Part B of Annexes II and III to the Order of 4 August 1993 laying down the requirements for applications for the authorisation of plant protection products contains the requirements for documentation which are required for active substances consisting of micro-organisms, including viruses, and for plant protection products containing them.

The differentiation of these requirements, with respect to those required for chemical substances, is essential, since the nature and properties of the micro-organisms and the existence of certain aspects, such as those relating to their possible infectious or pathogenic character, require specific tests and trials.

Following the experience gained during the evaluation of active substances consisting of micro-organisms, the European Commission has reviewed these requirements, setting out those to be applied in the future by means of the Directive. 2001 /36/EC of the European Parliament and of the Council of 16 May amending Council Directive 91 /414/EEC concerning the placing of plant protection products on the market.

This Order incorporates Directive 2001 /36/EC into national law and amends, as a result, Annexes II and III to the Order of 4 August 1993.

This provision is made in accordance with the power laid down in the final provision of Royal Decree No 2163/1994 of 4 November 1994 imposing a harmonised Community system of marketing authorisation and use plant protection products.

In the preparation of the project, the Autonomous Communities and the sectors affected have been consulted.

In its virtue, I have:

Single item. Amendment of Annexes II and III to the Order of 4 August 1993.

Annexes II and III to the Order of 4 August 1993 laying down the requirements for applications for the authorisation of plant protection products are amended as follows:

1. In the introduction to Annex II, a new paragraph 2.4 is included, with the content set out in Annex I to this Order.

2. Part B of Annex II is replaced by Annex II to this Order.

3. A new paragraph 2.6, which is set out in Annex III to this Order, is added to the introduction of Annex III.

4. Part B of Annex III is replaced by Annex IV to this Order.

Single end disposition. Entry into force.

This Order shall enter into force on the day following that of its publication in the "Official State Gazette".

Madrid, 25 March 2002.

CANETE ARIAS

ANNEX I

Addendum to Annex II of the Order of 4 August 1993

2.4 By way of derogation from point 2.1, as regards active substances consisting of micro-organisms or viruses, the tests and analyses carried out to obtain data on the properties or safety with respect to aspects other than human health may have been carried out in official or officially recognised facilities or testing bodies which at least comply with the requirements laid down in points 2.2 and 2.3 of the introduction to Annex III.

ANNEX II

Part B of Annex II to the Order of 4 August 1993

INTRODUCTION

(a) The active substances are defined in Article 2 (4) of Royal Decree 2163/1994 and comprise chemicals and micro-organisms, including viruses.

This part provides for the data requirements for active substances consisting of micro-organisms, including viruses.

For the purposes of this Part B, the following definition of micro-organism shall apply:

"Microbiological, cellular or non-cellular entity, capable of replicating or transferring genetic material."

This definition applies to bacteria, fungi, protozoa, viruses and viroids, but not limited to these groups.

(b) All relevant data available, as well as bibliographic information, should be submitted in respect of all micro-organisms which are the subject of the application.

The most important and instructive information is obtained with the characterization and identification of the microorganism. This information is found in Sections 1 to 3 (identification, biological properties and other data), which form the basis for the assessment of the effects on human health and the environment.

It is normally necessary to present data recently obtained from conventional toxicological or pathological experiments with laboratory animals, unless the applicant can justify, on the basis of the above information, that the use of the micro-organism under the proposed conditions has no harmful effects on human or animal health and on groundwater, as well as an unacceptable impact on the environment.

(c) In the absence of acceptance of specific guidelines at international level, the required information shall be obtained by applying available test guidelines which have been accepted by the competent authority (e.g. The guidelines of the USEPA (Microbial pesticide test guidelines, OPPTS, series 885, February 1996)]; if necessary, the test guidelines described in Part A of this Annex II shall be adapted in such a way as to be appropriate for the micro-organisms

Tests should include viable micro-organisms and, where appropriate, infeasible, as well as a blank check.

(d) In the case of tests, a detailed description (specification) of the material used and its impurities as set out in point 1.4 of Section 1 shall be provided. The material used must correspond to the specification applicable to the manufacture of the preparations for which authorisation is requested.

In the case of studies with micro-organisms produced in the laboratory or in a pilot plant production system, the studies must be repeated with micro-organisms as they are finally produced, unless otherwise possible. it is shown that the material used in the test is essentially the same for testing and evaluation purposes.

e) In the case of a genetically modified micro-organism, as defined in Royal Decree 951/1997 of 20 June 1997 on the deliberate release into the environment of genetically modified organisms, a copy of the study of the data relating to the environmental risk assessment referred to in Article 1 (2) of Royal Decree No 2163/1994 is submitted.

f) Where relevant, the data shall be analysed according to appropriate statistical methods. All details of the statistical analysis should be reported (for example, all point estimates should be given with confidence intervals and the exact p values should be collected rather than "significant").

g) In case of studies in which the administration is extended over a period, preference shall be given using a single batch of micro-organism, if stability is permitted.

If the studies are not carried out with a single batch of the micro-organism, the similarity of the different batches should be checked.

When a study involves the use of different doses, the relationship between dose and side effects should be reported.

h) If it is known that the plant health action is due to the residual effect of a toxin or metabolite, or if significant residues of toxins or metabolites are to be expected unrelated to the effect of the active substance, it must be submitted a dossier of the toxins or metabolites, in accordance with the requirements of Part A of this Annex II.

1. IDENTIFICATION OF THE MICRO-ORGANISM

The identification of the micro-organism: The identification, along with the characterization of the micro-organism, provides the most important information and is key to decision making.

1.1 Applicant.-The name and address of the applicant (permanent address in the European Community), as well as the name, function and telephone number and fax number of the contact person should be specified.

If, in addition, the applicant has an office, agent or representative in the Member State before which the application for inclusion in Annex I is submitted, and if different, in the rapporteur Member State designated by the Commission, the name and address of the local office, agent or representative, as well as the name, function and telephone number and fax number of the contact person must be given.

1.2 Producer.-The name and address of the producer or producers of the micro-organism should be provided, as well as the name and address of each of the facilities in which the micro-organism is produced. A point of contact (preferably a focal point of contact, including the name and telephone number and fax number) should be provided in order to provide up-to-date information and to respond to issues arising in connection with the process and production technology, as well as the quality of the product (if any, in relation to the different lots). Where, following the inclusion of the micro-organism in Annex I, there are changes in the location or number of the producers, the required information shall be notified to the Commission and the Member States again.

1.3 Name and description of the species, characterization of the strain:

(a) The micro-organism shall be deposited in an internationally recognized crop collection, in which it has received an entry number; this data shall be communicated.

(b) Each micro-organism which is the subject of the application shall be identified and named at the species level. The scientific name and taxonomic classification, i.e. family, genus, species, strain, serotype, patovar or any other relevant name of the micro-organism shall be indicated.

It will be specified if the microorganism:

It is or is not indigenous, at species level, in the intended area of application It is a wild type. It is a spontaneous or induced mutant. It has been modified by techniques described in Annexes I, A and B, of Royal Decree 951/1997.

In the last two cases all known differences between the modified micro-organism and the parental wild strain should be reported.

c) The best available technology should be used to identify and characterize the strain-level microorganism. The appropriate testing methods and the criteria used for identification (e.g. morphology, biochemistry, serology, molecular identification, etc.) should be reported.

(d) Any common or alternative and waste names, as well as the codes used during the development phase, must be indicated.

e) Possible relationships with known pathogens should be reported.

1.4 Specification of the material used in the manufacture of formulated products:

1.4.1 Microorganism content: The minimum and maximum content of the micro-organism must be indicated in the material used for the manufacture of the formulated products. The content shall be expressed in appropriate terms, such as the number of active units by volume or weight, or in any other way relevant to the micro-organism.

In the event that the information provided responds to the production system of a pilot plant and that, once the production methods and procedures have been stabilized on an industrial scale, the changes in production have as a result a modification of the specification of purity, the necessary information will be made available again to the Commission and the Member States.

1.4.2 Identity and content of impurities, additives and contaminating micro-organisms: It is appropriate to have a plant protection product free of contaminants (including contaminating micro-organisms) as far as possible. It shall be judged on the level and nature of the pollutants acceptable from the point of view of the risk assessment.

Where possible and relevant, the identity and maximum content of all the contaminating micro-organisms, expressed in the appropriate unit, shall be indicated. The information on the identity shall be provided, as far as possible, as indicated in point 1.3 of Section 1 of this Part B.

The relevant metabolites (i.e., which may affect human health or the environment) from which they are known to come from the micro-organism should be identified and characterised in the different stages of growth or states. of the micro-organism, paragraph (h) of the introduction to this Part B.

When relevant, detailed information on all components, such as condensates, culture medium, etc., should be provided.

In the case of the presence of chemical impurities that are relevant to human health or the environment, their identity and maximum content, expressed in appropriate terms, shall be indicated.

In the case of the presence of additives, their identity and their content must be indicated in g/kg.

Information on the identity of chemical substances, such as additives, shall be provided as set out in point 1.10 of Section 1 of Part A of this Annex II.

1.4.3 Analytical profile of lots: Where appropriate, the same data as referred to in point 1.11 of Section 1 of Part A of this Annex II shall be indicated using the appropriate units.

2. BIOLOGICAL PROPERTIES OF THE MICRO-ORGANISM

2.1 History of the micro-organism and its use.

Natural presence and geographical distribution: The availability of relevant data on the micro-organism should be indicated.

2.1.1 Background: The history of the micro-organism and its use (tests, research projects or commercial use) should be indicated.

2.1.2 Origin and natural presence: The geographical region and the place of the ecosystem (e.g. host plant, host animal or soil) from which the micro-organism has been isolated should be noted. The method of isolation of the micro-organism should be indicated. The natural presence of the micro-organism in the relevant environment shall be indicated, if possible, at the strain level.

In the case of a mutant or genetically modified organism (as defined in Annexes I, A and B to Royal Decree 951/1997), detailed information on their production and isolation and on the means by which they are used shall be presented. can be clearly distinguished from the parental wild strain.

2.2 Information about the target organism or organisms:

2.2.1 Description of the target organism or bodies: details of the harmful organisms to which protection is provided shall be provided, where appropriate.

2.2.2 Mode of action: The main mode of action should be indicated. In relation to the mode of action, it should also be indicated whether the micro-organism produces any toxin with residual effect on the target organism. In this case, the mode of action of the toxin should be described.

Where appropriate, information on the place of infection and the mode of entry into the target organism, as well as on the susceptible stages thereof, shall be given. The results of any experimental studies will be collected.

It should be indicated how the absorption of the micro-organism or its metabolites (especially toxins) can occur, such as contact, ingestion or inhalation. It should also be indicated whether the micro-organism or its metabolites are translocated in plants and, where appropriate, how this translocation takes place.

In case of a pathogenic effect on the target organism, the infectious dose (dose necessary to cause infection with the intended effect on a target species) and transmissibility (possibility of transmission of the target species) will be indicated. the micro-organism in the target population, but also of a target species to another species, whether objective or not) after implementation under the proposed conditions.

2.3 Gama of host specificity and effects on species other than the target harmful organism. -All available information on the effects on non-target organisms within the area to which it can be found will be presented. spread the micro-organism. The presence of non-target organisms which are closely related to the target species or which may be specially exposed shall be noted.

Any experience of the toxic effect of the active substance or its metabolic products in humans or animals shall be indicated as to whether the organism is capable of colonising or invading man or animals (including immune-suppressed individuals) and whether it is pathogenic. Any experience of whether the active substance or its products may irritate the skin, eyes or respiratory organs of man or animals, and whether they are allergens in contact with the skin or by inhalation, shall also be indicated.

2.4 Life cycle development phases of the micro-organism. -Information on the life cycle of the micro-organism and on its possible symbiosis, parasittisms, competitors, predators, etc., including organisms hosts, as well as the vectors of viruses.

The generation time and type of reproduction of the micro-organism will be indicated.

Information about the presence of forms of resistance and their time of survival, virulence, and potential for infection will be given.

The ability of the micro-organism to produce metabolites, including toxins that are important for human health or the environment, shall be indicated at its different stages of development after release.

2.5 Infecciousness, dispersion and colonization capacity. -The persistence of the microorganism must be indicated and information about its life cycle will be given in the typical environmental conditions of use.

In addition, any particular sensitivity of the micro-organism to certain aspects of the environment (e.g. ultraviolet light, soil, water) will be noted.

Environmental requirements (temperature, pH, humidity, nutrients, etc.) will be indicated for survival, reproduction, colonization, damage production (including human tissues) and the efficacy of the micro-organism.

The presence of specific virulence factors should be indicated.

The range of temperatures to which the micro-organism grows, including minimum, maximum and optimal temperatures, will be determined. This information has a special value as a basis for studies on human health effects (Section 5).

The possible effect of factors such as temperature, ultraviolet light, pH and the presence of certain substances on the stability of relevant toxins should also be reported.

Information should be given on the possible dispersal pathways of the micro-organism (by air, such as dust particles or aerosols, with host organisms, such as vectors, etc.) under typical environmental conditions. use.

2.6 Relations with known human, animal or plant pathogens. -It shall be indicated that one or more species of the genus of the active micro-organism or, where appropriate, the contaminating micro-organisms that are pathogenic to man, animals, crops or other non-target species, as well as the type of disease caused. It will be noted if it is possible to clearly distinguish the active micro-organism from pathogenic species and, if so, how.

2.7 Genetic stability and factors thereof. -When relevant, information on genetic stability (e.g., mutation rate of traits related to the mode of action or absorption of material) will be provided. exogenous genetic) in the environmental conditions of the proposed use.

Information should also be provided on the ability of the micro-organism to transfer genetic material to other organisms, as well as its ability to be pathogenic to humans, animals or plants. If the micro-organism has additional genetic elements of relevance, the stability of the coded traits shall be indicated.

2.8 Information on the production of metabolites (especially toxins). -If other strains belonging to the same microbial species as the strain of the application produce metabolites (especially toxins) with effect unacceptable to human health or the environment during or after the application, the nature and structure of this substance, its presence inside or outside the cell and its stability, its mode of action (including the internal and external factors of the micro-organism necessary for the action), as well as its effect on man, animals or other non-target species.

The conditions in which the microorganism produces the metabolites (especially toxins) should be described.

All available information on the mechanism by which the micro-organisms regulate the production of these metabolites will be presented.

All available information regarding the influence of the metabolites produced on the mode of action of the micro-organism shall be given.

2.9 Antibiotics and other antimicrobial agents. -Many microorganisms produce certain antibiotic substances. Interference with the use of antibiotics in medicine or veterinary medicine should be avoided at all stages of development of a microbial plant protection product.

Information on the resistance or sensitivity of the micro-organism to antibiotics or other antimicrobial agents should be given, in particular to the stability of the genes coding for antibiotic resistance, unless it can be justified that the micro-organism has no harmful effects on human or animal health or that it cannot transfer its resistance to antibiotics or other antimicrobial agents.

3. OTHER DATA ON THE MICROORCANISM

Introduction

(a) The data provided shall specify the intended purpose of the uses to be made or to be made of the preparations containing the micro-organism, as well as the dose and the current or proposed form of employment.

(b) The data provided shall specify the normal methods and precautions to be applied for the handling, storage and transport of the micro-organism.

(c) The studies and data presented shall demonstrate the adequacy of the proposed measures for emergency situations.

d) It is necessary to present the data referred to in relation to all the micro-organisms, unless otherwise specified.

3.1 Function. -The biological function of the following shall be specified:

Fight against bacteria, Fight against fungi, Fight against insects, Fight against mites, Fight against molluscs, Fight against nematodes, Fight against weeds, Other types (please specify).

3.2 Intended areas for use.-The current or proposed areas of use shall be specified for the preparations containing the micro-organism, including the following:

Field use, such as agriculture, horticulture, forestry, and viticulture.

Protected crops (e.g. in greenhouses).

Recreational activities.

Fighting weeds in uncultivated areas.

Gardening.

Interior plants.

Stored products.

Other (specify).

3.3 Crops or products protected or treated. -Details of current and planned uses will be provided in terms of crops, crop groups, plants or protected plant products.

3.4 Method of production and quality control. -All information on how the micro-organism is produced in bulk will be provided.

Both the process and the production methods and the product will be the subject of continuous quality control by the applicant. In particular, the occurrence of spontaneous changes in the main characteristics of the micro-organism, as well as the absence or presence of significant contaminants, should be studied.

The quality assurance criteria for production will be presented.

The techniques applied to ensure the uniformity of the product as well as the test methods relating to its normalisation, maintenance and purity of the micro-organism (e.g. HACCP) shall be described and specified.

3.5 Information on the occurrence or possible occurrence of resistance in the target organisms: Information should be provided on the possible occurrence of resistance or cross-resistance in the target organisms. target organisms. Where possible, appropriate strategies for managing the problem shall be described.

3.6 Methods to prevent the loss of virulence of the inoculum of the micro-organism. -Methods will be presented to avoid the loss of virulence of the starting crops.

In addition, all available methods that can prevent the loss of the effects of the micro-organism on the target species will be described.

3.7 Recommended measures and precautions for handling, storage, transport or, in the event of fire.-For each micro-organism a safety data sheet similar to that required for chemical substances shall be submitted Article 23 of the Regulation on the Notification of New Substances and Classification, Packaging and Labelling of Dangerous Substances, approved by Royal Decree 363/1995 of 10 March.

3.8 Destruction or decontamination procedures. -In many cases, the only or most appropriate means to safely remove microorganisms, contaminated materials or contaminated packaging is incineration. controlled in an authorised incinerator.

Methods to safely remove the microorganism or, in case

, should be fully described.

required, kill it before removal, as well as methods to remove contaminated packaging and materials. Data shall be provided on such methods to establish their effectiveness and safety.

3.9 Measures in the event of accidents.-Information on methods to ensure that the micro-organism is safe in the environment (e.g. water or soil) in the event of an accident.

4. ANALYTICAL METHODS

Introduction

The provisions of this Section apply only to the analytical methods necessary for post-registration control and monitoring.

Post-registration follow-up with respect to all areas of risk assessment could be considered.

This is especially so in relation to the approval of (strains of) microorganisms that are not indigenous to the intended area of application. Applicants shall justify the analytical methods used to obtain the data required in this Annex or for other purposes; if necessary, separate guidance shall be laid down for those methods, in accordance with the same requirements as the case of methods for post-registration control and monitoring.

Description of methods including equipment data, materials and conditions used shall be provided. The applicability of any internationally recognised methods should be reported.

As far as possible, these methods should be based on the simplest techniques, cost as little as possible and use material that can be easily obtained.

Data on specificity, linearity, accuracy and repeatability, as defined in points 4.1 and 4.2 of Part A of this Annex II, shall also be required in relation to the methods used to analyse the micro-organisms and their residues.

For the purposes of this Section,

following definitions shall apply:

"Impurities" means any component (including any micro-organisms or chemical substances) other than the specified micro-organism, the presence of which is due to the manufacturing process or degradation during storage.

Relevant impurities: impurities, as defined above, of importance for human or animal health or for the environment.

"Metabolites": Products derived from degradation and biosynthesis reactions occurring in the micro-organism or in other organisms used to produce the corresponding micro-organism.

Relevant Metabolites: Metabolites of importance for human or animal health or for the environment.

"Waste": viable micro organisms and substances produced in significant quantities by these micro-organisms, which persist after the disappearance of these and which are of importance to human or animal health or to the environment environment.

When requested, the following samples shall be provided:

a) Samples of the micro-organism as finally produced.

b) Analytical patterns of relevant metabolites (especially toxins) and all other components included in the definition of "waste".

c) If available, reference substance samples of the relevant impurities.

4.1 Methods of analysis of the micro-organism as finally produced:

Methods of identification of the micro-organism.

Methods for the presentation of information on the possible variability of the active micro-organism or the inoculum.

Methods for differentiating a mutant from the microorganism with respect to the wild parental strain.

Methods of determining the purity of the inoculum from which the batches and methods of achieving said purity are produced.

Methods for determining the content of the microorganism in the manufactured material used for the production of formulated products and demonstration methods that the level of microorganisms is acceptable.

Methods of determining relevant impurities in the material produced finally.

Methods of establishing absence and quantifying (with appropriate limits of determination) the possible presence of any pathogen for man and mammals.

Methods for determining stability during storage and time of storage of the micro-organism, where appropriate.

4.2 Methods to detect and quantify waste (viable and unviable) of:

Active microorganisms and relevant metabolites (especially toxins)

inside or on the surface of cultivated plants, in food and feed, in animal and human tissues and fluids, in soil, in water (including drinking water, groundwater and surface water) and in the air when applicable.

Also include analytical methods for the quantity or activity of protein products, such as the testing of exponential crops and crop supernatants in a bioassay with animal cells.

5. EFFECTS ON HUMAN HEALTH

Introduction

(a) Available information based on the properties of the micro-organism and the relevant bodies (sections 1 to 3), including health and medical reports, may be sufficient to decide whether the microorganism is capable or not capable of causing effects (of an infectious, pathogenic or toxic nature) on human health.

(b) The information submitted, together with the information provided in relation to one or more preparations containing the micro-organism, shall enable the assessment of the risks involved for man, directly or indirectly, to be carried out; the handling and use of plant protection products containing that micro-organism and the risks to the handlers of the treated products, as well as the risks to man derived from the residues or pollutants that remain in the food and in the water. In addition, the information provided must be sufficient to:

Decide whether or not the micro-organism can be included in Annex I.

Specify the relevant conditions or restrictions in case it is included in Annex I.

Specify the risk and safety phrases (once introduced) for the protection of man, animals and the environment to appear on the container (containers).

Determine appropriate first aid, diagnostic and therapeutic measures to be applied in case of infection or other adverse effect in man.

c) All effects observed during investigations should be reported. Investigations may also be carried out which may be necessary to assess the likely mechanism and the meaning of these effects.

d) In all studies the actual dose achieved in units of colony-forming per kilogram body weight (ufc/kg), as well as in any other suitable unit, should be reported.

e) The evaluation of the micro-organism should be carried out in stages.

The first stage (stage I) includes the basic information available and the basic studies to be carried out with all the micro-organisms. It will be necessary to have the opinion of experts to decide on the appropriate testing programme in each case. It is normally necessary to present data recently obtained from conventional toxicological or pathological experiments with laboratory animals, unless the applicant can justify, on the basis of the above information, that the use of the The micro-organism under the proposed conditions has no harmful effects on human and animal health. In the absence of acceptance of specific guidelines at international level, the required information will be obtained by applying available test guidelines (e.g. the USEPA OPPTS guidelines).

In the event that the tests performed in stage I have shown adverse health effects, stage II studies will be carried out. The type of study to be carried out depends on the effects observed in the studies in stage I. Before such studies are carried out, the applicant must obtain the agreement of the competent authorities on the type of study to be carried out.

Stage I

5.1 Basic information.-Basic information on the potential of microorganisms to produce adverse effects, such as the ability to colonize, cause harm, and to produce toxins and other relevant metabolites, is required.

5.1.1 Medical data: Where available and without prejudice to the provisions of Articles 4 to 15, the single additional provision and the single transitional provision of Royal Decree 664/1997 of 12 May 1997 on the protection of workers against risks related to exposure to biological agents at work, practical data and information relevant to the recognition of symptoms of infection or pathogenicity and the effectiveness of the exposure first aid and therapeutic measures. Where appropriate, the effectiveness of potential antagonists should be investigated and reported on. Where appropriate, the methods for killing the micro-organism or causing it to lose its infectiousness (point 3.8 of section 3) must be indicated.

When available and of the required quality, data and information on the effects of human exposure are particularly valuable in confirming the validity of the extrapolations made and the findings The effects of the effects of the treatment on the target organs, the virulence and the reversibility of the adverse effects. Such data may be obtained after accidental or professional exposure.

5.1.2 Medical control of staff in manufacturing facilities: The available reports of professional health surveillance programmes, supported by detailed information on the configuration of the facility, should be presented. programme and the exposure to the micro-organism. Where possible, these reports should include relevant data on the mechanism of action of the micro-organism. Where available, such reports shall include data for persons exposed to manufacturing facilities or after the application of the micro-organism (e.g. in the testing of efficacy).

Special attention should be paid to people whose sensitivity may be affected, for example, due to a previous illness, medication, weakened immunity, pregnancy or breast-feeding.

5.1.3 Sensitisation/Allergen observations, where appropriate: Information available on the awareness and allergenic response of workers, including plant workers, will be provided for the manufacture, agriculture and research, as well as other persons exposed to the micro-organism, and all relevant data should be collected on any case of hypersensitivity and chronic sensitisation. The information provided will include details on frequency, level and duration of exposure, observed symptoms and other relevant clinical data. Information will be given on whether workers have been the subject of allergy testing or if they have been asked about the presence of allergy symptoms.

5.1.4 Direct observation, e.g. clinical cases: The reports in the published documentation on the micro-organism or on the microorganism should be presented together with the reports of any follow-up studies carried out. very close members of the same taxonomic group (in relation to clinical cases), if they are from reference journals or from official reports. These reports shall be of special value and shall include full descriptions of the nature, level and duration of the exposure, as well as the clinical symptoms observed, first aid and therapeutic measures applied, and measurements and observations made. Summary information has a limited value.

When animal studies have been conducted, reports on clinical cases may be particularly valuable in confirming the validity of the interpretation of animal data with respect to man and for identify unexpected adverse effects that are specific to the human being.

5.2 Basic studies. In order to correctly interpret the results obtained, it is extremely important that the suggested methods of testing be appropriate for species sensitivity, route of administration, etc. as well as from the point of view of biology and toxicology. The method of administration of the microorganism examined depends on the main routes of exposure of man.

In order to assess the medium and long-term effects after acute, subacute or semi-chronic exposure to micro-organisms, it is necessary to use the options set out in most of the guidelines of the Organisation of Economic Cooperation and Development (OECD), to extend the studies corresponding to a period of recovery (after which a complete pathological study, both micro and macroscopic, should be carried out, including the search for micro-organisms in tissues and organs). This facilitates the interpretation of certain effects and offers the possibility of recognizing the infectiousness or pathogenicity, which in turn contributes to making decisions on other issues, such as the need to carry out studies in the long term. time limit (carcinogenicity, etc.) (point 5.3), or about whether or not to carry out waste studies (point 6.2).

5.2.1 Awareness (1): It is not appropriate to apply to micro-organisms the methods available for the study of skin sensitisation. Most likely, inhalation awareness is a much greater problem than skin exposure to microorganisms, but validated test methods are now lacking. It is therefore of the utmost importance to develop such methods. Until that time, all micro-organisms should be considered as potential sensitisers. This point of view also takes into account the existence of immune-deficient individuals or other types of sensitivity (e.g., pregnant women, newborn or elderly children).

Test target: The test shall provide sufficient information to determine the ability of the micro-organism to cause inhalation sensitisation reactions in addition to the skin exposure.

A test with maximized exposure should be done.

Circumstances in which (2): Due to the absence of appropriate testing methods, all micro-organisms will be considered as potential sensitisers, unless the applicant wishes to demonstrate the absence of this potential. sensitising by the presentation of data. This data requirement is therefore to be considered provisionally as non-compulsory but optional.

Information on awareness should be provided.

5.2.2 Acute toxicity, pathogenicity and infectiousness: The studies, data and information provided and evaluated shall be sufficient to identify the effects of a single exposure to the micro-organism, and in particular set or indicate:

The toxicity, pathogenicity and infectiousness of the micro-organism.

The temporal evolution and the characteristics of its effects, along with complete data of changes in behavior and the eventual macroscopic pathological observations of the autopsy.

As possible, the mode of toxic action.

The relative risks of different routes of exposure.

Blood tests throughout the studies to evaluate the elimination of the microorganism.

Acute pathogenic or pathogenic effects may be accompanied by infectiousness or longer-term effects that cannot be observed immediately. Therefore, with a view to the health assessment, it is necessary to carry out studies on the ability to infect test mammals in relation to oral intake, inhalation and intraperitoneal or subcutaneous injection.

During acute toxicity, pathogenicity and infectiousness studies, an estimate of the elimination of the microorganism or active toxin from the organs considered important for the examination should be made. microbiological (e.g. liver, kidney, spleen, lungs, brain, blood and point of administration).

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(1) It is not appropriate to apply to micro-organisms the methods available for the study of skin sensitisation. Most likely, inhalation awareness is a much greater problem than skin exposure to microorganisms, but validated test methods are now lacking. It is therefore of the utmost importance to develop such methods. Until that time, all micro-organisms should be considered as potential sensitisers. This view also takes into account the existence of immunodeficient individuals or other types of sensitivity (e.g., pregnant women, newborn or elderly children).

(2) Due to the absence of appropriate testing methods, all micro-organisms shall be considered as potential sensitisers, unless the applicant wishes to demonstrate the absence of this sensitising potential by presence data. This data requirement is therefore to be considered provisionally as non-compulsory but optional.

The comments to be made should reflect the opinion of expert scientists and may include the count of micro-organisms in all tissues that may be affected (for example, with lesions) and in organs. main: Rinons, brain, liver, lungs, spleen, bladder, blood, lymph nodes, gastrointestinal tract, thymus and lesions at the point of inoculation of dead or dying animals, as well as animals slaughtered throughout the study and end of the same.

The information generated from the acute toxicity, pathogenicity and infectiousness tests is of particular importance for the assessment of the risks that may arise in the event of an accident and the risks that may affect to the consumer due to exposure to possible waste.

5.2.2.1 Toxicity, pathogenicity and acute infectiousness by mouth. -Circumstances in which it is required:

Reports on the toxicity, pathogenicity and acute infectiousness of the microorganism should be submitted by mouth.

5.2.2.2 Toxicity, pathogenicity and acute infectiousness by inhalation. -Circumstances required: Reports on toxicity, pathogenicity and acute infectiousness of the microorganism by inhalation are required. (the inhalation study may be replaced by an intratracheal study).

5.2.2.3 Single intraperitoneal or subcutaneous administration. -Intra-peritoneal/subcutaneous testing is considered very sensitive to study, especially infectiousness.

Circumstances in which it is required: It is always necessary to make intraperitoneal injection with all microorganisms. However, expert opinion may be used to assess whether subcutaneous injection rather than intraperitoneal injection is preferable if the maximum growth and multiplication temperature is below 37 oC.

5.2.3 Test for genotoxicity. -Circumstances in which it is required. If the micro-organism produces exotoxins according to point 2.8, then it is necessary to also study the genotoxicity of these toxins and other relevant metabolites present in the culture medium.

These tests with the toxins and metabolites should be made, whenever possible, with the purified chemical.

If the basic studies do not indicate the formation of toxic metabolites, the need for studies of the micro-organism itself will be considered, according to the expert opinion on the relevance and validity of the basic data. In the case of viruses, the risk of mutagenesis by insertion into mammalian cells or the risk of carcinogenicity should be treated.

Test Objective: These studies are useful for:

Predict genotoxic potential.

Detect genotoxic carcinogens early.

Clarify the mechanism of action of certain carcinogens.

It is important to adopt a flexible approach, so that the selection of new tests is carried out according to the interpretation of the results obtained at each stage.

Test Conditions: As current testing methods are designed to be performed with soluble chemicals, it is necessary to develop methods that can be applied to microorganisms.

The genotoxicity of cell microorganisms will be studied after the cells are broken, whenever possible. The method used to prepare the sample shall be justified.

The genotoxicity of viruses will be studied in isolated infectious strains.

5.2.3.1 In vitro studies. -Circumstances required: Results of in vitro mutagenicity tests (gene mutation test in bacteria and, in mammalian cells, clastogenicity and/or laboratory tests) should be presented. gene mutation).

5.2.4 Cell culture study: This information should be given in relation to micro-organisms that replicate intracellularly, such as viruses, viroids or certain bacteria and protozoa, except that the data in Chapters 1 to 3 demonstrate clearly that the micro-organism does not replicate in warm-blooded animals. A study with cell or tissue cultures of different human organs should be performed. The selection may be based on the intended target organs for infection. If cell or tissue cultures of certain human organs are not available, other cell cultures and tissue cultures may be used.

With regard to viruses, it is essential to consider the capacity of interaction with the human genome.

5.2.5 Short-term toxicity and pathogenicity information:

Test target: Short-term toxicity studies should be designed to provide information on the amount of microorganism that can be tolerated without toxic effects under the conditions of the study.

Such studies should provide useful data on the risks to persons handling and using preparations containing the micro-organism. In particular, short-term studies provide fundamental information on the potential cumulative effect of the micro-organism and the risks to workers who may be exposed to it. In addition, short-term studies provide useful information for designing chronic toxicity studies.

The studies, data and information to be provided and evaluated shall be sufficient to enable the detection of the effects of repeated exposure to the micro-organism, in particular to establish or indicate:

The relationship between dose and side effects.

The toxicity of the micro-organism, including if necessary the NOAEL of the toxins.

The target organs, when relevant.

The temporal evolution and the characteristics of the effects, along with complete data of changes in behavior and any serious pathological observations of the autopsy.

The various toxic effects and pathological changes appeared.

Where appropriate, the persistence and reversibility of certain observed toxic effects, once the administration was interrupted.

As possible, the mode of toxic action.

The relative risks of different routes of exposure.

During the short-term toxicity study, an estimate of the elimination of the micro-organism from the main organs should be performed.

Research on pathogenicity and infectiousness parameters should be included.

Circumstances in which it is required: Reports on short-term toxicity (minimum of twenty-eight days) of the micro-organism should be submitted.

The selection of species used in the test must be justified. The length of the study will depend on the data on acute toxicity and elimination.

The opinion of experts is necessary to decide which route is preferable for administration.

5.2.5.1 Effects on health after repeated inhalation exposure: It is considered necessary to provide information regarding the health effects following repeated inhalation exposure, especially for the purposes of the assessment of professional risk. The repetition of the exposure may influence the ability to remove the microorganism (e.g., resistance) from the host (male). Furthermore, for an appropriate risk assessment it is necessary to treat toxicity after repeated exposure to contaminants, culture medium, adjuvants and micro-organisms. It should not be forgotten that adjuvants of plant protection products may influence the toxicity and infectiousness of micro-organisms.

Circumstances in which it is required: Information on the infectiousness, pathogenicity and short-term toxicity (by respiratory) of a micro-organism is required, unless the information presented above is sufficient to assess the effects on human health. This may occur when it has been demonstrated that the material studied has no inhalable fraction or that no repetition of the exposure is anticipated.

5.2.6 Proposed Treatment. First aid measures and medical treatment: First aid measures to be applied in the case of infection and in the case of contamination of the eyes shall be indicated.

The therapeutic treatments to be used in case of ingestion or contamination of the eyes and skin will be described in detail. Information based on practical experience, if available and available, and, in other cases, theoretical information on the effectiveness of alternative treatments, where appropriate, will be provided.

Information about antibiotic resistance will be given.

Stage II

5.3 Specific studies of toxicity, pathogenicity and infectiousness. -In some cases, additional studies may be required to clarify the adverse effects observed in man.

In particular, studies on chronic toxicity, pathogenicity and infectiousness, carcinogenicity and toxicity for reproductive function should be carried out if it follows from previous studies that the micro-organism may have effects in the long term on health. In addition, in the case of toxin production, kinetic studies should be carried out.

The required studies should be designed, on a case by case basis, in the light of the specific parameters to be investigated and the objectives to be achieved.

Prior to such studies, the applicant shall obtain the agreement of the competent authorities on the type of study to be carried out.

5.4 In-vivo tests on somatic cells. -Circumstances that are required:

If all results of in vitro studies are negative, further testing should be performed, taking into account the other relevant information available. The test may be an in vivo study or an in vitro study in which a system of metabolism other than those previously used is used.

If the result of the in vitro cytogenetic test is positive, an in vivo assay should be performed using somatic cells (analysis of the metafase of the rodent bone marrow or micronucleus assay in rodents).

If any of the in vitro gene mutation testing is positive, an in vivo test should be performed to investigate the unscheduled DNA synthesis or a test of the stain with mice.

5.5 Genotoxicity. In vivo tests with reproductive cells. -Target and test conditions:

See point 5.4.

Circumstances in which they are required: When any results of an in vitro test with somatic cells are positive, it may be justified to carry out in vivo tests to determine the effects on the reproductive cells. The need to carry out these tests should be assessed on a case-by-case basis from the rest of the relevant information available, including the planned use and exposure. It would be necessary to examine the interaction with DNA by appropriate tests (such as the dominant case-fatality test) to study the potential of producing hereditary effects and, if possible, to carry out a quantitative assessment of such effects. It is recognised that, given the complexity of the quantitative studies, their use would require them to be considered very justified.

5.6 Summary of toxicity, pathogenicity and infectiousness in mammals and overall assessment. -A summary of all data and information provided in points 5.1 to 5.5 should be provided and a detailed assessment will be included. and criticises such data in the context of relevant criteria and guidelines for assessment and decision-making, with particular reference to the risks that may arise for man and animals, and the extent, quality and reliability of the data. basic data.

It should be explained whether the exposure of animals or humans affects vaccination or serological monitoring.

6. RESIDUES INSIDE OR ON THE SURFACE OF TREATED PRODUCTS, FOOD AND FEED

Introduction

(a) The information submitted, together with the information corresponding to one or more preparations containing the micro-organism, shall be sufficient to carry out a risk assessment for man or animals derived from exposure to the micro-organism. microorganism and its residues and metabolites (toxins) that remain on the surface or inside plants or plant products.

b) In addition, the information provided will be sufficient for:

Decide whether or not the micro-organism can be included in Annex I to Royal Decree 2163/1994.

Specify the relevant conditions or restrictions in case it is included in Annex I to Royal Decree 2163/1994.

Where appropriate, set maximum residue limits and timeframes, pre-harvest intervals to protect consumers and waiting periods to protect workers in connection with the handling of waste. crops and treated products.

(c) For the risk assessment of waste, it may not be necessary to submit experimental data on the residue levels when it can be justified that the micro-organism and its metabolites are not dangerous for the man to the concentrations that could be given as a result of the authorized use. This justification may be based on the published literature, on the practical experience and on the information presented in Sections 1 to 3 and 5.

6.1 Persistence and probability of multiplication on the surface or inside of cultivated plants, feed or food.-A justified estimate of the persistence/competitiveness of the micro-organism and its relevant secondary metabolites (especially toxins) within or on the surface of plants grown under the prevailing environmental conditions during and after the intended use, taking into account in particular the information provided in Section 2.

Furthermore, the application shall state to what extent and on what basis the micro-organism is considered to be capable or not to be multiplied within or on the surface of the plant or plant product, or during the processing of raw materials.

6.2 Additional information required. -Consumers may be exposed to micro-organisms for a considerable period of time due to the consumption of treated food products; therefore, the potential effects of the on consumers from chronic or semi-chronic studies, so that a toxicological 'end point' can be established for risk management purposes, such as the acceptable daily intake (ADI).

6.2.1 Unviable waste: An unviable micro-organism is a micro-organism unable to replicate or transfer genetic material.

If points 2.4 and 2.5 of section 2 have shown that certain important quantities of the micro-organism or its metabolites produced, especially toxins, are persistent, it will be necessary to submit experimental data. complete on the waste as referred to in Section 6 of Part A of this Annex II, if concentrations of the micro-organism or its toxins are expected to occur within or on the surface of treated food or feed which are higher than concentrations under natural conditions or in a different phenotypic state.

According to the Order of 4 August 1993, the conclusion on the difference between natural concentrations and a high concentration due to treatment with the micro-organism should be based on data obtained experimentally, and not in extrapolations or calculations from models.

Prior to such studies, the applicant shall obtain the agreement of the competent authorities on the type of study to be carried out.

6.2.2 Viable wastes: If the information submitted in accordance with point 6.1 indicates the persistence of significant quantities of micro-organisms on the surface or inside the treated products, food or feed, they shall have to investigate possible effects on man or animals, unless it can be justified, on the basis of Section 5, that the micro-organism and its metabolites or degradation products are not dangerous to humans at concentrations and in the form that may be given as a result of the authorised use.

According to the Order of 4 August 1993, the conclusion on the difference between natural concentrations and a high concentration due to treatment with the micro-organism should be based on data obtained experimentally, and not in extrapolations or calculations from models.

Special attention should be paid to the persistence of viable residues if in points 2.3 or 2.5 or in Section 5 infectiousness or pathogenicity has been found with respect to mammals, or if any other information is found to there can be danger for consumers or workers. In that case, the competent authorities may require studies similar to those referred to in Part A.

Prior to such studies, the applicant shall obtain the agreement of the competent authorities on the type of study to be carried out.

6.3 Summary and evaluation of the behaviour of the waste, based on the data presented under points 6.1 and 6.2.

7. FATE AND BEHAVIOUR IN THE ENVIRONMENT

Introduction

(a) The basis of the assessment of the destination and the behaviour in the environment is composed of information on the origin, properties and survival of the micro-organism and its residual metabolites, as well as its use. intended.

It is usually necessary to provide experimental data, unless it can be justified to assess the fate and behaviour in the environment with the information already available. This justification can be based on published biobiography, on practical experience and on the information presented in Sections 1 to 6. The role of the micro-organism in environmental processes is of particular interest (according to section 2, point 2.1.2).

(b) The information submitted, together with the rest of the relevant information, and the information corresponding to one or more preparations containing the micro-organism, shall be sufficient to enable it to assess its destination and behaviour, such as those of their residues and toxins, in case they are relevant to human health or the environment.

c) In particular, the information provided will be sufficient for:

Decide whether or not the micro-organism can be included in Annex I.

Specify the relevant conditions or restrictions in case it is included in Annex I.

Specify symbols (once introduced) and hazard statements and type phrases on the nature of risks and safety measures for environmental protection to be included in packaging (containers).

Predict the distribution, destination and behaviour of the micro-organism and its metabolites in the environment, as well as the expected time evolution.

Point out the measures needed to minimize environmental pollution and the consequences for species other than the target species.

d) All relevant metabolites (i.e., of interest to human health or the environment) formed by the body studied in all relevant environmental conditions should be characterised.

If there are relevant metabolites present in or produced by the micro-organism, the data presentation may be required as indicated in Section 7 of Part A of this Annex II, if all of the relevant metabolites are present. Following conditions:

The relevant metabolite is stable outside the micro-organism (point 2.8), and the toxic effect of the relevant metabolite is independent of the presence of the micro-organism, and the relevant metabolite is expected to be present in the The environment is considerably higher than those in natural conditions.

e) Account should be taken of the available information on the relationship with related wild micro-organisms found in nature.

f) Before carrying out the studies referred to below, the applicant shall obtain the agreement of the competent authority on whether the studies are necessary and, if so, on the type of studies to be carried out. must be performed. The information from the other sections shall also be taken into account.

7.1 Persistence and multiplication.-Where appropriate, appropriate information on the persistence and multiplication of the micro-organism in all environmental compartments should be provided, unless the improbability of an exposure to the micro-organism in a particular environmental compartment. Particular attention shall be paid to the following:

Competitiveness in the prevailing environmental conditions during and after the intended use, and population dynamics in extreme regional or seasonal climates (especially, warm summer, cold winter and rain) and in relationship to the agricultural practices applied after the intended use.

The time evolution of the expected levels of the specified micro-organism following the use of the product under the proposed conditions shall be indicated.

7.1.1 Soil: Information on the viability or dynamics of the population in several soils, cultivated and uncultivated, representative of soils typical of the different regions where the use is foreseen or is given.

The provisions on soil selection and their collection and handling, as provided for in the introduction to Part A, point 7.1, shall be followed if the studied organism is to be used in association with other means. (for example, mineral wool), these should be included in the series studied.

7.1.2 Water: Information on the viability/dynamics of the population in natural sediment and water systems, in conditions of both darkness and illumination, should be provided.

7.1.3 Air: In case of special concern for an exposure of operators, workers or others, it may be necessary to provide information on concentrations in the air.

7.2 Mobility.-The possible spread of the micro-organism and its degradation products in the relevant environmental compartments should be assessed, unless the improbability of an exposure to the micro-organism can be justified. micro-organism in specific environmental compartments. In this context, the following aspects are particularly interesting: the intended use (e.g. in field or greenhouse, application to soil or plants), the phases of the life cycle, including the presence of vectors, persistence and the possibility of the organism colonizing some adjacent habitat.

It is necessary to pay particular attention to the spread, persistence and likely distances of transport, if signs of toxicity, infectiousness or pathogenicity have been reported, or if any other information suggests a possible danger to men, animals or the environment. In such a case, the competent authority may require studies similar to those referred to in Part A. Before such studies, the applicant shall obtain the agreement of the competent authority on the type of study to be carried out.

8. EFFECTS ON NON-TARGET ORGANISMS

Introduction

(a) Information on identity, biological properties and other data in Sections 1 to 3 and 7 constitutes the basis for the assessment of the effect on non-target species. Additional useful information on the fate and behaviour of the environment in Section 7 and on the levels of residues in plants in Section 6 may be found; this information, together with the information on the preparation and its mode of employment, defines the nature and extent of possible exposure. The information submitted in accordance with Section 5 shall provide essential data for the effects on mammals and the mechanisms involved.

It is usually necessary to provide experimental data, unless it can be justified to assess the effects on non-target organisms with the information already available.

(b) The selection of non-target organisms suitable for the testing of environmental effects shall be based on the identity of the micro-organism (including the specificity of the host, mode of action and ecology). of the body). From this data it should be possible to select the appropriate organisms for testing, such as organisms closely related to the target organism.

(c) The information provided, together with the information relating to one or more preparations containing the micro-organism, shall be sufficient to permit the assessment of the effects on non-target species (flora and fauna), which they possess environmental importance and that they may be at risk of exposure to the micro-organism. The effects may be the result of a single, prolonged or repeated exposure, and may be reversible or irreversible.

(d) In particular, the information provided on the micro-organism, together with other relevant data, and the information relating to one or more preparations containing it shall allow:

Decide whether or not the micro-organism can be included in Annex I.

Specify the relevant conditions or restrictions in case it is included in Annex I.

Allow an assessment of short-and long-term risks for non-target species (populations, communities, and processes), as appropriate.

Classify the microorganism according to the biological hazard.

Specify the precautions necessary for the protection of non-target species. Specify the symbols and indications of danger (once introduced), and the relevant phrases on the nature of the risks and safety measures for the protection of the environment to be mentioned in the package (containers).

e) It will be necessary to report all potentially adverse effects discovered during routine environmental investigations and to make and make known, upon request by the competent authority, additional studies they may be necessary to investigate the possible mechanisms involved and to assess the importance of such effects. All relevant biological data should be reported for the assessment of the ecological profile of the micro-organism.

f) All studies should indicate the average dose reached in ufc/kg body weight as well as any other appropriate unit.

g) It may be necessary to carry out separate studies of relevant metabolites (especially toxins) where such products may constitute an important risk to non-target organisms and where their effects cannot be assessed. from the available results for the micro-organism. Before carrying out such studies, the applicant shall obtain the agreement of the competent authority on whether it is necessary to carry out such studies and, if so, on the type of studies to be carried out. The information from Sections 5 and 7 shall also be taken into account.

h) In order to facilitate the assessment of the significance of the test results, the same strain (or the same registered origin) of each of the relevant species should be used whenever possible. different tests specified.

(i) The tests shall be carried out unless it can be justified that the non-target organism is not exposed to the micro-organism. If it is justified that the micro-organism does not cause toxic effects or is not pathogenic or infectious in relation to vertebrates or plants, it will only be necessary to investigate the reaction with the appropriate non-target organisms.

8.1 Effects on Birds. -Objective of the test: Data on toxicity, infectiousness and pathogenicity for birds should be reported.

8.2 Effects on aquatic organisms. -Objective of the test: Data on toxicity, infectiousness and pathogenicity for aquatic organisms should be reported.

8.2.1 Fish effects. -Test target: Data on toxicity, infectiousness and pathogenicity for fish should be reported.

8.2.2 Effects on freshwater invertebrates. -Objective of the test: Data on toxicity, infectiousness and pathogenicity for freshwater invertebrates should be reported.

8.2.3 Effects on algae growth. -Objective of the test: Data on effects on growth, growth rate and recovery capacity of algae should be reported.

8.2.4 Effects on plants other than algae. -Objective of the test: Data on effects on plants other than algae should be reported.

8.3 Effects on Bees. -Objective of the test:

Data on toxicity, infectiousness and pathogenicity for bees should be reported.

8.4 Effects on arthropods other than bees. -Objective of the test: Data on toxicity, infectiousness and pathogenicity for arthropods other than bees should be reported. The selection of the species studied will be based on the possible use of plant protection products (e.g. leaf application or soil). Particular attention should be paid to the organisms used in the biological control and to those involved in an important way in the integrated pest management.

8.5 Effects on earthworms. -Objective of the test: Data on toxicity, infectiousness and pathogenicity for earthworms should be reported.

8.6 Effects on non-target soil micro-organisms.-Information on the effects on the relevant non-target micro-organisms and on their predators (e.g. protozoa in case of bacterial inoculum) should be provided. The expert opinion should be sought to decide whether further studies are necessary.

Such a decision shall take into account the information available in the present and other sections, in particular the data on the specificity of the micro-organism and the expected exposure. Useful information may also be obtained from the observations made in the efficacy tests. Special attention should be paid to the bodies used in integrated crop management.

8.7 Additional studies. -Additionally, further studies of acute effects on other species or processes (such as wastewater systems) or higher stage studies, such as studies of chronic effects, may be included. sublethal or on the reproductive function in selected non-target organisms.

Prior to such studies, the applicant shall obtain the agreement of the competent authorities on the type of study to be carried out.

9. SUMMARY AND REVALUATION OF THE EFFECT ON THE ENVIRONMENT

A summary and an assessment of all data relating to the environmental effect should be made in accordance with the guidelines drawn up by the competent authorities of the Member States in respect of the presentation of the of such summaries and evaluations. A detailed and critical assessment of this data should be included in the context of the criteria and guidelines for assessment and decision-making, with particular emphasis on the risks, real or possible, for the environment and the non-target species, as well as the size, quality and reliability of the database. The following aspects shall be addressed in particular:

Distribution and destination in the environment, as well as corresponding temporal evolution.

Identification of non-target populations and species at risk, and importance of their potential exposure.

Presentation of necessary precautions to avoid or minimize environmental contamination and to protect non-target species.

ANNEX III

Addendum to Annex III of the Order of 4 August 1993

" 2.6 Notwithstanding the provisions of point 2.1, as regards active substances consisting of micro-organisms or viruses, the tests and analyses carried out to obtain data on the properties or safety with respect to aspects other than human health may have been carried out in official or officially recognised facilities or testing bodies which meet at least the requirements set out in points 2.2 and 2.3 of the introduction to this Annex III. '

ANNEX IV

Part B of Annex III to the Order of 4 August 1993

INTRODUCTION

(a) This part provides for the data requirements for the authorisation of a plant protection product on the basis of micro-organism preparations, including viruses.

The definition of the term "micro-organism" in the introduction of Part B of Annex II shall also apply to this Part B.

(b) Where relevant, the data shall be analysed according to appropriate statistical methods. All details of the statistical analysis should be reported (for example, all point estimates should be given with confidence intervals and the exact p values should be given instead of indicating "significant/non-significant").

(c) In the absence of acceptance of specific guidelines at international level, the required information shall be obtained by applying test guidelines accepted by the competent authority, such as the USEPA guidelines. (Microbial pesticide test guidelines, OPPTS Series 885, February 1996); if necessary, the test guidelines described in Part A of Annex II shall be adapted in such a way as to be suitable for micro-organisms. The tests shall include viable micro-organisms and, where appropriate, non-viable, as well as a blank check.

d) When a study involves the use of different doses, the relationship between dose and side effects should be reported.

e) In the case of tests, a detailed description (specification) of the material used and its impurities, as set out in point 1.4 of Section 1, shall be submitted.

(f) In the case of a new preparation, the extrapolation of Part B of Annex II may be accepted, provided that all possible effects of the adjuvants and other components are also assessed, in particular as regards the pathogenicity and infectiousness.

1. IDENTITY OF THE PLANT PROTECTION PRODUCT

The information submitted, together with the information concerning the micro-organism or micro-organisms, must be sufficient to identify and define precisely the preparations.

Except where otherwise indicated, the data referred to below shall be required for all plant protection products. The intention is to detect the possibility of any factor altering the properties of the micro-organism in the plant protection product in relation to those of the isolated micro-organism, which are the subject of Part B of Annex II to the Royal Decree 2163/1994.

1.1 Applicant.-The name and address of the applicant (permanent address in the Community), as well as the name, function and telephone number and fax number of the contact person must be specified.

When, in addition, the applicant has offices, agents or representatives in Spain, he must indicate his name and address, as well as the name, title and telephone number and fax number of the contact person corresponding.

1.2 Manufacturer of the preparation and of the micro-organisms.-The name and address of the manufacturer of the preparation and of each micro-organism incorporated therein must be indicated, as well as the name and address of all the factories in the preparation of the preparation and the micro-organisms.

For each manufacturer, a point of contact (preferably central, including name and telephone and fax numbers) must be indicated.

If the micro-organism comes from a producer which has not previously submitted data in accordance with Part B of Annex II, detailed information on the name and description of the species shall be provided, as well as on impurities as referred to in points 1.3 and 1.4 of Part B of Annex II respectively.

1.3 Trade name or proposed trade name and development code number assigned to the plant protection product by the manufacturer, if any. -All old, current and proposed trade names must be indicated, the development code numbers of the preparation referred to in the file and the current names and numbers. Any differences shall be specified in detail. (The proposed trade name should not give rise to confusion with the trade name of plant protection products already authorised.) 1.4 Detailed quantitative and quantitative information on the composition of the preparation:

(a) Each micro-organism which is the subject of the application shall be identified and appointed at the species level. The micro-organism shall be deposited in a recognised crop collection, in which it shall have received an entry number. The scientific name as well as the allocation to a group (bacteria, viruses, etc.) and any other relevant name of the micro-organism (e.g. strain or serotype) shall be indicated. The development phase of the micro-organism (e.g. spores or mycelium) present in the marketed product shall also be indicated.

b) The following data should be provided on the preparations:

Content of the micro-organisms or micro-organisms in the plant protection product and the content of the micro-organism in the material used for the manufacture of plant protection products; the maximum, minimum and nominal content shall be indicated of the viable and non-viable material.

Adjuvant content.

Content of other components (such as by-products, condensates, culture medium, etc.) and contaminating microorganisms, derived from the production process.

The content must be expressed in the terms indicated in Article 9 of the Technical-Health Regulations for the Manufacture, Marketing and Use of Pesticides, approved by Royal Decree 3349/1983, of 30 of November, in the case of chemical substances and in the appropriate terms in the case of micro-organisms (number of active units by volume or weight, or in any other way relevant to the micro-organism).

(c) Where possible, the adjuvants must be identified by their chemical name as specified in Annex I to Royal Decree 363/1995, as amended by Order of 5 April 2001, or not specified, agreement with the nomenclature of both the International Union of Pure and Applied Chemistry (UIQPA) and CA. Its structure or developed formula shall be indicated. The corresponding EEC numbers (Einecs or Elincs), as well as the CAS number, shall be indicated for each component of the adjuvants. Where the information provided is not sufficient for the total identification of an adjuvant, it shall be added as many additional data as necessary. The trade name of the adjuvants shall also be indicated, if any.

d) The function of the adjuvants must be indicated:

Adhesive.

Antifoaming.

binder.

Buffer.

Carrier.

Deodorant.

Dispersant.

Colorant.

Emetic.

Emulsifiers.

Fertilizer.

Odorant.

Perfume.

Conservant.

Propellant.

repellent.

Protector.

Solvent.

Stabilizer.

Synergistic.

Thickener.

Moisturiser.

Other type (specify).

e) Identification of contaminant microorganisms and other components derived from the production process.

Contaminating micro-organisms shall be identified as indicated in point 1.3 of Section 1 of Part B of Annex II.

Chemical substances (inert components, by-products, etc.) shall be identified as set out in point 1.10 of Section 1 of Part A of Annex II.

If the information provided is not sufficient to identify a component (such as condensates, culture media, etc.), detailed information on the composition of each of these components will be provided.

1.5 Physical status and nature of the preparation. -The type and code of the preparation must be indicated in accordance with the Catalogue of Pesticide Formulation Types and International Coding System (technical monograph number 2 of the GIFAP, 1989).

When any preparation is not exactly defined in this publication, a full description of the nature and physical state of the preparation must be provided, along with a valid description of the type of preparation and a proposal for a definition.

1.6 Function. -The biological function of the following will be specified:

Fight against bacteria.

Fight against fungi.

Fight against insects.

Fight against mites.

Fight against mollusks.

Fight nematodes.

Fight weed.

Other type (specify).

2. PHYSICAL, CHEMICAL AND TECHNICAL PROPERTIES OF THE PLANT PROTECTION PRODUCT

It shall be indicated to what extent the plant protection products for which the authorisation is requested are in accordance with the relevant specifications established by the pesticide specification experts in the specification group. on pesticides, registration conditions and implementing rules of the Food and Agriculture Organization of the United Nations (FAO).

They will be listed in detail and any differences with FAO specifications will be justified.

2.1 Appearance (color and odor).-A description of the color and odor (if any), as well as the physical state of the preparation.

2.2 Storage Stability and Conservation Term:

2.2.1 Effects of light, temperature and humidity on the technical characteristics of the plant protection product:

(a) The physical and biological stability of the preparation at the recommended storage temperature, including data on the growth of the contaminating micro-organisms, shall be studied and reported.

The conditions under which the study has been conducted should be justified.

(b) In addition, in the case of liquid preparations, the effect of low temperatures on physical stability shall be determined and reported, in accordance with CIPAC (3) MT 39, MT 48, MT 51 or MT 54, as appropriate.

c) The storage period of the preparation shall be indicated at the recommended storage temperature.

When this period is less than two years, it must be expressed in months and accompanied by indications on the appropriate temperatures. The monograph No 17 of GIFAP (4) provides information of interest.

2.2.2 Other factors affecting stability:

The effect of exposure to air, packaging, etc., on product stability should be explored.

2.3 Explosives and oxidising properties. The explosiveness and the oxidizing properties shall be determined as specified in Section 2 (2.2) of Part A of this Annex III, unless technical or technical justification is available. scientifically that such studies do not need to be conducted.

2.4 Inflammation point and other data on the flammability or spontaneous combustion. The flash point and the flammability shall be determined as indicated in paragraph 2.3 of Section 2 of Part A of this Annex III, unless it can be technically or scientifically justified that such studies are not necessary.

2.5 Acidity, alkalinity and, if necessary, pH.-The acidity, alkalinity and pH shall be determined as indicated in Section 2 of Section 2 of Part A of this Annex III, unless technical or technical reasons can be justified. scientifically that such studies do not need to be conducted.

2.6 Viscosity and surface tension. The viscosity and surface tension shall be determined as indicated in paragraph 2.5 of Section 2 of Part A of this Annex III, unless it can be technically or scientifically justified. no such studies need to be carried out.

2.7 Technical characteristics of the plant protection product-The technical characteristics of the preparation must be determined in order to be able to take a decision on their eligibility. If tests are to be performed, they shall be done at temperatures compatible with the survival of the micro-organism.

2.7.1 Mojability: The mojability of solid preparations that are diluted for use (e.g. wet powders and water-dispersible granules) shall be determined and pointed out in accordance with CIPAC Method MT 53.3.

2.7.2 Persistent foam formation: The persistence of foam formation in preparations to be diluted in water shall be determined and pointed out in accordance with the CIPAC MT 47 method.

2.7.3 Suspense and suspension stability:

It shall be determined and reported in accordance with CIPAC methods MT 15, MT 161 or MT 168, as appropriate, the suspension of water dispersible products (e.g. wet powders, water dispersible granules). or the suspension concentrates).

It shall be determined and reported in accordance with CIPAC methods MT 160 or MT 174, as appropriate, the spontaneity of the dispersion of the water dispersible products (e.g. suspension concentrates and granules). Water dispersible).

2.7.4 Dry sieve test and wet sieve test: To make sure the powder granulometry

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(3) International Council for Collaboration in Pesticide Analysis (Collaborative International Pesticides Analytical Council).

(4) International Group of National Associations of Agrochemical Manufacturers.

sprinkles are suitable for the ease of application, it is necessary to perform and to point to a dry test according to the CIPAC method MT 59.1.

In the case of water-dispersible products, a wet sieve test shall be performed and reported in accordance with CIPAC methods MT 59.3 or MT 167, as appropriate.

2.7.5 Granulometry (dusting and wettable powders, granules), powder or fine content (granules), wear resistance and friability (granules):

(a) In the case of powder preparations, its particle size shall be determined and reported in accordance with OECD Method 110.

The range of nominal sizes of the direct application granules, in accordance with the CIPAC method MT 58.3, and water dispersible granules shall be determined and reported in accordance with CIPAC Method MT 170.

(b) The powder content of the granules shall be determined and reported according to the CIPAC Method MT 171. If it is important for the operator to be exposed, the particle size of the powder must be determined and reported according to OECD Method 110.

(c) Where internationally accepted methods are available, the characteristics of friability and wear resistance of the granules shall be determined and reported. All the data that are already available shall be communicated, together with the methods used for their determination.

2.7.6 Emulsionability, reemulsisionability, and emulsion stability:

(a) Emulsification, emulsion stability and reemulsification of preparations forming emulsions shall be determined and reported in accordance with CIPAC methods MT 36 or MT 173, as appropriate.

(b) The stability of the diluted emulsions and preparations which are emulsions shall be determined and reported in accordance with CIPAC methods MT 20 or MT 173.

2.7.7 Flow, pour, and spray properties:

(a) The flow properties of granular preparations shall be determined and reported according to the CIPAP method MT 172.

(b) The dumping properties (including the washing residue) of the suspensions (e.g. suspension concentrates and subemulsions) shall be determined and reported in accordance with CIPAC Method MT 148.

(c) The spray properties of dusting powders shall be determined and reported in accordance with the CIPAC MT 34 method or other appropriate method.

2.8 Physical, chemical and biological compatibility with other products, including plant protection products with which the use may be authorised:

2.8.1 Physical compatibility: The physical compatibility of the recommended prepared mixtures should be determined and reported.

2.8.2 Chemical compatibility: The chemical compatibility of recommended prepared mixtures should be determined and noted, except where the examination of the individual properties of each preparation allows to discard reasonable assurance that reactions will be possible. In such cases, it is sufficient to provide such information to justify the failure to determine in practice the chemical compatibility.

2.8.3 Biological compatibility: The biological compatibility of the prepared mixtures should be determined and reported. The effects (e.g. antagonism or fungicidal effects) on the activity of the micro-organism after mixing with other micro-organisms or chemicals shall be described. The potential interaction of the plant protection product with other chemicals that apply to crops under the intended conditions of use of the preparation shall be investigated on the basis of data on efficacy. The intervals between the applications of the biological pesticide and the chemical pesticides should be specified, where appropriate, in order to avoid any effectiveness.

2.9 Adherence and distribution on seeds.

In the case of preparations intended for the treatment of seeds, their distribution and adhesion shall be investigated and noted; for distribution the CIPAC Method MT 175 shall be used.

2.10 Summary and evaluation of data submitted under points 2.1 to 2.9.

3. DATA ABOUT THE APPLICATION

3.1 Intended areas for use.-The current or proposed areas of use shall be specified for the preparations containing the micro-organism, including the following:

Field use, such as agriculture, horticulture, forestry, and viticulture.

Protected crops (e.g. in greenhouses).

Recreational activities.

Fighting weeds in uncultivated areas.

Gardening.

Interior plants.

Stored products.

Other (specify).

3.2 Mode of action.-The possible forms of absorption of the product (e.g. contact, ingestion, inhalation) or action against pests (fungitoxic, fungistatic, nutrient competition, etc.) should be indicated.

It shall also be specified whether or not the product is translocated in plants and, where appropriate, whether such translocation is apoplastic, simple or of both types.

3.3 Data on the intended use-details of the intended uses, such as types of harmful organisms, and protected plants or plant products should be provided.

The intervals between applications of the plant protection product with micro-organisms and those of chemical pesticides should also be specified or a list of active substances of chemical plant protection products not to be used in the same crop as the plant protection product with micro-organisms.

3.4 Application rate. -For each application method and each intended use, the application rate per unit (ha, m2, m3) treated, expressed in g, kg or l of preparation and in the appropriate units for the micro-organisms

In general, the application fees shall be expressed in g or kg/ha or kg/m3 and, where applicable, in g or kg/t; in the case of protected crops or domestic gardens, the rates shall be expressed in g or kg/100 m2 or in g or kg/m3.

3.5 Concentration of the micro-organism in the material used (e.g. in the diluted aerosol, baits or treated seeds). The micro-organism content shall be indicated, where relevant, in the number of active units/ml or g, or in any other appropriate unit.

3.6 Method of application.-The proposed method of application will be described in detail, indicating the type of equipment eventually required, as well as the type and volume of diluent to be used per unit of surface or volume.

3.7 Number and temporary distribution of applications and duration of protection-The maximum number of applications and their temporary distribution will be specified. Where appropriate, the growth stages of crops or plants intended to be protected and the stages of development of harmful organisms shall be indicated. If possible and necessary, the interval between applications, expressed in days, shall be indicated.

The duration of protection achieved with each application and the maximum number of applications must also be indicated.

3.8 Required waiting periods, or other precautions, to avoid the occurrence of phytopathogenic effects on subsequent crops. -Where appropriate, the minimum waiting time between the last application of the the product and the planting or planting of the next crop which are necessary to avoid phytopathogenic effects on subsequent crops. This data shall be deducted from those set out in point 6.6 of Section 6.

Any limitation on the choice of subsequent crops shall be indicated.

3.9 Proposed employment instructions.-The proposed instructions for use of the preparation, which should be included in the labels and leaflets, will be provided.

4. ADDITIONAL INFORMATION ON THE PLANT PROTECTION PRODUCT

4.1 Packaging and compatibility of the preparation with the proposed packaging materials:

(a) The proposed packaging shall be fully described and specified, with reference to the materials used, the method of construction (extrusion, welding, etc.), the size and capacity, the size of the opening and the types of closures and seals. The design of the packaging must comply with the criteria and guidelines laid down in the FAO Guidelines for Pesticide Packaging.

(b) The adequacy of the packages and their closures (depending on their robustness, impermeability and resistance to normal transport and handling operations) shall be determined and indicated in accordance with the ADR methods 3552, 3553, 3560, 3554, 3555, 3556 and 3558, or ADR methods suitable for intermediate containers for bulk products and, in the case of preparations requiring safety closures for children, in accordance with ISO 8317.

(c) The strength of the packaging material with respect to its contents shall be indicated in accordance with the monograph No 17 of the GIFAP.

4.2 Application Equipment Cleaning Procedures-The cleaning procedures of the application equipment and protective clothing will be described in detail. It will be determined (e.g. with biological testing) and the effectiveness of the cleaning procedures will be indicated.

4.3 Intervals to elapse before re-entering the plantation, waiting periods and other precautions necessary for the protection of people, livestock and the environment.-The information provided must derived from the data presented in relation to the micro-organism or micro-organisms and those listed in Sections 7 and 8.

(a) Where appropriate, any intervals before the harvest shall be indicated, the time limits before reentering the planting or the retention periods in order to minimise the presence of residues in crops, plants and plant products, or in

treated areas or areas, in order to protect people or livestock, such as:

Interval (in days) before the harvest of each of the corresponding crops.

Deadline (in days) before cattle graze the treated areas again.

Deadline (in hours or days) before people come back in contact with crops, buildings or treated areas, Retention Deadline (in days) for feed.

Wait time (in days) between application and handling of treated products.

(b) Where necessary, information shall be provided on the special agricultural, plant health or environmental conditions in which the preparation may or may not be used, on the basis of the results of the tests.

4.4 Recommended methods and precautions for handling, storage and transport or in the event of fire. -Detailed methods and precautions for handling procedures for the handling of the fire shall be specified in detail. storage of plant protection products, both in commercial warehouses and at user level, and in their transport, as well as in the event of fire. Where relevant, data on the products of combustion shall be provided. The possible risks and the methods and procedures necessary to reduce them to the maximum shall be indicated. Procedures shall be established to prevent or reduce the formation of waste or debris.

Where relevant, the assessment shall be carried out in accordance with ISO TR 9122.

The type and characteristics of the proposed protective clothing and equipment shall be indicated. Sufficient data shall be provided to assess the adequacy and effectiveness under realistic conditions of use (e.g. in the field or in the greenhouse).

4.5 Measures in the event of an accident.-The procedures for action in the event of an accident shall be detailed, either during the transport, storage or use of the products, including the following aspects:

Containment of discharges.

The decontamination of land, vehicles and buildings.

The removal of damaged packaging, adsorbents and other materials.

The protection of relief workers and others.

First aid measures.

4.6 Procedures for the destruction or decontamination of the plant protection product and its packaging. -Procedures for destruction and decontamination of the product will be developed in small quantities (in the user's power) and large (in warehouses).

These procedures should be in line with existing provisions on the disposal of toxic and non-toxic waste. The proposed disposal methods must be without harmful effects on the environment and be the most cost-effective and practical to be applied.

4.6.1 Controlled Incineration: On numerous occasions, the best or only means of safely removing plant protection products and, in particular, adjuvants containing, or contaminated materials and packaging, consists of: Controlled incineration in an authorised incinerator.

The applicant must provide detailed instructions for removing the product without danger.

4.6.2 Other types: The other methods proposed for the disposal of plant protection products, packaging and contaminated materials shall be described in detail. Data shall be provided on such methods to establish their effectiveness and safety.

5. ANALYTICAL METHODS

Introduction

The provisions of this Section shall only apply to the analytical methods necessary for post-registration monitoring and monitoring.

It is best to have a clean plant protection product where possible. The competent authority shall assess the level of pollutants acceptable from the point of view of the risk assessment.

Both production and the product will be subject to continuous quality control by the applicant. The quality criteria for the product shall be presented.

Applicants shall justify the analytical methods used to obtain the data required in this Annex or for other purposes; if necessary, separate guidance shall be established for those methods according to them. requirements imposed in the case of methods for post-registration control and monitoring.

Description of methods including equipment data, materials and conditions used shall be provided. The applicability of existing CIPAC methods should be noted.

As far as possible, these methods should be based on the simplest techniques, cost as little as possible and use material that can be easily obtained.

For the purposes of this Section,

following definitions shall apply:

"Impurities": Any component (including micro-organisms or chemical pollutants) other than the specified micro-organism, due to the manufacturing process or degradation during storage, " Impurity relevant ': impurities, as defined above, of importance for human or animal health or for the environment.

"Metabolites": Products derived from degradation and biosynthesis reactions occurring in the micro-organism or in other organisms used to produce the corresponding micro-organism.

Relevant Metabolites: Metabolites of importance for human or animal health or for the environment.

"Waste": viable micro organisms and substances produced in significant quantities by these micro-organisms, which persist after the disappearance of these micro-organisms and are of importance to human or animal health or to the environment environment.

If requested, the following samples shall be provided:

a) Samples of the preparation.

b) Samples of the micro-organism as finally produced.

c) Analytical patterns of the pure micro-organism.

(d) Analytical patterns of relevant metabolites and all other components included in the definition of 'waste'.

e) If available, reference substance samples of the relevant impurities.

5.1 Methods for analysis of the preparation:

Methods (for which a complete description will be given) shall be provided for the identification and determination of the content of the micro-organism in the preparation. In the case of a preparation containing more than one micro-organism, methods capable of identifying and determining the content of each of them shall be provided.

Methods of regular control of the final product (prepared) to show that it does not contain organisms other than those indicated and to determine its uniformity.

Methods of identification of the possible contaminant microorganisms of the preparation.

Methods for determining stability during storage and the storage time of the preparation.

5.2 Methods for detecting and quantifying waste. Analytical methods for the determination of residues as defined in point 4.2 of Section 4 of Part B of Annex II shall be submitted, unless the adequacy of the information already submitted in accordance with the requirements of this Regulation is justified. that point.

6. DATA ON EFFICACY

The provisions relating to data on effectiveness are already adopted under the Order of 11 December 1995 laying down the provisions relating to the authorisation of trials and experiments with the plant protection products.

7. EFFECTS ON HUMAN HEALTH

In order to correctly assess the toxicity of preparations, including pathogenicity and infectiousness, sufficient data on acute toxicity, irritation and sensitisation caused by the disease should be available. microorganism. If possible, further information on the toxic mode of action, the toxicological characteristics and all other known toxicological aspects of the micro-organism should be provided. Special attention should be paid to the interveners.

When any toxicological studies are organised, the signs of infection or pathogenicity should also be taken into account and the aspects of the elimination of the micro-organism should be included.

In relation to the influence of impurities and other components on toxicological behaviour, it is essential that a detailed description of the material is provided for each study submitted. employee. The tests shall be carried out using the plant protection product to be authorised.

In particular, it should be clear that the micro-organism used in the preparation and its growing conditions are the same as those for which information is presented in the context of Part B of Annex II.

A stage testing system for the study of the plant protection product shall be applied.

7.1 Basic acute toxicity studies. -Studies, data and information to be provided and evaluated shall be sufficient to identify the effects of a single exposure to the plant protection product and, in particular, to determine or indicate:

The toxicity of the plant protection product.

The toxicity of the plant protection product to the micro-organism.

The temporal evolution and the characteristics of its effects, along with complete data of changes in behavior and the eventual macroscopic pathological observations of the autopsy.

As possible, the mode of toxic action.

The relative dangers of different routes of exposure.

Although the emphasis should be placed on estimating the range of toxicity caused, the information to be obtained should also allow the classification of the plant protection product according to Royal Decree 162/1991 of 8 February, amend the Technical-Health Regulations for the manufacture, marketing and use of pesticides. The information obtained from the acute toxicity tests is of particular importance for the assessment of possible hazards in the event of an accident.

7.1.1 Acute toxicity by mouth. -Circumstances required: An acute oral toxicity test should always be carried out, unless the applicant can justify, to the satisfaction of the competent authority, that it can Article 3 (2) of Directive 78 /631/EEC is to be covered.

Test Guidelines: The test shall be carried out in accordance with Method B. 1 or B. 1a of Commission Directive 92/69/EEC.

7.1.2 Acute Inhalation Toxicity. -Objective of the test: The test will indicate the inhalation toxicity produced in rats by the plant protection product.

Circumstances in which it is required: The test must be performed when the plant protection product:

Be used with a nebulization equipment.

Be an aerosol.

Be a powder that contains a significant proportion of particles of diameter 50l (1 per 100 by weight).

Apply from an aircraft, if there is a risk of inhalation.

To be applied in such a way as to generate a considerable proportion of particles or droplets of 50l diameter (1 per 100 by weight).

Contains a volatile component in a ratio greater than 10 per 100.

Test Guidelines: The test shall be carried out in accordance with Method B. 2 of Directive 92 /69/EEC.

7.1.3 Acute toxicity via the skin.

-Circumstances in which it is required: A toxicity test must always be carried out by the skin, unless the applicant can justify, to the satisfaction of the competent authority, that he can avail himself of paragraph 2 of the Article 3 of Directive 78 /631/EEC.

Test Guidelines: The test shall be carried out in accordance with Method B. 3 of Directive 92 /69/EEC.

7.2 Additional acute toxicity studies:

7.2.1 Skin Irritation. -Objective of the test: The test should indicate the skin irritation capacity of the plant protection product, including the possible reversibility of the observed effects.

Circumstances in which it is required: The skin irritation capacity of the plant protection product must always be determined, except where the adjuvants are not expected to be skin irritants, or the micro-organism is shown to be is not a skin irritant, or is likely, as indicated in the test guidelines, that the presence of serious skin effects may be excluded.

Test Guidelines: The test shall be carried out in accordance with Method B. 4 of Directive 92 /69/EEC.

7.2.2 Eye Irritation-Test target: The test should indicate the eye irritation capacity of the plant protection product, including the possible reversibility of the observed effects.

Circumstances in which it is required: The eye irritation capacity of the plant protection product should be determined when the adjuvants are suspected to be eye irritants, except where the micro-organism is shown to be Eye irritant, or is likely, as indicated in the test guidelines, that serious eye effects may occur.

Test guidelines: Eye irritation should be determined in accordance with Method B. 5 of Directive 92 /69/EEC.

7.2.3 Skin sensitisation. -Objective of the test: The test must provide the information to determine the ability of the plant protection product to cause skin sensitisation reactions.

Circumstances in which it is required: The test must be performed when the adjuvants are suspected to have skin sensitising properties, except when it is known that the or the microorganisms or adjuvants have properties sensitisers of the skin.

Test Guidelines: Tests must be carried out in accordance with Method B. 6 of Directive 92 /69/EEC.

7.3 Exposure data. -Risks to those who are in contact with plant protection products (workers, outsiders, workers) depend on the physical, chemical and toxicological properties of these products. as of the type of product (undiluted or diluted), the type of formulation, the route of exposure and the degree and duration of the formulation. Sufficient information shall be obtained and provided in order to determine the extent of exposure to the plant protection product likely to be produced under the proposed conditions of use.

In case there is a particular concern about the possibility of skin absorption depending on the information on the micro-organism available under Section 5 of Part B of Annex II, or on the basis of the information submitted for the preparation of this Section 7 of this Part B, additional data on skin absorption may be required.

Results of the monitoring of exposure during the production or use of the product should be presented.

This information should be the starting point for the selection of appropriate protective measures, including personal protective equipment, to be applied by operators and workers and to be mentioned in the label.

7.4 Toxicological data available for inactive ingredients.-In relation to each adjuvant, a copy of the notification and the information sheet of the safety data submitted in accordance with the procedure shall be sent. Directive 1999 /45/EC of the European Parliament and of the Council and Commission Directive 91 /155/EEC of 5 March 1991 laying down and laying down, pursuant to Article 10 of Council Directive 88 /379/EEC, the detailed rules for the system of of specific information on dangerous preparations. Any other available information must be submitted.

7.5 Supplementary studies for associations of plant protection products. -Objective of the test: In some cases it may be necessary to carry out the studies mentioned in points 7.1 to 7.2.3 with product associations plant protection products, where the product label includes instructions for the use of the plant protection product with other plant protection products or with adjuvants in prepared mixtures. On the basis of the results of the studies on acute toxicity of the various plant protection products, the possibility of exposure to the association of the various plant protection products will be decided on a case-by-case basis. products in question and the information available on those products or similar products or the practical experience acquired with them.

7.6 Summary and Evaluation of Health Effects.-A summary of all data and information provided under points 7.1 to 7.5 shall be submitted and a detailed and critical assessment of such data shall be included. in the context of the relevant assessment and decision-making criteria and guidelines, with particular reference to the risks that arise or may arise for man and animals, and the extent, quality and reliability of the database.

8. RESIDUES INSIDE OR ON THE SURFACE OF TREATED PRODUCTS, FOOD AND FEED

The provisions of Section 6 of Part B of Annex II shall apply; the information required under this Section shall be provided, except where it is possible to extrapolate the behaviour of the plant protection product in the waste from the data available on the micro-organism. Particular attention should be paid to the influence of the substances present in the formulation on the residues of the micro-organism and its metabolites.

9. FATE AND BEHAVIOUR IN THE ENVIRONMENT

The provisions of Section 7 of Part B of Annex II shall apply; the information required under this Section shall be provided, except where it is possible to extrapolate the destination and behaviour of the product plant protection in the environment on the basis of the data available under Section 7 of Part B of Annex II.

10. EFFECTS ON NON-TARGET ORGANISMS

Introduction

(a) The information provided, together with the information relevant to the micro-organisms, shall be sufficient to permit the assessment of the effects of the plant protection product on non-target species (flora and fauna), when used of the proposed mode. The effects may be the result of a single, prolonged or repeated exposure and may be reversible or irreversible.

(b) The selection of the appropriate non-target organisms for the testing of environmental effects shall be based on the information on the micro-organism, required under Part B of Annex II, and on the information on the Adjuvants and other components, required under Sections 1 to 9 of this Part B. From this data it should be possible to select the appropriate testing organisms, such as closely related organisms. with the target organism.

(c) In particular, the information provided on the plant protection product, together with other relevant data, and the micro-organism, shall allow:

Specify the symbols of hazard indications, and the relevant phrases about the nature of the risks and safety measures for environmental protection to be mentioned in the container (container).

Allow an assessment of short-and long-term risks for non-target species (populations, communities and processes, as appropriate).

Allow an assessment of the need to adopt special precautions for the protection of non-target species.

d) It will be necessary to report all potentially adverse effects discovered during routine investigations on environmental effects and to make and release additional studies that may be necessary for investigate the mechanism involved and assess the importance of such effects.

e) In general, much of the data relating to the effect on non-target species required for the authorisation of plant protection products has been submitted and evaluated in relation to the inclusion of the micro-organism or micro-organisms in Annex I.

(f) When it is necessary to use exposure data to decide whether a study should be carried out, the data obtained in accordance with the provisions of Section 9 of this Part B shall be used.

To estimate the exposure of the organisms all relevant data on the plant protection product and on the micro-organism shall be taken into account. Where appropriate, the parameters referred to in this Section shall be used. Where the available data indicate that the plant protection product has a stronger effect than the micro-organism, the data relating to the effects of the plant protection product on non-target organisms shall be used to calculate the relationship between the effect and the exposure.

g) In order to facilitate the assessment of the importance of the results obtained in the tests, the same strain of each of the relevant species should be used in the different tests specified in the test. relationship with the effects on non-target organisms.

10.1 Effects on birds.-The same information as provided for in point 8.1 of Section 8 of Part B of Annex II shall be indicated where it is not possible to provide for the effects of the plant protection product on the basis of the data available on the micro-organism, unless the improbability of the exposure of the birds can be justified.

10.2 Effects on aquatic organisms.-The same information as provided for in point 8.2 of Section 8 of Annex II, Part B, shall be indicated where it is not possible to provide for the effects of the plant protection product from the data available on the micro-organism, unless it can be justified that the exposure of aquatic organisms is unlikely to occur.

10.3 Effects on bees. The same information as provided for in point 8.3 of Section 8 of Part B of Annex II shall be indicated where it is not possible to provide for the effects of the plant protection product on the basis of the data available on the micro-organism, unless the improbability of the exposure of bees can be justified.

10.4 Effects on arthropods other than bees.-The same information as provided for in point 8.4 of Section 8 of Part B of Annex II shall be indicated where it is not possible to provide for the effects of the plant protection product from the available data on the micro-organism, unless it is possible to justify the improbability of the exposure of arthropods other than bees.

10.5 Effects on earthworms.-The same information as provided for in point 8.5 of Section 8 of Part B of Annex II shall be indicated where it is not possible to provide for the effects of the plant protection product from of the data available on the micro-organism, unless it is possible to justify the improbability of the exposure of earthworms.

10.6 Effects on soil microorganisms. -Must

indicate the same information as referred to in point 8.6 of Section 8 of Part B of Annex II where it is not possible to provide for the effects of the plant protection product on the basis of the data available on the micro-organism, unless it can be justified that the exposure of non-target soil micro-organisms is unlikely to occur.

10.7 Additional studies.-The expert opinion should be sought to decide whether further studies are necessary. Such a decision shall take into account the information available under this and other sections, in particular data on the specificity of the micro-organism and the intended exposure.

Also, useful information may be obtained from the observations made in the efficacy tests.

Special attention should be paid to the possible effects on naturally occurring or artificially released organisms of importance for integrated pest management. The compatibility of the product with integrated pest management should be considered in particular.

Further studies may include further studies on additional species or higher stage studies, such as studies on selected non-target organisms.

Prior to such studies, the applicant shall obtain the agreement of the competent authorities on the type of study to be carried out.

11. SUMMARY AND ASSESSMENT OF THE EFFECT ON THE ENVIRONMENT

A summary and evaluation of all data related to the environmental effect should be made in accordance with the guidance developed by the Administration regarding the presentation of such summaries and evaluations. A detailed and critical evaluation of all data in the context of the relevant criteria and guidelines for assessment and decision-making should be included, with particular emphasis on the risks, real or possible, for the the environment and non-target species, as well as the size, quality and reliability of the database. The following aspects shall be addressed in particular:

Forecast of distribution and destination in the environment, as well as the corresponding temporal evolution.

Identification of non-target populations and species at risk, and forecast of the importance of their possible exposure.

Presentation of necessary precautions to avoid or minimize environmental contamination and to protect non-target species.