Guideline f or Food Safety Assessment of  Foods Pr oduced 
Using R ecombinant-DN A Micr oorganisms 
(Draft ) 
                                               
                                               
                                              
（In case of  any discrepancy betw een the Chinese text and the Eng lish transl ation 
thereof, the Chine se text shall go vern） 
 
 
 
CHAPTER ONE:  GENERAL PROVISIONS 
I. BASIS OF THE R ULE 
II. OBJECTIVE  
III. DEFINIT IONS  
IV. SCOPE  
CHAPTER TW O: FOOD SAFETY ASSESSMENT OF GM FOOD S 
ANNEX I - INFORMATION REQUIRED  FOR THE SAFETY  ASSESSMENT 
OF PR ODUCED USING RECOMBIN ANT -DNA MICR OOR GANISMS  
I. APPLICA TION MATERIALS  MUST  INCLUDE  THE  FOLLO WING  
INFORMA TION  
II. LITERA TURES  AND  REFERENCES  
ANNEX II - SAFETY ASSESSM ENT OF POSSIBLE T OXICITY  
ANNEX II I - SAFETY  ASSESSMENT OF POSSIBLE ALLER GENICITY  
ANNEX V - SAFETY ASSESSMEN T OF UNINTENTE D EFFECTS  
 
 1Chapter One:  General Provisions 
 
I. Basis of the rule 
 
This guideline is prescribed in accordance with  the pro vision of  parag raph 1 of  Article 14 
of the F ood Sanitation La w . 
 
II. Object ive 
 
This guidelin e explains the infor mation require d for food safety assessmen t of geneticall y 
modified foods (hereafter as GM f oods)  produced using recombinant-DNA 
microorg anisms . The original dev elopers are required to submit necess ary infor mation to  
register their g enetically modified org anisms (hereafter as GMO) to the De partment of  
Health (DO H) before introducing the GM foods on mark et. This document also pro vides 
guideline the GM food sa fety ev aluati ons for f ood man ufacturers , food traders , and health 
authorities to follo w. 
 
III. D efinitions 
 
1. Gene mod ification tec hniques 
 
Transfer or inser t genetic materials in to a living cell or org anisms via tec hniques suc h as 
gene engineering or mole cular biotec hnolog y, resulting in modification in g enes of  the cell 
or org anism. T he tec hnique does no t include co nventional b reeding, cell fusion with in 
taxonomic family , protoplast fusion within  taxonomic family , hybridiz ation, induced  
mutagenesis, ex vivo fertilization, soma tic m utation,  nor polyploidy induction.  
 
2. Geneticall y modified org anism (GMO) 
An org anism with g enetic material altered via g ene modification tec hniques . 
 
3. Geneticall y modified foods (GM foods) 
Foods and food additi ves produced or man ufactured from ra w materials consisting of  or 
containing g enetically modified org anisms . 
 
4. Con ventional counter part 
A related v ariety/speci es, its components and/or products for whic h there is experience 
of establishing safety bas ed on comm on use as food. 
 
5. Host  
An org anism of  which gene(s) or DN A fragment(s ) are ins erted or transfer red to  by gene 
 2modification tec hniques  
 
6. Vector  
An ag ent, suc h as a plasmid or virus, whic h is used to deli ver selected foreign DNA into host 
for prolife ration and e xpression. 
 
7. Transferred or i ntroduced or inserted g ene (or DNA fragment) 
Any foreign g ene (or DN A fragment) that is  transf erred/introduced/inser ted into host. 
 
8. Gene products 
Any product expressed b y the trans ferred or introduced or inser ted g ene(s) (or DN A 
fragment(s)).  
 
9. Gene (or DNA fragment) donor 
An org anism that pro vides g ene(s) (or DNA fragment(s )) for g ene modificati on process . 
 
10. Unintended effects 
By introducing a specific trait into an org anism through the inser tion of  DNA sequen ces, 
additional traits ma y, in some cas es, be ac quired or existing traits could be lost o r 
modified. 
 
IV. Scope 
 
This Guideline addresses  safety and  nutritiona l aspects  of foods consisti ng of, or derived 
from, microorganisms that have a his tory of safe use as sources of food, whichhave been 
modified by modern biotechnology to exhibit n ew or altered traits. Th is document does not 
address safety of microorganisms used in agricult ure (for p lant protection,  biofertilizers, in  
animal feed or food derived from animals fed the feed etc.), risks related to environmental 
releases of recombinant- DNA mi croorganisms use d in food pr oduction, saf ety of substances 
produced by microorganisms that are used as a dditives or processing aids, including enzymes  
for use in food production, specific purported he alth benefits or probiotic effects that may 
be attributed  to the use of microorganisms in food, or issues relating to the safety of food 
production workers handling recombinant-DNA microorganisms.  
  
 
  
  
 
 3Chapter Two: Food Safety Assessment of GM Foods 
 
This c hapter describes food safety as sessment of  GM foods deri ved from 
recombinant-DNA org anisms . Infor mation required v aries according to the sources of  the 
GM foods (microorg anisms , animals , or microorg anisms).  
 
Food safety assessment of  GM foods produ ced usi ng recombinant-DNA microorg anisms is  
conducted in three phases  as follo ws. 
 
I. Phase I asses sment is con ducted a ccording to the infor mation listed in Ann ex I. 
 
II. When the results of  the phase I assessment indicate th e presence of  possible to xin(s) 
and/or allerg en(s) in th e GM foods produ ced using recombinant-DNA microorg anisms, 
phase II assessment m ust be perfor med. Phase II assessmen t is conducted according to  
the follo wing infor mation: 
 
A. Safety assess ment of  possible to xicity (for details see Annex II ) 
 
B. Safety assess ment of  possible allerg enicity  (for details see Annex III )  
 
III. When phase I and phase II assessments o f the GM foods produced using 
recombinant-DNA microorg anisms indicate tha t the a vailable data are insufficient for a 
thorough safety ass essment, properly designed animal to xicity studies on th e whole foo ds1 
or a m ultidisciplinar y approac h for assessing  safety using th e con cept of substantial  
equivalence a re requested.   
                                                 
1 Whol e food is defined as t he gene ral eatable parts of the GM foods, of which the compone nt has not been 
refined, processed, concentrated, or purified.  
 4ANNEX I - INFORMATION REQUIRED FOR THE SAFETY 
ASSESSMENT OF PRODUCED USING RECOMBINANT-DNA 
MICROORGANISMS 
 
I. APPLICATION MATERIALS MUST  INCLU DE THE FOLLOW ING 
INFORMATION 
 
A. DESCRIPTION OF THE RECOMBINA NT-DNA MICR OOR GANISM  
A) Description of  the bacter ial, yeast, or fung al strain; 
B) Description of  the food produced using  the reco mbinant-DN A microorg anisms; 
C) Infor mation about th e preser vation and identification of  the recombina nt-DN A 
microorg anisms used in food production or contained in food  
 
B. DESCRIPTION OF THE HOST MICROORGANISM AND ITS USE AS 
FOOD  
The data and  infor mation should include , but need not be restri cted to: 
 
A) Identity  
a. scientific name , common name or ot her name(s) used to reference th e 
microorg anism; 
b. strain designation;  
c. infor mation about the str ain and its s ource, or accession n umbers or other 
infor mation from a recognized culture re positor y from whic h the org anism 
or its antecedents ma y be obtained; and  
d. if applicable , infor mation suppor ting its tax onomical assignment. 
B) Histor y of  use and culti vation, kno wn infor mation abou t 
strain dev elopment (including isolation of  mutations or 
anteceden t strains used in strain constr uction);  
C) Infor mation on th e recipient micro organism’ s and related  
species ’ genotype and ph enotype relev ant to safety , including  
a. any kno wn toxins, antibiotics , antibiot ic resistance factors or o ther factors 
related to pathog enicity , or imm unological impact;  
b. the g enetic stability of  the microorg anism including, as appropriate , the 
presence of  mobile DN A elem ents, i.e. inser tion sequences , transposons , 
plasmids , and prophag es. 
D) Histor y of safe use in food production or safe consumption 
in food, whic h ma y includ e infor mation on 
a. how the reci pient microo rganism is typically g rown;  
b. how the reci pient microo rganism is typically transp orted;  
c. how the reci pient microo rganism is typically stored ; 
d. quality assurance , including those to v erify strain  identity and production 
specification s for microorg anisms and foods; and 
e. wheth er these org anisms remain viable in the processed food or are 
remo ved or rendered non-viable as  a consequence of  processing . 
E) Infor mation on the relev ant production parameters used to 
 5culture the r ecipient mi croorg anism. 
 
C. DESCRIPTION OF THE DONOR ORGANISM(S)  
A) Identity .  
a. Scientific name , common name or other name(s ) used to reference the org anism;  
b. strain designation;  
c. infor mation about the strain and its source , or accession n umbers or other 
infor mation from a recognized culture re positor y from whic h the org anism or its  
anteceden ts ma y be obtai ned; and 
d. if applicable , infor mation suppor ting its tax onomic assignment; its usual or 
common name , scientific name and tax onomic clas sification; 
B)  infor mation about the org anism or related  organisms that co ncerns food safety; 
C)  infor mation on the org anism’ s genotype and  phenotype relev ant to its safety 
including any kno wn toxins, antibiotics , antibiotic resistance fa ctors or oth er factors  
related to pathog enicity , or imm unological impact; and 
D) infor mation on the pas t and present use , if any, in the food s upply and exposure 
route(s) o ther than intend ed food use ( e.g., possible presence as contaminants ). 
 
D. DESCRIPTION OF THE GE NETIC MODIFICATION(S) 
 Including v ector and co nstruct  
A) The descripti on of  the str ain constr uction process should include:  
a. infor mation on the specific method (s) used for g enetic modifica tion; 
b. infor mation on the DN A used to mod ify the micro organism, including  
a) the source (e .g. plant, microbial, viral, synthetic); 
b) identity;   
c) expected f unction in th e recomb inant-DNA microorg anism; and  
d) copy n umber for plasmids; 
c. intermedia te recipient org anisms2. 
B) Infor mation should b e provided o n the DN A added, inser ted, deleted, or modified, 
including:  
a. the characterization of  all genetic components , including  
a) mark er genes;  
b) vector g enes; 
c) regulator y elements; and  
d) other elem ents affecting the function of  the DNA; 
b. the size and identity; 
c. the location  and orientation of  the sequence in the final 
vector/cons truct; and  
d. the function.  
 
E. CHARACTERIZATION OF THE GE NETIC MODIFICATION(S)  
A) Information should be provided on the DNA modifications in the recombinant 
DNA micro organism; this should include:  
a. the characterization and  description of th e add ed, inserted, deleted, or o therwise 
modified genetic materials, including plasmids or other car rier DNA u sed to  
                                                 
2 Interm ediate recipient or ganisms mean the org anisms (e.g. other bacteria o r fungi) used to produce o r 
process DNA  prior to introduction into the fi nal recipien t organism.  
 6transfer desired genetic s equences. Thi s should include  
a) an analysis o f the poten tial for mobilization of an y plasmids 
or other genetic el emen ts used;  
b) the location s of the added, inserted, deleted, or otherwise 
modified genetic ma terials (site on  a chromosomal or 
extrachromosomal locati on); and  
c) if located o n a multico py plasmid, the cop y number of the 
plasmid; 
b. the number of insertion sites;  
c. the organization3 of the modified genetic material at each inserti on site inclu ding 
a) the copy nu mber and sequence data  of the inserted, modified, or deleted 
material;  
b) plasmids or carrier DNA used to tran sfer the desired genetic s equences; and   
c) the surrounding sequences4; 
d. identification  of any open reading frames5 within inserted DN A, or created  by the 
modifications to contiguous DNA in the chromosome or in a plasmid; and 
e. particular reference to a ny sequen ces known to  encode, or  to influence the 
expression of, potentially harmful func tions. 
B) Information should be provided on any newly expressed  substance(s )6 in the 
recombinant-DNA microorg anism.  
This should include infor mation listed in a to f . If the newly expressed substance(s) 
in the reco mbinant-DN A microorg anism were ev aluated to be subs tantially 
equivalent to  existing substances with kno wn histor y of safe use as foods, no further 
assessment would be required. Otherwise,  assessments listed in F-B) should be 
conducted. 
a. the gene pro duct(s) (e.g.  a protein or an untranslated RNA);  
b. the gene pro duct(s)’ function;  
c. the pheno typic descripti on of the new trait(s );  
d. the level an d site of expression (intracellular, periplasmic - for Gram-negative 
bacteria, organellar - in eukaryotic mi croor ganisms, secreted) i n the microorganism 
of the expressed gene product(s),  and, when  applicable,  the lev els of its  
metabolites in the organism;   
e. the amoun t of the inserted gene p roduct(s) if the function  of the exp ressed 
sequence(s)/ gene(s) is to alter the le vel of a specific endo genous mRNA or  
protein; and 
f. the absence of a gene product, or alter ations in metabolites related to gene 
products, if applicable to the intended fu nction(s) o f the genetic modification(s). 
  C) In addition, infor mation should be pro vided:  
a. to demons trate wheth er the ar rangement of the modified g enetic material ha s 
been conser ved or whether significant rear rangements ha ve occur red after  
                                                 
3 The i nformation s hould be  descri bed c omprehensi vely so t hat the identification of any  substances 
expresse d as a conseque nce of the inserted , modified or deleted  material i s possible.   
4 The information shou ld allow th e identificatio n of any possible newly expressed materials pre sented in 
foods being made.  
5 Including thos e that can re sult in fusion proteins. 
6 Newly expre ssed m aterials  are those expres sed m aterials, suc h as proteins , untra nslated RNA, or  
metab olites, etc., th at are expressed  by the foreign DNA inserted  thro ugh genetic m odificatio n, and are n ot 
natively in  the host strain.  
 7introduction to the cell and propag ation of  the recombinant s train to the exten t 
needed for its use(s) in food production, including those tha t may occur during its 
storag e; 
b. to demonstr ate whether deliberate m odifications made to the amino acid sequence 
of the expressed protein result in c hanges in its post-translational modification or 
affect sites critical for its str ucture or function; 
c. to demons trate whether the intend ed effect of the modification has been a chieved 
and that all expressed traits are expressed and inherited in a manner that is stable 
for the extent of  propag ation needed for its use(s) in food  production and is 
consistent with la ws of  inheritance . It ma y be necess ary to examine the 
inheritance of  the inser ted or modified DNA or the expression of  the 
corresponding RNA if  the phenotypic c haracteristics cannot b e measured di rectly; 
d. to demonstr ate wh ether the newl y expressed trait(s) is expressed as expected and 
targeted to the appropriate cellular location or  is secreted in a manner and at lev els 
that is consi stent wi th th e associated re gulator y sequences dri ving the expression 
of the cor responding g ene; 
e. to indicate whether there is any eviden ce to  suggest that one or more g enes in the 
recipient microorg anism has been affected  by the modifications or the g enetic 
exchange process; and 
f. to confir m the identity a nd expression patter n of any new fusi on proteins . 
 
F. SAFETY ASSESSMENT  
A) Compositional analyses of key components  
a. Analyses should be performed by comparing the concentrations of key 
components  of foods produced by r ecombinant-DNA microorganism s to a 
conventional  counterpart produced un der th e same conditions u sing an equivalent 
analysis. 
b. Ideally, the comparator(s) used in this assessmen t should be food produced using 
the near isogenic parent s train. 
B) Initial assessment of possible toxicity and allergenicity of newly expressed substances 
in recombinant-DNA microorganisms 
a. For initial assessment of possible toxicity of the n ewly express ed substances, the 
following information should be provided. 
a) Function and concen tration in the food; 
b) the expected  exposure, possible intake,  and possible effects on diets;  
c) history of safe use as food ; 
d) information should be provided to ensur e that genes coding for known toxins 
or anti-nutrients pres ent in the do nor organisms are not transferred to  
recombinant-DNA microorganisms; 
e) in the cas e of proteins, the assessm ent of potential toxicity shou ld focus on  
1. amino acid sequence s imilarity betw een the protein and kno wn protein to xins 
and anti-n utrients (e .g. protease inhibi tors, siderophores);  
2. stability to h eat or proces sing; and 
3. stability to  deg radation in appropriate re presentati ve 
gastrointesti nal model systems . 
4. Appropriate oral to xicity studies (Annex II) may be car ried 
out in cases where the pr oteins present in the food sho w no 
close similarity to protein s that ha ve been safely co nsumed in 
 8food, nor has been consu med safe ly in food previously , taking 
into account its biologica l function in microorg anisms wher e 
known.  
b. For initial assessment of  possible allerg enicity of  the newly expressed protei ns, the 
following infor mation should be pro vided. 
a) The source of the intro duced protei n 
1. Information should descr ibe any report s of allergenicity asso ciated with 
the donor organism.  
2. When evidence of IgE mediated oral, re spiratory or contact a llergy of the 
donor organism is available, the following information may be provided.  
1) The availability of  sera for screening pur poses;  
2) documen ted typ e, severity and frequency of  allergic reactions;  
3) str uctural  characteristics and amino acid sequence of  the kno wn 
allerg enic proteins from that source; a nd 
4) if  available , physicoc hemical and  imm unological proper ties of  the 
known allerg enic proteins  from the source . 
3. Genes derived from known allergenic  sources should be assumed to 
encode aller gens and be avoided unless scientific evidence d emonstrates  
otherwise. The transfer of genes from orga nisms known to elicit 
gluten-sensitive enteropathy in sensitive individuals should be avoided  
unless it is documented that the tran sferred gene does not code for an  
allergen or for a protein involved in gluten-sensitiv e enteropath y. 
4. When genes are derived from non-alle rgenic sources, the following 
information should be provided.  
1) Level and location of the newly expressed protei n; and 
2) function of the newly expressed protein. 
b) Amino aci d sequence homology   
1. Result on sequence ho mology search es comparin g the structure of all 
newly expressed protein s with all known allergens must be provided. 
Searches sho uld be condu cted using various algorithms7 to predi ct overal l 
structural similarities. 
2. Strategies su ch as step wise contiguous identical  amino acid  segment 
searches8 must be performed for iden tifying sequences that may 
represent linear epitopes.   
3. IgE cross-reacti vity betw een th e newly expressed  protein and  a kno wn 
allerg en should be considered a possibility when 
1) there is more than 35% identity in a segment of 80 or more amino 
acids (FAO/WHO 2001). 
2) linear epitope(s) is identified or there are other scientifically justified  
criteria. 
4. A positive sequence homology result9 indicates tha t the newly expressed  
protein is likely to be allergenic. If the product is to be considered further, 
                                                 
7 E.g. FASTA or BL ASTP . 
8 The size of the contiguo us amino acid search should be b ased on a sci entifically justified rationale in order to 
minimize the p otential  for false ne gative or false positi ve results . 
9 A n egative sequen ce homol ogy result indi cates that a newly expressed protein  shou ld be consi dered along 
with the  other data outlined under this  strategy in assessing  the allergenic p otential  of these pro teins. Further 
studies should be conducted as approp riate.  
 9it should be assessed using serum, if av ailable, fro m individuals allergic to 
the identified allergenic source. If  there is no available serum, other 
scientifically sound methods and tools may be used to assess the 
allergenicity potential of the newly expressed protei n(s).  
c) Pepsin res istance 
1. The assessm ent should be conducted with a consistent and well-validated  
pepsin degradation protocol. 
2. Further analyses are requ ired for a newly expressed protein with a pepsin  
digestion fra gment larger than 3.5 kDa.  
3. Alternative protocols may be used where a dequate justification is 
provided.  
c. For proteins from  sourc es not kno wn to be allerg enic, and whic h do not exhibit 
sequence homolog y to a kno wn allerg en, targ eted ser um screening or other related  
IgE ser um screenings and imm unological tests mi ght be consi dered. 
d. Initial assessment of  possible to xicity and/or allerg enicity of  the newly expressed  
substances i n recombinant-DNA microorg anisms ma y require the isolation of  the 
new substan ce from the recombinant-DNA micr oorganism, or the synth esis or 
production of  the subs tance from an alter native source, in whi ch case the material  
should be s hown to be bioc hemically , structurall y, and functi onally equi valent to 
that produced in the reco mbinant-DN A microorg anism.  
e. When the r esults of th e initial assessm ent ind icate that th e newly expressed  
substance is  possible toxin(s) and/or allergen(s), further assessment sho uld be 
conducted according to Annex II and/or III. 
C) Evaluatio n of metabol ites  
Some recombinant-DNA microorganisms may have been modi fied in a manner that 
could result in new or altered levels of various meta bolites in the food.  
a. Where altered residue or metabolite l evels are identified in foods, consideration 
should be given to the potential impacts on human health using conve ntional  
procedures10 for establishing the safety of such metabolites. 
b. New or altered levels of metabolites produced by a recombinant-DN A 
microorganism may change the popul ation of microorganisms in mixed culture, 
potentially in creasing the risk for growth  of harmful organisms or accumulation of  
harmful substances. Pos sible effects of genetic m odification of a microorganism 
on other microorganisms should be assess ed when a mixed culture of 
microorganisms is used for food processing. 
D) Nutritional modification  
Foods derived from re combinant- DNA microorganisms that have undergone 
modification to inten tionally alter n utritional quality or functionality sh ould be 
subjected  to additional nutritional assessm ent to assess the consequen ces of th e 
changes and wheth er the nutrient inta kes are likely to be altered by the introduction  
of such foods into the food supply.  
a. The likely in take of the food deri ved from the recombinant-DNA microorg anism 
should be estimated. T he expected in take of the fo od should be used to assess the 
nutritional implications of  the altered nutrient profile both at customar y and 
maximal lev els of consumption.   
b. Although the recombinant-DNA microorga nism components  may be individually 
                                                 
10 E.g. procedures for asse ssing the  human safety of chemicals i n foods.  
 10assessed as s afe, the impa ct of the cha nge on the overall nutrient profile should be  
determined.  
c. When the modification results in a food  product with a composition  that is  
significantly different from its con ventional counter part, it m ay be appropriate to  
use additional con ventional foods or food com ponents (i.e . foods or food 
components  whose n utritional composition is closer to that of  the food deri ved 
from recombinant-DNA microorg anism) as  appropriate comp arators to ass ess the 
nutritional impact of  the food. 
d. It is also i mportant to  ascer tain to what extent the mo dified n utrient is 
bioavailable and remains stable with ti me, processi ng and storag e. 
e. Animal feeding studies ma y be w arranted for food s deri ved from 
recombinant-DNA micr oorganisms if  changes in the bio availability of  nutrients  
are expected or if  the composition is not comparable to con ventional foods .  
f. Foods designed for health benefits , may require an assessment bey ond the scope 
of these guidelines suc h as specific n utritional, to xicological or other appropriate 
studies . 
g. In consideration of  geographical and cultural v ariation in food consumption 
patter ns, the nutrient a nd the pop ulations affected should  be identified for 
nutritional changes to a s pecific food.  
h. Attention s hould be paid to the par ticular ph ysiological c haracteristics and 
metabolic requirements of  specific populati on g roups suc h as infants , children, 
pregnant an d lacta ting w omen, th e elderl y and  those with  chronic dis eases or 
compromised imm une systems . 
i. If the c haracterization of  the food in dicates  that the a vailable data are insufficient 
for a thorough safety assessment, p roperly designed animal studies could be 
requested on  the whole f oods. 
E) Antibiotic resistance and g ene transfer11 
a. Antibiotic resistance 
a) When the microorg anisms contain antibiotic resistance g enes, 
describe the location of  the g enes in the cell;  
b) any indication of  the presence of  plasmids , transposons , and  
integ rons containing suc h resistance g enes should be 
specifically addressed.  
b. Gene transfer 
a) Note th e location of  the genetic m aterial to be inser ted into the g enome. 
Chromosomal integ ration of  the inser ted genetic material ma y be preferable to  
localization on a plasmid; 
b) where the recombinant-DNA microorg anism will remain viable in  the 
gastrointesti nal tract, g enes should be a voided in the g enetic constr uct that 
could pro vide a selecti ve advantage to recipient org anisms to whic h the g enetic 
material is unintentionall y transfer red; and 
c) sequences th at media te integration into other g enomes should be a voided  in 
constr ucting the introduc ed genetic m aterial.  
F) Viability and  residence of  microorg anisms in the h uman g astrointestinal tra ct 
For applications in whic h recombinant-DNA mi croorg anisms used in pr oduction 
                                                 
11 Please refer to th e “Gu idelines on  the assessmen t of the health foods for improving the gastro intestin al 
tract fun ctions” issu ed by the Dep artment of Health  for more details.  
 11remain viable in the final food product, the follo wing infor mation m ust be pro vided: 
a. Demonstrati on of  the viability or resi dence time of  the microorg anism alone and  
within the respecti ve food matrix in the dig estive tract. 
b. Assessmen ts of the impa ct on th e intestinal micro flora in appropriate system.  
G) Food processing 
a. The potentia l effects of food processi ng, including home preparation, on foods 
derived from recombinan t-DNA micr oorganisms should be con sidered. 
 
G. OTHER CONSIDE RATIONS   
 The safety assessmen t should be rev iewed in the light of  new scient ific infor mation that 
calls into question the con clusions of  the original safety assess ment.  
 
II. LITERATURES AND REFERENCES 
 
A. Documen tation reg arding the appr oval and consumption of  the GMO in other 
countries . 
B. Any oth er infor mation to  demonstrate safety of  the GMO as food. 
C. For safety as sessment of  unintended effects , refer to Annex IV . 
 
 12ANNEX II - SAFETY ASSESSMENT OF POSSIBLE 
TOXICITY 
I. Current dietary exposure and possible eff ects on population sub-groups should be 
considered.  
II. Appropriate oral toxicity studies12 may need to be carried o ut in cases  where the 
protein present in the f ood is not similar to proteins that have previously been 
consumed s afely in food, and taking into  account its biological function in the 
microorganism where kno wn.  
III. Potential tox icity of non- protein substances  that have not been sa fely consumed in 
food should be assessed on a case-by-ca se basis depending on the identity an d 
biological function in the microorganism of the substance and dietary expo sure. The 
type of studi es to be p erformed may include stu dies on metabolism, toxicokinetics,  
acute toxicity, sub-chronic toxicity, chroni c toxicity/carcinog enicity, repr oduction12 
and develop ment toxicity according to the tradition al toxicological approach . 
IV. Assessmen t of possible toxicity of the newly expressed substances i n 
recombinant-DNA microorganism may require  the isolatio n of the new substance  
from the re combinant- DNA microorganism, or the synthes is or produc tion of the 
substance from an al ternative source,  in wh ich case th e ma terial should be shown to 
be biochemi cally, structu rally, and functionally  equivalent to that produced in the 
recombinant-DNA microorganisms. 
 
 
 
                                                 
12 Please re fer to the “ Guideline s on the safety assessm ent of the health foods” issued by the Department of 
Health or the OECD Guideli nes for the Testing of Chem icals.  
 13ANNEX III - SAFETY ASSESSMENT OF POSSIBLE 
ALLERGENICITY 
 
I. Serum screening  
A. For those proteins that originate from a source known to be allergenic, or have  
sequence ho mology with  a known  allergen, specific serum s creenings sh ould be 
performed where sera are available.  
A) a minimum of 8 relevant sera is require d to achieve a 99% certainty that the new 
protein is not an allergen in the cas e of a major allergen13; and 
B) a minimum of 24 relevant sera is r equired to achieve the sa me level of certainty in  
the cas e of a minor allergen14.  
B. In the cas e of a newly expressed protein derived  from a known allergenic source,  a 
negative result in in vitro immunoas says15 may n ot be consi dered sufficient, but 
should prompt additio nal testing, such as the p ossible use of skin test and ex vivo 
protocols. A positive result in such tes ts would indicate a poten tial allergen. 
 
 
II. Other consid erations 
A. The types  of food processing would be applied and its effects on the presence of th e 
protein in the final food product; and 
B. Other sci entifically sound methods and tools16 may be con sidered in assessing the 
allergenicity potential of the newly expressed protei n(s).  
  
 
                                                 
13 A majo r allerg en is defined as one to whi ch more than  50 % of  individua ls sensiti ve to that subs tance react 
in IgE-sp ecific immunoassays. 
14 A minor allergen is defined as one to which less than 50 %  of individuals sensiti ve to that substan ce react in  
IgE-sp ecific imm unoassays. 
15 A neg ative result in in vitr o immunoassa ys may not b e considered suffici ent, a positi ve result in oth er tests 
would in dicate a pot ential allergen. 
16 These may incl ude targeted serum screenin g (i.e. the assessment of  binding to IgE in sera o f individuals wi th 
clinically v alidated allergic resp onses  to broadly-related categories of foods); th e development o f inter national 
serum banks ; use o f anim al models; and examination of newly exp ressed pro teins for T-cell e pitopes and 
structural motif s asso ciated with allergens. 
 14ANNEX V - SAFETY ASSESSMENT OF UNINTENTED 
EFFECTS 
 
I. Unintended effects mos t likely are r esulted  from  the insertio n of DNA sequences, 
subsequent conventional  breeding of the recomb inant-DNA microorganism,  and/or 
the random insertion of DNA sequences into th e microorganism genome which may  
cause disruption or silencing of existing genes, activation of silent  genes, or 
modifications in the expression of existing genes. 
II. Safety assess ment of unintended effects must include the related experimental data and  
information, so that the possible advers e effects  on human from unintended effects  
could be minimized.  
III. The assess ment of u ntended effects take s into accoun t the biochemical, an d 
physiological characteristics of the microor ganism tha t are typically s elected for 
improving st rains for commercial food or be verage uses. These determinations provide 
a first scree n for micro organisms t hat exhibit untended tr aits. Recom binant-DNA 
microorganisms that pas sed the safety assessm ent of unintended effect shall then 
conduct the safety ass essment des cribed in Annex I.   
 
 
 
 
 
 15