible.
The result of these efforts are a number of alternative test methods formally accepted by OECD and included in OECD test protocols that should be used for the safety assessment.
The use of suitable alternative methods in the context of safety assessment should not be limited to methods that have undergone formal validation by a national validation body. There are a number of useful alternative methods and approaches available that contribute useful safety information in the context of a weight-of-evidence safety assessment. Examples are in vitro tests, cell and tissue culture models, read-across approaches, structure-activity modeling data ((Q)SAR)), and results of in-silico computational methods.  Scientific evidence of the ability of an alternative test to predict a certain aspect of toxicity of an ingredient is of fundamental importance.
When there are no validated alternative methods, authorities may still require manufacturers to predict the toxicity of ingredients/chemical substances and formulations with or without using animal assays. However, the use of animal assays should in all cases be minimized as much as possible.
Approaches to non-animal safety assessment related to endpoints specifically relevant for cosmetic safety assessment have been published in the literature.5
5.3 Role of the party responsible for safety assessment
The party responsible for assessing the safety of a cosmetic product has an integral role in the process of safety assessment and has to possess the necessary qualifications to fulfill this role in a responsible and ethical way.
Those responsible for the safety assessment should:
•Have training and competence in analysis, evaluation and interpretation of toxicological data
•Have access both to the toxicological and analytical information relevant to safety. Consider the safety of the product impartially and objectively.
•Carry out the safety assessments based on a thorough analysis of all available data, conditions of exposure and appropriate consideration of weight of evidence.
In case of a written safety assessment , the credentials and the contact address of the party responsible for the safety assessment should be included.
5.4 Reasoning of the safety assessment
The reasoning of the safety assessment relates to the considerations, which lead the safety assessor from all available safety related information to an overall conclusion on the safety of a product.
5/10.ph.2009.04.004,
/10.ph.2009.04.003
/10.ph.2010.03.012