1. Adoption of the Agenda (doc. n° SCCNFP/0063/98) (Annex 1)

The agenda was adopted.

2. Approval of the minutes of the 4th plenary meeting of 23 September 1998

doc. n° SCCNFP/0050/98

The minutes were adopted subject to the following modification :

* point 4.3 Inventory : insertion of a paragraph on the work done concerning the botanicals and concerning section II of the inventory on fragrances;

* point 6 Questions raised by DG III - specific evaluation for children : is was stressed that future opinions must contain a special point addressing this issue. The following sentence was added to the minutes "It is proposed to note in a special keyword possible influences in children".

* orthographic corrections.

As a general remark, the secretariat was asked why the mandates received so far on alternative methods to animal testing and on the updating of the inventory have not been annexed to the minutes of the plenary meeting during which they were presented and discussed.

The Chairman proposed that next plenary of 20 January 1999, which is completely devoted to alternative methods, might be the right one to present all mandates received so far. This would simplify future searches for a specific mandate.

3. SCCNFP - Specific Working Parties

3.1 Alternatives to Animal Testing & Dossier

In his report, the co-ordinator said that his Working Party came to partial conclusions in relation to the mandate received. After consultation of the various parties concerned, namely ECVAM, the cosmetic industry and independent experts in specific fields, the WP approved draft opinions on (i) the use of human volunteers in the testing of potentially cutaneous irritant cosmetic ingredients or mixtures of ingredients, on (ii) in vitro methods to assess photo-toxicity in the safety evaluation of cosmetic ingredients or mixtures of ingredients and on (iii) in vitro methods to assess skin corrosivity in the safety evaluation of cosmetic ingredients or mixtures of ingredients.

(i) The use of human volunteers in the testing of potentially cutaneous irritant cosmetic ingredients or mixtures of ingredients - doc. n° SCCNFP/0003/98 rev. 11/98

The over-all aim of the document is to give special guidance on the development of irritancy test with the use of human volunteers.

The basic understanding of the document is that human testing is needed and appropriate and based on the fact that no validated alternative methods are approved for irritancy testing. Moreover, the rapporteurs stressed that in vivo tests, beside the fact that they will be banned in the future, are not very efficient. Test on human volunteers have been performed for several decades and a series of test procedures are used and agreed upon in European Union, the USA and Japan.

Some of the particular concerns of the WP were that the ethical problems are solved in a proper way, that the test performed are at no risk for the volunteers, and that tests assure high quality and optimal performance.

As a result of the discussion, the document was adopted by the plenary meeting, subject to the following modification :

on page 1, point 1.3 : points 1 and 2 of the second paragraph are merged so that the text reads : "The SCCNFP stresses three points :

1. Since tests in animals .... is available and that a high degree of safety is to be expected."

The Co-ordinator said that the document is to be inserted in the SCC's Notes of Guidance as Annex 10. As a consequence, its point 8.10 Human data is to be completed with the following sentence : 'Annex 10 of the Notes of Guidance presents the guidelines on the use of human volunteers in the testing of potential cutaneous irritant ingredients or mixture of ingredients'.

(ii) In vitro methods to assess photo-toxicity in the safety evaluation of cosmetic ingredients or mixtures of ingredients - doc. n° SCCNFP/0069/98, rev 11/98

The rapporteur illustrated the draft opinion which gives, besides the opinion of the SCCNFP, details on the background of the study, its organisation and stages, the critical questions which were raised and the answers thereto.

The meeting concluded by stating that the 3T3 NRU PT should be considered as the standard method for testing the photo-toxic potential of UV light absorbing chemicals, prior to their use in cosmetic formulations. A regulatory acceptance of this in vitro method is of particular importance as no accepted in vivo method exists.

The opinion was adopted subject to the following modifications :

* point 4 on page 2 : "used" is replaced by "considered";

* the word "Conclusion" is replaced by "Opinion of the SCCNFP";

* the text of the opinion is changed so that it reads ".... as the standard method for UV light absorbing chemicals for photo-toxic potential."

As a general remark, it was proposed that, for completeness, the spectrum of the solar simulator used should be annexed to the study results. Knowledge of this spectrum is of particular relevance as only irradiation with UV-A and visible light is currently carried out and as many chemicals show photo-toxic effects in the UVB range.

The Co-ordinator said that document n° SCCNFP/0069/98 is to be inserted in Annex 2 of the SCC's Notes of Guidance in the format it is adopted by the plenary.

(iii) In vitro methods to assess skin corrosivity in the safety evaluation of cosmetic ingredients or mixtures of ingredients - doc. n° SCCNFP/0070/98

The document is the result of the evaluation made and was illustrated by the rapporteur in order to get the approval of the SCCNFP.

It was adopted subject to the following modifications :

* point 3 Opinion of the SCCNFP : insert, as paragraph n° 2 the following sentence "Sixty chemicals were used for the validation of these two methodologies : 20 of them are used as cosmetic ingredients according to the European cosmetic inventory."

The aim of this paragraph is to give an indication when to use one of these specific in vitro methodologies as they are not related to specific end-points of immediate interest for the cosmetic safety evaluation.

* to add a complete list of references, analogous to the other opinions.

The Co-ordinator said that the document is to be inserted in the SCC's Notes of Guidance as Annex 11, with reference to point 8.3 Skin Irritation.

It was agreed to insert in these opinions an acknowledgement to thank members, and the members of the WP 'Alternatives' in particular, for their commitment.

To conclude his report, the Co-ordinator said the work of the WP will consist, for the coming month, (i) in revising the SCC's Notes of Guidance according to the opinions adopted today and (ii) in finalising and approve by the WP of a draft opinion on percutaneous absorption so that both documents can be presented to the plenary meeting of 20 January 1999.

For the coming year, work has to be done on the in vitro eye irritation method, on the definition of general criteria for human testing and on a complete guidance on human volunteers for the testing of finished products.

3.2 Hair Dyes

In his report, the co-ordinator mentioned that there have been one WP meeting on hair dyes since the 4th plenary meeting.

Working plan for the evaluation of pending hair dye dossiers :

The main concern of the WP is the list of pending issues. The secretariat prepared an overview of all the hair dye files ever received from the industry. Taking this list into account, the WP is of the opinion that, within its present organisation, it is not feasible to assess all these dossiers within a reasonable period of time.

Therefore, the Commission was asked to give the WP clear guidance on how to proceed this work. A first step might be to ask industry about the commercial interest for each of these hair dye constituents.

In the framework of this task, the Commission was asked about the necessity to evaluate the safety of the hair dyes at this point in time. The Commission replied by saying that hair dyes present a specific risk, as with the other 3 categories of ingredients (colorants, preservatives and UV filters) and which is not common to all cosmetic ingredients. Hair dyes are in intimate contact with the skin of the consumer and therefore present a certain risk. It is up to the Commission and the SCCNFP to legislate the framework by which the safety will be assessed.

There is indeed an interest in the safety evaluation of these chemicals because of the decision to assess all marketed hair dyes prior to the establishment of a positive list. The introduction of this list can only be abandoned because one believes a positive list is not the best way to protect consumer safety, but not because of a lack of resources.
The Commission stressed that a way out must be found before the possible establishment of the list in order to avoid serious disorientation of this specific market. Moreover, it was said that a solution to the problem is also important in the light of the forthcoming reorganisation of the Commission and in the Member States concerning health policy.

Reference samples :

The Co-ordinator said that the WP supports the request made by DG III to the industry to make samples of hair dyes available to the official laboratories of the Member States for analytical purposes, namely conformity checks of marketed cosmetic products. He stressed that the collection of samples supplied must be stable and that stability information and the conditions of storage must be sent at the same time.

DG III confirmed that such a letter was sent but said that the supply of samples for conformity purposes can only be requested for substances listed in an annex to the directive. So, there might be a point regarding 'hair dye'-samples as they are at present not subject to a specific piece of legislation. Nevertheless, the meeting underlined the importance it attaches to it and requested DG III to come to an agreement with the industry so that these sample can be made available.

Opinion on Hydroquinone as a skin depigmenting agent - doc. n° SCCNFP/0077/98

The Co-ordinator referred back to the WP meeting of 18 February 1998, during which a classification 2A was proposed for Hydroquinone as a skin depigmenting agent due to observed clinical side effects.

The document was adopted by the plenary without further observations.

Adopted classification : 2A

The draft opinion on Hydroquinone as a hair dye constituent will be discussed during the next WP meeting of 13 January 1999.

3.3 Preservatives, Colorants & Fragrances

In his report, the Co-ordinator mentioned the issues dealt with since the last plenary meeting :

* Fragrances : he mentioned that the work is progressing and that a working document was approved on fragrance allergy, and in particular on the size of the problem in epidemiological terms and on the importance of some fragrance ingredient identification on skin care products.

The document contains an exhaustive list of fragrance ingredients reported in literature as contact allergens. This list will be critically reviewed to come to a list of possibly about 20 substances of particular importance with regard to contact allergy.

He mentioned that a letter had been sent to EFFA to ask for information on the substances subject to IFRA restriction, and in particular the original data concerning their cutaneous toxicology (cutaneous safety).

Furthermore, a complete revision of section II on fragrance materials of the inventory has been undertaken making this section a useful resource.

* Acrylamide : the substance will be further discussed at the next WP meeting of 12.1.99, for which industry experts have been invited to answer the questions raised by the WP.

* Carbamide peroxide : the evaluation of the substance has also reached its final stage. A draft opinion is expected at the next WP meeting of 12.1.99. Industry was asked to demonstrate the long term safety of the substance. Their reply was asked for mid December at the very latest.

* Benzylhemiformal (P21) - doc. n° SCCNFP/0033/98 : The rapporteur presented the document and reported on the studies received as requested by the Committee. However, questions were raised concerning the reported mutagenicity data (e.g. positive Ames test).

As a result, it was decided to completely re-evaluate the submitted mutagenicity studies and to present the conclusions at the next WP meeting of 12.1.99.

As a general remark, it was proposed to ask for an use-test with a 0.15% formulation in people sensitised to formaldehyde.

Opinion on Benzalkonium chloride, bromide and saccharinate (P71) - doc. n° SCCNFP/0087/98

A classification 1 was adopted by the plenary meeting of 24.5.96 for this substance. However, there was concern, at Member State level, about the chain lengths of benzalkonium which would be suitable for 'other uses'.

Shorter chain lengths (C8-C14) are irritant to the skin and are used as preservatives at concentrations of up to 0.1%. Longer chain lengths (C16-C18) are much less irritant and are used in hair rinse-off products at up to 3% as conditioning agents.

Industry was asked to submit information on the distribution of the chain length typically used and a description of the chain length of the compounds tested.

Further to the evaluation of the data received, the SCCNFP adopted the opinion on P71 as presented by the rapporteur.

3.4 Inventory

In his report, the Co-ordinator said that, since the publication of the inventory in 1996, the former SCC adopted a series of recommendations to the industry for the first up-date of the inventory. A work programme was established and meetings were organised with the industry to discuss these recommendations and to adapt the inventory accordingly.

However, it appears that COLIPA, as the representative of the industry concerned, only took an restricted number of the committee's recommendations into consideration and postponed the remaining one to the second up-date.

In the mean time, the draft of the 1st up-date was submitted to the committee and the WP will now scientifically review the document and will prepare a draft opinion for adoption by the plenary meeting.

The Co-ordinator recalled that the WP is of the opinion that, at least, the following points must be included :

* solve to problem of the incorrect entries;

* correct the INCI names of the ethyl-hexyl derivatives;

* improve the functions corresponding to each ingredient entry;

* identify with more transparency the ingredients derived from plants (botanicals);

* revise the new entries proposed by European industry.

The representative of DG III said that, to their understanding and as no reference is made in the position papers adopted by the committee to a date by which a specific point should be included in the inventory, COLIPA might think that some modifications to the inventory are to be made for the 2nd or even 3rd up-date. A letter to COLIPA could clarify the committee's position.

3.5 UV Filters

In the absence of the Co-ordinator, the Chairman reported on the on-going issues. He said that 2 further meeting are already planned to finalise the draft opinions on 6 UV filters.

* Expert panel workshop : as reported earlier, the Committee envisages to organise early in 1999 an expert panel workshop to address health risks and health protection in relation to exposure to the sun. However, the organisation of a similar work shop in March 1999 by a private company came to the notice of the committee. Although it was found that the Committee's expert panel workshop would be considerably more focussed at health risks and health protection rather that the broader industry implications, it would not be opportune to organise it at nearly the same time. No new date was put forward, however great interest in this expert panel was already received from various sides.

5. Report of the Chairman

* Report of the meeting with Prof. Balls - ECVAM : The need for this meeting was determined by the present concern of the EC in view of the possible modification of the cosmetic legislation and of the discussion with the European Parliament. All those areas in which there seems to exist practicable alternative methods to the use of animals in the safety evaluation of cosmetics were discussed. As a result, the relevance of such discussions were stressed as well as the need to proceed with these contacts in the future, as a real and practical type of co-operation between ECVAM, DG XXIV and the SCCNFP.

The report presented by Prof. Loprieno is attached to the minutes.

6. Draft proposal for a 7th amendment to the Cosmetics Directive 76/768/EEC

The representative of DG III reported on the actual state of the 7th amendment.

The main changes to the present directive concern :

* the prohibition to test finished cosmetic products on animals. This requires however a proper definition of a finished cosmetic product;

* the prohibition to test ingredients on animals for those end-points validated alternative methods are available. A validated method will mean a method validated by the EU and not necessarily by OECD;

* to drop the dead-line to ban all animal testing because it is scientifically not realistic;

* to change the terms of the prohibition, namely to ban the testing on animals on the territory of the EU and not the marketing of products tested on animal;

* insert a procedure to request a derogation on these bans;

* changes in the terms of the safety assessor;

7. Any Other Business

* Diethylphthalate : request to review the safety of diethylphthalate due to its function as a cosmetic ingredient and its application in 'non-food' products. It was decided that the WP 'UV filters' would evaluate the safety of this substance.

Attendance List

Present : Mr K.E. Andersen, Mr R. Anton, Mr P. Blain, Mr J-F. Doré, Mr P. Elsner, Mr V. Kapoulas, Mr F. Kemper, Mr B. Lina, Mr N. Loprieno, Mr J. Parra, Mrs V. Rogiers, Mr T. Sanner, Mr J. Vives Rego, Mr I. White

External experts : Mr. L. Pons Gimier

Commission : Mr L. Bansil DG III, Mrs P. Decamps DG XXIV, Mrs M. de Solà DG XXIV, Mrs A. Duysens DG XXIV, Mrs F. Drion DG XXIV, Mr A. Van Elst DG XXIV

Apologies : Mr L. Celleno, Mrs Y. De Roeck-Holtzhauer, Mrs J.D. Johansen, Mr C.J. Powell

Agenda for the 5th plenary meeting

(Brussels, 25 November 1998)

1. Adoption of the agenda

SCCNFP/0063/98

2. Approval of the minutes of the 4th plenary meeting of 23.9.98

SCCNFP/0050/98

3. SCCNFP - Specific Working Parties

3.1 Alternatives

Report of the Co-ordinator :

Oral report on meeting 24.11.98

Guidelines on the use of human volunteers in the testing of potentially cutaneous irritant cosmetic ingredients

SCCNFP/0003/98

Opinion on in vitro methods to assess photo-toxicity in
the safety evaluation of cosmetic ingredients or mixtures
ingredients

SCCNFP/0069/98

Opinion on in vitro methods to assess skin corrosivity in
the safety evaluation of cosmetic ingredients or mixtures
of ingredients

SCCNFP/0070/98

3.2 Hair Dyes

Report of the Co-ordinator, including working programme

Draft opinion on Hydroquinone as a skin depigmenting agent

SCCNFP/0077/98
rapporteur : Prof. Kemper

3.3 Inventory

Report of the Co-ordinator

3.4 Preservatives

Report of the Co-ordinator

Draft opinion on Benzylhemiformal (P21)

SCCNFP/0033/98
rapporteur : Prof. Kemper

Draft opinion on Benzalkonium chloride, bromide &
saccharinate

SCCNFP/0087/98

3.5 UV Filters

Report of the Co-ordinator

4. Report of the Chairman

5. Draft proposal for a 7th amendment to the Cosmetics Directive 76/768/EEC

6. Any other business

VISIT TO ECVAM (ISPRA) BY M. DE SOLA (XXIV), F.KEMPER AND N.LOPRIENO (SCCNFP).

MEETING WITH M.BALLS (ECVAM), NOVEMBER 19th, 1998 - REPORT BY PROF. N.LOPRIEN0

The need for this meeting was determined by the present concern of the EC in view of the possible modification of the cosmetic legislation and of the discussion with the European Parliament.

It was decided to discuss all those areas in which there seems to exist practicable alternative methods to the use of animals in the safety evaluation of cosmetics.

1. FINISHED PRODUCTS

It has been confirmed by ECVAM the unjustified need of safety testing of finished cosmetic products on animals, as the safety depends mainly on the detailed knowledge of the toxicological profile of the individual cosmetic ingredients. The SCCNFP has stressed that this position has already been undertaken since 1990 (SPC/803-5/90) and reconfirmed in 1997 (XXIV/1878/97).

In practice, each cosmetic industry can rely on the safety of a finished product, by comparing it to similar marketed finished products.

The derogation from this principle could be advisable for exceptional cases, as indicated in the "Notes of Guidance for Testing of Cosmetic Ingredients for Their Safety Evaluation", Second Edition, p.44/46 (XXIV/1878/97).

2. PHOTOTOXICITY

On May 1998 a statement signed by ECVAM and DGXI/E/2, on the basis of the conclusions of the ECVAM Scientific Advisory Committee, recognised that the in vitro 3T3 NRU PT test had been demonstrated to be applicable for testing UV filters chemicals employed as UV filters in the cosmetic products for their photo-toxic potential.

Following a request from the Scientific Committee of Cosmetology of DGXXIV, eight UV filter chemicals from the positive list approved by the European Commission (Annex VII of Directive 76/768/EEC) were shown not to be photo-toxic in the validated 3T3 NRU PT test. These eight UV filter chemicals were recognised not to be photo-toxic in vivo in humans under use conditions. On the basis of this recent confirmatory study a draft proposal for an OECD Guideline on the in vitro 3T3 NRU Photo-toxicity test has been proposed by ECVAM.

A proposal for a final opinion on the use of this newly developed and already validated and confirmed in vitro method f or the safety evaluation of UV filter chemicals to be used in the cosmetic products, will be presented at the next SCCNFP Plenary Meeting scheduled on November 25th 1998.

It is however recognised that the impact from the introduction of this in vitro methodology in the safety evaluation of cosmetic ingredients will have a reduced significance, due to the low number of UV filter chemicals employed in cosmetology when compared to the large number of cosmetic ingredients of general use.

3. PHOTOMUTAGENICITY/PHOTOGENOTOXICITY

In another sector of the UV-induced photochemical damage of toxicological implication, namely Photo-mutagenicity , the SCCNFP Notes of Guidance (Doc. SPC/803-5/90) indicated two in vitro methodologies for testing the photo-mutagenic potential of the UV-filters employed in cosmetic products. Since 1990 cosmetic industries have been applying these two methods in the evaluation of new UV-filters under consideration of the SCCNFP. In all cases, the results of these new methodologies were recognised to be applicable, as they were demonstrated to be reliable in the safety evaluation of the cosmetic UV-chemical filters.

ECVAM stressed how it is not supposed to be involved in this sector of testing, by recognising the validity of the methodologies applied by the Cosmetic Industry.

4. SKIN CORROSIVITY/IRRITATION

Both ECVAM and SCCNFP recognised that the two in vitro methodologies validated so far (Pat Skin Transcutaneous Electrical Resistance (TER) Test and RISKIN Test) make possible the identification at the first step of "corrosive" and "non-corrosive' chemicals commonly used also in the cosmetic industrial sector, and the refinement of the following test procedures. The SCCNFP's SWP is currently preparing a draft

opinion to be submitted to the Plenary Meeting scheduled for November 25th 1998.

Studies for evaluating the potential for skin irritation are currently in progress, by using in vitro methodologies based on the application of human keratinocytes land pig ear monolayers. The final results are expected by the year 2000.

5. SKIN PENETRATION/PERCUTANEOUS ABSORPTION

Knowledge of in vitro testing procedures for assessing the percutaneous absorption of a cosmetic ingredient has considerably improved during recent years; many cosmetic ingredients were tested by one of these newly developed in vitro methodologies and many of these studies were accepted as a valid contribute to the evaluation of the toxicological profile of a given cosmetic ingredient by the SCCNFP.

COLIPA has presented to the SCCNFP all scientific and technical information based on the results of their continuous experience on the use of an in vitro approach to evaluate percutaneous absorption of cosmetic ingredients, such as UV-filters, hair dyes and preservatives.

At present, the SCCNFP together with COLIPA is selecting and organising, the available scientific data to support a set of several protocols already applied to different cosmetic ingredients.

It is a general opinion that by the end of 1998 it should be possible to conclude one or more in vitro methodologies, as suitable and adequate procedures for defining the level of percutaneous absorption of cosmetic ingredients.

The possibility to have in a short term a protocol approved by OECD seems unrealistic at the present, due to the controversial positions of the European and North American scientists.

ECVAM recognised that there are enough reasons to adopt in the specific sector of cosmetic ingredients in vitro test procedures for assessing skin penetration, due to' the long experience of cosmetic industries in this specific field.

SCCNFP's final opinion on the availability of in vitro test methods to assess the skin penetration of cosmetic ingredients should be transmitted to ECVAM, in order to be considered by its Advisory Committee (ESAC) as a contribution to the future positions of the European Commission.

6. EYE IRRITATION

ECVAM and SCCNFP have reviewed the sector of the validation studies concluded so far and have discussed the validity and a need for a long-term study on the basic mechanism of toxicity for eye irritation. However, they considered it unjustified when one considers the fact that, at present, there are some alternative methodologies (such as the HET-CAM and BCOP, for example) which are suitable to identify eye irritant chemicals of specific chemical classes.

ECVAM will investigate on the possibility to produce a scientific opinion on the possible use of some alternative methods for specific groups of cosmetic ingredients that could be recommended to SCCNFP and the European Commission. The practical value of such procedures depends also on the availability of a data base which allows the identification of "non-eye irritant" chemicals.

7. HUMAN VOLUNTEERS

Human volunteers are employed in the safety testing of cosmetics in the sector of skin compatibility and for evaluating the functions and efficacy of cosmetic products. ECVAM has been involved in a series of projects with dermatologists who apply non-invasive techniques in the evaluation of the efficacy. This aspect is requested by the new organisation of the Institute in Ispra for supporting consumers' protection, the efficacy being connected also to safety.

ECVAM is also to some extent co-operating with the EEMCO group, in the preparation of a report on "The Potential Use of Non-Invasive Measurements in Human Volunteers for the Safety Assessment of Cosmetics".

The SCCNFP is considering the possibility of using human volunteers for testing potentially cutaneous irritant cosmetic ingredients and mixtures of cosmetic ingredients. An opinion is currently being prepared to be submitted to the Plenary Meeting before the end of 1998.

Other areas of safety testing making use of human volunteers, seem unpredictable both to ECVAM and to the SCCNFP as well, for ethical reasons.

At the end of the meeting it was stressed the relevance of the discussion held during the meeting and the need to proceed with these contacts in the future, as a real and practical type of co-operation between ECVAM, D6XXXIV and the SCCNFP.