Biocidal Products Regulation

02012R0528-20210610 → 02012R0528-20220415

ANNEX II INFORMATION REQUIREMENTS FOR ACTIVE SUBSTANCES 1. This Annex sets out the information requirements for the preparation of the dossier referred to in point (a) of Article 6(1). 2. The data elements set down in this Annex comprise a Core Data Set (CDS) and an Additional Data Set (ADS). The data elements belonging to the CDS are considered as the basic data which should, in principle, be provided for all active substances. However, in some cases the physical or chemical properties of the substance may mean that it is impossible or unnecessary to provide specific data elements belonging to the CDS. With regard to the ADS, the data elements to be provided for a specific active substance shall be determined by considering each of the ADS data elements indicated in this Annex taking into account, inter alia, the physical and chemical properties of the substance, existing data, information which is part of the CDS and the types of products in which the active substance will be used and the exposure patterns related to these uses. Specific indications for the inclusion of some data elements are provided in column 1 of the Annex II table. The general considerations regarding adaptation of information requirements as set out in Annex IV shall also apply. In light of the importance of reducing testing on vertebrates, column 3 of the Annex II table gives specific indications for the adaptation of some of the data elements which might require the use of such tests on vertebrates. The information submitted shall, in any case, be sufficient to support a risk assessment demonstrating that the criteria referred to in Article 4(1) are met. The applicant should consult the detailed technical guidance regarding the application of this Annex and the preparation of the dossier referred to in point (a) of Article 6(1), which is available on the website of the Agency. The applicant has the obligation to shall initiate a pre-submission consultation. consultation with the prospective evaluating body. In addition to the obligation set down out in Article 62(2), applicants applicant may also consult with the competent authority that will evaluate the dossier with regard to the proposed information requirements and in particular the testing on vertebrates that the applicant proposes to carry out. The applicant shall document such pre-submission consultations and their outcomes and shall include the relevant documents in the application. Additional information may need to be submitted if it is necessary to carry out the evaluation as indicated in Article 8(2). 3. A detailed and full description of the studies conducted or referred to and of the methods used shall be included. It is important to ensure that the data available is relevant and is of sufficient quality to fulfil the requirements. Evidence should also be provided to demonstrate that the active substance upon which the tests have been carried out is the same as the substance for which the application has been submitted. 4. The formats made available by the Agency must be used for submission of the dossiers. In addition, IUCLID must be used for those parts of the dossiers to which IUCLID applies. Formats and further guidance on data requirements and dossier preparation are available on the website of the Agency. 5. Tests submitted for the purpose of the approval of an active substance shall be conducted according to in accordance with the methods described in Commission Regulation (EC) No 440/2008 Commission Regulation (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) OJ (OJ L 142, 31.5.2008, p. 1.. 1)., or any revised version of these methods not yet included in that Regulation. However, if a method is inappropriate or not described, described in Commission Regulation (EC) No 440/2008, other methods shall be used which are scientifically appropriate, whenever possible internationally recognised, appropriate and their appropriateness must shall be justified in the application. When test methods are applied to nanomaterials, nano-materials, an explanation shall be provided of their scientific appropriateness for nanomaterials, and where applicable, of the technical adaptations/adjustments adaptations or adjustments that have been made in order to respond to the specific characteristics of these materials. 6. Tests performed should comply with the relevant requirements of protection of laboratory animals, set out in Directive 2010/63/EU of the European Parliament and the Council … 377 unchanged words … for the purified active substance of stated specification. OJ L 20, 26.1.1980, p. 43. OJ L 372, 27.12.2006, p. 19. OJ L 348, 24.12.2008, p. 84. Column 1 Information required Column 2 All data is CDS unless indicated as ADS Column 3 Specific rules for adaptation from standard information concerning some of the information requirements that may require recourse to testing of vertebrates column 1 1. APPLICANT 1.1. Name and address 1.2. Contact person 1.3. Active substance manufacturer (name, address and location of manufacturing plant(s)) 2. IDENTITY OF THE ACTIVE SUBSTANCE (AND ITS PRECURSOR(S) IF THE ACTIVE SUBSTANCE IS GENERATED IN SITU) For the active substance, substance and, if applicable, its precursors, the information given in this Section shall be sufficient to enable the active substance to be identified. If it is not technically possible or if it does not appear scientifically necessary to give information on one or more of the items below, listed in this Section, the reasons shall be clearly stated 2.1. Common name proposed or accepted by ISO and synonyms (usual name, trade name, abbreviation) 2.2. Chemical name (IUPAC and CA nomenclature or other international chemical name(s)) 2.3. Manufacturer’s development code number(s) 2.4. CAS number plus EC, INDEX and CIPAC numbers 2.5. Molecular and structural formula (including SMILES notation, if available and appropriate) appropriate). For precursor(s) and for active substances generated in situ, information about all generated chemical substances (intended and unintended) In case it is not possible to exactly define the molecular structure of the precursor(s) and/or active substance, the molecular and structural formulas do not need to be provided 2.6. Information on optical activity and full details of any isomeric composition (if applicable and appropriate) 2.7. Molar mass 2.8. Method of manufacture (syntheses pathway) pathways) of active substance including information on starting materials and solvents including suppliers, specifications and commercial availability availability. For active substances generated in situ, a description of the reaction schemes including all intermediate reactions and their associated chemical substances (intended and unintended) shall be provided 2.9. Specification of purity of the active substance as manufactured in g/kg, g/l or %w/w (v/v) as appropriate, providing inclusively the upper and lower limit 2.10. The identity of any impurities and additives including by-products of synthesis, optical isomers, degradation products (if the substance is unstable) un-reacted and end-groups etc. of polymers and un-reacted starting materials of UVC-substances 2.11. Analytical profile of at least five representative batches (g/kg active substance) including information on content of the impurities referred to in 2.10. 2.11.1. Analytical profile of at least five representative samples taken from the in situ generated substance(s), providing information on the content of the active substance(s) and any other constituent above 0,1 % w/w, including residues of precursor(s) 2.12. The origin of the natural active substance or the precursor(s) of the active substance, e.g. an extract of a flower 3. PHYSICAL AND CHEMICAL PROPERTIES OF THE ACTIVE SUBSTANCE 3.1. Appearance 3.1.1. Aggregate state (at 20 °C and 101,3 kPa) 3.1.2. … 415 unchanged words … objects to be protected 6.3. Effects on representative target organism(s) 6.4. Likely concentration at which the active substance will be used in products and, where appropriate, in treated articles 6.5. Mode of action (including time delay) 6.6. Efficacy data to support these support: the innate activity of the active substance for the intended use(s), and any claims on biocidal products and, where label claims are made, made on treated articles, including articles regarding the biocidal properties conferred to the article. Efficacy data shall include any available standard protocols, laboratory tests or field trials used including and performance standards where appropriate appropriate, or data similar to those available for suitable reference products 6.7. Any known limitations on efficacy 6.7.1. Information on the occurrence or possible occurrence of the development of resistance and appropriate management strategies 6.7.2. Observations on undesirable or unintended side-effects, e.g. side effects on beneficial and other non-target organisms or on objects and material to be protected 7. INTENDED USES AND EXPOSURE 7.1. Field of use(s) envisaged for biocidal products and, where appropriate, treated articles 7.2. Product-type(s) 7.3. Detailed description of the intended use pattern(s) including in treated articles 7.4. Users e.g. industrial, trained professional, professional or general public (non-professional) 7.5. Likely tonnage to be placed on the market per year and, where relevant, for the envisaged major use categories 7.6. Exposure data in conformity with Annex VI to this Regulation 7.6.1. Information on human exposure associated with the intended uses and disposal of the active substance 7.6.2. Information on environmental exposure associated with the intended uses and disposal of the active substance 7.6.3. Information on exposure of food- producing animals and food and feeding stuffs associated with the intended uses of the active substance 7.6.4. Information on exposure from treated articles including leaching data (either laboratory studies or model data) 8. TOXICOLOGICAL PROFILE FOR HUMAN AND ANIMAL INCLUDING METABOLISM 8.1. Skin irritation corrosion or skin corrosion The assessment of this endpoint shall be carried out according to the sequential testing strategy for dermal irritation and corrosion set out in the Appendix to Test Guideline B.4. Acute Toxicity-Dermal Irritation/Corrosion (Annex B.4. to Regulation (EC) No 440/2008) 8.2. Eye irritation The assessment of this endpoint shall be carried out according to the sequential testing strategy for eye irritation and corrosion as set down in the Appendix to Test Guideline B.5.Acute Toxicity: Eye Irritation/Corrosion (Annex B.5. to Regulation (EC) No 440/2008) 8.3. Skin sensitisation The assessment of this endpoint shall comprise the following consecutive steps: 1. an tiers: (a) assessment of the available human, animal and alternative data 2. non-animal data; (b) skin corrosion, in vitro testing; (c) skin irritation, in vitro testing; (d) skin corrosion or irritation, in vivo testing The Murine Local Lymph Node Assay (LLNA) including, where appropriate, the reduced variant of the assay, is the first-choice method for study/ies in vivo testing. If another skin sensitisation test is used justification shall be provided Step 2 does column 1 do(es) not need to be conducted if: the available information indicates that the substance should be classified meets the criteria for classification for skin sensitisation corrosion or corrosivity, or irritation, the substance is a strong acid (pH < (pH≤ 2,0) or base (pH > 11,5) (pH≥ 11,5), the substance is spontaneously flammable in air or in contact with water or moisture at room temperature, the substance meets the classification criteria for acute toxicity (Category 1) by the dermal route, or an acute toxicity study by the dermal route provides conclusive evidence on skin corrosion or irritation adequate for classification. If results from one of the two studies listed in point (b) or point (c) in column 1 of this row already allow conclusive decision on the classification of a substance or on the absence of skin irritation potential, the second study does not need to be conducted An in vivo study for skin corrosion or irritation shall be considered only if the in vitro studies listed in points (b) and (c) in column 1 of this row are not applicable, or the results of these studies are not adequate for classification and risk assessment In vivo studies for skin corrosion or irritation that were carried out or initiated before 15 April 2022 shall be considered appropriate to address this information requirement 8.2. Serious eye damage or eye irritation The assessment shall comprise the following tiers: (a) assessment of the available human, animal and non-animal data; (b) serious eye damage or eye irritation, in vitro testing; (c) serious eye damage or eye irritation, in vivo testing The study/ies in column 1 do(es) not need to be conducted if: the available information indicates that the substance meets the criteria for classification for eye irritation or causing serious damage to eyes, the substance is a strong acid (pH≤ 2,0) or base (pH≥ 11,5), the substance is spontaneously flammable in air or in contact with water or moisture at room temperature, or the substance meets the classification criteria for skin corrosion leading to classification of the substance as serious eye damage (category 1). If results from a first in vitro study do not allow a conclusive decision on the classification of the substance or on the absence of eye irritation potential (an)other(s) in vitro study(ies) for this endpoint shall be considered. An in vivo study for serious eye damage or eye irritation shall be considered only if the in vitro study(ies) listed in point (b) in column 1 of this row are not applicable, or the results obtained from these studies are not adequate for classification and risk assessment In vivo studies for serious eye damage or eye irritation that were carried out or initiated before 15 April 2022 shall be considered appropriate to address this information requirement 8.3. Skin sensitisation The information shall allow to conclude whether the substance is a skin sensitiser and whether it can be presumed to have the potential to produce significant sensitisation in humans (Category 1A). The information should be sufficient to perform a risk assessment where required The assessment shall comprise the following tiers: (a) assessment of the available human, animal and non-animal data; (b) skin sensitisation, in vitro testing. Information from in vitro or in chemico test method(s) referred to in point 5 of the introductory part of this Annex and addressing each of the following key events of skin sensitisation: (i) molecular interaction with skin proteins; (ii) inflammatory response in keratinocytes; (iii) activation of dendritic cells; (c) skin sensitisation in vivo testing. The Murine Local Lymph Node Assay (LLNA) is the first-choice method for in vivo testing. Another skin sensitisation test may only be used in exceptional cases. If another skin sensitisation test is used, justification shall be provided The study/ies in column 1 do(es) not need to be conducted if: the available information indicates that the substance meets the criteria for classification for skin sensitisation or skin corrosion, the substance is a strong acid (pH≤ 2,0) or base (pH≥ 11,5), or the substance is spontaneously flammable in air or in contact with water or moisture at room temperature. In vitro tests do not need to be conducted if: an in vivo study referred to in point (c) of column 1 of this row is available, or the available in vitro or in chemico test methods are not applicable for the substance or the results obtained from those studies are not adequate for classification and risk assessment. If information from test method(s) addressing one or two of the key events described under point (b) in column 1 of this row allows for classification of the substance and risk assessment, studies addressing the other key event(s) do not need to be conducted An in vivo study for skin sensitisation shall be conducted only if in vitro or in chemico test methods described under point (b) in column 1 of this row are not applicable, or the results obtained from those studies are not adequate for classification and risk assessment In vivo skin sensitisation studies that were carried out or initiated before 15 April 2022 shall be considered appropriate to address this information requirement 8.4. Respiratory sensitisation ADS 8.5. Mutagenicity The assessment of this endpoint shall comprise the following consecutive steps: an assessment of the available in vivo genotoxicity data an in vitro test for gene mutations in bacteria, an in vitro cytogenicity test in mammalian cells and an in vitro gene mutation test in mammalian cells are required appropriate in vivo genotoxicity studies shall be considered in case of a positive result in any of the in vitro genotoxicity studies 8.5.1. In vitro gene mutation study in bacteria 8.5.2. In vitro cytogenicity study in mammalian cells 8.5.3. In vitro gene mutation study in mammalian cells 8.6. In vivo genotoxicity study The assessment of this endpoint shall comprise the following consecutive steps: tiers: (a) If there is a positive result in any of the in vitro genotoxicity studies as listed in 8.5 and there are no reliable results available from an appropriate in vivo study already, somatic cell genotoxicity study, an appropriate in vivo somatic cell genotoxicity study shall be proposed/conducted by the applicant If either of the in vitro gene mutation tests is positive, an in vivo test to investigate unscheduled DNA synthesis shall be conducted conducted; (b) A second in vivo somatic cell test genotoxicity study may be necessary, necessary depending on the in vitro and in vivo results, type of effects, quality and relevance of all the available data data; (c) If there is a positive result from an in vivo somatic cell genotoxicity study available, the potential for germ cell mutagenicity should be considered based on the basis of all available data, including toxicokinetic evidence to demonstrate that whether the substance reached has the tested organ. capacity to reach germ cells. If no clear conclusions about germ cell mutagenicity can be made, additional investigations shall be considered ADS The study/ies in column 1 do(es) not generally need to be conducted if: the results are negative for the three in vitro tests listed in 8.5 and if no other concern has been identified (e.g. metabolites of concern are formed in mammals mammals), or valid in vivo micronucleus data is generated within the substance meets the criteria to be classified as a repeat dose study and the in vivo micronucleus germ cell mutagen category 1A or 1B. The germ cell genotoxicity test is the appropriate test does not need to be conducted to address this information requirement if the substance is known meets the criteria to be carcinogenic classified as a carcinogen, category 1A or 1B or mutagenic and a germ cell mutagen category 1A, 1B or 2. 2 8.7. Acute toxicity In addition to the oral route of administration (8.7.1), for substances other than gases, the information mentioned under 8.7.2 to 8.7.3 shall be provided for at least one other route of administration The choice for the second route will … 1,304 unchanged words … human exposure and route-to-route extrapolation cannot be made. ADS 8.10. Reproductive toxicity For evaluation of consumer safety of active substances that may end up in food or feed, it is necessary to conduct toxicity studies by the oral route The studies do not need not to be conducted if: the substance is known meets the criteria to be classified as a genotoxic carcinogen (classified both as germ cell mutagen category 2, 1A or 1B and carcinogenic category 1A or 1B), and appropriate risk management measures are implemented including measures related to reproductive toxicity, or the substance is known meets the criteria to be classified as a germ cell mutagen category 1A or 1B and appropriate risk management measures are implemented including measures related to reproductive toxicity, or the substance is of low toxicological activity (no evidence of toxicity seen in any of the tests available provided that the dataset is sufficiently comprehensive and informative), it can be proven from toxicokinetic data that no systemic absorption occurs via relevant routes of exposure (e.g. plasma/blood plasma or blood concentrations below detection limit using a sensitive method and absence of the substance and of metabolites of the substance in urine, bile or exhaled air) and the pattern of use indicates that there is no or no significant negligible human exposure If a or animal exposure, the substance is known to have an adverse effect on fertility, meeting meets the criteria for classification to be classified as Reproductive reproductive toxicity Cat category 1A or 1B: May damage fertility (H360F), and the available data are adequate to support a robust risk assessment, then no further testing for sexual function and fertility will be necessary. However, testing A full justification must be provided and documented if investigations for developmental toxicity must be considered If a are not conducted, or the substance is known to cause developmental toxicity, meeting the criteria for classification as Reproductive reproductive toxicity Cat category 1A or 1B: May damage the unborn child (H360D), and the available data are adequate to support a robust risk assessment, then no further testing for developmental toxicity will be necessary. However, testing for effects on fertility A full justification must be considered provided and documented if investigations for sexual function and fertility is not conducted. Notwithstanding the provisions of this column of this row, studies on reproductive toxicity may need to be conducted to obtain information on endocrine disrupting properties as laid down in 8.13.3.1. 8.10.1. Pre-natal development toxicity study (OECD TG 414) on two species, preferred first species is rabbit (non-rodent) and preferred second species is rat (rodent); oral route of administration is the preferred route The study on the second species shall not be conducted if the study performed on the first species or other available data indicate that the substance causes developmental toxicity study, meeting the criteria for classification as toxic for reproduction category 1A or 1B: May damage the unborn child (H360D), and the available data are adequate to support a robust risk assessment 8.10.2. Extended One-Generation Reproductive Toxicity Study (OECD TG 443), with cohorts 1A and 1B and extension of cohort 1B to include the F2 generation with the aim to produce 20 litters per dose group, F2 pups must be followed to weaning and investigated similarly as F1 pups. Rat is the preferred species is rabbit; and oral route of administration is the preferred route. The study shall highest dose level should be initially performed based on one species 8.10.2. Two-generation toxicity and selected with the aim to induce reproductive and/or other systemic toxicity study, rat, oral route of administration is the preferred route. If another reproductive toxicity test is used justification shall be provided. The extended one-generation A two-generation reproductive toxicity study adopted at conducted in accordance with OECD level TG 416 (adopted 2001 or later) or equivalent information shall be considered as appropriate to address this information requirement, if the study is available and was initiated before 15 April 2022. 8.10.3. Developmental neurotoxicity Developmental Neurotoxicity Study in accordance with OECD TG 426, or any relevant study (set) providing equivalent information, or cohorts 2A and 2B of an alternative approach to Extended One-Generation Reproductive Toxicity study (OECD TG 443) with additional investigation for cognitive functions The study shall not be conducted if the multi-generation study 8.10.3. Further pre-natal available data: indicate that the substance causes developmental toxicity study. and meets the criteria to be classified as toxic for reproduction category 1A or 1B: May damage the unborn child (H360D), and are adequate to support a robust risk assessment 8.10.4. Further studies A decision on the need to perform additional studies including those informing on a second species or mechanistic studies the mechanisms should be based on the outcome outcomes of the first test (8.10.1) studies listed in 8.10.1, 8.10.2 and 8.10.3 and all other relevant available data (in particular rodent reprotox studies). Preferred species is rat, oral route of administration ADS 8.11. Carcinogenicity See 8.11.1 for new study requirements A carcinogenicity study does not need to be conducted if: the substance is classified as mutagen category 1A or 1B. The default presumption would be that a genotoxic mechanism for carcinogenicity is likely. In these cases, a carcinogenicity test will normally not be required 8.11.1. Combined carcinogenicity study and long-term repeated dose toxicity Rat, oral route of administration is the preferred route. If an alternative route is proposed a justification must be provided. For evaluation of consumer safety of active substances that may end up in food or feed, it is necessary to conduct toxicity studies by the oral route 8.11.2. Carcinogenicity testing in a second species (a) A second carcinogenicity study should normally be conducted using the mouse as test species species; (b) For evaluation of consumer safety of active substances that may end up in food or feed, it is necessary to conduct toxicity studies by the oral route The second carcinogenicity study does not need to be conducted if the applicant can justify on the basis of scientific grounds that it is not necessary 8.12. Relevant health data, observations and treatments Justification should be provided if data is not available 8.12.1. Medical surveillance data Information on manufacturing plant personnel 8.12.2. Direct observation, e.g. clinical cases, poisoning incidents 8.12.3. Health records, both from industry and any other available sources 8.12.4. Epidemiological studies on the general population 8.12.5. Diagnosis of poisoning including specific signs of poisoning and poisoning, clinical tests 8.12.6. Sensitisation/allergenicity observations 8.12.7. Specific treatment in case of an accident or poisoning: tests, first aid measures, antidotes antidotes, medical treatment and medical treatment, if known 8.12.8. Prognosis prognosis following poisoning 8.12.2. Epidemiological studies 8.12.3. Medical surveillance data, health records and case reports 8.13. Additional studies Additional data which may be required depending on the characteristics and intended use of the active substance Other available data: Available data from emerging methods and models, including toxicity pathway-based risk assessment, in vitro and omic (genomic, proteomic, metabolomic, etc.) studies, systems biology, computational toxicology, bioinformatics, and high-throughput screening shall be submitted in parallel ADS 8.13.1. Phototoxicity ADS 8.13.2. Neurotoxicity including developmental neurotoxicity The preferred test species If the active substance is an organophosphorus compound or if there is an indication, knowledge of the rat unless another test species is justified to be more appropriate For delayed neurotoxicity tests mechanism of action or knowledge from acute or repeated dose studies that the preferred species active substance may have neurotoxic properties, additional information or specific studies (such as OECD TG 424 or OECD TG 418 or 419 or equivalent) will be the adult hen required If anticholinesterase activity is detected a test for response to reactivating agents should be considered If the active substance is an organophosphorus compound or if there is any evidence e.g. knowledge of the mechanism of action or from repeat dose studies that the active substance may have neurotoxic or developmental neurotoxic properties then additional information or specific studies will be required. For evaluation of consumer safety of active substances that may end up in food or feed, it is necessary to conduct toxicity studies by the oral route ADS 8.13.3. Endocrine disruption The assessment of endocrine disruption shall comprise the following tiers: (a) An assessment of the available information from the following studies and any other relevant information, including in vitro and in silico methods: (i) 8.9.1 A 28-day oral toxicity study in rodents (OECD TG 407); (ii) 8.9.2 A 90-day oral toxicity study in rodents (OECD TG 408); (iii) 8.9.4 A repeated dose oral toxicity study in non-rodents (OECD TG 409); (iv) 8.10.1 A prenatal developmental toxicity study (OECD TG 414); (v) 8.10.2 An extended one-generation reproductive toxicity study (OECD TG 443) or two-generation reproductive toxicity study (OECD TG 416); (vi) 8.10.3 A developmental neurotoxicity study (OECD TG 426); (vii) 8.11.1 A combined carcinogenicity study and long-term repeated dose toxicity study (OECD TG 451-3); (viii) A systematic review of the literature including studies on mammals and non-mammalian organisms; (b) If there is any evidence from in vitro, repeat dose or reproduction toxicity studies, information suggesting that the active substance may have endocrine disrupting properties properties, or if there is incomplete information on key parameters relevant for concluding on endocrine disruption, then additional information or specific studies shall be required to: elucidate to elucidate: (1) the mode/mechanism mode or the mechanism of action provide sufficient evidence for action; and/or (2) potentially relevant adverse effects in humans or animals For evaluation of consumer safety of active substances that may end up in food or feed, it is necessary to consider the oral route and conduct toxicity animal studies by the oral route Where sufficient weight of evidence to conclude on the presence or absence of a particular endocrine disrupting mode of action is available: further testing on vertebrate animals for that effect shall be omitted for that mode of action, further testing not involving vertebrate animals may be omitted for that mode of action. In all cases, adequate and reliable documentation shall be provided 8.13.3.1. Specific additional studies to investigate potential endocrine disrupting properties may include, but are not limited to the following: (a) the mammalian toxicity studies listed in 8.13.3(a); (b) the in vitro assays: (i) Estrogen receptor transactivation assay (OECD TG 455); (ii) Androgen receptor transactivation assay, (OECD TG 458); (iii) H295R steroidogenesis assay (OECD TG 456); (iv) the Aromatase assay (human recombinant) OPPTS 890.1200; (c) Uterotrophic bioassay in rodents (OECD TG 440) and Hershberger bioassay in rats (OECD TG 441); (d) Pubertal development and Thyroid Function in Intact Juvenile or Peripubertal Male Rats (OPPTS 890.1500). The decision to carry out studies in mammals shall be taken based on all available information, including a systematic review of the literature (including information on endocrine disrupting effects in non-target organisms) and the availability of suitable in silico or in vitro methods ADS 8.13.4. Immunotoxicity including and developmental immunotoxicity If there is any evidence, evidence from skin sensitisation, repeat dose or reproduction reproductive toxicity studies, studies that the active substance may have immunotoxic properties properties, then additional information or specific studies shall be required to: elucidate to elucidate: (1) the mode/mechanism mode or the mechanism of action provide sufficient evidence for action; and/or (2) potentially relevant adverse effects in humans or animals. For evaluation of consumer safety of active substances that may end up in food or feed, it is necessary to consider the oral route and conduct toxicity animal studies by the oral route ADS 8.13.5. Mechanistic Further mechanistic studies A decision on the need to perform additional studies should be based on all relevant data — any studies necessary to clarify effects reported in toxicity studies ADS 8.14. Studies related to the exposure of humans to the active substance ADS 8.15. Toxic effects on livestock and pets ADS 8.16. Food and feeding stuffs studies including for food-producing animals and their products (milk, eggs and honey) Additional information … 366 unchanged words … of mammalian toxicology Provide overall evaluation and conclusion with regard to all toxicological data and any other information concerning the active substances including NOAEL 9. ECOTOXICOLOGICAL STUDIES 9.1. Toxicity to Aquatic Organisms 9.1.1. Short-term toxicity testing on fish When short-term fish toxicity data is required required, the threshold approach (tiered strategy) should be applied applied. A long-term toxicity testing on fish in accordance with point 9.1.6.1 shall be considered if the substance is poorly water soluble, i.e. below 1 mg/L The study does not need to be conducted if: a valid long-term aquatic toxicity study on fish is available, sufficient weight of evidence including the use of other data such as the Fish Embryo Acute Toxicity (FET, OECD TG 236) and/or results obtained from non-animal methods is available for this data requirement 9.1.2. Short-term toxicity testing on aquatic invertebrates 9.1.2.1. Daphnia magna 9.1.2.2. Other species ADS 9.1.3. Growth inhibition study on algae 9.1.3.1. Effects on growth rate of green algae 9.1.3.2. Effects on growth rate of cyanobacteria or diatoms 9.1.4. Bioconcentration The experimental determination may not need to be carried out if: it can be demonstrated on the basis of physico-chemical properties (e.g. log Kow < 3) or other evidence that the substance has a low potential for bioconcentration 9.1.4.1. Estimation methods 9.1.4.2. Experimental determination 9.1.5. Inhibition of microbial activity The study may be replaced by a nitrification inhibition test if available data show that the substance is likely to be an inhibitor of microbial growth or function, in particular nitrifying bacteria 9.1.6. Further Toxicity Studies on Aquatic Organisms If the results of the ecotoxicological studies, studies on fate and behaviour and/or the intended use(s) of the active substance indicate a risk for the aquatic environment, or if long-term exposure is expected, then one or more of the tests described in this Section shall be conducted ADS 9.1.6.1. Long term toxicity testing on Fish (a) Fish Early Life Stage (FELS) Test (b) Fish short term fish The information shall be provided from long-term toxicity test testing on embryo and sack fry stages (c) Fish juvenile growth test (d) Fish full life cycle test fish in which early life-stages (eggs, larvae or juveniles) are exposed ADS 9.1.6.2. Long term toxicity testing on invertebrates (a) Daphnia growth and reproduction study (b) Other species reproduction and growth (e.g. Mysid) (c) Other species development and emergence (e.g. Chironomus) ADS 9.1.7. Bioaccumulation in an appropriate aquatic species ADS 9.1.8. Effects on any other specific, non-target organisms (flora and fauna) believed to be at risk ADS 9.1.9. Studies on sediment- dwelling organisms ADS 9.1.10. Effects on aquatic macrophytes ADS 9.2. Terrestrial toxicity, initial tests ADS 9.2.1. Effects on soil micro-organisms 9.2.2. Effects on earthworms or other soil- dwelling non-target invertebrates 9.2.3. Acute toxicity to plants 9.3. Terrestrial tests, long term ADS 9.3.1. Reproduction study with earthworms or other soil-dwelling non-target invertebrates 9.4. Effects on birds ADS For endpoint 9.4.3 the study does not need to be conducted if: the dietary toxicity study shows that the LC50 is above 2000 mg/kg 9.4.1. Acute oral toxicity 9.4.2. Short-term toxicity — eight-day dietary study in at least one species (other than chickens, ducks and geese) 9.4.3. Effects on reproduction 9.5. Effects on arthropods ADS 9.5.1. Effects on honeybees 9.5.2. Other non-target terrestrial arthropods, e.g. predators 9.6. Bioconcentration, terrestrial ADS 9.7. Bioaccumulation, terrestrial ADS 9.8. Effects on other non-target, non-aquatic organisms ADS 9.9. Effects on mammals ADS Data are derived from the mammalian toxicological assessment. The most sensitive relevant mammalian long-term toxicological endpoint (NOAEL) expressed as mg test compound/kg bw/day shall be reported 9.9.1. Acute oral toxicity 9.9.2. Short term toxicity 9.9.3. Long term toxicity 9.9.4. Effects on reproduction 9.10. Identification Endocrine disruption The assessment of endocrine disruption properties shall comprise the following tiers: (a) An assessment of the mammalian data set in accordance with 8.13.3 to assess whether the substance has endocrine disrupting properties based on data in relation to mammals; (b) If it cannot be concluded based on the mammalian data in accordance with 8.13.3 or 9.1.6.1 that the substance has endocrine disrupting properties, then studies set out in 9.10.1 or 9.10.2 shall be considered taking account of any other available relevant information, including a systematic review of the literature 9.10.1. Endocrine disruption in fish Specific studies to investigate potential endocrine disrupting properties may include, but are not limited to the following data requirements: (a) Medaka extended one-generation test (MEOGRT, OECD TG 240); (b) Fish life cycle toxicity test (FLCTT, OPPTS 850.1500) covering all the estrogen-, androgen- and steroidogenic-mediated (EAS) parameters foreseen to be measured in the MEOGRT study The study does not need to be carried out if: there is no indication for endocrine activity or endocrine related effects from a sufficient mammalian data set in accordance with 8.13.3 or from any other relevant information (e.g. literature), and valid in vivo data is available, with no information suggesting that the active substance may elicit endocrine activity or effects potentially related to endocrine activity in either the Fish short term reproduction assay (FSTRA; OECD TG 229), or the 21-days fish assay (OECD TG 230) or Fish sexual developmental test (FSDT, OECD TG 234). If other data are available covering the estrogenic, androgenic and steroidogenic, (EAS) related modalities or parameters investigated in OECD TG 229 or OECD TG 230 or OECD TG 234, then those data can be used instead 9.10.2. Endocrine disruption in amphibians Specific additional studies to investigate potential endocrine disrupting properties may include, but are not limited to Larval amphibian growth and development assay (LAGDA; OECD TG 241) The study does not need to be carried out if: there is no indication for endocrine activity or endocrine related effects from a sufficient mammalian data set in accordance with 8.13.3 or from any other relevant information (e.g. literature), and valid in vivo data is available, with no information suggesting that the active substance may have endocrine disrupting properties in an Amphibian metamorphosis assay (AMA; OECD 231) 9.10.3. If there is information suggesting that the active substance may have endocrine disrupting properties, or if there is incomplete information on key parameters relevant for concluding on endocrine disruption, additional information or specific studies, as necessary, shall be required to elucidate: (a) the mode or the mechanism of action; and/or (b) potentially relevant adverse effects in humans or animals. ADS 10. ENVIRONMENTAL FATE AND BEHAVIOUR 10.1. Fate and behaviour in water and sediment 10.1.1. Degradation, initial studies If the assessment performed indicates the need to investigate further the degradation of the substance and its degradation products or the active substance has an … 776 unchanged words … that are set out in the appropriate test methods in Regulation (EC) No 440/2008 that are not repeated in column 3, also apply. Column 1 Information required Column 2 All data is CDS unless indicated as ADS Column 3 Specific rules for adaptation from standard information concerning some of the information requirements that may require recourse to testing of vertebrates column 1 1. APPLICANT 1.1. Name and address 1.2. Contact person 1.3. Manufacturer (name, address and location of manufacturing plant) 2. IDENTITY OF THE MICRO-ORGANISM 2.1. Common name of the micro-organism (including alternative and superseded names) 2.2. Taxonomic name and strain 2.3. Collection and culture reference number where the culture is deposited 2.4. Methods, procedures and criteria used to establish the presence and identity of the micro-organism 2.5. Specification of the technical grade active ingredient 2.4.1. Content of the active micro-organism and identity and content of relevant metabolites or toxins 2.4.2. Identity and content of impurities, additives, contaminating micro-organisms 2.4.3. Analytical profile of batches 2.5. Method of production and quality control 2.6. Method of production and quality control 2.7. Content of the micro-organism 2.8. Identity and content of impurities, additives, contaminating micro-organisms 2.9. Analytical profile of batches 3. BIOLOGICAL PROPERTIES OF THE MICRO-ORGANISM 3.1. General information on the micro-organism 3.1.1. Historical background 3.1.2. Historical uses 3.1.3. Origin, natural occurrence and geographical distribution 3.2. Development stages/life cycle of the micro-organism 3.3. Relationships to known plant or animal or human pathogens 3.4. Genetic stability and factors affecting it 3.5. Information on the production of relevant metabolites (especially toxins) and toxins 3.6. Production and resistance to antibiotics and other anti-microbial agents 3.7. Robustness to environmental factors 3.8. Further information on the micro-organism 4. METHODS OF DETECTION AND IDENTIFICATION 4.1. Methods, procedures and criteria used to establish the presence and identity of the micro-organism 4.2. Analytical methods for the analysis of the micro-organism as manufactured 4.2. 4.3. Methods used for monitoring purposes to determine and quantify residues (viable or non-viable) 5. EFFECTIVENESS AGAINST TARGET ORGANISM 5.1. Function and mode of control e.g. attracting, killing, inhibiting 5.2. Infectiveness, dispersal and colonisation ability 5.3. Representative organism(s) controlled and products, organisms … 597 unchanged words … LABELLING AND PACKAGING OF THE MICRO-ORGANISM 11.1. Relevant risk group specified in Article 2 of Directive 2000/54/EC 12. SUMMARY AND EVALUATION The key information identified from the endpoints in each subsection (2-12) is summarised, evaluated and a draft risk assessment is performed

02012R0528-20210610 → 02012R0528-20220415

ANNEX III INFORMATION REQUIREMENTS FOR BIOCIDAL PRODUCTS 1. This Annex sets out the information requirements that shall be included in the dossier for the biocidal product accompanying an application for the approval of an active substance in accordance with point (b) of Article 6(1) and the dossier accompanying an application for the authorisation of a biocidal product in accordance with point (a) of Article 20(1). 2. The data elements set down in this Annex comprise a Core Data Set (CDS) and an Additional Data Set (ADS). The data elements belonging to the CDS are considered as the basic data which should, in principle, be provided for all biocidal products. With regard to the ADS, the data elements to be provided for a specific biocidal product shall be determined by considering each of the ADS data elements indicated in this Annex taking into account, inter alia, the physical and chemical properties of the product, existing data, information which is part of the CDS and the types of products and the exposure patterns related to these uses. Specific indications for the inclusion of some data elements are provided in column 1 of the Annex III table. The general considerations regarding adaptation of information requirements as set out in Annex IV to this Regulation shall also apply. In light of the importance of reducing testing on vertebrates, column 3 of the table gives specific indications for the adaptation of some of the data elements which might require the use of such tests on vertebrates. For some of the information requirements set out in this Annex, it may be possible to satisfy these requirements based on available information of the properties of the active substance(s) contained in the product and the properties of non-active substance(s) included in the product. For non-active substances, applicants shall use the information provided to them in the context of Title IV of Regulation (EC) No 1907/2006, where relevant, and the information made available by the Agency in accordance with point (e) of Article 77(2) of that Regulation. However, the information may be not sufficient or adequate to determine whether a non-active substance contained in a biocidal product has hazardous properties and the evaluating body may conclude that further data are required. The relevant calculation methods used for the classification of mixtures as laid down in Regulation (EC) No 1272/2008 shall, where appropriate, be applied in the hazard assessment of the biocidal product. Such calculation methods shall not be used if, in relation to a particular hazard, synergistic and antagonistic effects between the different substances contained in the product are considered likely. Detailed technical guidance regarding the application of this Annex and the preparation of the dossier is available on the website of the Agency. The applicant has the obligation to shall initiate a pre-submission consultation. consultation with the prospective evaluating body. In addition to the obligation set out in Article 62(2), applicants the applicant may also consult with the competent authority that will evaluate the dossier with regard to the proposed information requirements and in particular the testing on vertebrates that the applicant proposes to carry out. The applicant shall document such pre-submission consultations and their outcomes and shall include the relevant documents in the application. Additional information may need to be submitted if necessary to carry out the evaluation as indicated in Article 29(3) or Article 44(2). The information submitted shall, in any case, be sufficient to support a risk assessment demonstrating that the criteria in Article 19(1)(b) are met. 3. A detailed and full description of studies conducted and of the methods used shall be included. It is important to ensure that the data available is relevant and is of sufficient quality to fulfil the requirements. 4. The formats made available by the Agency shall be used for submission of the dossiers. In addition, IUCLID shall be used for those parts of the dossiers to which IUCLID applies. Formats and further guidance on data requirements and dossier preparation are available on the Agency homepage. 5. Tests submitted for the purpose of authorisation shall be conducted according to in accordance with the methods described in Commission Regulation (EC) No 440/2008. 440/2008, or any revised version of these methods not yet included in that Regulation. However, if a method is inappropriate or not described, described in Commission Regulation (EC) No 440/2008, Commission Regulation (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) (OJ L 142, 31.5.2008, p. 1). other methods shall be used which are scientifically appropriate, whenever possible internationally recognised, appropriate and their appropriateness must shall be justified in the application. When test methods are applied to nanomaterials, nano-materials, an explanation shall be provided of their scientific appropriateness for nanomaterials, and, and where applicable, of the technical adaptations/adjustments adaptations or adjustments that have been made in order to respond to the specific characteristics of these materials. 6. Tests performed should comply with the relevant requirements of protection of laboratory animals, set out in Directive 2010/63/EU and, in the case of ecotoxicological and toxicological tests, good laboratory practice, set out in Directive 2004/10/EC or other international standards recognised as being equivalent by the Commission or the Agency. Tests on physico-chemical properties and safety-relevant substance data should be performed at least according to international standards. 7. Where testing is done, a detailed quantitative and qualitative description (specification) of the product used for each test and its impurities must be provided. 8. Where test data exist that have been generated before 17 July 2012 by methods other than those laid down in Regulation (EC) No 440/2008, the adequacy of such data for the purposes of this Regulation and the need to conduct new tests according to the Regulation (EC) No 440/2008 must be decided by the competent authority of the Member State, on a case-by-case basis, taking into account, among other factors, the need to avoid unnecessary testing. 9. New tests involving vertebrates shall be conducted as the last available option to comply with the data requirements set out in this Annex when all the other data sources have been exhausted. In vivo testing with corrosive substances at concentration/dose levels causing corrosivity shall also be avoided. TITLE 1 CHEMICAL PRODUCTS Core data set and additional data set for chemical products Information required to support the authorisation of a biocidal product is listed in the table below. For each information requirement set down in this Annex the indications given in columns 1 and 3 of Annex II for the same information requirement shall also apply. Eye-irritation test shall not be necessary where the biocidal product has been shown to have potential corrosive properties. Column 1 Information required: Column 2 All data is CDS unless indicated as ADS Column 3 Specific rules for adaptation from standard information concerning some of the information requirements that may require recourse to testing of vertebrates column 1 1. APPLICANT 1.1. Name and address, etc. 1.2. Contact person 1.3. Manufacturer and formulator of the biocidal product and the active substance(s) (names, addresses, including location of plant(s)) 2. IDENTITY OF THE BIOCIDAL PRODUCT 2.1. Trade name or proposed trade name 2.2. … 731 unchanged words … Representative organism(s) to be controlled and products, organisms or objects to be protected 6.3. Effects on representative target organisms 6.4. Likely concentration at which the active substance will be used 6.5. Mode of action (including time delay) 6.6. The proposed label claims for the product and, where label claims are made, for treated articles regarding the biocidal properties conferred to the article 6.7. Efficacy data to support these claims, including any available standard protocols, laboratory tests or field trials used including performance standards where appropriate and relevant 6.8. Any known limitations on efficacy 6.8.1. Information on the occurrence or possible occurrence of the development of resistance and appropriate management strategies 6.8.2. Observations on undesirable or unintended side effects e.g. side-effects on beneficial and other non-target organisms or on objects and material to be protected 6.9. Summary and evaluation 7. INTENDED USES AND EXPOSURE 7.1. Field(s) of use envisaged for biocidal products and, where appropriate, treated articles 7.2. Product-type 7.3. Detailed description of intended use pattern(s) for biocidal products and, where appropriate, treated articles 7.4. User e.g. industrial, trained professional, professional or general public (non-professional) 7.5. Likely tonnage to be placed on the market per year and, where relevant, for different use categories 7.6. Method of application and a description of this method 7.7. Application rate and, if appropriate, the final concentration of the biocidal product and active substance in a treated article or in the system in which the product is to be used, e.g. cooling water, surface water, water used for heating purposes 7.8. Number and timing of applications, and where relevant, any particular information relating to geographical location or climatic variations including necessary waiting periods, clearance times, withdrawal periods or other precautions to protect human health, animal health and the environment 7.9. Proposed instructions for use 7.10. Exposure data in conformity with Annex VI to this Regulation 7.10.1. Information on human exposure associated with production and formulation, proposed/expected uses and disposal 7.10.2. Information on environmental exposure associated with production and formulation, proposed/expected uses and disposal 7.10.3. Information on exposure from treated articles including leaching data (either laboratory studies or model data) 7.10.4. Information regarding other products that the product is likely to be used together with, in particular the identity of the active substances in these products, if relevant, and the likelihood of any interactions 8. TOXICOLOGICAL PROFILE FOR HUMANS AND ANIMALS 8.1. Skin corrosion or skin irritation The assessment shall comprise the following tiers: (a) assessment of this endpoint shall be carried out according to the sequential available human, animal and non-animal data; (b) skin corrosion, in vitro testing; (c) skin irritation, in vitro testing; (d) skin corrosion or irritation, in vivo testing strategy for dermal irritation and corrosion set out in Testing of the Appendix to Test Guideline B.4. Acute Toxicity-Dermal Irritation/Corrosion (Annex B.4. to Regulation (EC) No 440/2008) Testing on the product/mixture product or mixture does not need to be conducted if: there are sufficient valid data available on each component of the components in the product or mixture sufficient to allow its classification of the mixture according to the rules laid down in Directive 1999/45/EC and accordance with Regulation (EC) No 1272/2008 (CLP), 1272/2008, and synergistic effects between any of the components are not expected expected, the product or mixture is a strong acid (pH≤ 2,0) or base (pH≥ 11,5), the product or mixture is spontaneously flammable in air or in contact with water or moisture at room temperature, the product or mixture meets the classification criteria for acute toxicity category 1 by the dermal route, or an acute toxicity study by the dermal route provides conclusive evidence on skin corrosion or irritation adequate for classification. If results from one of the two studies listed in points (b) or (c) in column 1 of this row already allow conclusive decision on the classification of product or mixture or on the absence of skin irritation potential, the second study does not need to be conducted An in vivo study for skin corrosion or irritation shall be considered only if the in vitro studies listed in points (b) and (c) in column 1 of this row are not applicable, or the results of these studies are not adequate for classification and risk assessment and the calculation method or bridging principles laid down in Regulation (EC) No 1272/2008 are not applicable In vivo studies for skin corrosion or irritation that were carried out or initiated before 15 April 2022 shall be considered appropriate to address this information requirement 8.2. Eye Serious eye damage or eye irritation The assessment shall comprise the following tiers: (a) assessment of this endpoint shall be carried out according to the sequential available human, animal and non-animal data; (b) serious eye damage or eye irritation, in vitro testing; (c) serious eye damage or eye irritation, in vivo testing strategy for eye irritation and corrosion as set down in the Appendix to Test Guideline B.5.Acute Toxicity: Eye Irritation/Corrosion (Annex B.5. to Regulation (EC) No 440/2008) Testing on the product/mixture product or mixture does not need to be conducted if: there are sufficient valid data available on each component of the components in the product or mixture to allow its classification of the mixture according to the rules laid down in Directive 1999/45/ECand accordance with Regulation (EC) No 1272/2008 (CLP), 1272/2008, and synergistic effects between any of the components are not expected expected, the product or mixture is a strong acid (pH≤ 2,0) or base (pH≥ 11,5), the product or mixture is spontaneously flammable in air or in contact with water or moisture at room temperature, or the product or mixture meets the classification criteria for skin corrosion leading to its classification as serious eye damage category 1 If results from a first in vitro study do not allow a conclusive decision on the classification of the product or mixture or on the absence of eye irritation potential (an)other(s) in vitro study(ies) for this endpoint shall be considered An in vivo study for serious eye damage or eye irritation shall be considered only if the in vitro study(ies) under point (b) in column 1 of this row are not applicable, or the results obtained from these studies are not adequate for classification and risk assessment and the calculation method or bridging principles laid down in Regulation (EC) No 1272/2008 are not applicable In vivo studies for serious eye damage or eye irritation that were carried out or initiated before 15 April 2022 shall be considered appropriate to address this information requirement 8.3. Skin sensitisation The information shall allow to conclude whether the substance is a skin sensitiser and whether it can be presumed to have the potential to produce significant sensitisation in humans (Category 1A). The information should be sufficient to perform a risk assessment of this endpoint where required The assessment shall comprise the following consecutive steps: 1. an tiers: (a) assessment of the available human, animal and alternative data 2. non-animal data; (b) skin sensitisation, in vitro testing. Information from in vitro or in chemico test method(s) conducted in accordance with point 5 of the introductory part of this Annex and addressing each of the following key events of skin sensitisation: (i) molecular interaction with skin proteins; (ii) inflammatory response in keratinocytes; (iii) activation of dendritic cells. (c) skin sensitisation in vivo testing testing. The Murine Local Lymph Node Assay (LLNA) including, where appropriate, the reduced variant of the assay, is the first-choice method for in vivo testing. Another skin sensitisation test may only be used in exceptional circumstances. If another skin sensitisation test is used used, scientific justification shall be provided provided. Testing on the product/mixture product or mixture does not need to be conducted if: there are sufficient valid data available on each component of the components in the product or mixture to allow its classification of the mixture according to the rules laid down in Directive 1999/45/EC and accordance with Regulation (EC) No 1272/2008 (CLP), 1272/2008, and synergistic effects between any of the components are not expected expected, the available information indicates that the product or mixture should be classified for skin sensitisation or corrosivity; skin corrosion, the product or the substance mixture is a strong acid (pH < (pH≤ 2,0) or base (pH > 11,5) (pH≥ 11,5), or the product or mixture is spontaneously flammable in air or in contact with water or moisture at room temperature. In vitro tests do not need to be conducted if: an in vivo study referred to in point (c) in column 1 of this row is available, or the available in vitro or in chemico test methods are not applicable for the product or mixture or the results obtained from these studies are not adequate for classification and risk assessment. If information from test method(s) addressing one or two of the key events described in point (b) in column 1 of this row already allows for classification of the substance and risk assessment, studies addressing the other key event(s) do not need to be conducted An in vivo study for skin sensitisation shall be considered only if in vitro or in chemico studies referred to in point (b) in column 1 of this row are not applicable, or the results obtained from these studies are not adequate for classification and risk assessment and the calculation method or bridging principles laid down in Regulation (EC) No 1272/2008 are not applicable In vivo studies for skin sensitisation that were carried out or initiated before 15 April 2022 shall be considered appropriate to address this information requirement 8.4. Respiratory sensitisation ADS Testing on the product/mixture does not need to be conducted if: there are valid data available on each of the components in the mixture to allow classification of the mixture according to the rules laid down in Directive 1999/45/EC and Regulation (EC) No 1272/2008 (CLP), and synergistic effects between any of the components are not expected 8.5. Acute toxicity Classification using the tiered approach to classification of mixtures for acute toxicity in Regulation (EC) No 1272/2008 is the default approach Testing on the product/mixture does not need to be conducted if: there are valid data available on each of the components in the mixture to allow classification of the mixture according to the rules laid down in Directive 1999/45/EC and Regulation (EC) No 1272/2008 (CLP), and synergistic effects between any of the components are not expected 8.5.1. By oral route 8.5.2. By inhalation 8.5.3. By dermal route 8.5.4. For biocidal products that are intended to be authorised for use with other biocidal products, the risks to human health, animal health and the environment arising from the use of these product combinations shall be assessed. As an alternative to acute toxicity studies, calculations can be used. In some cases, for example where there are no valid data available of the kind set out in column 3, this may require a limited number of acute toxicity studies to be carried out using combinations of the products Testing on the mixture of products does not need to be conducted if: there are valid data available on each of the components in the mixture to allow classification of the mixture according to the rules laid down in Directive 1999/45/EC and Regulation (EC) No 1272/2008 (CLP), and synergistic effects between any of the components are not expected 8.6. Information on dermal absorption Information on dermal absorption when exposure occurs to the biocidal product. The assessment of this endpoint shall proceed using a tiered approach 8.7. Available toxicological data relating to: (a) non-active substance(s) (i.e. substance(s) of concern), or concern); and (b) a mixture that a substance(s) of concern is a component of If insufficient data are available for a non-active substance(s) and cannot be inferred through read-across or other accepted non-testing approaches, targeted test(s) described Tests listed in Section 8 of the table in Title 1 of Annex II shall be carried out for the substance(s) of concern or a mixture that a substance(s) of concern is a component of if insufficient data are available and cannot be inferred through read-across, in silico or other accepted non-testing approaches Testing on the product/mixture product or mixture does not need to be conducted if: if all of the following conditions are met: there are valid data available on each of the components in the mixture to allow classification of the mixture according to in accordance with the rules laid down in Directive 1999/45/EC and Regulation (EC) No 1272/2008 (CLP) 1272/2008, a conclusion can be made whether the biocidal product can be considered as having endocrine disrupting properties, synergistic effects between any of the components are not expected 8.8. Food and feedingstuffs studies ADS 8.8.1. If residues of the biocidal product remain in or on feedingstuffs for a significant period of time, then feeding and metabolism studies in livestock shall be required to permit evaluation of residues in food of animal origin ADS 8.9. Effects of industrial processing and/or domestic preparation on the nature and magnitude of residues of the biocidal product ADS 8.10. Other test(s) related to the exposure to humans Suitable test(s) and a reasoned case will be required for the biocidal product In addition, for certain biocides which are applied directly or around livestock (including horses) residue studies might be needed ADS 9. ECOTOXICOLOGICAL STUDIES 9.1. Information Available ecotoxicological data relating to to: (a) non-active substance(s) (i.e. substance(s) of concern); (b) a mixture that a substance(s) of concern is a component of Tests listed in Section 9 of Title 1 of Annex II shall be carried out for the ecotoxicity substance(s) of concern or a mixture that a substance(s) of concern is a component of if insufficient data are available and cannot be inferred through read-across, in silico or other accepted non-testing approaches Testing on the biocidal product which is sufficient to enable a decision or mixture does not need to be made concerning conducted if all the classification of the product is required Where following conditions are met: there are valid data available on each of the components in the mixture and to allow classification of the mixture in accordance with the rules laid down in Regulation (EC) No 1272/2008, a conclusion can be made whether the biocidal product can be considered as having endocrine disrupting properties, synergistic effects between any of the components are not expected, classification of the mixture can be made according to the rules laid down in Directive 1999/45/EC, Regulation (EC) No 1907/2006 (REACH) and Regulation (EC) No 1272/2008 (CLP) Where valid data on the components are not available or where synergistic effects may be expected then testing of components and/or the biocidal product itself may be necessary 9.2. Further Ecotoxicological studies Further studies chosen from among the endpoints referred to in Section 9 of Annex II for relevant components of the biocidal product or the biocidal product itself may be required if the data on the active substance … 643 unchanged words … down in this Annex the indications given in columns 1 and 3 of Annex II for the same information requirement shall also apply. Column 1 Information required: Column 2 All data is CDS unless indicated as ADS Column 3 Specific rules for adaptation from standard information concerning some of the information requirements that may require recourse to testing of vertebrates column 1 1. APPLICANT 1.1. Name and address 1.2. Contact person 1.3. Manufacturer and formulator of the biocidal product and the micro-organism(s) (names, addresses, including location of plant(s)) 2. IDENTITY OF THE BIOCIDAL PRODUCTS 2.1. Trade name or proposed trade name 2.2. Manufacturer’s development code and number of the biocidal product, if appropriate 2.3. Detailed quantitative (g/kg, g/l or g/l, % w/w (v/v)) (v/v), cfu/g, cfu/l or IU/mg or any other appropriate unit) and qualitative information on the constitution, composition and function of the biocidal product, e.g. micro-organism, active substance(s) and product non-active substances and any other relevant components. components All relevant information on individual ingredients and the final composition of the biocidal product shall be given 2.4. Formulation type and nature of the biocidal product 2.5. Where the biocidal product contains an active substance that has been manufactured in locations or according to processes or from starting materials other than those of the active substance evaluated for the purpose of approval pursuant to Article 9 of this Regulation, evidence has to be provided that technical equivalence has been established in accordance with Article 54 of this Regulation or has been established, following an evaluation having started before 1 September 2013, by a competent authority designated in accordance with Article 26 of Directive 98/8/EC 3. BIOLOGICAL, PHYSICAL, CHEMICAL AND TECHNICAL PROPERTIES OF THE BIOCIDAL PRODUCT 3.1. Biological properties of the micro-organism in the biocidal product 3.2. Appearance (at 20 °C and 101,3 kPa) 3.2.1. Colour (at 20 °C and 101,3 kPa) 3.2.2. Odour (at 20 °C and 101,3 kPa) 3.3. Acidity, alkalinity and pH value 3.4. Relative density 3.5. Storage stability, stability and shelf-life 3.5.1. Effects of light 3.5.2. Effects of temperature and humidity 3.5.3. Reactivity towards the container 3.5.4. Other factors affecting stability 3.6. Technical characteristics of the biocidal product 3.6.1. Wettability 3.6.2. Suspensibility and suspension stability 3.6.3. Wet sieve analysis and dry sieve test 3.6.4. Emulsifiability, re-emulsifiability, emulsion stability 3.6.5. Particle size distribution content of dust/fines, attrition and friability 3.6.6. Persistent foaming 3.6.7. Flowability/Pourability/Dustability 3.6.8. Burning rate — smoke generators 3.6.9. Burning completeness — smoke generators 3.6.10. Composition of smoke — smoke generators 3.6.11. Spraying patterns — aerosols 3.6.12. Other technical characteristics 3.6.8. Spraying patterns – aerosols 3.6.9. Other technical characteristics 3.7. Physical, chemical and biological compatibility with other products including biocidal products with which its use is to be authorised or registered 3.7.1. Physical compatibility 3.7.2. Chemical compatibility 3.7.3. Biological compatibility 3.8. Surface tension 3.9. Viscosity 4. PHYSICAL HAZARDS AND RESPECTIVE CHARACTERISITICS 4.1. Explosives 4.2. Flammable gases aerosols 4.3. Flammable aerosols liquids 4.4. Oxidising gases 4.5. Gases under pressure 4.6. Flammable liquids 4.7. Flammable solids 4.8. 4.5. Oxidising liquids 4.9. 4.6. Oxidising solids 4.10. Organic peroxides 4.11. 4.7. Corrosive to metals 4.12. 4.8. Other physical indications of hazard 4.12.1. 4.8.1. Auto-ignition temperatures of products (liquids and gases) 4.12.2. 4.8.2. Relative self-ignition temperature for solids 4.12.3. 4.8.3. Dust explosion hazard 5. METHODS OF DETECTION AND IDENTIFICATION 5.1. Analytical method for determining the concentration of the micro-organism(s) and substances of concern in the biocidal product 5.2. Analytical methods for monitoring purposes including recovery rates and the limit of quantification … 1,062 unchanged words … the active substance. Data are required unless it is scientifically justified that the fate of the components in the product is covered by the data provided for the active substance and other identified substances of concern ADS 10.3. Leaching behaviour and/or mobility ADS 10.4. If the biocidal product is to be sprayed outside or if potential for large scale formation of dust is given then data on overspray behaviour may be required to assess risks to bees under field conditions ADS 11. MEASURES TO BE ADOPTED TO PROTECT HUMANS, ANIMALS AND THE ENVIRONMENT 11.1. Recommended methods and precautions concerning: handling, storage, transport or fire 11.2. Measures in the case of an accident 11.3. Procedures for destruction or decontamination of the biocidal product and its packaging 11.3.1. Controlled incineration 11.3.2. Others 11.4. Packaging and compatibility of the biocidal product with proposed packaging materials 11.5. Procedures for cleaning application equipment where relevant 11.6. Monitoring plan to be used for the active micro-organism and other micro-organism(s) contained in the biocidal product including handling, storage, transport and use 12. CLASSIFICATION, LABELLING AND PACKAGING Example labels, instructions for use and safety data sheets shall be provided 12.1. Indication on the need for the biocidal product to carry the biohazard sign specified in Annex II to Directive 2000/54/EC 12.2. Precautionary statements including prevention, response, storage and disposal 12.3. Proposals for safety-data sheets should be provided, where appropriate 12.4. Packaging (type, materials, size, etc.), compatibility of the product with proposed packaging materials to be included 13. SUMMARY AND EVALUATION The key information identified from the endpoints in each subsection (2-12) is summarised, evaluated and a draft risk assessment is performed