1. Lecture by Dr. P. Cadby on fragrances and scents

It becomes normal practice that the scientific committee invites experts to give a presentation on an issue of particular interest to the committee. For the 3rd plenary meeting, Dr. Peter Cadby was invited to give a lecture on industry views on the safety aspects of fragrances and scents with respect to consumer's health including toxicological, dermato-(toxico)logical/allergenic aspects etc.

The lecture was followed by a discussion.

2. Adoption of the Agenda

The agenda was adopted.

3. Rules of Procedure

This version of the Rules of Procedure has been discussed and adopted by the Scientific Steering Committee. The document was now presented to the SCCNFP for comments. However, the member were reminded that it is the Commission's intention to have only one set of "Rules of Procedure" applicable to all of the 9 scientific committees. As a result, it was decided not to go into discussion during this meeting but to send comments directly to the secretariat for discussion at a later date.

As regards the two annexes to the document, namely the Annual statement of member's interest (annex 1) and the Declaration concerning confidentiality (annex 2), the members were asked to complete and to sign, if appropriate, and to send it to the secretariat.

4. Approval of the minutes of the 2nd plenary meeting of 21 January 1998

The minutes were adopted subject to the correction of the typographical errors.

5. SCCNFP – Specific Working Parties

5.1 Alternatives to Animal Testing & Dossier

In his report (Annex I), the co-ordinator gave an overview of the meetings held since the 2nd plenary meeting and of the issues discussed. He mentioned that the WP met several cosmetic industry scientific experts to discuss those aspects of alternative methods for which possibilities exist to conclude on the replacement of animals or on the reduction of the number of animals in a short period of time (before the year 2000). The main areas of concern are : eye irritation, in-vitro photo-irritation, human skin compatibility, percutaneous absorption and skin sensitisation.

Photo-toxicity : the Co-ordinator mentioned that an in-vitro methodology to identify the photo-toxicity of chemicals was defined and validated. Depending on the validity of the results obtained and on the availability of all the data, the WP should be in a position to conclude on this issue during 1999.

Percutaneous absorption : it is a general opinion that early 1999, it should be possible to conclude on some in vitro methodologies as the suitable or adequate procedures to define the level of percutaneous absorption of cosmetic ingredients.

Human testing : the SCCNFP is ready, upon request from the Commission, to work on a guideline on human testing for skin irritation for the evaluation of finished cosmetic products.

A revision of some of the annexes of the Notes of Guidance has started as a consequence of the

scientific and technical progress made by industry, and by the cosmetic industry in particular.

A mandate for the SCCNFP WP ‘Alternatives to animal testing' was drafted by DG III. It states that the SCCNFP shall act as a resource of technical expertise to the European Commission with regards to the development of alternative methods, to give pro-active advice to the cosmetic industry on research proposals or on-going studies and, if appropriate, to peer review study data.

The mandate was subsequently adopted by the plenary meeting subject to the correction of some typographical errors.

5.2 Hair Dyes

In his report, the co-ordinator gave an overview of the meetings held since the 2nd plenary meeting and of the issues discussed. Only one meeting took place during which a number of draft opinions were discussed and sent to the plenary meeting for adoption.

These draft opinion are :

A18 : 1,5-Dihydroxynaphthalene - doc n° XXIV/1285/97

This substance was given a classification B by the SCC in 1993. A further study on the chromosome aberration on mammalian cells grown in vitro was required and performed.

Based on the data presented, it was concluded that A18 does not pose a health hazard for the intended use and at the dose level of 1% in hair dye formulations, which corresponds to 0.5% upon application.

A classification 1 was adopted.

B31 : Kardinalrot - doc n° XXIV/1287/97, rev. 9/97

Based on the data presented, it was concluded that B31 does not pose a health hazard for the intended use in semipermanent hair tinting products, colouring setting lotions and permanent hair dye formulations at the dose level of 2.5% in semi-permanent and 1.25% in permanent respectively.

A classification 1 was adopted.

B49 : 1-Amino-2-nitro-4-(b -hydroxyethyl)-amino-5-chloro-benzene - doc n° XXIV/1288/97, rev. 9/97

This substance was given a classification C by the SCC in 1992. Adequate studies on dermal absorption, skin- and eye-irritation, sensitisation and teratogenicity were required.

Upon fulfilment of this requirements, a classification 1 was adopted.

B52 : 1-Methoxy-2-(b -hydroxyethyl)-amino-5-nitro-benzene - doc n° XXIV/1289/97

A classification 1 was adopted without further remarks.

B58 : 1(-2-Hydroxyethyloxy)-3-methylamino-4-nitro-benzene - doc n° XXIV/1290/97

A classification 1 was adopted without further remarks.

B66 : 1-Amino-3-methyl-4-(2-hydroxyethyl)-amino-6-nitrobenzene - doc n° XXIV/1291/97

A classification 1 was adopted without further remarks.

B67 : 1-(b -Aminoethylamino)4-(b -hydroxyethyloxy)-2-nitrobenzene - doc n° XXIV/1292/97

A classification 1 was adopted without further remarks.

B81 : 1,5-di-(b -Hydroxyethylamino)-2-nitro-4-chloro-benzene - doc n° XXIV/1293/97

A classification 1 was adopted without further remarks.

A21 : Hydroquinone

A draft opinion on Hydroquinone as a skin lightener was tabled. The draft opinion stated that hydroquinone should not be used as a skin de-pigmentation agent in cosmetic products due to its observed clinical side effects. This conclusion was endorsed by the plenary meeting. Consequently, hydroquinone, as a skin lightener, was classified 2a.

However, it was concluded that the use of hydroquinone as a hair dye constituent needed further investigation. A re-evaluation of its NOAEL data will be done and the margin of safety re-established. Therefore, the issue was re-addressed to the WP ‘Hair Dyes' with the request to draft an opinion for the next plenary meeting of 23 September 1998.

5.3 Inventory

In his report, the Co-ordinator said that this Working Party discussed the a number of issues in order to establish a suitable work programme for the improvement and updating of the present version of the inventory.

On each of these issues, namely on incorrect entries, on common names of cosmetic ingredients, on the correction of the INCI names of ethylhexyl- and ampho-derivatives and on nomenclature conventions of botanicals, documents were prepared. Each of these documents was commented by the co-ordinator, discussed, and subsequently, adopted by the plenary meeting. Meetings are planned to discuss each of these issues with representatives of the industry concerned.

A mandate for the SCCNFP WP ‘Inventory' was drafted by DG III, which defines the precise role of this Working Party and the working procedures to be followed for improving and updating the EU inventory. The documents was commented by the co-ordinator, discussed, and subsequently, adopted by the plenary meeting.

5.4 Preservatives, Colorants & Fragrances

In his report, the Co-ordinator commented the issues dealt with since the last plenary meeting. Although opinions on P71 and P91 has been adopted, the committee was asked to re-evaluate these two substances as to recent developments in the domain. Specific questions were asked to the cosmetic industry in this respect and a re-evaluation will start as soon as the respective replies are received.

Other pending issues are the a - and b -hydroxy acids, acrylamide and carbamide peroxide. For each of these items, dossiers were received and conclusions are expected later this year.

In response to the growing concern over the issue, the Working Party initiated its work on the review of the safety of fragrance materials. With reference to the questions asked, it was decided to start with the labelling of all known fragrance allergens on cosmetics and with defining a maximum concentration under which the labelling of such a fragrance might not be required. A meeting with EFFA to discuss their lists of restricted and not-recommended ingredients with a view to a possible inclusion of these ingredients in Annex II, respectively III and to discuss section 2 of the inventory is planned.

The assistance of the SCCNFP was requested over the claim ‘hypo-allergenic', commonly used on cosmetic products. The input of the SCCNFP was requested as to whether the claim is indeed necessary, and if so, the criteria to support it. A draft statement on the issue was produced in a sense that the consumer might be mislead by this term and that the use of the term should be discouraged in the description of cosmetic products. The statement was endorsed and adopted by the plenary meeting.

* Musk's, nitro & polycyclic – state of the art

In 1996, the SCC adopted an opinion on nitro musk's saying that the available data did not justify the assumption that their use in cosmetic products is safe. In 1997, the SCC adopted an opinion on Musk Moskene and Musk Tibetene which lead to the inclusion of these musk's in annex II of the cosmetic directive.

During 1996 and 1997, further safety data were received on musk ketone and xylene as well as on the polycyclic musk's AHTN and HHCB. The evaluation of these submissions is still on-going.

However, and to conclude on the musk issue, the committee stated not to take into consideration any safety data on these 4 remaining musk's received after September 30th 1998 for drafting its scientific opinion.

* Draft opinion on P21 - Benzylhemiformal, Boric acid, borates and tetraborates

The adoption of these opinions was postponed to the next plenary meeting as it was found that both files were not in a state for discussion and subsequent adoption.

5.5 UV Filters

The Co-ordinator reported on what has been discussed in the Working Party since the previous plenary meeting. He mentioned that the WP identified three imported issues on which work will start in the near future. These issues are the use of sun screen formulations and its relation with the risk of melanoma. Particular interest will be given to young children in this respect. The second issue is the question whether all UV filters should be compulsory assessed by the committee prior to their inclusion in a proper annex to the directive. The third one is a draft opinion or guidance on the Sun Protection Factor.

Next, an historical overview was given of work done since the very beginning. A list of compounds ever submitted to the committee was annexed to this overview. Some of the compounds listed appeared to have been abandoned by industry in the sense that the data submitted were scanty and there appeared to be no interest in generating further information about them and presenting it, with a view to obtaining approval for the use of these compounds in sunscreen preparations. The importance of these "abandoned' compounds lies in the fact that the directive states that the ultraviolet filters listed in Annex VII are those intended for use in sunscreen formulations. UV filters which are used in other cosmetics (e.g., hair preparations, creams, etc.) are specifically excluded from the scope of the directive, so that any of these compounds may perhaps be used in cosmetics other than sunscreen formulations. A formal letter in this respect will be sent to the industry concerned.

Expert panel workshop :

The committee envisages to organise an expert panel workshop to address issues such as the use of sunscreen formulation or other sun protection measures and their relation to melanoma or other (skin)diseases and/or to address health risks in general in relation to exposure to the sun.

6. Report of the Chairman

In his report, the Chairman repeated what he asked for while discussing the rules of procedure earlier the meeting, namely to send him or the secretariat comments on this document.

A document titled ‘Format and structure for the opinions of the Scientific Committees' was tabled. Also this document was previously presented to the SSC and although it does not fit in completely with way opinions are presented by the SCCNFP, it is an importing step in drawing a common look for opinions of the 9 committees. The Chairman asked for reactions or comments in view of a future discussion on this item.

The Chairman reported as well on the work done within the Scientific Steering Committee. He said that most of the time was dedicated to the BSE/TSE issue. Opinions were adopted by the SSC on the safety of tallow and gelatine, which are of interest to this committee as well.

Of interest of the SCCNFP is also the on-going work on exposure limits to electromagnetic fields.

7. Any Other Business

No topics were dealt with under this heading.

Attendance List

Present

Mr K. Andersen, Mr R. Anton, Mr J-F. Doré, Mr P. Elsner, Mr V. Kapoulas, Mr F. Kemper, Mr N. Loprieno, Mr J. Parra, Mr C.J. Powell, Mr T. Sanner, Mr J. Vives Rego, Mr I. White

External experts :

Mr P. Cadby, Mrs J.D. Johansen, Mr D. O'Mahony

Commission :

Mr L. Bansil DG III, Mrs M. Bernard DG III, Mr W. De Klerck DG XXIV, Mr A. Van Elst DG XXIV

Apologies :

Mr P. Blain, Mrs Y. De Roeck-Holtzhauer, Mr B. Lina, Mrs V. Rogiers

Annex I

Report of the Co-ordinator of the WP ‘Alternatives to Animal Testing & Dossier

Since our Second Plenary Meeting of 20 January 1998, the SWP has met 5 times (Feb.6, March 5/6 and 24/25, April 20/21, May 12/13).

The mandate given to SCCNFP specific working group on alternative methods has been discussed in two meetings and it was adopted on March 5/6 as a draft to be submitted to its adoption by the plenary (DOC. XXIV/XXXV/98). Briefly, the mandate states that the SCCNFP shall act as a resource of technical expertise to the European Commission with regards to the development of alternative methods; to give pro-active advice to the European Cosmetic Industry on research proposal and on-going studies; to offer, as appropriate, peer review of study data.

The SWP has met several Cosmetic Industry's scientific experts, COLIPA SCAAT representatives expert scientists in the field of phototoxicity and statistics, and the Director of ECVAM, to discuss the problems of concern giving priority to those aspects of Alternative Methods for which there is some possibility in a short period of time (before the year 2000) to conclude on the replacement or reduction of the number of animals employed in the safety testing of cosmetic ingredients and products.

In the meantime, a revision has stated on some of the Annexes of the "Notes of Guidance for Testing of Cosmetic Ingredients for Their Safety Evaluation" (DOC. XXIV/1878/97) taking into account the improvement in the scientific progress, and the technical progress in the Cosmetic Industry, as stated in the Introduction of the Document (p.8).

The main areas of concern of the SCAAT/COLIPA (Steering Committee on Alternatives to Animal Testing) are:

(a) Eye Irritation, (b) In Vitro Photoirritation (c) Human Skin Compatibility (d) Percutaneous Absorption (e) Skin Sensitization; more than 60% of their efforts is involved in these 5 fields.

The efforts made by ECVAM during the last period of time and at present, are on some alternative toxicity testing, such as:

(a) Eye Irritation, (b) Skin Corrosivity, (c) Skin Irritation, (d) Skin Sensitization, (e) Embryotoxicity/Teratogenicity, (f) Phototoxicity.

The following conclusions based on a series of discussions with other interested parties, can be made at present by SWP, relatively to only three areas.

Phototoxicity

This sector interests all those cosmetic ingredients which absorb UV light (See Annex VII, Council Directive 76/768/EEC and European Inventory: 96/335/ECC) and might modify their molecule so to present a toxicological potential for consumers' health (due to their acquired reactivity to cell's component and genetic material).

At present there are neither Animal Models defined in the OECD, nor EC Guidelines for the evaluation of phototoxic properties of chemicals.

At the conclusion of two intense research projects developed by the EC-ECVAM and the European Cosmetic Industry (COLIPA) it has been possible to define and validate and in vitro methodology, the so-called In Vitro Phototoxicity 3T3 Cell Neutral Red Uptake that is able to correctly identify phototoxic and non-phototoxic chemicals. A statistical model for the interpretation of results has also been defined.

On the basis of these results, DGXI and ECVAM have signed a Statement on the Scientific Validity of the 3T3 NRU PT Test (an In Vitro Test for Phototoxic Potential) on 3 November 1997.

At the request if the SCCNFP (formerly SCC) presented in 1996 COLIPA has developed and concluded a III Phase of the research which applies this in vitro methodology to the testing of all those UV-filters already approved by the Cosmetic Directive (76/768/ECC, Annex VII) on which an opinion of safety has been expressed by SCCNFP.

According to a letter of COLIPA on 30 April 1998, the Management Team of the Research Project on Photoirritation expects to finalise its proposed paper for publication by June 1998. The Management Team proposes to meet with the SCCNFP/SWP to discuss the results of the special study on UV-filters during its first meeting after the summer holiday period.

To be mentioned here, that a Report on the results of this special study has already been presented to the meeting of the ECVAM-ESAC at the end of March (a specific study on UV Filter Chemicals from Annex VII of the EU Directive 76/768 in the 3T3 NRU in vitro Phototoxicity Test) and that a draft OECD Guidelines for Testing of Chemicals in vitro 3T3 NRU phototoxicity test is being circulated since 19 march 1998.

Depending on the validity of the results obtained in this Special Study on the UV Filters (Phase III) and on the availability of all data, the SWP is of the opinion that it should be possible to conclude on this area during 1999.

For another field of Phototoxicity, namely the Photomutagenicity, the SCCNFP Notes of Guidance revised in 1990 indicated two in vitro methodologies for testing the photomutagenic potential of the UV-filters.

Since 1990 cosmetic industries have been applying these two methods for the evaluation of new UV-filters under evaluation by the SCCNFP. In all cases the opinion has been positive, thus demonstrating that a co-operation between the European Commission and the Cosmetic Industry has proved the safety of cosmetics.

Percutaneous absorption

The evaluation of the percutaneous absorption of cosmetic ingredients represents a parameter of great relevance for the safety assessor, when requested to express his opinion on the systemic exposure dose of various consumers to different cosmetic ingredients. This value provides an objective criteria for defining the safety margin.

At present there are two draft guidelines at the OECD level since 1996: an in vivo methodology, on animal models, and an in vitro methodology, on a tissue model. There are no agreements at the international level on those two draft guidelines for the complexity and difficulty of the procedure, and on the lack of a scientifically valid database.

COLIPA has presented to the SWP all scientific and technical information based on the results of their continuous experience on the use of in vitro approach for evaluating percutaneous absorption of cosmetic ingredients, such as UV-filters, Hair Dyes and Preservatives: many of these studies developed by Cosmetic Industries have already been evaluated in the last 5 years by the SCCNFP when analysing the toxicological dossiers presented to the Commission.

At present COLIPA is selecting and organizing the scientific data to support a series of few protocols already developed for different cosmetic ingredients: the data will be presented later on this year for a final discussion on this area.

ECAVM has also developed a Workshop on the percutaneous absorption and is participating in the present activity of comparing in vitro vs. in vivo results.

The SWP intends to continue to develop contact with the scientific and technical experts from Cosmetic Industry to define a common basis of acceptance of a new in vitro methodology. It is a general opinion that at the end of 1998 or at the beginning of 1999, it should be possible to conclude on some in vitro methodology(ies), as suitable and adequate procedures for defining the level of percutaneous absorption of cosmetic ingredients.

Human testing

The SCCNFP has already declared since 1997 that the purpose of experiments on humans is to confirm findings on safety and to verify the acceptability and the efficacy of cosmetic products (XXIV/1814/97: XXIV/1878/97).

At present, there is no Commission position on human testing (XXIV/1285/98); however, it is under development an OECD Test Guideline for use in tests with Human Volunteers (ENY/MC/CHEM/RD(98)1) which is based on the Helsinki Declaration. This states that human testing conducted for chemicals and consumer products, must be associated with minimal risk, as it is conducted:

a) to confirm non-clinical information;

b) to confirm that exposure will not cause significant harm;

c) in a controlled fashion, that minimises subject risk.

COLIPA has published a Test Guideline for Assessment of Skin Compatibility of Cosmetic Finished products in Man (Food and Chemical Toxicology 34 (1996), 651-660) and a Test Guideline for the Assessment of Skin Tolerance of Potentially Irritant Cosmetic Ingredients in Man (Food and Chemical Toxicology 35 (1997) 1099-1106).

ECVAM has organised a Skin Irritation Task Force which has published its first Report in 1998 (ATLA 26, 1-17, 1998).

At present, there are no validated alternative methodologies for testing skin irritation potential on an in vitro or computer model procedure.

The SWP has discussed the scientific problems related to the testing for skin irritation by different methods with some scientific experts from Cosmetic Industries, and has already planned a series of presentation by experts on Structure Activity Relationship (SAR) and on Human Testing.

The SWP has already prepared a draft "Guidelines on the use of human volunteers in the testing of potentially cutaneous irritant cosmetic ingredients" and a final draft will be submitted to the plenary of September 1998, for its adoption.

It is clear that SWP indicates that "the human testing is only for confirmation of situations where no irreversible damaging effects are to be expected for the volunteers and where the study goal is reasonably achievable with a study population of limited size. This is true for the confirmation of skin tollerability (absence of irritation) but not for eye irritation, sensitization and other toxicological events.

The SWP is ready, if requested specifically by the Commission, to work on a Guideline of Human testing for Skin Irritation for the Evaluation of Finished Cosmetic Products. The SWP has requested an external /Pexpert (Dr. P.MASSON) to prepare a report on the EU Member Countries legislation concerning the ethical procedures for cosmetic products and their ingredients safety testing.

Revision and updating of notes of guidance (XXIV/1878/97)

Annex 7 (Microbiological Quality of the Finished Cosmetic Products) has been submitted to an extensive scientific and technical revision, by discussing the subject with experts from COLIPA and Cosmetic Industries.

In particular, the Microbiological Quality has been analysed in relation to the two specific categories of cosmetics, namely: (a) Products specifically intended for children under 3 years of age, eye area and mucous membranes, and (b) Other Products.

The microbial contamination limits have been revised, in relation to the number and the species of contaminants.

The second area of revision has interested the challenge testing.

A draft document will be submitted to the plenary of September 1998, for its final adoption.

Before concluding this Report, the SWP "Alternatives and Dossier" wishes to draw the attention of the DGXXIV on the difficulties of communication between the SWP itself and other Parties, especially the ECVAM's Scientific Staff. The SWP considers relevant the confrontation and discussion with other Commission Offices, to speed up the timing of knowledge and decision, to avoid equivocal misunderstanding, to improve our scientific meetings, to better serving the Commission Services.

In the meantime, the SWP requests the DGXXIV to improve its relationship with other Services of the Commission interested in different actions concerning the cosmetics, such as legislation, efficacy testing, safety testing, training on safety evaluation, in order to provide the SCCNFP with all types of information and co-operation programs which may be of interest for its activity in the field of Alternative Methods.