<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>Maïskiemolie met fytosterolen en
vitamine E
Tweede beoordeling van de veiligheid voor de consument, volgens de Europese
verordening 258/97 betreffende nieuwe voedingsmiddelen en nieuwe voedselin-
grediënten
Maize-germ oil with phytosterols and
vitamin E
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 2002/01VNV, Den Haag, 16 mei 2002
No. 2002/01VNV, The Hague, May 16, 2002
</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 vraagstuk-
ken 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 & Mi-
lieubeheer, 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 overheids-
beleid.
     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.
Deze publicatie kan als volgt worden aangehaald:
Gezondheidsraad: Commissie Veiligheidsbeoordeling van nieuwe voedingsmiddelen.
Maïskiemolie met fytosterolen en vitamine E. Den Haag: Gezondheidsraad, 2002; publi-
catie nr. 2002/01VNV.
Preferred citation:
Health Council of the Netherlands: Committee on the Safety Assessment of Novel
Foods. Maize-germ oil with phytosterols and vitamin E. The Hague: Health Council of
the Netherlands, 2002; publication no. 2002/01VNV.
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 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 27
  Inhoud/Contents                                                  3
</pre>

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<pre>¢
Gezondheidsraad Vice-voorzitter 9
Health Gouncil of the Netherlands
Aan de Minister van Volksgezondheid, 9 /
Welzijn en Sport JA
Pa O
A
Onderwerp : Tweede beoordeling veiligheid maïskiemolie met fytosterolen en vitamine E

Uw kenmerk : GZB/VVB-2263217
Ons kenmerk 7 2002/01 VNV, U469/MR/al/622-BH
Datum : 16 mei 2002

Mevrouw de minister,

Dit schrijven dient ter beantwoording van de door u mede namens de Minister van Landbouw,
Natuurbeheer en Visserij aan de Gezondheidsraad voorgelegde adviesaanvraag over de veiligheid
van nieuwe voedingsmiddelen en nieuwe voedselingrediënten. Aan de orde is een zogenoemde
tweede beoordeling, conform de Europese verordening 258/97, van een maïskiemolie met
fytosterolen en rijk aan vitamine E. Het nieuwe product zal niet als spijsolie worden toegepast. Het
kan direct worden geconsumeerd als voedingssupplement, of verwerkt warden in allerlei
levensmiddelen. Deze beoordeling is verricht door de Commissie ‘Veiligheidsbeoordeling nieuwe
voedingsmiddelen’ van de Gezondheidsraad (Commissie VNV).

De eerste beoordeling van de aanvraag voor markttoelating is verricht door het Franse
voedselveiligheidsbureau ‘Agence frangaise de sécurité sanitaire des aliments' (AFSSA) De
AFSSA plaatst kritische kanttekeningen bij het innemen van vitamine E, bepaalde vetzuren en
fytosterolen die in de olie aanwezig zijn. De AFSSA heeft de maïskiemolie beoordeeld als veilig,
mits de dagelijkse consumptie niet meer is dan 2 g. Daarnaast concludeert de AFSSA dat
gezondheidclaims die inspelen op het mogelijk cholesterolverlagend effect van fytosterolen niet
zijn toegestaan. De bevoegde autoriteit, de Franse overheid, heeft dit advies integraal
overgenomen.

De Commissie VNV baseert haar oordeel op het rapport van de eerste beoordeling door de AFSSA
en op de informatie in het dossier. De Commissie VNV stemt slechts ten dele in met de Franse
beoordeling en is op een aantal onderdelen kritischer. Ten opzichte van de traditionele
maïskiemolie is, door een speciaal productieproces, het fytosterolgchalte van de nieuwe olie 7
maal groter en het vitamine E-gehalte (totaal tocoferolen) 20 maal groter. Daar staat tegenover dat
het totale vetzuurgehalte is afgenomen met ongeveer 10%. De vetzuursamenstelling is echter niet

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.nl wwii gr.ni

[ll a KAA M mm
</pre>

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<pre>Gezondheidsraad Vice-voorzitter —_
Health Council of the Netherlands Fh ved oO

Onderwerp : Tweede beoordeling veiligheid maïskiemolie (ss ‘ — 2
met fytosterolen en vitamine E os ‘
. O
Ons kenmerk : 2002/01 VNV, U469/MR/al/622-BH a
Pagina eo “ 2
Datum : 16 mei 2002

noemenswaardig gewijzigd. De kwaliteit van het productieproces lijkt gewaarborgd. De olie bevat
geen ongewenste bestanddelen of microbiologische verontreinigingen.

Aanvullend op de eerste beoordeling constateert de Commissie VNV dat de samenstelling-
gegevens niet eenduidig zijn weergegeven, Op meerdere plaatsen in het dossier worden gehalten
van oliefracties vermeld die soms van elkaar verschillen. Bij de productspecificatie maakt de
Commissie VNV er bezwaar tegen dat voor fytosterolen en vitamine E slechts cen minimaal
gehalte wordt vermeld. Zij concludeert dat de samenstelling duidelijker moet worden
gespecificeerd waarbij de aanvrager ook bovengrenzen voor de bestanddelen moet aangeven.

De Commissie VNV brengt onder de aandacht dat er voor inneming van vitamine E geen
Nederlandse of Europese bovengrens is vastgesteld, In de toelichting bij het Nederlandse
warenwetbesluit “Toevoeging miero-voedingsstoffen aan levensmiddelen’ wordt gesteld dat
inneming van 4 à 5 maal de aanbevolen dagelijkse hoeveelheid van 10 mg vitamine E (a-tocoferol
equivalenten) zeker geen schadelijk effect oplevert. Volgens dit warenwetbesluit mag, de dagportie
per verrijkt product ten hoogste de aanbevolen hoeveelheid vitamine E bevatten. De 11 mg a-
tocoferol equivalenten die de consument binnenkrijgt bij inneming van 2 g van de nieuwe
maïskiemolie is redelijk hiermee in overeenstemming. Recent is in de Verenigde Staten een veilige
bovengrens vastgesteld van 1000 mg per dag.

Het fytosterolgehalte van de maïskiemolie (7%) is vergelijkbaar met dat van fytosterol-
verrijkte smeerbare vetten (8%). De hoeveelheid dagelijks te consumeren olie die de aanvrager
voorstelt is echter laag (2 g) en bevat ongeveer 0,14 g fytosterolen, Hierdoor zal de hoeveelheid
die de doorsnee consument via de gewone voeding binnenkrijgt hooguit verdubbelen. De
Commissie VNV is daarom van mening dat een overmatige fytosterolinneming bij de voorgestelde
dagelijkse consumptie van de maïskiemalie niet aan de orde is. Zij is het eens met de AFSSA dat
deze fytosterolinneming onvoldoende groot is om een cholesterolverlagend effect te
bewerkstelligen.

De belangrijkste kritiek die de Commussie VNV heeft is dat de aanvrager geen voorstel doct
hoe hij wil voorkomen dat de voorgestelde olieconsumptie wordt overschreden. De commissie
heeft daarom bezwaar tegen het op de markt brengen van het nieuwe product tenzij de aanvrager
duidelijk aangeeft, welke maatregelen hij wil treffen om er voor te zorgen dat de consumptie
beperkt blijft tot de voorgestelde hoeveelheden, te weten 2 g maïskiemolie per dag. Dit is van
belang om de inneming van fytosterolen en vitamine E te begrenzen. Voor de directe consumptie
van deze olie dient informatie te worden verstrekt over de verpakkingsvorm en -groatte. Ook is de

Bezoekadres Pastadres
Farnassusplein 5 Postbus 16052

2511 VX Den Haag 2500 BB Den Haag
Telefoon (070) 3407520 Telefax (070) 3407523
E-mail: gr@gr.nl WWW. g7. nl

</pre>

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

Onderwerp : Tweede beoordeling veiligheid maïskiemolie
met fytosterolen en vitamine E

Ons kenmerk 2002/01 VNV, U469/MR/al/622-BH

Pagina oe

Datum : 16 mei 2002

commissie van mening dat het assortiment levensmiddelen waarin de maiskiemolie verwerkt zal

gaan worden, nader gespecificeerd moet worden.

Ik onderschrijf de conclusies en aanbevelingen van de commissie.

Hoogachtend,

ir

prof, dr Jt J Ha t

Bezoekadres
Farnassusplein 5

2511 VX Den Haag
Telefoon (070) 3407520
E-mail: gr@gr.nl

Postadres

Postbus 16052

2500 BB Den Haag
Telefax (070) 3407523
www.ogr.nl
</pre>

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<pre>Letter to the Dutch Minister of Health,
Welfare and Sport
On May 16, 2002, 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 so-called second
opinion, in accordance with European Regulation 258/97, concerning a maize-germ oil
with phytosterols and vitamin E. The new product will not be sold for traditional use as
salad or cooking oil. It can be consumed as such (food supplement), or incorporated in a
wide range of foodstuffs. 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 of the application for market introduction was carried out by
the French Food Safety Agency, ‘Agence française de sécurité sanitaire des
aliments’ (AFSSA). The AFSSA expressed a critical view on consumption levels of
vitamin E, certain fatty acids and phytosterols, all of which are present in the oil. After
assessing the maize-germ oil, the AFSSA has concluded that it is safe, provided that
daily consumption does not exceed 2 g. The AFSSA also concluded that no health
claims will be permitted in relation to phytosterols’ ability to reduce cholesterol levels.
The French government, which is the competent authority in this case, has fully adopted
this recommendation.
Letter to the Dutch Minister of Health, Welfare and Sport                                   7
</pre>

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<pre>The VNV Committee based its views on the report of the initial assessment by the
AFSSA, and on the information contained in the dossier. The VNV Committee agrees
only in part with the French assessment. A special production process is used to
increase phytosterol and vitamin E levels in the new oil. As a result, phytosterol levels
are seven times greater than those found in traditional maize-germ oil, while vitamin E
levels (total tocopherols) are 20 times greater. Conversely, total fatty acid content has
been reduced by approximately 10%, without considerable changes in fatty acid
composition. The quality of the production process appears to be guaranteed. The oil
contains neither undesirable components nor microbiological contaminants.
     In addition to the first assessment, the VNV Committee notes that the composition
data of the oil are not unequivocally indicated. Data on the levels of oil fractions are
presented several times in the dossier, yet the values given are not always the same.
With regard to the product specification, the VNV Committee objects to the fact that
only a minimum level is indicated for phytosterols and vitamin E. It concludes that the
composition should be specified more clearly, by requiring that the applicant also
indicates maximum levels for the various components.
     The VNV Committee would like to point out that both the Netherlands and the EU
have not established upper intake levels for vitamin E. The explanatory notes of the
Dutch Commodities Act Decree ‘Addition of micro-nutrients to food’ state that an
intake of 4 to 5 times the recommended daily allowance of 10 mg vitamin E
(á-tocopherol equivalents) definitely produces no harmful effects. According to this
Commodities Act, the daily allowance of a fortified product must contain no more than
the recommended amount of vitamin E. The 11 mg of á-tocopherol equivalents that
consumers receive when they ingest 2 g of the new maize-germ oil conforms
reasonably well with this limit. A safe upper intake level was recently established in the
United States. This amounts to 1000 mg per day.
     The phytosterol content of the maize-germ oil (7%) is comparable to that of fat
spreads that have been fortified with phytosterol (8%). However, the daily oil
consumption proposed by the applicant is quite low (2 g), and contains about 0.14 g of
phytosterols. At most, this will double the amount ingested by average consumers as
part of their normal diet. The VNV Committee therefore takes the view that limited
consumption of maize-germ oil poses no threat of excessive phytosterol intake. It
agrees with the AFSSA that the anticipated phytosterol intake is too low to effectively
reduce blood cholesterol levels.
     The applicant has not provided information how exceeding the proposed daily oil
consumption should be prevented. This is the major criticism of the VNV Committee. It
therefore objects to authorisation of the new oil on the European market unless the
applicant clearly indicates what measures the company will take to ensure that
consumption is restricted to the proposed amounts, namely 2 g of maize-germ oil per
Letter to the Dutch Minister of Health, Welfare and Sport                                  8
</pre>

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<pre>day. This is important, in order to limit the intake of phytosterols and vitamin E. With
regard to the direct consumption of this oil, information should be provided on the type
and size of the packaging to be used. The Committee also concludes that the range of
foodstuffs, into which the maize-germ oil is to be incorporated, should be specified more
clearly.
I endorse the conclusions and recommendations of the Committee,
(signed) professor JGAJ Hautvast
Letter to the Dutch Minister of Health, Welfare and Sport                                 9
</pre>

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<pre>       Literatuur/Literature
EC97   Regulation (EC) 258/97 (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)
EC97a  Recommendation 97/618/EC (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. Publicatieblad van de Europese Gemeenschappen 1997; L253: 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.
HCN92  Commissie Toxicologische aspecten van biotechnologisch bereide producten. Productveiligheid bij nieuwe
       biotechnologie. The Hague, Health Council of the Netherlands 1992, publication number 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                                                                                       10
</pre>

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<br><br>====================================================================== Pagina 11 ======================================================================

<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                                                                               11
</pre>

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<br><br>====================================================================== Pagina 12 ======================================================================

<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 voedingsmid-
        delen en nieuwe voedselingrediënten. Daarmee werd de veiligheidsbeoordeling onderdeel van een commu-
        nautaire 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 veilig-
        heidsbeoordeling 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 voedselingre-
        diënten. Het is namelijk een veiligheidsbeoordeling vóór het op de markt brengen van met name voedings-
        middelen van een genetisch gemodificeerde oorsprong en zogenaamd functional foods (nutriceutica). Daar-
        naast ga ik ervan uit dat de onafhankelijke wetenschappelijke advisering door de Gezondheidsraad het ver-
        trouwen 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 ge-
        volgde procedure en de beoordeling om de consument vertrouwen te geven in de veiligheid van de nieuwe
        De Adviesaanvraag/Request for advice                                                                           13
</pre>

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<br><br>====================================================================== Pagina 14 ======================================================================

<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 wor-
den 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 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
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 applicants (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 Con-
           trol 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
           Dr F Nagengast
           gastro-enteroloog; Academisch Ziekenhuis Nijmegen/gastro enterologist; Academic
           Hospital Nijmegen
        De commissie/The committee                                                              15
</pre>

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<pre>    Dr JMA van Raaij
    voedingsfysioloog; Wageningen Universiteit and Researchcentrum/food physiolo-
    gist; Wageningen University and Research centre
    Prof. dr G Schaafsmahoogleraar voeding; TNO Voeding, Zeist/professor of nutri-
    tion; TNO Nutrition and Food Research, Zeist
    Prof. dr EG Schoutenhoogleraar epidemiologie; Wageningen Universiteit and Re-
    searchcentrum/professor of epidemiology; Wageningen University and Research
    centre
    Dr GJA Speijerstoxicoloog; RIVM Bilthoven/toxicologist; National Institute of Pu-
    blic 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 ir M Rutgers, secretaris/scientific staff member
    Gezondheidsraad, Den Haag/Health Council of the Netherlands, The Hague
Administratieve ondersteuning/Administrative assistance: AD Lugtenburg; Gezond-
heidsraad, 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 (EC97). 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 ex-
        tractiemiddel, 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
        (EC97a). 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 FAO/WHO (FAO96, WHO91). Ook de Gezondheidsraad
        heeft zich al eerder over dit onderwerp gebogen (HCN92). Sinds het verschijnen van de
        aanbevelingen van de EU wordt in internationaal verband (FAO01, OECD98, OECD00,
        SCF99, SSC99, 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 veilig-
        heidsbeoordelingsautoriteit in actie. In Nederland is dat de Minister van Volksgezond-
        EU-procedure/EU-procedure                                                                 17
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<pre>heid, Welzijn en Sport. Zij heeft de Gezondheidsraad verzocht haar van advies te die-
nen. De Voorzitter van de Gezondheidsraad heeft hiertoe de commissie Veiligheidsbe-
oordeling 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 (EC97a, 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
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 (EC97a). 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 FAO/WHO (FAO96, WHO91). The Health
Council of the Netherlands has also considered the question earlier (HCN92). 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
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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 (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                                                                 19
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<pre>Bijlage D
        Samenvatting van het dossier/
        Executive summary of the dossier
        Samenvatting van het dossier/Executive summary of the dossier 20
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<pre>LABORATOIRES

PHARMASCIENCE”

RESUME

« HUILE DE GERME DE MAIS
CONCENTREE EN INSAPONIFIABLE »

Ce présent document a été rédigé suivant les recommandations de la Commission des
Communautés européennes du 29 juillet 1997 concernant les aspects scientifiques relatifs à la
présentation des informations requises pour étayer des demandes d'autorisation de mise sur le
marché de nouveaux aliments et de nouveaux ingrédients alimentaires au titre du reglement (CE) n°
258/97 du Parlement européen et du Conseil.

LABORATOIRES PHARMASCIENCE
Division Industrie
Rue des Quatre Filles = 28230 EPERNON- France ee KAA ME

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<pre>DOSSIER NOUVEL ALIMENT Huile de germe de mats concentrée en insaponifiable

PLAN DU DOSSIER

DONNEES ADMINISTRATIVES p-1

RESUME p.2

DESCRIPTION GENERALE ET CLASSIFICATION DU NOUVEL ALIMENT
SELON LE REGLEMENT (CE) n° 258/97 p.4

CORRESPONDANCE ENTRE LA CLASSIFICATION DU REGLEMENT
(CE) n° 258/97 ET LES CLASSES DE NOUVEL ALIMENT ETABLIES

PAR LE SCF (Comité scientifique de Palimentation humaine) p:5
IDENTIFICATION DES INFORMATIONS ESSENTIELLES REOUISES p-6
CONSULTATION DES PROTOCOLES p-7
I. Protocole 1 : Spécification du nouvel aliment p.7
IL Protocole II : Effet du procédé de production, appliqué au nouvel aliment p.13
III. Protocole III : Utilisation antérieure de l’organisme utilisé comme source de
nouvel aliment p.17
IV, Protocole IX : Consommation et niveau d'utilisation prévus du nouvel aliment p.20
Vv. Protocole X : Informations fournies par une exposition humaine antérieure
au nouvel aliment ou a sa source p.23
VI. _ Protocole XI : Informations d'ordre nutritionnel sur le nouvel aliment p.25
VII. - Protocole XII : Informations d'ordre microbiologigue sur le nouvel aliment p.32
VIIL Protocole XIII : Informations d'ordre toxicologigue sur le nouvel aliment p.33
EVALUATION ET CONCLUSION p.35
CAHIER DES CHARGES NOUVEL ALIMENT p.38

13/12/2001

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<pre>DOSSIER NOUVEL ALIMENT Huile de germe de maïs concentrée en insaponifiable

RESUME

Ce present document a pour objectif de démontrer l'innocuité d'un nouvel ingredient appele « huile
de germe de maïs concentrée en insaponifiable », dans le but d’obtenir l'autorisation de mise sur
le marché de ce nouvel aliment au sein de la Communauté européenne.

Le nouvel aliment est obtenu par concentration de la fraction insaponifiable de l'huile de germe de
mais alimentaire. Le procédé physique de séparation retenu pour cet enrichissement est la
distillation moléculaire. Cette technique évite la dégradation thermique de la fraction
insaponifiable, ne modifie pas la répartition en acides gras de la fraction triglyceridigue et preserve
les fractions triglyceridigues fortement insaturees.

L’huile de germe de mais concentrée en insaponifiable se compose en moyenne de 90 % d'acide
gras sous la forme de triglycérides, de 10 % d’insaponifiable dont 7 % de phytostérols et 2 % de
tocophérols.

De par sa composition chimique, le nouvel aliment se rapproche fortement de sa source. L’huile de
germe de mais alimentaire (source) est exploitée comme équivalence substantielle.

Sur le plan des contaminants de type aflatoxines et solvants, le nouvel aliment peut être compare a
une huile de germe de maïs alimentaire classique, qui doit être conforme aux spécifications en
vigueur pour chaque classe de contaminant.

L’absence de micropolluants de type pesticides (résidus organochlorés et organophosphores) et
métaux lourds a été vérifiëe dans l’huile de germe de mais concentrée en insaponifiable.

Sur le plan microbiologique et allergisant le nouvel aliment peut être comparé à une huile de germe
de maïs alimentaire classique.

Sur le plan toxicologique, le nouvel aliment a été classé dans la catégorie des préparations ne
présentant pas un danger pour l'homme. Le pouvoir mutagéne du nouvel aliment a été démontré
comme étant nul.

Le nouvel aliment, qui est une huile de germe de maïs concentrée en insaponifiable, ne présente
done aucun danger d'ordre microbiologigue, allergisant et toxicologique.

Sur le plan nutritionnel, le nouvel aliment est eguivalent substantiellement a l'huile de germe de
mais (source) pour les apports en acide linoléique essentiel (C18:2 n-6) et oléique (C18:1 n-9).

Le nouvel aliment est une source alimentaire concentree en vitamine E, couvrant |’Apport
Journalier Recommandé (A.J.R.). Le nouvel aliment présente aussi le benefice nutritionnel d'être
une source privilégiée en phytostérols dont on connait aujourd'hui le rôle hypocholesterolemiant.

Une dose quotidienne du nouvel aliment fixée 4 2 g, apporte 11 mg de vitamine E et 140 mg de
phytostérols totaux.

Le nouvel aliment est une source supplémentaire d’apport en vitamine E et en phytostérols ; il
ne remplace en aucun cas un aliment existant. Le nouvel aliment ne sera donc pas utilisé tel quel
pour la consommation en « huile de table », ce n'est pas un aliment de grande consommation.

13/12/2001

ba

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<pre>DOSSIER NOUVEL ALIMENT Huile de germe de mais concentrée en insaponifiable

L'utilisation du nouvel aliment sera recommandée comme ingrédient alimentaire, pour une dose
de 2 g par jour et par personne, permettant un rééquilibrage au plan nutritionnel des apports en

vitamine E et en phytostérols dans des produits alimentaires divers ou dans des aliments
fonctionnels.

13/12/2001

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<pre>Novel food dossier Maize-germ oil high in unsaponifiable matter

SUMMARY

The purpose of this document is to demonstrate the safety of a novel ingredient "maize-germ oil
high in unsaponifiable matter", with a view to obtaining the necessary authorisation to place this
novel food on the market in the European Community.

This novel food is obtained via concentration of the unsaponifiable fraction of edible maize-germ
oil. The concentrate is derived via a physical separation process known as molecular distillation.
This technique prevents thermal degradation of the unsaponifiable fraction, does not alter the
distribution of fatty acids in the triglyceride fraction and keeps triglyceride fractions highly
unsaturated.

Maize-germ oil high in unsaponifiable matter consists on average of 90% fatty acids, in the form
of triglycerides, and 10 “% unsaponifiable matter, which in turn consists of 7% phytosterols and
2% tocopherols.

The chemical composition of this novel food is very similar to that of its source. Edible maize-
germ oil (source) is used as a comparison for establishing substantial equivalence.

In terms of aflatoxin and solvent contamination, the novel food is comparable to ordinary edible
maize-germ oil, which must conform to the existing specifications for each class of contaminant.
Maize-germ oil high in unsaponifiable matter has been found to be free of pesticide micropollutants
(organochlorine and organophosphorous residues) and heavy metals.

The microbiology and allergenicity of the new oil are also comparable to those of ordinary edible
maize-germ oil,

From a toxicological point of view, the novel food has been categorised as a preparation which does
not present a risk to man if ingested. Tests have proved that it is also non-mutagenic.

The novel food, maize-germ oil high in unsaponifiable matter, thus presents no microbiological,
allergenic or toxicological risks.

From a nutritional point of view, the novel food is substantially equivalent to maize-germ oil
(source) in terms of essential linoleic (C18:2 n-6) acid content and oleic acid content (C18:1 n-9).

The novel food is a food source high in vitamin E, supplying the Recommended Daily Amount
(RDA). It is also nutritionally beneficial in that it is a prime source of phytosterols, the
hypocholesterolaemic effects of which are now well-known.

The recommended dose of 2 g of the novel food per day will provide 11 mg of vitamin E and
140 mg of total phytosterols.

The novel food is a supplementary source of vitamin E and phytosterols: it is not intended as a
replacement for any existing foodstuff. Consequently, the oil should not be used as a "salad
oil"; it is not a product intended for consumption in large quantities.

16/11/2001 z 2

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<pre>Novel food dossier Maize-germ oil high in unsaponifiable matter

It is recommended that this novel food be used as a food ingredient. A dose of 2 g per person per |
day tops up vitamin E and phytosterol intake from everyday foodstuffs and ‘functional foods’.

16/11/2001 a TT

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<pre>Bijlage E
        Eerste beoordeling/First assessment
        Eerste beoordeling/First assessment
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<pre>Initial assessment report concerning a request for an opinion on the use
of maize-germ oil high in unsaponifiable matter as a food ingredient

Maisons-Alfort, 27 July 2001
OPINION
of the French Food Safety Agency (Agence francaise de sécurité sanitaire des

aliments) concerning the assessment of the use of maize-germ oil high in
unsaponifiable matter as a novel food ingredient.

Application submitted under Regulation (EC) No 258/97 on novel foods and novel
food ingredients
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<pre>Contents

1. Introduction

2. Presentation of the dossier

2.1
2.2
2.3
2.4
2.5

Administrative data

General description of the food

Categorisation of the application

Scientific classification of novel food for the assessment of wholesomeness
Consultation of structured schemes for assessment of the novel food

Assessment of the dossier

Structured Scheme I: Specification of the novel food

Structured Scheme II: Effect of the production process applied to the novel
food

Structured Scheme III: History of the organism used as the source of the
novel food

Structured Scheme IX: Anticipated intake/extent of use of the novel food
Structured Scheme X: Information from previous human exposure to the
novel food or its source

Structured Scheme XI: Nutritional information on the novel food
Structured Scheme XII: Microbiological information on the novel food
Structured Scheme XIII: Toxicological information on the novel food

Conclusions

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<pre>Chapter 1

Introduction

A request for an assessment on the use of maize-germ oil high in unsaponifiable matter as
a novel food ingredient under Regulation (EC) No 258/97 on novel foods and novel food
ingredients was referred to the French Food Safety Agency by the Directorate-General
for Consumer Affairs, Competition and Fraud Prevention on 14 June 2000.

After consulting the Specialised Committee of Experts on Human Nutrition on 10
October 2000, the French Food Safety Agency issued an opinion on 20 December 2000.

In accordance with Article 6(2) of Regulation (EC) No 258/97 on novel foods and novel
food ingredients, this initial assessment report has been drawn up to accompany the
notification of the application to the European Commission.
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<pre>Chapter 2

Presentation of the dossier

2.1 Administrative data

The application has been submitted by Laboratoires PHARMASCIENCE® / Division
Industrie, 3 rue des Quatre Filles, 28230 EPERNON, France; the persons responsible for
the dossier are P. Msika - Directeur du Centre de Recherche, 73 Boulevard de la Mission
Marchand, BP 302 — 92402 COURBEVOIE CEDEX, France, and A. Piccirilli -
Responsable du Département Lipochimie, 51 rue Saint-Denis, BP 34 A - 28231 Epernon,
France.

2,2 General description of the product

The product is a maize-germ oil, concentrated in its unsaponifiable fraction, proposed by
the applicant as an ingredient for use as a supplementary source of vitamin E and
phytosterols in foodstuffs, The unsaponifiable fraction is a combination of compounds
with a molecular mass lower than that of triglycerides and obtained by a new process:
molecular distillation.

2.3 Categorisation of the application

The application has been made under Regulation (EC) No 258/97 of the European
Parliament and of the Council of 27 January 1997 on novel foods and novel food
ingredients. The effect of the manufacturing process on the chemical and nutritional
composition of the novel food places the novel food in category f, in accordance with
Article 1(2) of Regulation (EC) No 258/97, which includes:

“foods and food ingredients to which has been applied a production process not
currently used, where that process gives rise to significant changes in the composition or
structure of the foods or food ingredients which affect their nutritional value, metabolism
or level of undesirable substances."

2.4 Scientific classification of novel food for the assessment of wholesomeness

In accordance with the Commission's Recommendation of 29 July 1997 (97/618/EC)
concerning the scientific aspects of the presentation of information necessary to support
applications for the placing on the market of novel foods and novel food ingredients, the
novel food falls into Class 6, This class comprises "foods and food ingredients which
have been subjected to a process not currently used in food production. According to the
scape of Regulation (EC) No 258/97, the resulting product is only considered to be a
novel food if the process results in changes in the chemical composition or structure of
the food or food ingredtent, which affect its nutritional value, metabolism or level of
undesirable substances."

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<pre>2.5 Consultation of structured schemes for assessment of the novel food

As the novel food is in class 6, the following structured schemes must be followed in
order to assess the safety and properties of the novel food:

Structured Scheme I; Specification of the novel food

Structured Scheme II: Effect of the production process applied to the novel
food

Structured Scheme III: History of the organism used as the source of the novel
food

Structured Scheme LX: Anticipated intake/extent of use of the novel food

Structured Scheme X: Information from previous human exposure to the
novel food or its source

Structured Scheme XI: Nutritional information on the novel food

Structured Scheme XII: Microbiological information on the novel food

Structured Scheme XIII: Toxicological information on the novel food
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<pre>Chapter 3

Assessment of the dossier
3.1 Structured Scheme I: Specification of the novel food

Maize-germ oil is extracted from the germ of maize grains (Zea mais L.) during a process
involving two stages, crushing and refining. Refined maize-germ oil used as the source of
the novel food is an edible table oil which meets the requirements of the Codex
Alimentarius. It consists mainly of triglycerides, containing 98 to 99 % of fatty acids and
a small proportion of various substances (sterols, phytosterols), collectively termed the
unsaponifiable fraction (0.8 to 2 %).

The chemical compounds contained in the novel food are identical to those in the source
material. The novel food consists mainly of fatty acids, in particular oleic acid (20-42%)
and linoleic acid (34-65%), with a small amount of alpha-linolenic acid (< 2%),
tocopherols (1.3%), sterols and triterpenic alcohols (around 6%).

The quality criteria of the novel food (appearance, water, impurities, state of oxidation,
oxidative stability, metallic traces) have been assessed and are in accordance with the
recommendations for edible oils contained in the Codex Alimentarius. With regard to
contaminants (aflatoxins, solvents, pesticides and heavy metals), the applicant points out
that the novel food may be compared with ordinary edible maize-germ oil which must
comply with existing specifications for each type of contaminant. Furthermore, the
absence of organochlorine and organophosphorous pesticide residues and heavy metals
has been verified,

The Committee confirms that the novel food has the usual properties of ordinary
maize-germ oil and that the content and composition of fatty acids, tocopherols, sterols
and triterpenic alcohols are in accordance with the available data on that oil.

The Committee is of the opinion that the product has good oxidative stability, identical
to that of the source product. Since the source oil complies with existing regulations,
the results presented by the applicant make it possible te confirm that no
organochlorine and organophosphorous pesticide residues are detected in the novel
food after physical processing.

32 Structured Scheme IL: Effect of the production process applied to the novel
food

Molecular distillation is the industrial process by which maize-germ oil high in
unsaponifiable matter is produced from edible maize-germ oil. The principle of
molecular distillation is very brief vaporisation (0.1 second) under high vacuum (10° mm
Hg) at high temperature (200-300 °C). This process makes it possible to carry out
separation, purification, decolourisation and deodorisation operations. Applied to
vegetable oils, molecular distillation makes it possible to extract predominantly the
lightest compounds (unsaponifiable fraction). Under a high vacuum and at an adequate
temperature, the unsaponifiable fraction is vaporised then recondensed, thus forming the
distillate.

In the case of maize-germ oil distillation, the unsaponifiable fraction is concentrated by a
factor of 7, according to the applicant. This increase in unsaponifiable matter is
associated with the partial removal of triglycerides.

6

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<pre>The Committee points out that the maize-germ oil high in unsaponifiable matter is said
to contain approximately seven times more unsaponifiable matter than the source oil,
whereas the table comparing the distribution of the unsaponifiable fractions of the
source oil and the novel food shows a concentration factor of 8. Apart from the
concentration of the unsaponifiable fraction, the relative percentages of the various
compounds other than the unsaponifiable fraction of the source oil are not altered
significantly,

3.3 Structured Scheme III: History of the organism used as the source of the
novel food
Maize-germ is derived from maize (Zea mais L.), a member of the Graminaceae family.
The plant originates in Central America (Mexico), The applicant states that it is not
genetically modified, but gives no details of the traceability and control system used.
Maize is primarily intended for animal feed (65% of world production), followed by
human consumption (27% of world production) and industry (8 % of world production).
Maize-germ oil is mainly used as a foodstuff for direct consumption. It is a vegetable oil
for everyday consumption.
In 1997, the average consumption of maize-germ oil in France was around 0,5 kg per
year per inhabitant, equivalent to approximately 1.4 g of maize-germ oil per day per
inhabitant.
The applicant stresses that maize-germ oil has for a long time been recognised as
harmless to human health and is of particular interest from a nutritional point of view
because it is high in tocopherols and linoleic acid, which are essential for our organism,

The Committee notes that linoleic acid intake in the French diet at present probably
far exceeds requirements. The French population is more likely to be suffering from
an imbalanced intake of linoleic acid in relation to alpha-linolenic acid; the linoleic
acid/alpha-linolenic acid ratio in France is 8-10, while the recommended ratio is 5,
according to the literature.

It draws attention to the fact that the dossier refers, quite correctly, to the involvement
of linoleic acid in the composition of acyl-ceramides (lipids which play an important
role in the barrier function of the skin), but that it should be added, however, that
linoleic acid supplements should be given only in cases of linoleic acid deficiency.
Such linoleic acid deficiency is extremely rare in France.

3.4 Structured Scheme IX: Anticipated intake/extent of use of the novel food

The applicant recommends that maize-germ oil high in unsaponifiable matter be used as a
food ingredient, and points out that the novel food will not replace any other foods in the
diet and that its use will not be limited to a geographic area.

The applicant suggests that possible uses are food supplements and any food products
reguiring the addition of vitamin E and phytosterols ("functional foods"; supplemented
foods such as margarines, composite edible oils, milk and milk products, seasonings and
sauces, bakery and confectionery products, prepared and canned meals, prepared meat
products, etc.).

On average, 100 g of maize-germ oil high in unsaponifiable matter contains 10 g of
unsaponifiable matter, which in turn comprises 7 g of sterals, 2 g of tocopherols and 1 g
of various constituents (squalene, hydrocarbons). The triglyceride fraction makes up 90 g
of 100 g of the novel food.

The applicant recommends a daily intake of 2 to 8 g of the novel food.

T
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<pre>These figures are based on the substantial equivalence (for the unsaponifiable fraction:

sterols and tocopherols) with maize-germ oil (source):

* 2g of the novel food (18 kcal or 75 kJ) corresponds to 13 g (117 kcal or 489 kJ) or
one tablespoon of maize-germ oil (source)

e 8g of the novel food (72 kcal or 300 kJ) corresponds to 52 g (468 kcal or 1956 kJ) or
four tablespoons of maize-germ oil (source).

The Committee points out that this equivalence may be accepted for sterols, but not for
tocopherols, since for the same quantity of sterols, the novel food contains three times
more tocopherols (40 mg) than maize-germ oil (source) (13 mg). In any case, the
Committee confirms that the novel food has a calorific value (90% triglyceride
fraction) approximately 10% lower than that of the source oil (98.8% triglyceride
fraction).

3.5 Structured Scheme X; Information from previous human exposure to the
novel food or its source

The applicant states that maize-germ oil (source) is a product which is widely and
commonly consumed in all European countries by all ages and sectors of the population.
Furthermore, the maize-germ oil industrial production process is fully developed.

The applicant states that no information is available from previous human exposure to the
novel food.

As regards its unsaponifiable content, the novel food (10% unsaponifiable fraction) is
equivalent to other edible vegetable fats: shea-butter (7 to 10% unsaponifiable fraction)
and avocado oil (1 to 12% unsaponifiable fraction).

With regard to the fatty acid content, the novel food is substantially equivalent to its
source, refined maize-germ oil.

As regards its vitamin E content, the novel food is equivalent to a vegetable oil enriched
with vitamin E.

The Committee is of the opinion that the principle of equivalence with maize-germ oil,
an oil for everyday consumption in France, is justified, with the exception of vitamin E
and unsaponifiable matter.

3.6 Structured Scheme XI: Nutritional information on the novel food

In view of its composition, the arguments put forward by the applicant to demonstrate the
nutritional properties of the novel food are based on its fatty acid content, its vitamin E
content and its phytosterol content.

* Fatty acid content:

The applicant states that the novel food, like maize-germ oil (source) is a prime source of
linoleic acid (18-2 n-6) and oleic acid (18:1 n-9). The dossier gives the quantities present
in 100g of the novel food: oleic acid 18-38 g, linoleic acid 31-59 g, alpha-linolenic acid <
1.8 g.

With regard to oleic acid, the applicant refers to recent nutritional studies carried out on

olive oil which suggest that oleic acid leads to a decrease in LDL-cholesterol combined

with an increase in HDL-cholesterol, thus helping to protect against cardiovascular

diseases. The applicant adds that the novel food may likewise boost the intake of
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<pre>monounsaturated fatty acids via cleic acid, a dose of the novel food of between 2 and 8 g
per day providing 0.4 to 3.4 ¢ of oleic acid.

With regard to linoleic acid, which is an essential fatty acid, the applicant draws attention
to the role of these fatty acids in the synthesis of eicosanoids (prostaglandins,
thromboxanes and leukotrienes} via arachidonic acid, Eicosanoids act as oxygenated
chemical messengers in the platelet aggregation mechanism, but are also involved in the
contro] of renal function, inflammatory and immunity phenomena. The applicant adds
that in addition to its metabolic rele, linoleic acid plays a structural role and is included in
the composition of acyl-ceramides. One dose of the novel food of between 2 and 8 g per
day provides 0.7 to 5.2 g of linoleic acid, the recommended nutritional intake of lincleic
acid being between 8 and 10 g per day in adults. The applicant also states that the
reference intake adopted by the Conseil Supérieur de Alimentation Humaine (CSAH} is
4 ta 6 g of linoleic acid per day.

The Committee stresses, first of all, that the novel food's relative richness in oleic acid
might be a factor in the product's favour compared with equivalent producis based on
sunflower oil, but this aspect is ultimately of little consequence, given the objective of
reducing the intake of linoleic acid and increasing the intake of o-linolenic acid in the
French population. Secondly, the use of the novel food as a food ingredient at a dose
of 2 g per day is acceptable, since it would provide 0.7 g of tinoleic acid, ie. around
10% of the recommended nutritional intake, whereas the dose of 8 g per day wouid

provide 5.2 g of linoleic acid and 0.16 g per day of a-linolente acid, resulting in a very
high finolete acid/aipha-linelenic acid ratio. It therefore seems inappropriate to
supplement the diet with a dose of 8 g per day, since it would increase the finolelc
aci/alpha-linolenic acid ratio, which is already too high in France.

* Vitamin E content:

The applicant gives a brief presentation of the biological roles of vitamin E (the a-
tocopherol form, according to the applicant): it is an antioxidant which acts mainly on
membranes and lipoproteins by trapping the free radicals. Reference is also made to
vitamin E's other roles in preventing ischaemic cardiovascular diseases, preventing
cerlain cancers, stimulating the immune response in the elderly, decreasing the risk of
calaracts and slowing down the progression of depeneralive diseases.

With regard lo the intake of vitamin E, the applicant refers to two reference values, the
advised nutritional intake of 12 mg per day of a-locopherol equivalent (@-TE } or (18 [U)
and a recommended daily intake of 10 mg set in 1981. The applicant stresses that in order
to allain the recommended daily intake, it is sufficient to consume approximately 2 g of
the novel food or 5 g of wheat-germ oil or 28 g of maize-germ oll per day.

Wilh regard to the nisks of consuming too much vitamin E, taking into account the
maximum safe intake laid down by the Conseil Superieur d'Hygiene Publique de France
{CSHPF) (French Public Health Board) of 40 mg per day of a-TE in addition to food
intake, the applicant states thal a daily dose of the novel food of between 2 and 8 g

provides 11 lo 45 mg of o-TE, thus avoiding the risk of consuming too much vitamin E.

The Committee points out that, coutrary fo the statements made by the applicant, a-
tocopherel is not the only tocopherol known as vitamin E. Vitamin E occurs in the

form ef a series of vitamers a, By a which have different rates of vitamin activity.

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<pre>With regard to the dose recommended by the applicant, the Committee stresses that a
daily dose of 2 g of the novel food provides approximately 10 mg of a-TE
(approximately equivalent to the advised nutritional intake), but a daily dose of 8 g

provides approximately 45 mg of a-TE, which is too close to the maximum safe intake
authorised in France.

* Phytosterol content:

Phytosterols are natural plant constituents and are present in vegetable oils at a
proportion of between 0.1 and 0.5 %. They are mainly terpenic constituents of
unsaponifiable plant matter with a molecular structure similar to cholesterol. This
similarity is responsible for the inhibition of intestinal absorption of cholesterol. For this
reason they are added to some margarines intended for hypercholesterolaemic patients.
The applicant points out that nutritional studies carried out on phytosterols show that a
supplement of 0.8 to 3 g per day (depending on the population and the desired objectives)
of phytosterols reduces total cholesterol and LDL-cholesterol, and adds that there are no
significant harmful effects and no maximum safe intake has been set for phytosterols. A
daily dose of the novel food of between 2 and 8 g provides 140 to 560 mg of total
phytosterols,

The Committee confirms that the hypocholesterolaemic role of phytosterols is currently
well documented in scientific literature. A daily dose of the navel food of 2 to 8 g
provides on average 140 mg to 560 mg of total sterols, respectively, According to the
literature, the effective doses needed to achieve a 10-15% reduction in LDL cholesterol
range from 750 mg to 3000 mg per day.

3.7 Structured Scheme XII: Microbiological information on the novel food

The applicant states that on account of the lipophilic nature of the novel food, the lack of
water and solid impurities it contains and the microbial purity of the source, the risks of
bacterial proliferation are unlikely. Moreover, the temperature at which the novel food is
processed (230 °C) eliminates any risk of microorganisms being present. The novel food
is packed and stored away from light and under inert gas, which decreases both the risk
of microbial proliferation and contamination.

The Committee confirms that the process involving very brief vaporisation by heating
(0.1 second) under high vacuum (10° mm He) cannot present a risk of microbiological
contamination,

3.8 Structured Scheme XIII: Toxicological information on the novel food

The toxicological study of the novel food comprised:

e an assessment of acute oral toxicity in mice and rats:

The purpose of the tests was to give a qualitative and quantitative assessment of toxic
phenomena and the time taken for them to appear following a single oral dose of the
novel food at a dose of 18 g/kg of body weight in mice, and 5000 mg/kg of body weight
in rats.

The results of the autopsy carried out 14 days after administration of the novel food
showed that in these conditions, the novel food caused no deaths, caused no changes in
the general state of health and caused no visible organic changes.

e test for possible mutagenic potential using the Ames test:

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<pre>The Ames test was carried out on five bacterial strains (Salmonella typhimurium) and
showed that the novel food had no mutagenic potential.

The Committee accepts the applicant's conclusions and points out that the novel food's
quality criteria generally comply with the Codex Alimentarius recommendations.

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<pre>Chapter 4

Conclusions:

The French Food Safety Agency is of the opinion that:

s maize-germ oil high in unsaponifiable matter proposed as a food ingredient at a dose
of 2 g per day would make it possible to top up vitamin E intake (in particular for the
elderly and adolescents), without upsetting the linoleic acid/alpha-linolenic acid ratio
nor leading to an inappropriate supplementary energy intake;

e The applicant's proposed intake of 8 g per day is unacceptable:

because of the excessive vitamin E content, in the light of nutritional
recommendations and the risks of over-consumption, since it does not replace
another product;

because of the imbalance between linoleic and alpha-linolenic acids which it
might intensify among the French population;

* No nutritional claims can be made for phytosterols because the product does not
contain the effective dose necessary to reduce cholesterolaemia.
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