# Commission Implementing Decision of 25 November 2013 on Guidelines on Annex I to Regulation (EC) No 1223/2009 of the European Parliament and of the Council on cosmetic products (Text with EEA relevance) (2013/674/EU), Division 3.8.2: Toxicological profile of substances for all the relevant toxicological endpoints

Extent: E+W+S+N.I.

The toxicological profile for each substance is determined by the hazard identification and the dose-response characterisation.
The first essential step in developing the toxicological profile is to gather all the relevant information about the intrinsic properties of the substance. Such information should include the following:
(1) as the most valuable toxicity information, actual test data from in vivo or in vitro studies obtained in accordance with Commission Regulation (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), recognised international guidelines, or standards (e.g. OECD Test Guidelines), and performed in accordance with good laboratory practice principles;
(2) existing test data that have not been obtained in accordance with the latest adopted/accepted version of a test guideline or with good laboratory practice standards, but which are considered valid;
(3) in vitro data or alternative data from valid test systems, to be used as a screening study to predict toxicity;
(4) human data and/or experience. It is in general not acceptable to perform human toxicology studies for hazard identification, but, if data or experience exist, they should be included in the final assessment;
(5) human (clinical) data, including data from clinical trials and applications in other industries such as food and medicinal products;
(6) data gathered from post-marketing surveillance;
(7) human volunteer compatibility studies, which should only be used to confirm safe levels of use for a relevant target population;
(8) read-across approaches, based on the chemical structure and properties of related substances in order to predict the toxicity of the ingredient, grouping of substances, and non-testing data from QSAR model outputs.
Based on data obtained from all available sources, and taking into account the quality of the data, the safety assessor can evaluate the likelihood of adverse effects in humans through the ‘weight of evidence’ approach.
A prerequisite for a proper risk assessment is the availability of adequate data. For additional support on this matter, one may consult the guidance for the preparation of safety dossiers for submission to the Scientific Committee for Consumers Safety (SCCS), set out by the Committee itself in its Notes of Guidance. Though these Notes of Guidance are provided for substances where an authorisation is needed, i.e. for colorants, preservatives and UV filters, or which otherwise raise concern, the requirements they set out may be helpful for the safety assessment of all substances used in cosmetic products. In addition, a section of the most recent Notes of Guidance focuses on the safety assessment of finished cosmetic products.
The toxicological profile may address a number of different endpoints. A final decision about which endpoints are relevant is made by the safety assessor on a case-by-case basis, taking into account exposure, use of the product, the physico-chemical characteristics of the substances, experience with the substances, etc.. Attention should also be paid to local effects (e.g. irritation and photo-toxicity), when relevant. Where a certain endpoint is considered to be not relevant, this should be justified.
Endpoints that may be relevant for the toxicological profile are:
(1) acute toxicity via relevant routes of exposure;
(2) irritation and corrosivity;
(3) skin irritation and skin corrosivity;
(4) mucous membrane irritation (eye irritation);
(5) skin sensitisation;
(6) dermal/percutaneous absorption;
(7) repeated dose toxicity (normally 28- or 90-day studies);
(8) mutagenicity/genotoxicity;
(9) carcinogenicity;
(10) reproduction toxicity;
(11) toxicokinetics (ADME studies);
(12) photo-induced toxicity;
For the appropriate endpoints, the most relevant concentrations or No Observed Adverse Effect Levels (NOAEL) or Lowest Observed Adverse Effect Levels (LOAEL) should be identified for further use in the risk characterisation process.
Additional information regarding endpoint specific data and their interpretation can be found in the endpoint specific guidance prepared by the European Chemical Agency (ECHA) for the implementation of Regulation (EC) No 1907/2006 of the European Parliament and of the Council on Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).
For some cosmetic ingredients e.g. of mineral, animal, botanical and biotechnological origin (see also Substances of Unknown or Variable composition, Complex reaction products or Biological materials or ‘UVCB substances’ under REACH), their identification should carefully address source, process, organisms involved, etc., in order to evaluate their toxicological profile.
If certain hazards cannot be sufficiently addressed, or if doubts remain regarding the robustness of the data, additional uncertainty factors may be introduced or additional data may need to be generated.

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Source: https://www.legislation.gov.uk/eudn/2013/674/annex/division/3/division/3.8/division/3.8.2 (the official version)
Page: https://openlegislation.uk/eu-decision-2013-674/annex/division-3/division-3.8/division-3.8.2
Contains public sector information licensed under the Open Government Licence v3.0. Source: legislation.gov.uk, The National Archives.