<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>Nonisap
Noni juice
Tweede beoordeling van de veiligheid voor de consument, volgens de
Europese verordening 258/97 betreffende nieuwe voedingsmiddelen
en nieuwe voedselingrediënten
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 for Agriculture, Nature management and Fisheries
Nr 2001/03VNV, Den Haag, 13 december 2001
No. 2001/03VNV, The Hague, December 13, 2001
</pre>

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<pre>Deze publicatie kan als volgt worden aangehaald:
Gezondheidsraad: Commissie Veiligheidsbeoordeling van nieuwe voedingsmiddelen.
Nonisap. Den Haag: Gezondheidsraad, 2001; publicatie nr 2001/03VNV.
Preferred citation:
Health Council of the Netherlands: Committee on the Safety assessment of novel
foods. Noni juice. The Hague: Health council of the Netherlands, 2001; publication no.
2001/03VNV.
auteursrecht voorbehouden
all rights reserved
</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 6
  Literatuur/Literature 8
  Bijlagen/Annexes 10
A De adviesaanvraag/Request for advice 11
B De commissie/The committee 13
C EU-procedure/EU-procedure 15
D Samenvatting dossier/Executive summary of the dossier 18
E Eerste beoordeling/First assessment 39
  Inhoud/Contents                                               3
</pre>

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<pre>aanbiedingsbrief (2 vellen)</pre>

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<pre></pre>

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<pre>Letter to the Dutch Minister of
Health, Welfare and Sport
On December 13, 2001, professor JGAJ Hautvast, Vice-president of the Health
Council of the Netherlands wrote as follows to the Minister of Health, Welfare and
Sport:
This document has been prepared in response to your request, also on behalf of the
Minister for Agriculture, Nature Management and Fisheries for advice regarding the
safety of novel foods and food ingredients. At issue is a so-called second opinion, in
the context of European Regulation 258/97, for the foodstuff nonisap. 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 first assessment for this request was performed by the Health Council (Conseil
Supérieur d’Hygiène, CSH) of Belgium. The CSH considers the dossier to be
incomplete and has issued a negative assessment. Although the applicant has
conducted the correct toxicological test, a semi-chronic animal trial, the doses used are
too low relative to the intake proposed by the applicant himself. This intake also seems
to the CSH to underestimate actual consumption by the population. The CSH is calling
for sound substantiation of the position that nonisap is to occupy within the food range
and of the expected intake.
The VNV Committee bases its opinion on the reports of the initial assessment made by
the CSH, and on the information contained in the dossier.
Letter to the Dutch Minister of Health, Welfare and Sport                                 6
</pre>

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<pre>  The Committee agrees in part with the Belgian assessment. It also considers that it is
  unclear what position nonisap is to occupy within the food range and what quantities
  are drunk by consumers.
  If nonisap is marketed as a fruit drink, it is likely that children, too, will consume it and
  consumption will quickly exceed the safe limit determined in animal trials*. To regard
  a broad and high intake of nonisap as a fruit drink as safe, a higher dose should be
  tested in animal trials. The applicant does not substantiate the statement that this is
  impossible.
  Another option is to limit human consumption to the quantity regarded as the safe
  upper limit on the basis of experimental animal research. In that case, guarantees
  should be incorporated to ensure limited, low-level consumption. If nonisap is clearly
  marketed as a food supplement, for example in 30 ml capsules, and the labelling
  contains directions to take no more than one capsule daily, safe consumption by adults
  is reasonably guaranteed. In addition, the package must contain the statement that the
  product is not intended, or is not tested, for use by children.
  I agree with the conclusions and recommendations of the Committee,
  (signed) professor JGAJ Hautvast
* Apart from that, the Committee expressly refers here to a safe upper limit for intake and not to an acceptable daily
  intake (ADI) since a subchronic animal trial is insufficient to determine an ADI.
  Letter to the Dutch Minister of Health, Welfare and Sport                                                            7
</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.
EG97a  Aanbeveling nr 97/618/EG 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 1997; L253: 1-36.
FAO96  Biotechnology and Food Safety. Report of a joint FAO/WHO Consultation. Rome, FAO 1996
FAO01  Evalutation 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
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.
       Literatuur/Literature                                                                                     8
</pre>

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<pre>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                                                                               9
</pre>

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<pre>A De adviesaanvraag/Request for advice
B De commissie/The committee
C EU-procedure/EU-procedure
D Samenvatting dossier/Executive summary of the dossier
E Eerste beoordeling/First assessment
  Bijlagen/Annexes
                                                        10
</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
        nieuwe
        De adviesaanvraag/Request for advice                                                                     11
</pre>

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<pre>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 (under reference GZB/VVB 993428):
Since May 1977, 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
reponsibility 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 applicants (insofar as consistent with the need to protect the
conficentiality 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                                                                          12
</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 B Loos, adviseur/advisor
           COGEM, Den Haag/Committee on Genetic Modification, The Hague
           Prof. dr F Nagengast
           gastro-enteroloog; Academisch Ziekenhuis Nijmegen/ gastro enterologist;
           Academic Hospital Nijmegen
        De commissie/The committee                                                            13
</pre>

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<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 RA Woutersen
   Toxicoloog; TNO Voeding, Zeist/ toxicologist; TNO nutrition and Food Research,
   Zeist
   Dr JAG van de Wiel, wetenschappelijk stafmedewerker/scientific staff member
   Gezondheidsraad, Den Haag/ Health Council of the Netherlands, The Hague
Administratieve ondersteuning: C Nederpelt-Brussee; Gezondheidsraad, Den Haag/
Administrative assistance: C Nederpelt-Brussee; Health Council of the Netherlands,
The Hague.
De commissie/The committee                                                           14
</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 (WHO91, FAO96). 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 (FAO01, SSC99, SCF99, OECD98, OECD00,
        WHO00) gewerkt aan explicitering en aanpassing aan de stand van de wetenschap.
            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
        EU-procedure/EU-procedure                                                                15
</pre>

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<pre>veiligheidsbeoordelingsautoriteit in actie. In Nederland is dat de Minister van
Volksgezondheid, Welzijn en Sport. Zij heeft de Gezondheidsraad verzocht haar van
advies te die-nen. 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
assured. In 1997, a European Regulation (EC97) came into force, laying down the
procedure for approving the market introduction of novel foodstuffs. The procedure
recognises 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
substiantially equivalent to any existing product. (If a foodstuff is substiantially
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 (WHO91, FAO96). 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, SSC99, SCF99, OECD98, OECD00, 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,
EU-procedure/EU-procedure                                                                    16
</pre>

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<pre>this is the Minister of Health, Welfare and Sport, who is advised by the Health
Council. The President of the Health Council has created a Committee on the Safety
assessment of novel foods (VNV) 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 (EC97a, 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                                                                17
</pre>

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<pre>Bijlage D
        Samenvatting dossier/
        Executive summary of the dossier
        Samenvatting dossier/Executive summary of the dossier 18
</pre>

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<pre>Bijlage E
        Eerste beoordeling/First assessment
        Eerste beoordeling/First assessment 39
</pre>

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<br><br>