Esplanada dos Ministérios, Bloco E, Térreo ? Salas T-15/T-17

Brasilia- DF- Brazil CEP 70067-900

Phone numbers: (55)(061)317-7828/ 317-7827/ 317-7683 FAX: (55)(061) 317-7682

Law n. 8974, of January 5th 1995

Decree n. 1752, of December 20th 1995

Decree n. 2577, of April 30th 1998

CTNBio Internal Statute

CTNBio Institutional Acts

Institutional Acts by the Ministry of Agriculture and Supply

It regulates clauses I and IV of the 1st paragraph of article 255 of Brazil?s Federal Constitution, regulates the usage of genetic engineering techniques, and the delivery of genetically modified organisms in the environment. It also authorizes the Executive Power, represented by the President, to create the National Technical Biosafety Committee, and establishes other procedural measures.

It regulates Law n. 8974 of January 05th 1995, and also legislates about subordination, competence, and composition of the National Technical Biosafety Committee _ the CTNBio.

It changes the text of the 3rd article of Decree n. 1752, of December 20th 1995, which regulates Law n. 8974 of January 05th 1995, which legislates about subordination, competence, and composition of the National Technical Biosafety Committee _ the CTNBio.

It approves the internal statute of the National Technical Biosafety Committee _ CTNBio.

It legislates about requests and releases of Certificates of Quality in Biological Security _ CQB and the composition of Internal Biosafety Committee_ CIBio, as well as their functioning.

It legislates about the importing of genetically modified plants for research.

It legislates about the planned release of Genetically Modified Organisms_ GMOs in the environment.

It legislates about transportation of Genetically Modified Organisms _ GMOs.

It states that every request for importing of genetically modified plants, aiming planned release in the environment, shall have its proposal submitted and first approved by its reviser, in order to be evaluated by the Committee.

It establishes the classification of the experiences with Genetically Modified Plants _ GMP, according to their risk and containment levels.

It legislates about works under containment with Genetically Modified Organisms _ GMOs.

It legislates about genetic manipulation and about cloning of human beings.

It legislates about genetic intervention on human beings.

It legislates about planned release in the environment of Genetically Modified Plants _ GMP, previously approved by the CTNBio.

It legislates about the importing of genetically modified microorganisms for usage on work under containment.

It legislates about work under containment with Genetically Modified Animals _ GMAns.

It legislates about the importing of Genetically Modified Animals for usage on containment work.

It legislates about the expiry time of the request processes of the Biological Security Quality Certificates.

It legislates about the research and technological development works that employ non-genetically modified animals where Genetically Modified Organisms _ GMO, are manipulated under containment.

Rules for design and presentation of requested maps and drafts for planned release in the environment of Genetically Modified Organisms _ GMO.

It rules the activities of importing, commerce, transportation, storage, manipulation, consumption, release, and disposal of products derived from Genetically Modified Organisms _ GMO.

It rules the planned release in the environment and in the commerce of Roundup Ready Soybeans, as well as any germ plasm derived from «glyphosate tolerant soybean» (GTS 40-3-2) lineage or their progenies genetically modified to resist to glyphosate herbicide.

It rules the importing of material destined to scientific research.

Institutional Act n. 02, of the Brazilian Ministry of Agriculture and Supplying 134

It approves models of inspection term and infraction note for establishments that operate with genetically modified organisms.

It changes the text of the 3rd article of Decree n. 1752, of December 20th 1995, which rules Law n. 8974 of January 05th 1995, which legislates about subordination, competence, and composition of the Brazilian Committee of Biological Security _ the CTNBio.

THE PRESIDENT OF THE REPUBLIC, by the use of prerogatives conferred by the article 84, clauses IV and VI of Brazil?s Federal Constitution, in accordance with the Law n. 8,974, of January 5th 1995,

Art. 1st ? The article 3rd of Decree n. 1752 of December 20th 1995, shall now take effect having the following text:

"Art. 3rd ? The CTNBio, composed by permanent and substitute members, elected by the Minister of Science and Technology, shall be constituted by:

V ? a representative of legally constituted associations representing the biotechnology industry sector, who shall be chosen by the Minister of Science and Technology, out of triple lists sent by the mentioned associations;

§ 2nd The experts mentioned in clause I shall be chosen by the Minister of Science and Technology, out of scientists entitled with a pH, recommended by scientific and technologic institutions and associations related to biotechnology.

§ 5th The representative mentioned in the clause IV of this article shall be chosen by the Minister of Science and Technology, out of the names suggested, in a triple list, by public or non-governmental institutions for the customer?s defense, observing the same query and indication system established in the § 3rd.

§ 8th The representative specified by clause IV in this article shall be chosen by the Minister of Science and Technology out of suggestions given by the Ministries of Health and of Labor, as well as non-governmental institutions for laborer?s health defense, observing the same query and indication system established in the § 3rd."

Art. 2nd ? This decree shall take effect in the date of its publication.

Brasilia, April 30th 1998, 177th year of Independence and 110th year of Republic.

It approves the regiment of the National Technical Biosafety Committee _ CTNBio.

THE NATIONAL TECHNICAL BIOSAFETY COMMITTEE ? CTNBio, by the use of the competence ruled by the article 2nd , clause XVIII of the Decree n. 1,752, of December 20th 1995, states that:

Art. 1st The regiment of the National Technical Biosafety Committee ? CTNBio, which text is integrally published below, is approved.

Art. 2nd This resolution takes effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the Committee

CHAPTER I

ORGANIZATION

SECTION I

Art. 1st The National Technical Biosafety Committee _ CTNBio, ruled by the Decree n. 1,752, of December 20th 1995, subordinated to the Executive Secretary of the Ministry of Science and Technology, aims to follow the development and technique and scientific progress of genetic engineering in the fields of the Biotechnology, the Bioethic, the Biosafety and other related fields, respecting strictly the safety of customers and population in general, taking constant care with the defense of the environment, and it has the function of stimulating and proposing all researches and complementary studies in order to evaluate potential risks of new methods and available products.

SECTION II

Art. 2nd The following activities are competence of the National Technical Biosafety Committee _ CTNBio:

I - Proposing the National Biosafety Ethic Code for Politic and Genetic Manipulations;

II ? Supervising the development and the technical and scientific progress in biosafety and its related fields, aiming the safety of customers as well as the population in general, devoting constant care with the protection of the environment;

III ? establishing relations with institutions devoted to genetic engineering and biosafety, both in national and international fields;

IV ? stating rules and norms related to activities and projects aiming construction, cultivation, handling, usage, transportation, storage, commerce, consumption, release and disposal related to GMO;

V ? classifying the GMO according to their hazard level, defining the biosafety levels applied to them as well as to the activities considered unhealthy and dangerous;

VI ? creating the work mechanisms for the CIBios , as well as the biosafety norms and patterns for the functioning of such committees;

VII ? giving previous technical statements about the projects related to GMO belonging to group II, sending them to the qualified inspection department;

VIII - giving previous technical statements about the importing of products containing GMO for commerce or industrialization, sending them to the qualified inspection departments, taking into consideration technical reports from other countries when available;

IX ? giving previous technical statement about any release of GMO in the environment, sending it to the qualified inspection department;

X ? giving previous technical statements about registration, usage, transportation, storage, commerce, consumption, release and disposal of products containing GMO or GMO derived substances, sending such report to the qualified inspection department;

XI ? providing technical support to qualified departments concerning the inquiry processes of accidents and diseases observed during the execution of genetic engineering projects and activities, as well as inspecting and supervising such projects and activities;

XII ? publishing in the Federal Official Gazette (D.O. U.), before the analysis process, a resume of the requests submitted to its approval, concerning the release of GMO in the environment, excluding confidential information having commercial interest, which is object of the right of intellectual property, and shall be indicated and considered like this by the requestor;

XIII ? publishing in the DOU the result of the submitted requests, as well as the conclusion of related technical reports;

XIV ? informing the interested part about the result of the request submitted to the Committee and providing its publication in the DOU;

XV ? demanding, whenever it is considered necessary, an environmental impact study and an environment impact report of projects and appliance involving the release of GMO in the environment, besides the specific requirements in accordance with the applicable hazard level;

XVI ? giving the CQB referent to the installations destined to any activity or project involving GMO or derived substances, by requirement of the task?s proponent;

XVII ? recruiting ad hoc advisors whenever it is necessary;

XVIII ? proposing changes in the regulation of the Law n. 8,974, of January 5th 1995;

XIX ? sending the received requests to the Specific Departmental Commissions;

XX ? establishing necessary formularies and documents for the evaluation of issues related to GMO by the CTNBio; and

XXI ? defining the value of fines, starting from 16,110.80 UFIR, to be applied to the infringer by the inspection departments.

SECTION III

Art. 3rd The CTNBio, designated by the President of the Republic, composed by titular and substitute members, shall be composed as follows:

I ? eight experts having notorious scientific and technical knowledge, in exercise in the Biotechnology field, providing that two of then shall be from the field of human science, two from the vegetal field, two from the animal field, and two from the environmental field;

II ? one representative from each of the Ministries below, indicated by their respective Ministers:

1. Science and Technology;

2. Health

3. Environment, Water Resources and Legal Amazon;

4. Education and Sports;

5. International Relations.

III ? two representatives of the Ministry of Agriculture and Supply, one of the vegetal field and other of the animal field, both indicated by the respective Minister;

IV ? one representative from a legally constituted customer defense department;

V ? one representative of legally constituted associations, representing the biotechnology firms sector, which shall be indicated by the Minister of Science and Technology, from triple lists sent by the referred associations;

VI ? one representative from the legally constituted labor health?s defense department.

§ 1st The candidates indicated to compose the CTNBio shall present adequate qualification and professional experience in Biotechnology, proved by their respective curricula vitarum .

§ 2nd The experts mentioned in clause I shall be chosen by the Minister of Science and Technology, out of scientists entitled with a Ph.D., recommended by scientific and technologic institutions and associations related to biotechnology.

§ 3rd The indication mentioned in the paragraph above shall be done within a period of thirty days counting from the date when the query elaborated by the CTNBio?s Executive Secretary is received; such request shall be done respecting the same period, starting from the vacancy occurrence date.

§4th In case the proposed names are not approved, the Minister of Science and Technology may ask for alternative indication of other names.

§ 5th The representative mentioned in the clause IV of this article shall be chosen by the Minister of Science and Technology, out of the names suggested, in a triple list, by public or non-governmental institutions for the customer?s defense, observing the same query and indication system established in the § 3rd.

§ 6th It shall be considered as for customer?s defense the public or private institutions enrolled in the Department of the Customer?s Defense of the Ministry of Justice?s Economic Right Secretary.

§ 7th Each one of the Biotechnology business field representative associations, legally constituted and enrolled in the CTNBio Executive Secretary, shall send a triple list for the indication of the representative mentioned in clause V, observing the same query and indication system established in the § 3rd.

§ 8th The representative specified by clause IV in this article shall be chosen by the Minister of Science and Technology out of suggestions given by the Ministries of Health and of Labor, as well as non-governmental institutions for laborer?s health defense, observing the same query and indication system established in the § 3rd.

SECTION IV

Art. 4th The term of office of the members of the CTNBio shall be of three years, and its renewal is allowed only once.

§ 1st Every three years, the composition of the CTNBio shall be renewed on half of its members, providing that, in the first mandate, four out of the eight experts mentioned in the clause I of the art. 3rd shall be necessarily re-admitted.

§ 2nd the CTNBio shall evaluate the members that will be substituted obeying the following criteria:

1. manifestation of the member?s interest to leave the Committee;

2. interest of the member by the CTNBio?s activities, measured by the attendance to the meetings.

§ 3rd In case of parity, the choice shall be made by secret vote.

§ 4th In the occasion of the renewal of the CTNBio?s members, applicants shall fulfill the requirements stated in the § 1st of the art. 3rd.

§ 5th The CTNBio?s Executive Secretary shall elaborate the query to scientific and technological institutions and associations related to biotechnology and, within a period of thirty days from the date when the answer is received, shall submit the names to the Committee?s members? approval, for the designation of the experts mentioned in the clause I of the art. 3rd.

§ 6th Concerning the members mentioned in the clauses II, III, IV, V, and VI of the art. 3rd, the proceeding stated by the paragraph above shall also take into consideration what is determined by the art 3rd of the Decree n. 1,752, of December 20th 1995.

§ 7th The indication of new scientist members of the CTNBio shall be done by the permanent members exercising their term and sent to the Minister of Science and Technology for approval. In case of non-acceptance of any suggested name, the Committee shall send new names, chosen out of those indicated be the respective scientific and technological institutions and associations, customer defense departments, biotechnology business sector, or customer?s health department, in accordance with the case.

Art. 5th The chairman of the CTNBio shall be designed by the Minister of Science and Technology, out of a triple list elaborated by the council, with names taken out of its members.

§1st The term of office of the chairman of the CTNBio shall be of one year, and may be renewed for until two consecutive periods.

§ 2nd The CTNBio shall decide about proceeding or not the renewal of the president?s mandate.

SECTION V

Art. 6th The CTNBio shall form, out of its permanent and substitute members, Specific Sector Commissions to provide technical support to the inspection departments of the Ministries of Health, of the Agriculture and Supply, and of the Environment, Water Resources, and Legal Amazon, in accordance with the competencies attributed by the Law n. 8,974, of 1995.

§1st Each one of the Commissions mentioned in the caput of this article shall be constituted by the representative of its respective Ministry, responsible for the specific sector at the CTNBio, who will chief the commission, and by members of the CTNBio from areas related to the sector.

§ 2nd The members of the Specific Sector Commissions, either permanent or substitute ones, shall exercise their mandate for a period of three years, which can be renewed. The mandate in the Commissions shall expiry together with the mandate in the CTNBio.

§ 3rd The Specific Sector Commissions shall work as an extension of the CTNBio and shall count, in their respective Ministries, with the adequate working structure.

§ 4th The Specific Sector Commissions can recruit ad hoc advisors whenever it is necessary.

Art. 7th The Specific Sector Commissions have the following competencies:

I ? giving technical support to the inspection departments of the Ministries of Health, of the Agriculture and Supply, and of the Environment, Water Resources, and Legal Amazon;

II ? inspecting and supervising, in consonance with the competent inspection departments in the respective ministries, the registration, transportation, commerce, handling and release of products containing GMO or derived substances, in accordance with the report of the CTNBio;

III ? preparing technical statements about the requests submitted to CTNBio and informing the result of such reports to the inspection departments, for the necessary measures to be taken;

IV ? sending the processes back to CTNBio after the necessary analysis.

SECTION VI

Art. 8th The Executive Secretary have the following competencies:

I ? Executing a prior analysis of the documents sent to CTNBio, verifying if the requirements contained in the institutional acts are fulfilled;

II ? Evaluating the requests of legal entities to receive the Certificate of Quality in Biosafety ? CQB, giving its statement about the offered documents within a period of thirty days counting from the date when these documents were received, determining the exigencies judged necessary. Whenever it is pertinent, send the requests to a technical analysis of the Specific Sector Commissions, in accordance with their action fields;

III ? supervising the implementing of the regulation approached by the Decree n. 1,752, of December 20th 1995, and of the specific norms developed by the CTNBio, and taking the necessary measures to assure their execution;

IV ? organizing and operating the general supervision system of the CTNBio;

V ? analyzing, stating on reports and submitting to the CTNBio information about the technical, physical, and financial supervision of its work;

VI ? elaborating and showing to the CTNBio, for analysis and approval, the Commission Annual Activities Schedule, established from proposals sent by the Specific Sector Chambers;

VII ? proposing to the CTNBio the necessary reviews of the Annual Activities Schedule;

VIII ? taking the necessary measures, within its competence, to receive external resources destined for training and improvement of the members of the CTNBio and of the Executive Secretary, as well as those for the implementation and maintenance of national and international exchange programs;

IX ? elaborating an annual activity report, submitting it to the CTNBio, and proceeding its publication;

X ? preparing the meetings of the CTNBio and of the Specific Sector Commissions ? CSE, elaborating and distributing the minutes of the meetings, as well as providing the necessary administrative support to the CTNBio and to the CSEs;

XI ? sending to the members of the CTNBio the summons for the meetings, with their respective agenda and issues to be examined and discussed, with a minimal antecedence of 15 (fifteen) running days for the ordinary meetings and 5 (five) running days for the extraordinary ones;

XII ? providing, when necessary, the payment of tickets and lodging for members and persons invited by the CTNBio to attend the meetings;

XIII ? executing other activities attributed by the CTNBio.

SECTION VII

Art. 9th The chairman of the CTNBio has to:

I ? call the meetings of the CTNBio and approve their respective agenda proposed by the Executive Secretary;

II ? preside over the meetings and works of the CTNBio;

III ? submit to the CTNBio all the issues composing the agenda;

IV ? state resolutions and sign in the name of the CTNBio documents approved by the Committee;

V ? invite to attend meetings and debates, without the right to vote, after consulting the Committee, people who can contribute to the discussion of the examined issues;

VI ? propose, after the end of each meeting, the date of the ordinary or extraordinary subsequent meeting;

VII ? distribute the issues for the members? analysis and deliberation;

VIII - provide the fulfillment of the norms in this regiment and resolve questions of order;

IX ? represent the CTNBio when it is necessary, respecting the nature of his/her attributions.

Single Paragraph. If eventually the president is unable to attend a meeting, it shall be presided over by the Executive Secretary.

Art. 10th The members of the CTNBio have to:

I ? attend, participate, and vote in the meetings of the CTNBio;

II ? propose the summons of extraordinary meetings of the CTNBio;

III ? analyze and report correspondences distributed by the president, within the established terms;

§1st For the aims of quorum and deliberation, the condition of the members as permanent or substitute will not be taken into consideration, providing that all the technique-scientific fields of the Committee (vegetal, animal, environment and health) are represented.

§ 2nd Each pair of titular and substitute shall assure the presence of one of them in all the periods of all the meetings the titular is summoned for. Furthermore, the titular shall inform the Executive Secretary of the CTNBio whenever he/she is unable to attend, then his/her substitute will be summoned, and whether he/she is also unable to attend, another substitute from the same specialty or technical field shall be called.

CHAPTER II

THE FUNCTIONING

SECTION I

Art. 11th The CTNBio shall meet, ordinarily, every two months, and extraordinarily, whenever it is called by its chairman, by his/her own initiative or by request of the majority of its members.

§ 1st The ordinary meetings shall be called with an antecedence of 15 (fifteen) running days and the extraordinary ones with an antecedence of 5 (five) running days.

§ 2nd The meetings of the CTNBio shall be preferentially carried out in the Ministry of the Science and Technology, in Brasilia ? DF or in any part of the Brazilian territory, as established by the Committee.

§ 3rd The meetings of the CTNBio can only be carry out with the presence of, at least, two thirds of its members.

§ 4th In case a titular member ins eventually unable to attend all the days programmed for each meeting, he/she shall be represented by his/her respective substitute.

§ 5th The substitute members will have the right to vote in case of absence of their respective titular members, except in the case previewed by the §1st of the art. 10th.

Art. 12th The meetings of the CTNBio shall obey the agenda elaborated by its Executive Secretary and approved by its chairman.

Art. 13th Each meeting of the CTNBio shall have its minute registered, printed in separate sheets with its pages sequentially numbered, which shall be filed in the Executive Secretary after its approval.

§ 1st After approved, the minute of the meeting shall be signed by the chairman of the CTNBio;

§ 2nd The reading of the minute shall be executed only if it was not sent to the members of the CTNBio, with the summons for the meeting.

§ 3rd The amendments presented for the minute of a meeting shall be included in the minute of the meeting where the former minute was amended.

Art. 14th An issue under regime of urgency, approved by the CTNBio, can be included in the agenda for discussion and voting.

Single Paragraph. The issue to be proposed under regime of urgency shall be knew by the members of the committee at the opening of the works of the meeting where it will be discussed.

Art. 15th The analysis of issues shall obey the following order:

I ? The chairman shall expose the issue or give the speech for the reporter to present his/her written or oral report;

II ? after the reporter?s speech, the discussion shall be carried out;

III ? when the debates are finished, the voting shall be done.

Art. 16th The chairman can call the works to order or interrupt the meeting for a determined period of time, when he/she considers it necessary.

Single Paragraph. The debates shall occur obeying the order, in accordance with the rules of this regiment, observing the following:

I ? the presentation of propositions, indicators, requests, and communications, after carried out by its author, shall be given to the board in writing, on the adequate form, to be included in the minute of the meeting;

II ? the speeches of the members of the Committee shall be:

1. about the issue under debate;

2. obeying the sequence;

3. during the justification of vote.

Art. 17th Any member of the Committee can ask, in any moment of the meeting, for the exclusion of a subject of his/her authorship or ask to verify, a single time, the subject submitted to decision.

§ 1st The request of exclusion or verification of subject is forbidden whenever it is presented after the announcement of the voting, which includes the conduction for voting.

§ 2nd When the request of verification is formulated, the subject shall be automatically excluded from the order of the day, thus, its discussion and voting shall be transferred to the next ordinary or extraordinary meeting of the Committee, when a new request of verification about the same subject shall not be accepted.

Art. 18th Announced by the president the end of the discussion, the subject shall be submitted to voting.

§ 1st The voting shall be symbolic or nominal when there is a request;

§ 2nd The chairman shall have the deciding vote.

Art. 19th The decisions of the CTNBio shall be taken by single majority, counting with the presence of, at least, two thirds of the members of the Committee, excepted what is determined by the § 1st of the art 10th.

SECTION II

Art. 20th The participation in the National Technical Biosafety Committee will not be paid, and the departments or institutions represented in it shall provide to their representatives all technical and administrative supports necessary to their work in the Committee.

Art. 21st The omitted cases or doubts about the interpretation of this regiment shall be resolved by the Chairman, ad referendum of the CTNBio.

Art. 22nd The amendments to this regiment shall be decided by two thirds of the members of the Committee.

The National Technical Biosafety Committee ? CTNBio, using its legal attributions, decides:

Art. 1st The Request and Emission of Certificates of Quality in Biosafety, and the Implementation and Functioning of The Internal Biosafety Commissions ? CIBio, shall obey the rules included in the appendices I and II of the present Institutional Act.

Art. 2nd The present Institutional Act shall take effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the CTNBio

1. In accordance with the art. 2nd, § 3rd of the Law n., 8,974, of January 5th 1995, and the Chapter V of the Decree n. 1,752, of December 20th 1995, national, foreign, or international entities that develop or intend to develop activities and projects related to Genetically Modified Organisms (GMO) and derived substances, shall request to the National Technical Biosafety Committee - CTNBio, the Certificate of Quality in Biosafety ? CQB.

2. These entities include those devoted to the education, the scientific research, the technological development, the production and services rendered which involve GMO and derived substances, within the Brazilian territory. Public or private organizations, either national, foreign or international ones, which intend to finance or sponsor those activities either through agreement or contract, shall demand from the entities working in Brazilian territory, the CQB, on penalty of becoming co-responsible by eventual effects caused by the non-accomplishment of this requirement.

3. The CQB shall be delivered by the CTNBio, through requirement of the Internal Biosafety Commission ? CIBio of the interested entity, provided that the safety norms as well as other requirements stated by this commission. The request shall be received together with the documents listed below as well as the enclosed questionnaire filled.

4. The CQB is sent specially for the activity (ies) or project(s) requested by the institution, taking into consideration its competence and the suitability of the available staff and infrastructure for works with GMO from the GROUP I or the GROUP II.

5. The CQB shall be given to a Work Unit within an entity, and one or more laboratories or other kind of working infrastructure can constitute this unit.

6. After the request for the CQB, the Executive Secretary of the CTNBio shall, within a period of thirty days, give its opinion about the documents presented, asking for further information considered necessary. After the requirements are fulfilled and the inspection is carried out, when it is necessary, the CTNBio shall send the certificate within a period of thirty days. Depending on the nature of the activity developed by the entity, some of the documents listed in the item 3 of the Annex I may not be applicable to all the requests. The CTNBio reserves the right to ask for complementary information.

7. Whenever there is an alteration of any component which can modify previously approved conditions, the Internal Biosafety Commission ? CIBio shall inform the CTNBio about this alteration, and the Committee will have to judge the maintenance of the valid CQB or its cancellation, due to the executed alterations.

8. The CTNBio, together with the Inspection Departments of the Ministries, shall carry out annual inspections to the entities, and it may maintain or revoke the CQB previously given, based on the results of such inspections.

ANNEX I: Necessary information to obtain the Certificate of Quality in Biosafety ? CQB.

1 ? Constitution of the interested legal entity:

• CGC (Brazilian assessment roll)

• Location:

Complete address of the firm or institution (phone number, fax, e-mail) and the experimental station(s), if they exist.

• Name and address of the entity?s legal liable

• Name and address of the Work Unit?s legal liable

• The inclusion of an organization chart of the Work Unit the CQB is destined for, and the function of such unit within the institution

2 ? Financial Capacity (the proponent shall present, at least, two out of the documents below):

• Certificate given by the notary public attesting the absence of protested titles

• Certificate attesting the absence of suits in the court against the entity

• Bank references (two)

• Commercial references (two)

Tick one or more of the options described in the items below:

3 ? Proposed aim(s):

Research under containment [ ] Commerce [ ]

Evaluation in the field [ ] Transportation [ ]

Evaluation of the product [ ] Disposal [ ]

Education [ ] Storage [ ]

Commercial production [ ]

4- Activities developed with:

Animals [ ] Micro-organisms [ ]

Plants [ ] Fungi [ ]

5 ? In accordance with the Law n. 8,974, of January 5th 1995, these organisms belong to:

Group I [ ]

Group II [ ]

6- Make a list of the organisms that will be object of the activity

7- Detailed description of the installations (describe only the installations that will be used and the staff that will be involved in the activities with GMO that will be developed by the institution):

Physical structure:

• Specify Laboratories, Green Houses and/or Experimental Fields.

Some examples of relevant information:

• Location

• Size

• Special features related to biosafety

• Equipment for experiences

• Safety equipment

• Installations for emergency medical assistance

Staff

• Qualification of the professionals involved ( resumed curriculum vitae in the field of action of the graduated staff)

8- Composition of the Internal Biosafety Commission ? CIBio responsible for the Work Unit.

9- Declaration:

Formal declaration of the interested about the technical competence and infrastructure of the Work Unit for the execution of the programmed work (model enclosed).

D E C L A R A T I O N

We declare, aiming the acquisition of the Certificate of Quality in Biosafety ? CQB, to be sent by the National Technical Biosafety Committee ? CTNBio, created by the Law n. 8,974 of 01/05/95, that

(Name of the Work Unit) (Entity)

have adequate infrastructure and competent technical staff to develop with safety activities with with

nature of the activity (ies) (e.g.: research under containment regime)

______________________genetically modified from

kind(s) of organism(s) (e.g.: animals, plants, or micro-organisms)

the Group_______________ (I or II).

(Name of the Work Unit)

is disposed to receive the members of the CTNBio, at any time, for the evaluation of the institution?s physical, technical, infrastructure and staff conditions, aiming the delivery, maintenance, or revoking of the CQB.

(Legal Liable) (Responsible for the Work Unit)

ANNEX II

Rules for implementing and functioning of Internal Biosafety Commissions

ANNEX II ? Classification of Genetically Modified Organisms, in accordance with the Law n. 8,974 of January 5th 1995.

Group I:

Includes organisms that fulfill the following criteria:

A ? Receptor or parental organism:

• non-pathogenic;
• free of foreign agents;
• possessing a broad documented history of safe use, or the incorporation of biological barriers which, without interfering in the receptor or growth agent's optimal performance, allows for its limited survival and multiplication, with no negative effects for the environment.

B ? Vector/insert

• must be adequately characterized and free of know harmful sequences;
• its size must be limited, to the extent possible, to the genetic sequences needed to carry out the function for which it was designed;
• must not increase the stability of the modified organism in the environment;
• must be barely movable;
• must not transmit any resistance marker to organisms that, according to available knowledge, do not acquire this resistance naturally.

C - Genetically modified micro-organisms:

-non-pathogenic;

offering the same safety as the receptor or parental organism in the reactor or growth agent, but with limited survival and/or multiplication, with no negative effects on the environment.

D ? Other genetically modified micro-organisms that could be included in Group I, as long as they combine the conditions stipulated in item C above:

-microorganisms constructed entirely from a single prokaryotic receptor (including plasmids and endogenous viruses) or from a single eukaryotic receptor (including its chloroplasts, mitochondria and plasmids, but excluding virus) and organisms composed entirely by genetic sequences from different species that exchange such sequences though known physiological process.

Group II:

All those not included in Group I.

Internal Biosafety Commission ? CIBio

BACKGROUND

According to the articles 9th, and 10th of the Law n. 8,974 of January 5th 1995, every entity that uses techniques and methods of genetic engineering shall create an Internal Biosafety Commission (CIBio), besides indicating a Chief Researcher for each specific project, defined in the regulation as "Technical Responsible".

This document regulates the competencies and responsibilities of the CIBios. Any entity, firm, or organization, which works with genetic manipulation through techniques of genetic engineering manipulates, transports, produces or plan to release genetically modified organisms (GMO) shall obey this regulation.

The CIBio shall carry out its activities with the authority stated by law and shall be constituted and designed by the entity?s Legal Liable. Each entity will have one or more CIBios, depending on its administrative and technical structure.

The entities shall recognize the legal role of the CIBios and assure them the required authority and support to the accomplishment of their obligations, and the implementing of their instructions, assuring that they will be able to supervise the works.

The CIBios are essential components for the monitoring and inspection of the genetic engineering works, the handling, production, and transport of GMO and to assure the obedience to the biosafety regulation.

COMPOSITION

The CIBio shall include people with necessary knowledge and experience to access, evaluate and supervise the works with GMO carried out by the entity.

The CIBio shall be composed by, at least, three experts from fields compatible with the entity?s tasks. The Legal Liable of the entity shall design a chairman out of the expert members for the CIBio.

The inclusion of at least one unversed person, who can be an employee of the institution or not, in the CIBio, is recommended; and such person must be prepared to consider the community?s broadest interests.

RESPONSIBILITIES

The CIBio main responsibilities are:

Elaborate and publish norms and take decisions about specific issues in the domain of the institution about safety proceedings, always in consonance with the rules of the CTNBio;

Request the CQB and its eventual revisions to the CTNBio;

Evaluate and revise all the proposals of research in genetic engineering, handling, production, and transportation of GMO carried out by the entity; identify all the potential risks for researchers, community and environment; give instructions to the researchers about such risks and how to deal with them;

Maintain a register of the approved projects related to GMO and, when it is pertinent, their hazard evaluations;

Assure that its instructions, as well as those of the CTNBio, are received and observed by the Chief Researcher(s);

Determine containment levels (to be defined by the CTNBio rules), and the proceedings to be followed for all the experimental work with GMO, and for the maintenance, storage, transportation, and disposal of GMO included in the regulation of the law;

Send to the CTNBio the required documents for the requests of activities with Group II organisms and for releases in the environment, together with the analysis of risks, according to the CTNBio rules;

Inspect and attest the safety of the laboratories and other installations before and during their usage for works or experiences with GMO. The CIBio shall inspect and supervise the proceedings in all the laboratories and installations used for GMO. There shall be, at least, two annual inspections of such installations to assure that they will keep all the relevant requirements and containment patterns, keeping a registration of the inspections, instructions, and consequent measures taken;

Revise the qualification and experience of the staff involved in the proposed researches, in order to guarantee that they are adequate for good laboratory practices;

Maintain a list of people who work in containment installations and assure that new members of the staff or new employees are adapted to the proceedings to be adopted in the different containment levels, and to use correctly the laboratory equipment;

Carry out other functions according to the determination of the CTNBio.

MEETINGS

The CIBio shall meet, at least, every three months, and shall promote extraordinary meetings for the discussion of urgent issues, whenever requested by one of its members.

DEMANDED REPORTS

In the occasion of its implementation, and then once a year, the CIBio shall send to the CTNBio the following information:

Identification of the chairman and the other members of the CIBio;

List of the research projects either in progress or expected to begin, involving GMO, as well as the list of laboratories, specifying containment levels, according to the norms approved by the CTNBio;

List of green houses and installations for transgenic plants and animals;

Report about any accident directly related to works with GMO;

Any other occurrence that the CIBio judges necessary to report to the CTNBio

Whenever it is pertinent, the CTNBio shall send to the CIBio further information to be included in the report.

CHIEF RESEARCHER (S)? RESPONSIBILITIES

The Chief Researcher must be completely familiarized with the requirements of the biosafety legislation, and shall guarantee that they will be obeyed in the execution of any project involving the use of GMO.

Particularly, the Chief Researcher must:

Analyze the proposal to determine whether it is included in the regulation of the Biosafety Law. In case of doubt, the Chief Researcher shall query the CIBio, or, if necessary, the CTNBio, in writing;

Give any information about the project to subside the activities of evaluation and monitoring, when it is demanded;

Observe norms and instructions of the CTNBio and the CIBio in the research proposals;

Fill the CTNBio forms and submit an original and a copy to the chairman of the CIBio before starting any work in any project that is object of such regulation; assure that the activities will not start until they are approved by the CIBio (or by the CTNBio, whether it is a project with Group II organisms or releases in the environment);

Send the proposal to the CIBio, before making any substantial change in the components of the preciously approved experimental system;

Inform the CIBio about the intention of transporting biological material included in such regulation;

Guarantee that subordinates, students, and other collaborators have received proper training and that they are aware about the nature of the work?s potential risks;

Notify the CIBio about all the changes in the project staff;

Report to the CIBio all the accidents and diseases possibly related to the activities with GMO immediately;

Be responsible for the maintenance of equipment and infrastructure, as well as attend possible CIBio audits.

The National Technical Biosafety Committee ? CTNBio, using its legal attributions, decides:

Art. 1st The importing of genetically modified plants destined to research shall obey the provisory rules stated in the Appendix of the present Institutional Act.

Art. 2nd The present Institutional Act shall take effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the CTNBio

These norms are applicable to the introduction of genetically modified plants (GMP), and their parts, in the country, represented by small quantities or seeds samples, living plants, fruits, cuttings, or gems, bulbs, tubercles rhizomes, in vitro plants, or any parts of genetically modified plants, with capacity for reproduction or multiplication. Any introduction of GMP in the country must be authorized by an importing license.

To obtain the license to import genetically modified plants; the following norms shall be observed:

1. The interested Institution shall request to the Vegetal Defense and Inspection Department (DDIV) of the Ministry of Agriculture and Supply, the license for importing the genetically modified plant. The DDIV may concede the license or not, according to the technical statement of the National Technical Biosafety Committee (CTNBio), based on the analysis of the following information:

- Proponent?s name. Function.

• Institution?s name.

• Institution?s address and phone number.

• Ordinary name of the plant.

• Lineage and scientific name.

• Classification of the GMO.

• Genes inserted in the plant and their functions

• Methodology used for the modification.

• Technical justification of the importing

• Aimed use (whether laboratory, green house or field research)

• Historic of similar prior introductions

• Name and address of the donor institution.

• Sender?s name and address.

• Country and location where the material was collected developed and produced.

• Mean of introduction of the material (seeds, in vitro, tubercles, cuttings, etc.).

• List of the materials and respective quantities.

• Schedule and number of introductions (when it is more than one).

• Place of destination, where the researches will be carried out (Institution, laboratory, address)

• Research project expecting the use of the material to be imported, approved by the CIBio in case of group I plants, or by the CTNBio, in case of group II plants (please find enclosed the classification according to the law).

• Place of landing in Brazil.

• Approximate arrival date.

• Way of transportation.

• Quarantine place

• Quarantine conditions (when available by the proponent).

• Caution measures in the destination place, to avoid leaks.

• Description of the elimination or final disposal method.

1. The DDIV shall send the request to the CTNBio, for technical report.

2. The CTNBio shall send to the DDIV its technical statement about the request.

3. The DDIV will be in charge both of the importing license and the dispatch authorization in the place of entry of the GMP in the country, and both shall be submitted to the exigencies contained in the Decree n. 24,114, of April 12th 1934, and in the administrative rule n. 148 of June 15th 1992, of the present Ministry of Agriculture and Supply, which rules the introduction of plants for research in the country.

4. These norms are not applicable to genetically modified plants, from the same species and lineage, and with the same introduced genes, which had their commercialization already allowed by the competent authority. However, such plants shall be submitted to the sanitary legislation mentioned above.

5. The introduced material shall be used only under containment regime. The license does not allow the execution of field research, which will be authorized only by means of a conclusive report of the CTNBio in a different request, after analyzing the specific documents, in conformity with CTNBio norms.

The National Technical Biosafety Committee ? CTNBio, using its legal attributions, decides:

Art. 1st The planned release in the environment of Genetically Modified Organisms ? GMO shall obey the norms stated in the Annex of the present Institutional Act.

Art. 2nd The present Institutional Act shall take effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the CTNBio

Scope

These norms are applicable to the planned release in the environment of genetically modified viroid, viruses, cells or multicellular organisms (GMO).

Fig. 1 aims to help the proponents to follow the steps required by the norms. It is a summary to be used only as an initial direction, and shall not be taken as substitute of the exigencies detailed by the norms

Fig. 1 ? Summary of the proceedings

Proposition of the Chief Researcher to conduct a Field Trial of a GMO

Analysis by the Internal Biosafety Committee - CIBio

Publication in D.O.U. Analysis by the Specific Sector

Government Press Commission

CTNBio´s statement on the proposition

Final decision on the proposition

D.O.U. Publication Communication to the CIBio

In these norms, except if it is diversely indicated, certain terms will be defined as follows:

GMO ? Genetically Modified Organism.

CTNBio ? National Technical Biosafety Committee

CIBio ? Internal Biosafety Commission

Chief Researcher ? The proposal?s supervisor, indicated in accordance with these norms.

Proponent ? Any legal entity that proposes the execution of any release, in accordance with these norms.

Legal Liable - The individual whose responsibility for the execution of the planned release falls on, in accordance with the norms of the CTNBio. He/she can be the supervisor of the project, the proponent, or any other person with daily supervision responsibility.

Secretary ? The CTNBio?s Executive Secretary.

These norms are applicable to the release of GMO in the environment in Brazil (including imported GMO), either by means of field experiences or by any other mean, except for free releases, as described below. The norms are not applicable to containment regime works, which are conducted under CTNBio?s specific norms.

In case the Chief Researcher of a project has doubts about the applicability of these norms for a proposed release, he shall submit to the CIBio, in writing, a description of the work he intends to carry out, or directly to the CTNBio to receive information about the case.

EXEMPTIONS ? The release of GMO that has already been approved by the CTNBio for commerce, will be free from these norms.

The release of a GMO in the environment shall not be free from these norms in case the prior work was exempted because it was carried out under approved containment conditions.

A GMO that was previously approved by the CTNBio for planned release may be exempted from these norms providing that, according to the judgement of the CTNBio, the experience had shown acceptable risk levels.

An exemption may be unconditional or subject to conditions.

Proceedings

The Legal Liable and the CIBio are in charge of assuring the faithful fulfillment of these norms, concerning the proposed release of a GMO in the environment.

The responsibility includes the indication of a Chief Researcher (who can be the Legal Liable), guaranteeing that the work will be monitored by an appropriately constituted CIBio, familiarized with these norms, assuring also that all the people involved in the proposed release are aware and directed to obey these norms, as well as the CTNBio?s instructions.

Whenever the CIBio knows about a decision of release of GMO in the environment, it is in charge of assuring the obedience of these norms. The CIBio and its member are responsible for informing the CTNBio about any eventual non-accomplishment of these norms.

All the GMO handling proceedings shall be foreseen in order to give the most possible guarantee that no accidental release of a GMO will occur, and that all the introductions will be planned and executed in accordance with the norms. However, in case of any accidental release of a GMO that should be introduced in a planned way, according to these norms, such accident must be immediately communicated to the CIBio and to the CTNBio, enclosing a report about the corrective measures already taken (if appropriate) and the names of the notified people or authorities. The communication of such occurrence to the CTNBio does not exempt the proponent from any other obligation, according to the ordinary law and/or statutes, of informing the competent authorities or people who can be affected.

Before any planned release of GMO occurs, the proponent shall submit a proposal, in writing, to the CTNBio. As soon as the release of a GMO in the environment is done, the Legal Liable or the Chief Researcher of the project is in charge of giving total attention to the proposed release possible effects, specially the necessary steps for the obedience of these rules. The Secretary or the chairman of the CTNBio shall be available to queries about any issue related to these norms.

The obedience to these norms does not exempt the proponent from the obedience to any other norms regarded as relevant, or from requirements related to the ethic in works with humans and animals.

When the proposal reaches the adequate stage, the Legal Liable or Chief Researcher shall prepare the answers for the questions described below (core questions for the proponents) as well as the answers for questions from other sections. The answers shall be sent to the CIBio for the analysis. While doing this, the CIBio shall consider whether the data of works under containment conditions already executed are enough for the safe continuation of the planned release. The CIBio shall keep contact with the Legal Liable or the Chief Researcher, be informed, and give, if necessary, suggestions for the proposal?s review.

When the proposal is regarded as satisfactory, the CIBio shall send it to the CTNBio together with a filled frontispiece (annex 1.A), and the public information sheet (annex 1.B).

If the proposal includes confidential information, the proponent can mark relevant parts as "commercially confidential", explaining the reasons that justify such treatment. If there is any material clearly classified as confidential, the Secretary, the president and the reporter of the proposal shall treat it this way, except if the Committee regards such information as necessary. In this case, the CTNBio shall notify the proponent in writing and negotiate a consensual resolution. If a deal is not made, in the terms of the Decree n. 1,752, of December 20th 1995, the CTNBio, without loss or violation of secrecy may exclude the proposal at any time before the analysis. The proposal can be submitted again to the CTNBio for approval in another occasion.

When receiving a proposal the CTNBio shall: a) publish its reception in the DOU, with a brief description of the proposed release; b) publish the description of the proposed release among people and/or organizations registered in the CTNBio for this objective; c) send the description of the proposed release the competent authority from the location of the release. The public shall have thirty days to give a statement before the CTNBio about the proposed release, counting from the date of its publication in the Federal Official Gazette (DOU).

In order to express its statements about the proposal, the CTNBio shall send to the proponent any substantial comment received from the public. The proponent can answer such comments, in writing, to the CTNBio.

Each proposal shall be analyzed by a CTNBio Specific Sector Commission, which can demand the statement of ad hoc advisors when it is considered necessary. The proponents shall receive from the secretary the information about dates of any meetings. Ordinarily, it will take eight weeks between the reception of the proposal and the Committee?s initial opinions. The proponent can be called to attend the meetings to answer questions related to the proposal. The CTNBio?s statement about it shall be sent to the CIBio within a period of 4 weeks after the final analysis. If the CTNBio judges that the proposed release will cause any negative consequence to the environment, it shall be sent to the Ministry of Environment, Water Resources and Legal Amazon, which may demand an Environmental Impact Study ? EIA/RIMA, in conformity with the directions established in the Resolution n. 001/86 of the CONAMA, what may result in instructions about the conditions to be included to the proposal.

After the CTNBio has recognized that a determined planned release will be able to continue, the public info document submitted by the proponent shall be published in the Federal Official Gazette (DOU). Some copies of this document shall also be sent to those people who had done comments in the occasion of the first notification about the release, as well as to the competent authorities of the place where the release will be carried out.

The Main Researches and Legal Liable shall act in accordance with the monitoring protocols recommended by the CIBio, as approved by the CTNBio.

Any problem or unexpected incident shall be immediately reported to the CIBio and to the CTNBio, together with details of any measure already taken and the names of the notified authorities. Reporting an occurrence to the CTNBio does not exempt the proponent from any other obligation, according to the ordinary law and/or statutes, of informing the competent authorities or people who can be affected.

Within a period of six months from the conclusion of a planned release, the Legal Liable or the Chief Researcher shall submit to the CIBio a detailed report for review.

The CIBio shall do the review to determine if:

The protocols were adequately followed during the experiences.

The objectives of the experiences were reached.

Adverse effects had taken place.

The organism?s survival and dissemination features were those expected.

In the conclusion of the review, the CIBio shall submit a report to the CTNBio according to the annex 1C.

All the proposals for the release of GMO in the environment, obeying these rules, shall include the answers for the core questions set out in section A and in other sections relevant for the proposal. The proposal shall be prepared by the Legal Liable or Chief Researcher, and by the CIBio, as previously described.

Those involved in the preparation of the proposal are in charge of offering the best and most complete considerations that enable the detection of possible impacts of the intended release, and they shall make available relevant questions for the CIBio and the CTNBio. The impacts to be taken into consideration include the consequences to the public safety and health, the agriculture, other organisms and to the environment?s quality.

Crucial importance must be given to the experience obtained by works under containment related to the organism, and the results of a relevant bibliographic research, as well as to the queries to experts and public authorities.

Answers shall be based on adequate data and references, as well as on other prior experiences conducted in Brazil or abroad. In the absence of available data or reference, the support for the answer shall be mentioned. In case there is any doubt about the appropriate answer for a question, the nature of the doubt shall be stated. If the existence of a potential damage is noticed, the clearest possible explanation of the relative risks involved shall be provided and possible steps to eliminate or deal with the hazard shall be considered and suggested whenever it is adequate.

A.CORE QUESTIONS:

A1: What is the species of organism to be released? (when appropriate, give information on the scientific name, strain, cultivar, pathovar, lineage, and serotype.)

A2: What is the classification of the organism according to risk group (I or II), in conformity with the Law n. 8,974, of January 5th 1995?

A3: Is the GMO capable of causing diseases or other damages in humans, animals, or plants? If so, what are the possible effects?

A4: (I) What is the origin of the introduced DNA/RNA? (II) Was the exogenous DNA/RNA originated by an organism that causes diseases in humans, animals, or plants? If so, what are the possible effects?

A5: (I) What is the aim of the proposal? (II) What is the intended use of the GMO?

A6: Describe the size of the experiment, concerning area or volume and its location (please give address). Include map(s) in adequate scale(s) to allow the analysis of the chosen area under the requirements described in A7.

A7: (I) What are the reasons for the choice of location? (II) Describe in details relevant features of the physical environment, mainly those that may minimize or exacerbate any undesirable effects (e.g.: wind motion, ground water, proximity of water courses, and protected areas, etc.); (III) On what distance is the experiment location from population centers, agriculture activities centers, genetic diversity centers, habitats of biota that may be affected by such release of GMO in the environment?

A8: (I) What is the natural habitat of the parent organism in Brazil and in the world? (II) Are there any GMO parent organisms close to the release experiment? If so, please give information about the populations. (III) Is the released organism regarded as exotic in Brazil? (IV) Is there any biological diversity center in Brazil of the organism to be released? If so, please give information about the possibility of internal hybridization and the GMO selective or competitive advantage. (V) Where was the parent organism isolated?

A9: Is there any natural predator or parasite of the organism in Brazil? If so, describe it.

A10: May the release of GMO cause any harm to the positive functions that the original organism can execute in the environment?

A11: What are the introduced genes and which specific function do they have?

A12: (I) Present the nucleotide sequence of the transgenic variety, and point the present regulator elements (e.g.: promoters, "cis" regulation elements, resistance genes, replication origin, etc.).

A13: (I) How was the exogenous DNA/RNA introduced in the host organism? (II) Which was the vector employed? (III) Which is the scope of hosts for the vector? (IV) Present a restriction map and show the regions specifying functions (e.g.: promoters, "cis" regulation elements, resistance genes, replication origin, etc.).

A14: Present the final construct restriction map (transgenic/ vector). Use at least three restraint enzymes. (II) Is there any evidence that any of these elements is involved in cellular transformation processes? (III) Are there final construct elements that are potentially oncogenic? If so, describe them. (IV) Point out further risks that may exist and the measures to be taken to reduce them.

A15: Make a resume of the stages of the construct obtainment process.

A16: Describe in detail the product of the gene expression and its possible effects to human, animal and environmental health.

A17: (I) On which level may the genetic mutation be characterized? Give information that shows the scope of the characterization. (II) Was the introduction chromosomal or cytoplasmic? (III) Which phenotypic, cytogenetic, or molecular markers may provide the identification of the GMO under field conditions?

A18: Does the GMO have any potential genotype instability? Are there any known events of instability in the GMO using the same host?

A19: What are the known modifications that can change the phenotype of the GMO to be released?

A20 (I) Which intrinsic genetic features may the GMO have? In case they exist, what regulates their survival and dissemination in the environment? (II) Which is the stability of these features? (III) Which genetic modifications, if any, were introduced in the GMO to avoid or restraint its capacity to reproduce and transfer exogenous genes to other organisms?

A21: Based on the containment experiments, give information about the growth range (or lifetime of each generation) and survival, aiming the comparison between the GMO and the non-modified organism. Which is the frequency of reversion or loss of the genetic change?

A22: Based on the non-modified organism?s dispersion, which is the GMO dispersion capacity in the planned release area? What are the dispersal mechanisms in air, water and soil? Can the parent organism form long-term survival structures, such as seeds or spores?

A23: Is there any evidence that the novel trait can be transferred to other organisms found at the site of the planned release and surrounding environment? If so: (I) to what organisms at what frequencies? List the species that have been tested or evaluated for the receptivity and justify the reason for their choice. (II) what transfer mechanisms are involved? (III) what techniques have been employed to demonstrate the receptivity to transfer? (IV) Describe any possible adverse effects of the transfer.

A24: (I) Describe in detail the overall experimental protocol for the release and subsequent monitoring after the test is finished. Include the protocol for control, test, and challenge organisms, if relevant. (II) How many GMO will be released? (III) How many releases are intended and which is their schedule?

A25: What are the arrangements for producing the GMO in quantity, and transporting it to the experiment site? What will the release proceeding be?

A26: What methods will be used to control the quality batch to batch, if a large scale production of GMO is required for the release?

A27: (I) How will the survival of the GMO be monitored? Describe the techniques to be used in monitoring the occurrence of GMO or transferred genetic material beyond the release site, including specificity, sensitivity and reliability of the detection methods. (II) If the release is likely to affect the characteristics or the amount of other species, how will this be monitored?

A28: (I) Which potential hazards or deleterious effects can be postulated and how can these effects be evaluated during the release experiment? (II) Describe structures and procedures employed to reduce the dissemination of the GMO. (III) If the transfer of introduced genetic traits to other organisms is possible (see A23), which methods shall be used to minimize these effect?

A29: If the GMO remains in the environment after the release experiment: (I) How long will it happen and (II) What are the possible consequences? (III) Will any measure be taken to reduce GMO populations or dispose, after the release is completed? (IV) What kind of monitoring will be done after the release is completed?

A30: What measures will be taken to remove the GMO, in case of clear hazard during the execution of the release experiment?

A31: Describe the experiment site supervision proceedings, as well as the safety proceedings that will be carried out by staff. Make a list of the staff in charge of the experiment and describe the training received by the staff members.

A32: (I) Have the same or similar releases been made before, either within or outside the country? If so, give information about other proposals, including the positive or adverse effects. (II) Has another country rejected an application for the planned release of this GMO? If so, for what reason? (III) What factors may suggest greater or less risks concerning the presented proposal?

A33: Was the GMO imported, or was it made in Brazil? In case it is imported, attach documents of license, given by the competent inspection authority, and of quarantine services, when applicable.

A34: Is there any aspect related to the GMO that could constitute a hazard and was not considered in this proposal yet? If so, please explain it.

IMPORTANT: Give any other information that can help the CTNBio in the analysis of the presented proposal.

B. PLANTS

If the GMO will be produced for human or animal consumption, answer the questions in section L also.

B1: Is there any info about the history of cultivation and of safe use to the environment of the parent species, either for human and animal use? If not, explain.

B2: what kind of pleiotropic effects can be observed in the expression of a modified gene in the GMO (e.g.: reduced fertility, increased disease incidence, loss of productivity, and grain/fruit shedding)?

B3: (I) Describe the plant pollen dispersion mechanism (by insects or other vectors). (II) provide information about pollen viability. (III) Point out potential pollinators and their geographic distribution in Brazil.

B4: (I) Are there, in any Brazilian ecosystem, genus unmodified parent plants and/or wild parents of the same gender (including weeds)? If so, specify them. (II) Are there any literary reports about cross-pollination between the species to which the GMO belongs and its ancestors, and/or wild relatives, including weeds? If so, list them.

B5: (I) Does any sexually compatible plant live near the release site? If so, give details and quantify the chances for cross-pollination. (II) Provide quantitative data on about cross-pollination between the plant and its wild parents occurring in the release area. (III) If cross-pollination occurs, will the resultant plants or its progeny be able to survive and compete well? If so, list them.

B6: (I) Will the plants in this release be allowed to set seeds? If not, is any subsequent release planned? (II) If plants are allowed to set seed, does the mature seed normally remain contained within an ear, capsule, or pod so that practically all of the seed can readily be harvested, or is the seed shed soon after it matures? (III) Can the seed be dispersed by natural means? If so, describe them. (IV) Are the seeds capable of surviving in a dormant condition for a long time? If so, how long?

B7: Can the plant be dispersed by vegetative propagation? If so, describe possible mechanisms.

B8: (I) What is the likelihood of the introduced trait transference to other species with harmful effects? (II) If there were any possibility of such transference to occur, would it have potential to affect the distribution and abundance of other species? If so, please explain. (III) In case of any possibility of introgression, was any attempt to minimize the risks carried out (e.g. imparting male sterility or other reproductive isolation mechanisms)? If not, why not?

B9: Does the novel characteristic change the capacity of the plant to add substances or subtract substances from the soil (e.g. nitrogen, toxic compounds)? If so, describe the change.

B10: (I) Is there any likelihood that the introduced gene could cause an increase in toxicity of the plant for animals and humans? If so, provide available data. (II) Could any products of the GMO concentrate in the natural or human food chain to levels that become toxic? If so, explain. (III) Is there any known case of change in the plant biodegradability? If so, how?

B11: What secondary ecological effects might result from the release of the GMO (e.g. effect on endangered native species, resistance of insect populations to an insecticide, reduction or increases in the numbers of prey and parasites, etc.)?

B12: Does the construction involve resistance to a chemical agent (other than selective agents, such as antibiotics, used in strain construction)? (I) Provide data about the degradability, selectivity, and toxicity of the chemical concerned. (II) What is the biological activity of the chemical? (III) How is the chemical applied and used?

C. MICROORGANISMS LIVING IN OR ON ANIMALS

These questions refer to organisms such as those that will compose gut biota living in larger hosts and microorganisms applied externally to animals (e.g. bacteria to avoid fleece rot). Issues included here should also take into consideration the ecological interactions and behavior of host organisms that could have environmental impacts.

C1: What is the animal host species?

C2: Does the parent organism have an extended history of use in agriculture? If so, please elaborate.

C3: Is there any evidence that the GMO might be capable to form colonies in or on other animals, including feral ones?

C4: (I) What new capacity will the GMO provide for the host species (e.g. ability to degrade plants or plants toxins)? What secondary effects can be postulated from conferring that capacity to the host?

C5: Will the competitive advantage or reproductive fitness of the host be altered? Explain providing data to support your answer.

C6: What effects (including secondary ones) are likely on other plants or animal in the agricultural and natural environments? Please include in your answer any likely effect on host animals or feral populations.

C7: What secondary effects can be postulated from the introduction of a GMO into or onto the host? For instance, is there a possibility of the genetic insert being transferred to other organisms in the host, or to host cells?

C8: If a GMO lives in animals, will it be excreted or otherwise leave the host animal? If so, how long does it survive outside the animal?

C9: (I) What is the survival and dispersal of the GMO in natural waters and soil? (II) What are the possible effects of the GMO on water quality? (III) Does the GMO produce spores? (IV) Is the GMO resistant to desiccation?

C10: (I) What sterilizing and anti-microbial agents are active against the GMO?

D. MICROORGANISMS AS LIVE VACCINES FOR VETERINARY USE

D1: (I) What disease is to be controlled by the use of this vaccine? (II) On what host species is the vaccine to be used? (III) Which are the host organs colonized by the vaccine? (IV) What is the host range of the parent organism from which the vaccine was constructed?

D2: (I) Provide data about the level and the duration of the immunity produced in the host species after vaccination with the GMO. (II) Over what period can the vaccine organism be detected in vaccinated animals or their excretions? Provide supporting data.

D3: Can the vaccine organism spread from vaccinated to non-vaccinated animals or to other species, including humans? If so, what is the mechanism and frequency? Provide data, if available.

D4: Is there any evidence to indicate if the susceptibility of the host to the vaccine organism could be affected by the current state of the host (e.g. immunosuppression or superimposition of other disease) or by other treatments (for example, drugs)? If so, elaborate.

D5: Does the genetic material of the vaccine organism have the potential to become incorporated, totally or in part, into the genome of any cells of the vaccinated host?

D6: If this is a viral vaccine, can the nucleic acid of the virus in the vaccine be rescued or restored to wild type by recombination with intracellular viruses?

D7: (I) In trials with the vaccine, what destination is given to the waste containing vaccine organisms? Describe in detail the procedures. (II) What is the fate of the vaccinated animals after the tests?

D8: Will the host organisms carry live vaccine organisms at the end of the trial? If so: (I) Will they be likely to disseminate the live vaccine organisms to other individuals? (II) What measures, if any, will be taken to minimize this possibility? (III) Will the organisms be able to cross the placenta?

D9: (I) Is the vaccine likely to have any deleterious effects on pregnant animals? If so, specify. (II) Does the vaccine have teratogenic effects for the fetus at any stage of gestation? If so, elaborate. (III) What are the effectiveness and safety tests to be carried out?

D10: Is the use of this vaccine organism likely to preclude its subsequent use for vaccination against other diseases? Will its usefulness for other vaccinations be affected?

D11: (I) Does the GMO produce spores? (II) Is the GMO resistant to desiccation? (III) What sterilizing and anti-microbial agents are active against the GMO? (IV) Are these agents mutagenic to the GMO? (IV) Is the GMO susceptible to ultraviolet and ionizing radiation?

E. MICROORGANISMS NOT FALLING IN SECTIONS C OR D

These questions concern microorganisms associated with plants and microorganisms that can be applied to modify the physical or chemical environment (for example, microorganisms to modify soil properties).

E1: For microorganisms associated with plants, what is the partner plant species? Describe the specificity of the interaction and indicate the range of plant species with which the GMO can interact similarly.

E2: Is the parent organism used in agriculture? If so, describe its use.

E3: For microorganisms associated with plants: (I) What is the effect of the GMO on the partner plant species and how will this be monitored? (II) What other secondary effects might the GMO have on the plant? (III) Does the modification cause any change to the range of host plant species and other species available to the organism? (IV) What effect of the GMO, if any, is anticipated on the distribution and abundance of the host plant species and other species with which the GMO can interact?

E4: If the GMO is associated with plant species that are food crops, could it affect the suitability of the resultant product for human or animal consumption? If so, explain.

E5: Which are the effects expected on soil chemistry (e.g. pH, mineral leaching, kelation, and nutrient levels)?

E6: (I) Which effects might the GMO cause on water quality? (II) Does the GMO produce spores? (III) Is the GMO resistant to desiccation? (IV) What is the survival and dispersal of the GMO in natural waters and soil?

E7: What effects might the GMO have on soil organisms that are known to be beneficial to plants (e.g. Rhizobium, Azospirillum, Frankia and mycorrhizal fungi) and are likely to be found in the test area?

E8: What is known about the interactions between the GMO and closely related organisms in the partner plant (if applicable) or the environment of the release site?

E9: If the GMO are associated with plants, what effect might it have to animals (including humans) which may eat the plant?

E10: Does the GMO exchange genetic material with known plant pathogens? If so, elaborate.

E11: (I) What sterilizing and anti-microbial agents are active against the GMO? (II) Are these agents mutagenic to the GMO? (III) Is the GMO susceptible to ultraviolet and ionizing radiation?

F. VERTEBRATES (EXCLUDING FISH)

If these animals are to be consumed as food, answer the questions in section L also.

All works must be developed in accordance with the safety patterns and humanitary treatment of experimental animals, as stated by the legislation into force.

F1: What environmental or animal welfare effects may result from the planned release of the GMO, and what is their likelihood? (II) Are the expected gains of the introduction, somehow, linked to changes in other features of the species? If so, elaborate.

F2: What effects might the expression of the modified trait have on the physiology, behavior, and reproduction of the animal? Explain using data from studies with model animals, for instance.

F3: (I) Will the animals involved in the experiment be allowed to reproduce? If not, is the reproduction being planned for future experiments or the commercial phase? (II) What are the planned measures for handling and containment of the experimental animals? progeny? Are they different from those applied for parent animals? If so, specify. In case of slaughter and carcass treatment, specify the processes to be

F4: Do feral populations of the experimental species exist in the country? If so: (I) Do feral populations cause agricultural, environmental or sanitary problems? Specify them. (II) Is there any experimental data about the expression of the genetic material in feral animals (e.g. cross-breeding of GMO with captive feral animals)? If so, what were the results? (III) What effect might the entry of the novel genetic material have on the feral population distribution and abundance or in its ability to cause agricultural or environmental problems, or to contribute to spread infectious diseases? Provide data to support your answer. (IV) What effect may the entry of the new genetic material cause on the genetic feral species pool? (V) What are the possible effects on the feral population distribution, on in its ability to cause agricultural or environmental problems, or to contribute to spread infectious diseases? Specify.

F5: What management procedures and environmental factors are required for optimal expression of the novel trait? Provide data to support you answer.

F6: Can the GMO interbreed with Brazilian native species?

F7: If no feral populations exist in the country, comment on the likelihood that the novel characteristic can enhance the ability of the species to establish feral populations.

G. FISH AND AQUATIC ORGANISMS SUCH AS CRUSTACEANS

If these animals are to be consumed as food, answer the questions in section L also.

G1: (I) Could the GMO produce any new metabolites and toxins likely to have deleterious effects on parasites and predators? If so, elaborate. (II) What other unintended effects may result form the planned release of the GMO? Your answer should include considerations about the effect of the GMO on community ecology at the release site. (III) Does the genetic mutation cause effects on other characteristics of the organism?

G2: (I) Will the reproduction of the GMO involved in this release be allowed? If not, is their reproduction planned for later releases or commercial use? (II) Are the arrangements for handling the progeny the same as those for experimental organisms? If not, please specify the arrangements.

G3: Can the changed or added genetic material be transmitted to any other species by means other than conventional reproduction? If so, specify and describe its effects.

G4: (I) Are there natural populations of the parental organism in Brazil (including rivers, lakes, or coastal waters)? (II) Do the existent populations cause problems to other organisms? Specify the organisms and the problems.

G5: If no natural populations of the parental organism exist in Brazil, could the modified characteristics enhance the ability of the species to establish populations in aquatic habitants?

G6: Has any experimental work been done on phenotypic expression of the novel genetic material in naturally occurring organisms (e.g. cross-breeding of GMO with wild or farmed stocks)? If so, what were the results?

G7: What is the likelihood of the novel genetic material entering the gene pool of natural populations?

G8: What effects could the integration of the novel genetic material in the gene pool of a natural organism have? Would it have effects on the organism distribution and abundance, or on local fisheries, the environment or public health? If so, specify them.

G9: What mechanisms will be used to prevent the dispersal of the GMO to other ecosystems?

H. INVERTEBRATES

If these animals are to be consumed as food, answer the questions in section L also.

H1: (I) What effects might the GMO have on the food chain? (II) Could the GMO produce any new metabolites or toxins likely to cause any deleterious effects on parasites and predators? If so, elaborate. (III) Which negative effects could result from this release? Please include considerations on the effects of the release of the GMO in the local ecosystem.

H2: (I) Are the GMO used in this release fertile? If not, is the use of fertile GMO planned for later releases? (II) Will the genotype and phenotype of the progeny the same of the GMO to be released? If not, please specify the differences.

H3: Are there any natural populations of the parental organism in Brazil? If so, do these populations cause agricultural, environmental or public problems or benefits? Specify problems and benefits.

H4: (I) Can the changed or added genetic material be transmitted to other species by means other than conventional reproduction? If so, specify and describe its effects. (II) What is the likelihood of the novel genetic material entering gene pool of natural populations? (III) Can the changed or added genetic material be transmitted to any other species? If so, specify the mechanism of transfer and list the species.

H5: Has any experimental work been done on the phenotypic expression of the novel genetic material in cross-breeding (e.g. cross-breeding of modified strains with wild stock)? If so, what were the results?

H6: Could the entry of the novel genetic material into the gene pool of natural populations of the organism change its distribution and abundance? What would be the effects of this change?

H7: What mechanisms will be used to prevent the dispersal of the GMO into other ecosystems?

J. ORGANISMS FOR BIOLOGICAL CONTROL

J1: (I) What is the target species for biological control? (II) What direct effects does the parent organism have on target species? (III) What direct effects does the GMO have on the target species?

J2: (I) What is the host range of the GMO? If the host range of the GMO is different from that of the parental organism, explain why. (II) What non-target organisms have been tested for susceptibility to the GMO? (III) Which are the criteria used for the choice of the species tested?

J3: How is the GMO transferred form a target individual to another and what factors affect this transferability?

J4: What secondary effects can be envisaged on predators, prey, or parasites of the target species?

J5: (I) Describe the consequences of the removal or reduction of the target species on the management of agriculturally significant plants or farm animals. (II) What are the changes predicted in the environment, resulting from a reduction of the target species population?

J7: If the modified genetic traits can be transmitted to other organisms present in the environment, are these other organisms likely to affect non-target species?

J8: What genetic mutations can occur in populations of the target organism as a result of the use of the GMO (e.g. increased resistance to the modified organism)? Is there any evidence that this may occur?

K. ORGANISMS FOR BIOMEDIATION

K1: (I) What is the target substrate for bioremediation? (II) What effect does the parent organism have on the target substrate? (III) What effect does the GMO have on the target substrate?

K2: What other substance can be metabolized by the GMO that cannot be metabolized by the parent organism?

K3: Will the GMO be self-sufficient once exposed to the target substrate or will additional measures be required (e.g. provision of supplementary nutrients and growth factors or other environmental modifications)?

K4: Does the GMO produce any new metabolites or toxins likely to cause any deleterious effects on other species directly or indirectly, through the concentration in the food chain? If so, elaborate.

K5: What effects might the GMO have on water, air, and soil quality?

K6: What effects might the GMO have on organisms that ingest it?

K7: Will the GMO be dispersed from the site of application? If so, describe the mechanisms involved and the possible or probable consequences.

L.ORGANISMS TO BE CONSUMED AS FOOD

Note: These organisms require authorization from the competent federal regulation department to be consumed.

L1: Is the parent organism or the donor organism already used in food production or eaten as food? If so (I) What is the consumption level? (II) Is any processing needed before consumption?

L2: (I) Does the GMO produce any new metabolites likely to cause any adverse effects to the consumer (humans or animals)? If so, describe it. Provide available data about the toxicology, allergenic reactions and other adverse effects. (II) Can any products of the GMO concentrate on the food chain and become toxic? If so, elaborate.

L3: Will the nutritional quality of the food be changed by the genetic modification? If so, how?

L4: Does the GMO need to be processed before the consumption of the food? If so, elaborate.

L5: Is the GMO able to transfer transgenic strains to the consumer (genome and/or microbial biota)? If so, how frequently does it occur?

APPENDIX 1A ? PLANNED RELEASE ASSESSMENT

MODEL FOR THE PROPOSAL PRESENTATION

The proposal shall be typed in the typing machine or computer, and it shall contain the CIBio?s analysis. The Internal Commission shall send its analysis to the CTNBio together with any other relevant supplementary information.

Public Information Sheet

A completed public information sheet (see Appendix 1B) shall be attached to the proposal for press release.

Check the norms for planned release in the environment of genetically modified organisms (GMO) that apply to your proposal and provide the information bellow. If necessary contact the CTNBio?s Executive Secretary for further instructions.

1. Reference numbers (identification numbers of previous proposals, registered by the CTNBio and CIBio, from which this proposal has been developed).

2. Project title

3. Name of the sponsoring institution(s)

4. Address or contact for supervising CIBio

5. Name, function, and address of the Legal Liable or Chief Researcher.

6. Proposed location of the experiment or field test.

7. Name of the municipality in which the experiment or field test is planned.

8. Scheduled beginning date for the experiment

9. Scheduled conclusion date for the experiment

10. Specific details about the size of the experiment (area and number of organisms involved)

11. Schedule and dates of future experiments or tests.

12. Government authorities consulted about this proposal. Give names of agencies and officials contacted.

13. List of the obtained licenses (enclose copies)

14. CIBio statement: include comments about the Chief Researcher?s capability to manage the work, the adequacy of the project design, site selection and emergency safety procedures plan.

15. CIBio request for advice: specific points where the CIBio seeks the CTNBio?s advice.

16. Will a press release on the project be distributed? If yes, when and whom?

17. Provide details about any measure taken to inform or consult the public (e.g. the local community) about the project

18. Declaration: the information provided here is, to the best of my knowledge, complete, accurate and truthful (Name and signature of the Legal Liable and date)

19. Endorsement of the CIBio : the CIBio has assessed and endorsed this proposal (name and signature of the president of the CIBio and date)

20. Name and signature of the Legal Liable, and date.

At the conclusion of the experiment or field trial, the researcher shall submit a complete report to the CIBio. The CIBio shall submit at least a resume of such report to the CTNBio (see appendix 1C).

Confidential information must be clearly indicated. An additional copy of the proposal without such information shall also be submitted, having the following message clearly highlighted: «Confidential Information Excluded». The proponents shall also provide a justification to explain how the publishing of confidential information might be negative to their interests.

APPENDIX 1B ? PUBLIC INFORMATION SHEET

The information provided by this sheet is destined for press release. A clear language should be used.

Name of organization: __________________

Address of organization: __________________

Name of the contact person: ________________

Contact phone number: _____________

Fax: _________________________

E-mail: _______________________________________________

World Wide Web (www): __________________________________

Organism to be released: __________________________________

Location and size of planned release: ________________________

Proposal of planned release: ________________________________

Brief summary about the GMO to be released. The use of technical terms should be minimized.

Agencies consulted before the release, if applicable (list of approvals obtained): _____

APPENDIX 1C ? INTERNAL BIOSAFETY COMMISSION

REPORT ON PLANNED RELEASE AFTER ITS COMPLETION

Name of the chairman and address of the supervising Internal Biosafety Commission____

CTNBio process review number: _______________________

Project title______________________

Project Chief Researcher_____________________

Legal liable____________________

Agency or agencies approval received (dates) _____________________

Location of planned release ___________________________

Commencement date_________________

Completion date ___________________

Summary of report. Include answers to the following questions:

• What monitoring procedures were undertaken?

• Were the procedures undertaken in accordance with the protocol submitted for CTNBio review? Describe.

• Were the aims of the planned release achieved? Describe?

• Were there any unexpected effects? If there was any adverse effect, a report should be made immediately to the agency concerned and to the CTNBio at the time of the occurrence and reiterated at the time of writing this report.

• What is the number of genetically modified organisms surviving at the release site? What will be the fate of these organisms?

• Will the project be continued to a further stage? If so, provide details.

Signature of the chairman of the CIBio: _________________________

Date: ____________________

The National Technical Biosafety Committee ? CTNBio, using its legal attributions, decides:

Art. 1st The transportation of Genetically Modified Organisms ? GMO shall obey the norms stated in the Annex of the present Institutional Act.

Art. 2nd The present Institutional Act shall take effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the CTNBio

In accordance with the Law n. 8,974 of January 5th 1995, and with the art. 2nd, clause V of the Decree n. 1,752, of December 20th 1995, the regulation of activities concerning the transportation of GMO in Brazil is a competence of the National Technical Biosafety Committee ? CTNBio.

1. The license for transportation depends on the GMO classification and destination. Both the sender and the receiver entities, located within the Brazilian territory, shall have the Certificate of Quality in Biosafety ?CQB for the emission of the license.

2. Concerning Group I GMO, according to the classification described in the Law n.8974/95 and in the CTNBio complementary norms, the Chief Researcher shall notify previously the Internal Biosafety Commissions, both from the sender and the receiver entities about the material shipment (see enclosed flow chart).

3. Concerning Group II GMO, the interested Chief Researcher shall notify the CIBio from its institution, which shall deal with the CIBio from the sender or receiver institution and submit the transport license application to the CTNBio. The CTNBio shall inform the final statement to the involved CIBios (see enclosed flow chart).

4. The sender Chief Researcher shall inform the CIBio from his/her entity and that from the receiver entity about content, volume, local, and packing conditions, concerning both Group I and II GMO.

5. The sender Chief Researcher shall inform the CIBio and the transporter about transportation cautions and emergency measures to be taken in case of escape or accident during the process.

6. The sender Chief Researcher shall assure that the GMO to be transported will be contained in firmly closed packages, to avoid its escape. Two recipients, clearly identified, will always be used: an internal one (essay tube, petri dish, envelope containing seeds), containing the GMO to be transported within a second unbreakable recipient. The external recipient shall be carefully packed for the shipment, in a box made of carrd, wood, or other material that offers resistance during the transportation process.

7. Concerning the transportation of Group II GMO, the internal recipient shall be unbreakable, clearly identified and closed, in order to avoid the escape of the material. If several recipients containing GMO are sent, the external package shall have absorbent material and impact protectors disposed between them. The external package shall provide adequate protection as described in item 6.

8. Concerning the transportation of a set of GMO of several volumes, each recipient shall be involved with the adequate material for protection against shocks, besides the specifications disposed in the items 6 and 7.

9. Liquids of total volume until 50 ml.:

   The internal recipient (essay tube, flask) shall be carefully closed and enclosed within another unbreakable and shock resistant recipient. Both shall be adequately closed, in order to avoid the entry and/or escape of liquids. If necessary the internal recipient can be involved by more than one external recipient, for more safety. The external recipient shall contain absorbent material to avoid the escape of liquid from the internal recipient. The set shall be adequately packed, as described in item 6.

10. Liquids of total volume superior to 50 ml.:

    Besides the requirements described in item 9, an absorbent and shock proof material shall be used between the sets. Each internal recipient can not have more than 1000 ml. of material and the total shipment volume cannot be superior to 9000 ml.

11. Transport of frozen species - dry ice:

    The external recipient containing dry ice shall allow the escape of CO2 gas.

12. Transport of frozen species ? liquid nitrogen:

    Appropriate recipients or steel vessels shall be used for the liquid nitrogen. The conventional rules for the transportation of liquid nitrogen shall be obeyed.

13. For all cases above the packages shall be clearly identified with the «fragile» and the biosafety symbols, together with the following message: «Caution: only experts within the lab are authorized to open it». The external package shall contain name, phone number and complete address; both from the receiver and the sender.

14. In case of transportation to another country, the CIBio from the sender entity shall be responsible for the fulfillment of all these norms, furthermore sending to the CTNBio the application for authorization to transport group II GMO.

15. After the arrival of the material, the receiver shall notify the sender about the receipt and its conditions.

16. In case of importing and exporting, the Chief Researcher shall inform the local CIBio about the intention of receiving or sending the material, as well as send to the material sender or receiver relevant information about the transport, contained in these norms. The importing of GMO, both from groups I and II, shall obey the specific norms elaborated by the CTNBio for this proposal.

17. The cases that are not covered by these norms shall be submitted to The CTNBio?s assessment.

1. Sender institution?s name, address, phone number, fax, and e-mail.

2. Receiver institution?s name, address, phone number, fax, and e-mail.

3. Requester?s name, address, phone number, fax, e-mail, function and responsibility.

4. Sender and receiver institutions? CQB number

5. Objective of the requested license.

6. Identification and information about the way of transportation (personal release, mail, transporter, other ways)

7. Information referent to the GMO.

   7a. Donor organism

   7b. Recipient or host organism

   7c. Vector.

   7d. GMO?s genetic description

   7e. Ingredients? list, if it is a product.

   7f. GMO?s aims and uses.

   7g. Historic about prior transportation processes of the same GMO under the same conditions (please provide CTNBio?s authorization).

   7h. If the material is destined to release in the environment, please provide CTNBio?s authorization).

   7i. GMO handling and storage instructions, including its biosafety level.

8. Quantity and form of the GMO to be transported.

9. Package detailed description.

10. Number and date of the shipments.

11. GMO origin: in case of importing, identify the origin country and institution, entry location within the country, importing licenses and release from quarantine emitted by the competent departments.

12. List of biological materials (culture mean, host) accompanying the GMO during the transportation process.

13. Further Information:

    Plants

    -scientific name

    -GMO presentation (seed, seedling, etc.)

    Animals

    -scientific name

    Microorganisms

    -kind of culture mechanism

    -culture mean source

    -if animal serum is used, indicate percentage and animal species

    -origin of animal enzymes for culture, if applied

    -in case it is an hybridomas, please specify origin or derivation, fusion

14. Detailed description of the biosafety procedures to avoid contamination during the production, and the escape and accidental release during the GMO transportation.

15. Measures to be taken in case of accident.

16. Description of the GMO disposal methods.

17. CIBio president?s name and signature.

18. Chief Researcher?s name and signature.

? ?

? ?

? ?

TO THE CTNBio ?

?

?

The National Technical Biosafety Committee ? CTNBio, using its legal attributions, decides:

Art. 1st The requests for the importing of Genetically Modified Organisms ? GMO, destined to research, submitted to The CTNBio?s assessment in accordance with the Institutional Act n. 02, of September 10th 1996, when aiming the planned release in the environment, will be analyzed by the Committee only from the moment the proponent submits his correspondent proposal of planned release of GMO in the environment, in accordance with the Institutional Act n. 3, of November 12th 1996, and such proposal is approved by its reviser.

Art. 2nd The present Institutional Act shall take effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the CTNBio

The National Technical Biosafety Committee ? CTNBio, using its legal attributions, decides:

Art. 1st The classification of experiences with Genetically Modified Plants, concerning Risk and Containment Levels, shall obey the norms stated in the Annex of the present Institutional Act.

Art. 2nd The present Institutional Act shall take effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the CTNBio

These norms apply to the work under containment with genetically modified plants and other organisms associated to them, the last ones can be either genetically modified or not.

In these norms, except if it is indicated differently, some terms are defined as follows:

Greenhouse ? Refers to a structure containing walls, a ceiling and a floor, designed and used mainly for the growth of plants within a protected and controlled environment. The walls and the ceiling are generally build from a transparent or translucent material to allow the penetration of sun rays.

DNA- deoxyribonucleic acid

Exotic ? Organisms which species, varieties, stocks, lineage, or races do not have their occurrence registered in Brazil.

HEPA- High Efficiency Air philters for particles, which retains 99.00% of particles with 0.3 micrometers or more of diameter.

BL- Biosafety Level

GMO-Genetically Modified Organism

P- Plant

RNA ? Ribonucleic acid.

The containment level of an experience shall be based on the risk level of the organisms involved, and it shall be determined by the highest risk organism, either if it is a GMO or not.

Concerning the risk level determination, shall be considered:

-the transferred DNA/RNA;

-the employed vector;

-the host organism;

-the involved organism amount;

-the experiment?s location.

Concerning the transferred DNA/RNA, the transferred gene is necessary and shall be taken into consideration, as well as its expression in the host organism, the used vector system and the interactions between the gene and the vector system. For genes that codify products harmful for human, animal, or environmental health, the used vector system shall have limited ability to survive out of the lab.

-genetically modified plants which parent organisms historically cause diseases in humans, animals, or plants, which are not weeds or do not reproduce with them, or even that, due to their geographic location, do not reproduce with weeds;

plants, either genetically modified or not and non-exotic genetically modified organisms associated to them having no potential for fast dissemination or to cause serious negative impact in the natural or handled ecosystem (e.g. Rhizobium sp. and Agrobacterium sp.).

-genetically modified plants that are weeds or can cross with weeds, depending on the geographic location;

-plants where the introduced DNA/RNA represents an exotic infectious agent complete genome, or where the complete and functional reconstitution of this genome is possible by genome complementation in the plant;

-plants associated to non-exotic genetically modified organisms with potential to cause harmful effects in handled or natural ecosystems;

-plants where the introduced DNA/RNA represents an exotic infectious agent complete genome, or where the complete and functional reconstitution of this genome is possible by genome complementation in the plant without potential to cause harmful effects in handled or natural ecosystems;

-plants associated to genetically modified organisms without potential to cause harmful effects in handled or natural ecosystems;

-plants associated to arthropods or genetically modified small animals or microorganisms associated to them, if the genetically modified organism has no potential to cause harmful effects in handled or natural ecosystems.

-plants where the introduced DNA/RNA represents an exotic infectious transmissible agent complete genome, or where the complete and functional reconstitution of this genome is possible by genome complementation in the plant with potential to cause harmful effects in handled or natural ecosystems;

-plants or microorganisms associated to them where sequences that codify toxins to vertebrates were introduced;

-microorganisms that are pathogenic to insects and other small animals associated to plants if the genetically modified organism has potential to cause harmful effects in handled or natural ecosystems.

-small number (little amount or scale) of exotic infectious agent, transmissible in the presence of its vector with potential to be a dangerous pathogen to the species cultivated within the country. Such experiment is forbidden to be carried out in great scale.

The principles of the containment are based on the recognition that the employed organisms constitute hazard for human and superior animals? health, and that the containment conditions minimize the possibility of a harmful effect in organisms and ecosystems out of the experiment area.

Concerning the experiments with lab developed plants, under the containment levels from 1 to 4; the norms for working in the appropriate containment level shall be followed. These norms include the use of a culture room for in vitro plants, growth chambers within the labs, or work on benches. Additional biologic containment measures may be required when the reproductive botanic structures having release potential are produced.

BL-P 1, features-

Greenhouse floor:

Can be made of gravel or other porous material, however, concrete side-walks are recommended.

Loopholes: Windows and structures in the ceiling can be opened for airing. Pollen barriers are not required. They shall have webs in their gaps to prevent the entry of small flying animals.

Ventilation system:

Pollen or microorganisms barriers are not required in this case, only for small animals.

Access:

The greenhouse shall be kept locked, except when people are working inside it. The access shall be restraint to those directly involved in the current experiments.

Access- Requirements

Previous knowledge about the norms for BL-P 1.

Experiments registration:

An updated information record about the current experiments shall be maintained.

Decontamination ? Inactivation

The organisms must be biologically inactivated before their disposal.

Sanitary Control:

A program to control undesirable species is obligatory (e.g. weeds, rodents, arthropods, plagues or pathogens), as well as the vegetal sanitary control of plants similar to the GMO surrounding the greenhouse.

Accidents- Information:

The Chief Researcher must inform the CIBio from his/her institution about any accident concerning the release of genetically modified organism.

Concomitant experiment:

For a lower risk experiment carried out concomitantly the BL-P 1 level shall be adopted also.

Signaling:

There shall be a signaling indicating the experiments with GMO.

Materials Transference:

Plants containing living vegetal tissues can not be taken off from the greenhouse, except for containment research in labs of field experiments, in this case, after CTNBio?s authorization.

Special Procedures:

Arthropods and macro-organisms shall be in special cages to avoid their escape.

BL-P 2, features-

Greenhouse floor:

Shall be made of concrete or an equivalent substance.

Loopholes: Windows and structures in the ceiling can be opened for airing, however they shall have webs. Pollen or microorganisms barriers are not required, only for small flying animals.

Ventilation system:

Pollen or microorganisms barriers are not required in this case, only for small animals. The ventilator gaps for air entry shall be open only when they are functioning.

Access:

The greenhouse shall be kept locked, except when people are working inside it. The access shall be restraint to those directly involved in the current experiments.

Access- Requirements

Previous knowledge about the norms for BL-P 2.

Experiments registration:

An updated information form about the current experiments and about plants, animals or microorganisms introduced or picked up from the greenhouse shall be maintained in an easy access place at the greenhouse entry.

Decontamination ? Inactivation

The organisms must be biologically inactivated before their disposal.

Sanitary Control:

A program to control undesirable species is obligatory (e.g. weeds, rodents, arthropods, plagues or pathogens), as well as the vegetal sanitary control of plants similar to the GMO surrounding the greenhouse.

Accidents- Information:

The Chief Researcher must inform the CIBio from his/her institution about any accident concerning the release of genetically modified organism.

Concomitant experiment:

For a lower risk experiment carried out concomitantly the BL-P 2 level shall be adopted also.

Signaling:

There shall be a signaling indicating the current restrict experiments with GMO, indicating the responsible names, used plants and the specific requirements for the use of that area. The presence of organisms harmful to environmental or human health shall be indicated, when applicable.

Transference of Materials:

Microorganisms introduced or picked up from the greenhouse must be transported in closed and unbreakable recipients.

Autoclave:

Required for the decontamination of materials.

Special Procedures:

Arthropods and other macro-organisms shall be in special cages to avoid their escape.

The requirements for the safety level BL-P 2 can be satisfied when a growth chamber or growth room within a building is used, providing that its external physic structure limits the micro or macro-organisms access or escape, in order to satisfy the requirements above.

BL-P 3, features-

Greenhouse:

The greenhouse must be hedged in or protected by another safety measure, besides, it must be separate from other free areas of free access. It shall be a closed structure, with continuous covering which entry shall be protected by two automatic closing sets of doors. The internal walls and the floor shall be waterproof and chemical proof, in order to make cleaning and decontamination easier. All penetrations in the structure (e.g. water conducts, equipment) shall be closed. The floor, obligatorily, shall be made of concrete or an equivalent substance, with a liquid collection and decontamination system. The benches? surfaces shall be impermeable and resistant to acids, bases, organic solvents and moderate warm. The greenhouse shall have a double-door cabinet for changing clothes.

Loopholes: Windows and gaps must be closed. The glass used on the corners and on the ceiling must be unbreakable (e.g. double tempered glass panels)

Ventilation system:

The air that leaves the greenhouse shall pass through a HEPA philter. Such philter must be decontaminated before the machine is removed. The ventilators shall be equipped with a closing system, to be turned on when they are not functioning. The air entry and exit systems shall prevent its reflux.

Access:

The greenhouse shall be kept locked, except when people are working inside it. The access shall be restraint to those directly involved in the current experiments. The responsible for the greenhouse shall determine the staff that will have access authorized.

Access- Requirements

Previous knowledge about the norms for BL-P 3.

Access- Prior Information:

A greenhouse procedures manual shall be prepared or adopted and shall warn its users about the consequences of the disobedience to the rules, and also give information about the measures to be taken in case of an accidental release of organisms with potential to provoke serious adverse environmental impact.

Experiments registration:

An updated record about the current experiments and about plants, animals or microorganisms introduced or picked up from the greenhouse shall be maintained.

Decontamination ? Inactivation

All the materials and experiments must be sterilized and biologically inactivated before their disposal, this includes the water that entered in contact with microorganisms or materials exposed to them, as well as equipment and supplies.

Sanitary Control:

A program to control undesirable species is obligatory (e.g. weeds, rodents, arthropods, plagues or pathogens).

Accidents- Information:

The Chief Researcher must inform the CIBio from his/her institution about any accident concerning the release of any organism involved in the experiments.

Concomitant experiment:

For a lower risk experiment carried out concomitantly the BL-P 3 level shall be adopted also.

Signaling:

There shall be a signaling indicating the restrict current experiments with GMO, indicating the Chief Researcher name, used plants and any specific requirement for the use of that area. The presence of organisms harmful to environmental or human health shall be indicated, when applicable.

Materials Transference:

Viable experimental materials introduced or picked up from the greenhouse must be transported in a second closed and unbreakable recipient. If there is the possibility of propagating substances present on the second recipient?s surface; this shall be decontaminated by a process that proved to be efficient to produce the inactivation of the experimental organism.

Autoclave:

Required for the decontamination of materials. A double-door autoclave is recommended.

Protection Clothes:

Appropriate clothing for the experiments in course, preferentially disposable, shall be used. These clothes shall be taken off before leaving the greenhouse and shall be decontaminated before they are disposed or washed.

Special Procedures:

The hands must be carefully washed before leaving the greenhouse. The taps must be operated by foot or automatically, next to the exit door. All the procedures must be carried out carefully to minimize the generation of materials sprays or aspersions on the vessels during the irrigation, transplant, or any other handling procedure. Arthropods and other macro-organisms shall be in special cages to avoid their escape.

The requirements for the safety level BL-P 3 can be satisfied when a growth chamber or growth room within a building is used, providing that its external physic structure, access, air flux, and decontamination satisfy the requirements above.

BL-P 4: The norms related to this containment level will be published later by the CTNBio. While they are not published, any kind of experiment requiring this containment level is forbidden.

The National Technical Biosafety Committee ? CTNBio, using its legal attributions, decides:

Art. 1st The Containment Work with Genetically Modified Organisms ? GMO shall obey the norms stated in the Annex of the present Institutional Act.

Art. 2nd The present Institutional Act shall take effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the CTNBio

ANNEX I

NORMS FOR CONTAINMENT WORK WITH GENETICALLY MODIFIED ORGANISMS ? GMO

SCOPE

DEFINITIONS

In these norms, except if it is diversely indicated, certain terms will be defined as follows:

CIBio ? Internal Biosafety Commission

Risk Class ? level of hazard associated to the receptor or parent organism (host), which will generate the GMO.

CTNBio ? National Technical Biosafety Committee.

Great scale ? work with GMO in laboratory or production line employing volumes of more than 10 liters

Insertion ? DNA sequence introduced in the receptor or parent organism (host) by means of genetic engineering.

Biosafety Level (BL) ? containment level required to allow safe lab work with GMO, providing minimum risk for the operator and for the environment.

Great Scale Biosafety Level (GSBL) - containment level required to allow safe great scale work with GMO, providing minimum risk for the operator and for the environment.

Donor organism ? organism that supplies the DNA/RNA sequence to be introduced in the receptor organism by means of genetic engineering.

GMO ? Genetically Modified Organism.

Parent or receptor (host) organism ? original microorganism, non-modified by the genetic engineering process, to be used in the genetic engineering experiment.

Small scale ? lab works involving GMO and employing volumes of less than 10 liters

Chief researcher ? supervisor of the work involving GMO.

Work under containment ? activity with GMO under conditions that do not allow its escape or release in the environment, which can be carried out in small or great scale.

Vector ? insert carrier agent.

APPLICATION OF THE NORMS

These norms apply to:

1. Works concerning research, production, technological development, education, and quality control employing GMO under containment regime carried out within the Brazilian territory.

2. Works under containment with genetically non-modified microorganisms, assuring people, animals and environment biosafety.

3. Works in which with genetically non-modified microorganisms are cultivated in the same locations or environments as GMO.

These norms do not apply for the planned release of GMO in the environment, which follows specific rules.

Any doubt about the application of these norms shall be sent to the CIBio, which will ask for CTNBio?s advice, depending on the case.

PROCEDURES

Responsibilities to be fulfilled:

The entity Legal Liable and the CIBio are in charge of assuring the faithful fulfillment of these norms, concerning the proposed release of a GMO in the environment.

The Chief Researcher shall assure the fulfillment of these norms, in accordance with the CQB and under the supervision of the CIBio. He shall also assure that all the people involved in the work are aware about the risks involved and properly directed to obey these norms.

The CIBio and its members are responsible for informing the CTNBio about any eventual non-accomplishment of these norms.

ACCIDENTAL RELEASE

All the GMO containment activities shall be planned and executed according to these norms, in order to avoid any accidental release of a GMO.

However, in case of any accidental release of a GMO, such accident must be immediately communicated to the CIBio and to the CTNBio, enclosing a report about the corrective measures already taken and the names of the notified people or authorities.

The communication of such occurrence to the CTNBio does not exempt the proponent from any other obligation, according to the ordinary law and/or statutes, of informing the competent authorities or people who can be affected.

PRESENTATION OF PROPOSAL

For any activity involving Group I GMO (see annex I of the Law n. 8974, of January 5th 1995), according to the risk classification stated in these norms, the Chief Researcher shall send to the CIBio detailed information following the Application Model contained in the Appendix 1 of these norm.

The CIBio, in its turn, shall send information concerning these activities in its annual report to the CTNBio.

For any activity involving Group II GMO, the Chief Researcher shall submit a written proposal to the CTNBio, through the mediation of the CIBio, following the Application Model contained in the Appendix 1 of these norm.

A new proposal shall be presented for the CTNBio?s assessment whenever the employed organism or the experimental conditions are changed.

Works involving Group II GMO can be develop only after the proposal assessment and authorization by the CTNBio.

The Executive Secretary or the chairman of the CTNBio will be available to clear doubts about any issue related to these norms.

GMO RISK CLASSIFICATION

The GMO shall be classified in groups I and II, according to the Annex I of the Law n. 8974/95 (Appendix 3)

The falling of the GMO in Group I or Group II shall take into consideration the risks associated with the following components:

- the risk class according to the Appendix 2 of these norms, and the parent or receptor (host) organism features,

- the vector,

- the insert,

- the resultant GMO.

In accordance with the pathogenic criterion, the receptor or parent organism to be used in the work that will originate the GMO will be classified according to its pathogenic power for humans and animals (see Appendix 2 of these norms), in four risk class, as follows:

1. Risk class 1- (low individual and community risks) ? organism that does not cause any disease to humans and animals.

2. Risk class 2- (moderate individual risk and restraint community risk)- pathogen that causes diseases to humans and animals, but does not consist in serious risk to those who manipulate it under containment conditions, to the community, living beings and the environment.

   Laboratory exposures may cause infection, but the existence of effective treatment and prophylaxis measures restraint the risk and the dissemination risk is quite limited.

3. Risk class 3- (high individual risk and restraint community risk)- pathogen that usually causes serious diseases to humans or animals and can represent serious danger to those who manipulate it.

   It can be dangerous if it is disseminated in the community, but usually there are treatment and prophylaxis measures.

4. Risk class 4- (high individual and community risks)- pathogen that represents great threat for humans and animals, representing great danger to those who manipulate it and having a great transmission power from an individual to another.

Prophylaxis and treatment measures for these agents usually do not exist.

The GMO that falls in Group I fulfills the non-pathogeny criterion, and is product of a non-pathogenic parent or receptor organism (it falls in Risk Class 1, according to the Appendix 2 of these norms), besides fulfilling all other criteria stated by the Annex 1 of the Law n. 8974/95.

The GMO that falls in Group II is any organism that, within the pathogeny criterion, results from a parent or receptor organism regarded as pathogenic (falling in class 2, 3, or 4) for humans and animals (Appendix 2).

Some organisms are plant quarantine plagues (Appendix 3).

The organisms comprised in A1 list do not exist in Brazil and have their importing expressly forbidden, and can not be object of work.

Those comprised in A2 list already exist in the country, but are under official control by the Ministry of Agriculture, and can be handled only within the endemic area.

BIOSAFETY LEVEL (BL)

There are four biosafety levels: BL-1, BL-2, BL-3, and BL-4, of increasing containment range and protection level complexity.

The biosafety level of an experiment shall be determined by the higher risk class organism involved in the experiment.

When resultant GMO pathogenic power is not known, a detailed and meticulous assessment of all the experimental conditions shall be carried out.

1. BIOSAFETY LEVEL 1 ? BL-1: It is adequate for works involving agents of lowest risk for lab staff and the environment. In this case, the laboratory is not apart from the other dependencies of the building. The work is done mainly on the bench. Specific containment equipment is not required. The laboratory staff shall have specific training for the lab procedures and shall be supervised by a scientist trained in Microbiology or a correlated science.

   The receptor or parent organism falling in risk class 1 shall be manipulated under the conditions specified for the Biosafety Level 1.

   Only the GMO that fall in Group I can be handled under the conditions described in the BL 1.

   The GMO falling in Group II, shall be manipulated under the conditions prescribed in Biosafety Levels 2, 3 or 4, according to the risk class of the receptor or parent organism originating the GMO.

   MICROBIOLOGICAL PRACTICES REQUIRED FOR BL-1

   The access to the laboratory shall be restraint or limited according to the statement of the Chief Researcher, when the experiment is in course.

   The work surfaces shall be disinfected once a day or whenever viable material is spilled on it.

   Every infected liquid or solid waste shall be disinfected before disposal, as well as any material or equipment that has entered in contact with the GMO.

   A mechanic pipette device shall be used, for it is hazardous piping by mouth.

   It is forbidden eating, drinking, smoking, or using cosmetics in labor areas. Food must be stored in a specific area for this proposal, outside the laboratory.

   Before leaving the lab, the hands shall be washed whenever there has been manipulation of organisms containing recombinant RNA/DNA.

   Aiming the personal hygiene procedures, sinks to wash hands and protection clothes (uniforms and jackets) shall be used to minimize the GMO exposure risk.

   SPECIAL LABORARY PRACTICES FOR BL-1

   Infected materials can only be picked up from the lab in tough leak-proof recipients.

   A routine insects and rodents control program shall be provided.

   CONTAINMENT EQUIPMENT REQUIRED FOR BL-1

   Generally, containment equipment of agents falling in risk group I for BL-1 are not required.

   LABORATORIAL FACILITIES FOR BL-1

   The lab shall be designed to allow easy cleaning and disinfecting.

   It is recommended that the surfaces of the benches are impermeable and resistant to acids, alkalis, organic solvents and moderate warm.

   The spaces between the benches, cabinets and equipment shall be enough to allow easy cleaning.

   Each lab shall have a sink for washing hands.

2. BIOSAFETY LEVEL 2 ? BL-2: It is similar to BL-1 and it is adequate for works involving moderate risk for people and environment.

It differs from BL-1 in the following aspects: (1) lab staff shall have specific technical training for handling pathogenic agents and shall be supervised by competent scientists; (2) the access to the lab shall be limited during operational procedures; (3) some proceedings in which the formation of infectious sprays is likely to occur shall be carried in biological safety cabinets or physical containment equipment.

Every GMO falling in Group II originated by a receptor or parent organism falling in class 2 shall be handled under the parameters stated for BL-2.

MICROBIOLOGICAL PRACTICES REQUIRED FOR BL-2

The microbiological practices required for BL-2 are the same already described for BL-1.

SPECIAL PRACTICES FOR BL-2

Besides those special practices described for BL-1 the following practices shall be included for BL-2:

The Chief Researcher is responsible for restraining the access to the lab. He/ She is also responsible for analyzing any situation and defining who will be allowed to enter and work inside the lab.

The Chief Researcher shall state politics and procedures widely informed for everybody who works in the lab about potential hazard related to the activity, as well as the specific requirements for the access to the lab and the rooms where handling with animals will occur.

Inside the lab, people shall use appropriate clothes such as jackets, caps, masks, etc. Before leaving the lab to go to external areas (libraries, refectories, and administrative room) the protection cloth shall be taken off and left in the lab. When organisms containing recombinant DNA/RNA molecules are manipulated, special requirements are necessary to personnel access to the lab (e.g. vaccination). A warning message informing the risk, identifying the agent and the Chief Researcher?s name, complete address and ways to contact him/her or other responsible shall be put on the entry door. All necessary requirements to enter the lab shall be signaled on the entry door.

The entry of animals that are not related to the work in course inside the lab is forbidden.

Specific cautions must be applied to prevent skin infection by organisms containing recombinant DNA/RNA molecules; gloves shall be used for handling animals under experiment, and whenever the risk of GMO contact with the skin exists.

All laboratory and animals room waste shall be properly disinfected before disposal.

Hypodermic needles and syringes shall be used only for parent inoculation and aspiration of animal fluids from laboratory and from diaphragm bottles. Only two operational modes shall be used for activities concerning injection or aspiration of fluids containing recombinant DNA/RNA molecules: fixed needle syringes and single unit syringe and needle set.

Extreme caution shall be observed when handling needles and syringes to avoid self inoculation and the production of sprays during the use and the disposal processes. Needles can not be bent, broken, recapped, or removed from the syringe after use. Needle and syringe must be immediately put into a drilling-proof recipient and disinfected, preferentially autoclaved before disposal. The reutilization of syringes is not recommended.

Leaks or accidents resulting in the exposition of the organism containing recombinant DNA/RNA shall be immediately informed to the CIBio and the CTNBio, with medical assessment, surveillance and treatment procedures, keeping a record of accidents and adopted procedures.

When appropriate, depending on the manipulated agent, for future reference, some reference serum samples from lab staff or other people exposed to the risk, including cleaning and maintenance shall be kept. Additional serum samples shall be collected periodically, depending on the manipulated agent or lab facilities.

A Biosafety Manual shall be elaborated according to the specificity of the executed activities.

All personnel shall be instructed about possible risks and the necessity of following the procedures stated in the Manual.

CONTAINMENT EQUIPMENT REQUIRED FOR BL-2

Biological safety cabinets shall be used (Class I or II), according to Appendix 4, or other personal or physic containment mechanism whenever:

1. procedures of high spray formation power are carried out, such as centrifugation, triturating, homogenization, vigorous agitation, rupture by sonicator, opening of recipients containing material where inner pressure differs from environmental one, intranasal inoculation in animals and in infected tissues cultures;

2. high concentration or volume of organisms containing recombinant DNA/RNA. Such materials can be centrifuged outside safety cabinets only if safety centrifuges and locked vessels are used. These flasks can be open only inside the safety cabinet.

LABORATORIAL FACILITIES FOR BL-2

The lab facilities for the BL-2 shall fulfill the requirements stated for BL-1 and the following requirement:

An autoclave shall be available for disinfecting inside or next to the lab, in order to allow disinfecting all material before disposal.

1. BIOSAFETY LEVEL 3 ? BL-3: It is applicable for places where works involving GMO resulting from class 3 infectious agents are developed, which can cause serious and potentially lethal diseases, resulting from exposition by inhaling.

   Lab staff shall be trained specifically to handle pathogenic and potentially lethal agents, and shall be supervised by scientist widely experienced with this kind of agent.

   All procedures involving handling of infectious material shall be conducted within the biological safety cabinet or other physical containment apparatus. Operators shall use individual protection clothes.

   The lab shall have facilities compatible with BL-3.

   For some cases, when there are not specific conditions for BL-3, mainly in laboratory facilities without specific access area, sealed environments or unidirectional air flow, the routine tasks and repetitive operations can be done in a BL-2 facilities lab, following the procedures recommended for BL-3 and using BL-3 containment equipment.

   The decision of implementing such changes is a competence of the Chief Researcher, as well as informing them to the CIBio ant the CTNBio.

   MICROBIOLOGICAL PRACTICES REQUIRED FOR BL-3

   Besides microbiological practices stated for BL-2, the work with risk agents 3 does not allow the entry of people aged under 18 in the lab.

   If experiments with agents demanding a containment level inferior to BL-3 are carried out, they shall obey the lab procedures stated in BL-3.

   SPECIAL LABORARY PRACTICES FOR BL-3

   Besides microbiological practices stated for BL-2, the following procedures shall be observed:

   The safety cabinets working surfaces and other containment equipment shall always be disinfected after works with recombinant DNA/RNA molecules.

   Absorbent towels with a plastic face folded down, covering the surfaces of the benches, make the cleaning easier.

   A complete specific uniform shall be used for GMO work areas. The use of these clothes is forbidden outside the lab. They shall be disinfected before they are sent to the laundry or for disposal.

   Appropriate facial masks or respirators shall be used in rooms where experiment animals are handled.

   Lab animals in BL-3 shall be kept in partial confinement system (system of boxes and filters with tough walls or box containment system equipped with UV radiation and reflectors).

   Conventional boxes systems will be used only when all personnel use protection clothes and apparatus. It includes complete driving-dress and respirators.

   All staff shall take a shower before leaving such working areas.

   A HEPA filter and collectors containing disinfecting liquid shall protect the vacuum lines.

   CONTAINMENT EQUIPMENT REQUIRED FOR BL-3

   Biological safety cabinets (class I, II, or III) or other appropriate combination of personal protection and physical containment apparatus shall be used in any operation involving GMO. This includes handling of cultures and clinic or environmental material, animals trial operations, cultivation of tissues or fluids infected of animals under experiment or embryo eggs, and necropsy of experiment animals.

   LABORATORIAL FACILITIES FOR BL-3

   The lab shall be separated from free transit areas in the building. A double door system is required with basic requirement for the entry for the lab from the access alleys or to other contiguous areas.

   Physical separation between high containment lab and other laboratories or access alleys can be done by a double door system, with dressing room, showers, air block and other apparatus, for its two-stage access.

   The surface of the internal walls, floor and ceiling shall be waterproof, to allow easy cleaning access. All the surface shall be sealed without re-entries, to make cleaning and disinfecting easier.

   The surfaces of the benches shall be waterproof and resistant to acids, alkalis, organic solvents and moderate warm.

   The lab furniture shall be tough, with spaces between the benches, cabinets and equipment to allow easier cleaning.

   Next to the exit door there must be at least one sink for washing hands. The tap shall have an automatic activating or pedal activating system.

   The lab windows shall be closed or locked.

   The access doors to the lab or containment module shall have automatic closing system.

   There shall be and autoclave to disinfect wastes, located inside the lab or in a contiguous room, preferentially with a double-door system.

   The lab shall have an independent air system with unidirectional ventilation, where the air flux penetrates the lab from the entry area. There can not be air exhaustion to other areas of the building. The exhausting air must be recirculated and filtered through a HEPA filter before leaving the lab. There shall be periodic inspection of the air flow inside the lab.

   The exhausted air from the biological safety cabinets with HEPA filters (Class I or II) shall be immediately sent outwards the building.

   The exhausting air from the cabinets can recirculate within the lab if the cabinet is annually tested.

2. BIOSAFETY LEVEL 4 ? BL-4: This containment level shall be used whenever the work involves GMO resulting from parent or receptor organism falling in risk class 4 or whenever it involves a donator, parental, or receptor organism which pathogenic potential is unknown.

SPECIAL LABORARY PRACTICES FOR BL-4

The procedures stated for BL-3 shall be observed together with the following measures:

No material can be removed from the maximum containment lab, unless it has been previously autoclaved or disinfected, except those materials that have to be removed in viable or intact way.

Material supplies to be used in the lab shall be disinfected in double-door autoclave, fumigation chamber or pressurized ante-chamber system.

The viable biological material, to be removed from class III cabinets or containment lab shall be put within a sealed and unbreakable containment recipient, which shall pass through an immersion tank containing disinfectant, or by a fumigation chamber or an air barrier system.

Equipment or materials, which are not resistant to high temperatures, shall be disinfected by the use of gas or vapor in a specific chamber.

Only people working in the lab are allowed to enter.

The supervisor has the final responsibility for controlling the access to the lab.

As a matter of safety, hermetically locked doors shall block the access to the lab. The Chief researcher or other person responsible for the building shall control the entry.

Authorized personnel shall fulfill strictly the procedure instructions for entering and leaving the lab. There shall be a written record of the personnel entry and exit, with day, hour, and signatures. Protocols shall be defined for emergency events.

The entry and exit of personnel shall occur only after shower and dressing up.

The entry and exit of personnel by pressurized ante-chamber shall occur only in emergency events.

For entering the lab the common street clothing must be changed by a complete and disposable safety clothe. Before leaving the lab to the shower area, the safety cloth shall be left in a specific area, for disinfecting before disposal.

An accident, exposition, and absence of lab staff notification system shall be structured, as well as a medical surveillance system. A quarantine, isolation and medical care unit shall also be previewed for personal under infection suspect.

CONTAINMENT EQUIPMENT REQUIRED FOR BL-4

The handling of risk class 4 agents conducted inside the lab shall be carried out within a biological safety cabinet class III, or cabinets from classes I and II, in this case together with personal protection clothes with positive pressure, ventilated by a life support system.

LABORATORIAL FACILITIES FOR BL-4

The maximum containment unit shall be located in a separated building or clearly marked and isolated area of the building. Entry or exit chambers separated by shower shall be previewed, as well as a double-door autoclave system, fumigation chamber, ventilation system equipped with pressurized ante-chamber for the flux of materials to the interior of the lab.

Walls, ceiling and floor inside the lab shall be constructed with an internal sealing system, to allow greater efficiency in the fumigation, and to avoid the access of animals and insects. The internal surfaces of the lab shall be liquids and chemicals resistant. The soil drainage system shall have a chemical disinfectant effective for the aimed agent, directly connected with a collector system for disinfecting liquids. The sewer and ventilation systems shall be attached to HEPA filters.

Electricity system, air conducts, and utility lines shall, preferentially, be positioned vertically to avoid the accumulation of dust.

Material disinfecting shall be carried out through a automatic control autoclave system with double-door, to allow the removal of the material by the opposite side.

Materials and equipment that can not be disinfected by the autoclave shall pass through an immersion tank containing disinfectant, or fumigation chamber.

The effluent liquid, before it is released in the lab, shall be disinfected by heat treatment.

Chemicals or heat shall disinfect liquids released by the shower or WC.

The lab air system shall preview a differential pressure and unidirectional flow in order to assure pressure differential to avoid the exit of risk agents. Manometers with alarm system shall be attached to the air system, to warn about any alteration suffered in the pressure level required for the different rooms. The exhausting system shall be attached to HEPA filters.

The air released from the biological safety cabinets Class I and II can be eliminated inwards and outwards the lab provided that the exhausting system is attached to HEPA filters. Every six moths the biological cabinets shall be tested and attested.

The air exhaustion from Class III cabinets shall be carried out without recirculation using the serial double filtering HEPA filters system, by lab exhausting system.

The lab shall have a local for the personnel to dress specific clothes with positive pressure and life support system. The system shall have alarms and tanks of emergency respiration.

The lab shall have a shower for chemical disinfecting of the clothes? surface before leaving the area. the inflation air entry shall be protected by HEPA filter.

There shall be a disinfecting system, with double-door autoclave.

The installment of filters and sewers shall be confined to the containment area.

EXPERIMENTS INVOLVING MORE THAN 10 LITERS OF GMO CULTURE

Works involving GMO in laboratories or production line using volumes of more than 10 liters shall have additional confinement and supervision measures.

The risks related to great scale cultivation of organisms shall also be taken into consideration (e.g. products toxic power, physical, mechanic, and chemical aspects of GMO processing).

The institution shall keep a health monitoring program for personnel working with GMO in great scale, including periodic physical and medical exams, maintenance and analysis of serum samples for monitoring eventual changes resulting from the labor conditions.

Any uncommon or prolonged disease among the labors shall be investigated to determine its possible occupational origin.

The biosafety levels for great scale activities are: GSBL-1, GSBL-2, and GSBL-3.

GOOD GREAT SCALE PRACTICES

Institutional procedures shall be stated and applied in order to assure adequate health and safety control of people involved in the activity.

Written instructions and personnel training shall be provided to assure that the GMO cultures will be handled with care, and that the work area will be kept clean and organized.

Adequate facilities (sinks, showers, dressing room) and protection clothes (uniforms, lab jackets, etc.) shall be provided in order to minimize the contact with the GMO and assure adequate individual hygiene.

It is forbidden eating, drinking, smoking, using cosmetics, and piping with the mouth.

GMO cultures shall be manipulated in adequate dependencies.

Before any disposal, the GMO shall be inactivated, and the effluent liquids treatment shall be done under the specific norms.

The addition of a material to the system, the collection of samples and the transference of culture liquid within or between systems shall be conducted in order to minimize the exposure risk of the operators to the GMO.

An emergency protocol shall be stated, including adequate measures to contain and neutralize leaks.

GREAT SCALE BIOSAFETY LEVEL, GSBL-1

Besides the measures applicable for GMO great scale activities, the following requirements shall be included:

In order to avoid GMO escape, the manipulation of cultures with volume superior to 10 liters shall be carried out within a closed system (e.g. growing agent) or in primary containment dependency (e.g. biological safety cabinet.

Volumes until 10 liters can be handled outside the closed system or within primary containment system, provided that all the exigencies for BL-1 are fulfilled.

Culture liquids can only be removed from the closed system or primary containment system after the previous inactivation of the GMO, except for collection of samples.

The collection of samples, the addition of material, or the transference of culture liquid from a closed system to another shall be conducted in order to minimize spray formation or the infection of surfaces exposed in the work environment.

In order to minimize the escape of viable GMO, exhausting gas removed from the closed system or from the primary containment equipment shall pass through HEPA filters or an equivalent procedure (e.g. incineration).

Any closed system or primary containment equipment containing viable GMO can be open only after adequate sterilization.

Emergency protocols shall include adequate methods and procedures for eventual leaks or losses of GMO culture.

Leaks or accidents shall be immediately reported for the responsible for the lab or institution.

Medical evaluation, observation and treatment shall be provided according to the necessity, and written reports shall be elaborated and filed.

GREAT SCALE BIOSAFETY LEVEL, GSBL-2

Besides the norms for GSBL-1, the following measures are necessary:

The primary containment equipment, besides the GMO handling procedures in volumes until 10 liters, shall correspond, at least, to those demanded in BL-2.

The rotate seal and other mechanic apparatus directly associated to the closed system, using in the GMO growth and propagation, shall be constituted in order to avoid leaks, or shall be contained in a ventilated compartment with exhaustion through HEPA filters or an equivalent system.

The closed system, used for GMO growth or propagation, as well as the primary containment equipment used in GMO containment operations, shall have sensors to monitor the confinement integrity during the operations.

Tests shall be carried out before the GMO introduction and after any modification or change of containment essential apparatus.

The procedures and methods applied in tests shall be appropriate for the equipment design and for the recuperation and detection of the tested organism. Test results and reports shall be filed.

The containment system, used for GMO growth and propagation, shall be permanently identified. This identification shall be used in all tests, functioning and maintenance reports, and in all documents related to the use of this equipment for research or production activities with the GMO.

The universal biosafety symbol shall be fixed on closed systems and primary containment equipment, while used for GMO confinement.

Any leak or accident resulting from the exposure to a GMO shall be immediately informed to the Chief Researcher, the CIBio, the CTNBio, and the competent authorities.

GREAT SCALE BIOSAFETY LEVEL, GSBL-3

Besides the measures required for GSBL-2, the following items shall be observed:

Since the physical containment measures of NB-3 are observed, volumes until 10 liters can be handled out of a closed system.

In order to preserve the confinement integrity, the closed system employed for GMO growth or propagation shall be operated in order to maintain the space above the system culture site with the lowest pressure possible, consistent with the construction of the equipment.

The closed system and containment equipment, used for handling GMO cultures, shall be located in a controlled area with the following features:

The controlled area shall have a separate entry. It shall possess a two-door space, such as a pressurized ante-chamber or dressing room, separating the controlled area from other dependencies.

The walls, ceiling and pavement surface of the controlled area shall allow easy access for cleaning and disinfecting.

Eventual drillings in the controlled area shall be sealed to allow environment disinfecting with liquid or gas.

Water conducts and wires in the controlled area shall be protected against infection.

Sinks for washing hands, equipped with valves activated with the foot, elbow, or an automatic system shall be present in each main working area, next to each main exit. Furthermore, a shower shall be available next to the controlled area.

The controlled area shall be designed in order to avoid the exit of culture liquid to the external environment in case of accidental shedding from the closed systems or primary containment equipment.

The controlled area shall have a ventilation system able to control the air flow. It shall move from lower infection power areas to higher infection power ones.

If the ventilation system results in positive pressure, the system shall be designed to avoid the flow inversion, or it shall have an alarm to indicate an eventual inversion. The air exiting from he controlled area can not recirculate in other dependencies, and it shall be filtered through HEPA filters.

The following operational procedures are required:

The entry of people in the controlled area shall occur by the pressurized ante-chamber system, by the ante-room or dressing room.

People shall change their clothes or cover those they are using with coveralls, jackets, pants and shirts, caps, and shoes with shoe-protectors. At the controlled area exit, the protection clothes shall be put in specific closets or sent to the laundry after disinfecting

During the work operations in the controlled area the access shall be restraint to necessary staff for the execution of the program. Before entering the controlled area, people shall be informed about the operation and emergency procedures and about the kind of work to be executed.

The access of people aged under 18 to the controlled area is forbidden.

The universal biosafety symbol shall be fixed on the entry doors of the controlled area, and in the internal doors while the works with GMO are in course.

The charts containing the biosafety symbol shall also have information about the kind of GMO in use and about authorized personnel.

The controlled area shall be kept clean and organized. It is forbidden eating, drinking, smoking and storing food. Animals and plants shall not be allowed. A permanent combat program against insects and rodents shall be kept.

The access doors of the controlled area shall be kept closed, except while the work is in course. The service doors shall be closed and sealed during the operations.

People shall wash their hands before leaving the controlled area. the materials and equipment necessary to control accidents involving GMO shall be available.

In case of leakage or other unexpected releases of GMO, the controlled area shall be disinfected using the stated procedures.

APPENDIX 1

REQUEST OF AUTHORIZATION FOR WORK UNDER CONTAINMENT REGIME WITH GENETICALLY MODIFIED ORGANISM

Dear Sir Chairman of the CTNBio/CIBio

1. Name of the institution/work unit?s Legal Liable or president of the CIBio.

2. Institution and address CQB n.:____ Fax:______ Phone number:___ E-mail:______

3. Name of the Chief Researcher.

   Applies for authorization, conceded by the CTNBio/CIBio, for work under containment regime with the GMO described below.

4. Short description of the GMO, in accordance with the Annex I of Law n. 8,974, of 01/05/95, and with Appendix 2 of the Norms for Work Under Containment with GMO.

5. Classify the Biosafety Level of the Laboratory or Work Unit where the work with the GMO will be executed.

6. Specify maximum GMO volume and concentration to be used in this work.

7. Objective (research, production, development of methodology, teaching, etc.).

8. References about works with the GMO.

9. Specify whether the work under containment aims future releases in the environment.

10. List the equipment to be used during the work under containment with GMO

11. Short description of work procedures to be employed during the experiments and of the planned Biosafety Level ?BL

12. Short description about cleaning, disinfecting, and disposal of material/rests.

13. Critic analysis on foreseeable risks related to GMO.

14. Curricula Vitarum of the involved staff

15. Date and signature.

APPENDIX 2

CLASSIFICATION OF HUMAN AND ANIMAL ETIOLOGIC AGENTS BASED ON THE RISK PRESENTED

RISK CLASS 1

AGENTS:

Agents which do not fall in risk classes 2, 3, and 4 and proved not to cause any disease to humans and animals

The absence of an agent in risk classes 2, 3, and 4 does not imply the automatic inclusion of such agent in risk class 1; for this proposal, a risk assessment based on known and/or potential features of such agents shall be conducted.

RISK CLASS 2

BACTERIAL AGENTS, INCLUDING CLAMYDES:

Acinetobacter baumannii (previously Acinetobacter calcoaceticus)

Actinobacillus (all species)

Actinomyces pyogenes (previously Corynebacterium pyogenes)

Archanobacterium haemolyticum (previously Corynebacterium haemolyticum)

Arizona hinshawii (all soretypes)

Bordetella, including a B. pertussis

Burkholderia (previously Pseudomonii species) except those included in class 3

Escherichia coli (all the entero-pathogenic, entero-toxigen, entero-invasive e strain possessing the K 1 antigen, including the E. coli O157:H7)

Klebsiella (all species , except K. oxytoca, included in class 1)

Legionella, including a L. pneumophila

Leptospira interrogans (all soretypes)

Listeria (all species)

Moraxella (all species)

Mycobacterium (all species, except those listed in Class 3), including the M. avium, M. asiaticum, M. bovis BCG vacinal, M. cheloni, M. fortuitum, M. kansasii, M. leprae, M. malmoense, M. marinum, M. paratuberculosis, M. scrofulaceum, M. simiae, M. szulgai, M. ulcerans, M. xenopi complex

Mycoplasma (all species, except Mycoplasma mycoids e Mycoplasma agalactiae falling in risk class 4)

Salmonella, including S. arizonae, S. cholerasuis, S. enteritidis, S. gallinarum-pullorum, S. meleagridis, S. paratyphi, A, B, C, S. typhi, S. typhimurium

PARASITES:

Human and animal Ancylostoma, including A. duodenale, A. ceylanicum

Ascaris, including A. lumbricoides suum

Babesia, including B. microti e B. divergens

Brugia, including B. malayi, B. timori

Cryptosporidium, including C. parvum

Cysticercus cellulosae ( hydatic cyst ,and T. solium larva )

Echinococcus, including E. granulosis, E. multilocularis, E. vogeli

Fasciola, including F. gigantica, F. hepatica

Giardia, including G. lamblia

Hymenolepis,including H. diminuta, H. nana

Leishmania, including L. braziliensis, L. donovani. L. ethiopia, L. major, L. mexicana, L. peruvania, L. tropica

Opisthorchis (all species)

Plasmodium, including simian species, P. cynomolgi, P. falciparum, P. malariae, P. ovale, P. vivax

Sarcocystis, including S. sui hominis

Schistosoma, including S. haematobium, S. intercalatum, S. japonicum, S.mansoni, S.mekongi

Strongyloides , including S. stercoralis

Trypanosoma, including T. brucei brucei, T.brucei gambiense, T. brucei rhodesiense, T.cruzi

FUNGI :

VIRUSES:

Human Adenovirus (all types)

Chronicle neuropathic infection agents (except Kuru and CJD Viruses, which fall in class 3)

Astrovirus

Bunyanwera and correlate viruses

Calicivirus (all types)

Complexo Tacaribe (Tamiami, Tacaribe and Pichinde viruses)

Lymphocytic choriomeningitis virus (strains non-neurothropic)

Choronevirus (all types)

Coxsackie A and B viruses

Cytomegalovirus

Echovirus (all types)

California Encephalitis (La Crosse, Lumbo and Snowshoe hare)

Venezuelan equine Encephalitis (only strain TC 83)

Occidental equine encephalomyelitis

Oriental equine encephalomyelitis

Epstein Barr virus

Hepatitis A, B, C, D and E

Hepatitis virus (other non-classified types)

Herpesvirus [ except Herpesvirus simiae (Monkey B virus) which falls in Class 4 ]

Herpes simplex type 1 and 2

Herpes zoster

Influenza virus (all types A, B and C)

Orbivirus (all types )

Orthomyxovirus transmitted by ticks

Orthoreovirus (type 1, 2 and 3)

Parainfluenza virus (types 1, 2, 3 and 4)

Papovavirus (all types)

Parvovirus (all types)

Picornavirus (all types except human and monkey pox and aphtous fever viruses, which belong to class 4)

Pneumovirus (all viruses)

Poliovirus (all wild and attenuate types)

Reoviruses (all types)

Respiratory syncytial virus

Rhadinoviruses (all types)

Rhinoviruses (all types)

Vole Rickettsia

Tensaw virus

Turlock virus

Vaccinia virus

Vesicle virus (all laboratory adapted strains)

Equine arthritis virus

Bovine Diarrhea Virus

Rabies Virus (all strains)

Rubella Virus

Mumps virus

Dengue Viruses Dengue (serotypes 1, 2, 3 and 4)

Encephalomyocarditis Virus (EMC)

Vesicular stomatitis Virus (strains adapted in laboratory, including Indian, San Juan e Glasgow strains)

Yellow fever virus (17D vaccine strain)

Rift Valley fever virus ( MP-12 vaccine strain)

Flanders Virus

Langat Virus

Hart Park Virus

Measles virus

Simian viruses (all types, except Herpesvirus simiae (Monkey B virus) and Marburg virus, which fall in Class 4)

Varicella Virus

LOW RISK ONCOGENIC VIRUSES:

Adenovirus 7-Simian virus 40 (Ad7-SV40)

Adenovirus

Chick-embryo-lethal orphan (CELO) virus or avian 1 Adenovirus

Hamster Herpesvirus

Lucke (frog) virus

Mason-Pfizer monkey virus

Polyoma virus

Rous sarcoma virus

Shope fibrome virus

Shope papilloma virus

Simian virus 40 (SV-40)

Marek?s disease virus

Bovine enzootic leukosis virus

Hamsters leukemia virus

Murine leukemia virus

Rat leukemia virus

Avian leukosis virus

Bovine papilloma virus

Dog sarcoma virus

Murine sarcoma virus

Mouse mammary tumor virus.

MODERATE RISK ONCOGENIC VIRUSES:

Adenovirus 2-Simian virus 40 (Ad2-SV40)

Herpesvirus (HV) ateles

Herpesvirus (HV) saimiri

Epstein-Barr Virus (EBV)

Gibbon leukemia virus (GLV)

Feline leukemia virus (FeLV)

Feline sarcoma virus (FeSV)

Simian sarcoma virus (SSV) - 1

Yaba.

RISK CLASS 3

BACTERIAN AGENTS INCLUDING RICKETTSIAL:

Bartonella (all species)

Brucella (all species)

Burkolderia (Pseudomonas) mallei; B. pseudomallei

Mycobacterium bovis (all strains, except BCG)

Pasteurella multocida type B ("Buffalo" and other virulent strains)

Rickettsia akari, R. australis, R. canada, R. conorii, R. prowazeckii, R. rickettsii, R. siberica, R. tsutsugamushi, R. typhi (R. mooseri)

Yersinia pests.

PARASITES :

None.

FUNGI :

Coccidioides immitis (spore cultures; contaminated soil)

Histoplasma capsulatum (all types, including the var. duboisii )

Histoplasma capsulatum var. duboisii.

VIRUSES AND PRIONS:

Arbovirus (all strains, except those falling in Classes 2 and 4)

Chikungunya

Hantavirus, including Hantaan virus

Oncornavirus C and D

Powassan

Wild Vesicle virus

Human T-cell lynphotropic virus (HTLV), types 1 and 2

Lymphocytic choriomeningitis virus (LCM)- neurotropic strains

Venezuelan equine encephalitis virus, epidemic strains (except TC-83vaccine strain )

St. Louis encephalitis virus

Japanese encephalitis virus

Murray Valley encephalitis virus

Vesicular stomatitis virus

Yellow fever virus

Rift Valley fever virus

Semliki Forest virus

Human immune-deficiency Virus (HIV), types 1 and 2

Simian Immune-deficiency Virus (SIV)

Urban rabies virus

Monkey pox virus

Prions (transmissible sponge-form encephalopathy -TME, Creutzfeldt- Jacob disease and Kuru).

RISKCLASS 4

BACTERIAE :

None.

FUNGI:

None.

PARASITES :

None.

VIRUS AND MYCOPLASM:

Hemorrhagic fever agents (including Crimean hemorrhagic fever (Congo), Lassa, Junin, Machupo, Thrust, Guanarito and others still undefined)

Tick borne encephalitis (including Russian spring-summer encephalitis, Kyasanur Forest disease virus, Omsk hemorrhagic fever and Center European encephalitis virus)

Herpesvirus simiae (Monkey B virus)

Mycoplasma agalactiae (goats)

Mycoplasma mycoides (bovine contagious pleural-pneumonia)

African horse sickness virus

African swine fever virus

Goat pox virus

Camel pox virus

Nodular contagious dermatitis virus

Nairobi sheep disease virus

Teschen disease virus

Wesselsbron disease virus

Hare hemorrhagic disease virus

Swine vesicular disease virus

Duck viral enteritis virus

Aphtose fever virus (all types)

Malign catarrhous fever virus

Bovine ephemeral fever virus

Bovine infectious petechial fever virus

Duck viral hepatitis virus

Louping ill virus

Lumpy skin virus

Fowl disease virus

Bovine disease virus

Rickettsia ruminatium ? heart water

Swine classic disease virus (wild sample)

Marburg virus

Akabane virus

Vesicular exhantema virus

Ebola virus.

Version date: 4/3/97

A1 QUARANTINE PLANTS PLAGUES LIST

(MICROORGANISMOS AND NEMATOIDS)

ACARINE

Acarus siro Stored crops

Brevipalpus lewisi Citrus, grapevine e pistachio

Tetranychus pacificus. Grapevine, fruits and cotton.

NEMATOIDS

Anguina agrostis Agrostis sp., Dactyls sp. e Poa sp..

Anguina tritici Wheat and barley

Bursaphelenchus xylophilus Pinus sp..

Ditylenchus angustus Rice

Ditylenchus destructor Potato and floral bulbs

Ditylenchus dipsaci (all strains, except Polyphagus

garlic)

Globodera pallida Potato, tomato and eggplants

Globodera rostochiensis Potato, tomato and eggplants

Heterodera schachtii Red beet

Meloidogyne chitwoodi Potato

Nacobbus aberrans Potato and tomato

Pratylenchus fallax Fruit trees, rose, strawberry and chrysanthemum

Pratylenchus scribneri Corn, tomato, red beet, onion, soybean, potato and orchid

Pratylenchus thornei Apple, rose and ornamental plants

Pratylenchus vulnus Banana, citrus and tomato

Radopholus citrophilus Citrus

Rotylenchulus parvus Sugar cane

Subanguina radicicola Grass

Xiphinema italiae Grapevine, fruit trees, cone-trees.

PROCARIONTS

Apple chat fruit MLO Apple

Apple proliferation MLO Apple

Citrus greening Bacterium Citrus sp.

Clavibacter iranicus Wheat

Clavibacter michiganensis sp. Insidiosus Lucerne, clover

Clavibacter michiganensis sp. Sepedonicus Potato

Clavibacter michiganensis sp. Nebraskensis Corn

Clavibacter tritici Wheat

Curtobacterium flaccumfaciens pv. flaccumfaciens Leguminous

Erwinia amylovora Fruits and ornamental rose-plants

Erwinia stewartii Corn

(=Pantoea stewartii ssp. Stewartii)

Grapevine flavescence doree MLO Grapevine

Lethal yellowing MLO Cocoa and other palm-trees

Peach rosette MLO Peach

Peach yellow MLO Plum

Pear decline MLO Pearl

Pseudomonas syringae pv. Japonica Wheat and barley

Spiroplasma citri (Stubborn) Citrus

Xanthomonas campestris pv. cassavae Cassava

Xanthomonas campestris pv. citri(Biotypes B and E) Citrus

(Xanthomonas axonopodis pv. citri)

Xanthomonas campestris pv. oryzae Rice

Xanthomonas campestris pv. oryzicola Rice

Xylella fastidiosa Peach phony disease Peach

Xylophilus ampelinus Grapevine.

VIRUS AND VIROIDS

African cassava mosaic virus Cassava

Barley stripe mosaic virus Wheat and barley

Banana bunchy top virus Banana

Cadang-cadang viroid Cocoa

Fiji disease virus Sugar cane

Pea seed brorne mosaic virus Pea

Potato spindle tuber viroid (tomato bunch top viroid) Potato and tomato

Plum-pox virus Prunus spp.

Prune dwarf virus Prunus spp.

Prunus necrotic ring spot virus Prunus spp.

Sugarcane Sereh disease virus Sugar cane

Swollen shoot virus Cacao

Tomato ringspot virus. Tomato.

F U N G I

Alternaria vitis Grapevine

Alternaria triticina Wheat

Angiosorus solani Potato

Apiosporina morbosa Prunus spp.

Cladosporium pisicolum Peas

Colletotrichum coffeanum var. virulans Coffee

Dactyliochaeta glycines (Pyrenochaeta glycines) Soybean

Entyloma oryzae Rice

Ephelis oryzae Rice

Fusarium oxysporium f.sp. elaidis African palm

Gibberella fujikuroi Rice

Gibberella xylarioides Coffee

Glomerella cingulata Coffee

Glomerella manihotis Cassava

Gymnosporangium spp Pome-trees, ornamental rose-trees, Juniperus spp.

Haplobasidium musae Musa spp.

Helicoceras spp. Rice

Hemileia coffeicola Coffee

Hendersonia oryzae Rice

Hymenula cerealis Wheat

Moniliophthora roreri Cacao

Mycosphaerella fijiensis Banana

Mycosphaerella zeae-maydis Corn

Nectria galligena Apple e pearl

Oncobasidium theobromae Cacao

Oospora oryzetorum Rice

Oospora pustulans Potato

Ophiobolus oryzinus Rice

Periconia circinata Sorghum

Phakopsora ampelopsidis Grapevine

Phoma exigua var. foveata Potato

Phoma tracheiphila Citrus

Phomopsis anacardii Cashew

Phyllosticta solitaria Apple

Phymatotrichopsis omnivora Polyphagus

Physopella ampelopsidis Grapevine

Phytophthora boehmeriae Citrus

Phytophthora cryptogea Tomato

Phytophthora erythroseptica Potato

Phytophthora megasperma f. sp. Glycinea Soybean

Plasmopara halstedii(except raza 2) Sunflower

Polyspora lini Cotton

Puccinia erianthi Sugar cane

Puccinia kuchnii Sugar cane

Sphacelotheca sacchari Sugar cane

Stagonospora sacchari Sugar cane

Synchytrium endobioticum Potato

Urocystis agropyri Wheat.

A2 QUARANTINE PLANTS PLAGUES LIST

FUNGI

Tilletia indica Wheat, triticale, Agropyrum spp. e Festuca spp. South of Rio Grande do Sul State

PROCARIONTS

Xanthomonas campestris .pv. citri Citrus spp.

Xanthomonas xaxonopodis pv.citri)

Biotype A Disseminated in the States of São Paulo,

Mato Grosso do Sul, Paraná, Santa Catarina

and Rio de Janeiro.

Biotype C São Paulo State

ACARINA

Brevipalpus lewisi Citrus spp., grapevine, pistachio

Tetranychus pacificus Grapevine , fruits, cotton

NEMATOIDS

Anguina agrostis Agrostis spp., Festuca spp., Dactylis spp., Poa spp.

Anguina tritici Triticum spp., Secale spp. E other kinds of grass

Bursaphelenchus xylophilus Pinus spp

Ditylenchus destructor Potato, ornamental bulbs

Ditylenchus angustus Rice

Meloidogyne chitwoodi Potato

Pratylenchus fallax Fruits, strawberry, rose

Radopholus citrophilus Citrus spp.

Xiphinema italiae Grapevine, fruits, cone-trees

FUNGI

Apiosporina morbosa Prunus spp.

Cercoseptoria pini-densiflorae Pinus spp.

Colletotrichum coffeanum var. virulans Coffee

Cronartium spp. Pinus spp., Ribes spp.

Dactuliochaeta glycines(Pyrenochaeta glycines) Soybean

Gymnosporangium spp. Pome-trees ,ornamental rose-trees, Juniperus spp.

Hemileia coffeicola Coffee

Peridermium spp. Pinus spp.

Phoma exigua var. foveata Potato

Phoma tracheiphila Citrus spp.

Phyllosticta solitaria Apple

Physopella ampelopsidis(Phakopsora ampelopsidis) Grapevine

Phytophthora erythroseptica Potato

Phymatotrichopsis omnivora Polyphagous

Scirrhia acicola Pinus spp.

Synchytrium endobioticum Potato

PROCARYONTS

Aplanobacter populi(nov syn. Xanthomonas populi) Salicaceae

Apple proliferation MLO Apple

Apple rubbery wood disease Apple, pearl

Citrus greening bacterium Citrus spp., Fortunella spp.

Clavibacter michiganensis ssp. Insidiosus Lucerne, clover

Clavibacter michiganensis ssp. Sepedonicus Potato

Curtobacterium flaccumfaciens pv. Flaccumfaciens Leguminous

Erwinia amylovora Fruits and ornamental rose-trees

Erwinia salicis Salicaceae

Grapevine flavescence dorée MLO Grapevine

Lethal yellowing MLO Palm-trees

Peach rosette MLO plum tree, peach-tree

Peach yellows MLO Damask, peach-tree

Peach X disease MLO Cherry-tree, peach-tree, morello cherry-tree

Pear decline MLO Pearl, quince-tree

Spiroplasma citri (Stubborn) Citrus spp.

Xanthomonas campestris pv. Oryzae Rice

Xanthomonas campestris pv. Oryzicola Rice

Xanthomonas campestris pv. citri (Biotype E) Citrus spp.

(Xanthomonas axonopodis pv. citri)

Peach phony disease Peach-tree, damask

Xylophilus ampelinus(Xanthomonas ampelina) Grapevine

VIRUSES AND VIROIDS

African cassava mosaic virus Cassava

Banana bunchy top virus Banana and other Musaceae

Citrus Tristeza Virus (razas severas) Citrus spp.

Fiji disease virus Sugar cane

Sugarcane Sereh disease virus Sugar cane

WEEDS

Striga spp.

Group I:

Includes organisms that fulfill the following criteria:

A ? Receptor or parental organism:

• non-pathogenic;
• free of foreign agents;
• possessing a broad documented history of safe use, or the incorporation of biological barriers which, without interfering in the receptor or growth agent's optimal performance, allows for its limited survival and multiplication, with no negative effects for the environment.

B ? Vector/insert

• must be adequately characterized and free of know harmful sequences;
• its size must be limited, to the extent possible, to the genetic sequences needed to carry out the function for which it was designed;
• must not increase the stability of the modified organism in the environment;
• must be barely movable;
• must not transmit any resistance marker to organisms, which, according to available knowledge, do not acquire this resistance naturally.

C - Genetically modified microorganisms:

-non-pathogenic;

offering the same safety as the receptor or parental organism in the reactor or growth agent, but with limited survival and/or multiplication, with no negative effects on the environment.

D ? Other genetically modified microorganisms that could be included in Group I, as long as they combine the conditions stipulated in item C above:

-microorganisms constructed entirely from a single prokaryotic receptor (including plasmids and endogenous viruses) or from a single eukaryotic receptor (including its chloroplasts, mitochondria and plasmids, but excluding virus) and organisms composed entirely by genetic sequences from different species that exchange such sequences though known physiological process.

Group II:

All those not included in Group I.

APPENDIX 4

BIOLOGICAL SAFETY CABINET CLASS I

It is a modified version of the chapel used in the laboratories of chemistry. A class I cabinet is a ventilated cabinet with inward flow of air away from the operator. This cabinet can have three operational modes: with a full-width open front; with an installed front closure panel, or with an installed front closure panel equipped with arm-length rubber gloves. The exhaust air from the cabinet is filtered through a high-efficiency particulate air (HEPA) filter. There is no protection for the experiment, only for the environment and for the operator. UV lamps are used inside the cabinet, which is recommended for works with biological risk agents from groups 1, 2, and 3.

BIOLOGICAL SAFETY CABINET CLASS II

This cabinet is also known as Laminate Air Flow Biological Safety Cabinet, and its main principle is providing safety for the operator, the environment, and the experiment or product. It has an open front to allow the access to the operation surface, and a front panel, which safety height is of 8 inches, with an optional alarm for excessive opening. This cabinet is equipped with HEPA filter.

II A CLASS CABINET

This cabinet has a vertical laminate air flux, and the face velocity of the inward air flow is 75 feet per minute. After it is exhausted by the HEPA filter, the air mass is recirculated where the cabinet is installed (the cabinet shall be at least 8 inches apart from the ceiling). Toxic, explosive, flammable or radioactive substances should not be manipulated in this kind of cabinet because of the high percentage of recirculation of the air flow (70%). It is recommended for manipulations involving biologic risk agents from groups 1 and 2.

IIB 1 CLASS CABINET

This cabinet is equipped with an inward air flow filter. The air that enters the cabinet is filtered through a HEPA filter below the operation area, 30% of this air recirculates while the other 70% is exhausted outwards. The face velocity of the inward air flow is of 100 feet per minute. It is good for use with biological agents treated with minimal amounts of toxic chemicals and radioactive nucleotides traits. It is recommended for works involving biological risk agents from groups 1, 2, and 3.

IIB 2 CLASS CABINET

It is a full air-exhausting cabinet. The air enters through the top of the cabinet and passes trough a first filter and then through the HEPA filter on the operation area. The air exhausting shall be filtered through the HEPA filter, and set outwards through a conduit. It can be used for biological agents treated with toxic products and radioactive nucleotides It is recommended for works involving biological risk agents from groups 1, 2, and 3.

IIB 3 CLASS CABINET

It is similar to IIA Class Biological Safety cabinet. The face velocity of the inward flow varies from 75 to 100 feet per minute. The air is totally exhausted through a HEPA filter, and set outwards through a conduit.

BIOLOGICAL SAFETY CABINET CLASS III

It is a maximum containment cabinet. It is a closed-front ventilated cabinet of gas-tight stainless still construction and operates with negative pressure. The cabinet is fitted with arm-length rubber gloves. Exhaust air is filtered through two HEPA filters or one HEPA filter and incinerator. The introduction and removal of materials is done by double-door or double-door air flood-gate autoclave, immersion recipient with disinfectant solution. It can have other features, such as: refrigerators, brooders, freezers, centrifuges, water-bath, microscope, and animals handling system. IT CAN NOT CONTAIN GAS. Liquid waste is collected in a tank to be disinfected before it is discharged in the sewer. The cabinet provides the highest level of personal, environmental, and product protection of all biohazard safety cabinets. Some examples of biological risk microorganisms in class IV: Arboviruses (Machupo, Lassa, Marburg, and hemorrhagic fever viruses), high risk DNA material for research.

It legislates about genetic handling and cloning of human beings.

The National Technical Biosafety Committee ? CTNBio, using its legal attributions, decides:

Art. 1st For the proposals of this Institutional Act, it shall be defined as:

I ? Genetic manipulation in humans ? the set of activities which allow the manipulation of the human genome, either totally or partially, isolate or as part of natural or artificial compartments (e.g. nuclear transfer), excluding those mentioned in the art. 3rd, clause V, single paragraph, and in the art. 4th of Law n. 8974/95.

II ? Germinal cells ? trunk cells responsible for the formation of gametes present in female and male sexual glands and their direct descendents, with any ploidy level.

III- Totipotent Cells ? cells, either embryo or non-embryo ones, with any ploidy level, capable to form germinal cells or distinguish itself as individual.

IV ? Human cloning ? asexual reproduction process of a human being.

V ? Radical cloning ? cloning process of a human being form a cell, or a set of cells, either genetically manipulated or not.

Art.2nd It is forbidden, concerning activities with humans:

I ? the genetic manipulation of totipotent cells.

II ? radical cloning experiences through any cloning technique.

Art. 3rd The present Institutional Act shall take effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the CTNBio

The National Technical Biosafety Committee ? CTNBio, using its legal attributions, decides:

Art. 1st The Genetic Intervention in Human Beings shall obey the norms stated in the Annex of the present Institutional Act.

Art. 2nd The present Institutional Act shall take effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the CTNBio

ANNEX

NORMS ABOUT GENETIC INTERVENTION IN HUMAN BEINGS

1. Introduction

   A. Every experiment of genetic handling or intervention in humans shall be considered as Research in Human Beings, thus, treated by the Resolution n. 196/96, of the Brazilian Health Council, and obeying the principles of autonomy, no-harm, beneficence and justice. Only the proposals satisfying all the requisites described in the Resolution n. 196/96 can be object of analysis, as detailed bellow.

   B. Only the proposals involving somatic cells shall be regarded as genetic intervention in humans. Any genetic intervention or manipulation in human reproductive cells is forbidden, in accordance with the art. 8th of Law n. 8,974, of 01/05/95 and the Institutional Act n. 8/97, of the CTNBio .

   C. All the proposals of genetic intervention or handling in humans shall be analyzed by the CTNBio, under the prism of two major risk factors, from the biosafety point of view, namely: (1) risk of horizontal transmission of the transferred nucleotide sequence or the vector to other people the patient has contact with, and (2) risk of unexpected modification in the reproductive cells, with vertical transmission of the genetic alterations to the patient?s progeny.

2. Scope

   In accordance with the Law n. 8974/95, the intervention in genetic in vivo human material is forbidden, except for the treatment of genetic anomalies. Those anomalies that are inherited, or acquired during an individual?s life that may cause harm to human health are classified as genetic anomalies.

   Genetic anomalies can be caused by: point mutation, insertion, deletion, translocation, amplification, chromosomal win or loss, or by the presence of a whole infectious organism genome, or part of it.

   Somatic genetic therapy or genetic transfer to somatic cells are genetic intervention or handling methods that aim the production of genetic material in somatic cells by artificial techniques, in order to correct genetic anomalies or stimulate immune answers against the genetic anomaly phenotypic expression, or even to avoid its occurrence.

3. Requests for Proposals of Genetic Intervention or Manipulation in Humans

   The following documents shall be sent for the CTNBio's assessment:

   a. Certificate of Quality in Biosafety ? CQB, of the lab or institution;

   b. Proposal description, answering the listed requisites;

   c. Detailed experimental protocol, including the complete nucleotide sequence of the gene to be transferred and its vector;

   d. Documents showing the approval by the Internal Ethic and Research Commissions as stated by the Resolution n. 196/96 of the Brazilian Health Council, including Free and Cleared Authorization documents, signed by the research subject, according to the resolution mentioned above;

   e. Resumed curricula vitarum of the research staff, informing mainly the existence of prior experiments involving genetic intervention or manipulation in humans.

4. Specific requirements for Proposals of Genetic Intervention or Manipulation in Humans

   4.1 Proposal objectives and strategies

   4.1.1. Genetic intervention with therapeutic aims

   4.1.1.1 Why is the selected disease for treatment through genetic intervention adequate for this kind of treatment?

   4.1.1.2 Describe the selected disease natural evolution. Are there criteria to quantify the activity and the seriousness rages of such disease? Will the knowledge about this disease?s clinic evolution allow a precise evaluation of the efficiency of genetic intervention in humans?

   4.1.1.3 Is the protocol prepared to avoid the disease?s manifestations, prevent its progress after the appearance of the first symptoms, or to reverse such manifestations in seriously sick patients?

   4.1.1.4 Are there any alternative therapies? Which are their advantages and disadvantages in comparison with the genetic intervention in humans?

   4.1.1.5 Is there any genetic intervention experience concerning this disease already done in another country? If so, present literature about it.

   4.1.2 Genetic Intervention in Other Objects

   4.1.2.1 What is the aim of the genetic intervention protocol?

   4.1.2.2 Which cells shall be the target of the genetic intervention? Why is the genetic intervention necessary?

   4.1.2.3 Are there any alternative methodologies? Which are their advantages and disadvantages in comparison with the genetic intervention?

   4.2 Experimental draft, anticipated risks and benefits

   1. Biologic System Structure and Features

Please present a complete description of the methods and reagents employed in the genetic intervention, as well as the strategic reason for their use. Approach mainly the following points:

4.2.1.1 In case of genetic transfer, which is the cloned DNA structure to be employed?

4.2.1.1.1 Describe the gene origin (genome or DNA), the genetic transfer vehicle and form. Provide the complete nucleotide sequence, a detailed construction map and evidences that the material to be transferred corresponds to what is intended.

4.2.1.1.2 Which are the ruling elements present in the construction (e.g. promoters, enhancers, poliadenillation sites, replication origins, etc.). Which is the source of such elements? Make a resume of known information about the ruling feature of each element. Is the gene to be transferred potentially oncogenic? If so, which are the risks and which measures can be taken to reduce such risks?

4.2.1.1.3 Make a summary of the steps to obtain the construction.

4.2.1.2 Which is the structure of the material to be administrated to the patient, and how will it be administrated?

4.2.1.2.1 Describe preparation, structure and composition of the materials to be administrated to the patient, or to be used to treat the patient cells.

4.2.1.2.1.1 If it is a DNA, which is its purity range (concerning both if it is a unique molecular structure and the range of contamination with proteins, carbohydrates, lipids, etc.). which are the tests used to measure the purity range and how accurate is it?

4.2.1.2.1.2 If it is a virus, was it prepared from the DNA construction? In which cells the viruses were grown? Which were the serum and the environment used? How was the virus purification process done? Which are its structure and purity range? Which measures were taken (and how efficient were they) to detect the presence of contamination by other viruses, DNA, RNA, and/or proteins?

4.2.1.2.1.3 If co-cultivation was used, which were the cells employed? Which measures were taken (and how efficient were they) to detect the presence of any contamination?

4.2.1.2.2 Describe any other material to be used to prepare the inoculation. For instance, if a viral vector is used, which is the nature of the helper virus? If other carrier particles are used, which is their nature?

Describe the results of experiments with cells or animals cultures that attest the safety, the effectiveness, and the viability of the proposed procedures. Explain why the chosen experimental model is the most appropriate.

4.2.2.1 Genetic transference system

4.2.2.1.1 Which are the target cells for the transference? Which cells will be treated ex vivo and reintroduced in the patient? How will the section of the target cells that received transferred DNA be carried out? How will the characterization of the cells before and after the treatment be carried out? Which theoretic and practical data allow the assumption that only the target cells will receive the genetic material?

4.2.2.1.2 How efficient is the genetic transference system? Which is the estimated percentage of target cells contained in the transferred DNA?

4.2.2.1.3 How will the monitoring of the transfer sequences structure be carried out, and how accurate is the analysis? Is the transferred DNA extra-chromosomal or integrated? May the transferred DNA suffer re-arrangements?

4.2.2.1.4 How many copies of the transferred DNA per cell are expected? How stable is the transferred DNA?

4.2.2.2 Genetic Transference and expression concerning structural persistence and stability

4.2.2.2.1 Which experimental animal and tissue culture models were used in lab studies to evaluate the in vitro and in vivo effectiveness of the genetic transference system? Which are the resemblance and differences of these models in contrast with the proposal of genetic transference in humans?

4.2.2.2.2 What is the minimum transference level and/or genetic expression estimated as necessary for the genetic transference to be successful? How was this level stated?

4.2.2.2.3 Explain in detail the pre-clinic experiments attesting the efficiency of the transference system, concerning the minimum necessary levels for the genetic transference.

4.2.2.2.4 Does the integrate DNA modify the expression of other genes? How was it verified?

4.2.2.2.5 What is the percentage of cells that received the DNA where the gene expression occurs? Is the transferred gene product biologically active? Which proportion of the normal activity is derived from the transferred gene? How was it verified?

4.2.2.2.6 Does the transferred gene express itself in other cells besides the target cells? How was it verified?

4.2.2.3 Transference Systems based on retrovirus

4.2.2.3.1 Which are the cellular types to be infected by the retroviral vector? Is the production of viral particles expected?

4.2.2.3.2 How stable are the retroviral vector and the resultant pro-virus concerning deletion, re-arrangement, recombination and mutation? What is the available information about the risk of recombination with endogenous retroviruses or other virus that may eventually be present in the patient cells?

4.2.2.3.3 Is there any evidence that the genetic transference may have any adverse effects (e.g. development of neoplasm, degenerative mutations, regeneration of infectious particles, immune responses, etc.)? Which caution measures shall be taken to minimize the retroviral vector pathogenic power? Which were the pre-clinic experiments done to estimate this pathogenic power?

4.2.2.3.4 Is there any experimental evidence that the vector may penetrate in non-treated cells, mainly reproductive ones? How accurate are these analysis?

4.2.2.3.5 Has the genetic transference protocol for humans already been tested in non-human primates or other lab animals? In specific terms, is there any evidence of recombination of the retroviral vector with endogenous viruses or other viral sequences present in animals?

4.2.2.4 Non-retroviral genetic transference systems

4.2.2.4.1 Which experiences with animals were employed to determine if there is risk of undesirable or harmful consequences by the use of the genetic transference protocol (including the introduction of DNA in non-target cells, mainly reproductive ones)? How long were the animals studied after the treatment? Which further biosafety studies were carried out?

Describe the treatment to be applied to the patients and the diagnostic methods to be used to observe the response to the treatment. Describe equal or similar prior clinic studies. Answer mainly the following questions:

4.2.3.1 Will patient cells be removed for ex vivo treatment? Describe types and numbers of cells and the intervals when they will be removed.

4.2.3.2 Will the patients be treated to eliminate or reduce the number of non-modified target cells (e.g. radiation or chemotherapy)?

4.2.3.3 Which treated cells (or combinations vector/DNA) shall be administrated to the patients? How will the administration be carried out? Will the treatment be single or multiple? What is the interval between the treatments?

4.2.3.4 How will the gene transference and expression in the patient cells be verified? Will this expression be checked in non-target cells?

4.2.3.5 Which are the studies to be carried out in order to evaluation of infectious presence and effects?

4.2.3.6 What are the clinic final points of this study? Will any quantitative survey be employed to evaluate the disease?s natural history? How will the patients clinic supervision be carried out?

4.2.3.7 Which are the expectations concerning the major benefits or harms derived from the genetic transference? Which are the measures to be taken to prevent or reverse adverse effects, if they occur?

4.2.3.8. If a treated patient dies, which are the specific post-mortem studies to be carried out?

Discuss the possible risk of the genetic transference to other people than the patients. Answer, mainly, the following questions:

4.2.4.1 Is there any risk to public health?

4.2.4.2 Is there any probability of transmission of the transferred DNA to other people, or to the environment?

4.2.4.3 Which caution measures shall be taken to avoid the transmission?

4.2.4.4 Which measures shall be taken to minimize de risk for the public health?

4.2.4.5 Concerning the potential risks of progeny in patients, including vertical transmission, will any contraceptive measures be taken?

Describe the staff training course and experience. Describe the clinical and laboratory facilities to be used. Answer, mainly, the following questions:

4.2.5.1 Describe the installments where the materials to be used in the genetic intervention will be prepared, including environmental conditions for the eventual manipulation of ex vivo cells.

4.2.5.2 Which professionals will be involved in pre-clinic and clinic studies and what are their qualifications? Enclose resumed curricula.

4.2.5.3 In what hospital or clinic will the genetic intervention be carried out? Which facilities will be specifically important for the proposed study?

4.3 Patients selection

The patients? selection criteria shall obey the norms contained in the resolution n. 196/96, of the Brazilian Health Council.

Please estimate the number of patients involved in the study. Describe the patients? selection procedures. Answer, specifically, the following questions:

The National Technical Biosafety Committee ? CTNBio, using its legal attributions, decides:

Art. 1st The planned release in the environment of Genetically Modified Plants which has already been approved by the CTNBio shall obey the norms stated in the Annex of the present Institutional Act.

Art. 2nd The present Institutional Act shall take effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the CTNBio

ANNEX

SIMPLIFIED NORMS FOR PLANNED RELEASE IN THE ENVIRONMENT OF GMO WHICH HAS BEEN ALREADY APROVED BY THE CTNBio

Scope

These norms are applicable for planned release in the environment of Genetically Modified Plants which has already been approved by the CTNBio, according to the following cases:

I. Planned release in the environment of Genetically Modified Organisms of the same species (variety, lineage, etc) which the gene has been introduced, in the same transformation event, which has already been approved by the CTNBio;

II. Planned release in the environment of Genetically Modified Organisms of the same species (variety, lineage, etc.)which the gene has been introduced, which has already been approved by the CTNBio, but obtained by other transformation method or event;

III. Planned release in the environment of Genetically Modified Organisms of the same species (variety, lineage, etc.) which the gene has been introduced, which has already been approved by the CTNBio, but obtained by other transformation method or event, or other construction, with different ruling elements, marker gene or reporter gene.

The Fig. 1 aims to help the proponents to follow the steps required by the norms. It is a summary to be used only as an initial direction, and shall not be taken as substitute of the exigencies detailed by the norms.

Fig. 1 ? Summary of proceedings

Proposition of the Chief Researcher to conduct a Field Trial of a GMO Þ Analysis by the Internal Biosafety Committee - CIBIO Þ National technical Biosafety Committee - CTNBIO Þ Publication in D.O.U. Þ Analysis by the Specific Sector Committee Þ CTNBio´s statement on the propositionÞ Final decision on the proposition Þ D.O.U. Publication Þ Communication to the CIBio.

In these norms, except if it is diversely indicated, certain terms will be defined as follows:

GMO ? Genetically Modified Organism.

CTNBio ? National Technical Biosafety Committee

CIBio ? Internal Biosafety Commission

Chief Researcher ? The proposal?s supervisor, indicated in accordance with these norms.

Proponent ? Any legal entity that proposals the execution of any release, in accordance with these norms.

Legal Liable - The individual whose responsibility for the execution of the planned release falls on, in accordance with the norms of the CTNBio. He/she can be the supervisor of the project, the proponent, or any other person with daily supervision responsibility.

Secretary ? The CTNBio?s Executive Secretary.

These norms are applicable to the release of GMO in the environment in Brazil (including imported GMO), either by means of field experiences or by any other mean, except for free releases, as described below. The norms are not applicable to containment regime works, which are conducted under CTNBio?s specific norms.

In case the Chief Researcher of a project has doubts about the applicability of these norms for a proposed release, he shall submit to the CIBio, in writing, a description of the work he intends to carry out, or directly to the CTNBio to receive information about the case.

EXEMPTIONS ? The release of GMO that has already been approved by the CTNBio for commerce, will be free from these norms.

The release of a GMO in the environment shall not be free from these norms in case the prior work was exempted because it was carried out under approved containment conditions.

A GMO that was previously approved by the CTNBio for planned release may be exempted from these norms providing that, according to the judgement of the CTNBio, the experience had shown acceptable risk levels.

An exemption may be unconditional or subject to conditions.

The Legal Liable and the CIBio are in charge of assuring the faithful fulfillment of these norms, concerning the proposed release of a GMO in the environment.

The responsibility includes the indication of a Chief Researcher (who can be the Legal Liable), guaranteeing that the work will be monitored by an appropriately constituted CIBio, familiarized with these norms, assuring also that all the people involved in the proposed release are aware and directed to obey these norms, as well as the CTNBio?s instructions.

Whenever the CIBio knows about a decision of release of GMO in the environment, it is in charge of assuring the obedience of these norms. The CIBio and its member are responsible for informing the CTNBio about any eventual non-accomplishment of these norms.

All the GMO handling proceedings shall be foreseen in order to give the most possible guarantee that no accidental release of a GMO will occur, and that all the introductions will be planned and executed in accordance with the norms. However, in case of any accidental release of a GMO that should be introduced in a planned way, according to these norms, such accident must be immediately communicated to the CIBio and to the CTNBio, enclosing a report about the corrective measures already taken (if appropriate) and the names of the notified people or authorities. The communication of such occurrence to the CTNBio does not exempt the proponent from any other obligation, according to the ordinary law and/or statutes, of informing the competent authorities or people who can be affected.

Before any planned release of GMO occurs, the proponent shall submit a proposal, in writing, to the CTNBio. As soon as the release of a GMO in the environment is done, the Legal Liable or the Chief Researcher of the project is in charge of giving total attention to the proposed release possible effects, specially the necessary steps for the obedience of these rules. The Secretary or the chairman of the CTNBio shall be available to queries about any issue related to these norms.

The obedience to these norms does not exempt the proponent from the obedience to any other norms regarded as relevant, or from requirements related to the ethic in works with humans and animals.

When the proposal reaches the adequate stage, the Legal Liable or Chief Researcher shall prepare the answers for the questions described below (core questions for the proponents) as well as the answers for questions from other sections. The answers shall be sent to the CIBio for the analysis. While doing this, the CIBio shall consider whether the data of works under containment conditions already executed are enough for the safe continuation of the planned release. The CIBio shall keep contact with the Legal Liable or the Chief Researcher, be informed, and give, if necessary, suggestions for the proposal?s review.

When the proposal is regarded as accomplished, the CIBio shall send it to the CTNBio together with a filled frontispiece (annex 1.A), and the public info page (annex 1.B).

If the proposal includes confidential information, the proponent can mark relevant parts as "commercially confidential", explaining the reasons that justify such treatment. If there is any material clearly classified as confidential, the Secretary, the president and the reporter of the proposal shall treat it this way, except if the Committee regards such information as necessary. In this case, the CTNBio shall notify the proponent in writing and negotiate a consensual resolution. If a deal is not made, in the terms of the Decree n. 1,752, of December 20th 1995, the CTNBio, without loss or violation of secrecy may exclude the proposal at any time before the analysis. The proposal can be submitted again to the CTNBio for approval in another occasion.

When receiving a proposal the CTNBio shall: a) publish its reception in the DOU, with a brief description of the proposed release; b) publish the description of the proposed release among people and/or organizations registered in the CTNBio for this objective; c) send the description of the proposed release the competent authority from the location of the release. The public shall have thirty days to give an statement before the CTNBio about the proposed release, counting from the date of its publication in the Federal Official Gazette(DOU).

In order to express its statements about the proposal, the CTNBio shall send to the proponent any substantial comment received from the public. The proponent can answer such comments, in writing, to the CTNBio.

Each proposal shall be analyzed by a CTNBio Specific Sector Commission, which can demand the statement of ad hoc advisors when it is considered necessary. The proponents shall receive from the secretary the information about dates of any meetings. Ordinarily, it will take eight weeks between the reception of the proposal and the Committee?s initial opinions. The proponent can be called to attend the meetings to answer questions related to the proposal. The CTNBio?s statement about it shall be sent to the CIBio within a period of 4 weeks after the final analysis. If the CTNBio judges that the proposed release will cause a negative consequence to the environment, it shall be sent to the Ministry of Environment, Water Resources and Legal Amazon, which may demand an Environmental Impact Study ? EIA/RIMA, in conformity with the directions established in the Resolution n. 001/86 of the CONAMA, what may result in instructions about the conditions to be included to the proposal.

After the CTNBio have recognized that a determined planned release will be able to continue, the public info document submitted by the proponent shall be published in the Federal Official Gazette (DOU). Some copies of this document shall also be sent to those people who had done comments in the occasion of the first notification about the release, as well as to the competent authorities of the place where the release will be carried out.

The Main Researches and Legal Liable shall act in accordance with the monitoring protocols recommended by the CIBio, as approved by the CTNBio.

Any problem or unexpected incident shall be immediately reported to the CIBio and to the CTNBio, together with details of any measure already taken and the names of the notified authorities. Reporting an occurrence to the CTNBio does not exempt the proponent from any other obligation, according to the ordinary law and/or statutes, of informing the competent authorities or people who can be affected.

Within a period of six months from the conclusion of a planned release, the Legal Liable or the Chief Researcher shall submit to the CIBio a detailed report for review.

The CIBio shall do the review to determine if:

The protocols were adequately followed during the experiences.

The objectives of the experiences were reached.

Adverse effects had taken place.

The organism?s survival and dissemination features were those expected.

In the conclusion of the review, the CIBio shall submit a report to the CTNBio according to the annex 1C.

All the proposals for the release of GMO in the environment, obeying these rules, shall include the answers for the core questions set out in section A, and in other sections relevant for the proposal. The proposal shall be prepared by the Legal Liable or Chief Researcher, and by the CIBio, as previously described.

Those involved in the preparation of the proposal are in charge of offering the best and most complete considerations that enable the detection of possible impacts of the intended release, and they shall make available relevant questions for the CIBio and the CTNBio. The impacts to be taken into consideration include the consequences to the public safety and health, the agriculture, other organisms and to the environment?s quality.

Crucial importance must be given to the experience obtained by works under containment related to the organism, and the results of a relevant bibliographic research, as well as to the queries to experts and public authorities.

Answers shall be based on adequate data and references, as well as on other prior experiences conducted in Brazil or abroad. In the absence of available data or reference, the support for the answer shall be mentioned. In case there is any doubt about the appropriate answer for a question, the nature of the doubt shall be stated. If the existence of a potential damage is noticed, the clearest possible explanation of the relative risks involved shall be provided and possible steps to eliminate or deal with the hazard shall be considered and suggested, whenever it is adequate.

I. Release in the environment of GMO from the same species (variety, species, lineage, etc) in which the gene has been introduced, in the same transformation event, which has already been approved by the CTNBio. The procedures for the release in the environment described above, are those contained in the Institutional Act n. 3, of 11/12/96 of the CTNBio, with the modifications bellow:

1. Inform which was(were) the release(s) of this GMP approved by the CTNBio and the main differences between this project and the prior release(s).

2. Answer only the core questions listed bellow:

A.CORE QUESTIONS:

A1: What is the species of organism to be released? (when appropriate, give information on the scientific name, strain, variety, pathovar, lineage, and serotype.)

A2: (I) What is the aim of the proposal? (II) What is the intended use of the GMO?

A3: Describe the size of the experiment, concerning area or volume, and its location (please give address). Include map(s) in adequate scale(s) to allow the analysis of the chosen area under the requirements described in A7.

A4: (I) What are the reasons for the choice of location? (II) Describe in details relevant features of the physical environment, mainly those that may minimize or exacerbate any undesirable effects (e.g.: wind motion, ground water, proximity of water courses, and protected areas, etc.); (III) On what distance is the experiment location from population centers, agriculture activities centers, genetic diversity centers, habitats of biota that may be affected by such release of GMO in the environment?

A5: What are the introduced genes and which specific function do they have?

A6: Is there any evidence that the novel trait can be transferred to other organisms found at the site of the planned release and surrounding environment? If so: (I) to what organisms at what frequencies? List the species that have been tested or evaluated for the receptivity and justify the reason for their choice.(II) what transfer mechanisms are involved? (III) what techniques have been employed to demonstrate the receptivity to transfer? (IV) Describe any possible adverse effects of the transfer.

A7: (I) Describe in detail the overall experimental protocol for the release and subsequent monitoring after the test is finished. Include the protocol for control, test, and challenge organisms, if relevant. (II) How many GMO will be released? (III) How many releases are intended and which is their schedule?

A8: What are the arrangements for producing the GMO in quantity, and transporting it to the experiment site? What will the release proceeding be?

A9: What methods will be used to control the quality batch to batch, if a large scale production of GMO is required for the release?

A10: (I) How will the survival of the GMO be monitored? Describe the techniques to be used in monitoring the occurrence of GMO or transferred genetic material beyond the release site, including specificity, sensitivity and reliability of the detection methods. (II) If the release is likely to affect the characteristics or the amount of other species, how will this be monitored?

A11: (I) Which potential hazards or deleterious effects can be postulated and how can these effects be evaluated during the release experiment? (II) Describe structures and procedures employed to reduce the dissemination of the GMO. (III) If the transfer of introduced genetic traits to other organisms is possible (see A6), which methods shall be used to minimize these effect?

A12: If the GMO remains in the environment after the release experiment: (I) How long will it happen and (II) What are the possible consequences? (III) Will any measure be taken to reduce GMO populations or dispose, after the release is completed? (IV) What kind of monitoring will be done after the release is completed?

A13: What measures will be taken to remove the GMO, in case of clear hazard during the execution of the release experiment?

A14: Describe the experiment site supervision proceedings, as well as the safety proceedings that will be carried out by staff. Make a list of the staff in charge of the experiment and describe the training received by the staff members.

A15: (I) Provide information about prior proposals, including their results and positive or adverse effects. (II) What factors may suggest greater or less risks concerning the presented proposal?

IMPORTANT: Give any other information that can subside the CTNBio in the analysis of the presented proposal.

B. PLANTS

B1: (I) Does any sexually compatible plant live near the release site? If so, give details and quantify the chances for cross-pollination. (II) Provide quantitative data on about cross-pollination between the plant and its wild parents occurring in the release area. (III) If cross-pollination occurs, will the resultant plants or its progeny be able to survive and compete well? If so, list them.

B2: (I) Will the plants in this release be allowed to set seeds? If not, is any subsequent release planned? (II) If plants are allowed to set seed, does the mature seed normally remain contained within an ear, capsule, or pod so that practically all of the seed can readily be harvested, or is the seed shed soon after it matures?(III) Can the seed be dispersed by natural means? If so, describe them. (IV) Are the seeds capable of surviving in a dormant condition for a long time? If so, how long?

B3: What secondary ecological effects might result from the release of the GMO( e.g. effect on endangered native species, resistance of insect populations to an insecticide, reduction or increases in the numbers of prey and parasites, etc.)?

II. Release in the environment of GMO from the same species (variety, species, lineage, etc) in which the gene has been introduced, which has already been approved by the CTNBio, but obtained by other transformation method or event.

A.CORE QUESTIONS:

A1: What is the species of organism to be released? (when appropriate, give information on the scientific name, strain, cultivar, pathovar, lineage, and serotype.)

A2: (I) What is the aim of the proposal? (II) What is the intended use of the GMO?

A3: Describe the size of the experiment, concerning area or volume, and its location (please give address). Include map(s) in adequate scale(s) to allow the analysis of the chosen area under the requirements described in A7.

A4: (I) What are the reasons for the choice of location? (II) Describe in details relevant features of the physical environment, mainly those that may minimize or exacerbate any undesirable effects (e.g.: wind motion, ground water, proximity of water courses, and protected areas, etc.); (III) On what distance is the experiment location from population centers, agriculture activities centers, genetic diversity centers, habitats of biota that may be affected by such release of GMO in the environment?

A5: What are the introduced genes and which specific function do they have?

A6: (I) Present the nucleotide sequence of the transgenic variety, and point the present regulator elements (e.g.: promoters, "cis" regulation elements, resistance genes, replication origin, etc.).

A7: (I) How was the exogenous DNA/RNA introduced in the host organism? (II) Which was the vector employed? (III) Which is the scope of hosts for the vector? (IV) Present a restriction map and show the regions specifying functions (e.g.: promoters, "cis" regulation elements, resistance genes, replication origin, etc.).

A8: (I)On which level may the genetic mutation be characterized? Give information that show the scope of the characterization. (II) Was the introduction chromosomal or cytoplasmic? (III) Which phenotypic, cytogenetic, or molecular markers may provide the identification of the GMO under field conditions?

A9: Does the GMO have any potential genotype instability? Are there any known events of instability in the GMO using the same host?

A10: What are the known modifications that can change the phenotype of the GMO to be released?

A11: Based on the containment experiments, give information about the growth range (or lifetime of each generation) and survival, aiming the comparison between the GMO and the non-modified organism. Which is the frequency of reversion or loss of the genetic change?

A12: Is there any evidence that the novel trait can be transferred to other organisms found at the site of the planned release and surrounding environment? If so: (I) to what organisms at what frequencies? List the species that have been tested or evaluated for the receptivity and justify the reason for their choice.(II) what transfer mechanisms are involved? (III) what techniques have been employed to demonstrate the receptivity to transfer? (IV) Describe any possible adverse effects of the transfer.

A13: (I) Describe in detail the overall experimental protocol for the release and subsequent monitoring after the test is finished. Include the protocol for control, test, and challenge organisms, if relevant. (II) How many GMO will be released? (III) How many releases are intended and which is their schedule?

A14: What are the arrangements for producing the GMO in quantity, and transporting it to the experiment site? What will the release proceeding be?

A15: What methods will be used to control the quality batch to batch, if a large scale production of GMO is required for the release?

A16: (I) How will the survival of the GMO be monitored? Describe the techniques to be used in monitoring the occurrence of GMO or transferred genetic material beyond the release site, including specificity, sensitivity and reliability of the detection methods. (II) If the release is likely to affect the characteristics or the amount of other species, how will this be monitored?

A17: (I) Which potential hazards or deleterious effects can be postulated and how can these effects be evaluated during the release experiment? (II) Describe structures and procedures employed to reduce the dissemination of the GMO. (III) If the transfer of introduced genetic traits to other organisms is possible (see A12), which methods shall be used to minimize these effect?

A18: If the GMO remains in the environment after the release experiment: (I) How long will it happen and (II) What are the possible consequences? (III) Will any measure be taken to reduce GMO populations or dispose, after the release is completed? (IV) What kind of monitoring will be done after the release is completed?

A19: What measures will be taken to remove the GMO, in case of clear hazard during the execution of the release experiment?

A20: Describe the experiment site supervision proceedings, as well as the safety proceedings that will be carried out by staff. Make a list of the staff in charge of the experiment and describe the training received by the staff members.

A21: (I) Provide information about prior proposals, including their results and positive or adverse effects. (II) What factors may suggest greater or less risks concerning the presented proposal?

A22: Was the GMO imported, or was it made in Brazil? In case it is imported, attach documents of license, given by the competent inspection authority, and of quarantine services, when applicable.

IMPORTANT: Give any other information that can subside the CTNBio in the analysis of the presented proposal.

B. PLANTS

B1: what kind of pleiotropic effects can be observed in the expression of a modified gene in the GMO (e.g. : reduced fertility, increased disease incidence, loss of productivity, and grain/fruit shedding)?

B2: (I) Does any sexually compatible plant live near the release site? If so, give details and quantify the chances for cross-pollination. (II) Provide quantitative data on about cross-pollination between the plant and its wild parents occurring in the release area. (III) If cross-pollination occurs, will the resultant plants or its progeny be able to survive and compete well? If so, list them.

B3: (I) Will the plants in this release be allowed to set seeds? If not, is any subsequent release planned? (II) If plants are allowed to set seed, does the mature seed normally remain contained within an ear, capsule, or pod so that practically all of the seed can readily be harvested, or is the seed shed soon after it matures?(III) Can the seed be dispersed by natural means? If so, describe them. (IV) Are the seeds capable of surviving in a dormant condition for a long time? If so, how long?

B4: What secondary ecological effects might result from the release of the GMO( e.g. effect on endangered native species, resistance of insect populations to an insecticide, reduction or increases in the numbers of prey and parasites, etc.)?

If these GMO is to be consumed as food, answer the question in section C also.

C.ORGANISMS TO BE CONSUMED AS FOOD

Note: These organisms require authorization from the competent federal regulation department to be consumed.

C1: (I) Does the GMO produce any new metabolites likely to cause any adverse effects to the consumer (humans or animals)? If so, describe it. Provide available data about the toxicology, allergenic reactions and other adverse effects. (II) Can any products of the GMO concentrate on the food chain and become toxic? If so, elaborate.

III. Release in the environment of GMO from the same species (variety, species, lineage, etc) in which the gene has been introduced, which has already been approved by the CTNBio, but obtained by other transformation method or event, or other construction, with different ruling elements, marker gene or reporter gene.

A.CORE QUESTIONS:

A1: What is the species of organism to be released? (when appropriate, give information on the scientific name, strain, variety, pathovar, lineage, and serotype.)

A2: (I) What is the origin of the introduced DNA/RNA? (II) Was the exogenous DNA/RNA originated by an organism that causes diseases in humans, animals, or plants? If so, what are the possible effects?

A3: (I) What is the aim of the proposal? (II) What is the intended use of the GMO?

A4: Describe the size of the experiment, concerning area or volume, and its location (please give address). Include map(s) in adequate scale(s) to allow the analysis of the chosen area under the requirements described in A7.

A5: (I) What are the reasons for the choice of location? (II) Describe in details relevant features of the physical environment, mainly those that may minimize or exacerbate any undesirable effects (e.g.: wind motion, ground water, proximity of water courses, and protected areas, etc.); (III) On what distance is the experiment location from population centers, agriculture activities centers, genetic diversity centers, habitats of biota that may be affected by such release of GMO in the environment?

A6: May the release of GMO cause any harm to the positive functions that the original organism can execute in the environment?

A7: What are the introduced genes and which specific function do they have?

A8: (I) Present the nucleotide sequence of the transgenic variety, and point the present regulator elements (e.g.: promoters, "cis" regulation elements, resistance genes, replication origin, etc.).

A9: (I) How was the exogenous DNA/RNA introduced in the host organism? (II) Which was the vector employed? (III) Which is the scope of hosts for the vector? (IV) Present a restriction map and show the regions specifying functions (e.g.: promoters, "cis" regulation elements, resistance genes, replication origin, etc.).

A10: Present the final construct restriction map (transgenic/ vector). Use at least three restraint enzymes. (II) Is there any evidence that any of these elements is involved in cellular transformation processes? (III) Are there final construct elements that are potentially oncogenic? If so, describe them. (IV) Point out further risks that may exist and the measures to be taken to reduce them.

A11: Make a resume of the stages of the construct obtainment process.

A12: Describe in detail the product of the gene expression and its possible effects to human, animal and environmental health.

A13: (I)On which level may the genetic mutation be characterized? Give information that show the scope of the characterization. (II) Was the introduction chromosomal or cytoplasmic? (III) Which phenotypic, cytogenetic, or molecular markers may provide the identification of the GMO under field conditions?

A14: Does the GMO have any potential genotype instability? Are there any known events of instability in the GMO using the same host?

A15: What are the known modifications that can change the phenotype of the GMO to be released?

A16:(I) Which intrinsic genetic features may the GMO have? In case they exist, what regulates their survival and dissemination in the environment?(II) Which is the stability of these features? (III) Which genetic modifications, if any, were introduced in the GMO to avoid or restraint its capacity to reproduce and transfer exogenous genes to other organisms?

A17: Based on the containment experiments, give information about the growth range (or lifetime of each generation) and survival, aiming the comparison between the GMO and the non-modified organism. Which is the frequency of reversion or loss of the genetic change?

A18: Is there any evidence that the novel trait can be transferred to other organisms found at the site of the planned release and surrounding environment? If so: (I) to what organisms at what frequencies? List the species that have been tested or evaluated for the receptivity and justify the reason for their choice.(II) what transfer mechanisms are involved? (III) what techniques have been employed to demonstrate the receptivity to transfer? (IV) Describe any possible adverse effects of the transfer.

A19: (I) Describe in detail the overall experimental protocol for the release and subsequent monitoring after the test is finished. Include the protocol for control, test, and challenge organisms, if relevant. (II) How many GMO will be released? (III) How many releases are intended and which is their schedule?

A20: What are the arrangements for producing the GMO in quantity, and transporting it to the experiment site? What will the release proceeding be?

A21: What methods will be used to control the quality batch to batch, if a large scale production of GMO is required for the release?

A22: (I) How will the survival of the GMO be monitored? Describe the techniques to be used in monitoring the occurrence of GMO or transferred genetic material beyond the release site, including specificity, sensitivity and reliability of the detection methods. (II) If the release is likely to affect the characteristics or the amount of other species, how will this be monitored?

A23: (I) Which potential hazards or deleterious effects can be postulated and how can these effects be evaluated during the release experiment? (II) Describe structures and procedures employed to reduce the dissemination of the GMO. (III) If the transfer of introduced genetic traits to other organisms is possible (see A18), which methods shall be used to minimize these effect?

A24: If the GMO remains in the environment after the release experiment: (I) How long will it happen and (II) What are the possible consequences? (III) Will any measure be taken to reduce GMO populations or dispose, after the release is completed? (IV) What kind of monitoring will be done after the release is completed?

A25: What measures will be taken to remove the GMO, in case of clear hazard during the execution of the release experiment?

A26: Describe the experiment site supervision proceedings, as well as the safety proceedings that will be carried out by staff. Make a list of the staff in charge of the experiment and describe the training received by the staff members.

A27: (I) Have the same or similar releases been made before, either within or outside the country? If so, give information about other proposals, including the positive or adverse effects. (II) Has another country rejected an application for the planned release of this GMO? If so, for what reason? (III) What factors may suggest greater or less risks concerning the presented proposal?

A28: Was the GMO imported, or was it made in Brazil? In case it is imported, attach documents of license, given by the competent inspection authority, and of quarantine services, when applicable.

A29: Is there any aspect related to the GMO that could constitute a hazard and was not considered in this proposal yet? If so, please explain it.

IMPORTANT: Give any other information that can subside the CTNBio in the analysis of the presented proposal.

B. PLANTS

B1: what kind of pleiotropic effects can be observed in the expression of a modified gene in the GMO (e.g. : reduced fertility, increased disease incidence, loss of productivity, and grain/fruit shedding)?

B2: (I) Does any sexually compatible plant live near the release site? If so, give details and quantify the chances for cross-pollination. (II) Provide quantitative data on about cross-pollination between the plant and its wild parents occurring in the release area. (III) If cross-pollination occurs, will the resultant plants or its progeny be able to survive and compete well? If so, list them.

B3: (I) Will the plants in this release be allowed to set seeds? If not, is any subsequent release planned? (II) If plants are allowed to set seed, does the mature seed normally remain contained within an ear, capsule, or pod so that practically all of the seed can readily be harvested, or is the seed shed soon after it matures?(III) Can the seed be dispersed by natural means? If so, describe them. (IV) Are the seeds capable of surviving in a dormant condition for a long time? If so, how long?

B4: Does the novel characteristic change the capacity of the plant to add substances or subtract substances from the soil (e.g. nitrogen, toxic compounds)? If so, describe the change.

B5: (I) Is there any likelihood that the introduced gene could cause an increase in toxicity of the plant for animals and humans? If so, provide available data. (II) Could any products of the GMO concentrate in the natural or human food chain to levels that become toxic? If so, explain. (III) Is there any known case of change in the plant biodegradability? If so, how?

B6: What secondary ecological effects might result from the release of the GMO (e.g. effect on endangered native species, resistance of insect populations to an insecticide, reduction or increases in the numbers of prey and parasites, etc.)?

B7:Does the construction involves resistance to a chemical agent (other than selective agents, such as antibiotics, used in strain construction)? (I) Provide data about the degradability, selectivity, and toxicity of the chemical concerned. (II) What is the biological activity of the chemical? (III) How is the chemical applied and used?

If these GMO is to be consumed as food, answer the questions in section C also.

C.ORGANISMS TO BE CONSUMED AS FOOD

Note: These organisms require authorization from the competent federal regulation department to be consumed.

C1: (I) Does the GMO produce any new metabolites likely to cause any adverse effects to the consumer (humans or animals)? If so, describe it. Provide available data about the toxicology, allergenic reactions and other adverse effects. (II) Can any products of the GMO concentrate on the food chain and become toxic? If so, elaborate.

C2: Will the nutritional quality of the food be changed by the genetic modification? If so, how?

C3: Is the GMO able to transfer transgenic strains to the consumer (genome and/or microbial biota)? If so, how frequently does it occur?

APPENDIX 1A ? PLANNED RELEASE ASSESSMENT

MODEL FOR THE PROPOSAL PRESENTATION

The proposal shall be typed in the typing machine or computer, and it shall contain the CIBio?s analysis. The Internal Commission shall sent its analysis to the CTNBio together with any other relevant supplementary information.

Public Information Sheet

A completed public information sheet ( see Appendix 1B) shall be attached to the proposal for press release.

Check the norms for planned release in the environment of genetically modified organisms (GMO) that apply to your proposal and provide the information bellow. If necessary contact the CTNBio?s Executive Secretary for further instructions.

1. Reference numbers (identification numbers of previous proposals, registered by the CTNBio and CIBio, from which this proposal has been developed).

2. Project title

3. Name of the sponsoring institution(s)

4. Address or contact for supervising CIBio

5. Name, function, and address of the Legal Liable or Chief Researcher.

6. Proposed location of the experiment or field test.

7. Name of the municipality in which the experiment or field test is planned.

8. Scheduled beginning date for the experiment

9. Scheduled conclusion date for the experiment

10. Specific details about the size of the experiment (area and number of organisms involved)

11. Schedule and dates of future experiments or tests.

12. Government authorities consulted about this proposal. Give names of agencies and officials contacted.

13. List of the obtained licenses (enclose copies)

14. CIBio statement: include comments about the Chief Researcher?s capability to manage the work, the adequacy of the project design, site selection and emergency safety procedures plan.

15. CIBio request for advice: specific points where the CIBio seeks the CTNBio?s advice.

16. Will a press release on the project be distributed? If yes, when and whom?

17. Provide details about any measure taken to inform or consult the public (e.g. the local community) about the project

18. Declaration: the information provided here is, to the best of my knowledge, complete, accurate and truthful (Name and signature of the Legal Liable and date)

19. Endorsement of the CIBio : the CIBio has assessed and endorsed this proposal (name and signature of the president of the CIBio and date)

20. Name and signature of the Legal Liable, and date.

At the conclusion of the experiment or field trial, the researcher shall submit a complete report to the CIBio. The CIBio shall submit at least a resume of such report to the CTNBio (see appendix 1C).

Confidential information must be clearly indicated. An additional copy of the proposal without such information shall also be submitted, having the following message clearly highlighted : «Confidential Information Excluded». The proponents shall also provide a justification to explain how the publishing of confidential information might be negative to their interests.

APPENDIX 1B ? PUBLIC INFORMATION SHEET

The information provided by this sheet is destined for press release. A clear language should be used.

Name of the organization:__________________________

Address of the organization:________________________

Name of the contact person:________________________

Contact phone number:____________________________

Fax:___________________________________________

E-mail: ________________________________________

World Wide Web(www): __________________________

Organism to be released:___________________________

Location and size of planned release:__________________

Proposal of planned release:_________________________

Brief summary about the GMO to be released. The use of technical terms should be minimized.

Agencies consulted before the release, if applicable (list approvals obtained):______

APPENDIX 1C ? INTERNAL BIOSAFETY COMMISSION

REPORT ON PLANNED RELEASE AFTER ITS COMPLETION

Name of the chairman and address of the supervising Internal Biosafety Commission_______

CTNBio process review number:________________

Project title__________________

Project Chief Researcher_________________

Legal liable____________________

Agency or agencies approval received (dates) _______________

Location of planned release ___________

Commencement date_________

Completion date ___________

Summary of report. Include answers to the following questions:

• What monitoring procedures were undertaken?

• Were the procedures undertaken in accordance with the protocol submitted for CTNBio review? Describe.

• Were the aims of the planned release achieved? Describe?

• Were there any unexpected effects? If there was any adverse effect, a report should be made immediately to the agency concerned and to the CTNBio at the time of the occurrence and reiterated at the time of writing this report.

• What is the number of genetically modified organisms surviving at the release site? What will be the fate of these organisms?

• Will the project be continued to a further stage? If so, provide details.

Signature of the chairman of the CIBio:_____

Date:______

The National Technical Biosafety Committee ? CTNBio, using its legal attributions, decides:

Art. 1st The importing of genetically modified microorganisms for use in works under containment shall obey the norms stated in the Annex of the present Institutional Act.

Art 2nd The accomplishment of this Institutional Act does not exempt the proponent from the obedience to the specific legislation into force about the introduction of microorganisms in the country, whose competence belongs to the Ministries of Agriculture and Supply, Health, and Environment (art. 7th Law. n. 8974/95)

Art. 3rd The present Institutional Act shall take effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the CTNBio

ANNEX

NORMS FOR THE IMPORTING OF GENETICALLY MODIFIED MICROORGANISMS DESTINED FOR WORKS UNDER CONTAINMENT

SCOPE

These norms shall be applied to the importing of microorganisms (including bacteria, fungi, viruses, chlamydial and rickettsial agents, mycoplasma, cellular lineages, parasites and similar organisms, genetically modified for usage under containment regime.

Genetically modified plants and animals are cited in specific legislation.

LICENSE FOR IMPORTING

The importing must always be carried out by an entity with CQB (Certificate of Quality in Biosafety ? Law n. 8974/95).

The importing shall be done only for use under containment by the institution that carried out the importing.

The GMO transference from the importer institution to another one shall occur in accordance with the norms for transportation of GMO (Institutional Act n. 4, published in the DOU n. 247, of December 20th 1996, section I, pp. 27820-27821).

The importing license depends on GMO classification. The importing process shall be evaluated by the CIBio of the institution responsible for the importing, according to the norms for work under containment with genetically modified organisms (Law n. 8974/95 and Institutional Act n. 7, published in the DOU n. 133, of June 9th 1997, section I, pp. 11827-11833).

If the CIBio classifies the GMO as belonging to group I, the license shall be sent directly by the CIBio. The CIBio shall include notifications of all the imports done in its annual report to be sent to the CTNBio.

In case of importing of Group II microorganisms, the CIBio of the importer institution shall submit the request to the CTNBio, using the formulary described in the Appendix of this Institutional Act.

In case of doubt about the classification of the microorganism to be imported (Group I or II), the institution shall query the CTNBio through its CIBio. The Executive Secretary shall inform the proponent about the CTNBio?s final statement.

The caution measures with transportation and emergency procedures in case of escape or accident during the importing shall be previously informed to the CIBio by the responsible for the importing request.

Used packs shall obey the norms for transportation of genetically modified organisms (Law n. 8974/95 and Institutional Act n. 4, published in the DOU n. 247, of December 20th 1996, section I, pp. 27820-27821) or the specific legislation when relevant

APPENDIX

REQUEST OF AUTHORIZATION FOR IMPORTING OF GENETICALLY MODIFIED ORGANISM DESTINED FOR WORK UNDER CONTAINMENT

Dear Sir Chairman of the CTNBio/CIBio

1. Name of the institution/work unit?s Legal Liable or president of the CIBio.

2. Institution and address CQB n.:___Fax:___ Phone number:__ E-mail:__________

3. Name of the Chief Researcher.

   Applies for authorization, conceded by the CTNBio/CIBio, for importing the GMO described below.

4. Short description of the GMO, in accordance with the Annex I of Law n. 8,974, of 01/05/95, and with Appendix 2 of the Norms for Work Under Containment with GMO.

5. Classify the Biosafety Level of the Laboratory or Work Unit where the work with the GMO will be executed.

6. Specify maximum GMO volume and concentration to be used in this work.

7. Objective (research, production, development of methodology, teaching, etc.).

8. References about works with the GMO.

9. Specify whether the work under containment aims future releases in the environment.

10. List the equipment to be used during the work under containment with GMO

11. Short description of work procedures to be employed during the experiments and of the planned Biosafety Level ?BL

12. Short description about cleaning, disinfecting, and disposal of material/rests.

13. Critic analysis on foreseeable risks related to GMO.

14. Curricula Vitarum of the involved staff

15. Date and signature.

(*) Published again due to the existence of fails in the original publication, in the DOU n. 59-E, of 03/27/98, Section I, p. 3.

The National Technical Biosafety Committee ? CTNBio, using its legal attributions, decides:

Art. 1st The Work under Containment with Genetically Modified Animals ? GMAn shall obey the norms stated in the Annex of the present Institutional Act.

Art. 2nd The present Institutional Act shall take effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the CTNBio

ANNEX

NORMS FOR WORK UNDER CONTAINMENT WITH GENETICALLY MODIFIED ANIMALS

SCOPE

These norms are applicable for works under containment with genetically modified animals (GMAn). Genetically modified microorganisms and plants, as well as genetic manipulation of human beings, shall be treated separately by specific regulation.

The use of animals in experiments involving the inoculation of nucleic acid (e.g.: DNA vaccines or genetic therapy) shall be treated by specific regulation.

DEFINITIONS

In these norms, except if it is diversely indicated, certain terms will be defined as follows:

GMAn: genetically modified animal is any that has nucleic acid intentionally introduced in the genome of its reproductive or somatic cells.

CQB: Certificate of Quality in Biosafety

CIBio: Internal Biosafety Commission

CTNBio: National Technical Biosafety Committee

BL ? A: Containment level required to allow the work with the genetically modified animal

Work under containment: Activity with the genetically modified animal that does not allow escape or release to the environment.

Biosafety Levels: The GMAn will classified as belonging to biosafety levels 1, 2, 3, or 4.

Risk Group: Group I GMAn are the GMAn belonging to biosafety level 1; Group II GMAn belong to biosafety levels 2, 3, and 4.

APPLICATION

These norms are applicable to activities of research, production, technological development, teaching, and quality control that employ genetically modified animals, under containment regime, carried out within the Brazilian territory.

These norms do not apply for the planned release of genetically modified animals in the environment, which is ruled by a specific norm (Institutional Act n. 3, published in the DOU n.221, of November 13th 1996, Section I, pp. 23691-23694).

Any doubts about the application of these norms shall be solved by the CIBio, which, depending on the case, will ask for CTNBio?s advice.

Concerning any animal group, the institution shall request to the CTNBio the extension of its CQB to their vivariums. If it is a BL-A1 for work under containment with Group I GMAn, the CIBio itself can authorize the commencement of the operation in the vivarium and send to the CTNBio its plan and norms in the annual report. Concerning BL-A2, BL-A3, and BL-A4, for work under containment with Group II GMAn, the CTNBio will make a technical visit for authorization.

PROCEDURES

Responsibilities to be fulfilled:

The entity Legal Liable and the CIBio are in charge of assuring the faithful fulfillment of these norms, concerning the planned release of a GMAn in the environment.

Institutions applying for work with GMAn from any group shall have in its CIBio, a researcher with proved experience in handling genetically modified animals.

The Chief Researcher shall assure the fulfillment of these norms, in accordance with the CQB and under the supervision of the CIBio. He shall also assure that all the people involved in the work are aware about the risks involved and properly directed to obey these norms.

The CIBio and its members are responsible for informing the CTNBio about any eventual non-accomplishment of these norms.

ACCIDENTAL RELEASE OF GENETICALLY MODIFIED ANIMALS IN THE ENVIRONMENT

All the containment activities concerning genetically modified animals shall be planned and executed according to these norms, in order to avoid any accidental release of a GMO.

Every genetically modified animal shall have a genetic marker capable to identify it out of a population of animals from the same species during a DNA trial. Whenever it is possible, genetically modified animals shall have permanent marks to provide their identification in a macroscopic inspection.

However, in case of any accidental release of a genetically modified animal, such accident must be immediately communicated to the CIBio and to the CTNBio, enclosing a report about the corrective measures already taken and the names of the notified people or authorities.

The communication of such occurrence to the CTNBio does not exempt the proponent from any other obligation, according to the ordinary law and/or statutes, of informing the competent authorities or people who can be affected.

PRESENTATION OF PROPOSALS

For any activity involving genetically modified animals classified as Group I or Group II GMAn (see definitions bellow), the Chief Researcher shall send to the CIBio detailed information following the Application Model contained in the Appendix 1 of these norm. Concerning Group I GMAn, the authorization shall be given by the CIBio, which, in its turn, shall send information about these activities in its annual report to the CTNBio. If regarded as necessary or appropriate, the CIBio can ask for a conclusive statement by the CTNBio for works involving Group I GMAn.

For any activity involving Group II GMO, the Chief Researcher shall submit a written proposal to the CTNBio, through the mediation of the CIBio, following the Application Model contained in the Appendix of this norm. The Executive Secretary of the CTNBio shall inform the CIBio about the CTNBio?s statement.

A new proposal shall be presented for the CTNBio?s assessment whenever the employed organism or the experimental conditions are changed.

Works involving Group II GMAn can be developed only after the proposal assessment and authorization by the CTNBio.

The Executive Secretary or the chairman of the CTNBio will be available to clear doubts about any issue related to these norms.

GMAn CLASSIFICATION CONCERNING BIOSAFETY LEVEL

Biosafety Level 1 GMAn: all genetically modified animals that, after genetic manipulation, do not have changed their features concerning transmissibility of diseases to other animal or plant species, including humans, or do not present selective advantages when released in the environment. Animals that, after genetic manipulation, contain a genome, even a complete one, of viruses that do not cause any transmissible infectious disease, will fall in Biosafety Level 1.

Biosafety Level 2 GMAn: all genetically modified animals that, after genetic manipulation, express substances known as toxic for animals (including humans) or plants, provided that, for the action such toxins, there are effective ways of prophylaxis and treatment. Animals that, after genetic manipulation, carry more than 75% of genome of viruses handled in Biosafety Level 1 (Institutional Act n. 7, published in the DOU n. 133, of June 9th 1997, Section 3, pp. 11,827 ? 11,833)capable to provoke transmissible infectious diseases. Those animals that, after genetic manipulation, may be susceptible to infections that normally do not occur in the equivalent species (break of barrier between species), are also included in Biosafety Level 2.

Biosafety Level 3 GMAn: all genetically modified animals that, after genetic manipulation, carry more than 75% of genome of viruses handled in Biosafety Levels 2 and 3(Institutional Act n. 7, published in the DOU n. 133, of June 9th 1997, Section 3, pp. 11,827 ? 11,833). Those animals that, after genetic manipulation, are regarded as more able to survive in the environment than the equivalent, are also included in Biosafety Level 3.

Biosafety Level 4 GMAn: all genetically modified animals that, after genetic manipulation, carry more than 75% of genome of viruses handled in Biosafety Level 4 (Institutional Act n. 7, published in the DOU n. 133, of June 9th 1997, Section 3, pp. 11,.827 ? 11,833). Those animals that, after genetic manipulation, express substances known as toxic for animals (including humans) and plants having no effective way of prophylaxis and treatment, are also included in Biosafety Level 4.

GMAn CLASSIFICATION CONCERNING RISK GROUP

BIOSAFETY LEVEL FOR WORK WITH GENETICALLY MODIFIED ANIMALS (BL-A)

There are four biosafety levels for work with genetically modified animals. The safety level of the vivarium and the Experiment Rooms shall always be equal or higher than the safety level of the genetically modified animal to be used.

The functioning license of the BL-A1 vivariums and Experiment Rooms shall be given by the CIBio of the institution involved and informed to the CTNBio in its annual report. The CTNBio shall concede the functioning license of the BL-A2, BL-A3, and BL-A4 vivariums and Experiment Rooms, after requested by the CIBio of the institution involved. For each request, the CTNBio shall design a member to give technical statement about the adequacy of the laws into force concerning the GMAn biosafety level. This member can, if necessary, suggest procedures not previewed in this Institutional Act. For all biosafety levels the vivariums shall have, at least, the following features:

The main door shall be always locked. The access to the vivarium shall be restraint to authorized personnel, as determined by the institution?s CIBio.

The design of the vivarium shall make cleaning and disinfecting easier, and avoid the accumulation of dust.

Animals from different species that are not involved in the same experiment shall be located in physically separate areas.

All ventilation areas shall have physical barriers to avoid the entry of insects and other animals.

BL-A1 VIVARIUM AND EXPERIMENT ROOM

Good for works with Biosafety Level 1 genetically modified animals

They shall have the basic features described above

Every material originating from genetically modified animals shall be disposed in order to prevent its use as food for other animals, unless this is the objective of the experiment, or the CIBio, CTNBio, or other competent institution specifically authorizes it, if applicable.

All manipulation shall be carried out in other to avoid the accidental release of the genetically modified animal in the environment.

BL-A2 VIVARIUM AND EXPERIMENT ROOM

Good for works with Biosafety Levels 1 and 2 genetically modified animals.

Besides the requirements for BL-A1, these described bellow shall also be fulfilled.

The president of the CIBio shall state norms to restraint the access to the vivarium only to personnel authorized, qualified, and aware about the risks inherent to the experiment. When appropriate, these people shall be vaccinated against infectious agents involved in the experiment.

An ante-room between the free transit area and the area where the animals are lodged is necessary. All existent ways of ventilation shall have physical barriers to block the passage of insects and other animals.

Infected material shall be properly accommodated, in accordance with good laboratory procedures for disinfecting, which can be done outside the vivarium.

Needles, syringes or any other instrument likely to cause continuity solution of the skin shall be put into appropriate recipients, resistant until the moment of disinfecting

The use of mask, cap, gloves and feet protectors is obligatory. These materials shall always be disinfected after use.

BL-A3 VIVARIUM

Good for works with Biosafety Levels 1, 2 and 3 genetically modified animals.

Besides the requirements for BL-A2, these described bellow shall also be fulfilled.

The vivarium shall be composed by, at least, four distinct areas: ante-room, materials room, animals? room, and experiment room.

The air flow shall always occur from the ante-room to the materials room, the animals room and finally to the experiment room. Inflated air shall be sterilized. The air exit shall also contain sterilizing filters to purify the air that comes from the animals? room. The animals and experiment rooms shall, necessarily, have negative air pressure in contrast with the anterior room and throw the air outside after filtering it.

The vivarium shall have an automatic atmosphere pressure control system, to detect alterations in the atmospheric pressure and activate an alarm to accuse failure.

Animals shall always be lodged in micro-isolators system (cages equipped with microorganisms block filter).

Animals must never leave the appropriate rooms.

No biologic material capable of spreading the infectious agent can leave the vivarium before the infectious agent viability is eliminated (e.g. the extraction of nucleic acids from organs or cells shall be done inside the vivarium).

All liquid effluent from BL-A3 vivarium (sinks, drinking fountains, drains, autoclaves, etc.) shall be disinfected before released in the sewer system, through treatment in containment boxes. This procedure shall be evaluated by the CIBio and approved by the CTNBio.

The ante-room and the materials room shall have sink and shower, with taps that can be activated without the use of hands. No sinks, showers or drains can exist in the animals? room or in the experiment room, to reduce the possibility of escape of infected material.

The CIBio shall determine safety trials to allow the transportation of any biological material coming from animals to lower biosafety level dependencies.

It is necessary to provide ways to disinfect materials inside the vivarium. It shall occur by the use of double-door autoclave, one opening to the materials room and other opening to the animals? room or to the experiment room, if applicable. There shall be an incinerator inside the animals? room or the experiment room.

Animals shall be incinerated before disposal.

All surfaces shall be disinfected daily, and after the conclusion of every manipulation. Independent manipulations in a same day require different disinfecting processes.

No biological material likely to contain viable forms of the infectious agent can leave the vivarium before disinfecting.

It is necessary that personnel use appropriate clothes (aprons, caps, masks, pumps and shoe protectors, gloves, etc.), to be changed in the ante-room. This does not correspond simply to the use of apron on common clothes. The entry or exit of personnel without changing clothes is forbidden. The clothes used in the vivarium shall be autoclaved inside it before washing or disposal.

The CIBio shall state an emergency procedure for laboratory accidents, according to the risks represented by the agents to which users can have been exposed. Within each room there shall be an alarm system able to activate necessary measures, for the victim to leave the vivarium only after following disinfecting procedures, avoiding the increase of the accident seriousness.

The collection of users reference serum samples shall be required before starting works in the BL-A3 environment. The CIBio shall propose a users surveillance and monitoring system in order to detect possible infections by agents in use.

BL-A4 VIVARIUM

Good for works with Biosafety Levels 1, 2 and 3 genetically modified animals.

Besides the requirements for BL-A2, these described bellow shall also be fulfilled.

The building shall have an isolated construction, without any link to other ones. The area where this building is located must be under 24 hour?s surveillance.

The access to this area is totally restraint to personnel with proved experience, attested by the CIBio and approved by the CTNBio.

There shall be uninterrupted patrol, under the institution?s responsibility, in order to control the access not only to the vivarium, but also to any area giving access to it. Only people authorized by the CIBio can transit in the vivarium access area. The presence of 24 hours surveillance at the vivarium entry door is necessary. Besides the magnetic card or digital codes access system, the watchman shall also ask for the institutional identification of each user. All this information shall be registered and filed during a period equivalent to 5 times the greater incubation period out of those from the different diseases likely to be provoked by the infectious agents to which users are exposed.

The access to the vivarium shall be controlled by a system that allows the identification of each user, as well as the user?s operation time inside the vivarium. All doors shall be always kept locked and its opening shall be controlled by the use of magnetic cards or digital codes.

The vivarium shall have, at least, 6 distinct areas:

1) Ante-room with negative air pressure relating to the circulation area, and capability to sterilize the place.

2. Dressing room with three divisions, with a shower in the central one. In the first division (next to the ante-room), it shall have individual closets to put the clothes to be used by personnel. In the shower room, there shall be shower, sink, and a mechanism to sterilize the place. Sinks and showers shall be activated by a system without the use of hands. In the third division there shall be bags to put the clothes already used, which shall be autoclaved before disposal.

3. Materials room equipped with sink and mechanism to sterilize the place. In the materials room there shall be an autoclave for each animal room, Experiment room and Necropsy Room of the vivarium, with two doors, one opening to the materials room, other to the Animals, Experiment, or Necropsy room.

4. Animals room with sterilization mechanism. The passage between the Materials Room and the Animals Room shall be done by automatic opening double door, to avoid the use of hands.

5. Experiment Room with sterilization mechanism, communicating with the Animals Room by through an automatic double door.

6. Necropsy Room equipped with incinerator.

No sinks, showers, or drains can exist in the experiment room, to avoid possible escapes of infected material.

All rooms shall have negative air pressure in contrast with the anterior room, with an air flow system to prevent that the air from a room containing infected material flow back to clean areas. The vivarium shall have an automatic atmosphere pressure control system, to detect alterations in the atmospheric pressure and activate an alarm and lock all vivarium doors.

The air exhaustion system used shall have double filtering barrier, then if the first barrier fails, the second one will be enough to release sterilized air.

A firm with proved experience shall attest the air system.

The water feeding system shall have mechanisms to prevent the opposite water flow. All sewer system of the construction shall be independent, with disinfecting system before disposal.

When entering the vivarium the user shall leave the ante-room and leave his/her clothes in the first division of the dressing room to dress appropriate clothes (pants, shirts, jackets, gloves, caps, shoes and shoe protectors, etc.) that are sterilized. When leaving the vivarium the user shall leave these clothes in the room before the shower room, in a proper recipient for disinfecting. All user shall necessarily take a shower before every time he/she leaves the vivarium.

In the areas where animals are present, or in the experiment and necropsy rooms, there shall be 100% containment of the air circulating in the BL-A4 environment, concerning users. This can be obtained by «lifeline system» or by the use of total on line containment system. Thus, the space between the doors separating the materials room and the rooms of BL-A4 environment shall have space for changing clothes, in case of «lifeline» use. In case of on line containment, the same clothes can be used.

The entry of any material in the Animals Room shall be done by double door autoclave, or it shall be sterilized before its entry.

The watchman in charge of the patrol at the vivarium access area shall be able to activate the emergency mechanism, in case of accident, that will be informed by the user through the alarm system.

Animals shall be incinerated before disposal.

No biological material able to spread infectious agent can leave the vivarium. Any experiment using biologic material shall be done inside the experiment room.

IMPORTANT

The CTNBio can, at any moment, design a Technical Commission to judge if the norms stated here are adequate for work with genetically modified animals that can present particular hazards, or those unpredicted by present scientific knowledge.

APPENDIX

REQUEST OF AUTHORIZATION FOR IMPORTING OF GENETICALLY MODIFIED ANIMALS (GMAn) DESTINED FOR WORK UNDER CONTAINMENT REGIME

Dear Chairman of the CTNBio/CIBio

1- Name of the institution/work unit?s Legal Liable or president of the CIBio.

2. Institution and address

Fax/ Phone number/ E-mail

3- CQB number.

1. Name of the Chief Researcher.

Requests license for importing of genetically modified animals (GMAn), executing the Institutional Act n. 12/98.

5- Inform the animal species to be genetically modified.

6. Inform the genetic modification procedure to be executed.

7. Inform if there is the intent of forming a colony with the GMAn.

8. Inform the characteristics of the genetic material to be introduced.

9. Describe the biological activities that will be acquired/lost by the GMAn.

10. Define the possibilities of changes in the GMAn pathogenic features.

11. Define the possibilities of acquisition of any selective advantage by the GMAn in comparison with non-modified correspondents, considering a possible escape to the environment.

12. Define the risks of transmission of diseases, including humans, animals and plants.

13. Inform if the GMAn will express any protein with known toxic potential. If so, inform if there is a way of treatment or not.

14. Try to improve the CTNBio?s statement, giving information about other relevant aspects not mentioned in this request form, for a clear statement about the GMAn biosafety level.

15. Include scientific literature, which may enforce the CTNBio?s statement.

16. Date

17. Signature by the Chief Researcher and the Chairman of the CIBio.

The National Technical Biosafety Committee ? CTNBio, using its legal attributions, decides:

Art. 1st The importing of genetically modified animals, destined for works under containment, shall obey the norms stated in the Annex of the present Institutional Act.

Art 2nd The accomplishment of this Institutional Act does not exempt the proponent from the obedience to the specific legislation into force about the introduction of animals in the country, whose competence belongs to the Ministries of Agriculture and Supply, Health, and Environment (art. 7th Law. n. 8974/95)

Art. 3rd The present Institutional Act shall take effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the CTNBio

ANNEX

NORMS FOR THE IMPORTING OF GENETICALLY MODIFIED ANIMALS (GMAn) DESTINED TO WORK UNDER CONTAINMENT REGIME

SCOPE

These norms shall be applied to the importing of genetically modified animals (GMAn). Genetically modified microorganisms (including bacteria, fungi, viruses, chlamydial and rickettsial agents, and mycoplasma), cellular lineages, parasites and similar organisms, are cited in specific legislation.

The obedience of these norms does not exempt the importer from the fulfillment of the legal protocols stated by law.

IMPORTING LICENSE

The importing must always be carried out by an entity with CQB - Certificate of Quality in Biosafety (Law n. 8974/95, Institutional Act n. 1, published in the Federal Official Gazette ? DOU ? n. 174, of September 6th 1996, Section I, pp. 17,694 ? 17696.)extensive also to its animal confinement cage.

The importing shall be done only for use under containment by the institution that carried out the importing. The GMAn transference from the importer institution to another one shall occur in accordance with the norms for transportation of GMO (Institutional Act n. 4, published in the DOU n. 247, of December 20th 1996, section I, pp. 27820-27821).

The CIBio is responsible for the classification of the genetically modified animal as belonging to Group I or Group II. If the CIBio classifies the animal as belonging to group I (GMAn of biosafety level 1), the license shall be sent directly by the CIBio.

The CIBio shall include notifications of all the imports done in its annual report to be sent to the CTNBio.

In case of importing of Group II animals(GMAn of biosafety levels 2, 3, or 4), the license shall be sent by the CTNBio, through written request of the importer institution, using the formulary described in the Appendix of this Institutional Act.

The caution measures with transportation and emergency procedures in case of escape or accident during the importing shall be previously informed to the CIBio by the responsible for the importing request.

The packs used for transportation shall obey the norms for transportation of genetically modified organisms (Law n. 8974/95 and Institutional Act n. 4, published in the DOU n. 247, of December 20th 1996, section I, pp. 27820-27821) or the specific legislation when relevant

APPENDIX

REQUEST OF AUTHORIZATION FOR IMPORTING OF GENETICALLY MODIFIED ANIMALS (GMAn) DESTINED FOR WORK UNDER CONTAINMENT REGIME

Dear Chairman of the CTNBio/CIBio

1- Name of the institution/work unit?s Legal Liable or president of the CIBio.

2. Institution and address

   Fax/ Phone number/ E-mail

3. CQB number.

4. Name of the Chief Researcher.

Requests license for importing of genetically modified animals (GMAn) for work under containment regime, executing the Institutional Act n. 13. Please answer objectively the questions below:

5- Inform the animal species to be genetically modified.

6- Inform the genetic modification procedure to be executed.

7. Inform if there is the intent of forming a colony with the GMAn.

8. Inform the characteristics of the genetic material to be introduced.

9. Describe the biological activities that will be acquired/lost by the GMAn.

10. Define the possibilities of changes in the GMAn pathogenic features.

11. Define the possibilities of acquisition of any selective advantage by the GMAn in comparison with non-modified correspondents, considering a possible escape to the environment.

12. Define the risks of transmission of diseases, including humans, animals and plants.

13. Inform if the GMAn will express any protein with known toxic potential. If so, inform if there is a way of treatment or not.

14. Try to improve the CTNBio?s statement, giving information about other relevant aspects not mentioned in this request form, for a clear statement about the GMAn biosafety level.

15. Include scientific literature, which may enforce the CTNBio?s statement.

16. Date

17. Signature by the Chief Researcher and the Chairman of the CIBio.

The National Technical Biosafety Committee ? CTNBio, using its legal attributions, decides:

Art. 1st Concerning the request for the Certificate of Quality in Biosafety ? CQB, regulated by the Institutional Act n. 1, of September 6th 1996 of the CTNBio, if the presentation of further documents is necessary, the interested institution shall be notified to provide them within a period of ninety days from the date when the notification was received, under penalty of having its request filed.

Art. 2nd The present Institutional Act shall take effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the CTNBio

The National Technical Biosafety Committee ? CTNBio, using its legal attributions, decides:

Art. 1st The research and technological development works employing non-modified animals where Genetically Modified Organisms ? GMO are manipulated, under containment regime, shall obey the norms stated in the Annex of the present Institutional Act.

Art. 2nd The present Institutional Act shall take effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the CTNBio

ANNEX

NORMS FOR WORK UNDER CONTAINMENT REGIME WITH NON MODIFIED ANIMALS WHERE GENETICALLY MODIFIED ORGANISMS ? GMO ARE MANIPULATED

SCOPE

These norms are applicable for the handling under containment regime of Group I and II GMO, in non-modified animals.

Microorganisms, plants, genetically modified animals, as well as the genetic manipulation in human beings are treated separately by specific rules.

DEFINITIONS

In these norms, except if it is diversely indicated, certain terms will be defined as follows:

GMO: genetically modified organism(s).

CQB: Certificate of Quality in Biosafety

CIBio: Internal Biosafety Commission

CTNBio: National Technical Biosafety Committee

Work under containment: Activity with the genetically modified animal, which does not allow escape or release to the environment.

BL ? A: Containment level required to allow the work with the genetically modified animals. Defined by the annex of Institutional Act n. 12, published in the Federal Official Gazette ? DOU ? n. 100-E, of May 28th 1998, Section I, pp. 10 ? 12.

APPLICATION OF THE NORMS

These norms are applicable to research and technological development works employing non- modified animals where GMO are manipulated, under containment regime, within the Brazilian territory.

The planned release in the environment of non-modified animals where GMO are manipulated is forbidden. Any doubt about the applicability of this norm shall be cleared by the CIBio that, depending on the case, shall ask the CTNBio for information.

PROCEDURES

Whichever it may be the GMO Group to be manipulated in non-modified animals, the institution shall request to the CTNBio the extension of its CQB to confinement cages experiment rooms. If the works involve Group I GMO, the CIBio itself can allow the functioning of the confinement cage and the experiment room and send to the CTNBio a plant of the installations and their functioning rules in its annual report.

In case of work under containment regime with non-modified animals where Group II GMO are manipulated, the CTNBio shall carry out a technical inspection to approve the extension of the CQB. The norms for work under containment with GMO are described in the Institutional Act n. 7, published in the DOU n. 133, of June 9th 1997, Section I, pp. 11827 ?11833.

The vivariums and experiment rooms destined to such activity must have a biosafety level ? BL ?A equal or superior to that of the GMO to be manipulated.

Physic and working features of vivariums and experiment rooms for containment manipulation work with GMO in non-modified animals shall follow the rules described by the Institutional Act n. 12/98.

The Legal Liable and the CIBio are in charge of assuring the faithful fulfillment of these norms, concerning the containment work with Group I and II GMO in non-modified animals.

Institutions that wish to work with Group I and II GMO shall have in its CIBio a researcher with proved experience in manipulation of genetically modified animals. The Chief Researcher shall assure the fulfillment of these rules. He shall assure that all the professionals involved in this activity are aware about the risks involved and adequately trained for the fulfillment of these norms. The CIBio and its members are in charge of informing the CTNBio if these rules, in any eventuality, are not followed.

IMPORTANT NOTES

The CTNBio may, at any moment, entitle a technical commission to determine if the norms here stated satisfy the biosafety criteria for work under containment with non-modified animals where GMO are manipulated, and if the procedures adopted may present or not any of the specific hazards known at present.

The National Technical Biosafety Committee ? CTNBio, using its legal attributions, decides:

Art. 1st Concerning requests for the planned release in the environment of genetically modified organisms ? GMO, regulated by the CTNBio?s Institutional Act n. 3, of November 13th 1996, and for planned release in the environment of Genetically Modified Plants- GMP, which had been previously approved by the CTNBio, regulated by the CTNBio?s Institutional Act n. 10, of February 20th 1998, the elaboration and presentation of required maps and drafts shall obey the norms established in the Annex of the present Institutional Act.

Art. 2nd The present Institutional Act shall take effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the CTNBio

ANNEX

RULES FOR THE ELABORATION AND PRESENTATION OF MAPS AND DRAFTS REQUESTED FOR THE PLANNED RELEASE IN THE ENVIRONMENT OF GENETICALLY MODIFIED ORGANISMS ? GMO

SCOPE

These norms are applicable for the elaboration and presentation of maps and drafts requested for the planned release in the environment of Genetically Modified Organisms ? GMO and Genetically Modified Plants ? GMP, which has been previously approved by the CTNBio.

PROCEDURES

In the maps and drafts attached to the requests for planned release in the environment of Genetically Modified Organisms ? GMO, and Genetically Modified Plants ? GMP, which have been already approved by the CTNBio previously, the following information shall be included:

1. Name of the State and of the Municipality;

2. Name of the property and of its owner;

3. Complete address and phone and/or fax number;

4. Name of the main road to access the property, reference to the closest city, reference km mark to enter the farm and/or secondary road, and indication of geographic points (e.g.: forest reserves, woods, rivers, streams, hills, etc.);

5. Property identification at its entry;

6. Details about the access to the experimental area within the property;

7. Precise identification of the experiment within the experimental area;

8. Description of the experiment?s surrounding area;

9. Legend and Scale;

10. Whenever it is possible, locate the experiments by GPS - "Global Position Systems".

The National Technical Biosafety Committee ? CTNBio, using its legal attributions, decides:

Art. 1st The activities of importing, commerce, transportation, storage, handling, consumption, release, and disposal of products derived from Genetically Modified Organisms ? GMO shall obey the norms stated in the Annex of the present Institutional Act.

Art. 2nd The dispositions of this Institutional Act shall be applied for the aims disposed in the caput , and in clause V, article 7th of the Law n. 8974/95, and in the clause XII, article 2nd of the Decree n. 1752/95.

Art. 3rd The present Institutional Act shall take effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the CTNBio

ANNEX

Norms ruling the activities of importing, commerce, transportation, storage, handling, consumption, release and disposal of products derived form GMO.

These norms shall be applied to the activities of importing, commerce, transportation, storage, handling, consumption, release and disposal of products derived from GMO.

Products derived from GMO: Products obtained from a genetically modified organism, which does not have autonomous multiplication capacity, or does not contain viable forms of GMO.

Biosafety: For the proposals of this Institutional Act, the word biosafety has the same definition given by the article 1st of the Law n. 8974/95 as follows: "safety rules and inspection mechanisms for the use genetic engineering techniques concerning the construction, cultivation, handling, transportation, commerce, consumption, release and disposal of Genetically Modified Organism (GMO), aiming to protect life and health of humans, animals, and plants, as well as the environment."

1. The regulation of products derived from genetically modified organisms (GMO), concerning the different evaluation aspects of health or environment hazards, related to aspects of quality, chemical composition, range of purity or eventual contaminant agents, toxicity, and also their applications, is a competence that shall be exercised by the inspection departments of the Ministries of Health, Agriculture and Supply, and Environment and Legal Amazon, in accordance with their respective legislation into force.

2. The execution of activities described in the item above, by entities located in the national territory, does not imply that the entities must necessarily own or request the Certificate of Quality in Biosafety (CQB) or even have an Internal Biosafety Commission (CIBio).

3. Concerning the activities of importing, commerce, transportation, storage, handling, consumption, release and disposal of products derived from GMO for use as raw material, or even of purified final products, the quality analysis and regulation for their use shall compete and be exercised by the inspection departments of the Ministries of Health, Agriculture and Supply, and Environment and Legal Amazon, and shall obey the legislation into force.

4. The activities of commerce, transportation, storage, handling, consumption, release and disposal of products derived from GMO obtained within the Brazilian territory, which GMO will have already been analyzed by this Committee, are exempted from the necessity of a new technical statement, according to clause XII of the article 2nd of the Decree n. 1752/95. The quality analysis and regulation for their use shall compete and be exercised by the inspection departments of the Ministries of Health, Agriculture and Supply, and Environment and Legal Amazon.

5. In accordance with the article 7th of the Law n. 8974/95, the entities that carry out, or intend to carry out the activities mentioned here are responsible for the registration products derived from GMO in the inspection departments of the Ministries of Health, Agriculture and Supply, and Environment and Legal Amazon, as prescribed by the effective law.

6. The CTNBio shall give technical statement about any aspect related to this Institutional Act, when requested by the inspection departments of the Ministries of Health, Agriculture and Supply, and Environment and Legal Amazon. The Committee may also appeal to a higher court to examine eventual particular cases, if it is regarded as convenient.

The CTNBio may, at any time and when it is regarded as necessary, revise or modify the norms stated here for the activities included in this Institutional Act, due to eventual particular hazards, or risks unexpected by the present scientific knowledge.

The National Technical Biosafety Committee ? CTNBio, using its legal attributions, decides:

Art. 1st The present institutional act refers to the planned release in the environment and in the commerce of Roundup Ready Soybean, as well as any germ plasm derived from the glyphosate tolerant soybean (GTS 40-3-2) lineage or its progenies genetically modified to be resistant to the glyphosate herbicide. Such release must have already received favorable technical statement , in accordance with the ruling notice n. 54 of the CTNBio, published in the Federal Official Gazette ? DOU n. 188, of 01/01/98, Section 3, p. 59. The technical report refers only to the event of genetic transformation in the Roundup Ready Soybean (E35S promoter, region of the peptide of transport to the chloroplast, region of codification of the 5-enolpyruvate-shikimate-3-phosphate synthase ? EPSPS enzyme), aiming specifically the tolerance to the glyphosate herbicide.

Art. 2nd The activities of cultivation, registering, usage, essays, tests, transport, storage, commerce, consumption, importing and disposal of genetically modified tolerant to the glyphosate herbicide (Roundup Ready Soybean) are exempt from prior evaluation or the request of a new technical report of the CTNBio, provided that the specific regulations of the competent inspection departments are observed.

Art. 3rd The scientific monitoring of commercial planting of the varieties of genetically modified soybeans tolerant to glyphosate herbicide (Roundup Ready Soybean) shall be carried out within a period of five years as a competence of the firm Monsanto do Brasil Ltda., together with the competent inspection departments, supervised by experts designated by the CTNBio, subject to scientific audit by the interested organized civil society, with prior authorization of the CTNBio.

Art 4th The CTNBio reserves the right to revise this Institutional Act, based on the scientific justifications identified during the monitoring proceedings.

Art. 5th The present Institutional Act shall take effect in the date of its publication.

Luiz Antonio Barreto de Castro

Chairman of the CTNBio

THE STATE MINISTER OF THE AGRICULTURE AND SUPPLY, using his legal attribution conferred by the Art. 87th , Single Paragraph, clause II, of the Brazilian Federal Constitution, and considering the dispositions of the Vegetal Sanitary Defense Statute, approved by the Decree n. 24,114, of April 12th 1934,

Considering the importance of the international exchange of germ plasm either genetically modified or not, from organisms destined to biological and soil control, and other scientific aims, necessary to agricultural and cattle-raising researches;

Considering that such exchange is allowed only to institutions that provide technical quarantine conditions to assure the safety of the introduced phytogenetic resources;

Considering the necessity of assuring the supervision and safety of such exchange, harmonizing and simplifying the vegetal sanitary inspection procedures concerning the importing of these materials, without harm for the quarantine and vegetal sanitary inspection rules, in conformity with the proposals of the Defense and Vegetal Inspection Department-DDIV, of the Agriculture and Cattle-raising Defense Secretary-SDA, and those contained in the suit n. 21000.002152/98-68, decides:

Art. 1st Approve the NORMS FOR THE IMPORTING OF MATERIAL DESTINED TO SCIENTIFIC RESEARCH, enclosed bellow.

Art.2nd Determine the international transit of plants shall be carried out only in the locations where a Vegetal Sanitary Defense Service is available.

Art 3rd Determine that the quarantine shall be carried out at the quarantine stations qualified by the Ministry of Agriculture and Supply.

Art. 4th Revoke the Administrative Rules n. 148, of June 15th 1992, and n. 74, of March 7th 1994.

Art. 5th This Administrative Rule shall take effect within sixty days after the date of its publication.

FRANCISCO SÉRGIO TURRA

ANNEX

NORMS FOR THE IMPORTING OF MATERIAL DESTINED TO SCIENTIFIC RESEARCH

1. These norms are applicable for:

1. public and private institutions;

2. The introduction of plants and their parts in the country, either genetically modified or not, represented by small quantities of seeds, pollen, living plants, fruits, cuttings or gems, bulbs, tubercles, rhizomes, in vitro plants, or any parts of plants, with capacity for reproduction or multiplication, destined for scientific research;

3. The introduction of organisms for biologic and soil control, including substrate, and other scientific aims, destined for scientific research, which shall be subject to analysis of the DDIV/SDA; and

4. The donations of material destined to scientific research.

1. Eventual mistakes or imperfections in the Vegetal sanitary Certificate will not be an obstacle for the introduction of the material destined to scientific research in Brazil, provided that the Importing License is conceded, and that those mistakes shall be subject to the final analysis of the Vegetal Inspection Defense Department of the Ministry of Agriculture and Supply.

2. The annual vegetal material importing schedule aiming the establishment and maintenance of material exchange systems among Research Centers, qualified by the Ministry of Agriculture and Supply, and belonging to the institution itself, shall be submitted to the prior approval of the Vegetal Inspection Defense Department of the Ministry of Agriculture and Supply.

3. Every material donated for scientific research shall have its Importing License sent by the Vegetal Inspection Defense Department of the Ministry of Agriculture and Supply, shall be accompanied by the Vegetal sanitary Certificate, nevertheless, it shall be exempt from any additional declarations.

   PROCEDURES

4. The interested part shall request the Importing License of the desired material, in accordance with the form in Annex 1, in three copies, to the Vegetal Inspection Defense Department of the Ministry of Agriculture and Supply, through the Federal Stations of Agriculture and Supply in the States (DFA?S).

5. The requests for the importing of plants destined to research for the EMBRAPA units shall be sent by the CENARGEN/EMBRAPA to the Vegetal Inspection Defense Department of the Ministry of Agriculture and Supply, accompanied by a conclusive technical statement.

6. The requests for importing of organisms for biologic control and other aims, destined to the research of EMBRAPA units, shall be sent by the CENARGEN/EMBRAPA to the Vegetal Inspection Defense Department of the Ministry of Agriculture and Supply, accompanied by a conclusive technical statement.

7. In case the importing concerns genetically modified materials and/or organisms regulated by the National Technical Biosafety Committee ? CTNBio, the interested institution shall possess the Certificate of Quality in Biosafety (CQB), in order to allow the Vegetal Inspection Defense Department of the Ministry of Agriculture and Supply to refer the application to the National Technical biosafety Committee ? CTNBio to obtain a conclusive technical statement.

8. It is a competence of the Vegetal Inspection Defense Department of the Ministry of Agriculture and Supply to give or refuse the Importing License, based on the conclusive technical statement of the CTNBio or of an research institution belonging to the National Agriculture and Cattle-rising Research System.

9. The imported material shall be submitted to the inspection by the expert from the Ministry of Agriculture and Supply in the entry location, concerning both documents and physical departure, in order to obey the Decree n. 24,114, of April 12th 1934 and its complementary legislation.

10. The inspector from the Ministry of Agriculture and Supply has authority to:

1. authorize the departure dispatch, providing that the material is in accordance with the Brazilian vegetal sanitary legislation;

2. based on the art.12 of the Decree n. 24114/34, under the supervision of the Ministry of Agriculture and Supply, prescribe quarantine in adequate areas of a qualified research station and under its responsibility, such station shall be submitted to present vegetal sanitary reports every semester to the Vegetal Inspection Defense Department, signed by the stations technical liable.

3. Prescribe closed quarantine in institutions qualified and licensed by the Ministry of Agriculture and Supply.

4. Prescribe the destruction of the material, if the presence of quarantine plagues is observed, and there is not an efficient treatment, or there is no interest by the interested part in disinfecting the material.

5. Release the materials destined to closed quarantine to the execution of open quarantine.

6. Release the materials of the closed quarantine.

7. Release the materials of the open quarantine.

ANNEX 1

APPLICATION FOR THE IMPORTING OF MATERIAL DESTINED TO SCIENTIFIC RESEARCH

Dear Sir, Director of the Vegetal Inspection Defense Department,

Applicant?s name

Name of the institution he/she belongs to, institution?s CQB number (if necessary)

Institution?s phone number and address

Aware about the Brazilian vegetal sanitary and biosafety legislation, requests an Importing License for the material(s) described bellow:

1. Product

   ( ) plants and their parts

   ( ) organisms for biologic control and other scientific aims

   ( ) genetically modified organisms

   ( ) soil/substrate

   ( ) others (please specify)

2. Technical justification for the importing

3. Name and address of the institution that is sending the material

4. Way of transportation

   ( ) air transport ( ) road transport ( )sea/fluvial transport ( ) courrier

5. Way of introduction of the material (seeds, «in vitro», tubercles, cuttings, eggs, grubs, pupae, etc.)

6. Country and location where the material was collected, developed, produced, and certified

7. Arrival location in Brazil

8. Place of destine of the material

9. Quarantine station qualified by the Ministry of Agriculture

10. Intended use:

    ( ) laboratory

    ( ) greenhouse

    ( ) field

    ( ) others (please specify)

11. Historic resume of similar prior introductions

    If it is a genetically modified organism (GMO), inform:

    k.1) the genetically modified organism (GMO)classification

    k.2) the genes introduced in the genetically modified organism (GMO) and their functions

    k.3) the methodology employed in the transformation

12. List of the material (scientific name, variety, popular name, class, order, family, etc.).

    In case of organisms destined to biologic control, inform the scientific name of the natural host organism accompanying it(them); amounts, weight (grams, kilograms).

13. Schedule and number of introductions (when it is more than one)

14. Caution measures in the destiny location to avoid escapes

    In case of soil or substrate, inform the sterilizing or treatment process.

15. Description of the final disposal method of the material

16. Place and date

17. Name, signature, and professional registration number (CREA, CRB, etc.) of the technical liable

FOR DDIV USE ONLY

Importing License n. __________

( ) Conceded ( ) Rejected

Brasilia, DF,____/_____/_____

Director of the DDIV/SDA

It approves the Inspection Term and Infraction Note models for establishments that work with genetically modified organisms

THE AGRICULTURAL AND CATTLE-RISING DEFENSE SECRETARY, using his attributions conferred by the art. 83rd , item IV, of the Secretary?s Internal Statute, approved by the Ministerial Administrative Rule n. 574 of December 8th 1998, considering the dispositions of the Chapters I and II of the Decree n. 24,114, of April 12th 1934, and those contained in the suit n. 21000.006657/98-56, decides:

Art. 1st Approve the enclosed models of Inspection Term and Infraction Note, to be used by the inspectors of the Ministry of Agriculture and Supply in the fulfillment of the attributions described in the item II of the Article 7th of the Law n. 8,974, of January 5th 1995, and in the Article 12th of the Decree n. 1,752, of December 20th 1995.

Art. 2nd The present Institutional Act shall take effect in the date of its publication.

ENIO ANTONIO MARQUES FERREIRA

MINISTRY OF AGRICULTURE AND SUPPLY

AGRICULTURE FEDERAL STATION ? DFA

VEGETAL SANITY SERVICE ? SSF

At ____ of the ______ day of the month of ______ of ______, I, _____, inspection agent from Agriculture and Supply Federal Station of the State of _____________, exercising the inspection described by the Item II of the Article 7th of the Law n. 8,974, of January 5th 1995, and the Article 12th of the Decree n. 1,752, of December 20th 1995, registered the present INSPECTION TERM in the establishment ___CGC n. __ sited at ________ in the municipality of _____ in the State of ________.

Inspection Description:

And in order to register it, I recorded this INSPECTION TERM, in 4(four) copies, signed by me, by the technical or legal representative of the establishment, and before his/her absence or refusal to sign, it shall be signed by 2(two) witnesses.

Place and Date

_________________

Agronomic Engineer ? CREA Legal Representative/ CIBio Chairman

Inspection Agent RG(Registration Number)

________________________

Witness Witness

RG: RG:

3rd copy ? establishment by AR 4th copy ? Vegetal Sanity Service filing

MINISTRY OF AGRICULTURE AND SUPPLY

AGRICULTURE FEDERAL STATION ? DFA

VEGETAL SANITY SERVICE ? SSF

At ____ of the ______ day of the month of _____________ of ______, I, _____, inspection agent from Agriculture and Supply Federal Station of the State of ____, exercising the inspection described by the Item II of the Article 7th of the Law n. 8,974, of January 5th 1995, and the Article 12th of the Decree n. 1,752, of December 20th 1995, verified that the establishment ______ CGC n. ____ sited at _____ in the municipality of _____ in the State of _____, infringed the dispositions of the clause(s) n. ___of the Article 12th of the Decree n. 1,752, of December 20th 1995, by the observation of the following irregularities:

And in order to register it, I recorded this INFRACTION NOTE, in 4(four) copies, signed by me, by the technical or legal representative of the establishment, and before his/her absence or refusal to sign, it shall be signed by 2(two) witnesses.

_________________

Agronomic Engineer ? CREA Infractor?s Representative

Inspection Agent RG(Registration Number)

________________

Witness Witness

RG: RG:

Complete Address Complete Address

3rd copy ? establishment by AR 4th copy ? Vegetal Sanity Service filing