ANNEX IIU.K.REQUIREMENTS FOR THE DOSSIER TO BE SUBMITTED FOR THE INCLUSION OF AN ACTIVE SUBSTANCE IN ANNEX I
PART AU.K.Chemical substances()
[2. Physical and chemical properties of the active substance U.K.
(i)
The information provided, must describe the physical and chemical properties of active substances and together with relevant information, must serve to characterize them. In particular, the information provided must permit:
physical, chemical, and technical hazards associated with active substances, to be identified,
classification of active substance as to harzard,
appropriate restrictions and conditions to be associated with inclusions in Annex I to be selected, and
appropriate risk and safety phrases to be specified.
The information and data referred to are required for all active substances, except where otherwise specified.
(ii)
The information provided, taken together with that provided for relevant preparations, must permit the physical, chemical hazards associated with preparations, to be identified, permit preparations to be classified, and permit establishment that preparations can be used without unnecessary difficulty, and be such that exposure of man, animals, and the environment is minimized, taking account of manner of use.
(iii)
The extent to wich active substances of which inclusion in Annex I is sought, comply with relevant FAO specifications, must be stated. Divergences from FAO specifications must be described in detail, and justified.
(iv)
In certain specified instances, tests must be conducted using purified active substance of stated specification. In such cases the principles of the method(s) of purification must be reported. The purity of such test material, which must be as high as can be achieved using the best available technology, must be reported. A reasoned justification must be provided in cases where the degree of purity achieved is less than 980 g/kg.
Such justification must demonstrate that all technically feasible and reasonable possibilities for the production of the pure active substance have been exhausted.
2.1. Melting point and boiling point U.K.
2.1.1. The melting point or where appropriate the freezing or solidification point of purified active substance must be determined and reported according to EEC method A 1. Measurements should be taken up to 360 o C. U.K.
2.1.2. Where appropriate the boiling point of purified active substances must be determined and reported according to EEC method A 2. Measurements should be taken up to 360 o C. U.K.
2.1.3. Where melting point and/or boiling point cannot be determined because of decomposition or sublimation, the temperature at which decomposition or sublimation occurs, must be reported. U.K.
2.2. Relative density U.K.
In the case of active substances which are liquids or solids, the relative density of the purified active substance must be determined and reported according to EEC method A 3.
2.3. Vapour pressure (in Pa), volatility (e.g. Henry's law constant) U.K.
2.3.1. The vapour pressure of purified active substance must be reported according to EEC method A 4. Where vapour pressure is less than 10 −5 Pa, the vapour pressure at 20 or 25 o C may be estimated by a vapour pressure curve. U.K.
2.3.2. In the case of active substances which are solids or liquids, volatility (Henry's law constant) of purified active substance must be determined or calculated from its water solubility and vapour pressure and be reported (in Pa × m 3 × mol − 1 ). U.K.
2.4. Appearance (physical state, colour and odour; if known) U.K.
2.4.1. A description of both the colour, if any, and the physical state of both the active substance as manufactured and purified active substance, must be provided. U.K.
2.4.2. A description of any odour associated with the active substance as manufactured and purfied active substance, noted when handling the materials in laboratories or production plants, must be reported. U.K.
2.5. Spectra (UV/VIS, IR, NMR, MS), molecular extinction at relevant wavelengths U.K.
2.5.1. The following specta including a table of signal characteristica needed for interpretation must be determined and reported: Ultraviolet/Visible (UV/VIS), infrared (R), nuclear magnetic resonance (NMR), and mass spectra (MS) of purified active substance and molecular extinction at relevant wavelengths, must be determined and reported. U.K.
The wavelengths at which UV/visible molecular extinction occurs are to be determined and reported and must include where appropriate a wavelength at the highest absorption value above 290 nm.
In the case of active substances which are resolved optical isomers their optical purity must be measured and reported.
2.5.2. The UV/visible absorption spectra, IR, NMR and MS spectra, where necessary for the identification of the impurities considered to be of toxicological, ecotoxicological or environmental significance must be determined and reported. U.K.
2.6. Solubility in water including effect of pH (4 to 10) on solubility U.K.
The water solubility of purified active substances under atmospheric pressure must be determined and reported according to EEC method A 6. These water solubility determinations must be made in the neutral range (i.e. in distilled water in equilibrium with atmospheric carbon dioxide). Where the active substance is capable of forming ions, determinations must also be made in the acidic range (pH 4 to 6) and in the alkaline range (pH 8 to 10), and be reported. Where the stability of the active substance in aqueous media is such that water solubility cannot be determined, a justification based on test data must be provided.
2.7. Solubility in organic solvents U.K.
The solubility of the active substances as manufactured in the following organic solvents at 15 to 25 o C must be determined and reported if less than 250 g/kg; the temperature applied must 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.
If for a particular active substance, one or more of these solvents is unsuitable (e.g. reacts with test material), alternative solvents can be used instead. In such cases, choices made must be justified in terms of their structure and polarity.
2.8. Partition coefficient n-octanol/water including effect of pH (4 to 10) U.K.
The n-octanol/water partition coefficient of purified active substance must be determined and reported according to EEC method A 8. The effect of pH (4 to 10) must be investigated when the substance is acidic or basic as defined by its pKa value (< 12 for acids, > 2 for bases).
2.9. Stability in water, hydrolysis rate, photochemical degradation, quantum yield and identity of breakdown product(s), dissociation constant including effect of pH (4 to 9) U.K.
2.9.1. The hydrolysis rate of purified active substances (usually radiolabelled active substance, > 95 % purity), for each of the pH values 4, 7 and 9, under sterile conditions, in the absence of light, must be determined and report according to EEC method C 7. For substances with a low rate of hydrolysis, the rate can be determined at 50 o C, or another appropriate temperature. U.K.
If degradation is observed at 50 o C, degradation rate at another temperature must be determined, and an Arrhenius plot must be constructed to permit an estimate to be made of hydrolysis at 20 o C. The identity of hydrolysis products formed and the rate constantly observed, must be reported. The estimated DT 50 value must also be reported.
2.9.2. For compounds with a molar (decadic) absorption coefficient (ε) > 10 (1 × mol − 1 × cm − 1 ) at a wavelength λ ≥ 290 nm, direct phototransformation in purified (e.g. distilled) water at 20 to 25 o C, of purified active substance usually radio labelled using artificial light under sterile conditions, if necessary using a solubilizer, must be determined and reported. Sensitizers such as acetone must not be used as a cosolvent or solubilizer. The light source must simulate sunlight and be equipped with filters to exclude radiation at wavelengths λ < 290 nm. The identity of breakdown products formed which at any time during the study are present in quantities ≥ 10 % of the active substance added, a mass balance to account for at least 90 % of the applied radioactivity, as well as photochemical halflife must be reported. U.K.
2.9.3. Where necessary to investigate direct phototrans-formation, the quantum yield of direct photodegradation in water must be determined and reported, together with calculations to estimate theoretical lifetime of the active substance in the top layer of aqueous systems and the real lifetime of the substance. U.K.
The method is described in the FAO Revised Guidelines on Environmental Criteria for the Registration of Pesticides.
2.9.4. Where dissociation in water occurs, the dissociation constant(s) (pKa values) of the purified active substance must be determined and reported according to OECD Test Guideline 112. The identity of the dissociated species formed, based on theoretical considerations, must be reported. If the active, substance is a salt, the pKa value of the active principle must be given. U.K.
2.10. Stability in air, photochemical degradation, identity of breakdown product(s) U.K.
An estimation of the photochemical oxidative degradation (indirect hototransformation) of the active substance, must be submitted.
2.11. Flammability including auto-flammability U.K.
2.11.1. The flammability of active substances as manufactured, which are solids, gases, or are substances which evolve highly flammable gases, must be determined and reported according to EEC method A 10, A 11 or A 12 as as appropriate. U.K.
2.11.2. The auto-flamability of active substances as manufactured must be determined and reported according to EEC method A 15 or A 16 as appropriate, and/or, where necessary according to the UN-Bowes-Cameron-Cage-Test (UN-Recommendations on the Transport of Dangerous Goods, Chapter 14, No 14.3.4). U.K.
2.12. Flash point U.K.
The flash point of active substances as manufactured with a melting point below 40 o C, must be determined and reported according to EEC method A 9; only closed cup methods should be used.
2.13. Explosive properties U.K.
The explosive properties of active substances as manufactured, must be determined and reported according to EEC method A 14 where necessary.
2.14. Surface tension U.K.
The surface tension has to be determined and reported according to EEC method A 5.
2.15 Oxidizing properties U.K.
The oxidizing properties of active substances as manufactured, must be determined and reported according to EEC method A 17, except where examination of its sturctural formula, establishes beyond reasonable doubt that the active substance is incapable of reacting exothermically with a combustible material. In such cases, it is sufficient to provide that information as justification for not determining the oxidizing properties of the substance.]