<b>Bijsluiter</b>. De hyperlink naar het originele document werkt niet meer. Daarom laat Woogle de tekst zien die in dat document stond. Deze tekst kan vreemde foutieve woorden of zinnen bevatten en de opmaak kan verdwenen of veranderd zijn. Dit komt door het zwartlakken van vertrouwelijke informatie of doordat de tekst niet digitaal beschikbaar was en dus ingescand en vervolgens via OCR weer ingelezen is. Voor het originele document, neem contact op met de Woo-contactpersoon van het bestuursorgaan.<br><br>====================================================================== Pagina 1 ======================================================================

<pre>Fytosterolen (3)
Tweede beoordeling van de veiligheid voor de consument, volgens de Europese
verordening 258/97 betreffende nieuwe voedingsmiddelen
en nieuwe voedselingrediënten
Phytosterols (3)
Second opinion regarding consumer safety, in accordance with European
Regulation 258/97 concerning novel foods and novel food ingredients
Gezondheidsraad:
Commissie Veiligheidsbeoordeling nieuwe voedingsmiddelen (VNV)
Health Council of the Netherlands:
Committee on the Safety Assessment of Novel Foods
aan/to:
de Minister van Volksgezondheid, Welzijn en Sport/
the Minister of Health, Welfare and Sport
de Minister van Landbouw, Natuurbeheer en Visserij/
the Minister of Agriculture, Nature management and Fisheries
Nr. 2003/01VNV, Den Haag, 13 februari 2003
No. 2003/01VNV, The Hague, February 13, 2003
</pre>

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<pre>De Gezondheidsraad, ingesteld in 1902, is een adviesorgaan met als taak de regering en het
parlement “voor te lichten over de stand der wetenschap ten aanzien van vraagstukken op
het gebied van de volksgezondheid” (art. 21 Gezondheidswet).
    De Gezondheidsraad ontvangt de meeste adviesaanvragen van de bewindslieden van
Volksgezondheid, Welzijn & Sport; Volkshuisvesting, Ruimtelijke Ordening &
Milieubeheer; Sociale Zaken & Werkgelegenheid en Landbouw, Natuurbeheer & Visserij.
De Raad kan ook eigener beweging adviezen uitbrengen. Het gaat dan als regel om het
signaleren van ontwikkelingen of trends die van belang kunnen zijn voor het
overheidsbeleid.
    De adviezen van de Gezondheidsraad zijn openbaar en worden in bijna alle gevallen
opgesteld door multidisciplinair samengestelde commissies van - op persoonlijke titel
benoemde - Nederlandse en soms buitenlandse deskundigen.
The Health Council of the Netherlands, established in 1902, is an independent scientific
advisory body. Its remit is “to advise the government and Parliament on the current level of
knowledge with respect tot public health issues” (Section 21, Health Act).
    The Health Council receives most requests for advice from the Ministers of Health,
Welfare & Sport; Housing, Spatial Planning & the Environment; Social Affairs &
Employment, and Agriculture, Nature management & Fisheries. The Council can publish
advisory reports on its own initiative. It usually does this in order to ask attention for
developments or trends that are thought to be relevant to government policy.
    Most Health Council reports are prepared by multidisciplinary committees of Dutch or,
sometimes, foreign experts, appointed in a personal capacity. The reports are available to the
public.
Deze publicatie kan als volgt worden aangehaald:
Gezondheidsraad: Commissie Veiligheidsbeoordeling nieuwe voedingsmiddelen.
Fytosterolen. Den Haag: Gezondheidsraad, 2003; publicatie nr. 2003/01VNV.
Preferred citation:
Health Council of the Netherlands: Committee on the Safety Assessment of Novel
Foods. Phytosterols (3). The Hague: Health Council of the Netherlands, 2003;
publication no. 2003/01VNV.
auteursrecht voorbehouden/all rights reserved
U kunt dit advies downloaden van www.gr.nl/
This report can be downloaded from www.healthcouncil.nl
</pre>

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<pre>  Inhoud/Contents
  Brief aan de Minister van Volksgezondheid, Welzijn en Sport 4
  Letter to the Minister of Health, Welfare and Sport 7
  Literatuur/Literature 10
  Bijlage/Annexes 12
A De Adviesaanvraag/Request for advice 13
B De commissie/The committee 15
C EU-procedure/EU-procedure 17
D Samenvatting van het dossier/Executive summary of the dossier 20
E Eerste beoordeling/First assessment 28
  Inhoud/Contents                                                  3
</pre>

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<pre>Gezondheidsraad Vice-voorzitter
Health Council of the Netherlands

Aan de Minister van Volksgezondheid,
Welzijn en Sport

Onderwerp : Tweede beoordeling veiligheid Fytosterolen (3)
Uw kenmerk : VGB/VL 2345876

Ons kenmerk : 2003/01VNV, U-257/MR/cv/622-CC

Datum : 13 februari 2003

Mijnheer de minister,

Dit schrijven dient ter beantwoording van de adviesaanvraag over de veiligheid van nieuwe
voedingsmiddelen en nieuwe voedselingrediënten, die door u mede namens de Minister van
Landbouw, Natuurbeheer en Visserij aan de Gezondheidsraad is voorgelegd. Aan de orde is een
zogenoemde tweede beoordeling, conform de Europese verordening 258/97, van het gebruik van
fytosterolesters in verschillende voedingsmiddelen. Het ingrediënt zelf is niet nieuw. De
aanvrager, de firma Unilever, wil het assortiment van producten waaraan fytosterolesters mogen
worden toegevoegd uitbreiden naar producten op basis van yoghurt en melk. Met melk worden in
deze aanvraag, naast magere en halfvolle melk, ook melkvarianten op basis van plantaardige olie
bedoeld. Uit markmonitoringsgegevens heeft de aanvrager vastgesteld dat consumptie van de al in
de handel zijnde fytosterolester-houdende vetsmeersels beduidend minder is dan voorafgaande aan
de markttoelating was ingeschat. Dit ziet Unilever als rechtvaardiging voor verbreden van het
assortiment. De beoordeling is verricht door de Commissie ‘Veiligheidsbeoordeling nieuwe
voedingsmiddelen’ van de Gezondheidsraad (Commissie VNV).

De eerste beoordeling van de aanvraag voor markttoelating is verricht in het Verenigd Koninkrijk
door het Advisory Committee on Novel Foods and Processes (ACNFP) van de Engelse assortiment
producten verrijkt met fytosterolesters, zoals beschreven in het veiligheidsdossier,
voedselautoriteit Food Standard Agency. De ACNFP concludeert dat uitbreiding van het
toelaatbaar is op voorwaarde dat de aanvrager zich houdt aan de afspraken over etikettering en de
marktmonitoring zal voortzetten.

De Commissie VNV baseert haar oordeel op het rapport van de eerste beoordeling door de
ACNFP? en op de informatie in het dossier. Ook heeft zij de rapporten van het Wetenschappelijk
Comité voor de menselijke voeding die recent zijn verschenen over verhoogde inneming van

Bezoekadres Postadres
Parnassusplein 5 Postbus 16052

2511 VX Den Haag 2500 BB Den Haag
Telefoon (070) 340 7520 Telefax (070) 340 7523

E-mail: gr@gr.n! www.gr.nl
</pre>

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<pre>Gezondheidsraad Vice-voorzitter

Health Council of the Netherlands

Onderwerp : Tweede beoordeling veiligheid Fytosterolen (3)
Ons kenmerk : 2003/01VNV, U-257/MR/cv/622-CC

Pagina :2

Datum : 13 februari 2003

fytosterolen hierbij in beschouwing genomen (SCF02, SCF02a), De commissie beoordeelde zelf al
eerder de veiligheid van fytosterolen en fytosterolesters (GRO1a) en fytostanolesters* (GR99). De
Commissie VNV is het grotendeels eens met de ACNFP dat consumptie van fytosterol-houdende
melk- en yoghurtachtige producten veilig is in de hoeveelheden die de aanvrager voorstelt, ook in
combinatie met consumptie van fytosterolverrijkte vetsmeersels.

In de eerdere rapporten heeft de Commissie VNV gepleit tegen uitbreiding van het
productassortiment. De resultaten van de marktmonitoring die door de aanvrager is uitgevoerd
maken echter voldoende aannemelijk dat de huidige consumptie van fytosterolen verwerkt in
vetsmeersels achterblijft bij de verwachting. Door consumptie van andere producten met
toegevoegde fytosterolen kan de totale dagelijkse fytosterolenconsumptie toenemen tot het niveau
van inneming waarvoor in 2000 reeds toestemming is verleend door de Europese Commissie
(Beschikking 2000/500/EG). |

Aanvullend op de eerste beoordeling constateert de Commissie VNV dat het niet duidelijk is
hoeveel verschillende zuivelachtige producten met toegevoegde fytosterolen de aanvrager op de
markt wil brengen. De commissie pleit er voor dat het totale productassortiment voldoende beperkt
blijft om de fytosterolinneming te kunnen beteugelen, Zij stelt dat assortimentsverbreding alleen
toelaatbaar is onder voorbehoud dat er garanties moeten zijn dat consumptie tot de doelgroep
beperkt blijft. Te meer daar bepaalde zuivelachtige dranken mogelijk ook andere
bevolkingsgroepen dan de doelgroep aanspreken. Alhoewel het niet aan de commissie VNV is
definitief te besluiten welke producten wel en niet voor verrijking met fytosterolen in aanmerking
komen, beschouwt zij het als noodzakelijk dat hierover in Europees verband regie wordt gevoerd
(zie ook hieronder).

De Commissie VNV brengt onder de aandacht dat waarschijnlijk een deel van de cholesterol-
bewuste consumenten geneigd is meer dan de aanbevolen hoeveelheid van fytosterolverrijkte
producten te gaan gebruiken. Om ongewenst hoge innemingen te voorkomen (stapeling) is naast
beperking van productassortiment strikte etikettering noodzakelijk, De commissie is het eens met
de ACNFP dat de toelating van deze aanvraag, en daarmee samenhangend de
etiketteringsvoorschriften, niet los kan worden gezien van de andere aanvragen voor

* Fytosterol is de bioactieve component van de fytosterolester. Aan fytosterolen verwante verbindingen zijn
de fytostanolen (“verzadigde fytosterolen’) met een vergelijkbare cholesterolverlagende werking

Bezoekadres Postadres
Parnassusplein 5 Postbus 16052

2511 VX Den Haag 2500 BB Den Haag
Telefoon (070) 3407520 Telefax (070) 3407523

E-mail: gr@gr.nl www.gr.nl
</pre>

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<pre>Gezondheidsraad Vice-voorzitter
Health Council of the Netherlands

Onderwerp : Tweede beoordeling veiligheid Fytosterolen (3)
Ons kenmerk : 2003/01 VNV, U-257/MR/cv/622-CC

Pagina :3

Datum : 13 februari 2003

markttoelating van allerlei producten met fytosterolen en vergelijkbare verbindingen, die nu
worden beoordeeld op Europees niveau door het Wetenschappelijk Comité voor de menselijke
voeding (SCF02b). Niet alleen de Commissie VNV (GR01, GRO1a), ook het Europese
Wetenschappelijk Comité heeft geconcludeerd dat er meer onderzoek nodig is naar mogelijke
langetermijneffecten van inneming van toegevoegde fytosterolen (SCF02a).

Ten overvloede merkt de Commissie VNV op dat de veilige bovengrens van dagelijkse
Fytosterolinneming, die in het dossier wordt vermeld, verwijst naar de waarde die de aanvrager zelf
heeft afgeleid op basis van subchronisch toxicologisch onderzoek bij ratten. Deze is niet afkomstig
van evaluaties door de Joint FAO/WHO Expert Committee on Food Additives zoals de ACNFP
stelt. Volgens de Commissie VNV en het Europese Wetenschappelijk Comité voor de menselijke
voeding kan er op basis van het huidige totaal aan beschikbare gegevens nog geen veilige
bovengrens worden afgeleid voor levenslange, dagelijkse fytosterolinneming (SCFO2a).

Ik onderschrijf de conclusies en aanbevelingen van de Commissie VNV.

Hoogachtend,

prof, dr JGAJ Hautvast

Bezoekadres Postadres
Parnassusplein 5 Postbus 16052

2511 VX Den Haag 2500 BB Den Haag
Telefoon (070) 3407520 Telefax (070) 3407523

E-mail: gr@gr.nl www.gr.nl
</pre>

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<pre>Letter to the Dutch Minister of Health,
Welfare and Sport
On Februari 13, 2003, professor JGAJ Hautvast, Vice-president of the Health Council of
the Netherlands wrote as follows to the Minister of Health, Welfare and Sport:
     This letter has been prepared in reply to your request for advice regarding the safety
of novel foods and food ingredients, also made on behalf of the Minister of Agriculture,
Nature Management and Fisheries. The subject in question is a second opinion, in
accordance with European Regulation 258/97, concerning the use of phytosterol esters
in a range of food products. The ingredient itself is not novel. The applicant, the
company Unilever, would like to extend the range of products which are permitted to
contain added phytosterol esters, to include yoghurt and milk. The milk type products
referred to in the application include skimmed and semi-skimmed milk, as well as
vegetable-oil-based milk variants. The applicant concludes from post launch monitoring
results that consumption of the phytosterol-fortified yellow fat spreads already available
on the market is considerably lower than the level of consumption assumed in the
original Novel Foods submission. Unilever regards this as a justification for broadening
the range of phytosterol-fortified products. This assessment has been carried out by the
Committee on Safety Assessment of Novel Foods (VNV Committee) of the Health
Council of the Netherlands.
     The initial assessment of the application for market introduction was carried out in
the United Kingdom by the Advisory Committee on Novel Foods and Processes
(ACNFP) of the Food Standards Agency. The ACNFP concludes that it is acceptable to
extend the range of uses of phytosterols as described in the application dossier. Any
Letter to the Dutch Minister of Health, Welfare and Sport                                   7
</pre>

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<pre>  approval should, however, be subject to a requirement for further post launch
  monitoring and labelling measures.
       The VNV Committee bases its findings on the report of the initial assessment by the
  ACNFP and on the information contained in the dossier. In addition to this, it has also
  considered the recently published reports by the Scientific Committee on Food which
  examine increased intake of phytosterols (SCF02, SCF02a). The VNV Committee itself
  has previously assessed the safety of phytosterols and phytosterol esters (GR01a), and of
  phytostanol esters* (GR99). The Committee largely agrees with the British assessment
  that it is safe to consume phytosterol-fortified milk and yoghurt type products in the
  amounts proposed by the applicant, also when combined with an intake of yellow fat
  spreads with added phytosterols.
       In its previous reports, the VNV Committee objected to extension of the product
  range. However, the post launch monitoring results presented by the applicant provide
  sufficient evidence that the actual consumption of phytosterols incorporated in fat
  spreads does fall short of expectations. By using other products with added phytosterols,
  consumers can increase their total daily phytosterol intake to the level of intake already
  approved in 2000 by the European Commission (Decision 2000/500/EC).
       In addition to the first assessment, the Committee notes that it is not clear how many
  different fortified dairy products the applicant intends to introduce on the market. The
  Committee advices that sufficient restrictions should be imposed on the total range of
  products with a view to curbing phytosterol intake. It concludes that extension of the
  product range is only acceptable provided that there will be guarantees that consumption
  remains confined to the target group, especially since certain dairy drinks may also
  appeal to individuals outside the target group. Although it is not the VNV Committee’s
  task to decide which products are suitable for fortification with phytosterols, it does
  regard European regulation of this issue as essential (see also below).
       The Committee would also like to point out the likelihood that some cholesterol-
  conscious consumers will tend to exceed the recommended amount of phytosterol-
  fortified products. Apart from limits on the product range, strict labelling is also
  required to prevent cumulative intakes from different products. The Committee agrees
  with the ACNFP that approval of this application, and the attendant labelling
  requirements, cannot be considered independently of the other applications for
  admission to the market of various products with added phytosterols and related
  compounds, currently being assessed at European level by the Scientific Committee on
  Food (SCF02b). Both the VNV Committee (GR01, GR01a) and this European Scientific
* Phytosterol is the bioactive component of the phytosterol ester. Compounds related to phytosterols are the phytostanols,
  which are ‘saturated phytosterols’, having similar cholesterol-lowering effects.
  Letter to the Dutch Minister of Health, Welfare and Sport                                                               8
</pre>

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<pre>Committee have reached the conclusion that additional research is needed to evaluate
the possible effects of long-term exposure to elevated levels of phytosterols (SCF02a).
    Finally, the Committee would like to point out that the safe upper daily intake level
of phytosterol stated in the dossier refers to the value that has been deduced by the
applicant itself, based on sub-chronic toxicological studies in rats. This value does not
come from evaluations of exposure to phytosterols conducted by the Joint FAO/WHO
Expert Committee on Food Additives, as the ACNFP suggests. The VNV Committee
and the European Scientific Committee on Food agree that the sum of the available data
does not yet provide a basis for determining a safe upper level of lifelong daily
phytosterol intake.
I endorse the conclusions and recommendations of the VNV Committee,
(signed) professor JGAJ Hautvast
Letter to the Dutch Minister of Health, Welfare and Sport                                 9
</pre>

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<pre>      Literatuur/Literature
EG97  Verordening (EG) Nr. 258/97 van het Europees Parlement en de Raad van 27 januari 1997 betreffende
      nieuwe voedingsmiddelen en nieuwe voedselingrediënten. Publikatieblad van de Europese
      Gemeenschappen 1997; L43: 1-6. (Regulation (EC) No 258/97 of the European Parliament and of the
      Council of 27 January 1997 concerning novel foods and novel food ingredients. Official Journal 1997; L
      043: 1-6).
EG97a 97/618/EG: Aanbeveling van de Commissie van 29 juli 1997 betreffende de wetenschappelijke aspecten en
      de presentatie van de informatie die nodig is om aanvragen voor het in de handel brengen van nieuwe
      voedingsmiddelen en nieuwe voedselingrediënten te ondersteunen alsmede het opstellen van de verslagen
      van de eerste beoordeling uit hoofde van Verordening (EG) nr. 258/97 van het Europees Parlement en de
      Raad. Publicatieblad van de Europese Gemeenschappen 1997; L253: 1-36. (97/618/EC: Commission
      Recommendation of 29 July 1997 concerning the scientific aspects and the presentation of information
      necessary to support applications for the placing on the market of novel foods and novel food ingredients
      and the preparation of initial assessment reports under Regulation (EC) No 258/97 of the European
      Parliament of the Council. Official Journal 1997; L 253: 1-36).
FAO96 Biotechnology and Food Safety. Report of a joint FAO/WHO Consultation. Rome, FAO 1996.
FAO01 Evaluation of allergenicity of genetically modified foods. Report of a joint FAO/WHO expert consultation
      on allergenicity of foods derived from biotechnology. Rome, FAO 2001.
GR92  Commissie Toxicologische aspecten van biotechnologisch bereide producten. Productveiligheid bij nieuwe
      biotechnologie. Den Haag, Gezondheidsraad 1992, publicatienummer 1992/03.
GR99  Commissie Veiligheidsbeoordeling nieuwe voedingsmiddelen. Fytostanolesters. Den Haag,
      Gezondheidsraad 1999, publicatienummer 1999/5VNV.
      Literatuur/Literature                                                                                     10
</pre>

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<pre>GR01   Commissie Veiligheidsbeoordeling nieuwe voedingsmiddelen. Fytosterolen. Den Haag, Gezondheidsraad
       2001, publicatienummer 2001/01VNV (Committee on the Safety Assesment of Novel Foods. Phytosterols.
       The Hague, Health Council of the Netherlands 2001, publication no. 2001/01VNV).
GR01a  Commissie Veiligheidsbeoordeling nieuwe voedingsmiddelen. Fytosterolen (2). Den Haag,
       Gezondheidsraad 2001, publicatienummer 2001/04VNV (Committee on the Safety Assesment of Novel
       Foods. Phytosterols (2). The Hague, Health Council of the Netherlands 2001, publication no. 2001/
       04VNV).
OECD93 Safety evaluation of foods derived by modern biotechnology. Concepts and principles. Paris, OECD 1993.
OECD96 OECD Workshop on Food Safety Evaluation. Paris, OECD 1996.
OECD98 Report of the OECD workshop on the toxicological and nutritional testing of novel foods. Paris, OECD
       1998.
OECD00 Report of the task force for the safety of novel foods and feeds. Paris, OECD 2000.
SCF99  Opinion concerning the scientific basis for determining whether food products, derived from genetically
       modified maize, could be included in a list of food products which do not require labelling because they do
       not contain (detectable) traces of DNA or protein. Brussels, Scientific Committee on Food of the EU 1999.
SCF02  Opinion of the Scientific Committee on Food on a report on Post Launch Monitoring of “yellow fat spreads
       with added phytosterol-esters” (expressed on 26 september 2002). Brussels, Scientific Committee on Food
       of the EU, 2002.
SCF02a General view of the Scientific Committee on Food on the long-term effects of elevated levels of
       phytosterols from multi dietary sources, with particular attention to the effects on β-carotene (opinion
       expressed on 26 september 2002). Brussels, Scientific Committee on Food of the EU, 2002.
SCF02b Minutes’ statement of the Scientific Committee on Food on applications for approval of a variety of plant
       sterol-enriched foods (expressed on 4 December 2002). http://europa.eu.int/comm/food/fs/sc/scf/
       out152_en.pdf
SSC99  Opinion of the Scientific Steering Committee on microbial resistance, Brussels, Scientific Steering
       Committee of the EU 1999.
WHO91  Strategies for assessing the safety of foods produced by biotechnology. Report of a joint FAO/WHO
       Consultation. Geneva, WHO 1991.
WHO00  Safety aspects of genetically modified foods of plant origin. Report of a joint FAO/WHO expert
       consultation on foods derived from biotechnology. Geneva, WHO 2000.
       Literatuur/Literature                                                                                       11
</pre>

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<pre>A De adviesaanvraag/Request for advice
B De commissie/The committee
C EU-procedure/EU-procedure
D Samenvatting van het dossier/Executive summary of the dossier
E Eerste beoordeling/First assessment
  Bijlagen/Annexes
                                                                12
</pre>

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<pre>Bijlage A
        De Adviesaanvraag/Request for advice
        Op 18 augustus 1999 schreef de Minister van Volksgezondheid, Welzijn en Sport aan de
        Voorzitter van de Gezondheidsraad (brief kenmerk GZB/VVB 993428):
        Sinds mei 1997 is in de Europese Unie de Verordening (EG) 258/97 van kracht inzake nieuwe
        voedingsmiddelen en nieuwe voedselingrediënten. Daarmee werd de veiligheidsbeoordeling onderdeel van
        een communautaire procedure.
             Met u is reeds de mogelijkheid besproken de beoordeling door de Gezondheidsraad te laten uitvoeren.
        Ik verzoek u dan ook mede namens de Staatssecretaris van Landbouw, Natuurbeheer en Visserij, in deze
        eerste fase van uitvoering van de Europese Verordening (EG) 258/97 gedurende een aantal jaren, de
        veiligheidsbeoordeling gestalte te geven. Voor het onderbrengen bij de Gezondheidsraad pleit het
        experimentele karakter dat de beoordeling de eerste jaren zal hebben. Dit experimentele karakter komt voort
        uit het feit dat het een nieuw soort beoordeling betreft van deels nieuwe categorieën van voedingsmiddelen
        of voedselingrediënten. Het is namelijk een veiligheidsbeoordeling vóór het op de markt brengen van met
        name voedingsmiddelen van een genetisch gemodificeerde oorsprong en zogenaamd functional foods
        (nutriceutica). Daarnaast ga ik ervan uit dat de onafhankelijke wetenschappelijke advisering door de
        Gezondheidsraad het vertrouwen van de Europese Commissie en de andere lidstaten in het Nederlandse
        oordeel nog versterkt.
             Mijn beleid is erop gericht een zo groot mogelijke openheid en transparantie te realiseren van de
        gevolgde procedure en de beoordeling om de consument vertrouwen te geven in de veiligheid van de
        De Adviesaanvraag/Request for advice                                                                        13
</pre>

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<pre>nieuwe voedingsmiddelen. Ik verzoek de Gezondheidsraad hieraan bij te dragen door bijvoorbeeld inzage te
geven in de dossiers waarvoor een aanvraag wordt ingediend, waarbij uiteraard bedrijfsvertrouwelijke
gegevens worden beschermd en door de criteria, waarop de veiligheid zal worden beoordeeld, te publiceren.
De Minister van Volksgezondheid, Welzijn en Sport,
w.g. dr E Borst-Eilers
English translation
On 18 August 1999, the Minister of Health, Welfare and Sport wrote as follows to the
President of the Health Council of the Netherlands (under reference GZB/VVB
993428):
Since May 1997, Regulation (EC) 258/97 concerning novel foods and novel food ingredients has been in
force in the European Union. Under the Regulation, the safety of novel foods has to be assessed as part of a
community procedure.
     Following discussions regarding the possibility of the Health Council making such assessments, the
State Secretary for Agriculture, Nature Management and Fisheries and I wish the Council to take
responsibility for safety assessment for a period of several years during the fist phase of implementation of
European Regulation (EC) 258/97. It is considered appropriate that the Health Council should initially take
on this role because the assessment activities will be of an experimental nature, involving both a new form
of assessment (i.e. pre-marketing assessment) and, in many cases, new categories of foodstuff (primarily
foodstuffs with a genetically modified basis and functional foods or nutraceuticals). We also feel that if
assessments are made by a body with the Council's independent scientific status, this will support the
validity of the Netherlands' opinion in the eyes of the European Committee and other member states.
     My wish is to make the procedure and the assessment as open and transparent as possible, so as to
enhance consumer trust in the safety of novel foods. I would like the Health Council to support this
objective by, for example, allowing perusal of the application dossier (insofar as consistent with the need to
protect the confidentiality of commercially sensitive information) and publishing the criteria upon which
safety assessments are made.
The Minister of Health, Welfare and Sport,
(signed) dr E Borst-Eilers
De Adviesaanvraag/Request for advice                                                                           14
</pre>

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<pre>Bijlage B
        De commissie/The committee
        •  Prof. dr LM Schoonhoven, voorzitter/chairman
           emeritus hoogleraar entomologie; Wageningen Universiteit en Researchcentrum/
           emeritus professor of entomology; Wageningen University and Research centre
        •  Prof. dr CAFM Bruijnzeel-Koomen
           hoogleraar dermatologie/allergologie; Academisch Ziekenhuis Utrecht/
           professor of dermatology/allergology; Academic Hospital Utrecht
        •  Ir EJ Kok
           toxicoloog; RIKILT-DLO Wageningen/
           toxicologist; State Institute for Quality Control of Agricultural Products,
           Wageningen
        •  Dr CF van Kreijl
           moleculair-bioloog; RIVM Bilthoven/
           molecular biologist; National Institute of Public Health and the Environment,
           Bilthoven
        •  Prof. dr P van der Laan
           hoogleraar statistiek; Technische Universiteit Eindhoven/
           professor of statistics; Technical University Eindhoven
        •  Dr F Nagengast
           gastro-enteroloog; Academisch Ziekenhuis Nijmegen/
           gastro-enterologist; Academic Hospital Nijmegen
        De commissie/The committee                                                       15
</pre>

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<br><br>====================================================================== Pagina 16 ======================================================================

<pre>•  Dr JMA van Raaij
   voedingsfysioloog; Wageningen Universiteit and Researchcentrum/
   food physiologist; Wageningen University and Research centre
•  Prof. dr G Schaafsma
   hoogleraar voeding; TNO Voeding, Zeist/
   professor of nutrition; TNO Nutrition and Food Research, Zeist
•  Prof. dr EG Schouten
   hoogleraar epidemiologie; Wageningen Universiteit and Researchcentrum/
   professor of epidemiology; Wageningen University and Research centre
•  Dr GJA Speijers
   toxicoloog; RIVM Bilthoven/
   toxicologist; National Institute of Public Health and the Environment, Bilthoven
•  Prof. dr WJ Stiekema
   hoogleraar bioinformatica; Wageningen Universiteit en Researchcentrum/
   professor of bioinformatics; Wageningen University and Research centre
•  Ir R Top, adviseur/advisor
   Ministerie van VWS; Den Haag/
   Ministry of Health, Welfare and Sport; The Hague
•  Prof. dr WM de Vos
   hoogleraar microbiologie; Wageningen Universiteit en Researchcentrum/
   professor of microbiology; Wageningen University and Research centre
•  Dr ir F van der Wilk, adviseur/advisor
   COGEM, Den Haag/
   Committee on Genetic Modification, The Hague
•  Dr RA Woutersen
   toxicoloog; TNO Voeding, Zeist/
   toxicologist; TNO Nutrition and Food Research, Zeist
•  Dr ir M Rutgers, secretaris/scientific staff member
   Gezondheidsraad, Den Haag/
   Health Council of the Netherlands, The Hague
Administratieve ondersteuning/Administrative assistance: CL Vuijst; Gezondheidsraad,
Den Haag/Health Council of the Netherlands, The Hague.
Lay-out: J van Kan; Gezondheidsraad, Den Haag/Health Council of the Netherlands,
The Hague.
De commissie/The committee                                                           16
</pre>

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<pre>Bijlage C
        EU-procedure/EU-procedure
        Als een fabrikant een nieuw voedingsmiddel op de markt brengt, dient de veiligheid
        voor de consument gewaarborgd te zijn. In 1997 werd de Europese verordening van
        kracht waarin de procedure is geregeld voor de goedkeuring voor marktintroductie van
        een nieuw voedingsmiddel (EG97). Bij deze procedure zijn verschillende actoren
        betrokken. De aanvrager moet beoordelen of het product werkelijk 'nieuw' is, dat wil
        zeggen dat het nog niet eerder in de Europese Unie in substantiële mate voor menselijke
        voeding is gebruikt en ook niet wezenlijk gelijkwaardig is aan een bestaand product.
        (Voor een wezenlijk gelijkwaardig product kan worden volstaan met een kennisgeving
        van de marktintroductie.) Ook moet het niet gaan om een levensmiddelenadditief, aroma
        of extractiemiddel, omdat deze producten op een andere wijze worden beoordeeld. Voor
        een nieuw voedingsmiddel in de zin van de Europese verordening moet de aanvrager
        een veiligheidsdossier overleggen volgens aanbevelingen van de Europese Commissie
        (EG97a). Deze aanbevelingen zijn gebaseerd op rapporten van verschillende instanties
        die zich met het onderwerp nieuwe voedingsmiddelen bezighouden, te weten de OECD
        (OECD93, OECD96) en de WHO/FAO (FAO96, WHO91). Ook de Gezondheidsraad
        heeft zich al eerder over dit onderwerp gebogen (GR92). Sinds het verschijnen van de
        aanbevelingen van de EU wordt in internationaal verband gewerkt aan explicitering en
        aanpassing aan de stand van de wetenschap (FAO01, OECD98, OECD00, SCF99,
        SSC99, WHO00).
            De fabrikant levert het volgens de richtlijnen samengestelde dossier in bij het land
        waar het product het eerst op de markt zal komen. Daarop komt de nationale
        veiligheidsbeoordelingsautoriteit in actie. In Nederland is dat de Minister van
        EU-procedure/EU-procedure                                                                17
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<pre>Volksgezondheid, Welzijn en Sport. Zij heeft de Gezondheidsraad verzocht haar van
advies te dienen. De Voorzitter van de Gezondheidsraad heeft hiertoe de commissie
Veiligheidsbeoordeling nieuwe voedingsmiddelen (commissie VNV) ingesteld.
     De commissie beoordeelt op basis van de huidige stand van de wetenschap of de
door de fabrikant geleverde gegevens juist en volledig zijn en of zij het eens is met diens
conclusies. Zij maakt een verslag van haar bevindingen — ook volgens de Europese
aanbevelingen (EG97a, deel III) — en biedt dat de minister aan. De minister formuleert
het Nederlandse oordeel over een voedingsmiddel en brengt dat in bij het Europese
overleg in het Permanent Comité voor levensmiddelen. Alle Europese lidstaten worden
uitgenodigd hun oordeel (de zogeheten tweede beoordeling) te geven over het dossier en
over de eerste beoordeling alvorens genoemd Comité een eindoordeel velt. Als een
dossier veel vragen oproept, gaat er een adviesvraag van de Europese Commissie naar
het Wetenschappelijk Comité voor de menselijke voeding. Komt men dan nog niet tot
overeenstemming dan beslist de Europese Ministerraad.
English translation
When manufacturers bring novel foodstuffs onto the market, consumer safety has to be
ensured. In 1997, a European Regulation (EG97) came into force, laying down the
procedure for approving the market introduction of novel foodstuffs. The procedure
recognizes various actors. The applicant must decide whether a product is a novel
foodstuff, i.e. a substance that has not previously been available for human consumption
to any substantial extent within the European Union and is not substantially equivalent
to any existing product. (If a foodstuff is substantially equivalent to any existing
product, it is sufficient to inform the authorities of its market introduction). Food
additives, aromas and extracts are excluded from the provisions of the directive, since
they fall within the scope of an established assessment regime. Before marketing a novel
foodstuff, the applicant must compile a safety dossier that complies with the
Recommendations of the European Commission (EG97a). These Recommendations are
based on reports by a number of bodies that have studied the issue of novel foodstuffs, in
particular the OECD (OECD93, OECD96) and the WHO/FAO (FAO96, WHO91). The
Health Council of the Netherlands has also considered the question earlier (GR92).
Since publication of the EU recommendations, international efforts have been made to
clarify and adapt the latest scientific knowledge in the field (FAO01, OECD98,
OECD00, SCF99, SSC99, WHO00).
     Having compiled a dossier in line with the guidelines, the manufacturer has to
submit it to the competent authority in the country where the product is to be marketed
first. This dossier is assessed by the national safety assessment authority. In the
Netherlands, this is the Minister of Health, Welfare and Sport, who is advised by the
EU-procedure/EU-procedure                                                                   18
</pre>

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<pre>Health Council. The President of the Health Council has created a Committee on the
Safety Assessment of Novel Foods (VNV Committee) to advise the minister on behalf
of the Council.
     On the basis of the scientific state of the art, the committee has to decide whether the
information provided by the manufacturer is accurate and complete and whether the
manufacturer's conclusions are sound. The committee then draws up a report on its
findings for the minister; this report must also comply with the European
Recommendation (EG97a, part III). After considering the report, the minister formulates
the Netherlands' opinion regarding the foodstuff in question, which is discussed at
European level in the Standing Committee on Foodstuffs. All other European member
states are invited to express a 'second opinion' regarding the dossier and the first
opinion. The Standing Committee then arrives at a final judgement. If a dossier is
particularly contentious, the European Commission calls upon the Scientific Committee
on Food for advice. If consensus still cannot be reached, the issue is referred to the
European Council of Ministers.
EU-procedure/EU-procedure                                                                     19
</pre>

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<br><br>====================================================================== Pagina 20 ======================================================================

<pre>Bijlage D
        Samenvatting van het dossier/
        Executive summary of the dossier
        Samenvatting van het dossier/ Executive summary of the dossier 20
</pre>

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<pre>PHYTOSTEROL-ESTERS:
USE IN A RANGE OF FOOD PRODUCTS

SUMMARY

AUTHOR: LINDA LEA

SAFETY AND ENVIRONMENTAL ASSURANCE CENTRE
UNILEVER COLWORTH

SHARNBROOK
BEDFORD MK44 1LQ Date : July 2002
UK Document reference: D02-027

SEAC
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<pre>Phytosterol-esters: Use in a range of food products Page ii of ii

PHYTOSTEROL-ESTERS:

USE IN A RANGE OF FOOD PRODUCTS

CONTENTS
PAGE
1, ADMINISTRATI VE DATA | 1
2. APPLICATION 2

3. IDENTIFICATION OF ESSENTIAL INFORMATION REQUIREMENTS 3

4. ‘SUMMARY | 4

SEAC
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<pre>Phytosterol-esters: Use in a range of food products Page 1 of 5

1. ADMINISTRATIVE DATA

Applicant: Unilever Pic
Unilever House
Blackfriars
London EC4P 4BQ

Manufacturer: Unilever Bestfoods UK Limited
Brooke House
Manor Royal
Crawley
RH10 2RQ

Person responsible Linda Lea
for the dossier: Safety and Environmental Assurance Centre
Unilever Colworth |
Sharnbrook
Bedfordshire
MK44 1LA
UK

Tel: 0044 1234 264746
Fax: 0044 1234 264711

SEAC
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<pre>Phytosterol-esters: Use in a range of food products Page 2of 5

2. APPLICATION

This application seeks approval for the use of phytosterol-esters to be included as a
cholesterol-lowering ingredient in ‘milk’ and ‘yoghurt’ type products. This is in addition
to the approved use in Yellow Fat Spreads.

The ‘milk’ type products would include skimmed, semi-skimmed and vegetable oil
based milk variants. The ‘yoghurt’ type products would include a range of natural and
fruit flavoured yoghurts. It is understood that, under EU milk legislation (EC Directive
95/2) and the varying national legislation across member states covering yoghurt, the
addition of phytosterol-esters, and other ingredients required to stabilise the
products, will prevent the use of the term ‘milk’ and ‘yoghurt’, to describe these Novel
Foods.

Phytosterol-esters are considered to be the Novel Food Ingredient and the ‘milk’ and
‘yoghurt’ type products with added phytosterols-esters the Novel Foods.

SEAC
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<pre>Phytosterol-esters: Use in a range of food products Page 3 of 5

3. IDENTIFICATION OF ESSENTIAL INFORMATION REQUIREMENTS

The structured scheme (Table II, Part | under EC Regulation No. 258/97) has been
followed to determine which of schemes I-XIII are essential to provide data permitting
a safety and nutritional evaluation of the Novel Food Ingredient.

With phytosterol-esters falling into Class 1.1 the following information should be
provided:

1. Specification of the Novel Food

11. Effect of the production process applied to the Novel Food

Ill. History of the organism used as the source of the Novel Food
IX. Anticipated intake/extent of use of the Novel Food

X. Information from previous human exposure to the Novel Food or its source
XI. Nutritional information on the Novel Food
XII. _ Microbiological information on the Novel Food

XIII. Toxicological information on the Novel Food

This information is provided in document D02-018 ‘Phytosterol-esters: use in a range
of food products’. Where appropriate, reference has been made in D02-018 to
Unilever’s previous application for the use of phytosterol-esters in Yellow Fat
Spreads which was approved under Regulation (EC) No 258/97 in European
Commission Decision 2000/500/EC of 24 July 2000.

SEAC
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<pre>Phytosterol-esters: Use in a range of food products Page 4 of 5

4. SUMMARY

Under Regulation (EC) No 258/97 on Novel Foods and Food Ingredients, Unilever
received approval for the use of phytosterol-esters as a novel food ingredient in
Yellow Fat Spreads in European Commission Decision 2000/500/EC of 24 July 2000
(EC, 2000). Under Article 3 of this decision, Unilever was required to establish a
surveillance programme to accompany the marketing of the product. The results of
this surveillance programme, referred to as Post Launch Monitoring, showed that
intakes of the spread were lower than that assumed in the Novel Foods submission
with no evidence of adverse health effects.

This indicates that there is an opportunity to offer consumers alternative or additional
healthy foods to deliver optimal cholesterol-lowering benefits without increasing the
intake of phytosterols above the level already approved. This application seeks
approval for the use of phytosterol-esters to be included as a cholesterol-lowering
ingredient in ‘milk’ and ‘yoghurt’ type products. This is in addition to the approved
use in Yellow Fat Spreads.

The phytosterol-esters to be used in the ‘milk’ and ‘yoghurt’ type products are
identical to those currently used in Yellow Fat Spreads. The ‘milk’ and ‘yoghurt’ type
products containing phytosterol-esters have been tested for their microbiological and
chemical stability over time, including the impact of pasteurisation, and these have
been found to be similar to standard products.

The phytosterol-esters will be added to the product such that a 250ml serving of the
‘milk’ type product will provide 1g of free phytosterols. The ‘yoghurt’ type product will
be produced in individual serving pots with phytosterol-esters added such that each
individual pot provides 1g free phytosterols. The recommended intake will be 2-3g
free phytosterols/day.

The cholesterol-lowering effect of phytosterol-esters has been demonstrated in
various food types including ‘milk’ and ‘yoghurt’ type products. The effect is:
comparable to that seen with Yellow Fat Spreads.

The range of products will be labelled with clear instructions on how to eat an
appropriate amount of the spreads, ‘milk’ or ‘yoghurt’ type products to obtain an
average of 2-3g of free phytosterols per day to optimise cholesterol-lowering benefits.
Consumers will also be informed that consuming higher amounts will not provide any
significant additional cholesterol-lowering benefit. Labelling will continue to include
the information from the original approval indicating target consumers, lack of.
suitability for children, pregnant and lactating women and advice to those receiving
cholesterol-lowering medication. This will be adapted, if necessary, in line with the
Scientific Committee on Foods current deliberations on multiple intakes of phytosterol
products.

SEAC
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<pre>Phytosterol-esters: Use in a range of food products Page 5 of 5

If consumers use the product as recommended on the labelling then it is anticipated
that the intake will be 2-3g of free phytosterols per day. This level of intake does not
exceed that originally expected from the use of Yellow Fat Spreads containing 8%
phytosterol-esters approved by the EC.

There is no evidence to suggest that consumers will not follow the labelling advice
regarding recommended intakes, particularly as this states that there is no additional
cholesterol-lowering benefit from eating more than the recommended 2-3g free
phytosterols/day. However, should consumers not follow the labelling advice then
the potential daily intake of phytosterols has been modelled based on the
consumption patterns of unfortified products. This has been done using both intake
data from dietary surveys and consumer purchase data. This shows that even if
consumers do replace all spread, ‘milk’ and ‘yoghurt’ type product intake with
phytosterol-ester products the potential daily intake of phytosterol-esters is still within
the range of intakes considered in the original risk assessment and does not raise
any toxicological concerns.

However, it is highly unlikely that consumers will replace all intakes of spread, ‘milk’
and ‘yoghurt’ type products by the equivalent phytosterol-ester products in this way.
Post Launch Monitoring data and studies of consumer purchase data of phytostanol-
ester products in Finland and the UK indicates that intakes of cholesterol-lowering
foods are lower than those of the unfortified counterparts. This is confirmed by UK
consumer purchase data that indicates that consumers who buy phytosterol/stanol-
ester products also buy unfortified products.

In conclusion, this application demonstrates that extension of the range of
phytosterol-ester products available in the EU to include ‘milk’ and ‘yoghurt’ type
products in addition to Yellow Fat Spreads will not lead to over-consumption of
phytosterols resulting in adverse public health effects.

SEAC
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<br><br>====================================================================== Pagina 28 ======================================================================

<pre>Bijlage E
        Eerste beoordeling/First assessment
        Eerste beoordeling/First assessment 28
</pre>

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<pre>ADVISORY COMMITTEE FOR NOVEL FOODS AND PROCESSES.
UK 2002 / 002

Opinion On An Application Under The Novel Foods Regulation To Extend
The Range Of Uses Of Phytosterol Esters In Food Products

Applicant: Unilever '

Responsible Person: Dr George Gordon

Novel Food: «Extension In The Range Of Uses Of Phytosterol
Esters

EC Classification: 1.1

INTRODUCTION

1. An application was submitted by Unilever to the UK Competent Authority on

6" of August 2002 for approval of phytosterol esters for use in a range of food
products. A copy of the application dossier was placed on the FSA website at
the same time. | |

2. The applicant previously submitted, via the Netherlands, a successful

application under (EC) 258/97 for the same phytosterol ester component in a
single product type (yellow fat spreads). Approval was granted for use of the
phytosterol ester ingredient in yellow fat spreads up to a maximum of 8%
(Commission Decision 2000/500/EC). The UK discussed the issue of
approval extension with the Commission who were of the opinion that, as the
initial approval specified incorporation into a single product, a full application
made under the terms and conditions of (EC) 258/97 was reguired before an

extension could be granted.

3. The applicant is seeking permission to extend the current product range to

include milk and yoghurt products. Although these products differ from their
conventional counterparts only by the addition of phytosterol esters, the
applicant is aware that this fortification will contravene EU and domestic
regulations and mean that the products cannot be named milk or yoghurt. The
applicant will comply with the regulatory position in Member States as

necessary, and for the purposes of this opinion only, the products are referred
to as milk ‘type’ and yoghurt ‘type’ products.
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<pre>The novel ingredient has already been subject to a safety assessment and
granted approval up to a maximum level of use in spreads only. Therefore,
the application for an extension of the product range takes into account the .
existing conditions of approval. Data from post launch monitoring (PLM) that
shows that intake from spreads has not reached the level anticipated in the
previous application. The applicant uses data from the PLM, supplemented
with dietary survey data and consumer purchase data to show that an
extension of the product range will not lead to an intake of phytosterols above -
the level previously approved.

Specification of the Novel Ingredient
Information on this aspect is provided on page 4 of the application dossier.

The novel phytosterol esters ingredient is identical to that used in the yellow
fat spreads that have been previously approved under (EC) 258/97. A full
description of the ingredient and specification was given in the original
application which was approved in 2000.

Discussion. The Committee was satisfied that this ingredient is identical to
that previously approved under (EC) 258/97.

Effect of the production process applied to the novel food
Information on this aspect is provided on page 5 of the application dossier.

The production methods used to produce the phytosterol esters ingredient are
identical to those used to produce the ingredient used in the yellow fat
spreads that have been previously approved under (EC) 258/97.

The milk and yoghurt to be used are standard products. Storage and
distribution temperatures are as for conventional counterparts and no
additional controls are considered necessary. HACCP schemes are used to
control product safety and quality. The only additional process required is to
control the amount and quality of the phytosterol ester added.

Intended levels of fortification are the same as, or less than current yellow fat
spread fortification levels of 8% and are as follows:

Yoghurt 1g free phytosterols per pot (125 — 150g)
Milk 1g free phytosterols in 250mi milk

Discussion. The Committee was satisfied that the production process is
controlled and that the in-process monitoring steps are appropriate to ensure
safe and consistent products.
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<pre>The novel ingredient has already been subject to a safety assessment and
granted approval up to a maximum level of use in spreads only. Therefore,
the application for an extension of the product range takes into account the .
existing conditions of approval. Data from post launch monitoring (PLM) that
shows that intake from spreads has not reached the level anticipated in the
previous application. The applicant uses data from the PLM, supplemented
with dietary survey data and consumer purchase data to show that an
extension of the product range will not lead to an intake of phytosterols above -
the level previously approved.

Specification of the Novel Ingredient
Information on this aspect is provided on page 4 of the application dossier.

The novel phytosterol esters ingredient is identical to that used in the yellow
fat spreads that have been previously approved under (EC) 258/97. A full
description of the ingredient and specification was given in the original
application which was approved in 2000.

Discussion. The Committee was satisfied that this ingredient is identical to
that previously approved under (EC) 258/97.

Effect of the production process applied to the novel food
Information on this aspect is provided on page 5 of the application dossier.

The production methods used to produce the phytosterol esters ingredient are
identical to those used to produce the ingredient used in the yellow fat
spreads that have been previously approved under (EC) 258/97.

The milk and yoghurt to be used are standard products. Storage and
distribution temperatures are as for conventional counterparts and no
additional controls are considered necessary. HACCP schemes are used to
control product safety and quality. The only additional process required is to
control the amount and quality of the phytosterol ester added.

. Intended levels of fortification are the same as, or less than current yellow fat

spread fortification levels of 8% and are as follows:

Yoghurt 1g free phytosterols per pot (125 — 150g)
Milk 1g free phytosterols in 250mi milk

Discussion. The Committee was satisfied that the production process is
controlled and that the in-process monitoring steps are appropriate to ensure
safe and consistent products.
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<pre>These data are based on figures available for the daily consumption of similar
(unfortified) products, and the consumption of individual product types, and...
also consumption in combination with the others can be estimated. In -
addition, data showing current intake of all similar (fortified) products are also
presented.

(a) Dietary Survey Data

15. These data were obtained by consumers logging their food intake over a fixed -
time period. The applicant accessed data for the UK and the Netherlands.
Survey data for other MS were not deemed sufficiently detailed, out of date or
not available to third parties.

16.As the consumption information is obtained using un-fortified products the
implicit assumption that all spreads, yoghurts and milk consumed are
fortified, is made. Such an assumption is likely to lead to an overestimation of
phytosterol fortified products as no allowance can be made for the purchase
of both phytosterol fortified and unfortified products. In addition any
restrictions on consumption of the fortified product such as effective labelling
would not be seen.

17.As food consumption is not normally distributed, the applicant has used the
median (50" percentile) and 95" percentile figures as a basis for comparison.
In all cases data are presented as g phytosterols/person/day.

18.UK NDNS data (Application dossier pp 11-15).
The highest potential intake is in the age range 65+. Median values were
below 3g per day irrespective of whether 1 product or all three products were
consumed. All consumers ate at least one of the product and 11% consumers
all three. Consumption patterns are similar irrespective of age group and, as
listed on p13 Annex 1, 95" percentile data are in the range 2.16 - 3.67 for
consumption of any one product, and 3.22 - 5.01 for consumption of all three.

19. Netherlands data (Application dossier pp 11-15)

_ The Dutch data are grouped according to sex, with higher potential intake b y
males. Median values were highest in the 46-65 age group at 4.58 (95
percentile 6.63). Although the highest 95° percentile value was for males
aged between 6 and 16, because this group consumes the highest amounts
of the unfortified products, the group is unlikely to be seeking cholesterol
lowering products, and the applicant would not target products at such an age
group.

(b) Consumer Purchase Data

20.The applicant has purchased consumer purchase data for all EU countries
where such data are made available. No data were available for MS in
Southern Europe. UK Consumer Purchase Data were obtained from AC
Neilsen (Consumer Panel 2002) who collate information obtained from

</pre>

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<pre>21

households scanning barcodes after purchase.

«As for the dietary survey, data are presented as median (50° percentile) and

95" percentile values and potential intakes of phytosterols are calculated with
the same assumption that all products purchased contain phytosterol. A
number of other assumptions likely to lead to an over estimation of
phytosterol intake have been made. These are: All the ‘milk’ and ‘yoghurt’
products that are purchased are consumed during the 12 or 26 week period ~
of data collection; there is no spoilage or wastage of the food that is
purchased; use is also by individuals that live in the house. A further
assumption, that the products are not both purchased and consumed outside
the home, is an unlikely scenario, given the limited availability of the products.

22.As the data are collected at household level it is not possible to determine

who is actually consuming the product, if there is more than one person in the
house. However as reasonable estimates of intake can be obtained from one
member households these data are used.

23.Data showing consumption for one or all three products, were consistent with

the dietary survey data indicating that the highest consumption would be in
the target population group. The highest estimated intake of phytosterols in
the UK was for all three products and were 2.44 (median) and 5.75 (95°
percentile). Similar highest consumer age ranges and intake values were
calculated for France and Germany.

Consumption of existing cholesterol lowering foods
24.Although data presented to date indicate consumption levels of phytosterols

based on the consumption of all milk, yoghurt and yellow fat spreads, the
consumer purchase data also enabled consumption of phytosterol (Flora
pro.activ) and phytostanol (Benecol range) fortified products currently on the
market in the EU to be assessed. These data are particularly useful in that
they deal with a small, highly relevant product range, reflecting current
purchase patterns for equivalent products. |

25.The information was collected over a 26 week period. As there were

insufficient numbers of one member households, throughout the age range,
such data have only been included for individuals within the 45-64 (50-65
Finland) and 65+ age group, although ‘per household’ data have also been
included. In summary, median levels are not higher than 0.66g in the one

member households, whilst 95" percentile values do not exceed 2g (2.75 in
Finland).

26.1t should be noted that these figures are significantly less than for “total”

yoghurt, milk and yellow fat spread consumption and this is likely to be
because non-fortified equivalent products were also purchased during this
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<pre>period. Up to 90% of single member households in the target group also
purchased non-fortified spreads and yoghurt.

Determination of the estimated daily intake from new product range
27. This is discussed in para 39.

Labelling
28. The current approval for phytosterols in yellow fat spreads notes that they are -

not nutritionally appropriate for certain individuals such as infants and
lactating or pregnant mothers.

29.In view of the need for clear and unambiguous labelling which must be
maintained if the product range is increased, the applicant has sought to
clarify the labelling of products in terms of recommended daily intake, and the
amount of individual products that can be consumed. The applicant will also
include a statement to the effect that extra servings will not provide any
additional cholesterol lowering benefit.

30.In response to a large number of applications under (EC) 258/97 for approval
of phytosterol ingredients in a range of food products, the SCF are currently
considering the issue of elevated levels of phytosterols from multiple dietary
sources. The use of appropriate labelling may be considered as a means of
avoiding excess daily consumption and the applicant has indicated that the
new product range will be covered by a comprehensive labelling regime.
Furthermore the applicant has indicated a willingness to amend their
application in response to the SCF discussions.

Discussion. The Committee was content that the PLM data showed that
consumption levels for fortified yellow fat spreads was lower than anticipated.
The Committee reviewed the data obtained from the dietary surveys and was
content that the increase in the product range would not lead to consumption of
phytosterols at levels greater than those approved previously.

The Committee expressed concerns that although present levels of phytosterol
consumption are currently limited by a small product range, as more fortified
product become available the potential for over consumption increases and any
clearance should reflect any decisions made by the European Commission.

The Committee also sought reassurance that the any labelling for additional
product types should not only inform the consumer of the recommended number
of daily servings, but should also make the consumer aware that there are a

range of similar products on the market, including those from other
manufacturers.
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<pre>IV. Information on Previous Exposure
Information on this aspect is provided on page 20 of the application dossier -

31.Although there has been no exposure to phytosterol esters in ‘milk’ and
‘yoghurt’ products, the ingredient has been consumed in yellow fat spreads
and there is low level consumption of ‘free’ phytosterols in a normal diet.
Individuals have had significant exposure to phytostanol esters (hydrogenated
phytosterols) in a range of products including ‘milk’ and ‘yoghurt’ products.

Discussion The Committee accepted that the novel ingredient has been
consumed previously and that there were low levels of phytosterols in a normal
healthy diet.

V. Nutritional Aspects
Information on this aspect is provided on page 21 of the application dossier

32.The ability of phytosterols to reduce cholesterol absorption is well
documented. |

33.Data submitted by Unilever for the original approval have been considered
previously, and the applicant commissioned research that addresses specific
issues raised by the SCF. These include the PLM and the effect of
consumption of phytosterols in conjunction with cholesterol lowering drugs.
Studies have also looked at the effectiveness of phytosterols in children with
familial hypercholesterolaemia. Research in both areas indicated the
beneficial effect of phytosterols although the applicant does not intend to
market the product to either group.

34. The cholesterol lowering effect of phytosterols is not influenced by the food
matrix. The applicant has summarised research that shows that yoghurts and
milk fortified with phytosterols, were as efficacious in the reduction of LDL-
cholesterol as other foods containing this ingredient.

Effect on carotenoids

35.Studies indicate that the consumption of phytosterols can lead to modest
reduction in carotenoids, particularly the most lipophilic carotenoids such as
B-carotene. The applicant has updated studies in this field. Given that this
application does not seek to increase the amount of phytosterols in the diet
beyond that originally approved, the previous risk assessment conclusions
from the SCF in response to the original application are still appropriate.

Discussion The Committee was content that the fortification of foods with
phytosterols to help reduce cholesterol absorption is well recognised, provided
appropriate labelling is included on the products indicating that they are not
considered appropriate for certain subgseups of the population and that no new
safety issues will be raised by the extension of this product range.
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<pre>The Committee agreed that there was no effect of the food matrices on the
effectiveness of the ingredient. |

VI. Microbiological Information
Information on this aspect is provided on page 24 ofthe application dossier

36. The microbiological stability of the ‘milk’ and ‘yoghurt’ products containing -
phytosterol-esters is governed by the same principles as conventional
products.

37.The accepted principles of Good Manufacturing Practice used for
conventional milk and yoghurt will be used to control quality and safety during
manufacture.

Discussion The Committee was content with the information supplied by the
applicant and considered the production process, the quality control measures
and the nature of the final product to be sufficient to ensure no unintentional
microbiological contamination of the products

VIII Toxicological Aspects |

38. There is a history of safe consumption for phytosterols within the normal
dietary intake of 200-400mg/day. Given that the use of phytosterol esters in
yellow fat spreads would lead to a 5-10 fold increase, a thorough toxicological
examination of the product was carried out. Based on this assessment the
SCF set the limit of fortification at 8% in yellow fat spreads. The toxicological
examination of the novel ingredient did not identify any adverse health effects
up to the maximum dose levels it was possible to test, and human trials
involving large daily intakes of phytosterols have not reported any adverse
health effects. |

Determination of the estimated daily intake

39. The Joint FAO/WHO Expert Committee on Food Additives, (JECFA) NOAEL
Safety Factor for free phytosterols is 137mg/kg/day, equivalent to
9.6g/person/day for a 70kg adult, although this is a conservative estimate as
an effect level could not be established. The applicant notes that if the
products are used as recommended on the labelling then the intake will not
exceed 2-3g free phytosterols per day. The applicant also estimated the
highest intake levels if the labelling is ignored and all three fortified products
are consumed. These data (irrespective of source) list the highest potential
daily consumption for each country. The highest UK consumption is 2.79/5.8g
(median/95" percentile), (age group 45-64).

40.The applicant will extend their Post Launch Monitoring to take account of
consumption of all fortified products by the target groups, to assess levels of
phytosterol consumption and monitor any potential adverse health events.
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<pre>Discussion The Committee was content that providing the levels of fortification..
did not exceed those stipulated in the original approval, there were no specific -
toxicological issues that had not been covered in the previous approval.

The Committee agreed that if the products were labelled as described in the
application dossier no new toxicological issues would arise.

The Committee agreed that it would discuss consumption of phytosterols from
multiple sources in the light of the views expressed by the Scientific Committee -
on Foods.

OVERALL DISCUSSION

41.This applicant company is seeking to extend their product range of
phytosterol fortified products. Currently they have approval for a single
product, yellow fat spreads. This product was approved under (EC) 258/97 in
2000 and they wish to extend the range to include two further product types.
Phytosterol esters in yellow fat spreads have already been approved and the
product specification data, and the production process are unchanged.
Although the intention is to add the phytosterol esters to different products,
the current production processes are well monitored, with quality control and
safety measures in place. The products are manufactured using a standard
method, which has been shown to be reliable and reproducible, the only
additional process is to control the amount and quality of phytosterol esters
added. |

42.No nutritional, toxicological or microbial safety concerns have been raised.
Phytosterols are already present in human diets, occurring naturally in foods
at low levels and in fortified yellow fat spreads.

43.No issues were raised regarding the anticipated intake and extent of use as
sufficient data were provided to demonstrate that an increase in the product
range would not lead to an increase in the consumption of phytosterols
beyond those previously approved.

44. If the product extension is approved, the Applicant Company will impose strict
labelling criteria on the entire product range. These will clearly define the daily
servings reguired to affect a reduction in cholesterol and will also state that
consumption in excess of the recommended number of daily servings daily
servings will not provide additional cholesterol lowering benefit. The
Committee previously expressed their concerns regarding the over
consumption of phytosterol fortified products when they have been asked to
comment on previous applications made under (EC) 258/97. The Committee
agreed that the issue of over consumption should take into account all
products currently on the market, and those awaiting clearance under (EC)
258/97 and should be dealt with by the Commission. Members also
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<pre>acknowledged that the Scientific Committee for Foods had drafted a report
entitled “View on the long term effects of the intake of elevated levels of.
phytosterols from multiple dietary sources”. The company has stated that they -

will act in accordance with any decisions made by the Commission in the light
of this SCF report.

45.In view of the concerns of over consumption, and the stipulated requirement
for PLM in the previous approval for the fortified yellow fat spreads the -
company are willing to undertake a similar exercise if approval for the
extension of product range is given. The Committee recommends that any

approval for this extension in the product range is subject to a requirement for
further PLM.

CONCLUSION

The Advisory Committee on Novel Foods and Processes is satisfied by the
evidence provided by Unilever that the extension of the range of uses of
phytosterol esters as described in the application dossier is acceptable, subject
to the labelling and PLM requirements described above.

November 2002
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