Commission Regulation (EU) No 544/2011 of 10 June 2011 implementing Regulation (EC) No 1107/2009 of the European Parliament and of the Council as regards the data requirements for active substances Text with EEA relevance
1.1. include a technical dossier supplying the information necessary for evaluating the foreseeable risks, whether immediate or delayed, which the active substance may entail for humans, animals and the environment and containing at least the information and results of the studies referred to below; 1.2. where relevant, be generated using test guidelines, in accordance with the latest adopted version, referred to or described in this Annex; in the case of studies initiated before the entry into force of the modification of this Annex, the information shall be generated using suitable internationally or nationally validated test guidelines or, in the absence thereof, test guidelines accepted by the competent authority; 1.3. in the event of a test guideline being inappropriate or not described, or where another one than those referred to in this Annex has been used, include a justification, which is acceptable to the competent authority for the guidelines used. In particular, when reference is made in this Annex to a method laid down in Commission Regulation (EC) No 440/2008 OJ L 142, 31.5.2008, p. 1 .1.4. include, when required by the competent authority, a full description of test guidelines used, except if they are referred to or described in this Annex, and a full description of any deviations from them including a justification, which is acceptable to the competent authority, for these deviations; 1.5. include a full and unbiased report of the studies conducted as well as full description of them or a justification, which is acceptable to the competent authority where: particular data and information which would not be necessary owing to the nature of the product or its proposed uses, are not provided, or it is not scientifically necessary, or technically possible to supply information and data;
1.6. where relevant, have been generated in accordance with the requirements of Council Directive 86/609/EEC OJ L 358, 18.12.1986, p. 1 .
chemical name in accordance with IUPAC and CA nomenclature, ISO common name or proposed common name if available, CAS number, EC (Einecs or ELINCS) number, and CIPAC number if available, molecular and structural formula, molecular mass, and maximum content in g/kg.
chemical name in accordance with IUPAC and CA nomenclature, ISO common name or proposed common name if available, CAS number, EC (Einecs or ELINCS) number, and CIPAC number if available, molecular and structural formula, molecular mass, and maximum content in g/kg.
chemical name in accordance with IUPAC and CA nomenclature, ISO common name or proposed common name if available, CAS number, EC (Einecs or ELINCS) number, and CIPAC number if available, molecular and structural formula, molecular mass, and maximum content in g/kg.
antifoaming agent, antifreeze, binder, stabiliser, buffer, dispersing agent, other (specify).
physical, chemical, and technical hazards associated with active substances, to be identified, classification of active substance as to hazard, appropriate restrictions and conditions to be associated with approvals, and appropriate hazard and precautionary statements to be specified.
Aliphatic hydrocarbon: preferably n-heptane, Aromatic hydrocarbon: preferably xylene, Halogenated hydrocarbon: preferably 1,2-dichlorethane, Alcohol: preferably methanol or isopropyl alcohol, Ketone: preferably acetone, Ester: preferably ethyl acetate.
acaricide bactericide fungicide herbicide insecticide molluscicide nematicide plant growth regulator repellent rodenticide semio-chemicals talpicide viricide other (must be specified).
contact action stomach action inhalation action fungitoxic action fungistatic action desiccant reproduction inhibitor other (must be specified).
Field use, such as agriculture, horticulture, forestry and viticulture Protected crops Amenity Weed control on non-cultivated areas Home gardening House plants Plant products storage practice Other (specify).
chemical name in accordance with IUPAC and CA nomenclature, ISO common name or proposed common name, CAS EC-number EC (Einecs or ELINCS) number, and CIPAC number if available, empirical and structural formula, and molecular mass.
the processes, mechanisms and reactions involved, kinetic and other data concerning the rate of conversion and if known the rate limiting step, environmental and other factors effecting the rate and extent of conversion.
| Impurities, metabolites, relevant metabolites | as defined in Regulation (EC) No 1107/2009 |
| Relevant impurities | Impurities of toxicological and/or ecotoxicological or environmental concern |
| Significant impurities | Impurities with a content of ≥ 1 g/kg in the active substance as manufactured |
(i) analytical standards of the pure active substance; (ii) samples of the active substance as manufactured; (iii) analytical standards of relevant metabolites and all other components included in the residue definition; (iv) if available, samples of reference substances for the relevant impurities.
permit a decision to be made as to whether, or not, the active substance can be approved, specify appropriate conditions or restrictions to be associated with any approval, classify the active substance as to hazard, establish a relevant acceptable daily intake (ADI) level for man, establish acceptable operator exposure level(s) (AOEL), specify the pictograms, signal words, and relevant hazard and precautionary statements for the protection of man, animals and the environment to be included in packaging (containers), identify relevant first aid measures as well as appropriate diagnostic and therapeutic measures to be followed in the event of poisoning in man, and permit an evaluation to be made as to the nature and extent of the risks for man, animals (species normally fed and kept or consumed by man) and of the risks for other non-target vertebrate species.
an evaluation of the rate and extent of absorption, an evaluation of the tissue distribution and the rate and extent of excretion of the test substance and the relevant metabolites, the identification of metabolites and the metabolic pathway.
the toxicity of the active substance, the time course and characteristics of the effects with full details of behavioural changes and possible gross pathological findings at post-mortem, where possible mode of toxic action, and the relative hazard associated with the different routes of exposure.
a gas or liquified gas, is to be used as a fumigant, is to be included in a smoke generating, aerosol or vapour releasing preparation, is to be used with fogging equipment, has a vapour pressure > 1 × 10 –2 Pa and is to be included in preparations to be used in enclosed spaces such as warehouses or glasshouses,is to be included in preparations which are powders containing a significant proportion of particles of diameter < 50 μm (> 1 % on a weight basis), or is to be included in preparations to be applied in a manner which generates a significant proportion of particles or droplets of diameter < 50 μm (> 1 % on a weight basis).
the relationship between dose and adverse effects, toxicity of the active substance including where possible the Noael, target organs, where relevant, the time course and characteristics of poisoning with full details of behavioural changes and possible pathological findings at post-mortem, specific toxic effects and pathological changes produced, where relevant the persistence and reversibility of certain toxic effects observed, following discontinuation of dosing, where possible, the mode of toxic action, and the relative hazard associated with the different routes of exposure.
28-day dermal: the Annex to Regulation (EC) No 440/2008, Method B 9, repeated dose toxicity (dermal), 90-day dermal: the Annex to Regulation (EC) No 440/2008 Method B 28, sub-chronic dermal toxicity study, 28-day inhalation: the Annex to Regulation (EC) No 440/2008, Method B 8, repeated dose toxicity (inhalation), 90-day inhalation: the Annex to Regulation (EC) No 440/2008, Method B 29, sub-chronique inhalation toxicity study.
the prediction of genotoxic potential the early identification of genotoxic carcinogens the elucidation of the mechanism of action of some carcinogens.
Annex to Regulation (EC) No 440/2008, Method B 13/14 — reverse mutation test using bacteria, Annex to Regulation (EC) No 440/2008, Method B 10 — in vitro mammalian chromosome aberration test,Annex to Regulation (EC) No 440/2008, Method B 17 — in vitro mammalian cell gene mutation test.
Annex to Regulation (EC) No 440/2008, Method B 12 — In vivo mammalian erythrocyte micronucleus test,Annex to Regulation (EC) No 440/2008, Method B 24— Mouse spot test, Annex to Regulation (EC) No 440/2008, Method B 11 — In vivo Mammalian Bone-Marrow chromosome aberration test.
identify adverse effects resulting from exposure to the active substance, identify target organs, where relevant, establish the dose-response relationship, identify changes in toxic signs and manifestations observed, and establish the Noael.
to identify carcinogenic effects resulting from exposure to the active substance, to establish the species and organ specificity of tumours induced, to establish the dose-response relationship, and for non-genotoxic carcinogens, to identify the maximum dose eliciting no adverse effect (threshold dose).
identification of species and strain, name of the supplier, and specific colony identification, if the supplier has more than one geographical location, name of the laboratory and the dates when the study was performed, description of the general conditions under which animals were maintained, including the type or brand of diet and, where possible, the amount consumed, approximate age, in days, of the control animals at the beginning of the study and at the time of killing or death, description of the control group mortality pattern observed during or at the end of the study, and other pertinent observations (e.g. diseases, infections), name of the laboratory and the examining scientists responsible for gathering and interpreting the pathological data from the study, and a statement of the nature of the tumours that may have been combined to produce any of the incidence data.
impairment of male or female fertility, and impacts on the normal development of progeny (developmental toxicity).
identification of species and strain, name of the supplier, and specific colony identification, if the supplier has more than one geographical location, name of the laboratory and the dates when the study was performed, description of the general conditions under which animals were maintained, including the type or brand of diet and, where possible, the amount consumed, approximate age, in days, of the control animals at the beginning of the study and at the time of killing or death, description of the control group mortality pattern observed during or at the end of the study, and other pertinent observations (e.g. diseases, infections), and name of the laboratory and the examining scientist responsible for gathering and interpreting the toxicological data from the study.
to identify direct and indirect effects on reproduction resulting from exposure to the active substance, to identify any enhancement of general toxic effects (noted during short-term and chronic toxicity testing), to establish the dose-response relationship, to identify changes in toxic signs and manifestations observed, and to establish the Noael.
separate male and female studies, three segment designs, dominant lethal assay for male fertility, cross-matings of treated males with untreated females and vice versa, effects on spermatogenesis, effects on oogenesis, sperm motility, mobility and morphology, and investigation of hormonal activity.
to identify direct and indirect effects on embryonic and foetal development resulting from exposure to the active substance, to identify any maternal toxicity, to establish the relationship between observed responses and dose in both dam and offspring, to identify changes in toxic signs and manifestations observed, and to establish the Noael.
studies on absorption, distribution, excretion and metabolism, studies on the neurotoxic potential, studies on the immunotoxicological potential, studies on other routes of administration.
the type, level and duration of exposure, or ingestion, and varying time periods between exposure, or ingestion, and commencement of treatment.
permit a decision to be made as to whether, or not, the active substance can be approved, specify appropriate conditions or restrictions to be associated with any approval.
to provide an estimate of total terminal residues in the relevant portion of crops at harvest following treatment as proposed, to identify the major components of the total terminal residue, to indicate the distribution of residues between relevant crops parts, to quantify the major components of the residue and to establish the efficiency of extraction procedures for these components, to decide on the definition and expression of a residue.
to identify the major components of the total terminal residue in edible animal products, to quantify the rate of degradation and excretion of the total residue in certain animal products (milk or eggs) and excreta, to indicate the distribution of residues between relevant edible animal products, to quantify the major components of the residue and to show the efficiency of extraction procedures for these components, to generate data from which a decision on the need for livestock feeding studies as provided for in point 6.4 can be made, to decide on the definition and expression of a residue.
to quantify the highest likely residue levels in treated crops at harvest or outloading from store following the proposed good agricultural practice (GAP), and to determine, when appropriate, the rate of decline of plant protection product deposits.
when significant residues (≥ 0,1 mg/kg of the total diet as received, except special cases, such as active substances which accumulate) occur in crops or part of the crop (e.g. trimmings, waste) fed to animals, and when metabolism studies indicate that significant residues (0,01 mg/kg or above the limit of determination if this would be higher than 0,01 mg/kg) may occur in any edible animal tissue taking into account the residue levels in potential feedingstuffs obtained at the 1 × dose rate.
the importance of a processed product in the human or animal diet, the level of residue in the plant or plant product to be processed, the physico-chemical properties of the active substance or relevant metabolites, and the possibility that degradation products of toxicological significance may be found after processing of the plant or plant product.
to determine the quantitative distribution of residues in the various intermediate and end products, and to estimate transfer factors, to enable a more realistic estimate to be made of dietary intake of residues.
decide whether, or not, the active substance can be approved, specify appropriate conditions or restrictions to be associated with any approval, classify the active substance as to hazard, specify the pictograms, signal words and relevant hazard and precautionary statements for the protection of the environment, which are to be included on packaging (containers), predict the distribution, fate, and behaviour in the environment of the active substance and relevant metabolites, degradation and reaction products as well as the times courses involved, identify non-target species and populations for which hazards arise because of potential exposure, and identify measures necessary to minimise contamination of the environment and impact on non-target species.
they cover a range of organic carbon content, particle size distribution and pH values, and where on the basis of other information, degradation or mobility are expected to be pH dependent (e.g. solubility and hydrolysis rate — points 2.7 and 2.8), they cover the following pH ranges: 4,5 to 5,5, 6 to 7, and 8 (approximately).
identify, where feasible, the relative importance of the types of process involved (balance between chemical and biological degradation), identify the individual components present which at any time account for more than 10 % of the amount of active substance added, including, where feasible, non-extractable residues, identify where possible also individual components present which account for less than 10 % of the amount of active substance added, establish the relative proportions of the components present (mass balance), and permit the soil residue of concern and to which non-target species are or may be exposed, to be defined.
active substance, CO 2 ,volatile compounds other than CO 2 ,individual identified transformation products, extractable substances not identified, and non-extractable residues in soil.
where the nature and manner of use of preparations containing the active substance, preclude soil contamination such as uses on stored products or wound healing treatments for trees, or where a separate study for the metabolite, degradation or reaction product in accordance with point 7.1.2 or point 7.1.3.1 was performed.
the mobility in soil, the potential for leaching to ground water, the potential distribution in soil.
persistence in water systems (bottom sediment and water, including suspended particles), the extent to which water, sediment organisms and air are at risk, potential for contamination of surface water and groundwater.
identify the relative importance of the types of processes involved (balance between chemical and biological degradation), where possible, identify the individual components present, establish the relative proportions of the components present and their distribution as between water, including suspended particles, and sediment, and permit the residue of concern and to which non-target species are or may be exposed, to be defined.
decide whether, or not, the active substance can be approved, specify appropriate conditions or restrictions to be associated with any approval, permit an evaluation of short- and long-term risks for non-target species — populations, communities, and processes — as appropriate, classify the active substance as to hazard, specify the precautions necessary for the protection of non-target species, and specify the pictograms, signal words and relevant hazard and precautionary statements for the protection of the environment, to be mentioned on packaging (containers).
the bioconcentration factor is greater than 1000 and the elimination of the active substance during a depuration phase of 14 days is lower than 95 %, orthe substance is stable in water or sediment (DT 90 > 100 days).
food storage in enclosed spaces, non-systemic seed dressings, non-systemic preparations for application to soil, non-systemic dipping treatments for transplanted crops and bulbs, wound sealing and healing treatments, rodenticidal baits, use in glasshouses without pollinators.
food storage in enclosed spaces, wound sealing and healing treatments, rodenticidal baits.
Pictogram(s) Signal words Hazard statements Precautionary Statements.
is indigenous or non-indigenous at the species level to the intended area of application, is a wild type, is a spontaneous or induced mutant, has been modified, using techniques described in Part 2 of Annex IA and in Annex IB to Directive 2001/18/EC of the European Parliament and of the Council OJ L 106, 17.4.2001, p. 1 .
control of bacteria, control of fungi, control of insects, control of mites, control of molluscs, control of nematodes, control of weeds, other (must be specified).
field use, such as agriculture, horticulture, forestry, and viticulture, protected crops (e.g. in greenhouses), amenity, weed control on non-cultivated areas, home gardening, house plants, stored products, other (specify).
| Impurities, Metabolites, Relevant metabolites, Residues | As defined in Regulation (EC) No 1107/2009 |
| Relevant impurities | Impurities, as defined above, that are of concern for human or animal health and/or the environment |
(i) samples of the micro-organism as manufactured; (ii) analytical standards of relevant metabolites (especially toxins) and all other components included in the residue definition; (iii) if available, samples of reference substances for the relevant impurities.
Methods for the identification of the micro-organism, Methods for providing information on possible variability of seed stock/active micro-organism, Methods to differentiate a mutant of the micro-organism from the parent wild strain, Methods for the establishment of purity of seed stock from which batches are produced and methods to control that purity, Methods to determine the content of the micro-organism in the manufactured material used for the production of formulated products and methods to show that contaminating micro-organisms are controlled to an acceptable level, Methods for the determination of relevant impurities in the manufactured material, Methods to control the absence and to quantify (with appropriate limits of determination) the possible presence of any human and mammalian pathogens, Methods to determine storage stability, shelf-life of the micro-organism, if appropriate.
the active micro-organism(s), relevant metabolites (especially toxins).
permit a decision to be made as to whether, or not, the micro-organism can be approved, specify appropriate conditions or restrictions to be associated with any approval, specify risk and safety phrases (once introduced) for the protection of man, animals and the environment to be included on packaging (containers), identify relevant first aid measures as well as appropriate diagnostic and therapeutic measures to be followed in the event of infection or another adverse effect in man.
the toxicity, pathogenicity and infectiveness of the micro-organism, the time course and characteristics of the effects with full details of behavioural changes and possible gross pathological findings at post-mortem, where possible mode of toxic action, the relative hazards associated with the different routes of exposure, and blood analyses throughout the studies in order to evaluate the clearance of the micro-organism.
the prediction of genotoxic potential, the early identification of genotoxic carcinogens, the elucidation of the mechanism of action of some carcinogens.
the relationship between dose and adverse effects, toxicity of the micro-organism including where necessary the NOAEL for toxins, target organs, where relevant, the time course and characteristics of the effects with full details of behavioural changes and possible gross pathological findings at post-mortem, specific toxic effects and pathological changes produced, where relevant the persistence and reversibility of certain toxic effects observed, following discontinuation of dosing, where possible, the mode of toxic action, and the relative hazard associated with the different routes of exposure.
permit a decision to be made as to whether or not the micro-organism can be approved, specify appropriate conditions or restrictions to be associated with any approval, where relevant, set maximum residue levels, preharvest intervals to protect consumers and waiting periods, to protect workers handling the treated crops and products.
decide whether, or not, the micro-organism can be approved, specify appropriate conditions or restrictions to be associated with any approval, specify the pictograms (once introduced), signal words, and relevant hazard and precautionary statements for the protection of the environment, which are to be included on packaging (containers), predict the distribution, fate, and behaviour in the environment of the micro-organism and its metabolites as well as the time courses involved, identify measures necessary to minimise contamination of the environment and impact on non-target species.
the relevant metabolite is stable outside the micro-organism, see point 2.8, and a toxic effect of the relevant metabolite is independent of the presence of the micro-organism, and the relevant metabolite is expected to occur in the environment in concentrations considerably higher than under natural conditions.
competitiveness under the environmental conditions prevailing at and after the intended use, and population dynamics in seasonally or regionally extreme climates (particularly hot summer, cold winter and rainfall) and to agricultural practices applied after intended use.
decide whether, or not, the micro-organism can be approved, specify appropriate conditions or restrictions to be associated with any approval, permit an evaluation of short- and long-term risks for non-target species — populations, communities, and processes — as appropriate, classify the micro-organism as to biological hazard, specify the precautions necessary for the protection of non-target species, and specify the pictograms (once introduced), signal words, and relevant hazard and precautionary statements for the protection of the environment, to be mentioned on packaging (containers).
distribution and fate in the environment, and the time courses involved, identification of non-target species and populations at risk, and the extent of their potential exposure, identification of precautions necessary to avoid or minimise contamination of the environment, and for the protection of non-target species.