1991L0414 — EN — 01.07.2003 — 009.001 — 1
This document is meant purely as a documentation tool and the institutions do not assume any liability for its contents
►B COUNCILDIRECTIVE
of15July1991
concerningtheplacingofplantprotection productsonthemarket
(91/414/EEC)
(OJ L 230, 19.8.1991, p. 1)
Amended by:
Official Journal
No page date
►M1Commission Directive 93/71/EEC of 27 July 1993 L 221 27 31.8.1993
►M2Commission Directive 94/37/EC of 22 July 1994 L 194 65 29.7.1994
►M3Council Directive 94/43/EC of 27 July 1994 L 227 31 1.9.1994
►M4Commission Directive 94/79/EC of 21 December 1994 L 354 16 31.12.1994
►M5Commission Directive 95/35/EC of 14 July 1995 L 172 6 22.7.1995
►M6Commission Directive 95/36/EC of 14 July 1995 L 172 8 22.7.1995
►M7Commission Directive 96/12/EC of 8 March1996 L 65 20 15.3.1996
►M8Commission Directive 96/46/EC of 16 July 1996 L 214 18 23.8.1996
►M9Commission Directive 96/68/EC of 21 October 1996 L 277 25 30.10.1996
►M10Council Directive 97/57/EC of 22 September 1997 L 265 87 27.9.1997
►M11Commission Directive 97/73/EC of 15 December 1997 L 353 26 24.12.1997
►M12Commission Directive 98/47/EC of 25 June 1998 L 191 50 7.7.1998
►M13Commission Directive 1999/1/EC of 21 January 1999 L 21 21 28.1.1999
►M14Commission Directive 1999/73/EC of 19 July 1999 L 206 16 5.8.1999
►M15Commission Directive 1999/80/EC of 28 July 1999 L 210 13 10.8.1999
►M16Commission Directive 2000/10/EC of 1 March2000 L 57 28 2.3.2000
►M17Commission Directive 2000/49/EC of 26 July 2000 L 197 32 3.8.2000
►M18Commission Directive 2000/50/EC of 26 July 2000 L 198 39 4.8.2000
►M19Commission Directive 2000/66/EC of 23 October 2000 L 276 35 28.10.2000
►M20Commission Directive 2000/67/EC of 23 October 2000 L 276 38 28.10.2000
►M21Commission Directive 2000/68/EC of 23 October 2000 L 276 41 28.10.2000
►M22Commission Directive 2000/80/EC of 4 December 2000 L 309 14 9.12.2000
►M23Commission Directive 2001/21/EC of 5 March2001 L 69 17 10.3.2001
►M24Commission Directive 2001/28/EC of 20 April 2001 L 113 5 24.4.2001
►M25Commission Directive 2001/36/EC of 16 May 2001 L 164 1 20.6.2001
►M26Commission Directive 2001/47/EC of 25 June 2001 L 175 21 28.6.2001
►M27Commission Directive 2001/49/EC of 28 June 2001 L 176 61 29.6.2001
►M28Commission Directive 2001/87/EC of 12 October 2001 L 276 17 19.10.2001
►M29Commission Directive 2001/99/EC of 20 November 2001 L 304 14 21.11.2001
1991L0414 — EN — 01.07.2003 — 009.001 — 2
►M30Commission Directive 2001/103/EC of 28 November 2001 L 313 37 30.11.2001
►M31Commission Directive 2002/18/EC of 22 February 2002 L 55 29 26.2.2002
►M32Commission Directive 2002/37/EC of 3 May 2002 L 117 10 4.5.2002
►M33Commission Directive 2002/48/EC of 30 May 2002 L 148 19 6.6.2002
►M34Commission Directive 2002/64/EC of 15 July 2002 L 189 27 18.7.2002
►M35Commission Directive 2002/81/EC of 10 October 2002 L 276 28 12.10.2002
►M36Commission Directive 2003/23/EC of 25 March2003 L 81 39 28.3.2003
►M37Council Regulation (EC) No 806/2003 of 14 April 2003 L 122 1 16.5.2003
Corrected by:
►C1Corrigendum, OJ L 170, 25.6.1992, p. 40 (91/414/EEC)
►C2Corrigendum, OJ L 4, 6.1.1996, p. 16 (93/71/EEC)
►C3Corrigendum, OJ L 280, 23.11.1995, p. 58 (94/79/EC)
►C4Corrigendum, OJ L 221, 21.8.1999, p. 19 (1999/73/EC)
▼B
COUNCILDIRECTIVE
of15July1991
concerningtheplacingofplantprotectionproductsonthemarket
(91/414/EEC)
THE COUNCIL OF THE EUROPEAN COMMUNITIES,
Having regard to the Treaty establishing the European Economic
Community, and in particular Article 43 thereof,
Having regard to the proposal from the Commission (1),
Having regard to the opinion of the European Parliament (2),
Having regard to the opinion of the Economic and Social
Committee (3),
Whereas plant production has a very important place in the Commu-
nity;
Whereas plant production yields are continually affected by harmful
organisms including weeds; whereas it is absolutely essential to protectplants against these risks to prevent a decline in yields and to help toensure security of supplies;
Whereas one of the most important ways of protecting plants and plant
products and of improving agricultural production is to use plantprotection products;
Whereas these plant protection products can have non-beneficial effects
upon plant production; whereas their use may involve risks and hazardsfor humans, animals and the environment, especially if placed on themarket without having been officially tested and authorized and ifincorrectly used;
Whereas, in view of the hazards, there are rules in most Member States
governing the authorization of plant health products; whereas theserules present differences which constitute barriers not only to trade in
plant protection products but also to trade in plant products, and
thereby directly affect the establishment and operation of the internalmarket;
Whereas it is therefore desirable to eliminate such barriers by harmo-
nizing the provisions laid down in the Member States;
Whereas uniform rules on the conditions and procedures for the author-
ization of plant protection products must be applied by the Member
States;
Whereas such rules should provide that plant protection products
should not be put on the market or used unless they habe been offi-cially authorized and should be used properly having regard to the
principles of good plant protection practice and of integrated pest
control;
Whereas the provisions governing authorization must ensure a high
standard of protection, which, in particular, must prevent the authoriza-
tion of plant protection products whose risks to health, groundwater
and the environment and human and animal health should take priorityover the objective of improving plant production;
Whereas it is necessary, at the time when plant protection products are
authorized, to make sure that, when properly applied for the purposeintended, they are sufficiently effective and have no unacceptableeffect on plants or plant products, no unacceptable influence on theenvironment in general and, in particular, no harmful effect on humanor animal health or on groundwater;1991L0414 — EN — 01.07.2003 — 009.001 — 3
(1) OJ No C 89, 10. 4. 1989, p. 22.
(2) OJ No C 72, 18. 3. 1991, p. 33.
(3) OJ No C 56, 7. 3. 1990, p. 3.
▼B
Whereas authorization should be limited to plant protection products
containing certain active substances specified at Community level onthe basis of their toxicological and ecotoxicological properties;
Whereas it is therefore necessary to establish a Community list of
authorized active substances;
Whereas a Community procedure must be laid down for assessing
whether an active substance can be entered on the Community list;
whereas the information that interested parties must submit with aview to admission of a substance to the list should be specified;
Whereas the Community procedure should not prevent Member States
from authorizing for use in their territory for a limited period plantprotection products containing an active substance not yet entered onthe Community list, provided that the interested party has submitted a
dossier meeting Community requirements and the Member State has
concluded that the active substance and the plant protection productscan be expected to satisfy the Community conditions set in regard tothem;
Whereas, in the interests of safety, substances on the Community list
should be reviewed periodically, to take account of developments inscience and technology and of impact studies based on the actual use
of plant protection products containing the said substances;
Whereas it is in the interests of free movement of plant products as
well as of plant protection products that authorization granted by one
Member State, and tests carried out witha view to auth orization,should be recognized by other Member States, unless certain agricul-tural, plant health and environmental (including climatic) conditionsrelevant to the use of the products concerned are not comparable in
the regions concerned; whereas to this end there is a need to harmonize
the methods of experimentation and control applied by the MemberStates for the purpose of granting authorization;
Whereas it is therefore desirable that a system for the mutual supply of
information should be established and that Member States should makeavailable to each other on request the particulars and scientific docu-mentation submitted in connection withapplications for auth orization
of plant protection products;
Whereas, however, Member States must be enabled to authorize plant
protection products not complying withth e abovementioned conditions
when it is necessary to do so because of an unforeseeable danger threa-tening plant production which cannot be countered by other means;whereas such authorization should be reviewed by the Community inclose cooperation with the Member States in the framework of the
Standing Committee on Plant Health;
Whereas this Directive complements Community provisions on the
classification, packaging and labelling of pesticides; whereas together
with these provisions it considerably improves the protection of usersof plant protection products and consumers of plants and plantproducts; whereas it also contributes to the protection of the environ-ment;
Whereas it is necessary to maintain consistency between this Directive
and Community rules on the residues of plant protection products in
agricultural products and the free movement of the latter in the
Community; whereas this Directive complements Community provi-sions relating to maximum permissible levels for pesticide residuesand will facilitate the adoption of such levels in the Commission;whereas together with the latter provisions it considerably improvesthe protection of consumers of plants and plant products;1991L0414 — EN — 01.07.2003 — 009.001 — 4
▼B
Whereas resources devoted to the conduct of tests on vertebrate
animals should not be dissipated as a result of the differences in thelaws of the Member States and whereas considerations of public
interest and Council Directive 86/609/EEC of 24 November 1986 on
the approximation of laws, regulations and administrative provisionsof the Member States regarding the protection of animals used forexperimental and other scientific purposes (
1) militate against needless
repetition of tests on animals;
Whereas, in order to ensure that the requirements laid down are satis-
fied, Member States must make provision for appropriate control andinspection arrangements withregard to th e marketing and use of plant
protection products;
Whereas the procedures provided for by this Directive for the evalua-
tion of the risks to the environment presented by plant protection
products containing or composed of genetically modified organisms
correspond in principle to those laid down in Directive 90/220/EEC of23 April 1990 on the deliberate release into the environment of geneti-cally modified organisms (
2); whereas in future however the supply of
data in accordance withPart B of Annexes II and III is likely to be
subject to specific requirements, provision should be made to amend
this Directive accordingly;
Whereas the implementation of this Directive and the adaptation of its
Annexes to advances in technical and scientific knowledge necessitate
close cooperation between the Commission and the Member States, andwhereas the procedure of the Standing Committee on Plant Healthoffers a suitable basis for this cooperation,
HAS ADOPTED THIS DIRECTIVE:
Scope
Article 1
1. This Directive concerns the authorization, placing on the market,
use and control within the Community of plant protection products in
commercial form and the placing on the market and control within theCommunity of active substances intended for a use specified in Article2 (1).
2. This Directive shall apply without prejudice to Council Directive
78/631/EEC of 26 June 1978 on the approximation of the laws of theMember States relating to the classification, packaging and labelling ofdangerous preparations (pesticides) (
3), as last amended by Directive
84/291/EEC (4) and, where active substances are concerned, without
prejudice to the provisions concerning classification, packaging and
labelling of Council Directive 67/548/EEC of 27 June 1967 on theapproximation of laws, regulations and administrative provisionsrelating to the classification, packaging and labelling of dangeroussubstances (
5), as last amended by Directive 90/517/EEC (6).
3. This Directive applies to the authorization to place on the market
plant protection products containing or composed of genetically modi-fied organisms, provided that authorization to release them into the
environment has been granted after the risk to the environment has
been assessed in accordance withth e provisions of Parts A, B and Dand the relevant provisions of Part C of Directive 90/220/EEC.
The Commission shall submit to the Council, in sufficient time for the
latter to be able to act not later than two years after the date of notifi-cation of this Directive, a proposal for an amendment with a view to1991L0414 — EN — 01.07.2003 — 009.001 — 5
(1) OJ No L 358, 18. 12. 1986, p. 1.
(2) OJ No L 117, 8. 5. 1990, p. 15.
(3) OJ No L 206, 29. 7. 1978, p. 13.
(4) OJ No L 144, 30. 5. 1984, p. 1.
(5) OJ No 196, 16. 8. 1967, p. 1.
(6) OJ No L 287, 19. 10. 1990, p. 37.
▼B
including in this Directive (1) a specific procedure for evaluating the
risk to the environment analogous to that provided for the Directive90/220/EEC, and enabling this Directive to be placed on the list
provided for in Article 10 (3) of Directive 90/220/EEC in accordance
with the procedure laid down in the said Article 10.
Within five years of the date of notification of this Directive, the
Commission, on the basis of experience gained, shall provide theEuropean Parliament and the Council with a report on the operationof the arrangements described in the first and second subparagraphs.
4. This Directive shall apply without prejudice to Council Regula-
tion (EEC) No 1734/88 of 16 June 1988 concerning export from andimport into the Community of certain dangerous chemicals (
2).
Definitions
Article 2
For the purposes of this Directive the following definitions shall apply:1.‘plant protection products’
active substances and preparations containing one or more active
substances, put up in the form in which they are supplied to theuser, intended to:
1.1. protect plants or plant products against all harmful organisms or
prevent the action of such organisms, in so far as such substancesor preparations are not otherwise defined below;
1.2. influence the life processes of plants, other than as a nutrient, (e.g.
growthregulators);
1.3. preserve plant products, in so far as suchsubstances or products
are not subject to special Council of Commission provisions onpreservatives;
1.4. destroy undesired plants; or1.5. destroy parts of plants, check or prevent undesired growth of
plants;
2.‘residues of plant protection products’
one or more substances present in or on plants or products of plant
origin, edible animal products or elsewhere in the environment andresulting from the use of a plant protection product, including theirmetabolites and products resulting from their degradation or reac-tion;
3.‘substances’
chemical elements and their compounds, as they occur naturally or
by manufacture, including any impurity inevitable resulting from
the manufacturing process;
4.‘active substances’
substances or micro-organisms including viruses, having general
or specific action:
4.1. against harmful organisms; or4.2. on plants, parts of plants or plant products;5.‘preparations’
mixtures or solutions composed of two or more substances of
which at least one is an active substance, intended for use as plant
protection products;
6.‘plants’
live plants and live parts of plants, including freshfruit and seeds;
7.‘plant products’1991L0414 — EN — 01.07.2003 — 009.001 — 6
(1) This Directive was notified to the Member States on 26 July 1991.
(2) OJ No L 155, 22. 6. 1988, p. 2.
▼B
products in the unprocessed state or having undergone only simple
preparation suchas milling, drying or pressing, derived fromplants, but excluding plants themselves as defined in point 6;
8.‘harmful organisms’
pests of plants or plant products belonging to the animal or plant
kingdom, and also viruses, bacteria and mycoplasmas and otherpathogens;
9.‘animals’
animals belonging to species normally fed and kept or consumed
by man;
10.‘placing on the market’
any supply, whether in return for payment or free of charge, other
than for storage followed by consignment from the territory of theCommunity or disposal. Importation of a plant protection product
into the territory of the Community shall be deemed to constitute
placing on the market for the purposes of this Directive;
11.‘authorization of a plant protection product’
administrative act by which the competent authority of a Member
State authorizes, following an application submitted by an appli-
cant, the placing on the market of a plant protection product in
its territory or in a part thereof;
12.‘environment’
water, air, land, wild species of fauna and flora, and any interrela-
tionship between them, as well as any relationship with livingorganisms;
13.‘integrated control’
the rational application of a combination of biological, biotechno-
logical, chemical, cultural or plant-breeding measures whereby theuse of chemical plant protection products is limited to the strictminimum necessary to maintain the pest population at levelsbelow those causing economically unacceptable damage or loss.
General provisions
Article 3
1. Member States shall prescribe that plant protection products may
not be placed on the market and used in their territory unless they haveauthorized the product in accordance with this Directive, except wherethe intended use is covered by Article 22.
2. Member States shall not, on the grounds that a plant protection
product is not authorized for use in their territory, impede the produc-tion, storage or movement of suchproducts intended for use in anoth erMember State, provided that:
— the product is authorized in another Member State, and
— the inspection requirements laid down by the Member States in
order to ensure compliance withparagraph1 are satisfied.
3. Member States shall prescribe that plant protection products must
be used properly. Proper use shall include compliance with the condi-tions established in accordance with Article 4 and specified on the
labelling, and the application of the principles of good plant protection
practice as well as, whenever possible, the principles of integratedcontrol.
4. Member States shall prescribe that active substances may not be
placed on the market unless:
— they are classified, packaged and labelled in accordance with Direc-
tive 67/548/EEC, and
— where the active substance was not on the market two years after
notification of this Directive, a dossier has been forwarded to theMember States and to the Commission, in accordance with Article6, with the declaration that the active substance is intended for a1991L0414 — EN — 01.07.2003 — 009.001 — 7
▼B
use specified in Article 2 (1). This condition shall not apply to
active substances intended for a use under Article 22.
Granting,reviewandwithdrawalofauthorizationsofplantprotec-
tionproducts
Article 4
1. Member States shall ensure that a plant protection product is not
authorized unless:
(a) its active substances are listed in Annex I and any conditions laid
down therein are fulfilled,
and, withregard to th e following points (b), (c), (d) and (e),
pursuant to the uniform principles provided for in Annex VI,
unless:
(b) it is established, in the light of current scientific and technical
kowledge and shown from appraisal of the dossier provided for inAnnex III, that when used in accordance with Article 3 (3), andhaving regard to all normal conditions under which it may beused, and to the consequences of its use:
(i) it is sufficiently effective;
(ii) it has no unacceptable effect on plants or plant products;
(iii) it does not cause unnecessary suffering and pain to vertebrates
to be controlled;
(iv) it has no harmful effect on human or animal health, directly or
indirectly (e.g. through drinking water, food or feed) or ongroundwater;
(v) it has no unacceptable influence on the environment, having
particular regard to the following considerations:
— its fate and distribution in the environment, particularly
contamination of water including drinking water andgroundwater,
— its impact on non-target species;
(c) the nature and quantity of its active substances and, where appro-
priate, any toxicologically or ecotoxicologically significantimpurities and co-formulants can be determined by appropriatemethods, harmonized according to the procedure provided inArticle 21, or, if not, agreed by the authorities responsible for theauthorization;
(d) its residues, resulting from authorized uses, and which are of toxi-
cological or environmental significance, can be determined by
appropriate methods in general use;
(e) its physical and chemical properties have been determined and
deemed acceptable for the purposes of the appropriate use andstorage of the product;
(f) maximum residue levels in the agricultural products referred to in
the authorization have been provisionally established by the
Member State and notified to the Commission in accordance with
Article 12; within three months of the said notification, theCommission shall consider whether the provisional maximumlevels established by the Member State are acceptable, and inaccordance with the procedure laid down in Article 19 it shall
establish provisional maximum levels throughout the Community
and these shall remain in force until the corresponding maximumlevels are adopted pursuant to the procedure provided for in thesecond subparagraphof Article 1 (1) of Directive 90/462/EEC (
1)
and in Article 11 of Directive 86/362/EEC (2), as amended by
Directive 88/298/EEC (3).1991L0414 — EN — 01.07.2003 — 009.001 — 8
(1) OJ No L 350, 14. 12. 1990, p. 71.
(2) OJ No L 221, 7. 8. 1986, p. 36.
(3) OJ No L 126, 20. 5. 1988, p. 53.
▼B
In particular:
(i) Member States may not prohibit or impede the introduction
into their territory of products containing pesticide residues
provided the residue level does not exceed the provisional
maximum levels set in accordance with the first subparagraph;
(ii) Member States must ensure that the conditions for approval are
applied in such a way that the provisional maximum levels are
not exceeded.
2. The authorization must stipulate the requirements relating to the
placing on the market and use of the product or at least those aimed
at ensuring compliance withth e provisions of paragraph1 (b).
3. Member States shall ensure that compliance with the require-
ments set out in paragraph1 (b) to (f) is establish ed by official orofficially recognized tests and analyses carried out under agricultural,plant health and environmental conditions relevant to use of the plantprotection product in question and representative of these prevailingwhere the product is intended to be used, within the territory of the
Member State concerned.
4. Without prejudice to paragraphs 5 and 6, authorizations shall be
granted for a fixed period of up to 10 years only, determined by the
Member States; they may be renewed after verification that the condi-tions imposed in paragraph1 are still satisfied. Renewal may begranted for the period necessary to the competent authorities of theMember States, for suchverification, wh ere an application for renewalhas been made.
5. Authorizations may be reviewed at any time if there are indica-
tions that any of the requirements referred to in paragraph 1 are no
longer satisfied. In such instances the Member States may require the
applicant for authorization or party to whom an extension of the fieldof application was granted in accordance withArticle 9 to submitfurther information necessary for the review. The authorization may,where necessary, be extended for the period necessary to complete areview and provide suchfurth er information.
6. Without prejudice to Decisions already taken pursuant to Article
10, an authorization shall be cancelled if it is established that:
(a) the requirements for obtaining the authorization are not or are no
longer satisfied;
(b) false or misleading particulars were supplied concerning the facts
on the basis of which the authorization was granted;
or modified if it is established that:
(c) on the basis of developments in scientific and technical knowledge
the manner of use and amounts used can be modified.
It may also be cancelled or modified at the request of the holder of the
authorization, who shall state the reasons therefor; amendments can begranted only if it is established that the requirements of Article 4 (1)
continue to be satisfied.
Where a Member State withdraws an authorization, it shall immedi-
ately inform the holder of the authorization; moreover, it may grant a
period of grace for the disposal, storage, placing on the market and use
of existing stocks, of a length in accordance with the reason for thewithdrawal, without prejudice to any period provided for by decisiontaken under Council Directive 79/117/EEC of 21 December 1978prohibiting the placing on the market and use of plant protection
products containing certain active substances (
1), as last amended by
Directive 90/533/EEC (2), or Article 6 (1) or Article 8 (1) or (2) of
this Directive.1991L0414 — EN — 01.07.2003 — 009.001 — 9
(1) OJ No L 33, 8. 2. 1979, p. 36.
(2) OJ No L 296, 27. 10. 1990, p. 63.
▼B
InclusionofactivesubstancesinAnnexI
Article 5
1. In the light of current scientific and technical knowledge, an
active substance shall be included in Annex I for an initial period not
exceeding 10 years, if it may be expected that plant protection products
containing the active substance will fulfil the following conditions:
(a) their residues, consequent on application consistent with good plant
protection practice, do not have any harmful effects on human oranimal health or on groundwater or any unacceptable influence onthe environment, and the said residues, in so far as they are of toxi-
cological or environmental significance, can be measured by
methods in general use;
(b) their use, consequent on application consistent with good plant
protection practice, does not have any harmful effects on human
or animal health or any anacceptable influence on the environmentas provided for in Article 4 (1) (b) (iv) and (v).
2. For inclusion of an active substance in Annex I, the following
shall be taken into particular account:
(a) where relevant, an acceptable daily intake (ADI) for man;
(b) an acceptable operator exposure level if necessary;
(c) where relevant, an estimate of its fate and distribution in the envir-
onment as well as its impact on non-target species.
3. For the first inclusion of an active substance which was not yet
on the market two years after notification of this Directive, the require-ments shall be deemed to be satisfied where this has been establishedfor at least one preparation containging the said active substance.
4. Inclusion of an active substance in Annex I may be subject to
requirements suchas:
— the minimum degree of purity of the active substance,
— the nature and maximum content of certain impurities,— restrictions arising from evaluation of the information referred to in
Article 6, taking account of the agricultural, plant health and envir-onmental (including climatic) conditions in question,
— type of preparation,— manner of use.
5. On request, the inclusion of a substance in Annex I may be
renewed once or more for periods not exceeding 10 years; suchinclu-
sion may be reviewed at any time if there are indications that the
criteria referred to in paragraphs 1 and 2 are no longer satisfied.Renewal shall be granted for the period necessary to complete areview, where an application has been made for such renewal in suffi-cient time, and in any case not less than two years before the entry isdue to lapse, and shall be granted for the period necessary to provide
information requested in accordance withArticle 6 (4).
Article 6
1. Inclusion of an active substance in Annex I shall be decided in
accordance withth e procedure laid down in Article 19.
The following shall also be decided in accordance with that procedure:
— any conditions for inclusion,
— amendements to Annex I, where necessary,
— removal of an active substance form Annex I if it no longer satis-
fies the requirements of Article 5 (1) and (2).
2. A Member State receiving an application for the inclusion of an
active substance in Annex I shall without undue delay ensure that adossier which is believed to satisfy the requirements of Annex II isforwarded by the applicant to the other Member States and to theCommission togeth er witha dossier complying withAnnex III on at1991L0414 — EN — 01.07.2003 — 009.001 — 10
▼B
least one preparation containing that active substance. The Commission
shall refer the dossier to the Standing Committee on Plant Healthreferred to in Article 19 for examination.
3. Without prejudice to the provisions of paragraph 4, at the request
of a Member State, and within three to six months after the date ofreferral to the committee mentioned in Article 19, it shall be estab-lished by the procedure laid down in Article 20 whether the dossierhas been submitted in accordance with the requirements of Annexes II
and III.
4. If the assessment of the dossier referred to in paragraph 2 shows
that further information is necessary, the Commission may ask theapplicant to submit such information. The applicant or his authorizedrepresentative may be asked by the Commission to submit his remarks
to it, in particular whenever an unfavourable decision is envisaged.
These provisions shall also apply if, after inclusion of an active
substance in Annex I, facts emerge that cast doubt on its conformitywithth e requirements indicated in Article 5 (1) and (2), or if renewalin accordance withArticle 5 (5) is being considered.
5. The procedure concerning the submission and appraisal of appli-
cations for inclusion in Annex I and setting or varying any conditions
for inclusion shall be adopted in accordance with the procedure laiddown in Article 21.
Informationonpotentiallyharmfuleffects
Article 7
Member States shall prescribe that the holder of an authorization or
those to whom an extension of the field of application has been granted
in accordance withArticle 9 (1) must immediately notify th e compe-
tent authority of all new information on the potentially dangerouseffects of any plant protection product, or of residues of an activesubstance on human or animal health or on groundwater, or theirpotentially dangerous effects on the environment. Member States shall
ensure that the parties concerned immediately notify this information to
the other Member States and to the Commission, which shall refer theinformation to the committee referred to in Article 19.
Transitionalmeasuresandderogations
Article 8
1. By way of derogation from Article 4, a Member State may, to
enable a gradual assessment to be made of the properties of new active
substances and to make it easier for new preparations to be made avail-
able for use in agriculture, authorize, for a provisional period notexceeding three years, the placing on the market of plant protectionproducts containing an active substance not listed in Annex I and notyet available on the market two years after notification of this Direc-tive, provided that:
(a) following application of Article 6 (2) and (3) it is found that the
dossier on the active substance satisfies the requirements ofAnnexes II and III in relation to the projected uses;
(b) the Member State establishes that the active substance can satisfy
the requirements of Article 5 (1) and that the plant protectionproduct may be expected to satisfy the requirements of Article 4(1) (b) to (f).
In such cases the Member State shall immediately inform the other
Member States and the Commission of its assessment of the dossier
and of the terms of the authorization, giving at least the informationprovided for in Article 12 (1).
Following the evaluation of the dossier as provided for in Article 6 (3),
it may be decided, in accordance withth e procedure laid down inArticle 19, that the active substance does not satisfy the requirements1991L0414 — EN — 01.07.2003 — 009.001 — 11
▼B
specified in Article 5 (1). In such cases the Member States shall ensure
that the authorizations must be withdrawn.
By way of derogation from Article 6, if, on expiry of the three-year
period, a decision has not been taken concerning the inclusion of anactive substance in Annex I, a further period may be ordered by theprocedure referred to in Article 19 to enable a full examination to bemade of the dossier and, where appropriate, of any additional informa-tion requested in accordance withArticle 6 (3) and (4).
The provisions of Article 4 (2), (3), (5) and (6) shall apply to authori-
zations granted under the terms of this paragraph without prejudice tothe foregoing subparagraphs.
2. By way of derogation from Article 4 and without prejudice to
paragraph3 or to Directive 79/117/EEC, a Member State may, during
a period of 12 years following the notification of this Directive,
authorize the placing on the market in its territory of plant protectionproducts containing active substances not listed in Annex I that arealready on the market two years after the date of notification of thisDirective.
After the adoption of this Directive, the Commission shall commence a
programme of work for the gradual examination of these active
substances within the 12-year period referred to in the foregoingsubparagraph. This programme may require interested parties to submitall requisite data to the Commission and the Member States within aperiod provided for in the programme. A Regulation, adoptedaccording to the procedure laid down in Article 19, will set out all the
provisions necessary for the implementation of the programme.
Ten years following notification of this Directive the Commission shall
present to the European Parliament and the Council a progress reporton the programme. Depending upon the conclusions of the report, itmay be decided, according to the procedure laid down in Article 19,
whether, for certain substances, the 12-year period referred to in the
first subparagraphis to be extended for a period to be determined.
During the 12-year period referred to in the first subparagraph it may,
following examination by the Committee referred to in Article 19 ofsuch active substance, be decided by the procedure laid down in thatArticle that the substance can be included in Annex I and under which
conditions, or, in cases where the requirements of Article 5 are not
satisfied or the requisite information and data have not been submittedwithin the prescribed period, that such active substance will not beincluded in Annex I. The Member States shall ensure that the relevantauthorizations are granted, withdrawn or varied, as appropriate, within
a prescribed period.
3. Where they review plant protection products containing an active
substance in accordance withparagraph2, and before suchreview h astaken place, Member States shall apply the requirements laid down inArticle 4 (1) (b) (i) to (v), and (c) to (f) in accordance withnationalprovisions concerning the data to be provided.
4. By way of further derogation from Article 4, in special circum-
stances a Member State may authorize for a period not exceeding 120days the placing on the market of plant protection products notcomplying withArticle 4 for a limited and controlled use if suchameasure appears necessary because of an unforeseeable danger which
cannot be contained by other means. In this case, the Member State
concerned shall immediately inform the other Member States and theCommission of its action. It shall be decided without delay, in accor-dance with the procedure laid down in Article 19, whether and underwhich conditions the action taken by the Member State may beextended for a given period, repeated, or revoked.1991L0414 — EN — 01.07.2003 — 009.001 — 12
▼B
Applicationforauthorization
Article 9
1. Application for authorization of a plant protection product shall
be made by or on behalf of the person responsible for first placing it
on the market in a Member State to the competent authorities of each
Member State where the plant protection product is intended to beplaced on the market.
Official or scientific bodies involved in agricultural activities or profes-
sional agricultural organizations and professional users may requestthat the field of application of a plant protection product already
authorized in the Member State in question be extended to purposes
other than those covered by this authorization.
Member States shall grant an extension of the field of application of an
authorized plant protection product and shall be obliged to grant suchan extension when it is in the public interest to the extent that:
— the documentation and information to support an extension of the
field of application has been submitted by the applicant,
— they have established that the conditions referred to in Article 4 (1)
(b) (iii), (iv) and (v) are satisfied,
— the intended use is minor in nature,— users are fully and specifically informed as to instructions for use,
by means of an addition to the labelling or, failing that, by meansof an official publication.
2. Every applicant shall be required to have a permanent office
within the Community.
3. Member States may require that applications for authorization be
submitted in their national or official languages or one of those
languages. They may also require that samples of the preparation and
of its ingredients be provided.
4. EachMember State sh all agree to consider any application for
authorization made to it and shall decide thereon within a reasonableperiod, provided that it has the necessary scientific and technical struc-tures at its disposal.
5. Member States shall ensure that a file is compiled on each appli-
cation. Each file shall contain at least a copy of the application, arecord of the administrative decisions taken by the Member Stateconcerning the application and concerning the particulars and docu-mentation laid down in Article 13 (1) together with a summary of thelatter. Member States shall on request make available to the other
Member States and to the Commission the files provided for in this
paragraph; they shall supply to them on request all information neces-sary for full comprehension of applications, and shall where requestedensure that applicants provide a copy of the technical documentationlaid down in Article 13 (1) (a).
Mutualrecognitionofauthorizations
Article 10
1. At the request of the applicant, who must substantiate the claim
to comparability withdocumentary evidence, a Member State to wh ich
an application is made for the authorization of a plant protection
product already authorized in another Member State must:
— refrain from requiring the repetition of tests and analyses already
carried out in connection with the authorization of the product in
that Member State, and to the extent that agricultural, plant health
and environmental (including climatic) conditions relevant to theuse of the product are comparable in the regions concerned, and
— to the extent that the uniform principles have been adopted in
accordance with Article 23, where the product contains only activesubstances listed in Annex I, also authorize the placing of thatproduct on the market in its territory, to the extent that agricultural,1991L0414 — EN — 01.07.2003 — 009.001 — 13
▼B
plant health and environmental (including climatic) conditions rele-
vant to the use of the product are comparable in the regionsconcerned.
Authorization may be subject to conditions resulting from the imple-
mentation of other measures in accordance with Community law,relating to the conditions for distribution and use of plant protectionproducts intended to protect the health of the distributors, users and
workers concerned.
Subject to compliance with the Treaty, authorization may also be
accompanied by restrictions on use arising from differences in dietarypatterns and necessary in order to avoid exposure of consumers of
treated products to the risks of dietary contamination in excess of the
acceptable daily intake of the residues concerned.
Authorization may be subject, with the agreement of the applicant, to
changes in the conditions of use in order to render, in the regions
concerned, any non-comparable agricultural, plant health or environ-
mental (including climatic) conditions irrelevant for the purpose ofcomparability.
2. Member States shall inform the Commission of cases where they
have required repetition of a test and of cases where they have refused
to authorize a plant protection product already authorized in another
Member State, in respect of which the applicant had claimed that theagricultural, plant health and environmental (including climatic) condi-tions relevant to use of the product in the regions concerned in theMember State where the test was carried out or for which authorization
was granted were comparable to those in their own territory. They shall
notify the Commission of the grounds on which repetition of the testwas required or authorization was refused.
3. Without prejudice to Article 23, in cases where a Member State
refuses to recognize comparability and accept tests and analyses or
authorize the placing on the market of a plant protection product inthe relevant regions of its territory, the decision as to whether or notcomparability exists shall be taken in accordance with the procedurelaid down in Article 19 and, if the decision is negative, it shall alsospecify the conditions of use under which the non-comparability may
be deemed irrelevant. In this procedure account shall be taken, inter
alia, of the serious ecological vulnerability problems that may arise in
certain Community regions or zones thereby requiring, if they do arise,specific protection measures. The Member State shall without delayaccept the tests and analyses or authorize the placing of the plantprotection product on the market, subject in the latter case to any terms
which the above decision may set.
Article 11
1. Where a Member State has valid reasons to consider that a
product which it has authorized or is bound to authorize under Article
10 constitutes a risk to human or animal health or the environment, itmay provisionally restrict or prohibit the use and/or sale of that producton its territory. It shall immediately inform the Commission and theother Member States of such action and give reasons for its decision.
2. A decision shall be taken on the matter within three months in
accordance withth e procedure laid down in Article 19.
Exchangeofinformation
Article 12
1. Within a period of one month at the end of each quarter at least,
Member States shall inform each other and the Commission in writingof any plant protection products authorized or withdrawn, in accor-dance with the provisions of this Directive, indicating at least:
— the name or business name of the holder of the authorization,
— the trade name of the plant protection product,— the type of preparation,1991L0414 — EN — 01.07.2003 — 009.001 — 14
▼B
— the name and amount of each active substance which it contains,
— the use or uses for which it is intended,
— the maximum residue levels provisionally established where they
have not already been set by Community rules,
— where relevant, the reasons for withdrawal of an authorization,
— the dossier needed for the evaluation of the maximum residue levels
provisionally established.
2. Each Member State shall draw up an annual list of the plant
protection products authorized in its territory and shall communicate
that list to the other Member States and the Commission.
In accordance withth e procedure laid down in Article 21 a standar-
dized information system shall be set up to facilitate the application
of paragraphs 1 and 2.
Datarequirements, dataprotectionandconfidentiality
Article 13
1. Without prejudice to Article 10, Member States shall require that
applicants for authorization of a plant protection product submit withtheir application:
(a) a dossier satisfying, in the light of current scientific and technical
knowledge, the requirements set out in Annex III; and
(b) for eachactive substance in th e plant protection product, a dossier
satisfying, in the light of current scientific and technical knowl-edge, the requirements set out in Annex II.
2. By way of derogation from paragraph1, and with out prejudice to
the provisions of paragraphs 3 and 4, applicants shall be exemptedfrom supplying the information required under paragraph 1 (b) exceptfor that identifying the active substance if the active substance is
already listed in Annex I, taking into account the conditions of inclu-
sion in Annex I, and does not differ significantly in degree of purityand nature of impurities, from the composition registered in the dossieraccompanying the original application.
3. In granting authorizations, Member States shall not make use of
the information referred to in Annex II for the benefit of other appli-cants:
(a) unless the applicant has agreed with the first applicant that use may
be made of suchinformation; or
(b) for a period of 10 years from first inclusion in Annex I of an active
substance not on the market two years after the date of notificationof this Directive; or
(c) for periods not exceeding 10 years from the date of the decision in
eachMember State and provided for in existing national rules,concerning an active substance on the market two years after the
date of notification of this Directive; and
(d) for a period of five years from the date of a decision, following
receipt of further information necessary for first inclusion in AnnexI, or to vary the conditions for, or to maintain the inclusion of an
active substance in Annex I, which has been taken either to vary
the conditions for, or to maintain, the inclusion of an activesubstance in Annex I, unless the five-year period expires beforethe period provided for in paragraphs 3 (b) and (c), in which casethe period of five years shall be extended so as to expire on thesame date as those periods.1991L0414 — EN — 01.07.2003 — 009.001 — 15
▼C1
▼B
4. In granting authorizations, Member States shall not make use of
the information referred to in Annex III to the benefit of other appli-cants:
(a) unless the applicant has agreed with the first applicant that use may
be made of suchinformation; or
(b) for a period of 10 years from first authorization of the plant protec-
tion product in any Member State, where authorization follows theinclusion in Annex I of any active substance contained in theproduct; or
(c) for periods not exceeding 10 years and provided for in existing
national rules after the first authorization of the plant protectionproduct in each Member State, where that authorization precedes
inclusion in Annex I of any active substance contained in the
product.
5. Member States, on examination of an application for authoriza-
tion, shall inform the Commission of instances ►
C1where they
consider an active substance as listed ◄in Annex I, which has been
produced by a person or manufacturing process other than those speci-fied in the dossier on the basis of which the active substance was firstincluded in Annex I. They shall transmit to it all data regarding theidentify and impurities of the active substance.
6. By way of derogation from paragraph1, for active substances
already on the market two years after notification of this Directive,Member States may, with due regard for the provisions of the Treaty,continue to apply previous national rules concerning data requirementsas long as suchsubstances are not included in Annex I.
7. Notwithstanding paragraph 1, and without prejudice to Article 10,
where the active substance is listed in Annex I:
(a) applicants for authorization of plant protection products shall,
before carrying out experiments involving vertebrate animals,
enquire of the competent authority of the Member State to which
they intend making application:
— whether the plant protection product for which an application is
to be made is the same as a plant protection product for whichauthorization has been granted, and
— as to the name and address of the holder or holders of the
authorization or authorizations.
The enquiry shall be supported by evidence that the prospective
applicant intends to apply for authorization on his own behalf andthat the other information specified in paragraph 1 is available;
(b) the competent authority of the Member State, if satisfied that the
applicant intends to apply, shall provide the name and address ofthe holder or holders of previous relevant authorizations and shall
at the time inform the holders of the authorizations of the name and
address of the applicant.
The holder or holders of previous authorizations and the applicant shall
take all reasonable steps to reach agreement on the sharing of informa-
tion so as to avoid the duplication of testing on vertebrate animals.
Where data is requested with a view to inclusion in Annex I of an
active substance already on the market two years after notification ofthis Directive, the competent authorities of the Member State shallencourage data holders to cooperate in the provision of the requested
data, witha view to limiting th e duplication of testing on vertebrate
animals.
If, nevertheless, the applicant and holders of previous authorizations of
the same product can still not reach an agreement on the sharing of
data, Member States may introduce national measures obliging the
applicant and holders of previous authorizations located within theirterritory to share the data with a view to avoiding duplicative testingon vertebrate animals and determine bothth e procedure for utilizinginformation, and the reasonable balance of the interests of the partiesconcerned.1991L0414 — EN — 01.07.2003 — 009.001 — 16
▼B
Article 14
Member States and the Commission shall, without prejudice to Council
Directive 90/313/EEC of 7 June 1990 on the freedom of access toinformation on the environment (
1), ensure that information submitted
by applicants involving industrial and commercial secrets is treated as
confidential if the applicant wishing to have an active substanceincluded in Annex I or the applicant for authorization of a plant protec-tion product so requests, and if the Member State or the Commissionaccepts that the applicant's request is warranted.
Confidentiality shall not apply to:
— the names and content of the active substance or substances and the
name of the plant protection product,
— the name of other substances which are regarded as dangerous
under Directives 67/548/EEC and 78/631/EEC,
— physico-chemical data concerning the active substance and plant
protection product,
— any ways of rendering the active substance or plant protection
product harmless,
— a summary of the results of the tests to establish the substance's or
product's efficacy and harmlessness to humans, animals, plants andthe environment,
— recommended methods and precautions to reduce handling, storage,
transport, fire or other hazards,
— methods of analysis referred to in Articles 4 (1) (c) and (d) and 5
(1),
— methods of disposal of the product and of its packaging,
— decontamination procedures to be followed in the case of acciden-
tial spillage or leakage,
— first aid and medical treatment to be given in the case of injury to
persons.
If the applicant subsequently discloses previously confidential informa-
tion, he shall be required to inform the competent authority
accordingly.
Packagingandlabelling ofplantprotectionproducts
Article 15
Article 5 (1) of Directive 78/631/EEC shall apply to all plant protection
products not covered by Directive 78/631/EEC.
Article 16
Member States shall take all necessary measures to ensure that the
packaging of plant protection products satisfies the following require-
ments as to labelling.
1. All packaging must show clearly and indelibly the following:
(a) the trade name or designation of the plant protection product;
(b) the name and address of the holder of the authorization and the
authorization number of the plant protection product and, if
different, the name and address of the person responsible for
the final packaging and labelling or for the final labelling ofthe plant protection product on the market;
►
C1(c) the name and amount of each active substance expressed
as provided for in Article 6 of Directive 78/631/EEC and ◄in
particular paragraph(2) (d) of th at Article.
The name must be as given in the list contained in Annex I to
Directive 67/548/EEC or, if not included therein, its ISOcommon name. If the latter is not available, the active1991L0414 — EN — 01.07.2003 — 009.001 — 17
(1) OJ No L 158, 23. 6. 1990, p. 56.
▼B
substance shall be designated by its chemical designation
according to IUPAC rules;
(d) the net quantity of plant protection product given in legal units
of measurement;
(e) the formulation batch number or some means of identifying it;
(f) the particulars required under Article 6 of Directive 78/631/
EEC, in particular those mentioned in paragraph 2 (d), (g), (h)and (i), and paragraphs 3 and 4 of that Article and information
on first aid;
(g) the nature of any special risks for humans, animals or the envir-
onment, by means of standard phrases selected as appropriatefrom those given in Annex IV;
(h) safety precautions for the protection of humans, animals or the
environment, in the form of standard phrases selected as appro-priate from those given in Annex V;
(i) the type of action of the plant protection product (e.g. insecti-
cide, growthregulator, weedkiller, etc.);
(j) the type of preparation (e.g. wettable powder, emulsifiable
concentrate, etc.);
(k) the uses for which the plant protection product has been author-
ized and any specific agricultural, plant health andenvironmental conditions under which the product may be
used or should not be used;
(l) directions for use and the dose rate, expressed in metric units,
for each use provided for under the terms of the authorization;
(m) where necessary, the safety interval for each use between appli-
cation and:
— sowing or planting of the crop to be protected,
— sowing or planting of succeeding crops,
— access by humans or animals,— harvesting,— use or consumption;
(n) particulars of possible phytotoxicity, varietal susceptibility, and
any other direct or indirect adverse side effects on plants orproducts of plant origin together with the intervals to beobserved between application and sowing or planting of:
— the crop in question, or
— subsequent crops;
(o) if accompanied by a leaflet, as provided for in paragraph2, th e
sentence ‘Read accompanying instructions before use’;
(p) directions for safe disposal of the plant protection product and
of the packaging; and
(q) the expiry date relevant to normal conditions of storage where
the shelf life of the product is limited to less than two years.
2. Member States may permit the requirements in paragraph 1 (l), (m)
and (n) to be indicated on a separate leaflet accompanying thepackage if the space available on the package is too small. Such a
leaflet shall be regarded as part of the label for the purposes of this
Directive.
3. Taking account of the rules in force within their territories regarding
the supply of certain plant protection products to certain categories
of users, pending Community harmonization, the Member States
shall require that it be indicated on the label whether a product isrestricted to certain categories of users.
4. In no circumstances may the label of the packaging of a plant
protection product bear the indications ‘non-toxic’, ‘harmless’, or
similar indications. However, information to the effect that the plantprotection product may be used when bees or other non-targetspecies are active, or when crops or weeds are in flower or othersuch phrases to protect bees or other non-target species may be1991L0414 — EN — 01.07.2003 — 009.001 — 18
▼B
given on the label, if the authorization relates explicitly to use
during the season for bees or other specified organisms and presentsminimal hazard to them.
5. Member States may make the placing of plant protection products
on the market in their territories subject to their being labelled intheir national language or languages, and may require that samples,models or drafts of the packaging, labelling and leaflets referred toin this Article be submitted.
By way of derogation from paragraph1 (g) and (h ), Member States
may require additional phrases to be clearly and indelibly marked on
packaging where they are deemed to be necessary for the protection
of human beings, animals or the environment; in that event theyshall notify the other Member States and the Commission forthwithof each derogation granted and shall forward the additional phraseor phrases and the reasons for these requirements.
In accordance withth e procedure laid down in Article 19, a decision
shall be taken that the additional phrase or phrases is or are justified
and hence that Annexes IV and V must be amended accordingly, orthat the Member States concerned must no longer require suchphrase(s). The Member State shall be entitled to maintain itsrequirement until suchtime as a decision h as been taken.
Controlmeasures
Article 17
Member States shall make the necessary arrangements for plant protec-
tion products which have been placed on the market and for their useto be officially checked to see whether they comply with the require-ments of this Directive and in particular with the requirements of the
authorization and information appearing on the label.
The Member States shall report annually before 1 August to the other
Member States and the Commission on the results of the inspection
measures taken in the previous year.
Administrativeprovisions
Article 18
1. The Council, acting by a qualified majority on a proposal from
the Commission, shall adopt the ‘uniform principles’ referred to inAnnex VI.
2. In accordance withth e procedure laid down in Article 19 and
having regard to current scientific and technical knowledge, the neces-sary amendments to Annexes II, III, IV, V and VI shall be adopted.
Article 19
1. The Commission shall be assisted by the Standing Committee on
the Food Chain and Animal Health set up pursuant to Article 58 of
Regulation (EC) No 178/2002 (
1).
2. Where reference is made to this Article, Articles 5 and 7 of Deci-
sion 1999/468/EC (2) shall apply.
The period laid down in Article 5(6) of Decision 1999/468/EC shall be
set at three months.
3. The Committee shall adopt its Rules of Procedure.1991L0414 — EN — 01.07.2003 — 009.001 — 19
(1) OJ L 31, 1.2.2002, p. 1.
(2) OJ L 184, 17.7.1999, p. 23.▼M37
▼M37
Article 20
1. The Commission shall be assisted by the Standing Committee on
the Food Chain and Animal Health.
2. Where reference is made to this Article, Articles 5 and 7 of Deci-
sion 1999/468/EC shall apply.
The period laid down in Article 5(6) of Decision 1999/468/EC shall be
set at 15 days.
Article 21
1. The Commission shall be assisted by the Standing Committee on
the Food Chain and Animal Health.
2. Where reference is made to this Article, Articles 3 and 7 of Deci-
sion 1999/468/EC shall apply.
Researchanddevelopment
Article 22
1. The Member States shall prescribe that any experiment or test for
research or development purposes involving the release into the envir-
onment of an unauthorized plant protection product may only be
carried out after authorization for trial purposes has been granted andunder controlled conditions and for limited quantities and areas.
2. The persons concerned shall submit an application to the compe-
tent authority of the Member State in whose territory the experiment ortest is to be conducted, within time periods prescribed by the Member
State before the commencement of the experiment or test, together with
a dossier containing all the available data to permit an assessment to bemade of possible effects on human or animal health or the possibleimpact on the environment.
If the proposed experiments or tests referred to in paragraph 1 are
liable to have harmful effects on human or animal health or to have
an unacceptable adverse influence on the environment, the MemberState concerned may either prohibit them or permit them subject tosuchconditions as it considers necessary to prevent th ose conse-quences.
3. Paragraph 2 shall not apply if the Member State has granted the
person concerned the right to undertake certain experiments and testsand has determined the conditions under which the experiments andtests have to be undertaken.
4. Common conditions for the application of this Article, in parti-
cular the maximum quantities of pesticides that may be released
during experiments covered by paragraph1, and th e minimum data tobe submitted in accordance withparagraph2, sh all be adopted inaccordance withth e procedure laid down in Article 19.
5. This Article shall not apply to experiments or tests covered by
Part B of Directive 90/220/EEC.
ImplementationoftheDirective
Article 23
1. Member States shall bring into force the laws, regulations and
administrative provisions necessary to comply withth is Directivewithin two years following notification thereof. They shall immediatelyinform the Commission thereof. The uniform principles shall be
adopted one year after the date of notification.
When Member States adopt these measures, they shall contain a refer-
ence to this Directive or shall be accompanied by such reference on theoccasion of their official publication. The methods of making such areference shall be laid down by the Member States.1991L0414 — EN — 01.07.2003 — 009.001 — 20
▼B
▼B
2. Paragraph1 notwith standing, Member States need not bring into
force laws, regulations and administrative provisions implementingArticle 10 (1), second indent, until one year at the latest following
adoption of the uniform principles, and only in relation to the require-
ments of Article 4 (1) (b) to (e) which are covered by the uniformprinciples thus adopted.
Article 24
This Directive is addressed to the Member States.1991L0414 — EN — 01.07.2003 — 009.001 — 21
ANNEX I
ACTIVESUBSTANCESAUTHORISEDFORUSEINPLANTPROTECTIONPRODUCTS
General provisions applying to all substances listed in this Annex:
For the implementation of the uniform principles of Annex VI in relation to each substance, the conclusions of the
review report on it, and in particular the Appendices I and II thereof, as finalised in the Standing Committee on Plant
Health on the date indicated under ‘specific provisions’ for that substance shall be taken into account.
Member States shall keep available all review reports (except for confidential information within the meaning of
Article 14 of the Directive) for consultation by any interested parties or shall make it available to them on specific
request.
Numb-
erCommon name, identifi-
cation numbersIUPAC name Purity (1)Entry into
forceExpiration of
inclusionSpecific provisions
1 Imazalil
CAS No 73790-28-0,
35554-44-0
CIPAC No 335(±)-1-( β-allyloxy-2,4-
dichlorophenylethyl)imi-
dazole
or
(±)-allyl 1-(2,4-dichloro-
phenyl)-2-imidazol-1-
ylethyl ether975 g/kg 1.1.1999 31.12.2008 Only uses as fungicide may be authorised
For the following uses the following particular conditions apply:
— post harvest fruit, vegetable and potato treatments may only be authorised when an
appropriate decontamination system is available or a risk assessment has demonstrated
to the authorising Member State that the discharge of the treatment solution does not
have an unacceptable risk to the environment and in particular to aquatic organisms,
— post harvest treatment of potatoes may only be authorised when a risk assessment has
demonstrated to the authorising Member State that the discharge of the processing
waste from treated potatoes does not have an unacceptable risk to aquatic organisms,
— outdoor foliar uses may only be authorised when a risk assessment has demonstrated to
the authorising Member State that the use has no unacceptable effects on human and
animal health and the environment
Date of Standing Committee on Plant Health at which the review report was finalised:
11.7.1997.
2 Azoxystrobin
CAS No 131860-33-8CIPAC No 571Methyl (E)-2-{2[6-(2-
cyanophenoxy)pyri-
midin-4-yloxy] phenyl}-
3-methoxyacrylate930 g/kg (Z
isomer max.
25 g/kg)1.7.1998 1.7.2008 Only uses as fungicide may be authorised
In the decision-making according to the uniform principles, particular attention should be
given to the impact on aquatic organisms. Authorisation conditions should include appro-
priate risk mitigation measures
Date of Standing Committee on Plant Health at which the review report was finalised:
22.4.1998▼M221991L0414 — EN — 01.07.2003 — 009.001 — 22
Numb-
erCommon name, identifi-
cation numbersIUPAC name Purity (1)Entry into
forceExpiration of
inclusionSpecific provisions
3 Kresoxim-methyl
CAS No 143390-89-0
CIPAC No 568Methyl (E)-2-methoxyi-
mino-2-[2-(o-tolyloxy-
methyl) phenyl] acetate910 g/kg 1.2.1999 31.1.2009 Only used as fungicide may be authorised
In their decision-making according to the uniform principles, Member States shall pay
particular attention to the protection of groundwater under vulnerable conditions
Date of Standing Committee on Plant Health at which the review report was finalised:
16.10.1998
4 Spiroxamine
CAS No 1181134-30-8CIPAC No 572(8-tert-Butyl-1,4-dioxa-
spiro [4.5] decan-2-
ylmethyl)-ethyl-propyla-
mine940 g/kg
(diastereo-
mers A and
B combined)1.9.1999 1.9.2009 Only uses as a fungicide may be authorised
In their decision-making according to the uniform principles, Member States:— must pay particular attention to operator safety and must ensure that the conditions of
authorisation include appropriate protective measures, and
— must pay particular attention to the impact on aquatic organisms and must ensure that
the conditions of authorisation include, where appropriate, risk mitigation measures
Date of Standing Committee on Plant Health at which the review report was finalised:
12.5.1999
5 Azimsulfuron
CAS No 120162-55-2
CIPAC No 5841-(4,6-dimethoxypyri-
midin-2-yl)-3-[1-methyl-
4-(2-methyl-2H-tetrazol-
5-yl)-pyrazol-5-ylsul-
fonyl]-urea.980 g/kg 1.10.1999 1.10.2009 Only uses as herbicide may be authorised
Aerial application may not be authorised
In their decision making according to the uniform principles, Member States must pay
particular attention to the impact on aquatic organisms and terrestrial non-target plants
and must ensure that the conditions of authorisation include, where appropriate, risk miti-
gation measures (e. g. in rice cultivation minimum holding periods for water prior to
discharge)
Date of Standing Committee on Plant Health at which the review report was finalised:
2.7.1999
6 Fluroxypyr
CAS No 69377-81-7
CIPAC No 4314-amino-3,5-dichloro-6-
fluoro-2-pyridyloxyacetic
acid950 g/kg 1.12.2000 30.11.2010 Only uses as herbicide may be authorised
In their decision-making according to the uniform principles, Member States:
— shall take into account the additional information requested in point 7 of the review
report,
— must pay particular attention to the protection of groundwater,— must pay particular attention to the impact on aquatic organisms and must ensure that
the conditions of authorisation include, where appropriate, risk mitigation measures
Member States shall inform the Commission if the requested additional trials and informa-
tion as outlined in point 7 of the review report were not submitted by 1.12.2000
Date of Standing Committee on Plant Health at which the review report was finalised:
30.11.1999▼M221991L0414 — EN — 01.07.2003 — 009.001 — 23
Numb-
erCommon name, identifi-
cation numbersIUPAC name Purity (1)Entry into
forceExpiration of
inclusionSpecific provisions
7 Metsulfuron-methyl
CAS No 74223-64-6
EEC No 441Methyl-2-(4-methoxy-6-
methyl-1,3,5,-triazin-2-
ylcarbamoylsulfamoyl)-
benzoate960 g/kg 1.7.2001 30.6.2011 Only uses as herbicide may be authorised
In their decision making according to the uniform principles, Member States:
— must pay particular attention to the protection of groundwater,
— must pay particular attention to the impact on aquatic organisms and must ensure that
the conditions of authorisation include, where appropriate, risk mitigation measures
Date of Standing Committee on Plant Health at which the review report was finalised:
16.6.2000
8 Prohexadione-calcium
CAS No 127277-53-6
CIPAC No 567Calcium 3,5-dioxo-4-
propionylcyclohexane-
carboxylate890 g/kg 1.10.2000 1.10.2010 Only uses as plant growthregulator may be auth orised
Date of Standing Committee on Plant Health at which the review report was finalised:
16.6.2000
9 Triasulfuron
CAS No 82097-50-5CIPAC No 4801-[2-(2-chloroethoxy)-
phenylsulfonyl]-3-(4-
methoxy-6-methyl-1,3,5-
triazin-2-yl)urea940 g/kg 1.8.2001 31.7.2011 Only uses as herbicide may be authorised
In their decision making according to the uniform principles, Member States:— must pay particular attention to the protection of groundwater,
— must pay particular attention to the impact on aquatic organisms and must ensure that
the conditions of authorisation include, where appropriate, risk mitigation measures
Date of Standing Committee on Plant Health at which the review report was finalised:
13.7.2000
10 Esfenvalerate
CAS No 66230-04-4CIPAC No 481(S)-α-Cyano-3-phenoxy-
benzyl-(S)-2-(4-chloro-
phenyl)-3-methylbutyrate830 g/kg 1.8.2001 31.7.2011 Only uses as insecticide may be authorised
In their decision making according to the uniform principles, Member States:— must pay particular attention to the potential impact on aquatic organisms and non-
target arthropods and must ensure that the conditions of authorisation include, where
appropriate, risk mitigation measures
Date of Standing Committee on Plant Health at which the review report was finalised:
13.7.2000
11 Bentazone
CAS No 25057-89-0
CIPAC No 3663-isopropyl-(1H)-2,1,3-
benzothiadiazin-4-(3H)-
one-2,2-dioxide960 g/kg 1.8.2001 31.7.2011 Only uses as herbicide may be authorised
In their decision-making according to the uniform principles, Member States must pay
particular attention to the protection of groundwater
Date of Standing Committee on Plant Health at which the review report was finalised:
13.7.2000▼M221991L0414 — EN — 01.07.2003 — 009.001 — 24
Numb-
erCommon name, identifi-
cation numbersIUPAC name Purity (1)Entry into
forceExpiration of
inclusionSpecific provisions
12 Lambda-cyhalothrin
CAS No 91465-08-6
CIPAC No 463A 1:1 mixture of:
(S)-α-cyano-3-phenoxy-
benzyl (Z)-(1R,3R)-3-(2-
chloro-3,3,3-trifluoropro-
penyl)-2,2-dimethylcy-
clopropanecarboxylate,
and(R)-α-cyano-3-phenoxy-
benzyl (Z)-(1S,3S)-3-(2-
chloro-3,3,3-trifluoropro-
penyl)-2,2-dimethylcy-
clopropanecarboxylate810 g/kg 1.1.2002 31.12.2011 Only uses as insecticide may be authorised
In their decision-making according to the uniform principles, Member States:
— must pay particular attention to operator safety,
— must pay particular attention to the potential impact on aquatic organisms and non-
target arthropods including bees and must ensure that the conditions of authorisation
include, where appropriate, risk mitigation measures,
— must pay particular attention to the residues in food and especially the acute effects
thereof
Date of Standing Committee on Plant Health at which the review report was finalised:
19.10.2000
13 Fenhexamid
CAS No 126833-17-8
CIPAC No 603N-(2,3-dichloro-4-hydro-
xyphenyl)-1-methylcy-
clohexanecarboxamide≥950 g/
kg(
2)1 June 2001 31 May 2011 Only uses as a fungicide may be authorised.
In decision making according to the Uniform Principles Member States must pay particular
attention to the potential impact on aquatic organisms and must ensure that the conditions
of authorisation include, where appropriate, risk mitigation measures.
Date of Standing Committee on Plant Health at which the review report was finalised: 19
October 2000
14 Amitrole
CAS No 61-82-5
CIPAC No 90H-[1,2,4]-triazole-3-
ylamine900 g/kg 1.1.2002 31.12.2011 Only uses as herbicide may be authorised
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on amitrole, and in particular Appendices I and II thereof, as finalised in
the Standing Committee on Plant Health on 12 December 2000 shall be taken into account.
In this overall assessment Member States:
— must pay particular attention to the protection of operators
— must pay particular attention to the protection of the groundwater in vulnerable areas, in
particular withrespect to non-crop uses
— must pay particular attention to the protection of beneficial arthropods— must pay particular attention to the protection of birds and wild mammals. Use of
amitrole during the breeding season may only be authorised when an appropriate risk
assessment has demonstrated that there is no unacceptable impact and when the condi-
tions of authorisation include, where appropriate, risk mitigation measures▼M221991L0414 — EN — 01.07.2003 — 009.001 — 25▼M24
▼M23
Numb-
erCommon name, identifi-
cation numbersIUPAC name Purity (1)Entry into
forceExpiration of
inclusionSpecific provisions
15 Diquat
CAS No 2764-72-9
(ion), 85-00-7 (dibro-
mide)
CIPAC No 559,10-Dihydro-8a,10a-
diazoniaphenanthrene ion
(dibromide)950 g/kg 1.1.2002 31.12.2011 On the basis of currently available information, only uses as terrestrial herbicide and desic-
cant may be authorised. Uses in aquatic weed control shall not be authorised
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on diquat, and in particular Appendices I and II thereof, as finalised in the
Standing Committee on Plant Healthon 12 December 2000 sh all be taken into account. In
this overall assessment Member States:
— must pay particular attention to the potential impact on aquatic organisms and must
ensure that the conditions of authorisation include, where appropriate, risk mitigation
measures
— must pay particular attention to operator safety as related to non-professional use and
must ensure that the conditions of authorisation include, where appropriate, risk mitiga-
tion measures
16 Pyridate
CAS No 55512-33.9CIPAC No 4476-Chloro-3-phenylpyri-
dazin-4-yl S-octyl thio-
carbonate900 g/kg 1.1.2002 31.12.2011 Only uses as herbicide may be authorised
For the implementation of the uniform priciples of Annex VI, the conclusions of the review
report on pyridate, and in particular Appendices I and II thereof, as finalised in the
Standing Committee on Plant Healthon 12 December 2000 sh all be taken into account.
In this overall assessment Member States:
— must pay particular attention to the protection of groundwater
— must pay particular attention to the potential impact on aquatic organisms and must
ensure that the conditions of authorisation include, where appropriate, risk mitigation
measures
17 Thiabendazole
CAS No 148-79-8
CIPAC No 3232-Thiazol-4-yl-1H-benzi-
midazole985 g/kg 1.1.2002 31.12.2011 Only uses as fungicide may be authorised. Foliar spray applications shall not be authorised
For the implementation of the uniform priciples of Annex VI, the conclusions of the review
report on thiabendazole, and in particular Appendices I and II thereof, as finalised in the
Standing Committee on Plant Healthon 12 December 2000 sh all be taken into account.
In this overall assessment Member States:
— must pay particular attention to the protection of aquatic and sediment-dwelling organ-
isms and must ensure that the conditions of authorisation include, where appropriate,
risk mitigation measures
Suitable risk mitigation measures (e.g. depuration withdiatom earthor activated carbon)
have to be implemented to protect surface waters from unacceptable levels of contamina-
tion via wastewater▼M231991L0414 — EN — 01.07.2003 — 009.001 — 26
Numb-
erCommon name, identifi-
cation numbersIUPAC name Purity (1)Entry into
forceExpiration of
inclusionSpecific provisions
18 Paecilomyces fumo-
soroseus
Apopka strain 97, PFR
97 or CG 170,
ATCC20874Not applicable The absence
of secondary
metabolites
should be
checked in
eachfermen-
tation broth
by HPLC1 July 2001 30 June 2011 Only uses as an insecticide may be authorised
Each fermentation broth should be checked by HPLC to ensure that no secondary metabo-
lites are present
Date of Standing Committee on Plant Health at which the review report was finalised: 27
April 2001
19 DPX KE 459 (flupyr-
sulfuron-methyl)
CAS No 144740-54-5
CIPAC No 5772-(4,6-dimethoxypyri-
midin-2-ylcarbamoylsul-
famoyl)-6-trifluromethyl-
nicotinate monosodium
salt903 g/kg(3) 1 July 2001 30 June 2011 Only uses as a herbicide may be authorised.
In decision-making according to the Uniform Principles Member States must pay particular
attention to the protection of groundwater.
Date of Standing Committee on Plant Health at which the review report was finalised: 27
April 2001.
20 Acibenzolar-s-methyl
CAS No 135158-54-2
CIPAC No 597Benzo[1,2,3]thiadiazole-
7-carbothioic acid S-
methyl ester970 g/kg 1 November
200131 October
2011Only uses as a plant activator may be authorised.
Date of Standing Committee on Plant Health at which the review report was finalised: 29
June 2001.
21 Cyclanilide
CAS No 113136-77-9
CIPAC No 586Not available 960 g/kg 1 November
200131 October
2011Only uses as a plant growthregulator may be auth orised.
The maximum content of the impurity 2,4-dichloroaniline (2,4-DCA) in the active
substance as manufactured should be 1 g/kg.
Date of Standing Committee on Plant Health at which the review report was finalised: 29
June 2001.
22 Ferric phosphate
CAS No 10045-86-0CIPAC No 629Ferric phosphate 990 g/kg 1 November
200131 October
2011Only uses as a molluscicide may be authorised.
Date of Standing Committee on Plant Health at which the review report was finalised: 29
June 2001
23 Pymetrozine
CAS No 123312-89-0CIPAC No 593(E)-6-methyl-4-[(pyridin-
3-ylmetylene)amino]-4,5-
dihydro-2H-[1,2,4]-
triazin-3 one950 g/kg 1 November
200131 October
2011Only uses as an insecticide may be authorised.
In decision-making according to the uniform principles Member States must pay particular
attention to the protection of aquatic organisms.
Date of Standing Committee on Plant Health at which the review report was finalised: 29
June 2001.▼M231991L0414 — EN — 01.07.2003 — 009.001 — 27▼M26
▼M27
▼M28
Numb-
erCommon name, identifi-
cation numbersIUPAC name Purity (1)Entry into
forceExpiration of
inclusionSpecific provisions
24 Pyraflufen-ethyl
CAS No 129630-19-9
CIPAC No 605Ethyl-2-chloro-5-(4-
chloro-5-difluoro-
methoxy-1-mhypyrazol-
3-yl)-4-fluorophenoxya-
cetate956 g/kg 1 November
200131 October
2011Only uses as a herbicide may be authorised.
In decision-making according to the uniform principles Member States must pay particular
attention to the protection of algae and aquatic plants and should apply, where appropriate,
risk mitigation measures.
Date of Standing Committee on Plant Health at which the review report was finalised: 29
June 2001.
25 Glyphosate
CAS No 1071-83-6CIPAC No 284N-(phosphonomethyl)-
glycin950 g/kg 1 July 2002 30 June 2012 Only uses as herbicide may be authorised
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on glyphosate, and in particular Appendices I and II thereof, as finalised in
the Standing Committee on Plant Health on 29 June 2001 shall be taken into account. In
this overall assessment Member States:
— must pay particular attention to the protection of the groundwater in vulnerable areas, in
particular withrespect to non-crops uses
26 Thifensulfuron-methyl
CAS No 79277-27-3CIPAC No 452Methyl 3-(4-methoxy-6-
methyl-1,3,5-triazin-2-
ylcarbamoyl-sulfamoyl)
thiophene-2-carboxylate960 g/kg 1 July 2002 30 June 2012 Only uses as herbicide may be authorised.
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on thifensulfuron-methyl, and in particular Appendices I and II thereof, as
finalised in the Standing Committee on Plant Health on 29 June 2001 shall be taken into
account. In this overall assessment Member States:
— must pay particular attention to the protection of groundwater,
— must pay particular attention to the impact on aquatic plants and must ensure that the
conditions of authorisation include, where appropriate, risk mitigation measures
27 2,4-D
CAS No 94-75-7
CIPAC No 1(2,4-dichlorophenoxy)
acetic acid960 g/kg 1.10.2002 30.9.2012 Only uses as herbicide may be authorised
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on 2,4-D, and in particular Appendices I and II thereof, as finalised in the
Standing Committee on Plant Healthon 2 October 2001 sh all be taken into account. In
this overall assessment Member States:
— must pay particular attention to the protection of the groundwater, when the active
substance is applied in regions withvulnerable soil and/or climatic conditions
— must pay particular attention to the dermal absorption
— must pay particular attention to the protection of non-target arthropods and must ensure
that the conditions of authorisation include, where appropriate, risk mitigation measures▼M281991L0414 — EN — 01.07.2003 — 009.001 — 28▼M29
▼M30
Numb-
erCommon name, identifi-
cation numbersIUPAC name Purity (1)Entry into
forceExpiration of
inclusionSpecific provisions
28 Isoproturon
CAS No 34123-59-6
CIPAC No 3363-(4-isopropylphenyl)-
1,1-dimethylurea970 g/kg 1 January
200331 December
2012Only uses as herbicide may be authorised
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on isoproturon, and in particular Appendices I and II thereto, as finalised in
the Standing Committee on Plant Health on 7 December 2001 shall be taken into account.
In this overall assessment Member States:
— must pay particular attention to the protection of the groundwater, when the active
substance is applied in regions withvulnerable soil and/or climatic conditions or at
use rates higher than those described in the review report and must apply risk mitiga-
tion measures, where appropriate,
— must pay particular attention to the protection of aquatic organisms and must ensure
that the conditions of authorisation include, where appropriate, risk mitigation measures
29 Ethofumesate
CAS No 26225-79-6CICAP No 223(±)-2-ethoxy-2,3-
dihydro-3,3-dimethylben-
zofuran-5-ylmethanesul-
fonate960 g/kg 1 March
200328 February
2013Only uses as herbicide may be authorised
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on ethofumesate, and in particular Appendices I and II thereof, as finalised
in the Standing Committee on the Food Chain and Animal Health on 26 February 2002
shall be taken into account. In this overall assessment Member States may pay particular
attention to the protection of the groundwater, when the active substance is applied in
regions withvulnerable soil and/or climatic conditions and must apply risk mitigation
measures, where appropriate.
30 Iprovalicarb
CAS No 140923-17-7CICAP No 620{2-Methyl-1-[1-(4-
methylphenyl)ethylcar-
bonyl] propyl}-carbamic
acid isopropylester950 g/kg
(provisional
specifica-
tion)1 July 2002 30 June 2011 Only uses as fungicide may be authorised.
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on iprovalicarb, and in particular Appendices I and II thereof, as finalised
in the Standing Committee on the Food Chain and Animal Health on 26 February 2002
shall be taken into account. In this overall assessment:
— the specification of the technical material as commercially manufactured must be
confirmed and supported by apporpriate analytical data. The test material used in the
toxicity dossier should be compared and verified against this specification of the tech-
nical material,
— Member States must pay particular attention to the protection of operators.▼M311991L0414 — EN — 01.07.2003 — 009.001 — 29▼M32
▼M33
Numb-
erCommon name, identifi-
cation numbersIUPAC name Purity (1)Entry into
forceExpiration of
inclusionSpecific provisions
31 Prosulfuron
CAS No 94125-34-5
CICAP No 5791-(4-methoxy-6-methyl-
1,3,5-triazin-2-yl)-3-[2-
(3,3,3-trifluoropropyl)-
phenylsulfonyl]-urea950 g/kg 1 Juli 2002 30 June 2011 Only uses as herbicide may be authorised.
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on prosulfuron, and in particular Appendices I and II thereof, as finalised in
the Standing Committee on the Food Chain and Animal Health on 26 February 2002 shall
be taken into account. In this overall assessment Member States:
— must carefully consider the risk to aquatic plants if the active substance is applied adja-
cent to surface waters. Risk mitigation measures should be applied where appropriate,
— must pay particular attention to the protection of groundwater, when the active
substance is applied in regions withvulnerable soil and/or climate conditions. Risk
mitigation measures should be applied where appropriate.
32 Sulfosulfuron
CAS No 141776-32-1CICAP No 6011-(4,6-dimethoxypyri-
midin-2-yl)-3-[2-ethane-
sulfonyl-imidazo[1,2-
a]pyridine) sulfonyl]urea980 g/kg 1 July 2002 30 June 2011 Only uses as a herbicide may be authorised.
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on sulforsulfuron, and in particular Appendices I and II thereof, as finalised
in the Standing Committee on the Food Chain and Animal Health on 26 February 2002
shall be taken into account. In this overall assessment:
— Member States must pay particular attention to the protection of aquatic plants and
algae. Where apporpriate, risk mitigation measures should be applied,
— Member States must pay particular attention to the protection of the groundwater, when
the active substance is applied in regions with vulnerable soil and/or climatic conditons.
33 Cinidon-ethyl
CAS No 142891-20-1CIPAC No 598(Z)-ethyl 2-chloro-3-[2-
chloro-5-(cyclohex-1-
ene-1,2-dicarboximido)-
phenyl]acrylate940 g/kg 1 October
200230
September
2012Only uses as herbicide may be authorised.
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on cinidon-ethyl, and in particular Appendices I and II thereof, as finalised
in the Standing Committee on the Food Chain and Animal Health on 19 April 2002 shall
be taken into account. In this overall assessment Member States:
— should pay particular attention to the potential for groundwater contamination, when the
active substance is applied in regions withvulnerable soil (e.g. soils withneutral or
high pH values) and/or climatic conditions,
— should pay particular attention to the protection of aquatic organisms.
Conditions of authorisation must include risk-mitigation measures, where appropriate.▼M331991L0414 — EN — 01.07.2003 — 009.001 — 30
▼M34
Numb-
erCommon name, identifi-
cation numbersIUPAC name Purity (1)Entry into
forceExpiration of
inclusionSpecific provisions
34 Cyhalofop butyl
CAS No 122008-85-9
CIPAC No 596Butyl-(R)-2-[4(4-cyano-
2-fluorophenoxy)
phenoxy]propionate950 g/kg 1 October
200230
September
2012Only uses as herbicide may be authorised.
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on cyhalofop butyl, and in particular Appendices I and II thereof, as finalised
in the Standing Committee on the Food Chain and Animal Health on 19 April 2002 shall
be taken into account. In this overall assessment:
— Member States must carefully consider the potential impact of aerial applications to
non-target organisms and in particular to aquatic species. Conditions of authorisation
must include restrictions or risk mitigation measures, where appropriate,
— Member States must carefully consider the potential impact of terrestrial applications
on aquatic organisms within paddy fields. Conditions of authorisation must include
risk-mitigation measures, where appropriate.
35 Famoxadone
CAS No 131807-57-3
CIPAC No 5943-anilino-5-methyl-5-(4-
phenoxyphenyl)-1,3-
oxazolidine-2,4-dione960 g/kg 1 October
200230
September
2012Only uses as fungicide may be authorised.
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on famoxadone, and in particular Appendices I and II thereof, as finalised
in the Standing Committee on the Food Chain and Animal Health on 19 April 2002 shall
be taken into account. In this overall assessment:
— Member States must pay particular attention to potential chronic risks of the parent
substance or metabolites to earthworms,
— Member States must pay particular attention to the protection of aquatic organisms and
must ensure that the conditions of authorisation include, where appropriate, risk-mitiga-
tion measures,
— Member States should pay particular attention to the protection of operators.
36 Florasulam
CAS No 145701-23-1
CIPAC No 6162′,6′, 8-Trifluoro-5-
methoxy-[1,2,4]-triazolo
[1,5-c] pyrimidine-2-
sulphonanilide970 g/kg 1 October
200230
September
2012Only uses as herbicide may be authorised.
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on florasulam, and in particular Appendices I and II thereof, as finalised in
the Standing Committee on the Food Chain and Animal Health on 19 April 2002 shall be
taken into account. In this overall assessment Member States:
— should pay particular attention to the potential for groundwater contamination, when the
active substance is applied in regions withvulnerable soil and/or climatic conditions.
Conditions of authorisation must include risk-mitigation measures, where appropriate.▼M341991L0414 — EN — 01.07.2003 — 009.001 — 31
Numb-
erCommon name, identifi-
cation numbersIUPAC name Purity (1)Entry into
forceExpiration of
inclusionSpecific provisions
37 Metalaxyl-M
CAS No 70630-17-0
CIPAC No 580Methyl(R)-2-{[(2,6-
dimethylphenyl)me-
thoxy-acetyl] amino}
propionate910 g/kg 1 October
200230
September
2012Only uses as fungicide may be authorised.
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on Metalaxyl-M, and in particular Appendices I and II thereof, as finalised
in the Standing Committee on the Food Chain and Animal Health on 19 April 2002 shall
be taken into account. In this overall assessment:
— particular attention should be given to the potential for groundwater contamination by
the active substance or its degradation products CGA 62826, and CGA 108906 when
the active substance is applied in regions with vulnerable soil and/or climatic condi-
tions. Risk-mitigation measures should be applied, where appropriate.
38 Picolinafen
CAS No 137641-05-5
CIPAC No 6394′-Fluoro-6-[( α,α,α-
trifluoro-m-tolyl)oxy]pi-
colinanilide970 g/kg 1 October
200230
September
2012Only uses as herbicide may be authorised.
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on picolinafen, and in particular Appendices I and II thereof, as finalised in
the Standing Committee on the Food Chain and Animal Health on 19 April 2002 shall be
taken into account. In this overall assessment Member States:
— must pay particular attention to the protection of aquatic organisms. Conditions of
authorisation should include risk-mitigation measures, where appropriate.
39 Flumioxazine
CAS No 103361-09-7
CICAP No 578N-(7-fluoro-3,4-dihydro-
3-oxo-4-prop-2-ynyl-2H-
1,4-benzoxazin-6-yl)cy-
clohex-1-ene-1,2-dicar-
boximide960 g/kg 1 January
200331 December
2012Only uses as herbicide may be authorised.
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on flumioxazine, and in particular Appendices I and II thereof, as finalised
in the Standing Committee on the Food Chain and Animal Health on 28 June 2002 shall be
taken into account. In this overall assessment Member States:
— must carefully consider the risk to aquatic plants and algae. Conditions of authorisation
must include risk mitigation measures, where appropriate.
41 Imazamox
CAS No 114311-32-9CIPAC No 619(±)-2-(4-isopropyl-4-
methyl-5-oxo-2-imida-
zolin-2-yl)-5-(methoxy-
methyl) nicotinic acid950 g/kg 1 July 2003 30 June 2013 Only uses as herbicide may be authorised.
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on imazamox, and in particular Appendices I and II thereof, as finalised in
the Standing Committee on the Food Chain and Animal Health on 3 December 2002 shall
be taken into account.
In this overall assessment Member States should pay particular attention to the potential for
groundwater contamination, when the active substance is applied in regions with vulnerable
soil and/or climate conditions. Risk mitigation measures should be applied where appro-
priate.▼M341991L0414 — EN — 01.07.2003 — 009.001 — 32▼M35
▼M36
Numb-
erCommon name, identifi-
cation numbersIUPAC name Purity (1)Entry into
forceExpiration of
inclusionSpecific provisions
42 Oxasulfuron
CAS No 144651-06-9
CIPAC No 626Oxetan-3-yl 2[(4,6-
dimethylpyrimidin-2-yl)
carbamoyl-sulfamoyl]
benzoate960 g/kg 1 July 2003 30 June 2013 Only uses as herbicide may be authorised.
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on oxasulfuron, and in particular Appendices I and II thereof, as finalised in
the Standing Committee on the Food Chain and Animal Health on 3 December 2002 shall
be taken into account.
— Member States must pay particular attention to the protection of groundwater, when the
active substance is applied in regions withvulnerable soil and/or climate conditions.
Risk mitigation measures should be applied, where appropriate.
43 Ethoxysulfuron
CAS No 126801-58-9
CIPAC No 5913-(4,6-dimethoxypyri-
midin-2-yl)-1-(2-ethoxy-
phenoxy-sulfonyl)urea950 g/kg 1 July 2003 30 June 2013 Only uses as herbicide may be authorised.
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on ethoxysulfuron, and in particular Appendices I and II thereof, as finalisedin the Standing Committee on the Food Chain and Animal Health on 3 December 2002
shall be taken into account.
Member States should pay particular attention to the protection of non-target aquatic plants
and algae in drainage canals. Risk mitigation measures should be applied where appro-
priate.
44 Foramsulfuron
CAS No 173159-57-4CIPAC No 6591-(4,6-dimethoxypyri-
midin-2-yl)-3-(2-
dimethylcarbamoyl-5-
formamidophenylsulfo-
nyl)urea940 g/kg 1 July 2003 30 June 2013 Only uses as herbicide may be authorised.
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on foramsulfuron, and in particular Appendices I and II thereof, as finalised
in the Standing Committee on the Food Chain and Animal Health on 3 December 2002
shall be taken into account.
In this overall assessment Member States should pay particular attention to the protection
of aquatic plants. Risk mitigation measures should be applied, where appropriate.
45 Oxadiargyl
CAS No 39807-15-3
CIPAC No 6045-tert-butyl-3-(2,4-
dichloro-5-propargyloxy-
phenyl)-1,3,4 oxadiazol-
2-(3H)-one980 g/kg 1 July 2003 30 June 2013 Only uses as herbicide may be authorised.
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on oxadiargyl, and in particular Appendices I and II thereof, as finalised in
the Standing Committee on the Food Chain and Animal Health on 3 December 2002 shall
be taken into account.
In this overall assessment Member States should pay particular attention to the protection
of algae and aquatic plants. Risk mitigation measures should be applied where appropriate.▼M361991L0414 — EN — 01.07.2003 — 009.001 — 33
Numb-
erCommon name, identifi-
cation numbersIUPAC name Purity (1)Entry into
forceExpiration of
inclusionSpecific provisions
46 Cyazofamid
CAS No 120116-88-3
CIPAC No 6534-chloro-2cyano-N,N-
dimethyl-5-P-tolylimida-
zole -1-sulfonamide935 g/kg 1 July 2003 30 June 2013 Only uses as fungicide may be authorised.
For the implementation of the uniform principles of Annex VI, the conclusions of the
review report on cyazofamid, and in particular Appendices I and II thereof, as finalised in
the Standing Committee on the Food Chain and Animal Health on 3 December 2002 shall
be taken into account. In this overall assessment
— Member States must pay particular attention to the protection of aquatic organisms;
— Member States must pay particular attention to the degradation kinetics of the metabo-
lite CTCA in soil, especially for Northern European regions.
Risk mitigation measures or use restrictions should be applied where appropriate.
(1) Further details on identity and specification of active substances are provided in their review reports.
►M24(2) Further details on identity and specification of active substance are provided in the review report (doc. 6797/VI/99 rev. 2). ◄
►M27(3) Further details on identity and specification of active substances are provided in the review report for DPX KE 459 (flupyrsulfuron-methyl) (5050/ VI/97). ◄▼M361991L0414 — EN — 01.07.2003 — 009.001 — 34▼M22
▼B
ANNEX II
REQUIREMENTS FOR THE DOSSIER TO BE SUBMITTED FOR THE
INCLUSIONOFANACTIVESUBSTANCEINANNEXI
INTRODUCTION
The information required shall:
1.1. include a technical dossier supplying the information necessary for evalu-
ating the foreseeable risks, whether immediate or delayed, which the
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, according to 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 guide-
lines 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,
inlcude a justification, which is acceptable to the competent authority for
the guidelines used. ►M4In particular, when reference is made in this
Annex to an EEC Method which consists in the transposal of a method
developed by an international organization (e.g. OECD), Member States
may accept that the required information is generated according to the
latest version of that method if at the initiation of the studies the EEC
Method has not yet been updated; ◄
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 infor-
mation and data;
1.6. where relevant, have been generated in accordance with the requirements
of Directive 86/609/EEC.
2.1. Tests and analyses must be conducted in accordance withth e principles
laid down in Directive 87/18/EEC (1) where testing is done to obtain data
on the properties and/or safety with respect to human or animal health or
the environment.
2.2. By way of derogation from point 2.1, Member States may provide that tests
and analyses, performed on their territory in order to obtain data on the
properties and/or safety of the substances with respect to honey-bees and
beneficial arthropods other than bees shall be conducted by official or offi-
cially-recognized testing facilities or organizations which satisfy at least the
requirements as set out under points 2.2 and 2.3 of the introduction to
Annex III.
This derogation applies to trials actually started on or before 31 December
1999.
2.3. By way of derogation from point 2.1, Member States may provide that
supervised residue trials performed on their territory in accordance with
the provisions of Section 6 ‘Residues in or on treated products, food and
feed’ on plant protection products containing active substances already on
the market two years after notification of the Directive shall be conducted1991L0414 — EN — 01.07.2003 — 009.001 — 35
(1) OJ No L 15, 17. 1. 1987, p. 29.▼M1
▼M4
▼M1
▼M5
▼M5
by official or officially-recognized testing facilities or organizations which
satisfy at least the requirements under points 2.2 and 2.3 of the introduction
to Annex III.
This derogation applies for supervised residue trials actually started on or
before 31 December 1997.
2.4. By way of derogation from point 2.1, for active substances consisting of
micro-organisms or viruses, tests and analyses done to obtain data on the
properties and/or safety with respect to other aspects than human health,
may have been conducted by official or officially recognised testing facil-
ities or organisations which satisfy at least the requirements under points
2.2 and 2.3 of the introduction of Annex III.
PART A
Chemicalsubstances (1)
1.Identityoftheactive substance
The information provided must be sufficient to identify with precision
eachactive substance, to define it in terms of its specification and to
characterize it as to its nature. The information and data referred to,
unless otherwise specified, are required for all active substances.
1.1. Applicant (name, address, etc.)
The name and address of the applicant (permanent Community
address) must be provided as must the name, position, telephone and
telefax number of the appropriate person to contact.
Where, in addition, the applicant has an office, agent or representative
in the Member State to which the application for inclusion in Annex I
is submitted, and if different, in the Rapporteur Member State
appointed by the Commission, the name and address of the local
office, agent or representative must be provided, as must the name,
position, telephone and telefax number of the appropriate person to
contact.
1.2. Manufacturer (name, address, including location of plant)
The name and address of the manufacturer or manufacturers of the
active substance must be provided as must the name and address of
each manufacturing plant in which the active substance is manufac-
tured. A contact point (preferably a central contact point, to include
name, telephone and telefax number) must be provided, with a view
to providing updating information and responding to queries arising,
regarding manufacturing technology, processes and the quality of
product (including where relevant, individual batches). Where
following inclusion of the active substances in Annex I, there are
changes in the location or number of manufacturers, the information
required must again be notified to the Commission and the Member
States.
1.3. Common name proposed or ISO-accepted, and synonyms
The ISO common name, or proposed ISO common name and where
relevant, other proposed or accepted common names (synonyms),
including the name (title) of the nomenclature authority concerned,
must be provided.
1.4. Chemical name (IUPAC and CA nomenclature)
The Chemical name as given in Annex I to Directive 67/548/EEC, or,
if not included in th is Directive, in accordance withbothIUPAC and
CA nomenclature, must be provided.
1.5. Manufacturer's development code number(s)
Code numbers used to identify the active substance, and where avail-
able, formulations containing the active substance, during
development work, must be reported. For eachcode number reported,1991L0414 — EN — 01.07.2003 — 009.001 — 36
(1) Substance within the meaning of the definition of Article 2, point 3.▼M25
▼B
▼M2
▼M2
the material to which it relates, the period for which it was used, and
the Member States or other countries in which it was used and is
being used, must be stated.
1.6. CAS, EEC and CIPAC numbers (if available)
Chemical Abstracts, EEC (EINECS or ELINCS), and CIPAC
numbers, where they exist, must be reported.
1.7. Molecular and structural formula, molecular mass
The molecular formula, molecular mass and structural formula of the
active substance, and where relevant, the structural formula of each
stereo and optical isomer present in the active substance, must be
provided.
1.8. Method of manufacture (synthesis pathway) of the active substance
The method of manufacture, in terms of the identity of the starting
materials, the chemical pathways involved, and the identity of by-
products and impurities present in the final product, must be provided,
for eachmanufacturing plant. Generally process engineering informa-
tion is not required.
Where the information provided relates to a pilot plant production
system, the information required must again be provided once indus-
trial scale production methods and procedures have stabilized.
1.9. Specification of purity of the active substance in g/kg
The minimum content in g/kg of pure active substance (excluding
inactive isomers) in the manufactured material used for production
of formulated products, must be reported.
Where the information provided relates to a pilot plant production
system, the information required must again be provided to the
Commission and the Member States once industrial scale production
methods and procedures have stabilized, if production changes result
in a changed specification of purity.
1.10. Identity of isomers, impurities and additives (e.g. stabilizers), together
with the structural formula and the content expressed as g/kg
The maximum content in g/kg of inactive isomers as well as the ratio
of the content of isomers/diastereo-isomers, where relevant, must be
provided. In addition, the maximum content in g/kg of each further
component other than additives, including by-products, and impuri-
ties, must be provided. In the case of additives the content in g/kg
must be provided.
For eachcomponent, present in quantities of 1 g/kg or more, th e
following information, where relevant, must be provided:
— chemical name according to IUPAC and CA nomenclature,
— ISO common name or proposed common name if available,— CAS number, EEC (EINECS or ELINCS) number, and CIPAC
number if available,
— molecular and structural formula,— molecular mass, and
— maximum content in g/kg.
Where the manufacturing process is such that impurities and by-
products which are particularly undesirable because of their toxicolo-
gical, ecotoxicological or environmental properties could be present in
the active substance, the content of each such compound must be
determined and reported. In such cases, the analytical methods used
and the limits of determination, which must be sufficiently low, for
eachcompound of concern, must be reported. Additionally th e
following information, where relevant, must be provided:
— chemical name according to IUPAC and CA nomenclature,
— ISO common name or proposed common name if available,
— CAS number, EEC (EINECS or ELINCS) number, and CIPAC
number if available,
— molecular and structural formula,— molecular mass, and— maximum content in g/kg.1991L0414 — EN — 01.07.2003 — 009.001 — 37
▼M2
Where the information provided relates to a pilot plant production
system, the information required must again be provided once indus-
trial scale production methods and procedures have stabilized, if
production changes result in a changed specification of purity.
Where the information provided does not fully identify a component
viz. condensates, detailed information on the composition must be
provided for eachsuchcomponent.
The trade name of components added to the active substance, prior to
manufacture of formulated product, to preserve stability and facilitate
ease of handling, where they are used, must also be provided. Addi-
tionally the following information, where relevant, must be provided
for suchadditives:
— chemical name according to IUPAC and CA nomenclature,
— ISO common name or proposed common name if available,
— CAS number, EEC (EINECS or ELINCS) number, and CIPAC
number if available,
— molecular and structural formula,
— molecular mass, and
— maximum content in g/kg.
For added components, other than active substance and other than
impurities resulting from the manufacturing process, the function of
the component (additive) must be given:
— antifoaming agent,
— antifreeze,— binder,
— other (specify),
— buffer,— dispersing agent,
— stabilizer.
1.11. Analytical profile of batches
Representative samples of the active substance must be analysed for
content of pure active substance, inactive isomers, impurities and
additives, as appropriate. The analytical results reported must include
quantitative data, in terms of g/kg content, for all components present
in quantities of more than 1 g/kg and typically should account for at
least 98 % of the material analysed. The actual content of components
which are particularly undesirable because of their toxicological,
ecotoxicological or environmental properties, must be determined
and reported. Data reported must include the results of the analysis
of individual samples and a summary of that data, to show the
minimum or maximum and typical content of eachrelevant compo-
nent, as appropriate.
Where an active substance is produced in different plants this infor-
mation must be provided for eachof th e plants separately.
In addition, where available and relevant, samples of the active
substance produced in laboratory scale or pilot production systems,
must be analyzed, if suchmaterial was used in generating toxicolo-
gical or ecotoxicological data.
2.Physicalandchemical propertiesoftheactive substance
(i) The information provided, must describe the physical and
chemical properties of active substances and together with rele-
vant 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 withpreparations, to be identified, permit preparations
to be classified, and permit establishment that preparations can1991L0414 — EN — 01.07.2003 — 009.001 — 38
▼M2
be used without unnecessary difficulty, and be such that expo-
sure 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 puri-
fied active substance of stated specification. In suchcases th e
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
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 ºC.
2.1.2. Where appropriate the boiling point of purified active substances must
be determined and reported according to EEC method A 2. Measure-
ments should be taken up to 360 ºC.
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.
2.2. Relative density
In the case of active substances which are liquids or solids, the rela-
tive 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)
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
10−5Pa, the vapour pressure at 20 or 25 ºC may be estimated by a
vapour pressure curve.
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 deter-
mined or calculated from its water solubility and vapour pressure
and be reported (in Pa × m3× mol−1).
2.4. Appearance (physical state, colour and odour; if known)
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.
2.4.2. A description of any odour associated withth e active substance as
manufactured and purfied active substance, noted when handling the
materials in laboratories or production plants, must be reported.
2.5. Spectra (UV/VIS, IR, NMR, MS), molecular extinction at relevant
wavelengths
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.
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 of1991L0414 — EN — 01.07.2003 — 009.001 — 39
▼M2
toxicological, ecotoxicological or environmental significance must be
determined and reported.
2.6. Solubility in water including effect of pH (4to 10) on solubility
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 withatmosph eric
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
The solubility of the active substances as manufactured in the
following organic solvents at 15 to 25 ºC must be determined and
reported if less than 250 g/kg; the temperature applied must be speci-
fied:
— 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 withtest material), alternative solvents can be
used instead. In suchcases, ch oices made must be justified in terms
of their structure and polarity.
2.8. Partition coefficient n-octanol/water including effect of pH (4to 10)
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 (4to 9)
2.9.1. The hydrolysis rate of purified active substances (usually radiola-
belled active substance, > 95 % purity), for eachof th e 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 ºC, or
another appropriate temperature.
If degradation is observed at 50 ºC, 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 ºC.
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 witha molar (decadic) absorption coefficient ( ε)>1 0
(1 × mol
−1×c m−1) at a wavelength λ≥290 nm, direct phototrans-
formation in purified (e.g. distilled) water at 20 to 25 ºC, of purified
active substance usually radio labelled using artificial light under
sterile conditions, if necessary using a solubilizer, must be determined
and reported. Sensitizers suchas acetone must not be used as a cosol-
vent or solubilizer. The light source must simulate sunlight and be
equipped withfilters to exclude radiation at wavelength s 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.
2.9.3. Where necessary to investigate direct phototrans-formation, the
quantum yield of direct photodegradation in water must be deter-
mined and reported, together with calculations to estimate theoretical1991L0414 — EN — 01.07.2003 — 009.001 — 40
▼M2
lifetime of the active substance in the top layer of aqueous systems
and the real lifetime of the substance.
The method is described in the FAO Revised Guidelines on Environ-
mental 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.
2.10. Stability in air, photochemical degradation, identity of breakdown
product(s)
An estimation of the photochemical oxidative degradation (indirect
hototransformation) of the active substance, must be submitted.
2.11. Flammability including auto-flammability
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.
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).
2.12. Flash point
The flash point of active substances as manufactured with a melting
point below 40 ºC, must be determined and reported according to
EEC method A 9; only closed cup methods should be used.
2.13. Explosive properties
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
The surface tension has to be determined and reported according to
EEC method A 5.
2.15 Oxidizing properties
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 suffi-
cient to provide that information as justification for not determining
the oxidizing properties of the substance.
3.Furtherinformationontheactivesubstance
(i) The information provided must describe the intended purposes
for which preparations containing the active substance are used,
or are to be used and the dose and manner of their use or
proposed use.
(ii) The information provided must specify the normal methods and
precautions to be followed, in the handling, storage and transport
of the active substance.
(iii) The studies, data and information submitted, together with other
relevant studies, data and information, must bothspecify and
justify the methods and precautions to be followed in the event
of fire. The possible products of combustion in the event of fire
should be estimated, based on the chemical structure and the
chemical and physical properties of the active substance.
(iv) The studies, data and information submitted, together with other
relevant studies, data and information, must demonstrate the suit-
ability of measures proposed for use in emergency situations.1991L0414 — EN — 01.07.2003 — 009.001 — 41
▼M2
(v) The informaton and data referred to are reqired for all active
substances, except where otherwise specified.
3.1. Function, e.g. fungicide, herbicide, insecticide, repellant, growth
regulator
The function must be specified from among the following:
— acaricide
— bactericide
— fungicide
— herbicide
— insecticide— molluscicide
— nematicide
— plant growthregulator
— repellant
— rodenticide— semio-chemicals
— talpicide
— viricide
— other (must be specified)
3.2. Effects on harmful organisms, e.g. contact poison, inhalation poison,
stomach poison, fungitoxic, etc. systematic or not in plants
3.2.1. The nature of the effects on harmful organisms must be stated:
— contact action
— stomachaction
— inhalation action— fungitoxic action
— fungistatic action
— desiccant
— reproduction inhibitor
— other (must be specified)
3.2.2. It must be stated whether or not the active substance is translocated in
plants and where relevant whether such translocation is apoplastic,
symplastic or both.
3.3. Field of use envisaged, e.g. field, protected crops, storage of plant
products, home gardening
The field(s) of use, existing and proposed, for preparations containing
the active substance must be specified from among the following:
— Field use, suchas agriculture, h orticulture, forestry and viticulture
— Protected crops
— Amenity
— Weed control on non-cultivated areas— Home gardening
— House plants
— Plant products storage practice
— Other (specify)
3.4. Harmful organisms controlled and crops or products protected or
treated
3.4.1. Details of existing and the intended use in terms of crops, groups of
crops, plants, or plant products treated and where relevant protected,
must be provided.
3.4.2. Where relevant, details of harmful organisms against which protection
is afforded, must be provided.
3.4.3 Where relevant, effects achieved e.g. sprout suppression, retardation
of ripening, reduction in stem length, enhanced fertilization etc.,
must be reported.
3.5. Mode of action
3.5.1. To the extent that is has elucidated, a statement must be provided as
to the mode of action of the active substance in terms, where relevant,1991L0414 — EN — 01.07.2003 — 009.001 — 42
▼M2
of the biochemical and physiological mechanism(s) and biochemical
pathway(s) involved. Where availble, the results of relevant experi-
mental studies must be reported.
3.5.2. Where it is known that to exert its intended effect, the active
substance must be converted to a metabolite or degradation product
following application or use of preparations containing it, the
following information, cross referenced to and drawing on informa-
tion provided in the context of paragraphs 5.6, 5.11, 6.1, 6.2, 6.7,
7.1, 7.2 and 9, where relevant, must be provided for active metabolite
or degradation product:
— chemical name according to IUPAC and CA nomenclature,
— ISO common name or porposed common name,— CAS EEC-number EEC (EINECS or ELINCS) number, and
CIPAC number if available,
— empirical and structural formula, and— molecular mass.
3.5.3. Available information relating to the formation of active metabolites
and degradation products, must be provided, to include:
— 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.
3.6. Information on the occurrence or possible occurrence of the develop-
ment of resistance and appropriate management strategies
Where available information on possible occurrence of the develop-
ment of resistance or cross-resistance must be provided.
3.7. Recommended methods and precautions concerning handling,
storage, transport or fire
A safety data sheet pursuant to Article 27 of Council Directive 65/
548/EEC (
1) must be provided for all active substances.
3.8. Procedures for destruction or decontamination
3.8.1. Controlled incineration
In many cases the preferred or sole means to safely dispose of active
substances, contaminated materials, or contaminated packaging, is
through controlled incineration in a licensed incinerator.
Where the content of halogens of the active substance is greater than
60 %, the pyrolytic behaviour of the active substance under controlled
conditions (including where relevant supply of oxygen and defined
residence time), at 800 ºC and the content of polyhalogenated
dibenzo-p-dioxins and dibenzo-furans in the products of pyrolysis
must be reported. The application must provide detailed instructions
for safe disposal.
3.8.2. Others
Other methods to dispose of the active substance, contaminated
packaging and contaminated materials, where proposed, must be fully
described. Data must be provided for such methods, to establish their
effectiveness and safety.
3.9. Emergency measures in case of an accident
Procedures for the decontamination of water in case of an accident
must be provided.1991L0414 — EN — 01.07.2003 — 009.001 — 43
(1) OJ No L 196, 16. 8. 1967, p. 1.
▼M8
4.Analyticalmethods
Introduction
The provisions of this section only cover analytical methods required
for post-registration control and monitoring purposes.
For analytical methods used for generation of data as required in this
Directive or for other purposes the applicant has to provide a justifi-
cation for the method used; where necessary separate guidance will be
developed for such methods on the basis of the same requirements as
defined for methods for post-registration control and monitoring
purposes.
Descriptions of methods must be provided and include details of
equipment, materials and conditions used.
As far as practicable these methods must employ the simplest
approach, involve the minimum cost, and require commonly available
equipment.
For this section the following applies:
Impurities Any component other than the pure active
substance which is present in the active
substance as manufactured (including non-
active isomers) originating from the manu-
facturing process or from degradation during
storage,
Relevant impurities Impurities of toxicological and/or ecotoxico-
logical or environmental concern,
Significant impurities Impurities witha content of ≥1 g/kg in the
active substance as manufactured,
Metabolites Metabolites include products resulting from
degradation or reaction of the active
substance,
Relevant metabolites Metabolites of toxicological and/or ecotoxi-
cological or environmental concern.
On request the following samples must be provided:
(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 compo-
nents included in the residue definition;
(iv) if available, samples of reference substances for the relevant
impurities.
4.1.Methodsfortheanalysisoftheactivesubstanceasmanufactured
For this point the following definitions apply:
(i)Specificity
Specificity is the ability of a method to distinguish between the
analyte being measured and other substances.
(ii)Linearity
Linearity is defined as the ability of the method, within a given
range, to obtain an acceptable linear correlation between the
results and the concentration of analyte in samples.
(iii)Accuracy
The accuracy of a method is defined as the degree to which the
determined value of analyte in a sample corresponds to the
accepted reference value (for example ISO 5725).
(iv)Precision
Precision is defined as the closeness of agreement between inde-
pendent test results obtained under prescribed conditions.1991L0414 — EN — 01.07.2003 — 009.001 — 44
▼M8
Repeatability: Precision under repeatability conditions, i.e. condi-
tions where independent test results are obtained with the same
method on identical test material in the same laboratory by the
same operator using the same equipment within short intervals
of time.
The reproducibility is not required for the active substance as
manufactured (for definition of reproducibility see ISO 5725).
4.1.1. Methods, which must be described in full, must be provided for the
determination of pure active substance in the active substance as
manufactured as specified in the dossier submitted in support of inclu-
sion in Annex I to Directive 91/414/EEC. The applicability of
existing Cipac methods must be reported.
4.1.2. Methods must also be provided for the determination of significant
and/or relevant impurities and additives (e.g. stabilizers) in the active
substance as manufactured.
4.1.3. Specificity, linearity, accuracy and repeatability4.1.3.1. Specificity of methods submitted, must be demonstrated and reported.
In addition the extent of interference by other substances present in
the active substance as manufactured (e.g. isomers, impurities or addi-
tives), must be determined.
While interferences due to other components may be identified as
systematic errors in the assessment of the accuracy of methods
proposed for the determination of pure active substance in the active
substance as manufactured, an explanation must be provided for any
interference occurring which contributes more than ± 3 % to the total
quantity determined. The degree of interference for methods for the
determination of impurities must also be demonstrated.
4.1.3.2. The linearity of proposed methods over an appropriate range must be
determined and reported. For the determination of pure active
substance, the calibration range must extend (by at least 20 %) the
highest and lowest nominal content of the analyte in relevant analy-
tical solutions. Duplicate calibration determinations must be made atthree or more concentrations. Alternatively, five concentrations, each
as single measurements, are acceptable. Reports submitted must
include the equation of the calibration line and the correlation coeffi-
cient and representative and properly labelled documentation from the
analysis, e.g. chromatograms.
4.1.3.3. Accuracy is required for methods for the determination of pure active
substance and significant and/or relevant impurities in the active
substance as manufactured.
4.1.3.4. For the repeatability in the determination of the pure active substance
in principle a minimum of five determinations must be made. The
relative standard deviation (% RSD) must be reported. Outliers iden-
tified through an appropriate method (e.g. Dixons or Grubbs test),
may be discarded. Where outliers have been discarded, that fact
must be clearly indicated. An explanation as to the reason for the
occurrence of individual outliers, must be attempted.
4.2.Methodsforthedeterminationofresidues
The methods must be capable of determining the active substance
and/or relevant metabolites. For eachmeth od and for eachrelevant
representative matrix, the specificity, precision, recovery, and limit
of determination must be experimentally determined and reported.
In principle, residue methods proposed should be multi-residue
methods; a standard multi-residue method must be assessed and
reported as to its suitability for residue determination. Where residue
methods proposed are not multi-residue methods, or are not compa-
tible with such methods, an alternative method must be proposed.
Where this requirement results in an excessive number of methods
for individual compounds, a ‘common moiety method’ may be accep-
table.
For this section the following definitions apply:
(i)Specificity
Specificity is the ability of a method to distinguish between the
analyte being measured and other substances.1991L0414 — EN — 01.07.2003 — 009.001 — 45
▼M8
(ii)Precision
Precision is defined as the closeness of agreement between inde-
pendent test results obtained under prescribed conditions.
Repeatability: Precision under repeatability conditions, i.e. condi-
tions where independent test results are obtained with the same
method on identical test material in the same laboratory by the
same operator using the same equipment within short intervals
of time.
Reproducibility: As the definition of reproducibility in relevant
publications (for example, in ISO 5725) is in general not practic-
able for residue analytical methods, reproducibility in the context
of this Directive is defined as a validation of repeatability of
recovery, from representative matrices and at representative
levels, by at least one laboratory which is independent from that
which initially validated the study (this independent laboratory
may be within the same company) (independent laboratory vali-
dation).
(iii)Recovery
The percentage of the amount of active substance or relevant
metabolite originally added to a sample of the appropriate matrix
which contains no detectable level of the analyte.
(iv)Limit of determination
The limit of determination (often referred to as limit of quantifi-
cation) is defined as the lowest concentration tested, at which an
acceptable mean recovery is obtained (normally 70 to 110 % with
a relative standard deviation of preferably ≤20 %; in certain
justified cases lower or higher mean recovery rates as well as
higher relative standard deviations may be acceptable).
4.2.1. Residues in and/or on plants, plant products, foodstuffs (of plant and
animal origin), feedingstuffs
Methods submitted must be suitable for the determination of all
components included in the residue definition as submitted according
to the provisions of section 6, points 6.1 and 6.2 in order to enable
Member States to determine compliance withestablish ed MRL's or
to determine dislodgeable residues.
The specificity of the methods must enable all components included
in the residue definition to be determined, using an additional confir-
matory method if appropriate.
The repeatability must be determined and reported. The replicate
analytical portions for test can be prepared from a common field
treated sample, containing incurred residues. Alternatively the repli-
cate analytical portions for test can be prepared from a common
untreated sample withaliquots fortified at th e required level(s).
The results from an independent laboratory validation must be
reported.
The limit of determination including the individual and mean
recovery must be determined and reported. The overall relative stan-
dard deviation, as well as the relative standard deviation for each
fortification level must be experimentally determined and reported.
4.2.2. Residues in soil
Methods for analysis of soil for parent compound and/or relevant
metabolites must be submitted.
The specificity of the methods must enable the parent compound and/
or relevant metabolites to be determined, using an additional confir-
matory method if appropriate.
The repeatability, recovery and the limit of determination including
the individual and mean recovery must be determined and reported.
The overall relative standard deviation, as well as the relative stan-
dard deviation for eachfortification level must be experimentally
determined and reported.
The proposed limit of determination must not exceed a concentration
which is of concern with regard to exposure of non-target organisms
or because of phytotoxic effects. Normally the proposed limit of
determination should not exceed 0,05 mg/kg.1991L0414 — EN — 01.07.2003 — 009.001 — 46
▼M8
4.2.3. Residues in water (including drinking water, ground water and surface
water)
Methods for analysis in water for parent compound and/or relevant
metabolites must be submitted.
The specificity of the methods must enable the parent compound and/
or relevant metabolites to be determined, using an additional confir-
matory method if appropriate.
The repeatability, recovery and the limit of determination including
the individual and mean recovvery must be determined and reported.
The overall relative standard deviation, as well as the relative stan-
dard deviation for eachfortification level must be experimentally
determined and reported.
For drinking water the proposed limit of determination must not
exceed 0,1 µg/l. For surface water the proposed limit of determination
must not exceed a concentration which has an impact on non-target
organisms deemed to be unacceptable according to the requirements
of Annex VI.
4.2.4. Residues in air
Methods for the analysis in air of the active substance and/or relevant
metabolites formed during or shortly after application must be
submitted unless it can be justified that exposure of operators,
workers or bystanders is not likely to occur.
The specificity of the methods must enable the parent compound and/
or relevant metabolites to be determined, using an additional confir-
matory method if appropriate.
The repeatability, recovery and the limit of determination including
the individual and mean recovery must be determined and reported.
The overall relative standard deviation, as well as the relative stan-
dard deviation for eachfortification level must be experimentally
determined and reported.
The proposed limit of determination must take into account relevant
health based limit values or relevant exposure levels.
4.2.5. Residues in body fluids and tissues
Where an active substance is classified as toxic or highly toxic appro-
priate analytical methods must be submitted.
The specificity of the methods must enable the parent compound and/
or relevant metabolites to be determined, using an additional confir-
matory method if appropriate.
The repeatability; recovery and the limit of determination including
the individual and mean recovery must be determined and reported.
The overall relative standard deviation, as well as the relative stan-
dard deviation for eachfortification level must be experimentally
determined and reported.
5. Toxicological and metabolism studies
Introduction
(i) The information provided, taken together with that provided for
one or more preparations containing the active substance, must
be sufficient to permit an evaluation to be made as to the risks
for man, associated with the handling and use of plant protec-
tion products containing the active substance, and the risk for
man arising from residual traces remaining in food and water.
In addition, the information provided must be sufficient to:
— permit a decision to be made as to whether, or not, the
active substance can be included in Annex I,
— specify appropriate conditions or restrictions to be asso-
ciated withany inclusion in Annex I,
— classify the active substance as to hazard,— establisha relevant acceptable daily intake (ADI) level for
man,
— establishacceptable operator exposure level(s) (AOEL),— specify the hazard symbols, the indications of danger, and
the risk and safety phrases for the protection of man,1991L0414 — EN — 01.07.2003 — 009.001 — 47
▼M4
▼M4
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.
(ii) There is a need to investigate and report all potentially adverse
effects found during routine toxicological investigations
(including effects on organs and special systems suchas immu-
notoxicity and neurotoxicity) and to undertake and report such
additional studies which may be necessary to investigate the
probable mechanism involved, to establish Noaels (no observed
adverse effect levels), and to assess the significance of these
effects. All available biological data and information which is
relevant to the assessment of the toxicological profile of the
substance tested, must be reported.
(iii) In the context of the influence that impurities can have on toxi-
cological behaviour, it is essential that for each study submitted,
a detailed description (specification) of the material used, as
mentioned under section 1 point 11 be provided. Tests should
be conducted using active substance of that specification to be
used in the manufacture of preparations to be authorized, except
where radiolabelled material is required or permitted.
(iv) Where studies are conducted using an active substance
produced in the laboratory or in a pilot plant production system,
the studies must be repeated using the active substance as
manufactured, unless it can be justified that the test material
used is essentially the same, for the purposes of toxicological
testing and assessment. In cases of uncertainty, appropriate
bridging studies must be submitted to serve as a basis for a
decision as to the possible need for repetition of the studies.
(v) In the case of studies in which dosing extends over a period,
dosing should preferably be done using a single batch of active
substance if stability permits.
(vi) For all studies actual achieved dose in mg/kg body weight, as
well as in other convenient units, must be reported. Where
dosing via the diet is utilized the test compound must be
distributed uniformly in the diet.
(vii) Where, as a result of metabolism or other processes in or on
treated plants, or as a result of processing of treated products,
the terminal residue (to which consumers or workers as defined
in Annex III, point 7.2.3 will be exposed) contains a substance
which is not the active substance itself and is not identified as a
metabolite in mammals, it will be necessary to carry out toxi-
city studies on these components of the terminal residue unless
it can be demonstrated that consumer or worker exposure to
these substances does not constitute a relevant risk to health.
Toxicokinetic and metabolism studies relating to metabolites
and degradation products should only be conducted if toxicity
findings of the metabolite cannot be evaluated by the available
results relating to the active substance.
(viii) The way of administration of the test substance depends on the
main exposure routes. In cases where exposure is mainly by the
gas phase, it can be more appropriate to perform inhalation
studies instead of oral studies.
5.1.Studies on absorption, distribution, excretion and metabolism in
mammals
Quite limited data, as described below and restricted to one test
species (normally the rat) may be all that is required in this area.These data can provide information useful in the design and interpre-
tation of subsequent toxicity tests. However, it must be remembered
that information on interspecies differences may be crucial in extrapo-
lation of animal data to man and information on percutaneous
penetration, absorption, distribution, excretion and metabolism may
be useful in operator risk assessments. It is not possible to specify
detailed data requirements in all areas, since the exact requirements
will be dependant upon the results obtained for each particular test
substance.1991L0414 — EN — 01.07.2003 — 009.001 — 48
▼M4
Aim of the test:
The tests should provide sufficient data to permit:
— an evaluation of the rate and extent of absorption,
— 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 effect of dose level on these parameters and whether results are
different after single versus repeated doses, should also be investi-
gated.
Circumstances in which required
A single dose toxicokinetic study in rats (oral route of administration)
in at least two dose levels as well as a repeated dose toxicokinetic
study in rats (oral route of administration) at a single dose level,
must be conducted and reported. It may be necessary in some cases
to perform additional studies on another species (such as goat or
chicken).
Test guideline
Commission Directive 87/302/EEC of 18 November 1987 adapting to
technical progress for the ninth time Council Directive 67/548/EEC
on the approximation of laws, regulations and administrative provi-
sions relating to the classification, packaging and labelling of
dangerous substances(1), part B, Toxicokinetics.
5.2.Acutetoxicity
The studies, data and information to be provided and evaluated must
be sufficient to permit the identification of effects following a single
exposure to the active substance, and in particular to establish, or
indicate:
— 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 expo-
sure.
While the emphasis must be on estimating the toxicity ranges
involved, the information generated must also permit the active
substance to be classified in accordance withCouncil Directive 67/
548/EEC. The information generated through acute toxicity testing is
of particular value in assessing hazards likely to arise in accident
situations.
5.2.1. Oral
Circumtances in which requiredThe acute oral toxicity of the active substance must always be
reported.
Test guidelineThe test must be carried out in accordance with the Annex to
Commission Directive 92/69/EEC of 31 July 1992 adapting to tech-
nical progress for the seventeenth time Council Directive 67/548/
EEC on the approximation of laws, regulations and administrative
provisions relating to the classification, packaging and labelling of
dangerous substances(
2), Method B1 or B1 bis.
5.2.2. Percutaneous
Circumstances in which requiredThe acute percutaneous toxicity of the active substance must always
be reported.1991L0414 — EN — 01.07.2003 — 009.001 — 49
(1) OJ No L 133, 30. 5. 1988, p. 1.
(2) OJ No L 383A, 29. 12. 1992, p. 1.
▼M4
Test guideline
Bothlocal and systemic effects must be investigated. Th e test must be
carried out in accordance withDirective 92/69/EEC meth od B3.
5.2.3. Inhalation
Circumstances in which required
The inhalation toxicity of the active substance must be reported where
the active substance is:
— 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 withfogging equipment,
— has a vapour pressure > 1 × 10&minus;2Pa and is to be included in
preparations to be used in enclosed spaces suchas wareh ouses or
glasshouses,
— is to be included in preparations which are powders containing a
significant proportion of particles of diameter ►C3< 50µm ◄
(> 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 < 50µm (> 1 % on a weight basis).
Test guidelineThe test must be carried out in accordance with Directive 92/69/EEC
Method B2.
5.2.4. Skin irritation
Aim of the test
The test will provide the potential of skin irritancy of the active
substance including the potential reversibility of the effects observed.
Circumstances in which required
The skin irritancy of the active substance must be determined except
where it is likely, as indicated in the test guideline, that severe skin
effects may be produced or that effects can be excluded.
Test guideline
The acute skin irritation must be carried out in accordance with
Directive 92/69/EEC Method B4.
5.2.5. Eye irritation
Aim of test
The test will provide the potential of eye irritancy of the active
substance including the potential reversibility of the effects observed.
Circumstances in which required
Eye irritation tests must be conducted except where it is likely, as
indicated in the test guideline, that severe effects on the eyes may be
produced.
Test guidelines
The acute eye irritation must be determined in accordance with Direc-
tive 92/69/EEC Method B5.
5.2.6. Skin sensitization
Aim of test
The test will provide sufficient information to assess the potential of
the active substance to provoke skin sensitization reactions.
Circumstances in which required
The test must always be carried out except where the substance is a
known sensitizer.1991L0414 — EN — 01.07.2003 — 009.001 — 50
▼M4
Test guideline
The test must be carried out in accordance with Directive 92/69/EEC
Method B6.
5.3.Short-termtoxicity
Short-term toxicity studies must be designed to provide information
as to the amount of the active substance that can be tolerated without
toxic effects under the conditions of the study. Such studies provide
useful data on the risks for those handling and using preparations
containing the active substance. In particular, short-term studies
provide an essential insight into possible cumulative actions of the
active substance and the risks to workers who may be intensively
exposed. In addition short-term studies provide information useful in
the design of chronic toxicity studies.
The studies, data and information to be provided and evaluated, must
be sufficient to permit the identification of effects following repeated
exposure to the active substance, and in particular to further establish,
or indicate:
— 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 expo-
sure.
5.3.1. Oral 28-day study
Circumstances in which required
Although it is not mandatory to perform 28-day short term studies,
they can be useful as range finding tests. Where conducted they
must be reported, since the results could be of particular value in the
identification of adaptive responses which can be masked in chronic
toxicity studies.
Test guideline
The test must be carried out in accordance with Directive 92/69/EEC
Method B7.
5.3.2. Oral 90-day study
Circumstances in which required
The short-term oral toxicity (90 day) of the active substance to both
rat and dog, must always be reported. Where there is evidence that
the dog is significantly more sensitive and where such data are likely
to be of value in extrapolating results obtained to man, a 12-month
toxicity study in dogs must be conducted and reported.
Test guidelines
Directive 87/302/EEC, Part B, sub-chronic oral toxicity test.
5.3.3. Other routes
Circumstances in which required
For the assessment of operator exposure additional percutaneous
studies may be useful.
For volatile substances (vapour pressure >10
−2Pascal) expert judg-
ment is required to decide whether the short term studies have to be
performed by oral or inhalation exposure.
Test guidelines— 28-day dermal: Directive 92/69/EEC Method B9,1991L0414 — EN — 01.07.2003 — 009.001 — 51
▼M4
— 90-day dermal: Directive 87/302/EEC, Part B, sub-chronic dermal
toxicity study,
— 28-day inhalation: Directive 92/69/EEC Method B8,
— 90-day inhalation: Directive 87/302/EEC, Part B, sub-chronic
inhalation toxicity study.
5.4.Genotoxicitytesting
Aim of the test
These studies are of value in:
— the prediction of genotoxic potential
— the early identification of genotoxic carcinogens
— the elucidation of the mechanism of action of some carcinogens
To avoid responses that are artifacts of the test system, excessively
toxic doses must not be used in either in vitroorin vivoassays for
mutagenicity. This approach should be regarded as general guidance.
It is important that a flexible approach is adopted, with selection of
further tests being' dependant upon interpretation of results at each
stage.
5.4.1. In vitro studies
Circumstances in which requiredIn vitromutagenicity tests (bacterial assay for gene mutation, test for
clastogenicity in mammalian cells and test for gene mutation in
mammalian cells) must always be performed.
Test guidelinesAcceptable test guidelines are:Directive 92/69/EEC Method B14 — Salmonella Typhimurium
reverse mutation assay
Directive 92/69/EEC Method B10 — in vitromammalian cytogenetic
test
Directive 87/302/EEC, Part B — in vitromammalian cell gene muta-
tion test
5.4.2. In vivo studies in somatic cells
Circumstances in which requiredIf all the results of the in vitrostudies are negative further resting
must be done withconsideration of oth er relevant information avail-
able (including toxicokinetic, toxicodynamic and physico-chemical
data and data on analogous substances). The test can be an in vivo
study or an in vitrostudy using a different metabolizing system from
that/those previously used.
If thein vitrocytogenetic test is positive, an in vivotest using somatic
cells (metaphase analysis in rodent bone marrow or micronucleus test
in rodents) must be conducted.
If either of the in vitrogene mutation tests are positive, an in vivotest
to investigate unscheduled DNA synthesis or a mouse spot test must
be conducted.
Test guidelinesAcceptable test guidelines are:Directive 92/69/EEC Method B12 — Micronucleus test,Directive 87/302/EEC Part B — Mouse spot test,Directive 92/69/EEC Method B11 — In vivoMammalian Bone-
Marrow cytogenetic test, Chromosomal analysis.
5.4.3. In vivo studies in germ cells
Circumstances in which requiredWhen any result of an in vivostudy in somatic cells is positive, in
vivotesting for germ cell effects may be justified. The necessity for
conducting these tests will have to be considered on a case by case
basis, taking into account information regarding toxicokinetics, use1991L0414 — EN — 01.07.2003 — 009.001 — 52
▼M4
and anticipated exposure. Suitable tests would need to examine inter-
action with DNA (such as the dominant lethal assay), to look at the
potential for inherited effects and possibly make a quantitative assess-
ment of heritable effects. It is recognized that in view of their
complexity, the use of quantitative studies would require strong justi-
fication.
5.5.Longtermtoxicityandcarcinogenicity
Aim of the test
The long-term studies conducted and reported, taken together with
other relevant data and information on the active substance, must be
sufficient to permit the identification of effects, following repeated
exposure to the active substance, and in particular must be sufficient
to:
— 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— establishth e Noael.
Similarly, the carcinogenicity studies taken together with other rele-
vant data and information on the active substance, must be sufficient
to permit the hazards for humans, following repeated exposure to the
active substance, to be assessed, and in particular must be sufficient:
— to identify carcinogenic effects resulting from exposure to the
active substance,
— to establishth e 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).
Circumstances in which required
The long-term toxicity and carcinogenicity of all active substances
must be determined. If in exceptional circumstances, it is claimed
that such testing is unnecessary, that claim must be fully justified,
viz.toxicokinetic data demonstrates that absorption of the active
substance does not occur from the gut, through the skin or via the
pulmonary system.
Test conditions
A long-term oral toxicity and carcinogenicity study (two years) of the
active substance must be conducted using the rat as test species; these
studies can be combined.
A carcinogenicity study of the active substance must be conducted
using the mouse as test species.
Where a non-genotoxic mechanism for carcinogenicity is suggested, a
well argued case, supported withrelevant experimental data,
including that necessary to elucidate the possible mechanism
involved, must be provided.
While the standard reference points for treatment responses are
concurrent control data, historical control data, may be helpful in the
interpretation of particular carcinogenicity studies. Where submitted,
historical control data should be from the same species and strain,
maintained under similar conditions and should be from contempora-
neous studies. The information on historical control data provided
must include:
— 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,1991L0414 — EN — 01.07.2003 — 009.001 — 53
▼M4
— 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.
The doses tested, including the highest dose tested, must be selected
on the basis of the results of short-term testing and where available at
the time of planning the studies concerned, on the basis of metabo-
lism and toxicokinetic data. The highest dose level in the
carcinogenicity study should elicit signs of minimal toxicity such as
slight depression in body-weight gain (less than 10 %), without
causing tissue necrosis or metabolic saturation and without substan-
tially altering normal lifespan due to effects other than tumours. If
the long-term toxicity study is carried out separately, the highest
dose level should elicit definite signs of toxicity without causing
excessive lethality. Higher doses, causing excessive toxicity are not
considered relevant to evaluations to be made.
In the collection of data and compilation of reports, incidence of
benign and malignant tumours must not be combined, unless there is
clear evidence of benign tumours becoming malignant withtime.
Similarly, dissimilar, un-associated tumours, whether benign or malig-
nant, occurring in the same organ, must not be combined, for
reporting purposes. In the interests of avoiding confusion, terminology
such as that developed by American Society of Toxicologic Patholo-
gists(1), or the Hannover Tumour Registry (RENI) should be used in
the nomenclature and reporting of tumours. The system used must be
identified.
It is essential that biological material selected for histopathological
examination includes material selected to provide further information
on lesions identified during gross pathological examination. Where
relevant to the elucidation of mechanism of action and available,
special histological (staining) techniques, histochemical techniques
and electron microscopic examinations, must be conducted and
reported.
Test guideline
The studies must be carried out in accordance with Directive 87/302/
EEC, part B, Chronic toxicity test, Carcinogenicity test or combined
chronic toxicity/carcinogenicity test.
5.6.Reproductivetoxicity
Adverse reproductive effects are of two main types:
— impairment of male or female fertility, and
— impacts on the normal development of progeny (developmental
toxicity).
Possible effects on all aspects of reproductive physiology in both
males and females, as well as possible effects on pre-natal and post-
natal development, must be investigated and reported. If in excep-
tional circumstances, it is claimed that such testing is unnecessary,
that claim must be fully justified.
While the standard reference point for treatment responses are concur-
rent control data, historical control data may be helpful in the
interpretation of particular reproductive studies. Where submitted,
historical control data should be from the same species and strain,
maintained under similar conditions and should be from contempora-
neous studies. The information on historical control data provided
must include:
— 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,1991L0414 — EN — 01.07.2003 — 009.001 — 54
(1)Standardized System of Nomenclature and Diagnostic Criteria — Guides for Toxico-
logic Pathology
▼M4
— 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.
5.6.1. Multi-generation studies
Aim of the test
The studies reported, taken together with other relevant data and
information on the active substance, must be sufficient to permit the
identification of effects for reproduction, following repeated exposure
to the active substance, and in particular must be sufficient:
— 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 establishth e Noael.
Circumstances in which requiredA reproduction toxicity study in rats over at least two generations
must always be reported.
Test guideline
The tests must be carried out in accordance with Directive 87/302/
EEC, Part B, two-generation reproduction toxicity test. In addition
organ weight of reproductive organs must be reported.
Supplementary studiesWhere necessary for a better interpretation of the effects on reproduc-
tion and as far as this information is not yet available it could be
necessary to perform supplementary studies in order to provide the
following information:
— separate male and female studies,
— three segment designs,
— dominant lethal assay for male fertility,— cross-matings of treated males withuntreated females and vice
versa,
— effects on spermatogenesis,
— effects on oogenesis,
— sperm motility, mobility and morphology, and— investigation of hormonal activity.
5.6.2. Developmental toxicity studies
Aim of the test
The studies reported, taken together with other relevant data and
information on the active substance, must be sufficient to permit
effects on embryonic and foetal development, following repeated
exposure to the active substance, to be assessed, and in particular
must be sufficient:
— 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 bothdam and offspring,
— to identify changes in toxic signs and manifestations observed,
and
— to establishth e Noael.
Furthermore, the tests will give additional information on any
enhancement of general toxic effects of pregnant animals.1991L0414 — EN — 01.07.2003 — 009.001 — 55
▼M4
Circumstances in which required
The tests must always be carried out.Test conditionsDevelopmental toxicity must be determined bothto rat and rabbit by
the oral route. Malformations and variations should be reported sepa-
rately. A glossary of terminology and diagnostic principles for
malformations and variations must be given in the report.
Test guidelineThe tests must be carried out in accordance with Directive 87/302/
EEC, Part B, teratogenicity test — rodent and non-rodent.
5.7.Delayedneurotoxicitystudies
Aim of the test
The test shall provide sufficient data to evaluate if the active
substance could provoke delayed neurotoxicity after acute exposure.
Circumstances in which required
These studies have to be performed for substances of similar or
related structures to those capable of inducing delayed neurotoxicity
such as organophosphates.
Test guidelines
The test must be carried out in accordance with OECD Guideline 418.
5.8.Othertoxicological studies
5.8.1. Toxicity studies of metabolites as referred to in the introduction point
(vii)
Supplementary studies, where they relate to substances other than the
active substance, are not a routine requirement.
Decisions as to the need for supplementary studies must be made on a
case by case basis.
5.8.2. Supplementary studies on the active substance
In certain cases it can be necessary to carry out supplementary studies
to further clarify observed effects. These studies could include:
— studies on absorption, distribution, excretion and metabolism,
— studies on the neurotoxic potential,— studies on the immunotoxicological potential,— studies on other routes of administration.
Decisions as to the need for supplementary studies must be made on a
case by case basis, taking into account the results of the available
toxicological and metabolism studies and the most important exposure
routes.
Studies required must be designed on an individual basis, in the light
of the particular parameters to be investigated and the objectives to be
achieved.
5.9.Medicaldata
Where available, and without prejudice to the provisions of Article 5
of Council Directive 80/1107/EEC of 27 November 1980 on the
protection of workers from the risks related to chemical, physical
and biological agents at work (
1), practical data and information rele-
vant to the recognition of the symptoms of poisoning, and on the
effectiveness of first aid and therapeutic measures have to be
submitted. More specific references to the investigation for antidotal
pharmacology or safety pharmacology using animals should be
provided. Where relevant, the effectiveness of potential antagonists
to poisoning, should be investigated and reported.1991L0414 — EN — 01.07.2003 — 009.001 — 56
(1) OJ No L 327, 3. 12. 1980, p. 8.
▼M4
Data and information relevant to the effects of human exposure,
where available and of the necessary quality, are of particular value,
in confirming the validity of extrapolations made and conclusions
reached with respect to target organs, dose-response relationships,
and the reversibility of toxic effects. Such data can be generated
following accidental or occupational exposure.
5.9.1. Medicinal surveillance on manufacturing plant personnel
Reports of occupational health surveillance programmes, supported
with detailed information on the design of the programme, on expo-
sure to the active substance and exposure to other chemicals, must be
submitted. Such reports should, where feasible, include data relevant
to the mechanism of action of the active substance. These reports
shall, where available, include data from persons exposed in manufac-
turing plants or after application of the active substance (e.g.: in
efficacy trials).
Available information on the sensitization including allergenic
response of workers and others exposed to the active substance, must
be provided, and include where relevant details of any incidence of
hypersensitivity. The information provided should include details of
frequency, level and duration of exposure, symptoms observed and
other relevant clinical information.
5.9.2. Direct observation, e.g.: clinical cases and poisoning incidents
Available reports from the open literature, relating to clinical cases
and poisoning incidents, where they are from refereed journals or offi-
cial reports, must be submitted together with reports of any follow-up
studies undertaken. Suchreports sh ould contain complete descriptions
of the nature, level and duration of exposure, as well as the clinical
symptoms observed, first aid and therapeutic measures applied and
measurements and observations made. Summary and abstract informa-
tion is not of value.
Where supported with the necessary level of detail, such documenta-
tion can be of particular value in confirming the validity of
extrapolations from animal data to man and in identifying unexpected
adverse effects which are specific to humans.
5.9.3. Observations on exposure of the general population and epidemiolo-
gical studies if appropriate
Where available, and supported with data on levels and duration of
exposure, and conducted in accordance withrecognized standards (1),
epidemiological studies are of particular value and must be submitted.
5.9.4. Diagnosis of poisoning (determination of active substance, metabo-
lites), specific signs of poisoning, clinical tests
A detailed description of the clinical signs and symptoms of
poisoning, including the early signs and symptoms and full details of
clinical tests useful for diagnostic purposes, where available, must be
provided and include full details of the time courses involved relevant
to the ingestion, dermal exposure or inhalation of varying amounts of
the active substance.
5.9.5. Proposed treatment: first aid measures, antidotes, medical treatment
The first aid measures to be used in the event of poisoning (actual and
suspected) and in the event of contamination of eyes must be
provided.
Therapeutic regimes for use in the event of poisoning or contamina-
tion of eyes, including where available the use of antidotes, must be
described in full. Information based on practical experience, where it
exists and is available, in other cases on theoretical grounds, as to the
effectiveness of alternative treatment regimes, where relevant, must
be provided. Contraindications associated withparticular regimes,
particularly those relating to ‘general medical problems’ and condi-
tions, must be described.1991L0414 — EN — 01.07.2003 — 009.001 — 57
(1)Guidelines for Good Epidemiology Practices for Occupational and Environmental
Research, developed by the Chemical Manufacturers Association's Epidemiology TaskGroup, as part of the Epidemiology Resource and Information Centre (ERIC), Pilot
Project, 1991
▼M4
5.9.6. Expected effects of poisoning
Where known, the expected effects and the duration of these effects
following poisoning must be described and include the impact of:
— the type, level and duration of exposure, or ingestion, and
— varying time periods between exposure, or ingestion, and
commencement of treatment.
5.10.Summaryofmammaliantoxicity andoverallevaluation
A summary of all data and information provided under paragraphs 5.1
through 5.10, must be submitted, and include a detailed and critical
assessment of those data in the context of relevant evaluative and
decision making criteria and guidelines, withparticular reference to
the risks for man and animals that may or do arise, and the extent,
quality and reliability of the data base.
Where relevant, in the light of findings with respect to the analytical
profile of batches of the active substance (paragraph 1.11) and any
bridging studies conducted (paragraphs 5 (iv)), the relevance of the
data as submitted to the assessment of the toxicological profile of
the active substance as manufactured, must be argued.
On the basis of an assessment of the data base, and the relevant deci-
sion making criteria and guidelines, justifications must be submitted
for the Noaels proposed for each relevant study.
On the basis of these data scientifically reasoned proposals for the
establishment of ADI and AOEL(s) for the active substance must be
submitted.
6. Residues in or on treated products, food and feed
Introduction
(i) The information provided, taken together with that provided for
one or more preparations containing the active substance, must
be sufficient to permit an evaluation to be made as to the risks
for man, arising from residues of the active substance and rele-
vant metabolites, degradation and reaction products remaining
in food. In addition, the information provided must be sufficient
to:
— permit a decision to be made as to whether, or not, the active
substance can be included in Annex I,
— specify appropriate conditions or restrictions to be associated
withany inclusion in Annex I.
(ii) A detailed description (specification) of the material used, as
provided under Section 1, point 11 must be provided.
(iii) Studies should be performed according to the guidance available
on regulatory testing procedures for residues of plant protection
products in food(1).
(iv) Where relevant, data should be analyzed using appropriate statis-
tical methods. Full details of the statistical analysis should be
reported.
(v) Stability of residues during storage.
If may be necessary to perform studies on the stability of resi-
dues during storage. Provided samples are frozen within
generally 24 hours after sampling and unless a compound is
otherwise known to be volatile or labile, data are not normally
required for samples extracted and analysed within 30 days
from sampling (six months in the case of radio-labelled mate-
rial).
Studies withnon-radio-labelled substances sh ould be carried out
withrepresentative substratets and preferably on samples from
treated crops or animals withincurred residues. Alternatively, if
this is not possible, aliquots of prepared control samples should
be spiked witha known amount of ch emical before storage under
normal storage conditions.
Where the degradation during storage is significant (more than
30 %) it may be necessary to change the storage conditions or1991L0414 — EN — 01.07.2003 — 009.001 — 58
(1) Guidance under development.▼M9
▼M9
not to store the samples prior to analysis and repeat and studies
where the unsatisfactory storage conditions were used.
Detailed information withrespect to th e sample preparation and
storage conditions (temperature and duration) of samples and
extracts must be submitted. Storage stability data using sample
extracts will also be required unless samples are analysed within
24 hours of extraction.
6.1.Metabolism,distributionandexpressionofresidueinplants
Aim of the tests
The objectives of these studies are:
— 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.
Circumstances in which required
These studies must always be performed unless it can be justified that
no residues will remain on plants/plant products which are used as
food or feedingstuffs.
Test conditions
Metabolism studies have to involve crops or categories of crops in
which plant protection products containing the active substance in
question would be used. If a wide range of uses in different crop cate-
gories or in the category fruits is envisaged, studies have to be carried
out on at least three crops unless it can be justified that a different
metabolism is unlikely to occur. In cases where use is envisaged in
different categories of crops, the studies must be representative for
the relevant categories. For this purpose crops can be considered as
falling into one of five categories: root vegetables, leafy crops, fruits,
pulses and oilseeds, cereals. If studies are available for crops from
three of these categories and the results indicate that the route of
degradation is similar in all three categories then it is unlikely that
any more studies will be needed unless it could be expected that a
different metabolism will occur. The metabolism studies have also to
take into account the different properties of the active substance and
the intended method of application.
An evaluation of the results from different studies has to be submitted
on the point and path of uptake (e.g. via leaves or roots), and on the
distribution of residues between relevant parts of the crop at harvest
(with particular emphasis on edible parts for man or animals). If the
active substance or relevant metabolites are not taken up by the crop,
this must be explained. Information on the mode of action and the
physico-chemical properties of the active substance may be helpful
in assessing trial data.
6.2.Metabolism,distributionandexpressionofresidueinlivestock
Aim of tests
The objectives of these studies are:
— 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.1991L0414 — EN — 01.07.2003 — 009.001 — 59
▼M9
Circumstances in which required
Metabolism studies on animals, suchas lactating ruminants (e.g. goat
or cow) or laying poultry, are only required when pesticide use may
lead to significant residues in livestock feed ( ≥0,1 mg/kg of the total
diet as received, except special cases e.g. active substances which
accumulate). Where it becomes apparent that metabolic pathways
differ significantly in the rat as compared to ruminants a pig study
must be conducted unless the expected intake by pigs is not signifi-
cant.
6.3.Residuetrials
Aim of the tests
The objectives of these studies are:
— to quantify the highest likely residue levels in treated crops at
harvest or outloading from store following the propopsed good
agricultural practice (GAP),
and
— to determine, when appropriate, the rate of decline of plant protec-
tion product deposits.
Circumstances in which required
These studies must always be performed where the plant protection
product will be applied to plants/plant products which are used as
food or feedingstuffs or where residues from soil or other substrates
can be taken up by suchplants except wh ere extrapolation from
adequate data on another crop is possible.
Residue trial data shall be submitted in the Annex II dossier for those
uses of plant protection products for which authorization is sought at
the moment of introduction of a dossier for inclusion of the active
substance in Annex I.
Test conditions
Supervised trials should corrspond to proposed critical GAP. The test
conditions must take into account the highest residues which may
reasonably arise (e.g. maximum number of proposed applications,
use of the maximum envisaged quantity, shortest pre-harvest intervals,
withholding periods or storage periods) but which remain representa-
tive of the realistic worst case conditions in which the active
substance would be used.
Sufficient data must be generated and submitted to confirm that
patterns determined hold for the regions and the range of conditions,
likely to be encountered in the regions concerned for which its use is
to be recommended.
When establishing a supervised trial programme, normally factors
suchas climatic differences existing between production areas, differ-
ences in production methods (e.g. outdoor versus glasshouse uses),
seasons of production, type of formulations, etc. should be taken into
account.
In general, for a comparable set of conditions, trials should be carried
out over a minimum of two growing seasons. All exceptions should
be fully justified.
The precise number of trials necessary is difficult to determine in
advance of a preliminary evaluation of the trial results. Minimum
data requirements only apply where comparability can be established
between production areas, e.g. concerning climate, methods and
growing seasons of production, etc. Assuming all other variables
(climate, etc.) are comparable, a minimum of eight trials representa-
tive of the proposed growing area is required for major crops. For
minor crops normally four trials representative of the proposed
growing area are required.
Due to the inherently higher level of homogeneity in residues arising
from post-harvest treatments or protected crops, trials from one
growing season will be acceptable. For post-harvest treatments, in
principle a minimum of four trials are required, carried out preferably
at different locations withdifferent cultivars. A set of trials h as to be
carried out for each application method and store type unless the
worst case residue situation can be clearly identified.1991L0414 — EN — 01.07.2003 — 009.001 — 60
▼M9
The number of studies per growing season to be performed can be
reduced if it can be justified that the residue levels in plants/plant
products will be lower than the limit of determination.
Where a significant part of the consumable crop is present at the time
of application, half of the supervised residue trials reported should
include data to show the effect of time on the level of residue present
(residue decline studies) unless it can be justified that the consumable
crop is not affected by the application of the plant protection product
under the proposed conditions of use.
6.4.Livestockfeedingstudies
Aim of the tests
The objective of these studies is to determine the residue in products
of animal origin which will result from residues in feedingstuffs or
fodder crops.
Circumstances in which required
Feeding studies are only required:
— when significant residues ( ≥0,1 mg/kg of the total diet as
received, except special cases, suchas active substances wh ich
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.
Where appropriate separate feeding studies for lactating ruminant and/
or laying poultry should be submitted. Where it appears from the
metabolism studies submitted in accordance withth e provisions of
point 6.2 that metabolic pathways differ significantly in the pig as
compared to ruminants, a pig feeding study must be conducted unless
the expected intake by pigs is not significant.
Test conditions
In general, the feed is administered in three dosages (expected residue
level, three to five times, and 10 times the expected residue level).
When setting the 1 × dose, a theoretical feed ration must be compiled.
6.5.Effectsofindustrialprocessingand/orhouseholdpreparations
Circumstances in which required
The decision as to whether it is necessary to carry out processing
studies will depend on:
— 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 signifi-
cance may be found after processing of the plant or plant product.
Processing studies are not normally necessary if no significant or no
analytically determinable residues occur in the plant or plant product
which would be processed, or if the total theoretical maximum daily
intake (TMDI) is less than 10 % of the ADI. In addition, processing
studies are not normally required for plants or plant products mostly
eaten raw except for those with inedible portions such as citrus,
banana or kiwi fruit where data on the distribution of the residue in
peel/pulp may be required.
‘Significant residues’ generally refer to residues above 0,1 mg/kg. If
the pesticide concerned has a high acute toxicity and/or a low ADI,
consideration must be given to conducting processing studies for
determinable residues below 0,1 mg/kg.
Studies on the effects on the nature of the residue are not normally
required where only simple physical operations, not involving a1991L0414 — EN — 01.07.2003 — 009.001 — 61
▼M9
change in temperature of the plant or the plant product, are involved
suchas wash ing, trimming or pressing.
6.5.1. Effects on the nature of the residue
Aim of the testsThe objective of these studies is to establish whether or not break-
down or reaction products arise from residues in the raw products
during processing which may require a separate risk assessment.
Test conditionsDepending upon the level and chemical nature of the residue in the
raw commodity, a set of representative hydrolysis situations (simu-
lating the relevant processing operations) should be investigated,
where appropriate. The effects of process other than hydrolysis, may
also have to be investigated, where the properties of the active
substance or metabolites indicate that toxicologically significant
degradation products may occur as a result of these processes. The
studies are normally conducted witha radio-labelled form of th e
active substance.
6.5.2. Effects on the residue levels
Aim of the testsThe main objectives of these studies are:
— 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.
Test conditionsProcessing studies should represent household processing and/or
actual industrial processes.
In the first instance it is usually only necessary to carry out a core set
of ‘balance studies’ representative of the common processes relevant
to the plants or plant products containing significant residues. Justifi-
cation should be given for the selection made of these representative
process(es). The technology to be used in processing studies should
always correspond as closely as possible to the actual conditions that
are normally used in practice. A balance sheet should be made in
which the mass balance of residues in all intermediate and end
products is investigated. In drawing up sucha balance sh eet any
concentrations or reductions in residues in individual products can be
recognized and the corresponding transfer factors can also be deter-
mined.
If the processed plant products play an important part in the diet, and
if the ‘balance study’ indicates that a significant transfer of residue
into the processed products could occur, then three ‘follow-up studies’
to determine residue concentration or dilution factors must be carried
out.
6.6.Residuesinsucceedingcrops
Aim of the test
The objective of these studies is to permit an evaluation of possible
residues in succeeding crops.
Circumstances in which required
Where data generated in accordance with Annex II, Section 7, point
7.1 or Annex III, Section 9, point 9.1, shows that significant residues
(> 10 % of the applied active substance as a total of unchanged active
substance and its relevant metabolites or degradation products) remain
in soil or in plant materials, suchas straw or organic material up to
sowing or planting time of possible succeeding crops, and which
could lead to residues above the limit of determination in succeeding
crops at harvest, consideration should be given to the residue situa-
tion. This should include consideration of the nature of the residue
in the succeeding crops and involve at least a theoretical estimation
of the level of these residues. If the likelihood of residues in
succeeding crops can not be excluded, metabolism and distribution
studies should be carried out, if necessary followed by field trials.1991L0414 — EN — 01.07.2003 — 009.001 — 62
▼M9
Test conditions
If a theoretical estimation of residues in succeeding crops is done, full
details and a justification shall be be given.
Metabolism and distribution studies and field trials, if necessary, shall
be carried out on representative crops chosen to represent normal
agricultural practice.
6.7.Proposedmaximumresiduelevels(MRLs)andresiduedefiniton
A full justification for the propsoed MRLs must be provided,
including, where relevant, full details of the statistical analysis used.
When judging which compounds are to be included in the residue
definition, account has to be taken of the toxicological significance
of the compounds, amounts likely to be present and the practicality
of the analytical methods proposed for post-registration control and
monitoring purposes.
6.8.Proposedpre-harvest intervals for envisaged uses,or withholding
periodsorstorageperiods,inthecaseofpost-harvestuses
A full justification for the proposals must be provided.
6.9.Estimation of the potential and actual exposure through diet and
othermeans
Consideration will be given to the calculation of a realistic prediction
of dietary intake. This may be done in a step-wise fashion leading to
an increasingly realistic predictions of intake. Where relevant, other
sources of exposure suchas residues arising from th e use of medi-
cines or veterinary drugs have to be taken into acocunt.
6.10.Summaryandevaluationofresiduebehaviour
A summary and evaluation of all data presented in this Section should
be carried out according to the guidance given by the competent
authorities of the Member States concerning the format of such
summaries and evaluations. It should include a detailed and critical
assessment of those data in the context of relevant evaluative and
decision-making criteria and guidelines, withparticular reference to
the risks for man and animals that may or do arise, and the extent,
quality and reliablity of the data base.
In particular, the toxicological significance of any non-mammalian
metabolites must be addressed.
A schematic diagram should be prepared of the metabolic pathway in
plants and animals witha brief explanation of th e distribution and
chemical changes involved.
7.Fateandbehaviourintheenvironment
Introduction
(i) The information provided, taken together with that for one or
more preparations containing the active substance, must be suffi-
cient to pemit an assessment of the fate and behaviour of the
active substance in the environment, and of the non-target
species likely to be at risk from exposure to the active substance,
its metabolites, degradation and reaction products, where they
are of toxicological or environmental significance.
(ii) In particular, the information provided for the active substance,
together with other relevant information, and that provided for
one or more preparations containing it, should be sufficient to:
— decide whether, or not, the active substance can be included
in Annex I,
— specify appropriate conditions or restrictions to be associated
withany inclusion in Annex I,
— classify the active substance as to hazard;
— specify the hazard symbols, the indications of danger, and
relevant risk and safety phrases for the protection of the
environment, which are to be included on packaging
(containers),1991L0414 — EN — 01.07.2003 — 009.001 — 63
▼M6
▼M6
— predict the disribution, fate, and behaviour in the environ-
ment 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
a rise because of potential exposure, and
— identify measures necesary to minimize contamination of the
environment and impact on non-target species.
(iii) A detailed description (specification) of the material used, as
provided for under Section 1, point 11 must be provided. Where
testing is done using active substance the material used should be
of that specification that will be used in the manufacture of
preparations to be authorized except where radio-labelled mate-
rial is used.
Where studies are conducted using active substance produced in
the laboratory or in a pilot plant production system, the studies
must be repeated using active substance as manufactured, unless
it can be justified that the test material used is essentially the
same for the purposes of environmental testing and assessment.
(iv) Where radio-labelled test material is used, radio-labels should be
positioned at sites (one or more as necessary), to facilitate eluci-
dation of metabolic and degradative pathways and to facilitate
investigation of the distribution of the active substance and of
its metabolite, reaction and degradation products in the environ-
ment.
(v) It may be necessary to conduct separate studies for metabolites,
degradation or reaction products, where these products can
constitute a relevant risk to non-target organisms or to the quality
of water, soil and air and where their effects cannot be evaluated
by the available results relating to the active substance. Before
such studies are performed the information from the Sections 5
and 6 has to be taken into account.
(vi) Where relevant, tests should be designed and data analysed using
appropriate statistical methods.
Full details of the statistical anaylsis should be reported (e.g. all
point estimates should be given with confidence intervals, exact
p-values should be given rather than stating significant/non
significant).
7.1.Fateandbehaviourinsoil
All relevant information on the type and the properties of the soil
used in the studies, including pH, organic carbon content, cation
exchange capacity, particle size distribution and water holding capa-
city, particle size distribution and water holding capacity at pF = 0
and pF = 2,5 has to be reported in accordance with relevant ISO or
other international standards.
The microbial biomass of soils used for laboratory degradation studies
must be determined just prior to the commencement and at the end of
the study.
It is recommended to use as muchas possible th e same soils
throughout all laboratory soil studies.
The soils used for degradation or mobility studies must be selected
such that they are representative of the range of soils typical of the
various Community regions where use exists or is anticipated, and
be suchth at:
— they cover a range of organic carbon content, particle size distri-
bution 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 — paragraphs 2.7 and 2.8), they cover the following pH
ranges:
— 4,5 to 5,5
— 6 to 7, and
— 8 (approximately).
Soils used must, wherever possible, be freshly sampled. If use of
stored soils is unavoidable, storage should be properly carried out for
a limited time under defined and reported conditions. Soils stored for
longer periods of time can only be used for adsorption/desorption
studies.1991L0414 — EN — 01.07.2003 — 009.001 — 64
▼M6
The soil chosen to begin studying should not have extreme character-
istics withrespect to parameters suchas particle size distribution,
organic carbon content and pH.
Soils should be collected and handled in accordance with ISO 10381-
6(Soil quality — Sampling — Guidance on the collection, handling
and storage of soil for the assessment of microbial processes in the
laboratory) . Any deviations must be reported and justified.
Field studies should be carried out in conditions as close to normal
agricultural practice as possible on a range of soil types and climatic
conditions representative of the area(s) of use. Weather conditions
shall be reported in cases where field studies are conducted.
7.1.1. Route and rate of degradation
7.1.1.1. Route of degradation
Aim of the tests
The data and information provided, together with other relevant data
and information, should be sufficient to:
— identify, where feasable, the relative importance of the types of
process involved (balance between chemical and biological degra-
dation),
— 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.
Where a reference is made to non-extractable residues these are
defined as chemical species originating from pesticides used
according to good agricultural practice that cannot be extracted by
methods which do not significantly change the chemical nature of
these residues. These non-extractable residues are not considered to
include fragments through metabolic pathways leading to natural
products.
7.1.1.1.1. Aerobic degradation
Circumstances in which required
The degradation pathway or pathways must always be reported except
where the nature and manner of use of preparations containing the
active substance, preclude soil contamination suchas uses on stored
products or wound healing treatments for trees.
Test conditions
The degradation pathway or pathways must be reported for one soil.Results obtained must be presented in the form of schematic drawings
showing the pathways involved, and in the form of balance sheets
which show the distribution of radio-label as a function of time, as
between:
— active substance,
—C O
2,
— volatile compounds other than CO2,
— individual identified transformation products,— extractable substances not identified, and— non-extractable residues in soil.
The investigation of degradation pathways must include all feasible
steps to characterise and quantify non-extractable residues formed
after 100 days when exceeding 70 % of the applied dose of the active
substance. The techniques and methodologies applied are best
selected on a case-by-case basis. A justification must be provided
where the compounds involved are not characterized.
The duration of the study is normally 120 days, except where after a
shorter period the levels of non-extractable residues and CO
2are such
that they can be extrapolated in a reliable way to 100 days.1991L0414 — EN — 01.07.2003 — 009.001 — 65
▼M6
Test guideline
Setac — Procedures for assessing the environmental fate and ecotoxi-
city of pesticides (1).
7.1.1.1.2. Supplementary studies
— Anaerobic degradation
Circumstances in which required
An anaerobic degradation study must be reported unless it can be
justified that exposure of the plant protection products containing
the active substance to anaerobic conditions is unlikely to occur.
Test conditions and test guideline
The same provisions as provided for under the corresponding
paragraphof point 7.1.1.1.1 apply.
— Soil photolysis
Circumstances in which required
A soil photolysis study must be reported unless it can be justified
that deposition of the active substance at the soil surface is unli-
kely to occur.
Test guideline
Setac — Procedures for assessing the Environmental fate and
ecotoxicity of pesticides.
7.1.1.2. Rate of degradation
7.1.1.2.1. Laboratory studies
Aim of the testsThe soil degradation studies should provide best possible estimates of
the time taken for degradation of 50 % and 90 % (DT
50laband DT90lab),
of the active substance, and of relevant metabolites, degradation and
reaction products under laboratory conditions.
— Aerobic degradation
Circumstances in which required
The rate of degradation in soil must always be reported, except
where the nature and manner of use of plant protection products
containing the active substance preclude soil contamination such
as uses on stored products or wound healing treatments for trees.
Test conditions
The rate of aerobic degradation of the active substance in three
soil types additional to that referred to in paragraph 7.1.1.1.1.
must be reported.
In order to investigate the influence of temperature on degrada-
tion, one additional study at 10 ºC has to be performed on one of
the soils used for the investigation of degradation at 20 ºC until a
validated Community calculation model for the extrapolation of
degradation rates at low temperatures is available.
The duration of the study is normally 120 days except if more
than 90 % of the active substance is degraded before that period
expires.
Similar studies for three soil types must be reported for all rele-
vant metabolites, degradation and reaction products which occur
in soil and which at any time during the studies account for
more than 10 % of the amount of active substance added, except
where their DT50values were able to be determined from the
results of the degradation studies with the active substance.
Test guideline
Setac — Procedures for assessing the environmental fate and
ecotoxicity of pesticides.
— Anaerobic degradation
Circumstances in which required
The rate of anaerobic degradation of the active substance must be
reported where an anaerobic study has to be performed according
to point 7.1.1.1.2.
Test conditions1991L0414 — EN — 01.07.2003 — 009.001 — 66
(1) Society of Environmental Toxicology and Chemistry (SETAC), 1995. Procedures for
assessing the environmental fate and ecotoxicity of pesticides, ISBN 90-5607-002-9.
▼M6
The rate of anaerobic degradation of the active substance must be
carried out in the soil used in the anaerobic study performed
according to point 7.1.1.1.2.
The duration of the study is normally 120 days except if more
than 90 % of the active substance is degraded before that period
expires.
Similar studies for one soil must be reported for all relevant meto-
bolites, degradation and reaction products which occur in soil and
which at any time during the studies account for more than 10 %
of the amount of active substance added, except where their DT50values were able to be determined from the results of the degrada-tion studies withth e active substance.
Test guideline
Setac — Procedures for assessing the environmental fate and
ecotoxicity of pesticides.
7.1.1.2.2. Field studies
— Soil dissipation studies
Aim of the test
The soil dissipation studies should provide estimates of the time
taken for dissipation of 50 % and 90 % (DT
50fand DT90f), of the
active substance under field conditions. Where relevant, informa-
tion on relevant metabolites, degradation and reaction products
must be reported.
Circumstances in which requiredThe tests have to be conducted in those conditions where DT
50labdetermined at 20 ºC and at a moisture content of the soil related
to a pF value of 2 to 2,5 (suction pressure) is greater than 60 days.
Where plant protection products containing the active substance
are intended to be used in cold climatic conditions, the tests have
to be conducted where DT50lab, determined at 10 ºC and at a
moisture content of the soil related to a pF value of 2 to 2,5
(suction pressure) is greater than 90 days.
Test conditions
Individual studies on a range of representative soils (normally four
different types) must be continued until > 90 % of the amount
applied have dissipated. The maximum duration of the studies is
24 months.
Test guideline
SETAC — Procedures for assessing the environmental fate and
ecotoxicity of pesticides.
— Soil residue studies
Aim of the test
Soil residue studies should provide estimates of the soil residue
levels at harvest or at time of cowing or planting succeeding
crops.
Circumstances in which required
Soil residue studies must be reported where DT50labis greater than
one-third of the period between the application and harvest and
where absorption by the succeeding crop is possible, except where
soil residues at sowing or planting of a succeeding crop can be
reliably estimated from the data of the soil dissipation studies or
where it can be justified that these residues can not be phytotoxic
to or leave unacceptable residues in rotational crops.
Test conditions
Individual studies must be continued until harvest or time of
sowing or planting succeeding crops, unless > 90 % of the amount
applied have dissipated.
Test guidelineSETAC — Procedures for assessing the environmental fate and
ecotoxicity of pesticides.
— Soil accumulation studies
Aim of the tests
The tests should provide sufficient data to evaluate the possibility
of accumulation of residues of the active substance and of relevant
metabolites, degradation and reaction products.
Circumstances in which required
Where on the basis of soil dissipation studies it is established that
DT
90f> one year and where repeated application is envisaged,
whether in the same growing season or in succeeding years, the
possibility of accumulation of residues in soil and the level at1991L0414 — EN — 01.07.2003 — 009.001 — 67
▼M6
which a plateau concentration is achieved must be investigated
except where reliable information can be provided by a model
calculation or another appropriate assessment.
Test conditions
Long term field studies must be done on two relevant soils and
involve multiple applications.
Before performing these studies the applicant shall seek the agree-
ment of the competent authorities on the type of study to be
performed.
7.1.2. Adsorption and desorption
Aim of the test
The data and information provided, together with other relevant data
and information, should be sufficient to establish the absorption coef-
ficient of the active substance and of relevant metabolites,
degradation and reaction products.
Circumstances in which required
The studies must always be reported except where the nature and
manner of use of preparations containing the active substance,
preclude soil contamination suchas uses on stored products or wound
healing trees.
Testo conditions
Studies on the active substance must be reported for four soil types.Similar studies, for at least three soil types, must be reported for all
relevant metabolites, degradation and reaction products which in soil
degradation studies account at any time for more than 10 % of the
amount of active substance added.
Test guidelineOECD method 106
7.1.3. Mobility in the soil
7.1.3.1. Column leaching studies
Aim of the test
The test should provide sufficient data to evaluate the mobility and
leaching potential of the active substance and if possible of relevant
metabolities, degradation and reaction products.
Circumstances in which requiredStudies in four soils must be carried out where in the absorption and
desorption studies provided for under point 7.1.2 it is not possible to
obtain reliable absorption coefficient values.
Test guideline
SETAC — Procedures for assessing the environmental fate and
ecotoxicity of pesticides.
7.1.3.2. Aged residue column leaching
Aim of the testThe test should provide sufficient data to estimate the mobility and
leaching potential of relevant metabolites, degradation and reaction
products.
Circumstances in which required
The studies must be performed except:
— where the nature and manner of use of preparations containing the
active substance, preclude soil contamination suchas uses on
stored products or wound healing treatments for trees, or
— where a separate study for the metabolite, degradation or reaction
product in accordance to point 7.1.2 or 7.1.3.1 was performed.
Test conditions
The period(s) of ageing should be determined from inspection of the
degradation patterns of active substance and metabolites to ensure that
a relevant spectrum of metabolites is present at the time of leaching.1991L0414 — EN — 01.07.2003 — 009.001 — 68
▼M6
Test guideline
SETAC — Procedures for assessing the environmental fate and
ecotoxicity of pesticides.
7.1.3.3. Lysimeter studies or field leaching studies
Aim of the testsThe test should provide data on:
— the mobility in soil,
— the potential for leaching to ground water,
— The potential distribution in soil.
Circumstances in which requriedExpert judgement will be necessary to decide whether lysimeter
studies or field leaching studies should be carried out, taking into
account the results of degradation and other mobility studies and the
predicted environmental concentrations in groundwater (PEC
GW),
calculated in accordance withth e provisions of Annex III, Section 9.
The type and conditions of the study to be conducted should be
discussed with the competent authorities.
Test conditions
Great care is necessary in design of bothexperimental installations
and individual studies, to ensure that results obtained can be used for
assessment purposes. Studies should cover the realistic worst case
situation, taking into account the soil type, climatic conditions, the
application rate and the frequency and period of application.
Water percolating from soil columns must be analyzed at suitable
intervals, while residues in plant material must be determined at
harvest. Residues in the soil profile in at least five layers must be
determined on termination of experimental work. Intermediate
sampling must be avoided, since removal of plants (except for
harvesting according to normal agricultural practice) and soil cross
influences the leaching process.
Precipitation, soil and air temperatures have to be recorded at regular
intervals (at least on a weekly base).
—Lysimeter studies
Test conditions
The minimal depth of the lysimeters should be 100 cm; their
maximal depth should be 130 cm. The soil cross must be undis-
turbed. Soil temperatures must be similar to those pertaining in
the field. Where necessary, supplementary irrigation must be
provided to ensure optimal plant growth and to ensure that the
quantity of infiltration water is similar to that in the regions for
which authorization is sought. When during the study the soil has
to be disturbed for agricultural reasons it must not be disturbed
deeper than 25 cm.
— Field leaching studies
Test conditions
Information on the groundwater table in the experimental fields
must be submitted. If soil cracking is observed during the study
this must be fully described.
Great attention should be given to the number and the location of
water collection devices. The placement of these devices in the
soil should not result in preferential flow paths.
Test guidelineSETAC — Procedures for assessing the environmental fate and
ecotoxicity of pesticides.
7.2.Fateandbehaviourinwaterandair
Aim of the tests
The information and data provided, taken together with that provided
for one or more preparations containing the active substance, and
other relevant information, should be sufficient to establish, or permit
estimation of:
— 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.1991L0414 — EN — 01.07.2003 — 009.001 — 69
▼M6
7.2.1. Route and rate of degradation in aquatic systemes (as far as not
covered by point 2.9)
Aim of the testsThe data and information provided, together with other relevant data
and information, should be sufficient to:
— 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.
7.2.1.1. Hydrolytic degradation
Circumstances in which required
The test must always be performed for relevant metabolites, degrada-
tion and reaction products which account at any time for more than
10 % of the amount of active substance added unless sufficient infor-
mation on their degradation is available from the test performed in
accordance withpoint 2.9.1.
Test conditions and test guidelineThe same provisions as provided under the corresponding paragraphs
of point 2.9.1 apply.
7.2.1.2. Photochemical degradation
Circumstances in which requiredThe test must always be performed for relevant metabolites, degrada-
tion and reaction products which account at any time for more than
10 % of the amount of active substance added unless sufficient infor-
mation on their degradation is available from the test performed in
accordance withpoints 2.9.2 and 2.9.3.
Test conditions and test guidelineThe same provisions as provided under the corresponding paragraphs
of points 2.9.2 and 2.9.3 apply.
7.2.1.3. Biological degradation7.2.1.3.1. ‘Ready biodegradability’
Circumstances in which requiredThe test must always be performed unless it is not required under the
provisions of Annex VI to Directive 67/548/EEC for the classification
of the active substance.
Test guidelineEEC method C4.
7.2.1.3.2. Water/sediment study
Circumstances in which requiredThe test must be reported unless it can be justified that contamination
of surface water will not occur.
Test guidelineSETAC — Procedures for assessing the environmental fate and
ecotoxicity of pesticides.
7.2.1.4. Degradation in the saturated zone
Circumstances in which requiredTransformation rates in the saturated zone of active substances and of
relevant metabolites, degradation and reaction products can provide
useful information on the fate of these substances in the groundwater.
Test conditionsExpert judgement is required to decide whether this information is
necessary. Before performing these studies the applicant shall seek1991L0414 — EN — 01.07.2003 — 009.001 — 70
▼M6
the agreement of the competent authorities on the type of study to be
performed.
7.2.2. Route and rate of degradation in air (as far as not covered by point
2.10)
Guidance under development.
7.3.Definitionoftheresidue
In the light of the chemical composition of residues occurring in soil,
water or air, resulting from use, or proposed use, of a plant protection
product containing the active substance a proposal for the definition
of the residue must be submitted, taking account of both the levels
found and their toxicological and environmental significance.
7.4.Monitoringdata
Available monitoring data concerning fate and behaviour of the active
substance and relevant metabolites, degradation and reaction products
must be reported.
8.Ecotoxicological studies
Introduction
(i) The information provided, taken together with that for one or
more preparations containing the active substance, must be suffi-
cient to permit an assessment of the impact on non-target species
(flora and fauna), likely to be at risk from exposure to the active
substance, its metabolites, degradation and reaction products,
where they are of environmental significance. Impact can result
from single, prolonged or repeated exposure and can be rever-
sible or irreversible.
(ii) In particular, the information provided for the active substance,
together with other relevant information, and that provided for
one or more preparations containing it, should be sufficient to:
— decide whether, or not, the active substance can be included
in Annex I,
— specify appropriate conditions or restrictions to be associated
withany inclusion in Annex I,
— 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 hazard symbols, the indications of danger, and
relevant risk and safety phrases for the protection of the
environment, to be mentioned on packaging (containers).
(iii) There is a need to report all potentially adverse effects found
during routine ecotoxicological investigations and to undertake
and report, where required by the competent authorities, such
additional studies which may be necessary to investigate the
probable mechanisms involved and assess the significance of
these effects. All available biological data and information which
is relevant to the assessment of the ecotoxicological profile of
the active substance must be reported.
(iv) The information on fate and behaviour in the environment,
generated and submitted in accordance withpoints 7.1 to 7.4,
and on residue levels in plants generated and submitted in accor-
dance withpoint 6 is central to th e assessment of impact on non-
target species, in that together with information on the nature of
the preparation and its manner of use, it defines the nature and
extent of potential exposure. The toxicokinetic and toxicological
studies and information submitted in accordance withpoints 5.1
to 5.8 provide essential information as to toxicity to vertebrate
species and the mechanisms involved.
(v) Where relevant, tests should be designed and data analysed using
appropriate statistical methods. Full details of the statistical
analysis should be reported (e. g. all point estimates should be
given withconfidence intervals, exact p-values sh ould be given
rather than stating significant/non significant).1991L0414 — EN — 01.07.2003 — 009.001 — 71
▼M7
▼M7
Testsubstance
(vi) A detailed description (specification) of the material used, as
provided for under point 1.11 must be provided. Where testing
is done using active substance the material used should be of
that specification that will be used in the manufacture of
preparations to be authorized except where radiolabelled mate-
rial is used.
(vii) Where studies are conducted using active substance produced in
the laboratory or in a pilot plant production system, the studies
must be repeated using active substance as manufactured,
unless it can be justified that the test material used is essentially
the same, for the purposes of ecotoxicological testing and
assessment. In cases of uncertainty, appropriate bridging studies
must be submitted to serve as a basis for a decision as to the
possible need for repetition of the studies.
(viii) In the case of studies in which dosing extends over a period,
dosing should preferably be done using a single batch of active
substance if stability permits.
Whenever a study implies the use of different doses, the rela-
tionship between dose and adverse effect must be reported.
(ix) For all feeding studies, average achieved dose must be reported,
including where possible the dose in mg/kg body weight.
Where dosing via the diet is utilized the test compound must
be distributed uniformly in the diet.
(x) It may be necessary to conduct separate studies for metabolites,
degradation or reaction products, where these products can
constitute a relevant risk to non-target organisms and where
their effects cannot be evaluated by the available results relating
to the active substance. Before such studies are performed the
information from points 5, 6 and 7 has to be taken into account.
Testorganisms
(xi) In order to facilitate the assessment of the significance of test
results obtained, including the estimation of intrinsic toxicity
and the factors affecting toxicity, the same strain (or recorded
origin) of each relevant species should, where possible, be used
in the various toxicity tests specified.
8.1.Effectsonbirds
8.1.1. Acute oral toxicity
Aim of the test
The test should provide, where possible, LD50values, the lethal
threshold dose, time courses of response and recovery and the
NOEL, and must include relevant gross pathological findings.
Circumstances in which requiredThe possible effects of the active substance on birds must be investi-
gated except where the active substance is intended solely to be
included in preparations for exclusive use in enclosed spaces (e.g. inglasshouses or in food storage practice).
Test conditionsThe acute oral toxicity of active substance to a quail species (Japa-
nese quail (Coturnix coturnix japonica) or Bobwhite quail (Colinus
virginianus) or to mallard duck (Anas platyrhynchos) must be deter-
mined. The highest dose used in tests need not exceed 2 000 mg/kg
body weight.
Test guidelineSetac — Procedures for assessing the environmental fate and ecotoxi-
city of pesticides (
1).
8.1.2. Short-term dietary toxicity
Aim of the testThe test should provide the short term dietary toxicity (LC
50values,
lowest lethal concentration (LLC), where possible no observed effect1991L0414 — EN — 01.07.2003 — 009.001 — 72
(1) Society of Environmental Toxicology and Chemistry (Setac), 1995. Procedures for
Assessing the Environmental Fate and Ecotoxicity of Pesticides, ISBN 90-5607-002-9.
▼M7
concentrations (NOEC), time courses of response and recovery) and
include relevant gross pathological findings.
Circumstances in which required
The dietary (five-day) toxicity of the active substance to birds must
always be investigated on one species except where a study in accor-
dance with the provisions of point 8.1.3 is reported. Where its acute
oral NOEL is ≤500 mg/kg body weight or where the short-term
NOEC < 500 mg/kg food the test must be performed on a second
species.
Test conditions
The first species to be studied must be either a quail species or
mallard duck. If a second species must be tested it should not be
related to the first species tested.
Test guideline
The test must be carried out in accordance with OECD Method 205.
8.1.3. Subchronic toxicity and reproduction
Aim of the test
The test should provide the subchronic toxicity and reproductive toxi-
city of the active substance to birds.
Circumstances in which required
The subchronic and reproductive toxicity of the active substance to
birds must be investigated, unless it can be justified that continued
or repeated exposure of adults, or exposure of nest sites during the
breeding season is unlikely to occur.
Test guideline
The test must be carried out in accordance with OECD Method 206.
8.2.Effectsonaquaticorganisms
The data of the tests referred to in points 8.2.1, 8.2.4 and 8.2.6 have
to be submitted for every active substance even when it is not
expected that plant protection products containing it could reach
surface water following the proposed conditions of use. These data
are required under the provisions of Annex VI to Directive 67/548/
EEC for the classification of the active substance.
Data reported must be supported withanalytical data on concentra-
tions of the test substance in the test media.
8.2.1. Acute toxicity to fish
Aim of the test
The test should provide the acute toxicity (LC50), and details of
observed effects.
Circumstances in which required
The test must always be carried out.
Test conditions
The acute toxicity of the active substance must be determined for
rainbow trout (Oncorhynchus mykiss) and for a warm water fish
species. Where tests with metabolites, degradation or reaction
products have to be performed the species used must be the more
sensitive of the two species tested with the active substance.
Test guideline
The test must be carried out in accordance with the Annex to
Commission Directive 92/69/EEC (1) adapting to technical progress
for the 17th time Directive 67/548/EEC on the approximation of
laws, regulations and administrative provisions relating to the classifi-
cation and labelling of dangerous, substances, Method C1.
8.2.2. Chronic toxicity to fish1991L0414 — EN — 01.07.2003 — 009.001 — 73
(1) OJ No L 383, 29. 12. 1992, p. 113.
▼M7
Circumstances in which required
A chronic toxicity study must be carried out unless it can be justified
that continued or repeated exposure of fish is unlikely to occur or
unless a suitable microsom or mesocosm study is available.
Expert judgment is required to decide which test has to be performed.
In particular for active substance for which there are indications of
particular concerns (related to the toxicity of the active substance for
fish or the potential exposure) the applicant shall seek the agreement
of the competent authorities on the type of test to be performed.
A fish early life stage toxicity test might be appropriate where
bioconcentration factors (BCF) are between 100 and 1 000 or where
EC50of the active substance < 0,1 mg/l.
A fish life cycle test might be appropriate in cases where
— the bioconcentration factor is greater tan 1 000 and the elimination
of the active substance during a depuration phase of 14 days is
lower than 95 %,
or
— the substance is stable in water or sediment (DT90> 100 days).
It is not necessary to perform a chronic toxicity test on juvenile fish
wh en a fishearly life stage toxicity test or a fishlife cycle test h as
been performed; it is likewise not necessary to perform a fishearly
life stage toxicity test when a fish life cycle test has been performed.
8.2.2.1. Chronic toxicity test on juvenile fish
Aim of the testThe test should provide effects on growth, the threshold level for
lethal effects and for observed effects, the NOEC and details of
observed effects.
Test conditions
The test must be conducted on juvenile rainbow trout, following
exposure of 28 days to the active substance. Data on the effects on
growthand beh aviour must be generated.
8.2.2.2. Fishearly life stage toxicity test
Aim of the testThe test should provide effects on development, growth and beha-
viour, the NOEC and details of observed effects on fish early life
stages.
Test guidelineThe test must be carried out in accordance with OECD Method 210.
8.2.2.3. Fishlife cycle test
Aim of the testThe test will provide effects on reproduction of the parental and the
viability of the filial generation.
Test conditionsBefore performing these studies the applicant shall seek the agree-
ment of the competent authorities on the type and conditions of the
study to be performed.
8.2.3. Bioconcentration in fish
Aim of the testThe test should provide the steady-state bioconcentration factors,
uptake rate constants and depuration rate constants, calculated for
eachtest compound, as well as relevant confidence limits.
Circumstances in which requiredThe bioconcentration potential of active substances, of metabolites
and of degradation and reaction products, likely to partition into fatty
tissues (suchas log p
ow≥3 — see point 2.8 or other relevant indica-
tions of bioconcentration), must be investigated and be reported,
unless it can be justified that exposure leading to bioconcentration is
not likely to occur.1991L0414 — EN — 01.07.2003 — 009.001 — 74
▼M7
Test guideline
The test must be carried out in accordance with OECD Method 305E.
8.2.4. Acute toxicity to aquatic invertebrates
Aim of the testThe test should provide the 24 and 48-hour acute toxicity of the
active substance, expressed as the median effective concentration
(EC
50) for immobilization, and where possible the highest concentra-
tion causing no immobilization.
Circumstances in which required
The acute toxicity must always be determined for Daphnia (prefer-
ablyDaphnia magna) . Where plant protection products containing
the active substance are intended to be used directly on surface water
additional data have to be reported on at least one representative
species from eachof th e following groups: aquatic insects, aqautic
crustaceans (on a species not related to Daphnia) and aquatic
gastropod molluscs.
Test guidelineThe test must be carried out in accordance with Directive 92/69/EEC,
Method C2.
8.2.5. Chronic toxicity to aquatic invertebrates
Aim of the testThe test should provide where possible EC
50values for effects suchas
immobilization and reproduction and the highest concentration at
which no effect such as on martality or reproduction occurs (NOEC)
and details of observed effects.
Circumstances in which requiredA test on Daphnia and on at least one representative aquatic insect
species and an aquatic gastropod mollusc species must be carried out
unless it can be justified that continued or repeated exposure is notlikely to occur.
Test conditionsThe test with Daphnia must be continued for 21 days.
Test guidelineThe test must be carried out in accordance with OECD Method 202,
Part II.
8.2.6. Effects on algal growth
Aim of the testThe test should procide EC
50values for growthand growthrate,
NOEC values, and details of observed effects.
Circumstances in which requiredPossible effects on algal growthof active substances must always be
reported.
For herbicides a test on a second species from a different taxonomic
group has to be performed.
Test guidelineThe test must be carried out in accordance with Directive 92/69/EEC,
Method C3.
8.2.7. Effects on sediment dwelling organisms
Aim of testThe test will measure effects on survival and development (including
effects on emergence of adults for Chironomus), the relevant EC
50values and the NOEC values.
Circumstances in which requiredWhere environmental fate and behaviour data required in point 7
report that an active substance is likely to partition to and persist in
aquatic sediments, expert judgement should be used to decide whether
an acute or a chronic sediment toxicity test in required. Such expert1991L0414 — EN — 01.07.2003 — 009.001 — 75
▼M7
judgement should take into account whether effects on sediment
dwelling invertebrates are likely by comparing the aquatic inverte-
brate toxicity EC50data from points 8.2.4 and 8.2.5 withth e
predicted levels of the active substances in sediment from data in
Annex III, point 9.
Test conditionsBefore performing these studies the applicant shall seek the agree-
ment of the competent authorities on the type and conditions of the
study to be performed.
8.2.8. Aquatic plants
A test on aquatic plants has to be performed for herbicides.
Before performing these studies the applicant shall seek the agree-
ment of the competent authorities on the type and conditions of the
study to be performed.
8.3.Effectonarthropods
8.3.1. Bees
8.3.1.1. Acute toxicity
Aim of the testThe test should provide the acute oral and contact LD
50value of the
active substance.
Circumstances in which requiredPotential impact on bees must be investigated, except where prepara-
tions containing the active substance are for exclusive use in
situations where bees are not likely to be exposed such as:
— 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.
Test guideline
The test must be carried out in accordance with EPPO Guideline 170.
8.3.1.2. Bee brood feeding test
Aim of the testThe test should provide sufficient information to evaluate possible
risks from the plant protection product on honeybee larvae.
Circumstances in which requiredThe test must be carried out when the active substance may act as an
insect growthregulator unless it can be justified th at it is not likely
that bee brood would be exposed to it.
Test guideline
The test must be carried out in accordance with ICPBR Method (e.g.
P. A. Oomen, A. de Riujter and J. van der Steen. Method for
honeybee brood feeding tests with insect growth-regulating insecti-
cides.EPPO Bulletin, Volume 22, pp 613 to 616, 1992.)
8.3.2. Other arethropods
Aim of the testThe test should provide sufficient information to evaluate the toxicity
(mortality and sublethal effects) of the active substance to selected
arthropod species.
Circumstances in which required
Effects on non-target terrestrial arthropods (e.g. predators or parasi-
toids of harmful organisms) must be investigated. The information
obtained for these species can also be used to indicate the potential
for toxicity to other non-target species inhabiting the same environ-
ment. This information is required for all active substances except1991L0414 — EN — 01.07.2003 — 009.001 — 76
▼M7
where preparations containing the active substance are for exclusive
use in situations where non-target arthropods are not exposed such as:
— food storage in enclosed spaces,
— wound sealing and healing treatments,— rodenticidal baits.
Test conditionsThe test must be performed initially in the laboratory on an artificial
substrate (i.e. glass plate or quartz sand, as appropriate) unless
adverse effects can be clearly predicted from other studies. In these
cases, more realistic substrates may be used.
Two sensitive standard species, a parasitoid and predatory mite (e.g.
Aphidius rhopalosiphi andTyphlodromus pyri) should be tested. In
addition to these, two additional species must also be tested, which
should be relevant to the intended use of the substance. Where
possible and if appropriate, they should represent the other two majorfunctional groups, ground dwelling predators and foliage dwelling
predators. Where effects are observed with species relevant to the
proposed use of the product, further testing may be carried out at the
extended laboratory/semi-field level. Selection of the relevant test
species should follow the proposals outlined in Setac — Guidance
document on regulatory testing procedures for pesticides withnon-
target arthropods(
1). Testing must be conducted at rates equivalent
to the highest rate of field application to be recommended.
Test guidelineWhere relevant, testing should be done according to appropriate
guidelines which satisfy at least the requirements for testing as
included in Setac — Guidance document on regulatory testing proce-
dures for pesticides withnon-target arth ropods.
8.4.Effectsonearthworms
8.4.1. Acute toxicity
Aim of the testThe test should provide the LC
50value of the active substance to
earthworms, where possible the highest concentration causing no
mortality and the lowest concentration causing 100 % mortality, and
must include observed morphological and behavioural effects.
Circumstances in which requiredEffects on earthworms must be investigated, where preparations
containing the active substance are applied to soil, or can contaminate
soil.
Test guidelineThe test must be carried out in accordance with Commission Direc-
tive 88/302/EEC (
2) adapting to technical progress for the ninth time
Council Directive 67/548/EEC on the approximation of laws, regula-tions and administrative provisions relating to the classification,
packaging and labelling of dangerous substances, Part C, Toxicity
for earthworms: Artificial soil test.
8.4.2. Sublethal effects
Aim of the testThe test should provide the NOEC and the effects on growth, repro-
duction and behaviour.
Circumstances in which required
Where on the basis of the proposed manner of use of preparations
containing the active substance or on the basis of its fate and beha-
viour in soil (DT
90> 100 days), continued or repeated exposure of
earthworms to the active substance, or to significant quantities of
metabolites, degradation or reaction products, can be anticipated
expert judgement is required to decide whether a sublethal test can
be useful.1991L0414 — EN — 01.07.2003 — 009.001 — 77
(1) From the Workshop European Standard Characteristics of beneficials Regulatory
Testing (Escort), 28 to 30 March1994, ISBN 0-95-22535-2-6.
(2) OJ No L 133, 30. 5. 1988, p. 1.
▼M7
Test conditions
The test must be carried out on Eisenia foetida.
8.5.Effectsonsoilnon-targetmicro-organisms
Aim of the test
The test should provide sufficient data to evaluate the impact of the
active substance on soil microbial activity, in terms of nitrogen trans-
formation and carbon mineralization.
Circumstances in which required
The test must be carried out where preparations containing the active
substance are applied to soil or can contaminate soil under practical
conditions of use. In the case of active substances intended for use
in preparations for soil sterilization, the studies must be designed to
measure rates of recovery following treatment.
Test conditions
Soils used must be freshly sampled agricultural soils. The sites from
which soil is taken must not have been treated during the previous
two years with any substance that could substantially alter the diver-
sity and levels of microbial populations present, other than in a
transitory manner.
Test guideline
Setac — Procedures for assessing the environmental fate and ecotoxi-
city of pesticides.
8.6.Effects on other non-target organisms (flora and fauna) believed
tobeatrisk
A summary of available data from preliminary tests used to assess the
biological activity and dose range finding, whether positive or nega-
tive, which may provide information with respect to possible impact
on other non-target species, both flora and fauna, must be provided,
together with a critical assessment as to its relevance to potential
impact on non-target species.
8.7.Effectsonbiological methodsforsewagetreatment
Effects on biological methods for sewage treatment must be reported
where the use of plant protection products containing the active
substance can give rise to adverse effects on sewage treatment plants.
9. Summary and evaluation of points 7 and 8
10. Proposals including justification for the proposals for the classifica-
tion and labelling of the active substance according to Council
Directive 67/548/EEC
— Hazard symbol(s)
— Indications of danger— Risk phrases
— Safety phrases
11. A dossier as referred to in Annex III, part A, for a representative
plant protection product
PART B
Introduction
(i) Active substances are defined in Article 2(4) and include chemical
substances and micro-organisms including viruses.
This Part provides data requirements for active substances consisting of
micro-organisms, including viruses.1991L0414 — EN — 01.07.2003 — 009.001 — 78
▼B
▼M25
▼M25
For the purposes of Annex II, Part B, the term ‘micro-organism’ is used
and is defined as follows: ‘A microbiological entity, cellular or non-
cellular, capable of replication or of transferring genetic material’.
The definition applies to, but is not limited to, bacteria, fungi, protozoa,
viruses and viroids.
(ii) For all micro-organisms that are subject to application all available rele-
vant knowledge and information in literature should be provided.
The most important and informative information is obtained by the char-
acterisation and identification of a micro-organism. Suchinformation is
found in sections 1 to 3 (identity, biological properties and further infor-
mation) which form the basis for an assessment of human health and
environmental effects.
Newly generated data from conventional toxicological and/or pathological
experiments on laboratory animals are normally required unless the appli-
cant can justify, on the basis of the previous information, that the use of
the micro-organism, under the proposed conditions of use, does not have
any harmful effects on human and animal health or on groundwater or any
unacceptable influence on the environment.
(iii) Pending the acceptance of specific guidelines at international level, the
information required shall be generated using available test guidelines
accepted by the competent authority (e.g. USEPA guideline (1)); where
appropriate test guidelines as described in Annex II, Part A, should be
adapted in such a way that they are appropriate for micro-organisms.
Testing should include viable and, if appropriate, non-viable micro-organ-
isms, and a blank control.
(iv) Where testing is done, a detailed description (specification) of the material
used and its impurities, according to the provisions of section 1, point 1.4,
must be provided. The material used should be of that specification that
will be used in the manufacture of preparations to be authorised.
Where studies are conducted using micro-organisms produced in the
laboratory or in a pilot plant production system, the studies must be
repeated using micro-organisms as manufactured, unless it can be demon-
strated that the test material used is essentially the same for the purposes
of the testing and assessment.
(v) Where the micro-organism has been genetically modified, as defined in
Council Directive 90/220/EEC of 23 April 1990 on the deliberate release
into the environment of genetically modified organisms (2), a copy of the
evaluation of the data concerning the assessment of risk to the environ-
ment, as stated in Article 1(3) of Directive 91/414/EEC, has to be
submitted.
(vi) Where relevant, data should be analysed using appropriate statistical
methods. Full details of the statistical analysis should be reported (e.g.
all point estimates should be given with confidence intervals, exact p-
values should be given rather than stating significant/non significant).
(vii) In the case of studies in which dosing extends over a period, dosing
should preferably be done using a single batch of the micro-organism, if
stability permits.
If the studies are not performed using a single batch of the micro-
organism, the similarity of the different batches has to be stated.
Whenever a study implies the use of different doses, the relationship
between dose and adverse effect must be reported.
(viii) If the plant protection action is known to be due to the residual effect of a
toxin/metabolite or if significant residues of toxins/metabolites are to be
expected not related to the effect of the active substance, a dossier for
the toxin/metabolite has to be submitted in accordance with the require-
ments of Annex II, Part A.
1. IDENTITY OF THE MICRO-ORGANISM
The identification together with the characterisation of the micro-
organism provides the most important information and is a key point
for decision-making.
1.1.Applicant
The name and address of the applicant (permanent community
address) must be provided, as must the name, position, telephone
and fax number of the appropriate person to contact.1991L0414 — EN — 01.07.2003 — 009.001 — 79
(1)USEPA Microbial Pesticide Test Guidelines, OPPTS Series 885, February 1996
(http://www.epa.gov/oppbppd1/biopesticides/guidelines/series885.htm).
(2) OJ L 117, 8.5.1990, p. 15.
▼M25
Where, in addition, the applicant has an office, agent or representative
in the Member State to which the application for inclusion in Annex I
is submitted, and if different, in the rapporteur Member State
appointed by the Commission, the name and address of the local
office, agent or representative must be provided, as must the name,
position, telephone and fax number of the appropriate person to
contact.
1.2.Producer
The name and address of the producer or producers of the micro-
organism must be provided as must the name and address of each
plant in which the micro-organism is produced. A contact point
(preferably a central contact point, to include name, telephone and
fax number) must be provided, witha view to providing updating
information and responding to queries arising, regarding production
technology, processes and the quality of product (including where
relevant, individual batches). Where, following inclusion of the
micro-organism in Annex I, there are changes in the location or
number of producers, the information required must again be notified
to the Commission and the Member States.
1.3.Nameandspeciesdescription,straincharacterisation
(i) The micro-organism should be deposited at an internationally
recognised culture collection and given an accession number and
these details must be submitted.
(ii) Each micro-organism that is subject to the application should be
identified and named at the species level. The scientific name and
taxonomic grouping, i.e. family, genus, species, strain, serotype,
pathovar or any other denomination relevant to the micro-
organism, must be stated.
It must be indicated whether the micro-organism:
— 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 Annex IA,
Part 2, and Annex IB to Directive 90/220/EEC.
In the latter two cases, all known differences between the modi-
fied micro-organism and the parent wild strain must be provided.
iii) Best available technology should be used to identify and charac-
terise the micro-organism at the strain level. The appropriate test
procedures and criteria used for identification (e.g. morphology,
biochemistry, serology, molecular identification) must be
provided.
iv) Common name or alternative and superseded names and code
names used during the development, if any, must be provided.
(v) Relationships to known pathogens should be indicated.
1.4.Specification of the material used for manufacturing of formu-
latedproducts
1.4.1. Content of the micro-organism
The minimum and maximum content of the micro-organism in the
material used for manufacturing of formulated products, must be
reported. The content should be expressed in appropriate terms, such
as number of active units per volume or weight or any other manner
that is relevant to the micro-organism.
Where the information provided relates to a pilot plant production
system, the information required must again be provided to the
Commission and the Member States once industrial scale production
methods and procedures have stabilised, if production changes result
in a changed specification of purity.
1.4.2. Identity and content of impurities, additives, contaminating micro-
organisms
It is desirable to have a plant protection product without contaminants
(including contaminating micro-organisms), if possible. The level and
nature of acceptable contaminants should be judged from a risk
assessment point of view, by the competent authority.1991L0414 — EN — 01.07.2003 — 009.001 — 80
▼M25
If possible and appropriate, the identity and maximum content of all
contaminating micro-organisms, expressed in the appropriate unit,
must be reported. The information on identity must be provided
where possible as outlined in Annex II, Part B, section1, point 1.3.
Relevant metabolites (i.e. if expected to be of concern to human
health and/or the environment) known to be formed by the micro-
organism should be identified and characterised at different states or
growthstages of th e micro-organism (see Annex IIB, Introduction,
(viii)).
Where relevant detailed information on all components such as
condensates, culture medium, etc. must be provided.
In the case of chemical impurities that are relevant for human health
and/or the environment, the identity and maximum content, expressed
in appropriate terms, must be provided.
In the case of additives, the identity and content in g/kg must be
provided.
The information on identity of chemical substances such as additives
must be provided as outlined in Annex II, Part A, section 1, point
1.10.
1.4.3. Analytical profile of batches
Where relevant, the same data as outlined in Annex II, Part A, section
1, point 1.11, have to be reported, using the appropriate units.
2. BIOLOGICAL PROPERTIES OF THE MICRO-ORGANISM2.1.History of the micro-organism and its uses. Natural occurrence
andgeographicaldistribution
Familiarity, interpreted as the availability of relevant knowledge of
the micro-organism, should be presented.
2.1.1. Historical background
The historical background of the micro-organism and its use (tests/
researchprojects or commercial use) must be provided.
2.1.2. Origin and natural occurrence
The geographical region and the place in the ecosystem (e.g. host
plant, host animal, or soil from which the micro-organism was
isolated) must be stated. The method of isolation of the micro-
organism should be reported. The natural occurrence of the micro-organism in the relevant environment shall be given if possible at
strain level.
In the case of a mutant, or a genetically modified micro-organism (as
defined in Annex IA, Part 2, and Annex IB to Directive 90/220/EEC),
detailed information should be provided on its production and isola-
tion and on the means by which it can be clearly distinguished from
the parent wild strain.
2.2.Informationontargetorganism(s)
2.2.1. Description of the target organism(s)
Where relevant, details of harmful organisms against which protection
is afforded, must be provided.
2.2.2. Mode of action
The principal mode of action should be indicated. In connection with
the mode of action it should also be stated if the micro-organism
produces a toxin witha residual effect on th e target organism. In
that case, the mode of action of this toxin should be described.
If relevant, information on the site of infection and mode of entry into
the target organism and its susceptible stages should be given. The
results of any experimental studies must be reported.
It should be stated by which way an uptake of the micro-organism, or
its metabolites (especially toxins) may occur (e.g. contact, stomach,
inhalation). It must also be stated whether or not the micro-organism1991L0414 — EN — 01.07.2003 — 009.001 — 81
▼M25
or its metabolites are translocated in plants and, where relevant, how
this translocation takes place.
In case of pathogenic effect on the target organism, infective dose
(the dose needed to cause infection with the intended effect on a
target species) and transmissibility (possibility of spread of the
micro-organism in the target population, but also from one target
species to another (target) species) after application under the
proposed condition of use shall be indicated.
2.3.Hostspecificity range andeffects onspeciesother thanthe target
harmfulorganism
Any available information on the effects on non-target organisms
within the area to which the micro-organism may spread shall be
given. The occurrence of non-target organisms being either closely
related to the target species or being especially exposed shall be indi-
cated.
Any experience of the toxic effect of the active substance or its meta-
bolic products on humans or animals, of whether the organism is
capable of colonising or invading humans or animals (including
immunosuppressed individuals) and whether it is pathogenic shall be
stated. Any experience of whether the active substance or its products
may irritate skin, eyes or respiratory organs of humans or animals and
whether it is allergenic in contact with skin or when inhaled shall be
stated.
2.4.Developmentstages/lifecycle ofthemicro-organism
Information on the life cycle of the micro-organism, described
symbiosis, parasitism, competitors, predators, etc., including host
organisms, as well as vectors for viruses, must be presented.
The generation time and the type of reproduction of the micro-
organism must be stated.
Information on the occurrence of resting stages and their survival
time, their virulence and infection potential must be provided.
The potential of the micro-organism to produce metabolites, including
toxins that are of concern for human health and/or the environment, in
its different development stages after the release, must be indicated.
2.5.Infectiveness,dispersalandcolonisationability
The persistence of the micro-organism and information on its life
cycle under the typical environmental conditions of use must be indi-
cated. In addition, any particular sensitivity of the micro-organism to
certain compartments of the environment (e.g. UV light, soil, water)
must be stated.
The environmental requirements (temperature, pH, humidity, nutrition
requirements, etc.) for survival, reproduction, colonisation, damage
(including human tissues) and effectiveness of the micro-organism
must be stated. The presence of specific virulence factors should be
indicated.
The temperature range at which the micro-organism grows must be
determined, including minimum, maximum and optimum tempera-
tures. This information is of particular value as a trigger for studies
of effects on human health (section 5).
The possible effect of factors such as temperature, UV light, pH, and
the presence of certain substances on the stability of relevant toxins
must also be stated.
Information on possible dispersal routes of the micro-organism (via
air as dust particles or aerosols, withh ost organisms as vectors, etc.),
under typical environmental conditions relevant to the use, must be
provided.
2.6.Relationshipstoknownplantoranimalorhumanpathogens
The possible existence of one or more species of the genus of the
active and/or, where relevant, contaminating micro-organisms known
to be pathogenic to humans, animals, crops or other non-target species
and the type of disease caused by them shall be indicated. It shall be
stated whether it is possible, and if so, by which means to clearly
distinguish the active micro-organism from the pathogenic species.1991L0414 — EN — 01.07.2003 — 009.001 — 82
▼M25
2.7.Geneticstabilityandfactorsaffectingit
Where appropriate, information on genetic stability (e.g. mutation rate
of traits related to the mode of action or uptake of exogenous genetic
material) under the environmental conditions of proposed use must be
provided.
Information must also be provided on the micro-organism's capacity
to transfer genetic material to other organisms as well as its capacity
to being pathogenic for plants, animals or man. If the micro-organism
carries relevant additional genetic elements, the stability of the
encoded traits should be indicated.
2.8.Informationontheproductionofmetabolites(especially toxins)
If other strains belonging to the same microbial species as the strain
subject to the application are known to produce metabolites (espe-
cially toxins) with unacceptable effects on human health and/or the
environment during or after application, the nature and structure of
this substance, its presence inside or outside the cell and its stability,
its mode of action (including external and internal factors of the
micro-organism necessary to action) as well as its effect on humans,
animals or other non-target species shall be provided.
The conditions under which the micro-organism produces the metabo-
lite(s) (especially toxin(s)) must be described.
Any available information on the mechanism by which the micro-
organisms regulate the production of the(se) metabolite(s) should be
provided.
Any available information on the influence of the produced metabo-
lites on the micro-organism's mode of action should be provided.
2.9.Antibioticsandotheranti-microbialagents
Many micro-organisms produce some antibiotic substances. Interfer-
ence with the use of antibiotics in human or veterinary medicine
must be avoided at any stage of the development of a microbial plant
protection product.
Information on the micro-organism's resistance or sensitivity to anti-
biotics or other anti-microbial agents must be provided, in particular
the stability of the genes coding for antibiotic resistance, unless it can
be justified that the micro-organism has no harmful effects on human
or animal health, or that it can not transfer its resistance to antibiotics
or other anti-microbial agents.
3. FURTHER INFORMATION ON THE MICRO-ORGANISM
Introduction
(i) The information provided must describe the intended purposes
for which preparations containing the micro-organism are used,
or are to be used and the dose and manner of their use or
proposed use.
(ii) The information provided must specify the normal methods and
precautions to be followed in the handling, storage and transport
of the micro-organism.
(iii) The studies, data and information submitted, must demonstrate
the suitability of measures proposed for use in emergency situa-
tions.
(iv) The information and data referred to are required for each micro-
organism, except where otherwise specified.
3.1.Function
The biological function must be specified from among the following:
— 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).1991L0414 — EN — 01.07.2003 — 009.001 — 83
▼M25
3.2.Fieldofuseenvisaged
The field(s) of use, existing and proposed, for preparations containing
the micro-organism must be specified from among the following:
— field use, suchas agriculture, h orticulture, forestry, and viticulture,
— protected crops (e.g. in greenhouses),— amenity,— weed control on non-cultivated areas,— home gardening,
— house plants,
— stored products,— other (specify).
3.3.Cropsorproductsprotectedortreated
Details of existing and intended use in terms of crops, groups of
crops, plants, or plant products protected, must be provided.
3.4.Methodofproductionandqualitycontrol
Full information on how the micro-organism is produced in bulk must
be provided.
Bothproduction meth od/process and product must be subject to a
continuous quality control by the applicant. In particular, the occur-
rence of spontaneous changing of major characteristics of the micro-
organism and of the absence/presence of significant contaminants
should be monitored. The quality assurance criteria for the production
should be submitted.
The techniques used to ensure a uniform product, and the assay
methods for its standardisation, maintenance and purity of the micro-
organism must be described and specified (e.g. HACCP).
3.5.Information on the occurrence or possible occurrence of the
developmentofresistanceofthetargetorganism(s)
Available information on the possible occurrence of the development
of resistance or cross-resistance of the target organism(s) must be
provided. Where possible, appropriate management strategies should
be described.
3.6.Methods to prevent loss of virulence of seed stock of the micro-
organism
Methods to prevent loss of virulence of starting cultures are to be
provided.
In addition, any method, if available, that could prevent the micro-
organism from losing its effects on the target species must be
described.
3.7.Recommended methods and precautions concerning handling,
storage,transportorfire
A safety data sheet similar to that required for chemical active
substances in Article 27 of Directive 67/548/EEC (
1) must be provided
for eachmicro-organism.
3.8.Proceduresfordestructionordecontamination
In many cases the preferred or sole means of safe disposal of micro-
organisms, contaminated materials, or contaminated packaging, is
through controlled incineration in a licensed incinerator.
Methods to dispose safely of the micro-organism or, where necessary,
to kill it prior to disposal, and methods to dispose of contaminated
packaging and contaminated materials, must be fully described. Data
must be provided for such methods to establish their effectiveness and
safety.1991L0414 — EN — 01.07.2003 — 009.001 — 84
(1) See doc. 6853/VI/98, Concise outline report of the first peer review meeting on micro-
organisms.
▼M25
3.9.Measuresincaseofanaccident
Information on procedures for rendering the micro-organism harmless
in the environment (e.g. water or soil) in case of an accident must be
provided.
4. ANALYTICAL METHODS
Introduction
The provisions of this section only cover analytical methods required
for post-registration control and monitoring purposes.
Post-approval monitoring might be considered for all areas of risk
assessment. This is particularly the case when (strains of) micro-
organisms that are non-indigenous to the intended area of application
are considered for approval. For analytical methods used for genera-
tion of data as required in this Directive or for other purposes the
applicant has to provide a justification for the method used; where
necessary separate guidance will be developed for suchmeth ods on
the basis of the same requirements as defined for methods for post-
registration control and monitoring purposes.
Descriptions of methods must be provided and include details of
equipment, materials and conditions used. The applicability of any
internationally recognised method must be reported.
As far as practicable these methods must employ the simplest
approach, involve the minimum cost, and require commonly available
equipment.
Data on specifity, linearity, accuracy and repeatability, as defined in
Annex II, Part A, points 4.1 and 4.2, are also required for methods
used to analyse micro-organisms and their residues.
For this section the following applies:
Impurities Any component (including contaminating
micro-organisms and/or chemical substances)
other than the specified micro-organism, origi-
nating from the manufacturing process or from
degradation during storage
Relevant impurities Impurities, as defined above, that are of
concern for human or animal health and/or
the environment
Metabolites Metabolites include products resulting from
degradative and biosynthetic reactions taking
place within the micro-organism or other
organisms used to produce the micro-organism
of interest
Relevant metabolites Metabolites that are of concern for human or
animal health and/or the environment
Residues Viable micro-organisms and substances
produced in significant quantities by these
micro-organisms which persist after the disap-
pearance of the micro-organisms and are of
concern for human or animal health and/or
the environment.
On request the following samples must be provided:
(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.
4.1.Methodsfortheanalysisofthemicro-organismasmanufactured
— 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.1991L0414 — EN — 01.07.2003 — 009.001 — 85
▼M25
— 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-organ-
isms are controlled to an acceptable level.
— Methods for the determination of relevant impurities in the manu-
factured 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.
4.2.Methodstodetermineandquantifyresidues(viableornon-viable)
of:
— the active micro-organism(s),
— relevant metabolites (especially toxins),
on and/or in crop, in foodstuffs and feeding stuffs, in animal and
human body tissues and fluids, in soil, in water (including drinking
water, ground water and surface water) and in air where relevant.
Analytical methods for amount or activity of proteinaceous products
should also be included, e.g. by testing exponential cultures and
culture supernatants in an animal cell bioassay.
5. EFFECTS ON HUMAN HEALTH
Introduction
(i) Available information based on the properties of the micro-
organism and corresponding organisms (sections 1 to 3),
including health and medical reports may be sufficient for a deci-
sion whether the micro-organism would cause health effects
(infectious/pathogenic/toxic) in humans or not.
(ii) The information provided, taken together with that provided for
one or more preparations containing the micro-organism, must be
sufficient to permit an evaluation to be made as to the risks for
man, directly and/or indirectly associated with the handling and
use of plant protection products containing the micro-organism,
and the risk for man handling treated products, and the risk for
man arising from residual traces or contaminants remaining in
food and water. In addition, the information provided must be
sufficient to:
— permit a decision to be made as to whether, or not, the
micro-organism can be included in Annex I,
— specify appropriate conditions or restrictions to be associated
withany inclusion in Annex I,
— 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.
(iii) All effects found during investigations should be reported. Inves-
tigations which may be necessary in order to evaluate the
probable mechanism involved, and to assess the significance of
these effects, must also be performed.
(iv) For all studies actual achieved dose in colony forming units per
kg body weight (cfu/kg), as well as in other appropriate units,
must be reported.
(v) Evaluation of the micro-organism should be carried out in a tier-
wise manner.
The first tier (Tier I) includes available basic information and
basic studies, which have to be performed for all micro-organ-
isms. Expert judgment will be necessary to decide about the
appropriate test programme on a case-by-case basis. Newly
generated data from conventional toxicological and/or patholo-
gical experiments on laboratory animals are normally required
unless the applicant can justify, on the basis of the previous
information, that the use of the micro-organism, under the
proposed conditions of use, does not have any harmful effects
on human and animal health. Pending the acceptance of specific
guidelines at international level, the information required shall be1991L0414 — EN — 01.07.2003 — 009.001 — 86
▼M25
generated using available test guidelines (e.g. USEPA OPPTS
Guidelines).
Tier II studies must be conducted if tests under Tier I have
shown adverse health effects. The type of study to be performed
depends on the effects observed in the Tier I studies. Before
performing such studies, the applicant shall seek agreement of
the competent authorities on the type of study to be performed.
TIERI
5.1.Basicinformation
Basic information is required about the micro-organism's potential to
cause adverse effects suchas ability to colonise, to cause damage and
to produce toxins and other relevant metabolites.
5.1.1. Medical data
Where available, and without prejudice to the provisions of Article 5
of Council Directive 80/1107/EEC of 27 November 1980 on the
protection of workers from the risks related to chemical, physical
and biological agents at work(1) and Articles 5 to 17 of Council
Directive 90/679/EEC of 26 November 1990 on the protection of
workers from the risks related to biological agents at work(2), prac-
tical data and information relevant to the recognition of the
symptoms of infection or pathogenicity and on the effectiveness of
first aid and therapeutic measures have to be submitted. Where rele-
vant, the effectiveness of potential antagonists, should be investigated
and reported. Where relevant, methods to kill or render the micro-
organism uninfective must be indicated (see section 3, point 3.8).
Data and information relevant to the effects of human exposure,
where available and of the necessary quality, are of particular value,
in confirming the validity of extrapolations made and conclusions
reached with respect to target organs, virulence, and the reversibility
of adverse effects. Suchdata can be generated following accidental or
occupational exposure.
5.1.2. Medical surveillance on manufacturing plant personnel
Available reports of occupational health surveillance programmes,
supported with detailed information on the design of the programme
and on exposure to the micro-organism must be submitted. Such
reports should, where feasible, include data relevant to the mechanism
of action of the micro-organism. These reports shall, where available,
include data from persons exposed in manufacturing plants or after
application of the micro-organism (e.g. in efficacy trials).
Special attention should be devoted to those whose susceptibility may
be affected, e.g. pre-existing disease, medication, compromised
immunity, pregnancy or breast feeding.
5.1.3. Sensitisation/allergenicity observations, if appropriate
Available information on the sensitisation and allergenic response of
workers, including workers in manufacturing plants, agricultural and
research workers and others exposed to the micro-organism must be
provided, and include, where relevant, details of any incidences of
hypersensitivity and chronic sensitisation. The information provided
should include details of frequency, level and duration of exposure,
symptoms observed and other relevant clinical observation. Informa-
tion should be given about whether workers have been subjected to
any allergy tests or interviewed about allergenic symptoms.
5.1.4. Direct observation, e.g. clinical cases
Available reports from the open literature on the micro-organism or
closely related members of the taxonomic group (relating to clinical
cases), where they are from reference journals or official reports,
must be submitted together with reports of any follow-up studies
undertaken. Suchreports are of particular value and sh ould contain
complete descriptions of the nature, level and duration of exposure,
as well as the clinical symptoms observed, first aid and therapeutic1991L0414 — EN — 01.07.2003 — 009.001 — 87
(1) OJ L 327, 3.12.1980, p. 8.
(2) OJ L 374, 31.12.1990, p. 1.
▼M25
measures applied and measurements and observations made.
Summary and abstract information is of limited value.
If there are animal studies performed, reports relating to clinical cases
can be of particular value in confirming the validity of interpretations
from animal data to man and in identifying unexpected adverse
effects which are specific to humans.
5.2.Basicstudies
In order to make it possible to correctly interpret the obtained results,
it is of greatest importance that the suggested test methods are rele-
vant regarding species sensitivity, administration route, etc., and
relevant from a biological and toxicological point of view. The way
of administration of the test micro-organism depends on the main
exposure routes to humans.
To evaluate medium- and long-term effects after acute, sub-acute or
semi-chronic exposure to micro-organisms, it is necessary to use the
options provided in most of the OECD guidelines, to extend the
studies concerned witha recovery period (after wh ichfull macro-
scopic and microscopic pathology is to be performed, including an
exploration for micro-organisms in the tissues and organs). This facil-
itates the interpretation of certain effects and provides the possibility
to recognise infectiveness and/or pathogenicity, which in turn helps
taking decisions on other issues such as the necessity to perform
long-term studies (carcinogenicity etc., see point 5.3), and whether
or not to perform residue studies (see point 6.2).
5.2.1. Sensitisation (1)
Aim of the test
The test will provide sufficient information to assess the potential of
the micro-organism to provoke sensitisation reactions by inhalation as
well as withdermal exposure. A maximised test h as to be performed.
Circumstances in which required (2)
Information on sensitisation must be reported.
5.2.2. Acute toxicity, pathogenicity and infectiveness
The studies, data and information to be provided and evaluated must
be sufficient to permit the identification of effects following a single
exposure to the micro-organism, and in particular to establish, or indi-
cate:
— 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 expo-
sure, and
— blood analyses throughout the studies in order to evaluate the
clearance of the micro-organism.
Acute toxic/pathogenic effects may be accompanied by infectiveness
and/or more long-term effects which cannot be observed immediately.
With a view to health evaluation, it is therefore necessary to carry out
studies on the ability to infect in connection with oral intake, inhala-
tion and intraperitoneal/subcutaneous injection by test mammals.1991L0414 — EN — 01.07.2003 — 009.001 — 88
(1) The available methods for testing dermal sensitisation are not suitable for testing
micro-organisms. Sensitisation by inhalation is most probably a greater problemcompared withdermal exposure to micro-organisms but so far, th ere are no validatedtest methods. Development of these kinds of methods is therefore of great importance.Until then, all micro-organisms should be regarded as potential sensitisers. This
approachalso takes into consideration immuno-compromised or oth er sensitive indivi-
duals in the population (e.g. pregnant women, new-born children or elderly).
(
2) As a consequence of the absence of proper test methods all micro-organisms will be
labelled as potential sensitisers, unless the applicant wants to demonstrate the non-sensitising potential by submitting data. Therefore, this data requirement should be
regarded as not obligatory but optional, on a provisional base.
▼M25
During the acute toxicity, pathogenicity and infectiveness studies, an
estimation of the micro-organism and/or the active toxin clearance in
the organs deemed to be relevant for microbial examination (e.g.
liver, kidneys, spleen, lungs, brain, blood and site of administration)
must be performed.
The observations to be made should reflect expert scientific judge-
ment and may include the micro-organism numeration in all thetissues likely to be affected (e.g. showing lesions) and in the main
organs: kidneys, brain, liver, lungs, spleen, bladder, blood, lymphatic
ganglia, gastrointestinal tract, thymus gland and lesions at the inocu-
lation site in the dead or moribund animals and at interim and final
sacrifice.
The information generated through acute toxicity, pathogenicity and
infectiveness testing is of particular value in assessing hazards likely
to arise in accident situations and consumer risks due to exposure to
possible residues.
5.2.2.1. Acute oral toxicity, pathogenicity and infectiveness
Circumstances in which required
The acute oral toxicity, pathogenicity and infectiveness of the micro-
organism must be reported.
5.2.2.2. Acute inhalation toxicity, pathogenicity and infectiveness
Circumstances in which required
The inhalation toxicity (
1), pathogenicity and infectiveness of the
micro-organism must be reported.
5.2.2.3. Intraperitoneal/subcutaneous single dose
The intraperitoneal/subcutaneous test is considered a highly sensitive
assay to elicit in particular infectiveness.
Circumstances in which required
The intraperitoneal injection is always required for all micro-organ-
isms, however, expert judgement may be exercised to evaluate
whether subcutaneous injection is preferred instead of intraperitoneal
injection if the maximum temperature for growth and multiplication is
lower than 37oC.
5.2.3. Genotoxicity testing
Circumstances in which required
If the micro-organism produces exotoxins according to point 2.8, then
these toxins and any other relevant metabolites in the culture medium
must also be tested for genotoxicity. Suchtests on toxins and metabo-
lites should be performed using the purified chemical if possible.
If basic studies do not indicate that toxic metabolites are formed,
studies on the micro-organism itself should be considered depending
on expert judgement on the relevance and validity of the basic data.
In the case of a virus the risk of insertional mutagenesis in mammal
cells or the risk of carcinogenicity has to be discussed.
Aim of the test
These studies are of value in:
— the prediction of genotoxic potential,
— the early identification of genotoxic carcinogens,— the elucidation of the mechanism of action of some carcinogens.1991L0414 — EN — 01.07.2003 — 009.001 — 89
(1) An inhalation study may be replaced by an intratracheal study.
▼M25
It is important that a flexible approach is adopted, with selection of
further tests being dependent upon interpretation of results at each
stage.
Test conditions (1)
Genotoxicity of cellular micro-organisms will be studied after
breaking of the cells, wherever possible. Justification should be
provided on the method of sample preparation used.
Genotoxicity of viruses should be studied on infectious isolates.
5.2.3.1. In vitro studies
Circumstances in which required
Results of in vitromutagenicity tests (bacterial assay for gene muta-
tion, test for clastogenicity in mammalian cells and test for gene
mutation in mammalian cells) must be provided.
5.2.4. Cell culture study
This information must be reported for intracellular replicating micro-
organisms, suchas viruses, viroids or specific bacteria and protozoa,
unless the information from sections 1 to 3 clearly demonstrates that
the micro-organism does not replicate in warm-blooded organisms. A
cell culture study should be performed in human cell or tissue
cultures of different organs. Selection can be based on expected target
organs after infection. If human cell or tissue cultures of specific
organs are not available, other mammal cell and tissue cultures can
be used. For viruses, the ability to interact with the human genome
is a key consideration.
5.2.5. Information on short-term toxicity and pathogenicity
Aim of the test
Short-term toxicity studies must be designed to provide information
as to the amount of the micro-organism that can be tolerated without
toxic effects under the conditions of the study. Such studies provide
useful data on the risks for those handling and using preparations
containing the micro-organism. In particular, short-term studies
provide an essential insight into possible cumulative actions of the
micro-organism, and the risks to workers who may be intensively
exposed. In addition short-term studies provide information useful in
the design of chronic toxicity studies.
The studies, data and information to be provided and evaluated, must
be sufficient to permit the identification of effects following repeated
exposure to the micro-organism, and in particular to further establish,
or indicate:
— 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 expo-
sure.
During the short-term toxicity study, an estimation of the micro-
organism clearance in the main organs must be performed.
Investigations should be included for pathogenicity and infectiveness
end points.1991L0414 — EN — 01.07.2003 — 009.001 — 90
(1) As the present test methods are designed to be performed on soluble chemicals, it is
necessary that the methods are developed so as to become relevant for micro-organ-
isms.
▼M25
Circumstances in which required
The short-term toxicity (minimum 28 days) of the micro-organism
must be reported.
The choice of test species has to be justified. The choice of study
lengthdepends on acute toxicity and clearance data.
Expert judgement is required to decide what route of administration is
preferable.
5.2.5.1. Healtheffects after repeated inh alatory exposure
Information on the health effects after repeated inhalatory exposure is
considered necessary, particularly for the risk assessment of the occu-
pational setting. Repeated exposure might influence the clearance
capacity (e.g. resistance) of the host (human). Furthermore, for proper
risk assessment the toxicity after repeated exposure to contaminants,
growthmedium, co-formulants and th e micro-organism needs to be
addressed. It should be kept in mind that the formulants in the plant
protection product can influence the toxicity and infectiveness of a
micro-organism.
Circumstances in which required
Information on the short-term infectiveness, pathogenicity and toxi-
city (respiratory route) of a micro-organism is required, unless the
information already provided is sufficient to assess human health
effects. This can be the case if it is demonstrated that the test material
has no inhalable fraction and/or repeated exposure is not expected.
5.2.6. Proposed treatment: first aid measures, medical treatment
The first aid measures to be used in the event of infection and in the
event of contamination of eyes must be provided.
Therapeutic regimes for use in the event of ingestion or contamination
of eyes and skin must be described in full. Information based on prac-
tical experience, where it exists and is available, in other cases on
theoretical grounds, as to the effectiveness of alternative treatment
regimes, where relevant, must be provided.
Information on resistance to antibiotics must be provided.
(END OF TIER I)
TIERII
5.3.Specifictoxicity,pathogenicityandinfectivenessstudies
In certain cases, it can be necessary to carry out supplementary
studies to further clarify the adverse human effects.
In particular, if results from earlier studies indicate that the micro-
organism may cause long-term health effects, studies on chronic toxi-
city, pathogenicity and infectiveness, carcinogenicity and reproductive
toxicity must be carried out. Furthermore, where a toxin is produced,
kinetic studies must be performed.
Studies required must be designed on an individual basis, in the light
of the particular parameters to be investigated and the objectives to be
achieved. Before performing such studies, the applicant shall seek
agreement of the competent authorities on the type of study to be
performed.
5.4. In vivostudiesinsomaticcells
Circumstances in which required
If all the results of the in vitrostudies are negative further testing
must be done withconsideration of oth er relevant information avail-
able. The test can be an in vivostudy or an in vitrostudy using a
different metabolising system from that/those previously used.
If thein vitrocytogenetic test is positive, an in vivotest using somatic
cells (metaphase analysis in rodent bone marrow or micronucleus test
in rodents) must be conducted.1991L0414 — EN — 01.07.2003 — 009.001 — 91
▼M25
If either of the in vitrogene mutation tests are positive, an in vivotest
to investigate unscheduled DNA synthesis or a mouse spot test must
be conducted.
5.5.Genotoxicity— In vivostudiesingermcells
Aim of the test and test conditions
See point 5.4.
Circumstances in which required
When any result of an in vivostudy in somatic cells is positive, in
vitrotesting for germ cell effects may be justified. The necessity for
conducting these tests will have to be considered on a case-by-case
basis, taking into account other relevant information available
including use and expected exposure. Suitable tests would need to
examine interaction with DNA (such as the dominant lethal assay),
to look at the potential for inherited effects and possibly make a quan-
titative assessment of heritable effects. It is recognised that in view of
their complexity, the use of quantitative studies would require strong
justification.
(END OF TIER II)
5.6.Summary of mammalian toxicity, pathogenicity and infectiveness
andoverallevaluation
A summary of all data and information provided under points 5.1
through 5.5, must be submitted, and include a detailed and critical
assessment of those data in the context of relevant evaluative and
decision making criteria and guidelines, withparticular reference to
the risks for man and animals that may or do arise, and the extent,
quality and reliability of the data base.
It must be explained whether exposure of animals or humans has any
implications for vaccination or serological monitoring.
6. RESIDUES IN OR ON TREATED PRODUCTS, FOOD AND FEED
Introduction
(i) The information provided, taken together with that for one or
more preparations containing the micro-organism, must be suffi-
cient to permit an evaluation to be made as to the risk for man
and/or animals, arising from exposure to the micro-organism and
its residual traces and metabolites (toxins) remaining in or on
plants or plant products.
(ii) In addition, the information provided must be sufficient to:
— permit a decision to be made as to whether or not the micro-
organism can be included in Annex I to Directive 91/414/
EEC,
— specify appropriate conditions or restrictions to be associated
withany inclusion in Annex I to Directive 91/414/EEC,
— where relevant, set maximum residue levels, preharvest inter-
vals to protect consumers and waiting periods, to protect
workers handling the treated crops and products.
(iii) For the evaluation of risk arising from residues, experimental
data on levels of exposure to the residue may not be required
where it can be justified, that the micro-organism and its metabo-
lites are not hazardous to humans in the concentrations that could
occur as a result of authorised use. This justification can be
based on open literature, on practical experience and on informa-
tion submitted in sections 1 through 3 and section 5.
6.1.Persistance and likelihood of multiplication in or on crops,
feedingstuffsorfoodstuffs
A substantiated estimation of persistance/competitiveness of the
micro-organism and relevant secondary metabolites (especially toxins)
in or on the crop under the environmental conditions prevailing at and
after the intended use, taking into account in particular the informa-
tion provided in section 2, has to be delivered.
Moreover, the application shall state to which extent and on which
basis it is considered that the micro-organism can (or cannot) multiply1991L0414 — EN — 01.07.2003 — 009.001 — 92
▼M25
in or on the plant or plant product or during processing of raw
products.
6.2.Furtherinformationrequired
Consumers may be exposed to micro-organisms for a considerable
time as a result of the consumption of treated food commodities;
potential effects on the consumers must, therefore, be derived from
chronic or semi-chronic studies, so that a toxicological end point,
such as the ADI, can be established for risk management.
6.2.1. Non-viable residues
A non viable micro-organism is a micro-organism that is not capable
of replication or of transferring genetic material.
If relevant quantities of the micro-organism or of produced metabo-
lites, especially toxins, have been found to be persistant in section 2,
points 2.4 and 2.5, full experimental residue data as provided for in
Annex II, Part A, section 6, is required, if concentrations of the
micro-organism and/or its toxins in or on the treated foodstuffs or
feedingstuffs are expected to occur in concentrations higher than
under natural conditions or in a different phenotypic state.
In agreement withDirective 91/414/EEC, th e conclusion concerning
the difference between natural concentrations and an elevated concen-
tration due to treatment withth e micro-organism, is to be based on
experimentally obtained data, and not on extrapolations or calcula-
tions using models.
Before performing such studies, the applicant shall seek agreement of
the competent authorities on the type of study to be performed.
6.2.2. Viable residues
If the information submitted according to point 6.1 suggests persis-
tance of relevant amounts of the micro-organism in or on treated
products, food or feed, possible effects on humans and/or animals
must be investigated, unless it can be justified from section 5, thatthe micro-organism and its metabolites and/or degradation products
are not hazardous to humans in the concentrations and of the nature
that could occur as a result of authorised use.
In agreement withDirective 91/414/EEC, th e conclusion concerning
the difference between natural concentrations and an elevated concen-
tration due to treatment withth e micro-organism, is to be based on
experimentally obtained data, and not on extrapolations or calcula-
tions using models.
The persistence of viable residues needs special attention if infective-
ness or pathogenicity to mammals have been found in sections 2.3,
2.5 or 5 and/or if any other information suggests a hazard to consu-
mers and/or workers. In this case the competent authorities may
require studies similar to those provided for in Part A.
Before performing such studies, the applicant shall seek agreement of
the competent authorities on the type of study to be performed.
6.3.Summaryandevaluationofresiduebehaviourresultingfromdata
submittedunderpoints6.1and6.2
7. FATE AND BEHAVIOUR IN THE ENVIRONMENT
Introduction
(i) Information on the origin, the properties, and the survival of the
micro-organism and its residual metabolites as well as its
intended use form the basis for an assessment of environmental
fate and behaviour.
Experimental data are normally required unless it can be justified
that an assessment of its fate and behaviour in the environment
can be performed with the information already available. This
justification can be based on open literature, on practical experi-
ence and, on information submitted in sections 1 through 6. The
function of the micro-organism in environmental processes (as
defined in section 2, point 2.1.2) is of particular interest.1991L0414 — EN — 01.07.2003 — 009.001 — 93
▼M25
(ii) The information provided, taken together with other relevant
information, and that for one or more preparations containing
the micro-organism, must be sufficient to permit an assessment
of its fate and behaviour as well as that of its residual traces
and toxins, where they are of significance for human health
and/or the environment.
(iii) In particular, the information provided should be sufficient to:
— decide whether, or not, the micro-organism can be included
in Annex I,
— specify appropriate conditions or restrictions to be associated
withany inclusion in Annex I,
— specify the hazard symbols (once introduced), the indications
of danger, and relevant risk and safety phrases for the protec-
tion of the environment, which are to be included on
packaging (containers),
— predict the distribution, fate, and behaviour in the environ-
ment 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.
(iv) Any relevant metabolites (i.e. of concern for human health and/
or the environment) formed by the test organism under any rele-
vant environmental conditions should be characterised. If
relevant metabolites are present in or produced by the micro-
organism, data as outlined under Annex II, Part A, point 7 may
be required, if all of the following conditions are met:
— 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 environ-
ment in concentrations considerably higher than under
natural conditions.
(v) Available information on the relationship with naturally occur-
ring wild type relatives should be taken into account.
(vi) Before performing studies as referred to below, the applicant
shall seek agreement of the competent authorities on whether
studies need to be performed and, if so, the type of study to be
conducted. The information from the other sections has, also, to
be taken into account.
7.1.Persistence andmultiplication
Where relevant, appropriate information on the persistence and multi-
plication of the micro-organism, in all environmental compartments
has to be given, unless it can be justified that exposure of the parti-
cular environmental compartment to the micro-organism is unlikely to
occur. Special attention shall be given to
— 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 agricul-
tural practices applied after intended use.
Estimated levels of the specified micro-organism in a time course
after use of the product under the proposed conditions of use shall
be given.
7.1.1. Soil
Information on viability/population dynamics should be reported in
several cultivated and uncultivated soils representative of soils typical
of the various Community regions where use exists or is anticipated.
The provisions on choice of soil and its collection and handling, as
referred to in Part A, point 7.1, Introduction, have to be followed. If
the test organism is to be used in association with other media, e.g.
rockwool, this must be included in the test range.
7.1.2. Water
Information should be reported on viability/population dynamics in
natural sediment/water systems under bothdark and illuminated
conditions.1991L0414 — EN — 01.07.2003 — 009.001 — 94
▼M25
7.1.3. Air
In case of particular concerns for operator, worker or bystander expo-
sure, information on the concentrations in air might be necessary.
7.2.Mobility
The possible spread of the micro-organism and its degradation
products in relevant environmental compartments has to be evaluated,
unless it can be justified that exposure of the particular environmental
compartments to the micro-organism is unlikely to occur. In this
context, the intended use (e.g. field or greenhouse, application to soil
or to crops), life cycle stages, including occurrence of vectors, persis-
tence and the ability of the organism to colonise adjacent habitats are
of particular interest.
The spread, the persistence and probable transport ranges need special
attention if toxicity, infectiveness or pathogenicity have been reported
or if any other information suggests possible hazard to humans,
animals or to the environment. In this case the competent authorities
may require studies similar to those provided for in Part A. Before
performing such studies, the applicant shall seek agreement of the
competent authorities on the type of study to be performed.
8. EFFECTS ON NON-TARGET ORGANISMS
Introduction
(i) The information on identity, biological properties and further
information in sections 1 to 3 and 7 is central to the assessment
of impact on non-target species. Additional useful information
may be found on fate and behaviour in the environment in
section 7 and on residue levels in plants in section 6 which,
together with information on the nature of the preparation and
its manner of use, defines the nature and extent of potential
exposure. The information submitted in accordance with section
5 will provide essential information as to effects to mammals
and the mechanisms involved.
Experimental data are normally required, unless it can be justi-
fied that an assessment of effects on non-target organisms can
be performed withth e information already available.
(ii) The choice of the appropriate non-target organisms for testing
of environmental effects should be based on the identity of the
micro-organism (including the host specificity, mode of action
and ecology of the organism). From such knowledge it would
be possible to choose the appropriate test-organisms, such as
organisms closely related to the target organism.
(iii) The information provided, taken together with that for one or
more preparations containing the micro-organism, must be
sufficient to permit an assessment of the impact on non-target
species (flora and fauna), likely to be at risk from exposure to
the micro-organism, where they are of environmental signifi-
cance. Impact can result from single, prolonged or repeated
exposure and can be reversible or irreversible.
(iv) In particular, the information provided for the micro-organism,
together with other relevant information, and that provided for
one or more preparations containing it, should be sufficient to:
— decide whether, or not, the micro-organism can be included
in Annex I,
— specify appropriate conditions or restrictions to be asso-
ciated withany inclusion in Annex I,
— 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 hazard symbols (once introduced), the indica-
tions of danger, and relevant risk and safety phrases for the
protection of the environment, to be mentioned on packa-
ging (containers).
(v) There is a need to report all potentially adverse effects found
during routine investigations on environmental effects, to under-
take and report, where required by the competent authorities,
suchadditional studies wh ichmay be necessary to investigate1991L0414 — EN — 01.07.2003 — 009.001 — 95
▼M25
the probable mechanisms involved and to assess the signifi-
cance of these effects. All available biological data and
information which is relevant to the assessment of the ecology
profile of the micro-organism must be reported.
(vi) For all studies, average achieved dose in cfu/kg body weight as
well as in other appropriate units must be reported.
(vii) It may be necessary to conduct separate studies for relevant
metabolites (especially toxins), where these products can consti-
tute a relevant risk to non-target organisms and where their
effects cannot be evaluated by the available results relating to
the micro-organism. Before such studies are performed, the
applicant shall seek agreement of the competent authorities on
whether such studies need to be performed and, if so, the type
of study to be conducted. The information from sections 5, 6
and 7 has to be taken into account.
(viii) In order to facilitate the assessment of the significance of test
results obtained, the same strain (or recorded origin) of each
relevant species should, where possible, be used in the various
tests specified.
(ix) Tests must be performed unless it can be justified that the non-
target organism will not be exposed to the micro-organism. If it
is justified that the micro-organism does not cause toxic effects
or is not pathogenic or infective to vertebrates or plants, only
reaction to appropriate non-target organisms must be investi-
gated.
8.1.Effectsonbirds
Aim of the test
Information on toxicity, infectiveness and pathogenicity to birds must
be reported.
8.2.Effectsonaquaticorganisms
Aim of the test
Information on toxicity, infectiveness and pathogenicity to aquatic
organisms must be reported.
8.2.1. Effects on fish
Aim of the test
Information on toxicity, infectiveness and pathogenicity to fish must
be reported.
8.2.2. Effects on freshwater invertebrates
Aim of the test
Information on toxicity, infectiveness and pathogenicity to freshwater
invertebrates must be reported.
8.2.3. Effects on algae growth
Aim of the test
Information on effects on algal growth, growth rate and capacity to
recover must be reported.
8.2.4. Effects on plants other than algae
Aim of the test
Information on effects on plants other than algae must be reported.
8.3.Effectsonbees
Aim of the test
Information on toxicity, infectiveness and pathogenicity to bees must
be reported.1991L0414 — EN — 01.07.2003 — 009.001 — 96
▼M25
8.4.Effectsonarthropodsotherthanbees
Aim of the test
Information on toxicity, infectiveness and pathogenicity to arthropods
other than bees must be reported. The selection of the test species
should be related to the potential use of the plant protection products
(e.g. foliar or soil application). Special attention should be given to
organisms used for biological control and organisms playing an
important role in integrated pest management.
8.5.Effectsonearthworms
Aim of the test
Information on toxicity, infectiveness and pathogenicity to earth-
worms must be reported.
8.6.Effectsonnon-targetsoilmicro-organisms
Impact on relevant non-target micro-organisms and on their predators
(e.g. protozoa for bacterial inoculants) should be reported. Expert
judgement is required to decide whether additional studies are neces-
sary. Suchdecision will take into consideration th e available
information in this and other sections, in particular data on the speci-
ficity of the micro-organism, and the expected exposure. Useful
information may also be available from the observations carried out
in efficacy testing. Special attention should be given to organisms
used in integrated crop management (ICM).
8.7.Additionalstudies
The additional studies might include further acute studies on addi-
tional species or processes (such as sewage systems) or higher tier
studies such as chronic, sub-lethal or reproductive studies on selected
non-target organisms.
Before performing such studies, the applicant shall seek agreement of
the competent authorities on the type of study to be performed.
9. SUMMARY AND EVALUATION OF ENVIRONMENTAL
IMPACT
A summary and evaluation of all data relevant to the environmental
impact, should be carried out according to the guidance given by the
competent authorities of the Member States concerning the format of
suchsummaries and evaluations. It sh ould include a detailed and
critical assessment of those data in the context of relevant evaluative
and decision making criteria and guidelines, withparticular reference
to the risks for the environment and non-target species that may or do
arise, and the extent, quality and reliability of the data base. In parti-
cular the following issues should be addressed:
— 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.1991L0414 — EN — 01.07.2003 — 009.001 — 97
▼B
ANNEX III
REQUIREMENTS FOR THE DOSSIER TO BE SUBMITTED FOR THE
AUTHORIZATIONOFAPLANTPROTECTIONPRODUCT
INTRODUCTION
The information required shall:
1.1. include a technical dossier supplying the information necessary for evalu-
ating efficacy and the foreseeable risks, whether immediate or delayed,
which the plant protection product 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, according to 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 guide-
lines 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. ►M4In particular, when reference is made in this
Annex to an EEC Method which consists in the transposal of a method
developed by an international organization (e.g. OECD), Member States
may accept that the required information is generated according to the
latest version of that method if at the initiation of the studies the EEC
Method has not yet been updated; ◄
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 a 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 infor-
mation and data.
1.6. where relevant, have been generated in accordance with the requirements
of Directive 86/609/EEC.
2.1. Tests and analyses must be conducted in accordance withth e principles
laid down in Directive 87/18/EEC where testing is done to obtain data on
the properties and/or safety with respect to human or animal health or the
environment.
2.2. Tests and analyses, required under the provisions of Section 6 points 6.2 to
6.7 of this Annex, shall be conducted by official or officially recognized
testing facilites or organizations which satisfy at least the following
requirements:
— have at their disposal sufficient scientific and technical staff, having the
necessary education, training, technical knowledge and experience for
their assigned functions,
— have at their disposal suitable items of equipment required for correct
performance of the tests and measurements which it claims to be
competent to carry out. This equipment shall be properly maintained
and calibrated where appropriate before being put into service and
thereafter according to an established programme,
— have at their disposal appropriate experimental fields and, where neces-
sary glasshouses, growth cabinets or storage rooms. The environment in
which the tests are undertaken shall not invalide its results or adversely
effect the required accuracy of measurement,
— make available to all relevant personnel operating procedures and
protocols used for the trials,1991L0414 — EN — 01.07.2003 — 009.001 — 98
▼M1
▼M4
▼M1
▼M1
— make available, where requested by the competent authority, prior to
the commencement of a test, detailed information on it, containing at
least its location and the plant protection products included in it,
— ensure that the quality of the work performed is appropriate to its type,
range, volume and intended purpose,
—►C2maintain records of all original observations, calculations and
derived data, ◄calibration records and the final test report as long as
the product concerned authorized in the Community.
2.3. Member States shall require that officially recognized testing facilities and
organizations, and, where requested, official facilities and organizations:
— report to the relevant national authority all detailed information neces-
sary to demonstrate that they can satisfy the requirements provided for
in point 2.2,
— accept at any time the inspections, which each Member State shall
regularly organize on its territory in order to verify the compliance
withth e requirement as laid down in point 2.2.
2.4. By way of derogation from point 2.1, Member States may apply the provi-
sions of points 2.2 and 2.3, by extension, to tests and analyses performed
on their territory in order to obtain data on the properties and/or safety of
the preparations with respect to honey-bees and beneficial arthropods other
than bees and actually started on or before 31 December 1999.
2.5. By way of derogation from point 2.1, Member States may apply the provi-
sions of points 2.2 and 2.3, by extension, to supervised residue trials
performed on their territory in accordance with the provisions of Section 8
‘Residues in or on treated products, food and feed’ withplant protection
products containing active substances already on the market two years after
notification of the Directive and actually started on or before 31 December
1997.
2.6. By way of derogation from point 2.1, for active substances consisting of
micro-organisms or viruses, tests and analyses done to obtain data on the
properties and/or safety with respect to other aspects than human health,
may have been conducted by official or officially recognised testing facil-
ities or organisations which satisfy at least the requirements under points
2.2 and 2.3 of the introduction of Annex III.
3. The information required shall include the proposed classification and
labelling of the plant protection product in accordance with relevant
Community Directives.
4. In individial cases it may be necessary to require certain information as
provided for in Annex II, Part A, for formulants. Before suchinformation
will be required and before possible new studies have to be performed, all
information on the formulant, made available to the competent authority,
will be considered, in particular when:
— the use of the formulant is permitted in food, animal feeding stuffs,
medicines or cosmetics in accordance withCommunity legislation,
or
— a safety data sheet has been submitted for the formulant in accordance
withCouncil Directive 67/548/EEC.
PART A
Chemicalpreparations
1.Identityoftheplantprotectionproduct
The information provided, taken together with that provided for the
active substance(s), must be sufficient to precisely identify prepara-
tions and define them in terms of their specification and nature. The
information and data referred to, unless otherwise specified, are
required for all plant protection products.
1.1. Applicant (name and address, etc.)
The name and address of the applicant (permanent community
address) must be provided as must the name, position, telephone and
telefax number of the appropriate person to contact.1991L0414 — EN — 01.07.2003 — 009.001 — 99
▼M5
▼M25
▼M1
▼B
▼M2
▼M2
Where in addition, the applicant has an office, agent or representative
in the Member State in which the authorization is being sought, the
name and address of the local office agent or representative should
be provided, as should the name, position, telephone and telefax
number of the appropriate person to contact.
1.2. Manufacturer of the preparation and the active substance(s) (names
and addresses etc. including location of plants)
The name and address of the manufacturer of the preparation and of
eachactive substance in th e preparation must be provided as must
the name and address of each manufacturing plant in which the
preparation and active substance are manufactured.
A contact point (preferable a central contact point, to include name,
telephone and telefax numbers) must be provided for each.
If the active substance originates from a manufacturer from which data
according to Annex II had not been submitted previously, a statement
of purity and detailed information on the impurities in Annex II have
to be provided.
1.3. Trade name or proposed trade name, and manufacturer's development
code number of the preparation if appropriate
All former and current trade names and proposed trade names and
development code numbers of the preparation as well as the current
names and numbers must be provided. Where trade names and code
numbers referred to, relate to similar but different preparations
(possibly absolete), full details of the differences, must be provided.
(The proposed trade name may not give rise to confusion with the
trade name of already registered plant protection products.)
1.4. Detailed quantitative and qualitative information on the composition
of the preparation (active substance(s), and formulants)
1.4.1. For preparations the following information must be reported:
— the content of both technical active substance(s) and pure active
substance(s);
— the content of formulants.
The concentrations should be expressed in terms as provided for in
Article 6 (2) of Directive 78/631/EEC.
1.4.2. For active substances their ISO common names or proposed ISO
common names and their CIPAC numbers, and, where available, the
EEC (EINECS or ELINCS) numbers must be provided. Where rele-
vant it must be stated which salt, ester, anion or cation is present.
1.4.3. Formulants must where possible, be identified both by their chemical
name as given in Annex I to Directive 67/548/EEC, or, if not included
in th is Directive, in accordance withbothIUPAC and CA nomencla-
ture. Their structure or structural formula must be provided. For each
component of the formulants the relevant EEC (EINECS or ELINCS)
number and CAS number where they exist, must be provided. Where
the information provided does not fully identify a formulant, an appro-
priate specification must be provided. The trade name of formulants,
where they exist, must also be provided.
1.4.4. For formulants the function must be given:
— adhesive (sticker),
— antifoaming agent,
— antifreeze,
— binder,— buffer,
— carrier,
— deodorant,— dispersing agent,— dye,
— emetic,
— emulsifier,— fertilizer,
— preservative,
— odourant,— perfume,1991L0414 — EN — 01.07.2003 — 009.001 — 100
▼M2
— propellant,
— repellent,
— safener,— solvent,— stabilizer,
— synergist,
— thickener,— wetting agent,— miscellaneous (specify).
1.5. Physical state and nature of the preparation (emulsifiable concentrate,
wettable powder, solution etc).
1.5.1. The type and code of preparation must be designated according to the
‘Catalogue of pesticide formulation types and international coding
system (GIFAP Technical Monograph No 2. 1989)’.
Where a particular preparation is not defined precisely in this publica-
tion a full description of the physical nature and state of the
preparation must be provided, together with a proposal for a suitable
description of the type of preparation and a proposal for its definition.
1.6. Function (herbicide, insecticide, etc.)
The function must be specified from among the following:
— acaricide,
— bactericide,
— fungicide,— herbicide— insecticide,
— molluscicide,
— nematicide,— plant growthregulator,— repellant,
— rodenticide,
— semio-chemicals,— talpicide,— viricide,
— other (must be specified).
2.Physical,chemicalandtechnicalpropertiesoftheplantprotection
product
The extent to which plant protection products for which authorization
is sought, comply with relevant FAO specifications as agreed by the
Group of Experts on Pesticide Specifications, of the FAO Panel of
Experts on Pesticide Specifications, Registration Requirements and
Application Standards, must be stated. Divergences from FAO specifi-
cations must be described in detail, and justified.
2.1. Appearance (colour and odour)
A description of both the colour and odour, if any, and the physical
state of the preparation, must be provided.
2.2. Explosivity and oxidizing properties
2.2.1. The explosive properties of preparations must be reported according to
EEC method A 14. Where available thermodynamic information
establishes beyond reasonable doubt that the preparation is incapable
of exothermic reaction, it is sufficient to provide that information as
a justification for not determining the explosive properties of the
preparation.
2.2.2. Oxidizing properties of preparations which are solids must be deter-
mined and exported according to EEC method A 17. For other
preparations the method used must be justified. The oxidizing proper-
ties do not have to be determined if it can be shown without
reasonable doubt on the basis of thermodynamic information, that the
preparation is incapable of reacting exothermically with combustible
materials.1991L0414 — EN — 01.07.2003 — 009.001 — 101
▼M2
2.3. Flash point and other indications of flammability or spontaneous igni-
tion
The flash point of liquids which contain flammable solvents, must be
determined and reported according to EEC Method A 9. The flamm-
ability of solid preparations and gases must be determined and
reported according to EEC methods A 10, A 11 and A 12 as appro-
priate. The auto-flammability of preparations must be determined and
reported in accordance withEEC meth ods A 15 or A 16 as appro-
priate, 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).
2.4. Acidity/alkalinity and if necessary pH value
2.4.1. In the case of preparations which are acidic (pH < 4) or alkaline (pH
> 10) the acidity or alkalinity and the pH value must be determined
and reported according to CIPAC Method MT 31 and MT 75 respec-
tively.
2.4.2. Where relevant (if to be applied as aqueous dilution) the pH of a 1 %
aqueous dilution, emulsion or dispersion of the preparation, must bedetermined and reported according to CIPAC Method MT 75.
2.5. Viscosity and surface tension
2.5.1. In the case of liquid preparations for Ultra Low Volume use (ULV)
the kinematic viscosity must be determined and reported according to
OECD Test Guideline 114.
2.5.2. For non newtonian liquids the viscosity must be determined and
reported together with the test conditions.
2.5.3. In the case of liquid preparations the surface tension has to be deter-
mined and reported according to EEC method A 5.
2.6. Relative density and bulk density
2.6.1. The relative density of liquid preparations must be determined and
reported according to EEC Method A 3.
2.6.2. The bulk (tap) density of preparations which are powders or granules,
must be determined and reported according to CIPAC Methods MT
33, MT 159 or MT 169 as appropriate.
2.7. Storage — stability and shelf-life: Effects of light, temperature and
humidity on technical characteristics of the plant protection product
2.7.1. The stability of the preparation after storage for 14 days at 54 ºC must
be determined and reported according to CIPAC Method MT 46.
Other times and/or temperatures may be needed (e.g. eight weeks at
40 ºC or 12 weeks at 35 ºC or 18 weeks at 30 ºC) if the preparation
is heat sensitive.
If the active substance content after the heat stability test has
decreased by more than 5 % of the initially found content, the
minimum content shall be declared and information on the degradation
products shall be supplied.
2.7.2. Additionally in the case of liquid preparations, the effect of low
temperatures on stability, must be determined and reported according
to CIPAC Methods MT 39, MT 48, MT 51 or MT 54 as appropriate.
2.7.3. The shelf life of the preparation at ambient temperature must be
reported. Where shelf life is less than two years, the shelf life in
months, with appropriate temperature specifications, must be reported.
Useful information is given in GIFAP MonographNo. 17.
2.8. Technical characteristics of the plant protection product
The technical characteristics of the preparation must be determined to
permit a decision to be made as to its acceptability.
2.8.1. Wettability
The wettability of solid preparations which are diluted for use (e.g.
wettable powders, water soluble powders, water soluble granules and
water dispersible granules), must be determined and reported
according to CIPAC Method MT 53.3.1991L0414 — EN — 01.07.2003 — 009.001 — 102
▼M2
2.8.2. Persistent foaming
The persistence of foaming of preparations to be diluted with water,
must be determined and reported according to CIPAC Method MT 47.
2.8.3. Suspensibility and suspension stability
— The suspensibility of water dispersible products (e.g. wettable
powders, water dispersible granules, suspension concentrates)
must be determined and reported according to CIPAC Method
MT 15, MT 161 or MT 168 as appropriate.
— The spontaneity of dispersion of water dispersible products (e.g.
suspension concentrates and water dispersible granules) must be
determined and reported according to CIPAC Methods MT 160 or
MT 174 as appropriate.
2.8.4. Dilution stability
The dilution stability of water soluble products must be determined
and reported according to CIPAC Method MT 41.
2.8.5. Dry sieve test and wet sieve test
In order to ensure that dustable powders have a suitable particle size
distribution for ease of application, a dry sieve test must be conducted
and reported according to CIPAC Method MT 59.1.
In the case of water dispersible products, a wet sieve test must be
conducted and reported according to CIPAC Method MT 59.3 or MT
167 as appropriate.
2.8.6. Particle size distribution (dustable and wettable powders,
granules), content of dust/fines (granules), attrition and
friability (granules)
2.8.6.1. The size distribution of particles in the case of powders, must be
determined and reported according to OECD Method 110.
The nominal size range of granules for direct application must be
determined and reported in accordance withCIPAC MT 58.3, for
water dispersible granules in accordance withCIPAC MT 170.
2.8.6.2. The dust content of granular preparations, must be determined and
reported according CIPAC Method MT 171. If relevant for operator
exposure the particle size of dust must be determined and reported
according to OECD Method 110.
2.8.6.3. The friability and attrition characteristics of granules, must be deter-
mined and reported once internationally agreed methods are
available. Where already data are available they must be reported
together with the method used.
2.8.7. Emulsifiability, Re-emulsifiability, emulsion stability
2.8.7.1. The emulsifiability, emulsion stability and re-emul-sifiability of
preparations which form emulsions, must be determined and reported
according to CIPAC Methods MT 36 or MT 173 as appropriate.
2.8.7.2. The stability of dilute emulsions and of preparations which are emul-
sions, must be determined and reported according to CIPAC Method
MT 20 or MT 173.
2.8.8. Flowability, pourability (rinsability) and dustability
2.8.8.1. The flowability of granular preparations must be determined and
reported according to CIPAC Mehtod MT 172.
2.8.8.2. The pourability (including rinsed residue) of suspensions (e.g. suspen-
sion concentrates, suspo-emulsions), must be determined and reported
according to CIPAC Method MT 148.
2.8.8.3. The dustability of dustable powders following accelerated storage
according 2.7.1 must be determined and reported according to CIPAC
Method MT 34 or another suitable method.1991L0414 — EN — 01.07.2003 — 009.001 — 103
▼M2
2.9. Physical and chemical compatibility with other products including
plant protection products with which its use is to be authorized
2.9.1. The physical compatibility of tank mixes must be reported based on
in-house test methods. A practical test would be an acceptable alterna-tive.
2.9.2. The chemical compatibility of tank mixes must be determined and
reported except where examination of the individual properties of the
preparations would establish beyond reasonable doubt that there is no
possibility of reaction taking place. In suchcases it is sufficient to
provide that information as justification for not practically determining
the chemical compatibility.
2.10. Adherence and distribution to seeds
In the case of preparations for seed treatment, both distribution and
adhesion must be investigated and reported; in the case of distribution
according to CIPAC Method MT 175.
2.11. Summary and evaluation of data presented under points 2.1. to 2.10
3.Dataonapplication
3.1. Field of use envisaged, e.g. field, protected crops, storage of plant
products, home gardening
The field(s) of use, existing and proposed, for preparations containing
the active substance must be specified from among the following:
— field use, suchas agriculture, h orticulture, forestry and viticulture,
— protected crops,
— amenity,
— weed control on non-cultivated areas,
— home gardening,
— house plants,— plant products storage practice,
— other (specify).
3.2. Effects on harmful organisms, e.g. contact, inhalation or stomach
poison, fungitoxic or fungistatic, etc., systemic or not in plants
The nature of the effects on harmful organisms must be stated:
— contact action,
— stomachaction,— inhalation action,
— fungitoxic action,
— fungistatic action,
— desiccant,
— reproduction inhibitor,
— other (must be specified).
It must be stated whether or not the product is translocated in plants.
3.3. Details of intended use e.g. types of harmful organisms controlled and/
or plants or plant products to be protected
Details of the intended use must be provided.Where relevant, effects achieved e.g. sprout suppression, retardation of
ripening, reduction in stem length, enhanced fertilization etc. must be
reported.
3.4. Application rate
For eachmeth od of application and eachuse, th e rate of application
per unit (ha, m
2,m3) treated, in terms of g or kg of bothpreparation
and active substance, must be provided.
Application rates shall normally be expressed in g or kg/ha or in kg/m3
and where appropriate in g or kg/tonne; for protected crops and home
gardening use rates shall be expressed in g or kg/100 m2or g or kg/m3.1991L0414 — EN — 01.07.2003 — 009.001 — 104
▼M2
3.5. Concentration of active substance in material used (e.g. in the diluted
spray, baits or treated seed)
The content of active substance shall be reported, as appropriate, in g/
l, g/kg, mg/kg or in g/tonne.
3.6. Method of application
The method of application proposed must be described fully, indi-
cating the type of equipment to be used, if any, as well as the type
and volume of diluent to be used per unit of area or volume.
3.7. Number and timing of applications and duration of protection
The maximum number of applications to be used and their timing,
must be reported. Where relevant the growth stages of the crop or
plants to be protected and the development stages of the harmful
organisms, must be indicated. Where possible the interval between
applications, in days, must be stated.
The duration of protection afforded both by each application and by
the maximum number of applications to be used, must be indicated.
3.8. Necessary waiting periods or other precautions to avoid phytotoxic
effects on succeeding crops
Where relevant, minimum waiting periods between last application
and sowing or planting of succeeding crops, which are necessary to
avoid phytotoxic effects on succeeding crops, must be stated, and
follow from the data provided under paragraph 6.6.
Limitations on choice of succeeding crops, if any, must be stated.
3.9. Proposed instructions for use
The proposed instructions for use of the preparation, to be printed on
labels and leaflets, must be provided.
4.Furtherinformationontheplantprotectionproduct
4.1. Packaging (type, materials, size etc.), compatibility of the preparation
with proposed packaging materials
4.1.1. Packaging to be used must be fully described and specified in terms of
the materials used, manner of construction (e.g. extruded, welded etc.),
size and capacity, size of opening, type of closure and seals. It must be
designed in accordance with the criteria and guidelines specified in the
FAO ‘Guidelines for the Packaging of Pesticides’.
4.1.2. The suitability of the packaging, including closures, in terms of its
strength, leakproofness and resistance to normal transport and hand-
ling, must be determined and reported according to ADR Methods
3552, 3553, 3560, 3554, 3555, 3556 3558, or appropriate ADR
Methods for intermediate bulk containers, and, where for the prepara-
tion child-resistant closures are required, according to ISO standards
8317.
4.1.3. The resistance of the packaging material to its contents must be
reported according to GIFAP MonographNo 17.
4.2. Procedures for cleaning application equipment
Cleaning procedures for bothapplication equipment and protective
clothing must be described in detail. The effectiveness of the cleaning
procedure, must be fully investigated and reported.
4.3. Re-entry periods, necessary waiting periods or other precautions to
protect man, livestock and the environment
The information provided must follow from and be supported by the
data provided for the active substance(s) and that provided under
sections 7 and 8.
4.3.1. Where relevant pre-harvest intervals, re-entry periods or withholding
periods necessary to minimize the presence of residues in or on crops,
plants and plant products, or in treated areas or spaces, witha view to
protecting man or livestock, must be specified e.g.:
— pre-harvest interval (in days) for each relevant crop,1991L0414 — EN — 01.07.2003 — 009.001 — 105
▼M2
— re-entry period (in days) for livestock, to areas to be grazed,
— re-entry period (in hours or days) for man to crops, buildings or
spaces treated,
— withholding period (in days) for animal feedingstuffs,— waiting period (in days), between application and handling treated
products, or
— waiting period (in days), between last application and sowing or
planting succeeding crops.
4.3.2. Where necessary, in the light of the test results, information on any
specific agricultural, plant health or environmental conditions under
which the preparation may or may not be used must be provided.
4.4. Recommended methods and precautions concerning: handling,
storage, transport or fire
The recommended methods and precautions concerning handling
procedures (detailed) for the storage, at both warehouse and user level
of plant protection products, for their transport and in the event of fire
must be provided. Where available information on combustion
products must be provided. The risks likely to arise and the methods
and procedures to minimize the hazards arising, must be specified.
Procedures to preclude or minimize the generation of waste or left-
overs must be provided.
Where relevant assessment has to be done according to ISO — TR
9122.
Where appropriate the nature and characteristics of protective clothing
and equipment proposed must be provided. The data provided must be
sufficient to evaluate the suitability and effectiveness under realistic
conditions of use (e.g. field or glasshouse circumstances).
4.5. Emergency measures in the case of an accident
Whether arising during transport, storage or use, detailed procedures to
be followed in the event of an emergency, must be provided; and
include:
— containment of spillages,
— decontamination of areas, vehicles and buildings,— disposal of damaged packaging, adsorbents and other materials,
— protection of emergency workers and bystanders,
— first aid measures.
4.6. Procedures for destruction or decontamination of the plant protection
product and its packaging
Procedures for destruction and decontamination must be developed for
bothsmall quantities (user level) and large quantities (wareh ouse
level). The procedures must be consistent with provisions in placerelating to the disposal of waste and of toxic waste. The means of
disposal proposed should be without unacceptable influence on the
environment and be the most cost effective and practical means of
disposal feasible.
4.6.1. Possibility of neutralization
Neutralization procedures (e.g by reaction withalkali to form less
toxic compounds) for use in the event of accidental spillages, must
where they are feasible, be described. The products produced after
neutralization should be practically or theoretically evaluated and
reported.
4.6.2. Controlled incineration
In many cases the preferred or sole means to safely dispose of active
substances as well as plant protection products containing it, contami-
nated materials, or contaminated packaging, is through controlled
incineration in a lincensed incinerator.
Where the content of halogens of the active substance(s) in the
preparation is greater than 60 %, the pyrolytic behaviour of the active
substance under controlled conditions (including where relevant supply
of oxygen and defined residence time) at 800 ºC and the content of
polyhalogenated dibenzo-p-dioxins and dibenzo-furans in the products1991L0414 — EN — 01.07.2003 — 009.001 — 106
▼M2
of pyrolysis must be reported. The applicant must provide detailed
instructions for safe disposal.
4.6.3. Others
Other methods to dispose of plant protection products, packaging and
contaminated materials, where proposed, must be fully described. Data
must be provided for such methods, to establish their effectiveness and
safety.
5.Analyticalmethods
Introduction
The provisions of this section only cover analytical methods required
for post-registration control and monitoring purposes.
For analytical methods used for generation of data as required in this
Directive or for other purposes the applicant has to provide a justifica-
tion for the method used; where necessary separate guidance will be
developed for such methods on the basis of the same requirements as
defined for methods for post-registration control and monitoring
purposes.
Descriptions of methods must be provided and include details of
equipment, materials and conditions used.
As far as practicable these methods must employ the simplest
approach, involve the minimum cost, and require commonly available
equipment.
For this section the following applies:
Impurities Any component other than the pure active
substance which is present in the active
substance as manufactured (including non-
active isomers) originating from the manu-
facturing process or from degradation during
storage
Relevant impurities Impurities of toxicological and/or ecotoxico-
logical or environmental concern
Metabolites Metabolites include products resulting from
degradation or reaction of the active
substance
Relevant metabolites Metabolites of toxicological and/or ecotoxi-
cological or environmental concern
On request the following samples must be provided:
(i) samples of the preparation;
(ii) analytical standards of the pure active substance;
(iii) samples of the active substance as manufactured;
(iv) analytical standards of relevant metabolites and all other compo-
nents included in the residue definition;
(v) if available, samples of reference substances for the relevant
impurities.
For definitions see Annex II, Section 4, points 4.1 and 4.2.
5.1.Methodsfortheanalysisofthepreparation
5.1.1. Methods, which must be described in full, must be provided for the
determination of the active substance in the preparation. In the case
of a preparation containing more than one active substance a method
capable of determining each, in the presence of the other, should be
provided. If a combined method is not submitted, the technical reasons
must be stated. The applicability of existing Cipac methods must be
reported.
5.1.2. Methods must also be provided for the determination in the prepara-
tion of relevant impurities, if the composition of the preparation is
such that — on the basis of theoretical consideration — such impuri-
ties may be formed by its manufacturing process or from degradation
during storage.1991L0414 — EN — 01.07.2003 — 009.001 — 107
▼M8
▼M8
If required, methods for the determination of formulants or constitu-
ents of formulants in the preparation must be submitted.
5.1.3. Specificity, linearity, accuracy and repeatability5.1.3.1. Specificity of methods submitted, must be demonstrated and reported.
In addition the extent of interference by other substances present in the
preparation must be determined.
While interferences due to other components may be identified as
systematic errors in the assessment of the accuracy of methods
proposed, an explanation must be provided for any interference occur-
ring which contribute more than ± 3 % to the total quantity
determined.
5.1.3.2. The linearity of proposed methods over an appropriate range, must be
determined and reported. The calibration range must extend (by at
least 20 %) the highest and lowest nominal content of the analyte in
relevant analytical solutions of the preparation. Duplicate calibration
determinations must be made at three or more concentrations. Alterna-
tively, five concentrations, eachas single measurements, are
acceptable. Reports submitted must include the equation of the calibra-
tion line and the correlation coefficient and representative and
properly labelled documentation from the analysis, e.g. chromato-
grams.
5.1.3.3. Accuracy will normally only be required for methods for the determi-
nation of pure active substance and relevant impurities in the
preparation.
5.1.3.4. For the repeatability in principle a minimum of five determinations
must be made. The relative standard deviation (% RSD) must be
reported. Outliers identified through an appropriate method (e.g.
Dixons or Grubbs test), may be discarded. Where outliers have been
discarded, that fact must be clearly indicated. An explanation as to
the reason for the occurrence of individual outliers, must be attempted.
5.2.Analyticalmethodsforthedeterminationofresidues
Analytical methods for the determination of residues must be
submitted unless it is justified that the methods already submitted
according to the requirements of Annex II, Section 4, point 4.2 can
be applied.
The same provisions as provided in Annex II, Section 4, point 4.2
apply.
6. Efficacy data
General
The data supplied must be sufficient to permit an evaluation of the
plant protection product to be made. In particular it must be possible
to evaluate the nature and extent of benefits that accrue following use
of the preparation, where they exist in comparison to suitable refer-
ence products and damage thresholds, and to define its conditions of
use.
The number of trials to be conducted and reported depends mainly on
factors such as the extent to which the properties of the actieve
substance(s) it contains are known and on the range of conditions
that arise, including variability in plant health conditions, climatic
differences, the range of agriculral practices, the uniformity of the
crops, the mode of application the type of harmful organism and the
type of plant protection product.
Sufficient data must be generated and submitted to confirm that
patterns determined hold for the regions and the range of conditions,
likely to be encountered in the regions concerned, for which its use
is to be recommended. Where an applicant claims that tests in one or
more of the proposed regions of use are unnecessary because condi-
tions are comparable with those in other regions where tests have
been carried out, the applicant must substantiate the claim for compar-
ability withdocumentary evidence.
In order to assess seasonal differences, if any, sufficient data must be
generated and submitted to confirm the performance of the plant
protection product in eachagronomically and climatically different
region for eachparticular crop (or commodity)/h armful organism1991L0414 — EN — 01.07.2003 — 009.001 — 108
▼M1
▼M1
combination. Normally trials on effectiveness or phytotoxicity, where
relevant, in at least two growing seasons must be reported.
If to the opinion of the applicant the trials from the first season
adequately confirm the validity of claims made on the basis of extra-
polation of results from other crops, commodities or situations or from
tests withclosely similar preparations, a justification, wh ichis accep-
table to the competent authority for not carrying out a second seaons's
work must be provided. Conversely, where, because of climatic or
plant health conditions or other reasons the data obtained in any parti-
cular season are of limited value for the assessment of performance,
trials in one or more further seasons must be conducted and reported.
6.1. Preliminary tests
Reports in summary form of preliminary tests, including glasshouse
and field studies, used to assess the biological activity and dose range
finding of the plant protection product and of the active substance(s) it
contains, must be submitted when requested by the competent
authority. These reports will provide additional information for the
competent authority when it evaluates the plant production product.
Where this information is not submitted a justification which is accep-
table to the competent authority must be provided.
6.2. Testing effectiveness
Aim of the tests
The tests shall provide sufficient data to permit an evaluation of the
level, duration and consistency of control or protection or other
intended effects of the plant protection product in comparison to
suitable reference products, where they exist.
Test conditions
Normally a trial consists of three components: test product, reference
product and untreated control.
The performance of the plant protection product must be investigated
in relation to suitable reference products, where they exist. A suitable
reference product is defined as an authorized plant protection product
which has proved a sufficient performance in practice under the agri-
cultural, plant health and environmental (including climatic)
conditions in the area of proposed use. In general, formulation type,effects on the harmful organisms, working spectrum and method of
application should be close to those of the tested plant protection
product.
Plant protection products must be tested in circumstances where the
target harmful organism has been shown to have been present at a
level causing or known to cause adverse effects (yield, quality, opera-
tional benefit) on an unprotected crop or area or on plants or plant
products which have not been treated or where the harmful organism
is present at such a level that an evaluation of the plant protection
product can be made.
Trials to provide data on plant protection products for control of
harmful organisms must show the level of control of the species of
harmful organisms concerned or of species representative of groups
for which claims are made. Trials must include the different stages of
growth of life cycle of the harmful species, where this is relevant and
the different strains or races, where these are likely to show different
degrees of susceptibility.
Similarly, trials to provide data on plant protection products which are
plant growth regulators, must how the level of effects on the species to
be treated, and include investigation of differences in the response of a
representative sample of the range of cultivars on which its use is
proposed.
In order to clarify the dose response, dose rates lower than the recom-
mended one must be included in some trials in order to enable to
assess whether the recommended rate is the minimum necessary to
achieve the desired effect.
The duration of the effects of treatment must be investigated in rela-
tion to the control of the target organism or effect on the treated plants
or plant products, as appropriate. When more than one application is
recommended, trials must be reported which establish the duration of1991L0414 — EN — 01.07.2003 — 009.001 — 109
▼M1
the effects of an application, the number of applications necessary and
the desired intervals between them.
Evidence must be submitted to show that the dose, timing and
medthod of application recommended give adequate control, protec-
tion or have the intended effect in the range of circumstances likely
to be encountered in practical use.
Unless there are clear indications that the performance of the plant
protection production is unlikely to be affected to a significant degree
by environemental factors, suchas temperature or rain, an investiga-
tion of the effects of such factors on performace must be carried out
and reported, particularly where it is known that the performance of
chemically related products os so affected.
Where proposed label claims include recommendations for the use of
the plant protection product with other plant protection product(s) or
adjuvant(s) information on the performance of the mixture must be
provided.
Test guideline
Trials must be designed to investigate specified issues, to minimize the
effects of random variation between different parts of eachsite and to
enable statistical analysis to be applied to results amenable to such
analysis. The design, analysis and reporting of trials must be in accor-
dance withEuropean and Mediterranean Plant Protection Organization
(EPPO) guidelines 152 and 181. The report shall include a detailed
and critical assessment of the data.
The trials must be carried out in accordance to specific EPPO guide-
lines, where available, or when a requires so and when the test is
carried out on the territory of this, with guidelines satisfying at least
the requirements of the corresponding EPPO guideline.
A statistical analysis of results amenable to suchanalysis must be
carried out; where necessary the test guideline used must be adapted
to enable suchanalysis.
6.3. Information on the occurrence or possible occurrence of
the development of resistance
Laboratory data and where it exists, field information relating to the
occurrence and development of resistance or cross-resistance in popu-
lations of harmful organisms to the active substance(s), or to related
actived substances, must be provided. Where such information is not
directly relevant to the uses for which authorization is ought or to be
renewed (different species of harmful organism or different crops), it
must, if available, nevertheless be provided, as it may provide and
indication of the likelihood of resistance developing in the target
population.
Where there is evidence or information to suggest that, in commercial
use, the development of resistance is likely, evidence must be gener-
ated and submitted as to the sensitivity of the population of the
harmful organism concerned to the plant protection product. In such
cases a management strategy designed to minimize the likelihood of
resistance or cross-resistance developing in target species must be
provided.
6.4. Effects on the yield of treated plants or plant products in
terms of quantity and/or quality
6.4.1. Effects on the quality of plants or plant product
Aim of the tests
The tests shall provide sufficient data to permit an evaluation of the
possible occurrence of taint or odour or other quality aspects of plants
or plant products after treatment withth e plant protection product.
Circumstances in which requiredThe possibility of the occurrence of taint or odour in food crops must
be investigated and be reported where:
— the nature of the products or its use is such that a risk of occur-
rence of taint or odour might be expected,
or1991L0414 — EN — 01.07.2003 — 009.001 — 110
▼M1
— other products based on the same or a closely similar active ingre-
dient have been shown to present a risk of occurrence of taint or
odour.
The effects of plant protection products on other quality aspects of
treated plants or plant products must be investigated and reported
where:
— the nature of the plant protection product or it use could have an
adverse influence on other quality aspects (for example in the case
of use of plant growthregulators close or h arvest), or
— other products based on the same or a closely similar active ingre-
dient have been shown to have an adverse influence on the quality.
Testing should be conducted initially on the main crops on which the
plant protection product is to be used, at twice the normal rates of
application and using, where relevant, the main methods of processing.
Where effects are observed it is necessary to perform testing at the
normal rate of application.
The extent of investigation necessary on other crops will depend on
their degree of similarity of the main crops already tested, the quantity
and quality of data available on those main crops and how far the
manner of use of the plant protection product and methods of proces-
sing the crops, are similar. It is generally sufficient to perform the test
with the main formulation type to be authorized.
6.4.2. Effects on transformation processes
Aim of the testsThe tests shall provide sufficient data to permit an evaluation of the
possible occurrence of adverse effects after treatment withth e plant
protection product on transformation processes or on the quality of
their products.
Circumstances in which requiredWhen the treated plants or plant products are normally intended for
use in transformation process suchas wine making, brewing or bread
making and when at harvest significant residues are present, the possi-bility of the occurrence of adverse effects must be investigated and
reported where:
— there are indications that the use of the plant protection product
could have an influence on the processes involved (for example
in the case of use of plant growth regulators or fungicides close
to harvest),
or
— other products based on the same or a closely similar active ingre-
dient have been shown to have an adverse influence on these
processes or its products.
It is generally sufficient to perform the test with the main formulation
type to be authorized.
6.4.3. Effects on the yield of treated plants or plant products
Aim of the testsThe test shall provide sufficient data to permit an evaluation of the
performance of the plant protection product and of possible occurrence
of yield reduction or loss in storage of treated plants or plant products.
Circumstances in which requiredThe effects of plant protection products on the yield or yield compo-
nents of treated plant products must be determined where relevant.
When treated plants or plant products are likely to be stored the effect
on the yield after storage, including data on starage life must be deter-
mined where relevant.
This information will normally be available from the tests required
under the provisions of point 6.2.1991L0414 — EN — 01.07.2003 — 009.001 — 111
▼M1
6.5. Phytotoxicity to target plants (including different culti-
vars), or to target plant products
Aim of the tests
The test shall provide sufficient data to permit an evaluation of the
performance of the plant protection product and of the possible occur-
rence of phytotoxicity after treatment with the plant protection
product.
Circumstances in which required
For herbicides and for other plant protection products for which
adverse effects, however transitory, are seen during the trials,
performed in accordance to point 6.2, the margins of selectivity on
target crops must be established, using twice the recommended rate
of application. Where serious phytotoxic effects are seen, an inter-
mediate application rate must also be investigated.
Where adverse effects occur, but are claimed to be unimportant in
comparison withth e benefits of use or transient, evidence to support
this claim is required. If necessary yield measurement must be
submitted.
The safety of a plant protection product to the main cultivars of the
main crops for which it is recommended must be demonstrated,
including effects of crop growh stage, vigour, and other factors which
may influence suspectibility to damage or injury.
The extent of investigation necessary on other crops will depend on
their degree of similarity to the main crops already tested, the quantity
and quality of data available on those main crops and how far the
manner of use of the plant protection product, if relevant, is similar.
It is generally sufficient to perform the test with the main formulation
type to be authorized.
Where proposed label claims include recommendations for the use of
the plant protection product with other plant protection product(s), the
provisions of the previous paragraphs apply for the mixture.
Test guideline
Observations concerning phytotoxicity must be performed in the tests
provided for under point 6.2.
Where phytotoxic effects are seen, they must be accurately assessed
and recorded in accordance withEPPO guideline 135 or wh en a
Member State requires so and when the test is carried out on the terri-
tory of this Member State, with guidelines satisfying at least the
requirements of this EPPO guideline.
A statistical analysis of results amenable to suchanalysis must be
carried out, where necessary the test guideline used must be adapted
to enable suchanalysis.
6.6. Observations on undesirable or unintended side-effects, e.
g. on beneficial and other non-target organisms, on
succeeding crops, other plants or parts of treated plants
used for propagating purposes (e. g. seeds, cuttings,
runners)
6.6.1. Impact on succeeding crops
Aim of the information required
Sufficient data must be reported to permit an evaluation of possible
adverse effects of a treatment withth e plant protection product on
succeeding crops.
Circumstances in which required
Where data, generated in accordance with Section 9, point 9.1, shows
that signification residues of the active substance, its metabolites or
degradation products, which have or may have biological activity on
succeeding crops, remain in soil or in plant materials, suchas straw
or organic material up to sowing or planting time of possible
succeeding crops, observations must be submitted on effects on the
normal range of succeedings crops.1991L0414 — EN — 01.07.2003 — 009.001 — 112
▼M1
6.6.2. Impact on other plants, including adjacent crops
Aim of the information requiredSufficient data must be reported to permit an evaluation of possible
adverse effects of a treatment withth e plant protection product on
other plants, including adjacent crops.
Circumstances in which required
Observations must be submitted on adverse effects on other plants,
including the normal range of adjacent crops, when there are indica-
tions that the plant protection product could affect these plants via
vapour drift.
6.6.3. Impact on treated plants or plant products to be used for
propagation
Aim of the information required
Sufficient data must be reported to permit an evaluation of possible
adverse effects of a treatment withth e plant protection product on
plants or plant products ot be used for propagation.
Circumstances in which requiredObservations must be submitted on the impact of plant protection
products on plant parts used for propagation except where the
proposed uses preclude use on crops intended for production of seeds,
cuttings, runners or tubers for planting, as appropriate.
(i) for seeds — viability, germination and vigour;
(ii) cuttings — rooting and growthrates;
(iii) runners — establishment and growth rates;
(iv) tubers — sprouting and normal growth.
Test guideline
Seeds testing shall be done according to ISTA Methods(
1).
6.6.4. Effects on beneficial and other non-target organisms
Any effects, positive or negative, on the incidence of other harmful
organisms, observed in the tests performed in accordance with therequirements of this section, shall be reported. Any observed environ-
mental effects must also be reported, especially effects on wildlife
and/or beneficial organisms.
6.7. Summary and evaluation of data presented under 6.1 to 6.6
A summary of all data and informations provided under points 6.1 to
6.6 must be provided, together with a detailed and a critical assess-
ment of the data, with particular reference to the benefits that the
plant protection product offers, adverse effects that do or may arise
and measures necessary to avoid or minimize adverse effects.
7. Toxicological studies
For proper evaluation of the toxicity of preparations sufficient infor-
mation should be available on acute toxicity, irritation and
sensitization of the active substance. If possible, additional information
on mode of toxic action, toxicological profile and all other known
toxicological aspects of the active substance should be submitted.
In the context of the influence that impurities and other components
can have on toxicological behaviour, it is essential that for each study
submitted, a detailed description (specification) of the material used,
be provided. Tests must be conducted using the plant protection
product to be authorized.
7.1.Acutetoxicity
The studies, data and information to be provided and evaluated, must
be sufficient to permit the identification of effects following a single1991L0414 — EN — 01.07.2003 — 009.001 — 113
(1) International rules for seed testing, 1985. Proceedings of the International Seed Testing
Association, Seed Science and Technology , Volume 13, No 2, 1985.▼M4
▼M4
exposure to the plant protection product, to be assessed, and in parti-
cular to establish, or indicate:
— the toxicity of the plant protection products,
— toxicity of the plant protection product relative to the active
substance,
— the time course and characteristics of the effect with full details of
behavioural changes and possible gross pathological findings at
post-mortem,
— where possible the mode of toxic action, and
— the relative hazard associated with the different routes of exposure.
While the emphasis must be on estimating the toxicity ranges
involved, the information generated must also permit the plant protec-
tion product to be classified in accordance withCouncil Directive 78/
631/EEC. The information generated through acute toxicity testing is
of particular value in assessing hazards likely to arise in accident
situations.
7.1.1. Oral
Circumstances in which required
An acute oral test should always be carried out unless the applicant
can justify to the satisfaction of the competent authority that Article
3.2 of Council Directive 78/631/EEC can be invoked.
Test guidelines
The test must be carried out in accordance with Directive 92/69/EEC
Method B1 or B1 bis.
7.1.2. Percutaneous
Circumstances in which requiredAn acute percutaneous test should always be carried out unless the
applicant can justify to the satisfaction of the competent authority
that Article 3.2 of Council Directive 78/631/EEC can be invoked.
Test guideline
The test must be carried out in accordance with Directive 92/69/EEC
Method B3.
7.1.3. Inhalation
Aim of the test
The test will provide the inhalation toxicity to rats of the plant protec-
tion product or of the smoke it generates.
Circumstances in which required
The test must be carried out where the plant protection product:
— is a gas or liquified gas,
— is a smoke generating formulation or fumigant,— is used withfogging equipment,— is a vapour releasing preparation,
— is an aerosol,
— is a powder containing a significant proportion of particles of
diameter <50 µm (> 1 % on a weight basis),
— is to be applied from aircraft in cases where inhalation exposure is
relevant,
— contains an active substance witha vapour pressure > 1 × 10
−2Pa
and is to be used in enclosed spaces suchas wareh ouses or glass-
houses,
— is to be applied in a manner which generates a significant propor-
tion of particles or droplets of diameter <50 µm (> 1 % on a
weight basis).
Test guideline
The test must be carried out in accordance with Directive 92/69/EEC
Method B2.1991L0414 — EN — 01.07.2003 — 009.001 — 114
▼M4
7.1.4. Skin irritation
Aim of the test
The test will provide the potential of skin irritancy of the plant protec-
tion product including the potential reversibility of the effects
observed.
Circumstances in which required
The skin irritancy of the plant protection product must be determined
except where it is likely, as indicated in the test guideline, that severe
skin effects may be produced or that effects can be excluded.
Test guideline
The test must be carried out in accordance with Directive 92/69/EEC
Method B4.
7.1.5. Eye irritation
Aim of the test
The test will provide the protential for eye irritation of the plant
protection product, including the potential reversibility of the effects
observed.
Circumstances in which required
Eye irritation tests must be conducted except where it is likely, as
indicated in the test guideline, that severe effects on the eyes may be
produced.
Test guideline
The eye irritation must be determined in accordance with Directive 92/
69/EEC Method B5.
7.1.6. Skin sensitization
Aim of the test
The test will provide sufficient information to assess the potential of
the plant protection product to provoke skin sensitization reactions.
Circumstances in which required
The tests must always be carried out except where the active
substance(s) or co-formulants are known to have sensitizing properties.
Test guidelineThe tests have to be carried out in accordance with Directive 92/69/
EEC Method B6.
7.1.7. Supplementary studies for combinations of plant protection products
Aim of the test
In certain cases it may be necessary to carry out the studies as referred
to under points 7.1.1 to 7.1.6 for a combination of plant protection
products where the product label includes requirements for use of the
plant protection product withoth er plant protection products and/or
withadjuvants as a tank mix. Decisions as to th e need for supplemen-
tary studies must be made on a case by case basis, taking into account
the results of the acute toxicity studies of the individual plant protec-
tion products, the possibility for exposure to the combination of the
products concerned and available information or practical experience
withth e products concerned or similar products.
7.2.Dataonexposure
When measuring exposure to a plant protection product in the air
within the breathing area of operators, bystanders or workers the
requirements for measuring procedures described in Annex II A to
Council Directive 80/1107/EEC of 27 November 1980 on the protec-
tion of workers from the risks related to exposure to chemical,
physical and biological agents at work (
1) have to be taken into
account.1991L0414 — EN — 01.07.2003 — 009.001 — 115
(1) OJ No L 327, 3. 12. 1980, p. 8.▼M9
▼M4
7.2.1. Operator exposure
The risks for those using plant protection products depend on the
physical, chemical and toxicological properties of the plant protection
product as well as the type of the product (undiluted/diluted), and on
the route, the degree and duration of exposure. Sufficient information
and data must be generated and reported to permit an assessment of
the extent of exposure to the active substance(s) and/or toxicologically
relevant compounds in the plant protection product likely to occur
under the proposed conditions of use. It must also provide a basis for
the selection of the appropriate protective measures including personal
protective equipment to be used by operators and to be specified on
the label.
7.2.1.1. Estimation of operator exposure
Aim of the estimationAn estimation shall be made, using where available a suitable calcula-
tion model, in order to permit an evaluation of the operator exposure
likely to arise under the proposed conditions of use.
Circumstances in which required
An estimation of operator exposure must always be completed.
Estimation conditionsAn estimation shall be made for each type of application method and
application equipment proposed for use of the plant protection product
taking account of the requirements resulting from the implementation
of the classification and labelling provisions of Directive 78/631/EEC
for handling the undiluted or diluted product as well as the different
types and sizes of containers to be used, mixing, loading operations,
application of the plant protection product, the climatic conditions
and cleaning and routine maintenance of application equipment.
At first an estimation shall be made with the assumption that the
operator is not using any personal protective equipment.
Where appropriate, a second estimation shall be made with the
assumption that the operator is using effective and readily obtainable
protective equipment which is feasible to be used by the operator.
Where protective measures are specified on the label, the estimation
will take these into account.
7.2.1.2. Measurement of operator exposure
Aim of the testThe test shall provide sufficient data to permit an evaluation of the
operator exposure likely to arise under the proposed conditions of use.
Circumstances in which required
Actual exposure data for the relevant exposure route(s) must be
reported where the risk assessment indicates that a health-based limit
value is exceeded. This will, for example, be the case when the results
of the estimation of operator exposure provided for under point 7.2.1.1
indicate that:
— the Acceptable Operator Exposure Level(s) (AOEL) established in
the context of inclusion of the active substance(s) in Annex I, and/
or
— the Limit Values established for the active substance and/or toxico-
logically relevant compound(s) of the plant protection product in
accordance withCouncil Directive 80/1107/EEC and Council
Directive 90/394/EEC of 28 June 1990 on the protection of
workers from the risks related to exposure to carcinogens at
work(
1),
may be exceeded.Actual exposure data must also be reported when no appropriate
calculation model or no appropriate data are available to do the esti-
mation provided for under point 7.2.1.1.1991L0414 — EN — 01.07.2003 — 009.001 — 116
(1) OJ No L 196, 26. 7. 1990, p. 1.
▼M4
In cases where dermal exposure is the most important exposure route,
a dermal absorption test or the results of a sub-acute dermal study, if
not already available, may be a useful alternative test to provide data
in order to refine the estimate provided for under point 7.2.1.1.
Test conditions
The test must be done under realistic exposure conditions taking into
account the proposed conditions of use.
7.2.2. Bystander exposure
Bystanders can be exposed during the application of plant protection
products. Sufficient information and data must be reported to provide
a basis for the selection of appropriate conditions of use, including the
exclusion of bystanders from treatment areas and separation distances.
Aim of the estimation
An estimation shall be made, using where available a suitable calcula-
tion model in order to permit an evaluation of the bystander exposure
likely to arise under the proposed conditions of use.
Circumstances in which required
An estimation of bystander exposure must always be completed.
Estimation conditionsAn estimation of bystander exposure must be made for eachtype of
application method. The estimation shall be made with the assumption
that bystanders do not use any personal protective equipment.
Measurement of bystander exposure may be required when estimates
indicate a cause for concern.
7.2.3. Worker exposure
Workers can be exposed following application of plant protection
products, when entering treated fields or premises or handling treated
plants or plant products on which residues remain. Sufficient informa-
tion and data must be reported to provide a basis for the selection of
appropriate protective measures, including waiting and re-entry
periods.
7.2.3.1. Estimation of worker exposure
Aim of the estimationAn estimation shall be made using where available a suitable calcula-
tion model, in order to permit an evaluation of the worker exposure
likely to arise under the proposed conditions of use.
Circumstances in which required
The estimation of worker exposure must always be completed.Estimation conditions
An estimation of worker exposure must be made for eachcrop and
task to be carried out.
At first the estimation shall be made using available data on the expo-
sure to be expected with the assumption that the worker is not using
any personal protective equipment.
Where appropriate, a second estimation shall be made with the
assumption that the worker is using effective and readily obtainable
protective equipment which is feasible to be used.
Where appropriate, a further estimation shall be made using data
generated on the amount of dislodgeable residues under the proposed
conditions of use.
7.2.3.2. Measurement of worker exposure
Aim of the testThe test shall provide sufficient data to permit an evaluation of the
worker exposure likely to arise under the proposed conditions of use.
Circumstances in which requiredActual exposure data for the relevant exposure route(s) must be
reported where the risk assessment indicates that a health-based limit
value is exceeded. This will, for example, be the case where the1991L0414 — EN — 01.07.2003 — 009.001 — 117
▼M4
results of the estimation of worker exposure provided for under point
7.2.3.1 indicate that:
— the AOEL(s) established in the context of inclusion of the active
substance(s) in Annex I,
and/or
— the Limit Values established for the active substance and/or toxico-
logically relevant compound(s) of the plant protection product in
accordance withCouncil Directives 80/1107/EEC and 90/394/
EEC,
may be exceeded.Actual exposure data must also be reported when no appropriate
calculation model or no appropriate data are available to do the esti-
mation provided for under point 7.2.3.1.
Where dermal exposure is the most important exposure route, a dermal
absorption test, if not already available, may be a useful alternative
test to provide data in order to refine the estimate provided for under
point 7.1.3.1.
Test conditions
The test must be done under realistic exposure conditions taking into
account the proposed conditions of use.
7.3.Dermalabsorption
Aim of the test
The test shall provide a measurement of the absorption of the active
substance and toxicologically relevant compounds through the skin.
Circumstances in which requiredThe study must be conducted when dermal exposure is a significant
exposure route and where the risk assessment indicates that a health-
based limit value is exceeded. This will, for example, be the case
where the results of the estimation or measurement of operator expo-
sure provided for under points 7.2.1.1 or 7.2.1.2 indicate that:
— the AOEL(s) established in the context of inclusion of the active
substance(s) in Annex I,
and/or
— the limit values established for the active substance and/or toxico-
logically relevant compound(s) of the plant protection product in
accordance withCouncil Directives 80/1107/EEC and 90/394/
EEC may be exceeded.
Test conditions
In principle data of an in vivorat skin absorption study must be
reported. If, when the results of the estimation using these in vivo
skin absorption data are incorporated in the risk assessment, there
remains an indication of excessive exposure, it may be necessary to
perform an in vivocomparative absorption study on rat and human
skin.
Test guideline
Appropriate elements of OECD guideline 417 are to be used. For the
design of the studies it may be necessary to take into account the
results of the skin absorption studies with the active substance(s).
7.4.Availabletoxicological datarelating tonon-activesubstances
Where available, a copy of the notification and the safety data sheet
submitted in the context of Directive 67/548/EEC and Commission
Directive 91/155/EEC of 5 March1991 defining and laying down th e
detailed arrangements for the system of specific information relating
to dangerous preparations in implementation of Article 10 of Council
Directive 88/379/EEC (
1) must be submitted for eachformulant. All
other available information should be submitted.1991L0414 — EN — 01.07.2003 — 009.001 — 118
(1) OJ No L 76, 22. 3. 1991, p. 35.
▼M9
8. Residues in or on treated products, food and feed
Introduction
The provisions of Annex II, Section 6, Introduction apply.
8.1.Metabolism, distribution and expression of residue in plants or
livestock
Aim of the tests
The objectives of these studies are:
— to provide an estimate of total terminal residues in the relevant
portion of crops at harvest following treatment as proposed,
— to quantify the rate of degradation and excretion of the total
residue in certain animal products (milk or eggs) and excreta,
— to identify the major components of the total terminal residue in
crops and in edible animal products respectively,
— to indicate the distribution of residues between relevant crop parts
and between relevant edible animal products respectively,
— 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 8.3 can be made,
— to decide on the definition and expression of a residue.
Circumstances in which requiredSupplementary metabolism studies only need to be performed where it
is not possible to extrapolate from data obtained on the active
substance in accordance to the requirements of Annex II, Section 6,
points 6.1 and 6.2. This might be the case for crops or for livestock
for which data were not submitted in the framework of inclusion of
the active substance in Annex I or were not necessary for amending
the conditions of its inclusion in Annex I or where it could be
expected that a different metabolism will occur.
Test conditionsThe same provisions as provided under the corresponding paragraphs
of Annex II, Section 6, points 6.1 and 6.2 apply.
8.2.Residuetrials
Aim of the tests
The objectives of these studies are:
— to quantify the highest likely residue levels in treated crops at
harvest or outloading from store following the proposed good agri-
cultural practice (GAP),
and
— to determine, when appropriate, the rate of decline of pesticide
deposits.
Circumstances in which required
Supplementary residue trials only need to be performed where it is not
possible to extrapolate from data obtained on the active substance in
accordance to the requirements of Annex II, Section 6, point 6.3.
This might be the case for special formulations, for special application
methods or for crops for which data were not submitted in the frame-
work of inclusion of the active substance in Annex I or were not
necessary for amending the conditions of its inclusion in Annex I.
Test conditionsThe same provisions as provided under the corresponding paragraphs
of Annex II, Section 6, point 6.3 apply.
8.3.Livestockfeedingstudies
Aim of the tests
The objective of these studies is to determine the residue in products
of animal origin which will result from residues in feedingstuffs or
fodder crops.1991L0414 — EN — 01.07.2003 — 009.001 — 119
▼M9
Circumstances in which required
Supplementary feeding studies for the purpose of assessing maximum
residue levels for products of animal origin are only required where it
is not possible to extrapolate from data obtained on the active
substance in accordance to the requirements of Annex II, Section 6,
point 6.4. This might be the case where additional fodder crops are
to be authorized which leads to an increased intake of residues of live-
stock for which data were not submitted in the framework of inclusion
of the active substance in Annex I or were not necessary for amending
the conditions of its inclusion in Annex I.
Test conditions
The same provisions as provided under the corresponding paragraphs
of Annex II, Section 6, point 6.4 apply.
8.4.Effectsofindustrialprocessingand/orhouseholdpreparations
Aim of the testsThe main objectives of these studies are:
— to establish whether or not breakdown or reaction products arise
from residues in the raw products during processing which may
require a separate risk assessment,
— 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.
Circumstances in which requiredSupplementary studies only need to be performed where it is not
possible to extrapolate from data obtained on the active substance in
accordance to the requirements of Annex II, Section 6, point 6.5.
This might be the case for crops for which data were not submitted
in the framework of inclusion of the active substance in Annex I or
were not necessary for amending the conditions of its inclusion in
Annex I.
Test conditions
The same provisions as provided under the corresponding paragraphs
of Annex II, Section 6, point 6.5 apply.
8.5.Residuesinsucceedingcrops
Aim of the test
The objective of these studies is to permit an evaluation of possible
residues in succeeding crops.
Circumstances in which required
Supplementary studies are only required where it is not possible to
extrapolate from data obtained on the active substance in accordance
to the requirements of Annex II, Section 6, point 6.6. This might be
the case for special formulations, for special application methods or
for crops for which data were not submitted in the framework of inclu-
sion of the active substance in Annex I or were not necessary for
amending the conditions of its inclusion in Annex I.
Test conditions
The same provisions as provided under the corresponding paragraphs
of Annex II, Section 6, point 6.6 apply.
8.6.Proposedmaximumresiduelevels(MRLs)andresiduedefinition
A full justification for the proposed MRLs must be provided,
including, where relevant, full details of the statistical analysis used.
If the metabolism studies submitted in accordance with the provisions
of point 8.1 indicate that the residue definition should be changed
taking into account the actual residue definition and the necessary
judgement as outlined under the corresponding paragraph of Annex
II, Section 6, point 6.7, a re-evaluation of the active substance may
be necessary.1991L0414 — EN — 01.07.2003 — 009.001 — 120
▼M9
8.7.Proposed pre-harvest intervals for envisaged uses, or withholding
periodsorstorageperiods,inthecaseofpost-harvestuses.
A full justification for the proposals must be provided.
8.8.Estimation of the potential and actual exposure through diet and
othermeans
Consideration will be given to the calculation of a realistic prediction
of dietary intake. This may be done in a step-wise fashion leading to
an increasingly realistic prediction of intake. Where relevant, other
sources of exposure suchas residues arising from th e use of medicines
or veterinary drugs have to be taken into account.
8.9.Summaryandevaluationofresiduebehaviour
A summary and evaluation of all data presented in this Section should
be carried out according to the guidance given by the competent
authorities of the Member States concerning the format of such
summaries and evaluations. It should include a detailed and critical
assessment of those data in the context of relevant evaluative and deci-
sion-making criteria and guidelines, withparticular reference to th e
risks for man and animals that may or do arise, and the extent, quality
and reliability of the data base.
Where metabolism data have been submitted the toxicological signifi-
cance of any non-mammalian metabolites must be addressed.
A schematic diagram should be prepared of the metabolic pathway in
plants and animals witha brief explanation of th e distribution and
chemical changes involved if metabolism data have been submitted.
9.Fateandbehaviourintheenvironment
Introduction
(i) The information provided, taken together with that for the active
substance as provided for in Annex II, must be sufficient to
permit an assessment of the fate and behaviour of the plant
protection product in the environment, and of the non-target
species likely to be at risk from exposure to it.
(ii) In particular, the information provided for the plant protection
product, together with other relevant information, and that
provided for the active substance, should be sufficient to:
— specify the hazard symbols, the indications of danger, and
relevant risk and safety phrases for the protection of the envir-
onment, which are to be included on packaging (containers),
— predict the distribution, fate, and behaviour in the environ-
ment as well as the time courses involved,
— identify non-target species and populations for which hazards
arise because of potential exposure, and
— identify measures necessary to minimize contamination of the
environment and impact on non-target species.
(iii) Where radio-labelled test material is used, the provisions of
Annex II, Chapter 7, introduction, point (iv) apply.
(iv) Where relevant tests should be designed and data analysed using
appropriate statistical methods.
Full details of the statistical analysis should be reported (e.g. all
point estimates should be given with confidence intervals, exact
p-values should be given rather than stating significant/non
significant).
(v) Predicted environmental concentrations in soil (PECS), water
(PECSWand PECGW) and air (PECA).
Justified estimates must be made of the expected concentrations
of the active substance and relevant metabolites, degradation and
reaction products, in soil, groundwater, surface water and air,
following use as proposed or already occurring. In addition a
realistic worst-case estimation must be made.
For the purposes of the estimation of such concentrations the
following definitions apply:
—Predicted environmental concentration in soil (PECS)
The level of residues in the top layer of the soil and to which
non-target soil organisms may be exposed (acute and chronic
exposure).1991L0414 — EN — 01.07.2003 — 009.001 — 121
▼M6
▼M6
—Predicted environmental concentration in surface water
(PECSW)
The level of residues, in surface water to which non-target
aquatic organisms may be exposed (acute and chronic expo-
sure).
—Predicted environmental concentration in groundwater
(PECGW)
The level of residues in groundwater.
—Predicted environmental concentration in air (PECA)
The level of residues in air, to which man, animals and other
non-target organisms may be exposed (acute and chronic
exposure).
For the estimation of these concentrations all relevant information
on the plant protection product and on the active substance must
be taken into account. A useful approachfor th ese estimations is
provided in the EPPO schemes for environmental risk assess-
ment (1). Where relevant the parameters provided for in this
section should be used.
When models are used for estimation of predicted environmental
concentrations they must:
— make a best-possible estimation of all relevant processes
involved taking into account realistic parameters and assump-
tions,
— where possible be reliably validated with measurements
carried out under circumstances relevant for the use of the
model,
— be relevant to the conditions in the area of use.
The information provided must, where relevant, include that referred
to in Annex II, Part A, point 7: and
9.1Fateandbehaviourinsoil
Where appropriate, the same provisions relating to the information to
be provided on the soil used and on its selection apply as provided for
under Annex II, point 7.1.
9.1.1. Rate of degradation in soil
9.1.1.1. Laboratory studies
Aim of the testThe soil degradation studies should provide best possible estimates of
the time taken for degradation of 50 and 90 % (DT
50laband DT90lab)o f
the active substance under laboratory conditions.
Circumstances in which requiredThe persistence and behaviour of plant protection products in soil
must be investigated unless it is possible to extrapolate from data
obtained on the active substance and relevant metabolites, degradation
and reaction products in accordance to the requirements of Annex II,
point 7.1.1.2. This extrapolation is, for example, not possible for slow
release formulations.
Test conditionsThe rate of aerobic and/or anaerobic degradation in soil must be
reported.
The duration of the study is normally 120 days except if more than
90 % of the active substance is degraded before that period expires.
Test guidelineSETAC — Procedures for assessing the environmental fate and
ecotoxicity of pesticides.
9.1.1.2. Field studies
— Soil dissipation studies
Aim of the test1991L0414 — EN — 01.07.2003 — 009.001 — 122
(1) OEPP/EPPO (1993). Decision-making schemes for the environmental risk assessment
of plant protection products. Bulletin OEPP/EPPO Bulletin 23, 1-154 and Bulletin 24,
1-87.
▼M6
The soil dissipation studies should provide best-possible estimates
of the time taken for dissipation of 50 and 90 % (DT50fand DT90f),
of the active substance under field conditions. Where relevant,
information on relevant metabolites, degradation and reaction
products must be collected.
Circumstances in which required
The dissipation and behaviour of plant protection products in soil
must be investigated unless it is possible to extrapolate from data
obtained on the active substance and relevant metabolites, degrada-
tion and reaction products in accordance to the requirements of
Annex II, point 7.1.1.2. This extrapolation is, for example, not
possible for slow-release formulations.
Test conditions and test guideline
The same provisions as provided under the corresponding para-
graphof Annex II, point 7.1.1.2.2. apply.
— Soil residue studies
Aim of the test
Soil residue studies should provide estimates of the soil residue
levels at harvest or at time of sowing or planting succeeding crops.
Circumstances in which required
Soil residue studies must be reported unless it is possible to extra-
polate from data obtained on the active substance and relevant
metabolites, degradation and reaction products in accordance with
the requirements of Annex II, point 7.1.1.2.2. This extrapolation is,
for example, not possible for slow-release formulations.
Test conditionsThe same provisions as provided under the corresponding para-
graphof Annex II, point 7.1.1.2.2. apply.
Test guideline
SETAC — Procedures for assessing the environmental fate and
ecotoxicity of pesticides.
— Soil accumulation studies
Aim of the tests
The tests should provide sufficient data to evaluate the possibility
of accumulation of residues of the active substance and of relevant
metabolites, degradation and reaction products.
Circumstances in which requiredSoil accumulation studies must be reported unless it is possible to
extrapolate from data obtained on the active substance and relevant
metabolites, degradation and reaction products in accordance with
the requirements of Annex II, point 7.1.1.2.2. This extrapolation is,
for example, not possible for slow-release formulations.
Test conditions
The same provisions as provided under the corresponding para-
graphof Annex II, point 7.1.1.2.2. apply.
Test guideline
SETAC — Procedures for assessing the environmental fate and
ecotoxicity of pesticides.
9.1.2. Mobility in the soil
Aim of the test
The test should provide sufficient data to evaluate the mobility and
leaching potential of the active substance and relevant metabolites,
degradation and reaction products.
9.1.2.1. Laboratory studies
Circumstances in which required
The mobility of plant protection products in soil must be investigated
unless it is possible to extrapolate from data obtained in accordance
with the requirements of Annex II, points 7.1.2 and 7.1.3.1. This extra-
polation is, for example, not possible for slow-release formulations.
Test guidelineSETAC — Procedures for assessing the environmental fate and
ecotoxicity of pesticides.
9.1.2.2. Lysimeter studies or field leaching studies
Aim of the tests1991L0414 — EN — 01.07.2003 — 009.001 — 123
▼M6
The test should provide data on:
— the mobility of the plant protection product in soil,
— the potential for leaching to ground water,— the potential distribution in soils.
Circumstances in which required
Expert judgement will be necessary to decide whether field leaching
studies or lysimeter studies should be carried out, taking into account
the results of degradation and mobility studies and the calculated
PEC
s. The type of study to be conducted should be discussed with
the competent authorities.
These studies must be performed unless it is possible to extrapolate
from data obtained on the active substance and relevant metabolites,
degradation and reaction products in accordance withth e requirements
of Annex II, point 7.1.3. This extrapolation is, for example, not
possible for slow release formulations.
Test conditions
The same provisions as provided for under the corresponding para-
graphof Annex II, point 7.1.3.3 apply.
9.1.3. Estimation of expected concentrations in soil
PECsestimations must relate both to a single application at the highest
rate of application for which authorization is sought, and to the
maximum number and highest rates of application for which authori-
zation is sought, for each relevant soil tested, and are expressed in
terms of mg of active substance and of relevant metabolites, degrada-
tion and reaction products per kg of soil.
The factors to be considered in making PECsestimations relate to
direct and indirect application to soil, drift, run off, and leaching and
include processes such as volatilization, adsorption, hydrolysis, photo-
lysis, aerobic and anaerobic degradation. For the purposes of PECscalculations, the bulk density of soils can be assumed to be 1,5 g/cm3
dry weight, while the depth of the soil layer is assumed to be 5 cm for
applications at the soil surface and 20 cm when incorporation in the
soil is involved. Where ground cover is present at time of application,
it is to be assumed that 50 % (minimum) of the applied dose reaches
the soil surface unless actual experimental data give more specific
information.
Initial, short-term and long-term PECscalculations (time weighted
averages) must be provided:
— initial: immediately after application,
— short-term: 24 hours, 2 days and 4 days after last application,— long-term: 7, 28, 50 and 100 days after last application, where
relevant.
9.2.Fateandbehaviourinwater
9.2.1. Estimation of concentrations in groundwater
The groundwater contamination routes have to be defined taking into
account relevant agricultural, plant health, and environmental
(including climatic) conditions.
Suitable estimations (calculations) of predicted environmental concen-
tration in groundwater PEC
GW, of active substance and relevant
metabolites, degradation and reaction products, must be submitted.
PEC estimations must relate to the maximum number and highest rates
of application, for which authorization is sought.
Expert judgment is required to decide if additional field tests could
provide useful information. Before performing these studies the appli-
cant shall seek the agreement of the competent authorities on the typeof study to be performed.
9.2.2. Impact on water treatment procedures
In cases where this information is necessary in the framework of a
conditional authorization as meant in Annex VI, Part C, point 2.5.1.2
(b), the information provided should permit to establish or to estimate
effectiveness of water treatment procedures (drinking water and1991L0414 — EN — 01.07.2003 — 009.001 — 124
▼M6
sewage treatment), and impact on suchprocedures. Before performing
any studies the applicant shall seek the agreement of the competent
authorities on the type of information to be provided.
9.2.3. Estimation of concentrations in surface water
The surface water contamination routes have to be defined taking into
account relevant agricultural, plant health, and environmental
(including climatic) conditions.
Suitable estimations (calculations) of predicted environmental concen-
tration in surface water PECsw, of active substance and relevant
metabolites, degradation and reaction products, must be submitted.
PEC estimations must relate to the maximum number and highest rates
of application, for which authorization is sought, and be relevant to
lakes, ponds, rivers, canals, streams, irrigation/drainage canals and
drains.
The factors to be considered in making PECswestimations relate to
direct application to water, drift, run-off, discharge via drains and
atmospheric deposition, and include processes such as volatilization,
adsorption, advection, hydrolysis, photolysis, biodegradation, sedimen-
tation and re-suspension.
Initial, short-term and long-term PECswcalculations relevant to static
and slow moving water bodies (time weighted averages) must be
provided:
— initial: immediately after application,
— short-term: 24 hours, 2 days and 4 days after last application,
— long-term: 7, 14, 21, 28, and 42 days after last application, where
relevant.
Expert judgment is required to decide if additional field tests could
provide useful information. Before performing these studies the appli-
cant shall seek the agreement of the competent authorities on the type
of study to be performed.
9.3.Fateandbehaviourinair
Guidance under development.
10.Ecotoxicological studies
Introduction
(i) The information provided, taken together with that for the active
substance(s), must be sufficient to permit an assessment of the
impact on non-target species (flora and fauna), of the plant
protection product, when used as proposed. Impact can result
from single, prolonged or repeated exposure, and can be rever-
sible, or irreversible.
(ii) In particular, the information provided for the plant protection
product, together with other relevant information, and that
provided for the active substance, should be sufficient to:
— specify the hazard symbols, the indications of danger, and
relevant risk and safety phrases for the protection of the
environment, to be mentioned on packaging (containers),
— permit an evaluation of the short- and long-term risks for
non-target species — populations, communities, and
processes as appropriate,
— permit an evaluation of whether special precautions are
necessary for the protection of non-target species.
(iii) There is a need to report all potentially adverse effects found
during routine ecotoxicological investigations and to undertake
and report suchadditional studies wh ichmay be necessary to
investigate the mechanisms involved and assess the significance
of these effects.
(iv) In general, muchof th e data relating to impact on non-target
species, required for authorization of plant protection products,
will have been submitted and evaluated for the inclusion of the
active substance(s) in Annex I. The information on fate and
behaviour in the environment, generated and submitted in accor-
dance withpoints 9.1 to 9.3, and on residue levels in plants
generated and submitted in accordance withpoint 8 is central1991L0414 — EN — 01.07.2003 — 009.001 — 125
▼M7
▼M7
to the assessment of impact on non-target species, in that it
provides information on the nature and extent of potential or
actual exposure. The final PEC estimations are to be adapted
according to the different groups of organisms taking in parti-
cular into consideration the biology of the most sensitive
species.
The toxicological studies and information submitted in accor-
dance withpoint 7.1 provide essential information as to
toxicity to vertebrate species.
(v) Where relevant, tests should be designed and data analysed
using appropriate statistical methods. Full details of the statis-
tical analysis should be reported (e.g. all point estimates should
be given withconfidence intervals, exact p-values sh ould be
given rather than stating significant/non significant).
(vi) Whenever a study implies the use of different doses, the rela-
tionship between dose and adverse effect must be reported.
(vii) Where exposure data are necessary to decide whether a study
has to be performed, the data obtained in accordance with the
provisions of Annex III, point 9 should be used.
For the estimation of exposure of organisms all relevant infor-
mation on the plant protection product and on the active
substance must be taken into account. A useful approachfor
these estimations is provided in the EPPO/Council of Europe
schemes for environmental risk assessment(1). Where relevant
the parameters provided for in this section should be used.
Where it appears from available data that the plant protection
product is more toxic as the active substance, the toxicity data
of the plant protection product have to be used for the calcula-
tion of relevant toxicity/exposure ratios.
(viii) In the context of the influence that impurities can have on
ecotoxicological behaviour, it is essential that for each study
submitted, a detailed description (specification) of the material
used as provided for under point 1.4, be provided.
(ix) In order to facilitate the assessment of the significance of test
results obtained the same strain of each relevant species should
where possible be used in the various toxicity tests specified.
10.1.Effectsonbirds
Possible effects on birds must be investigated except where the possi-
bility that birds will be exposed, directly or indirectly, can be ruled out
suchas for use in enclosed spaces or wound h ealing treatments.
The acute toxicity/exposure ratio (TERa), the short term dietary toxi-
city/exposure ratio (TERst) and the long term dietary toxicity/
exposure ratio (TERlt) must be reported, where:
TERa=L D50(mg a.s./kg body weight) / ETE (mg a.s./kg body weight)
TERst=L C50(mg a.s./kg food) / ETE (mg a.s./kg food)
TERlt= NOEC (mg a.s./kg food) / ETE (mg a.s./kg food)
where ETE = estimated theoretical exposure.In the case of pellets, granules or treated seeds the amount of a.s. in
eachpellet, granule or seed must be reported as well as th e proportion
of the LD
50for the a.s. in 100 particles and per gram of particles. The
size and shape of pellets or granules must be reported.
In the case of baits the concentration of a.s. in the bait (mg/kg) must
be reported.
10.1.1. Acute oral toxicity
Aim of the test
The test should provide, where possible, LD50values, the lethal
threshold dose, time courses of response and recovery, the NOEL,
and must include relevant gross pathological findings.
Circumstances in which requiredThe acute oral toxicity of preparations must be reported, where TER
aor TERstfor the active substance(s) in birds are between 10 and 1001991L0414 — EN — 01.07.2003 — 009.001 — 126
(1) OEPP/EPPO (1993). Decision-making schemes for the environmental risk assessment
of plant protection products. Bulletin OEPP/EPPO Bulletin 23, 1-154 and Bulletin 24,
1-87.
▼M7
or where results from mammal testing give evidence of a significantly
higher toxicity of the prepration compared to the active substance
unless it can be justified that it is not likely that birds are exposed to
the plant protection product itself.
Test conditionsThe study must be conducted on the most sensitive species identified
in the studies provided for in Annex II, point 8.1.1 or 8.1.2.
10.1.2. Supervised cage or field trials
Aim of the testThe test will provide sufficient data to evaluate the nature and the
extent of the risk in practical conditions of use.
Circumstances in which requiredWhere the TER
aand TERstare > 100 and when there is no evidence of
risk from any further study on the active substance (e.g. reproduction
study) no further testing is required. In the other cases, expert judge-
ment is necessary to decide whether there is a need to carry out further
studies. This expert judgement will take into account, where relevant,
foraging behaviour, repellency, alternative food, actual residue content
in the food, persistence of the compound in the vegetation, degrada-
tion of the formulated product or treated produce, the amount of
predation of the food, acceptance of bait, granules or treated seed and
the possibility for bioconcentration.
Where TERaand TERst≤10 or TERlt≤5, cage or field trials must
be conducted and reported unless a final assessment is possible on the
basis of studies according to point 10.1.3.
Test conditions
Before performing these studies the applicant should seek the agree-
ment of the competent authorities on the type and conditions of the
study to be performed.
10.1.3. Acceptance of bait, granules or treated seeds by birds
Aim of the testThe test will provide sufficient data to evaluate the possibility of
consumption of the protection product or plant products treated with it.
Circumstances in which requiredIn the case of seed dressings, pellets, baits and preparations which are
granules and where TER
a≤10, acceptability (palatability) tests must
be conducted.
10.1.4. Effects of secondary poisoning
Expert judgment is required to decide whether the effects of secondary
poisoning should be investigated.
10.2.Effectsonaquaticorganisms
Possible effects on aquatic species must be investigated except where
the possibility that aquatic species will be exposed can be ruled out.
TERaand TERltmust be reported, where:
TERa= acute LC50(mg a.s./l)/realistic worst case PECsw(initial or
short-term, in mg a.s./l)
TERlt= chronic NOEC (mg a.s./l)/long term PECsw(mg a.s./l)
10.2.1. Acute toxicity to fish, aquatic invertebrates or effects on algal growth
Circumstances in which requiredIn principle tests should be carried out on one species from each of the
three groups of aquatic organisms as referred to in Annex II, point 8.2
(fish, aquatic invertebrates and algae) in case the plant protection
product itself can contaminate water. However where the available
information permits to conclude that one of these groups is clearly
more sensitive, tests on only the most sensitive species of the relevant
group have to be performed.
The test must be performed where:
— the acute toxicity of the plant protection product can not be
predicted on the basis of the data for the active substance which1991L0414 — EN — 01.07.2003 — 009.001 — 127
▼M7
is especially the case if the formulation contains two or more
active substances or formulants suchas solvents, emulgators,
surfactants, dispersants, fertilizers which are able to increase the
toxicity in comparison withth e active substance, or
— the intended use includes direct application on water
unless suitable studies referred to under point 10.2.4 are available.
Test conditions and test guidelines
The relevant provisions as under the corresponding paragraphs of
Annex II, points 8.2.1, 8.2.4 and 8.2.6 apply.
10.2.2. Microcosm or mesocom study
Aim of the test
The tests must provide sufficient data to evaluate the essential impact
on aquatic organisms under field conditions.
Circumstances in which required
Where TERa≤100 or where TERlt≤10, expert judgment must be
used to decide whether a microcosm or mesocom study is appropriate.
This judgment will take into account the results of any additional data
over and above those required by the provisions of Annex II, point 8.2
and of point 10.2.1.
Test conditions
Before performing these studies the applicant shall seek the agreement
of the competent authorities on the specific aims of the study to be
performed and consequently on the type and conditions of the study
to be performed.
The study should include at least the highest likely exposure rate,
whether from direct applicaiton, drift, drainage or run-off. The dura-
tion of the study must be sufficient to permit evaluation of all effects.
Test guideline
Appropriate guidelines are included in:
Setac — Guidance document on testing procedures for pesticides in
freshwater mesocosms/Workshop Huntingdon, 3 and 4 July 1991
or
Freshwater field tests for hazard assessment of chemicals — European
Workshop on Freshwater Field Tests (EWOFFT).
10.2.3. Residue data in fish
Aim of the testThe test will provide sufficient data to evaluate the potential for occur-
rence of residues in fish.
Circumstances in which required
In general data are available from bioconcentration studies in fish.
Where bioconcentration has been observed in the study performed in
accordance withAnnex II, point 8.2.3 expert judgement is required to
decide whether a long-term microcosm or mesocosm study has to be
carried out in order to establishth e maximum residues likely to be
encountered.
Test guideline
Setac — Guidance document on testing procedures for pesticides in
freshwater mesocosms/Workshop Huntingdon, 3 and 4 July 1991.
10.2.4. Additional studies
The studies referred to in Annex II, points 8.2.2 and 8.2.5 may be
required for particular plant protection products where it is not
possible to extrapolate from data obtained in the corresponding studies
on the active substance.
10.3.Effectsonterrestrial vertebratesotherthanbirds
Possible effects on wild vertebrate species must be investigated except
where it can be justified that it is not likely that terrestrial vertebrates1991L0414 — EN — 01.07.2003 — 009.001 — 128
▼M7
other than birds are exposed, directly or indirectly. TERa, TERstand
TERltmust be reported, where:
TERa=L D50(mg a.s./kg body weight) / ETE (mg a.s./kg body weight)
TERst= subchronic NOEL (mg a.s./kg food) / ETE (mg a.s./kg food)
TERlt= chronic NOEL (mg a.s./kg food) / ETE (mg a.s./kg food)
where ETE = estimated theoretical exposure.
In principle the evaluation sequence for the assessment of risks to such
species is similar to that for birds. In practice it is not often necessary
to perform further testing as the studies conducted in accordance with
the requirements of Annex II, point 5 and Annex III, point 7 would
provide the required information.
Aim of the test
The test will provide sufficient information to evaluate the nature and
the extent of risks for terrestrial vertebrates other than birds in prac-
tical conditions of use.
Circumstances in which required
Where TERaand TERst> 100 and where there is no evidence of risk
from any further study no further testing is required. In the other
cases, expert judgment is necessary to decide whether there is a need
to carry out further studies. This expert judgment will take into
account, where relevant, foraging behaviour, repellency, alternative
food, actual residue content in the food, persistence of the compound
in the vegetation, degradation of the formulated product or treated
produce, the amount of predation of the food, acceptance of bait, gran-
ules or treated seed and the possibility for bioconcentration.
Where TERaand TERst≤10 or TERlt≤5 cage or field trials or
other appropriate studies must be reported.
Test conditions
Before performing these studies the applicant shall seek the agreement
of the competent authorities on the type and conditions of the study to
be performed and whether the effects of secondary poisoning should
be investigated.
10.4.Effectsonbees
The possible effects on bees must be investigated except where the
product is for exclusive use in situations where bees are not likely to
be exposed suchas:
— 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.
The hazard quotients for oral and contact exposure (Q
HOand QHC),
must be reported:
QHO= dose/oral LD50(µg a.s. per bee)
QHC= dose/contact LD50(µg a.s. per bee)
where
dose = the maximum application rate, for which authorization is
sought, in g of active substance per hectare.
10.4.1. Acute oral and contact toxicity
Aim of the test
The test should provide the LD50values (by oral and contact expo-
sure).
Circumstances in which requiredTesting is required if:
— the product contains more than one active substance;1991L0414 — EN — 01.07.2003 — 009.001 — 129
▼M7
— the toxicity of a new formulation cannot be reliably predicted to be
either the same or lower than a formulation tested according to the
provisions of Annex II, point 8.3.1.1 or of this point.
Test guidelineThe test must be carried out according to EPPO Guideline 170.
10.4.2. Residue test
Aim of the testThe test should provide sufficient information to evaluate possible
risks to foraging bees from residual traces of plant protection products
remaining on crops.
Circumstances in which required
Where Q
HC≥50, expert judgment is required to decide whether the
effect of residues must be determined unless there is evidence that
there are no significant residual traces remaining on crops which could
affect foraging bees or unless sufficient information is available from
cage, tunnel or field tests.
Test conditionsThe median lethal time (LT
50) (in hours) following 24-hour exposure
to residues on leaves aged during eight hours must be determined,
and reported. Where LT50is more than eight hours, no further testing
is required.
10.4.3. Cage tests
Aim of the test
The test should provide sufficient information to evaluate possible
risks from the plant protection product for bee survival and behaviour.
Circumstances in which requiredWhere Q
HOand QHCare < 50, further testing is not required except if
significant effects are observed in the bee brood feeding test or if there
are indications for indirect effects suchas delayed action or modifica-
tion of bee behaviour, in those cases cage and/or field tests shall be
carried out.
Where QHOand QHCare > 50, cage and/or field testing is required.
Where field testing is conducted and reported in accordance with point
10.4.4, it is not necessary to conduct cage tests. However, cage tests
where conducted, must be reported.
Test conditionsThe test should be carried out using healthy bees. If bees have been
treated, e.g. witha varroacide, it is necessary to wait for four weeks
before using the colony.
Test guidelineThe tests must be conducted in accordance with EPPO Guideline 170.
10.4.4. Field tests
Aim of the test
The test should provide sufficient information to evaluate possible
risks from the plant protection product on bee behaviour, colony
survival and development.
Circumstances in which requiredField tests must be conducted where on the basis of expert judgement,
taking into account the proposed manner of use and the fate and beha-
viour of the active substance, significant effects are observed in cage
testing.
Test conditions
The test should be carried out using healthy honeybee colonies of
similar natural strength. If bees have been treated, e.g. with a varroa-
cide, it is necessary to wait for four weeks before using the colony.
The tests shall be conducted under conditions reasonably representa-
tive of the proposed use.1991L0414 — EN — 01.07.2003 — 009.001 — 130
▼M7
Special effects (larval toxicity, long residual effect, disorienting effects
on bees) identified by the field tests may require further investigation
using specific methods.
Test guideline
The tests must be conducted in accordance with EPPO Guideline 170.
10.4.5. Tunnel tests
Aim of the test
The test should provide sufficient information to evaluate the impact
on bees resulting from feeding on contaminated honey dew or flowers.
Circumstances in which required
Where it is not possible to investigate certain effects in cage or field
trials, a tunnel test should be carried out, e.g. in the case of plant
protection products intended for control of aphids and other sucking
insects.
Test conditions
The test should be carried out using healthy bees. If bees have been
treated, e.g. witha varroacide, it is necessary to wait for four weeks
before using the colony.
Test guideline
The test must be carried out in accordance with EPPO Guideline 170.
10.5.Effectsonarthropodsotherthanbees
The effects of plant protection products on non-target terrestrial arthro-
pods (e.g. predators or parasitoids of harmful organisms) must be
investigated. The information obtained for these species can also be
used to indicate the potential for toxicity to non-target species inha-
biting the same environment.
10.5.1. Laboratory, extended laboratory and semi-field tests
Aim of the test
The test should provide sufficient information to evaluate the toxicity
of the plant protection product for selected arthropod species that are
relevant to the intended use of the product.
Circumstances in which required
Testing is not required where severe toxicity (> 99 % effect on the
organisms compared to control) can be predicted from relevant avail-
able data or where the plant protection product is for exclusive use in
situations where non-target arthropods are not exposed such as:
— food storage in enclosed spaces,
— wound sealing and healing treatments,— rodenticidal baits.
Testing is required when significant effects on the organisms in
comparison with the control are reported in the laboratory tests at the
maximum recommended dose, conducted in accordance withth e
requirements of Annex II, point 8.3.2. Effects on a particular test
species are considered to be significant when they exceed the
threshold values as defined in the EPPO schemes for the environ-
mental risk assessment unless species-specific threshold values are
defined in the respective test guidelines.
Testing is also required if:
— the product contains more than one active substance,
— the toxicity of a new formulation cannot be reliably predicted to be
either the same or lower than a formulation tested according to the
provisions of Annex II, point 8.3.2 or of this point,
— on the basis of the proposed manner of use or on the basis of the
fate and behaviour continued or repeated exposure can be antici-
pated,
— there is a significant change in the proposed use, e.g. from arable
crops to orchards, and species relevant to the new use have not
previously been tested,
— there is an increase in the recommended application rate, above
that previously tested under Annex II.1991L0414 — EN — 01.07.2003 — 009.001 — 131
▼M7
Test conditions
Where significant effects were observed in the studies performed in
accordance with the requirements of Annex II, point 8.3.2, or in the
case of change of use such as arable crops to orchards, the toxicity
of two additional relevant species must be investigated and reported.
These must be different to the relevant species already tested under
Annex II, point 8.3.2.
For a new mixture or formulation, the toxicity should initially be
assessed using the two most sensitive species as identified in studies
already performed for which the threshold values were exceeded but
effects still remain below 99 %. This will enable a comparison to be
made; if it significantly more toxic two species relevant to its
proposed use must be tested.
Testing must be conducted at a rate equivalent to the maximum rate of
application for which authorization is sought. A sequential testing
approachsh ould be adopted, i.e. laboratory, and if necessary extended
laboratory and/or semi-field.
Where there will be more than one application per season, the product
should be applied at twice the recommended application rate unless
this information is already available from studies performed in accor-
dance withAnnex II, point 8.3.2.
Where on the basis of the proposed manner of use or on the basis of
the fate and behaviour continued or repeated exposure can be antici-
pated (such as the product is to be applied more than three times per
season witha re-application of 14 days or less), expert judgment is
required to examine whether further testing is required, beyond initial
laboratory testing, which will reflect the proposed use pattern. These
tests may be performed in the laboratory or under semi-field condi-
tions. When the test is done in the laboratory a realistic substrate
suchas plant material or a natural soil sh ould be used. However it
may be more appropriate to carry out field tests.
Test guideline
Where relevant testing should be done according to appropriate guide-
lines which satisfy as least the requirements for testing as included in
Setac - Guidance document on regulatory testing procedures for pesti-
cides withnon-target arth ropods.
10.5.2. Field tests
Aim of the test
The tests should provide sufficient information to evaluate the risk of
the plant protection product for arthropods under field conditions.
Circumstances in which requiredWhere significant effects are seen following laboratory and semi-field
exposure, or where on the basis of the proposed manner of use or on
the basis of the fate and behaviour continued or repeated exposure can
be anticipated expert judgment is required to examine whether more
extensive testing is necessary to permit an accurate risk assessment.
Test conditions
The tests must be conducted under representative agricultural condi-
tions and in accordance withth e proposed recommendations for use,
resulting in a realistic worst case study.
A toxic standard should be included in all tests.Test guidelineWhere relevant testing should be done according to appropriate guide-
lines which satisfy at least the requirements for testing as included in
Setac — Guidance document on regulatory testing procedures for
pesticides withnon-target arth ropods.
10.6.Effectsonearthwormsandothersoilnon-targetmacro-organisms,
believed tobeatrisk
10.6.1. Effects on earthworms
The possible impact on earthworms must be reported except where it
can be justified that it is not likely that earthworms are exposed,
directly or indirectly.1991L0414 — EN — 01.07.2003 — 009.001 — 132
▼M7
TERaand TERltmust be reported where:
TERa=L C50(mg a.s./kg)/realistic worst case PECs(initial or short-
term, in mg a.s./kg)
TERlt= NOEC (mg a.s./kg)/long term PECs (mg a.s./kg).
10.6.1.1. Acute toxicity tests
Aim of the testThe test should provide the LC
50, where possible the highest concen-
tration causing no mortality and the lowest concentration causing
100 % mortality and must include observed morphological and beha-
vioural effects.
Circumstances in which requiredThese studies are only required where
— the product contains more than one active substance,
— the toxicity of a new formulation cannot be reliably predicted from
the formulation tested according to the provisions of Annex II,
point 8.4 or of this point.
Test guidelineThe tests must be conducted in accordance to OECD Method 207.
10.6.1.2. Tests for sublethal effects
Aim of the testThe test should provide the NOEC and the effects on growth, repro-
duction and behaviour.
Circumstances in which requiredThese studies are only required where
— the product contains more than one active substance,
— the toxicity of a new formulation cannot be reliably predicted from
the formulation tested according to the provisions of Annex II,
point 8.4 or of this point,
— there is an increase in the recommended application rate, above
that previously tested.
Test conditionsThe same provisions as under the corresponding paragraphs of Annex
II, point 8.4.2 apply.
10.6.1.3. Field studies
Aim of the test
The test should provide sufficient data to evaluate the effects on earth-
worms in field conditions.
Circumstances in which required
Where TER
lt< 5 a field study to determine effects under practical
field conditions must be conducted and reported.
Expert judgment is required to decide whether residue contents of
earthworms should be investigated.
Test conditions
Fields selected shall have a reasonable earthworm population.
The test must be carried out at the maximum proposed application
rate. A toxic reference product must be included in the test.
10.6.2. Effects on other soil non-target macro-organisms
Aim of the testThe test should provide sufficient data to evaluate the impact of the
plant protection product on macro-organisms that contribute to the
breakdown of dead plant and animal organic matter.
Circumstances in which required
Testing is not required where in accordance with Annex III, point 9.1,
it is evident that DT
90values are less than 100 days, or the nature and
manner of use of the plant protection product are such that exposure
does not occur or when data from studies on the active substance1991L0414 — EN — 01.07.2003 — 009.001 — 133
▼M7
performed in accordance withth e provisions of Annex II, points 8.3.2,
8.4 and 8.5 indicate that there is no risk for soil macrofauna, earth-
worms or soil microflora.
Impact on organic matter breakdown must be investigated and
reported, where the DT90fvalues determined in field dissipation studies
(point 9.1) are > 365 days.
10.7.Effectsonsoilnon-targetmicro-organisms
10.7.1. Laboratory testing
Aim of the test
The test should provide sufficient data to evaluate the impact of the
plant protection product on soil microbial activity in terms of nitrogen
transformation and carbon mineralization.
Circumstances in which requiredWhere the DT
90fvalues determined in field dissipation studies (point
9.1) are > 100 days, impact on soil non-target micro-organisms must
be investigated through laboratory testing. Testing is, however, not
required if in the studies performed in accordance with the provisions
of Annex II, point 8.5 deviations from control values in terms of meta-
bolic activity of the microbial biomass after 100 days is < 25 %, and
such data are relevant to the uses, nature, and properties of the parti-
cular preparation to be authorized.
Test guidelineSetac — Procedures for assessing the environmental fate and ecotoxi-
city of pesticides.
10.7.2. Additional testing
Aim of the test
The test should provide sufficient data to evaluate the impact of the
plant protection product under field conditions on microbial activitiy.
Circumstances in which required
Where at the end of 100 days, measured activity deviates by more
than 25 % from the control, in the laboratory testing further testing
in the laboratory, under glass and/or in the field may be necessary.
10.8.Available data from biological primary screening in summary
form
A summary of available data from preliminary tests used to assess the
biological activity and dose range finding whether positive or nega-
tive, which provides information with respect to possible impact on
non/target species, bothflora and fauna, must be provided, togeth er
witha critical assessment as to its relevance to potential impact on
non-target species.
11. Summary and evaluation of points 9 and 10
A summary and evaluation of all data presented in points 9 and 10
should be carried out according to the guidance given by the compe-
tent authorities of the Member States concerning the format of such
summaries and evaluations. It should include a detailed and critical
assessment of those data in the context of relevant evaluative and deci-
sion making criteria and guidelines, withparticular reference to th e
risks for the environment and non-target species that may or do arise,
and the extent, quality and reliability of the data base. In particular the
following issues should be addressed:
— predicting distribution and fate in the environment, and the time
courses involved,
— identifying non-target species and populations at risk, and
predicting the extent of potential exposure,
— evaluation as to the short- and long-term risks for non-target
species — populations, communities, and processes — as appro-
priate,
— evaluation as to the risk of fish kills, and fatalities in large verte-
brates, or terrestrial predators, regardless of effects at population or
community level, and1991L0414 — EN — 01.07.2003 — 009.001 — 134
▼M7
— identification of precautions necessary to avoid or minimize
contamination of the environment, and for the protection of non-
target species.
12. Further information
12.1. Information on authorizations in other countries
12.2. Information on established maximum residue limits (MRL) in other
countries
12.3. Proposals including justification for the classification and labelling
proposed in accordance withDirective 67/548/EEC and Directive 78/
631/EEC
— Hazard symbol(s)
— Indications of danger— Risk phrases— Safety phrases
12.4. Proposals for risk and safety phrases in accordance with Article 15 (1),
(g) and (h) and proposed label
12.5. Specimens of proposed packaging
PART B
Introduction
(i) This Part provides data requirements for the authorisation of a plant protec-
tion product based on preparations of micro-organisms including viruses.
The term ‘micro-organism’ as defined in the introduction of Annex II, Part
B, also applies to Annex III, Part B.
(ii) Where relevant, data should be analysed using appropriate statistical
methods. Full details of the statistical analysis should be reported (e.g. all
point estimates should be given with confidence intervals, exact p-values
should be given rather than stating significant/non significant).
(iii) Pending the acceptance of specific guidelines at international level, the
information required shall be generated using test guidelines accepted bythe competent authority (e.g. USEPA guideline (
1)); where appropriate test
guidelines as described in Annex II, Part A, should be adapted in such a
way that they are appropriate for micro-organisms. Testing should include
viable and, if appropriate, non-viable micro-organisms, and a blank control.
(iv) Whenever a study implies the use of different doses, the relationship
between dose and adverse effect must be reported.
(v) Where testing is done, a detailed description (specification) of the material
used and its impurities, according to the provisions of section 1, point 1.4,
must be provided.
(vi) In cases where a new preparation is to be dealt with, extrapolation from
Annex II, Part B, could be acceptable, provided that all the possible effects
of the formulants and other components, especially on pathogenicity and
infectiveness, are also evaluated.
1. IDENTITY OF THE PLANT PROTECTION PRODUCT
The information provided, taken together with that provided for the
micro-organism(s), must be sufficient to precisely identify and define
preparations. The information and data referred to, unless otherwise
specified, are required for all plant protection products. This is with
the view to identify if any factor could alter the properties of the
micro-organism as a plant protection product in comparison to the
micro-organism as such, which is treated in Annex II, Part B, to
Directive 91/414/EEC.
1.1.Applicant
The name and address of the applicant (permanent community
address) must be provided as must the name, position, telephone and
fax number of the appropriate person to contact.1991L0414 — EN — 01.07.2003 — 009.001 — 135
(1)USEPA Microbial Pesticide Test Guidelines, OPPTS Series 885, February 1996
(http://www.epa.gov/oppbppd1/biopesticides/guidelines/series885.htm).▼B
▼M25
▼M25
Where, in addition, the applicant has an office, agent or representative
in the Member State in which the authorisation is being sought, the
name and address of the local office, agent or representative should
be provided, as should the name, position, telephone and fax number
of the appropriate person to contact.
1.2.Manufacturerofthepreparationandthemicro-organism(s)
The name and address of the manufacturer of the preparation and of
each micro-organism in the preparation must be provided as must the
name and address of each manufacturing plant in which the prepara-
tion and micro-organism are manufactured.
A contact point (preferable a central contact point, to include name,
telephone and fax numbers) must be provided for each manufacturer.
If the micro-organism originates from a producer from which data
according to Annex II, Part B, had not been submitted previously,
detailed information on the name and species description, as required
in Annex II, Part B, section 1.3, and on impurities, as required in
Annex II, Part B, section 1.4, have to be provided.
1.3.Tradenameorproposedtradename,andmanufacturer'sdevelop-
mentcodenumberofthepreparationifappropriate
All former and current trade names and proposed trade names and
development code numbers of the preparation referred to in the dossier
as well as the current names and numbers must be provided. Full
detail of any differences must be provided. (The proposed trade name
must not give rise to confusion withth e trade name of already
authorised plant protection products.)
1.4.Detailed quantitative and qualitative information on the composi-
tionofthepreparation
(i) Each micro-organism that is subject to the application should be
identified and named at the species level. The micro-organismshould be deposited at a recognised culture collection and given
an accession number. The scientific name must be stated, as well
as the group assignment (bacteria, virus, etc.) and any other
denomination relevant to the micro-organism (e.g. strain, sero-
type). In addition, the development phase of the micro-organism
(e.g. spores, mycelium) in the marketed product shall be stated.
(ii) For preparations the following information must be reported:
— the content of the micro-organism(s) in the plant protection
product and the content of the micro-organism in the material
used for manufacturing of plant protection products. These
must include the maximum, minimum and nominal content
of the viable and non-viable material,
— the content of formulants,
— the content of other components (such as by-products,
condensates, culture medium, etc.) and contaminating micro-
organisms, derived from production process.
The contents should be expressed in terms as provided for in
Article 6(2) of Directive 78/631/EEC for chemicals and appro-
priate terms for micro-organisms (number of active units per
volume or weight or any other manner that is relevant to the
micro-organism).
(iii) Formulants must where possible, be identified either by their
chemical name as given in Annex I to Directive 67/548/EEC, or,
if not included in this Directive, in accordance with both IUPAC
and CA nomenclature. Their structure or structural formula must
be provided. For each component of the formulants the relevant
EC (Einecs or Elincs) number and CAS number where they exist,
must be provided. Where the information provided does not fully
identify a formulant, an appropriate specification must be
provided. The trade name of formulants, where they exist, must
also be provided.
(iv) For formulants the function must be given:
— adhesive (sticker)
— antifoaming agent
— antifreeze
— binder— buffer
— carrier1991L0414 — EN — 01.07.2003 — 009.001 — 136
▼M25
— deodorant
— dispersing agent— dye— emetic
— emulsifier
— fertiliser— odorant— parfume— preservative
— propellant
— repellent— safener— solvent
— stabiliser
— synergist— thickener— wetting agent— miscellaneous (specify).
(v) Identification of contaminating micro-organisms and other
components derived from production process.
Contaminating micro-organisms must be identified as outlined in
Annex II, Part B, section 1, point 1.3.
Chemicals (inert components, by-products, etc.) must be identi-
fied as outlined in Annex II, Part A, section 1, point 1.10.
Where the information provided does not fully identify a compo-
nent, suchas condensate, culture medium, etc., detailed
information on the composition must be provided for each such
component.
1.5.Physicalstateandnatureofthepreparation
The type and code of preparation must be designated according to the
‘Catalogue of pesticide formulation types and international coding
system (GIFAP Technical Monograph No 2, 1989)’.
Where a particular preparation is not defined precisely in this publica-
tion a full description of the physical nature and state of the
preparation must be provided, together with a proposal for a suitable
description of the type of preparation and a proposal for its definition.
1.6.Function
The biological function must be specified from among the following:
— 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).
2. PHYSICAL, CHEMICAL AND TECHNICAL PROPERTIES OF
THE PLANT PROTECTION PRODUCT
The extent to which plant protection products for which authorisation
is sought comply with relevant FAO specifications, as agreed by the
Group of Experts on Pesticide Specification of the FAO Panel of
Experts on Pesticide Specifications, Registration Requirements and
Application Standards, must be stated. Divergences from FAO specifi-
cations must be described in detail, and justified.
2.1.Appearance(colourandodour)
A description of both the colour and odour, if any, and the physical
state of the preparation, must be provided.1991L0414 — EN — 01.07.2003 — 009.001 — 137
▼M25
2.2.Storagestabilityandshelf-life
2.2.1. Effects of light, temperature and humidity on technical characteristics
of the plant protection product
(i) The physical and biological stability of the preparation at the
recommended storage temperature including information on the
growthof contaminating micro-organisms must be determined
and reported. The conditions under which the test has been
performed must be justified.
(ii) Additionally in the case of liquid preparations, the effect of low
temperatures on physical stability, must be determined and
reported according to CIPAC(1) Methods MT 39, MT 48, MT
51 or MT 54 as appropriate.
(iii) The shelf life of the preparation at the recommended storage
temperature must be reported. Where shelf life is less than two
years, the shelf life in months, with appropriate temperature
specifications, must be reported. Useful information is given in
GIFAP(2) MonographNo 17.
2.2.2. Other factors affecting stability
Effect of exposure to air, packaging, etc., on the product stability must
be explored.
2.3.Explosivityandoxidisingproperties
Explosivity and oxidising properties will be determined as defined in
Annex III, Part A, section 2, point 2.2, unless it can be justified that it
is technically or scientifically not necessary to perform such studies.
2.4.Flash point and other indications of flammability or spontaneous
ignition
Flashpoint and flammability must be determined, as defined in Annex
III, Part A, section 2, point 2.3, unless it can be justified that it is tech-
nically or scientifically not necessary to perform suchstudies.
2.5.Acidity,alkalinityandifnecessarypHvalue
Acidity, alkalinity and pH will be determined as defined in Annex III,
Part A, section 2, point 2.4, unless it can be justified that it is techni-
cally or scientifically not necessary to perform suchstudies.
2.6.Viscosityandsurfacetension
Viscosity and surface tension will be determined as defined in Annex
III, Part A, section 2, point 2.5, unless it can be justified that it is tech-
nically or scientifically not necessary to perform suchstudies.
2.7.Technicalcharacteristics oftheplantprotectionproduct
The technical characteristics of the preparation must be determined to
permit a decision to be made as to its acceptability. If tests have to be
performed, they must be done at temperatures compatible with
survival of the micro-organism.
2.7.1. Wettability
The wettability of solid preparations which are diluted for use (e.g.
wettable powders and water dispersible granules), must be determined
and reported according to CIPAC Method MT 53.3.
2.7.2. Persistent foaming
The persistence of foaming of preparations to be diluted with water,
must be determined and reported according to CIPAC Method MT 47.
2.7.3. Suspensibility and suspension stability
— The suspensibility of water dispersible products (e.g. wettable
powders, water dispersible granules, suspension concentrates)1991L0414 — EN — 01.07.2003 — 009.001 — 138
(1) Collaborative International Pesticides Analytical Council.
(2) International Group of National Pesticide Manufacturers' Associations.
▼M25
must be determined and reported according to CIPAC Method MT
15, MT 161 or MT 168 as appropriate.
— The spontaneity of dispersion of water dispersible products (e.g.
suspension concentrates and water dispersible granules) must be
determined and reported according to CIPAC Methods MT 160 or
MT 174 as appropriate.
2.7.4. Dry sieve test and wet sieve test
In order to ensure that dustable powders have a suitable particle size
distribution for ease of application, a dry sieve test must be conducted
and reported according to CIPAC Method MT 59.1.
In the case of water dispersible products, a wet sieve test must be
conducted and reported according to CIPAC Method MT 59.3 or MT
167 as appropriate.
2.7.5. Particle size distribution (dustable and wettable powders, granules),
content of dust/fines (granules), attrition and friability (granules)
(i) The size distribution of particles in the case of powders, must be
determined and reported according to OECD Method 110.
The nominal size range of granules for direct application must be
determined and reported in accordance withCIPAC MT 58.3, for
water dispersible granules in accordance withCIPAC MT 170.
(ii) The dust content of granular preparations, must be determined
and reported according to CIPAC Method MT 171. If relevant
for operator exposure the particle size of dust must be determined
and reported according to OECD Method 110.
(iii) The friability and attrition characteristics of granules, must be
determined and reported once internationally agreed methods are
available. Where already data are available they must be reported
together with the method used.
2.7.6. Emulsifiability, re-emulsifiability, emulsion stability
(i) The emulsifiability, emulsion stability and re-emulsifiability of
preparations which form emulsions, must be determined and
reported according to CIPAC Method MT 36 or MT 173 as appro-
priate.
(ii) The stability of dilute emulsions and of preparations which are
emulsions, must be determined and reported according to CIPAC
Method MT 20 or MT 173.
2.7.7. Flowability, pourability (rinsability) and dustability
(i) The flowability of granular preparations must be determined and
reported according to CIPAC Method MT 172.
(ii) The pourability (including rinsed residue) of suspensions (e.g.
suspension concentrates, suspo-emulsions), must be determined
and reported according to CIPAC Method MT 148.
(iii) The dustability of dustable powders must be determined and
reported according to CIPAC Method MT 34 or another suitable
method.
2.8.Physical, chemical and biological compatibility with other
products including plant protection products with which its use is
tobeauthorised
2.8.1. Physical compatibility
The physical compatibility of recommended tank mixes must be deter-
mined and reported.
2.8.2. Chemical compatibility
The chemical compatibility of recommended tank mixes must be
determined and reported except where examination of the individual
properties of the preparations would establish beyond reasonable doubt
that there is no possibility of reaction taking place. In such cases it is
sufficient to provide that information as justification for not practically
determining the chemical compatibility.1991L0414 — EN — 01.07.2003 — 009.001 — 139
▼M25
2.8.3. Biological compatibility
The biological compatibility of tank mixes must be determined and
reported. Effects (e.g. antagonism, fungicidal effects) on the activity
of the micro-organism after mixing with other micro-organisms or
chemicals must be described. The possible interaction of the plant
protection product with other chemical products to be applied on the
crops under the expected condition of use of the preparation should
be investigated, based on the efficacy data. Intervals between applica-
tion of the biological pesticide and chemical pesticides should be
specified, if appropriate, in order to avoid loss of efficacy.
2.9.Adherenceanddistributiontoseeds
In the case of preparations for seed treatment, both distribution and
adhesion must be investigated and reported; in the case of distribution
according to CIPAC Method MT 175.
2.10.Summaryandevaluationofdatapresentedunderpoints2.1to2.9
3. DATA ON APPLICATION
3.1.Fieldofuseenvisaged
The field(s) of use, existing and proposed, for preparations containing
the micro-organism must be specified from among the following:
— field use, suchas agriculture, h orticulture, forestry and viticulture,
— protected crops (e.g. in glasshouses),
— amenity,
— weed control on non-cultivated areas,— home gardening,
— house plants,
— stored products,
— other (specify).
3.2.Modeofaction
The way by which uptake of the product may occur (e.g. contact,
stomach, inhalation) or the pest controlling action (fungitoxic, fungi-
static action, nutrient competition, etc.) must be stated.
It must also be stated whether or not the product is translocated in
plants and, where relevant, if such translocation is apoplastic,
symplastic or both.
3.3.Detailsofintendeduse
Details of the intended use, e.g. types of harmful organisms controlled
and/or plants or plant products to be protected, must be provided.
Intervals between the application of the plant protection product
containing micro-organisms and chemical pesticides, or a list with
active substances of chemical plant protection products not to be
used together with the plant protection product containing micro-
organisms on the same crop, should also be provided.
3.4.Applicationrate
For eachmeth od of application and eachuse, th e rate of application
per unit (ha, m
2,m3) treated, in terms of g or kg or l for the prepara-
tion and in terms of appropriate units for the micro-organism, must be
provided.
Application rates shall normally be expressed in g or kg/ha or in kg/m3
and where appropriate in g or kg/tonne; for protected crops and home
gardening use rates shall be expressed in g or kg/100 m2or g or kg/m3.
3.5.Content of micro-organism in material used (e.g. in the diluted
spray,baitsortreated seed)
The content of micro-organism shall be reported, as appropriate, in
number of active unit/ml or g or any other relevant unit.1991L0414 — EN — 01.07.2003 — 009.001 — 140
▼M25
3.6.Methodofapplication
The method of application proposed must be described fully, indi-
cating the type of equipment to be used, if any, as well as the type
and volume of diluent to be used per unit of area or volume.
3.7.Numberandtimingofapplicationsanddurationofprotection
The maximum number of applications to be used and their timing,
must be reported. Where relevant the growth stages of the crop or
plants to be protected and the development stages of the harmful
organisms, must be indicated. Where possible and necessary the
interval between applications, in days, must be stated.
The duration of protection afforded both by each application and by
the maximum number of applications to be used, must be indicated.
3.8.Necessary waiting periods or other precautions to avoid phyto-
pathogeniceffectsonsucceedingcrops
Where relevant, minimum waiting periods between last application
and sowing or planting of succeeding crops, which are necessary to
avoid phytopathogenic effects on succeeding crops, must be stated,
and follow from the data provided under section 6, point 6.6.
Limitations on choice of succeeding crops, if any, must be stated.
3.9.Proposedinstructionsforuse
The proposed instructions for use of the preparation, to be printed on
labels and leaflets, must be provided.
4. FURTHER INFORMATION ON THE PLANT PROTECTION
PRODUCT
4.1.Packaging and compatibility of the preparation with proposed
packagingmaterials
(i) Packaging to be used must be fully described and specified in
terms of the materials used, manner of construction (e.g.
extruded, welded, etc.), size and capacity, size of opening, type
of closure and seals. It must be designed in accordance withth e
criteria and guidelines specified in the FAO ‘Guidelines for the
Packaging of Pesticides’.
(ii) The suitability of the packaging, including closures, in terms of
its strength, leakproofness and resistance to normal transport and
handling, must be determined and reported according to ADR
methods 3552, 3553, 3560, 3554, 3555, 3556, 3558, or appro-
priate ADR Methods for intermediate bulk containers, and,
where for the preparation child-resistant closures are required,
according to ISO standard 8317.
(iii) The resistance of the packaging material to its contents must be
reported according to GIFAP MonographNo 17.
4.2.Proceduresforcleaningapplicationequipment
Cleaning procedures for bothapplication equipment and protective
clothing must be described in detail. The effectiveness of the cleaning
procedure must be determined, using e.g. biotests, and reported.
4.3.Re-entry periods, necessary waiting periods or other precautions
toprotectman,livestockandtheenvironment
The information provided must follow from and be supported by the
data provided for the micro-organism(s) and that provided under
sections 7 and 8.
(i) Where relevant pre-harvest intervals, re-entry periods or with-
holding periods necessary to minimise the presence of residues in
or on crops, plants and plant products, or in treated areas or
spaces, witha view to protecting man or livestock, must be speci-
fied e.g.:
— pre-harvest interval (in days) for each relevant crop,
— re-entry period (in days) for livestock, to areas to be grazed,
— re-entry period (in hours or days) for man to crops, buildings
or spaces treated,
— withholding period (in days) for animal feedingstuffs,1991L0414 — EN — 01.07.2003 — 009.001 — 141
▼M25
— waiting period (in days), between application and handling
treated products.
(ii) Where necessary, in the light of the test results, information on
any specific agricultural, plant health or environmental conditions
under which the preparation may or may not be used must be
provided.
4.4.Recommended methods and precautions concerning: handling,
storage,transportorfire
The recommended methods and precautions concerning handling
procedures (detailed) for the storage, at both warehouse and user level
of plant protection products, for their transport and in the event of fire
must be provided. Where relevant, information on combustion
products must be provided. The risks likely to arise and the methods
and procedures to minimise the hazards arising, must be specified.
Procedures to preclude or minimise the generation of waste or left-
overs must be provided.
Where relevant, assessment has to be done according to ISO TR 9122.
The nature and characteristics of protective clothing and equipment
proposed must be provided. The data provided must be sufficient to
evaluate the suitability and effectiveness under realistic conditions of
use (e.g. field or glasshouse circumstances).
4.5.Measuresinthecaseofanaccident
Whether arising during transport, storage or use, detailed procedures to
be followed in the event of an accident, must be provided and include:
— containment of spillages,
— decontamination of areas, vehicles and buildings,
— disposal of damaged packaging, adsorbents and other materials,
— protection of emergency workers and bystanders,— first aid measures.
4.6.Proceduresfordestructionordecontaminationoftheplantprotec-
tionproductanditspackaging
Procedures for destruction and decontamination must be developed for
bothsmall quantities (user level) and large quantities (wareh ouse
level). The procedures must be consistent with provisions in place
relating to the disposal of waste and of toxic waste. The means of
disposal proposed should be without unacceptable influence on the
environment and be the most cost effective and practical means of
disposal feasible.
4.6.1. Controlled incineration
In many cases the preferred or sole means to safely dispose of plant
protection products and in particular the formulants contained in it,
contaminated materials, or contaminated packaging, is through
controlled incineration in a licensed incinerator.
The applicant must provide detailed instructions for safe disposal.
4.6.2. Others
Other methods to dispose of plant protection products, packaging and
contaminated materials, where proposed, must be fully described. Data
must be provided for such methods, to establish their effectiveness and
safety.
5. ANALYTICAL METHODS
Introduction
The provisions of this section only cover analytical methods required
for post-registration control and monitoring purposes.
It is desirable to have a plant protection product without contaminants,
if possible. The level of acceptable contaminants should be judged
from a risk assessment point of view, by the competent authority.
Bothproduction and product must be subject to a continuous quality
control by the applicant. The quality criteria for the product should
be submitted.1991L0414 — EN — 01.07.2003 — 009.001 — 142
▼M25
For analytical methods used for generation of data as required in this
Directive or for other purposes the applicant has to provide a justifica-
tion for the method used; where necessary separate guidance will be
developed for such methods on the basis of the same requirements as
defined for methods for post-registration control and monitoring
purposes.
Descriptions of methods must be provided and include details of
equipment, materials and conditions used. The applicability of existing
CIPAC methods must be reported.
As far as practicable these methods must employ the simplest
approach, involve the minimum cost, and require commonly available
equipment.
For this section the following applies:
Impurities Any component (including contaminating
micro-organisms and/or chemical substances)
other than the specified micro-organism, origi-
nating from the manufacturing process or from
degradation during storage
Relevant impurities Impurities, as defined above, that are of
concern for human or animal health and/or the
environment
Metabolites Metabolites include products resulting from
degradative and biosynthetic reactions taking
place within the micro-organism or other
organisms used to produce the micro-organism
of interest
Relevant metabolites Metabolites that are of concern for human or
animal health and/or the environment
Residues Viable micro-organisms and substances
produced in significant quantities by these
micro-organisms which persist after the disap-
pearance of the micro-organisms and are of
concern for human or animal health and/or the
environment.
On request the following samples must be provided:
(i) samples of the preparation;
(ii) samples of the micro-organism as manufactured;
(iii) analytical standards of the pure micro-organism;
(iv) analytical standards of relevant metabolites and all other compo-
nents included in the residue definition;
(v) if available, samples of reference substances for the relevant
impurities.
5.1.Methodsfortheanalysisofthepreparation
— Methods, which must be described in full, must be provided for
the identification and the determination of the content of the
micro-organism in the preparation. In the case of a preparation
containing more than one micro-organism, methods capable of
identifying and determining the content of each one should be
provided.
— Methods to establish regular control of the final product (prepara-
tion) in order to show that it does not contain other organisms than
the indicated ones and to establish its uniformity.
— Methods to identify any contaminating micro-organisms of the
preparation.
— Methods used to determine the storage stability and shelf life of
the preparation must be provided.
5.2.Methodstodetermineandquantifyresidues
Analytical methods for the determination of residues, as defined in
Annex II, Part B, section 4, point 4.2, must be submitted unless it is
justified that the information already submitted according to the
requirements of Annex II, Part B, section 4, point 4.2, is sufficient.1991L0414 — EN — 01.07.2003 — 009.001 — 143
▼M25
6. EFFICACY DATA
The provisions for efficacy data have already been adopted under
Commission Directive 93/71/EEC (1).
7. EFFECTS ON HUMAN HEALTH
For proper evaluation of the toxicity including potential for pathogeni-
city and infectiveness of preparations sufficient information should be
available on acute toxicity, irritation and sensitisation of the micro-
organism. If possible, additional information on mode of toxic action,
toxicological profile and all other known toxicological aspects of the
micro-organism should be submitted. Special attention should be given
to co-formulants.
While performing toxicology studies, all signs of infection or patho-
genicity should be noted. Toxicology studies should include clearance
studies.
In the context of the influence that impurities and other components
can have on toxicological behaviour, it is essential that for each study
submitted, a detailed description (specification) of the material used,
be provided. Tests must be conducted using the plant protection
product to be authorised. In particular, it must be clear that the
micro-organism used in the preparation, and the conditions of
culturing it, are the same for which information and data are submitted
in the context of Annex II, Part B.
A tiered testing system will be applied to the study of the plant protec-
tion product.
7.1.Basicacutetoxicity studies
The studies, data and information to be provided and evaluated, must
be sufficient to permit the identification of effects following a single
exposure to the plant protection product, and in particular to establish,
or indicate:
— the toxicity of the plant protection product,
— toxicity of the plant protection product relative to the micro-
organism,
— the time course and characteristics of the effect with full details of
behavioural changes and possible gross pathological findings at
post-mortem,
— where possible the mode of toxic action, and— the relative hazard associated with the different routes of exposure.
While the emphasis must be on estimating the toxicity ranges
involved, the information generated must also permit the plant protec-
tion product to be classified in accordance withDirective 78/631/EEC.
The information generated through acute toxicity testing is of parti-
cular value in assessing hazards likely to arise in accident situations.
7.1.1. Acute oral toxicity
Circumstances in which required
An acute oral test should always be carried out unless the applicant
can justify to the satisfaction of the competent authority that Article
3(2) of Directive 78/631/EEC can be invoked.
Test guideline
The test must be carried out in accordance with Method B.1 or B.1 bis
of Commission Directive 92/69/EEC (
2).
7.1.2. Acute inhalation toxicity
Aim of the test
The test will provide the inhalation toxicity to rats of the plant protec-
tion product.1991L0414 — EN — 01.07.2003 — 009.001 — 144
(1) OJ L 221, 31.8.1993, p. 27.
(2) OJ L 383, 29.12.1992, p. 113.
▼M25
Circumstances in which required
The test must be carried out where the plant protection product:
— is used withfogging equipment,
— is an aerosol,
— is a powder containing a significant proportion of particles of
diameter < 50 micrometre (> 1 % on a weight basis),
— is to be applied from aircraft in cases where inhalation exposure is
relevant,
— is to be applied in a manner which generates a significant propor-
tion of particles or droplets of diameter < 50 micrometre (> 1 %
on a weight basis),
— contains a volatile component at greater than 10 %.
Test guideline
The test must be carried out in accordance with Method B.2 of Direc-
tive 92/69/EEC.
7.1.3. Acute percutaneous toxicity
Circumstances in which required
An acute percutaneous test should always be carried out unless the
applicant can justify to the satisfaction of the competent authority
that Article 3(2) of Directive 78/631/EEC can be invoked.
Test guideline
The test must be carried out in accordance with Method B.3 of Direc-
tive 92/69/EEC.
7.2.Additionalacutetoxicitystudies
7.2.1. Skin irritation
Aim of the test
The test will provide the potential of skin irritancy of the plant protec-
tion product including the potential reversibility of the effects
observed.
Circumstances in which required
The skin irritancy of the plant protection product must always be
determined, except where the formulants are not expected to be skin
irritant or the micro-organism is shown not to be skin irritant or where
it is likely, as indicated in the test guideline, that severe skin effects
can be excluded.
Test guideline
The test must be carried out in accordance with Method B.4 of Direc-
tive 92/69/EEC.
7.2.2. Eye irritation
Aim of the test
The test will provide the potential for eye irritation of the plant protec-
tion product, including the potential reversibility of the effects
observed.
Circumstances in which required
The eye irritancy of the plant protection product must be determined,
where the formulants are suspected to be eye irritant, except where the
micro-organism is eye irritant or where it is likely, as indicated in the
test guideline, that severe effects on the eyes may be produced.
Test guideline
The eye irritation must be determined in accordance with Method B.5
of Directive 92/69/EEC.1991L0414 — EN — 01.07.2003 — 009.001 — 145
▼M25
7.2.3. Skin sensitisation
Aim of the test
The test will provide sufficient information to assess the potential of
the plant protection product to provoke skin sensitisation reactions.
Circumstances in which required
The test must be carried out where the formulants are suspected to
have skin sensitising properties, except where the micro-organism(s)
or the formulants are known to have skin sensitising properties.
Test guideline
The tests have to be carried out in accordance with Method B.6 of
Directive 92/69/EEC.
7.3.Dataonexposure
The risks for those in contact with plant protection products (opera-
tors, bystanders, workers), depend on the physical, chemical and
toxicological properties of the plant protection product as well as the
type of the product (undiluted/diluted), formulation type, and on the
route, the degree and duration of exposure. Sufficient information and
data must be generated and reported to permit an assessment of the
extent of exposure to the plant protection product likely to occur under
the proposed conditions of use.
In the cases where there is particular concern on the possibility of
dermal absorption based on the information for the micro-organism
available in Annex II, Part B, section 5, or from the information
provided for the preparation in the present section of Annex III, Part
B, further dermal absorption data can be necessary.
Results from exposure monitoring during production or use of the
product must be submitted.
The abovementioned information and data must provide the basis for
the selection of appropriate protective measures including personal
protective equipment to be used by operators and workers and to be
specified on the label.
7.4.Availabletoxicological datarelating tonon-activesubstances
A copy of the notification and the safety data sheet submitted in the
context of European Parliament and Council Directive 1999/45/EC (1)
and Commission Directive 91/155/EEC of 5 March1991 defining and
laying down the detailed arrangements for the system of specific infor-
mation relating to dangerous preparations in implementation of Article
10 of Directive 88/379/EEC (2) must be submitted for eachformulant.
All other available information should be submitted.
7.5.Supplementary studies for combinations of plant protection
products
Aim of the test
In certain cases it may be necessary to carry out the studies as referred
to under points 7.1 to 7.2.3 for a combination of plant protection
products where the product label includes requirements for use of the
plant protection product withoth er plant protection products and/or
withadjuvants as a tank mix. Decisions as to th e need for supplemen-
tary studies must be made on a case-by-case basis, taking into account
the results of the acute toxicity studies of the individual plant protec-
tion products, the possibility for exposure to the combination of the
products concerned and available information or practical experience
withth e products concerned or similar products.
7.6.Summaryandevaluationofhealtheffects
A summary of all data and information provided under paragraphs 7.1
through 7.5, must be submitted, and include a detailed and critical1991L0414 — EN — 01.07.2003 — 009.001 — 146
(1) OJ L 200, 30.7.1999, p. 1.
(2) OJ L 76, 22.3.1991, p. 35.
▼M25
assessment of those data in the context of relevant evaluative and deci-
sion-making criteria and guidelines, withparticular reference to th e
risks for man and animals that may or do arise, and the extent, quality
and reliability of the database.
8. RESIDUES IN OR ON TREATED PRODUCTS, FOOD AND FEED
The same provisions as detailed in Annex II, Part B, section 6, apply;
the information required according to this section has to be provided
unless it is possible to extrapolate the residue behaviour of the plant
protection product on the basis of the data available for the micro-
organism. Special attention should be paid towards the influence of
formulation substances on the residue behaviour of the micro-
organism and its metabolites.
9. FATE AND BEHAVIOUR IN THE ENVIRONMENT
The same provisions as detailed in Annex II, Part B, section 7, apply;
the information required according to this section has to be provided
unless it is possible to extrapolate the fate and behaviour of the plant
protection product in the environment on the basis of the data avail-
able in Annex II, Part B, section 7.
10. EFFECTS ON NON-TARGET ORGANISMS
Introduction
(i) The information provided, taken together with that for the micro-
organism(s), must be sufficient to permit an assessment of the
impact on non-target species (flora and fauna), of the plant
protection product, when used as proposed. Impact can result
from single, prolonged or repeated exposure, and can be rever-
sible, or irreversible.
(ii) The choice of the appropriate non-target organisms for testing of
environmental effects should be based on the information on the
micro-organism, as required in Annex II, Part B, and on the
information on the formulants and other components, as required
by sections 1 to 9 of the present Annex. From such knowledge it
would be possible to choose the appropriate test organisms, such
as organisms closely related to the target organism.
(iii) In particular, the information provided for the plant protection
product, together with other relevant information, and that
provided for the micro-organism, should be sufficient to:
— specify the hazard symbols, the indications of danger, and
relevant risk and safety phrases for the protection of the
environment, to be mentioned on packaging (containers),
— permit an evaluation of the short- and long-term risks for
non-target species — populations, communities, and
processes as appropriate,
— permit an evaluation whether special precautions are neces-
sary for the protection of non-target species.
(iv) There is a need to report all potentially adverse effects found
during routine investigations of environmental effects and to
undertake and report suchadditional studies wh ichmay be
necessary to investigate the mechanisms involved and assess the
significance of these effects.
(v) In general, muchof th e data relating to impact on non-target
species, required for authorisation of plant protection products,
will have been submitted and evaluated for the inclusion of the
micro-organism(s) in Annex I.
(vi) Where exposure data are necessary to decide whether a study has
to be performed, the data obtained in accordance with the provi-
sions of Annex III, Part B, section 9, should be used.
For the estimation of exposure of organisms all relevant informa-
tion on the plant protection product and on the micro-organism
must be taken into account. Where relevant the parameters
provided for in this section should be used. Where it appears
from available data that the plant protection product has a
stronger effect than the micro-organism, the data on effects on
non target organisms of the plant protection product have to be
used for the calculation of relevant effect/exposure ratios.
(vii) In order to facilitate the assessment of the significance of test
results obtained, the same strain of each relevant species should
where possible be used in the various specified tests for effects
on non target organisms.1991L0414 — EN — 01.07.2003 — 009.001 — 147
▼M25
10.1.Effectsonbirds
The same information as provided in Annex II, Part B, section 8, point
8.1, has to be reported where it is not possible to predict the effects of
the plant protection product on the basis of the data available for the
micro-organism, unless it can be justified that exposure of birds is
unlikely to occur.
10.2.Effectsonaquaticorganisms
The same information as provided in Annex II, Part B, section 8, point
8.2, has to be reported where it is not possible to predict the effects of
the plant protection product on the basis of the data available for the
micro-organism, unless it can be justified that exposure of aquatic
organisms is unlikely to occur.
10.3.Effectsonbees
The same information as provided in Annex II, Part B, section 8, point
8.3, has to be reported where it is not possible to predict the effects of
the plant protection product on the basis of the data available for the
micro-organism, unless it can be justified that exposure of bees is unli-
kely to occur.
10.4.Effectsonarthropodsotherthanbees
The same information as provided in Annex II, Part B, section 8, point
8.4, has to be reported where it is not possible to predict the effects of
the plant protection product on the basis of the data available for the
micro-organism, unless it can be justified that exposure of arthropods
other than bees is unlikely to occur.
10.5.Effectsonearthworms
The same information as provided in Annex II, Part B, section 8, point
8.5, has to be reported where it is not possible to predict the effects of
the plant protection product on the basis of the data available for the
micro-organism, unless it can be justified that exposure of earthworms
is unlikely to occur.
10.6.Effectsonsoilmicro-organisms
The same information as provided in Annex II, Part B, section 8, point
8.6, has to be reported where it is not possible to predict the effects of
the plant protection product on the basis of the data available for the
micro-organism, unless it can be justified that exposure of non target
soil micro-organisms is unlikely to occur.
10.7.Additionalstudies
Expert judgement is required to decide whether additional studies are
necessary. Suchdecision will take into consideration th e available
information in this and other sections, in particular data on the speci-
ficity of the micro-organism, and the expected exposure. Useful
information may also be available from the observations carried out
in efficacy testing.
Special attention should be given to possible effects on naturally
occurring and deliberately released organisms of importance in IPM.
In particular the compatibility of the product with IPM should be
taken into consideration.
Additional studies might include further studies on additional species
or higher tier studies such as studies on selected non-target organisms.
Before performing such studies, the applicant shall seek agreement of
the competent authorities on the type of study to be performed.
11. SUMMARY AND EVALUATION OF ENVIRONMENTAL IMPACT
A summary and evaluation of all data relevant to the environmental
impact should be carried out according to the guidance given by the
competent authorities of the Member States concerning the format of
suchsummaries and evaluations. It sh ould include a detailed and
critical assessment of those data in the context of relevant evaluative
and decision making criteria and guidelines, withparticular reference
to the risks for the environment and non-target species that may or do1991L0414 — EN — 01.07.2003 — 009.001 — 148
▼M25
arise, and the extent, quality and reliability of the database. In parti-
cular the following issues should be addressed:
— prediction of distribution and fate in the environment, and the time
courses involved,
— identification of non-target species and populations at risk, and
prediction of the extent of potential exposure,
— identification of precautions necessary to avoid or minimise
contamination of the environment, and for the protection of non-
target species.1991L0414 — EN — 01.07.2003 — 009.001 — 149
▼B
ANNEX IV
RISKPHRASES1991L0414 — EN — 01.07.2003 — 009.001 — 150
▼B
ANNEX V
SAFETYPHRASES1991L0414 — EN — 01.07.2003 — 009.001 — 151
▼M10
ANNEX VI
UNIFORM PRINCIPLES FOR EVALUATION ANDAUTHORIZATION
OFPLANTPROTECTIONPRODUCTS
CONTENTS
A.INTRODUCTION
B.EVALUATION
1.General principles
2.Specific principles
2.1. Efficacy
2.2. Absence of unacceptable effects on plants or plant products
2.3. Impact on vertebrates to be controlled2.4. Impact on human or animal health2.4.1. arising from the plant protection product
2.4.2. arising from residues
2.5. Influence on the environment2.5.1. Fate and distribution in the environment
2.5.2. Impact on non-target species
2.6. Analytical methods2.7. Physical and chemical properties
C.DECISION-MAKING
1.General principles
2.Specific principles
2.1. Efficacy
2.2. Absence of unacceptable effects on plants or plant products2.3. Impact on vertebrates to be controlled
2.4. Impact on human or animal health
2.4.1. arising from the plant protection product2.4.2. arising from residues
2.5. Influence on the environment
2.5.1. Fate and distribution in the environment2.5.2. Impact on non-target species
2.6. Analytical methods
2.7. Physical and chemical properties1991L0414 — EN — 01.07.2003 — 009.001 — 152
▼M10
A.INTRODUCTION
1. The principles developed in this Annex aim to ensure that evalua-
tions and decisions withregard to auth orization of plant protection
products, provided they are chemical preparations, results in the
implementation of the requirements of Article 4 (1) (b), (c), (d)
and (e) of this Directive by all the Member States at the high level
of protection of human and animal health and the environment.
2. In evaluating applications and granting authorizations Member
States shall:
(a) — ensure that the dossier supplied is in accordance with the
requirements of Annex III, at the latest at the time of fina-
lization of the evaluation for the purpose of decision-
making, without prejudice, where relevant, to the provisions
of Article 13 (1) (a), (4) and (6) of this Directive,
— ensure that the data submitted are acceptable in terms of
quantity, quality, consistency and reliability and sufficient
to permit a proper evaluation of the dossier,
— evaluate, where relevant, justifications submitted by the
applicant for not supplying certain data;
(b) take into account the Annex II data concerning the active
substance in the plant protection product, submitted for the
purpose of inclusion of the active substance concerned in
Annex I, and the results of the evaluation of those data, without
prejudice, where relevant, to the provisions of Article 13 (1)
(b), (2), (3) and (6) of this Directive;
(c) take into consideration other relevant technical or scientific
information they can reasonably possess with regard to the
performance of the plant protection product or to the poten-
tially adverse effects of the plant protection product, its
components or its residues.
3. Where in the specific principles on evaluation reference is made to
Annex II data, this shall be understood as being the data referred to
in point 2 (b).
4. Where the data and information provided are sufficient to permit
completion of the evaluation for one of the proposed uses, applica-
tions must be evaluated and a decision made for the proposed use.
Taking account of justifications provided and withth e benefit of
any subsequent clarifications, Member States shall reject applica-
tions for which the data gaps are such that it is not possible to
finalize the evaluation and to make a reliable decision for at least
one of the proposed uses.
5. During the process of evaluation and decision-making, Member
States shall cooperate with the applicants in order to resolve any
questions on the dossier quickly or to identify at an early stage
any additional studies necessary for a proper evaluation of the
dossier, or to amend any proposed conditions for the use of the
plant protection product or to modify its nature or its composition
in order to ensure full satisfaction of the requirements of this
Annex or of this Directive.
Member States shall normally come to a reasoned decision within
12 months of receiving a technically complete dossier. A techni-
cally complete dossier is one that satisfies all the requirements of
Annex III.
6. The judgements made by the competent authorities of the Member
States during the evaluation and decision-making process must be
based on scientific principles, preferably recognized at international
level (for example, by the EPPO), and be made with the benefit of
expert advice.
B.EVALUATION
1.Generalprinciples
1. Having regard to current scientific and technical knowledge,
Member States shall evaluate the information referred to in Part
A, point 2, and in particular:
(a) assess the performance in terms of efficacy and phytotoxi-
city of the plant protection product for each use for which
authorization is sought; and1991L0414 — EN — 01.07.2003 — 009.001 — 153
▼M10
(b) identify the harzards arising, assess their significance and
make a judgment as to the likely risks to humans, animals
or the environment.
2. In accordance with the terms of Article 4 of this Directive,
whichinter alia specifies that Member States shall have regard
to all normal conditions under which the plant protection
product may be used, and to the consequences of its use,
Member States shall ensure that evaluations carried out have
regard to the proposed practical conditions of use and in parti-
cular to the purpose of use, the dose, the manner, frequency
and timing of applications, and the nature and composition of
the preparation. Whenever possible Member States shall also
take into account the principles of integrated control.
3. In the evaluation of applications submitted, Member States shall
have regard to the agricultural, plant health or environmental
(including climatic) conditions in the areas of use.
4. In interpreting the results of evaluations, Member States shall
take into consideration possible elements of uncertainty in the
information obtained during the evaluation, in order to ensure
that the chances of failing to detect adverse effects or of under-
estimating their importance are reduced to a minimum. The
decision-making process shall be examined to identify critical
decision points or items of data for which uncertainties could
lead to a false classification of risk.
The first evaluation made shall be based on the best available
data or estimates reflecting the realistic conditions of use of the
plant protection product.
This should be followed by a repeat evaluation, taking account
of potential uncertainties in the critical data and of a range of
use conditions that are likely to occur and resulting in a realistic
worst-case approach, to determine whether it is possible that the
initial evaluation could have been significantly different.
5. Where specific principles of Section 2 provide for the use of
calculation models in the evaluation of a plant protection
product, those models shall:
— make a best possible estimation of all relevant processes
involved taking into account realistic parameters and
assumptions,
— be submitted to an analysis as referred to in B, point 1.4,
— be reliably validated withmeasurements carried out under
circumstances relevant for the use of the model,
— be relevant to the conditions in the area of use.
6. Where metabolites, degradation or reaction products are referred
to in the specific principles, only those that are relevant for the
proposed criterion shall be taken into consideration.
2.Specificpriciples
Member States shall, for the evaluation of the data and information
submitted in support of applications, and without prejudice to the
general principles of Section 1, implement the following principles.
2.1. Efficacy
2.1.1. Where the proposed use concerns the control of or protection
against an organism, Member States shall evaluate the possibility
that this organism could be harmful under the agricultural, plant
health and environmental (including climatic) conditions in the
area of the proposed use.
2.1.2. Where the proposed use concerns an effect other than the control of
or protection against an organism, Member States shall evaluate
whether significant damage, loss or inconvenience could occur
under the agricultural, plant health and environmental (including
climatic) conditions in the area of proposed use if the plant protec-
tion product were not used.
2.1.3. Member States shall evaluate the efficacy data on the plant protec-
tion product as provided for in Annex III having regard to the
degree of control or the extent of the effect desired and having
regard to the relevant experimental conditions such as:
— the choice of the crop or cultivar,1991L0414 — EN — 01.07.2003 — 009.001 — 154
▼M10
— the agricultural and environmental (including climatic) condi-
tions,
— the presence and density of the harmful organism,— the development stage of crop and organism,
— the amount of the plant protection product used,
— if required on the label, the amount of adjuvant added,— the frequency and timing of the applications,
— the type of application equipment.
2.1.4. Member States shall evaluate the performance of the plant protec-
tion product in a range of agricultural, plant health and
environmental (including climatic) conditions likely to be encoun-
tered in practice in the area of proposed use and in particular:
(i) the level, consistency and duration of the effect sought in rela-
tion to the dose in comparison with a suitable reference product
or products and an untreated control;
(ii) where relevant, effect on yield or reduction of loss in storage,
in terms of quantity and/or quality, in comparison witha
suitable reference product or products and an untreated control.
Where no suitable reference product exists, Member States shall
evaluate the performance of the plant protection product to deter-
mine whether there is a consistent and defined benefit under the
agricultural, plant health and environmental (including climatic)
conditions in the area of proposed use.
2.1.5. Where the product label includes requirements for use of the plant
protection product withoth er plant protection products and/or with
adjuvants as a tank mix, Member States shall make the evaluations
referred to in points 2.1.1 to 2.1.4 in relation to the information
supplied for the tank mix.
Where the product label includes recommendations for use of the
plant protection product withoth er plant protection products and/
or with adjuvants as a tank mix, Member States shall evaluate the
appropriateness of the mix and of its conditions of use.
2.2. Absence of unacceptable effects on plants or plant products
2.2.1. Member States shall evaluate the degree of adverse effects on the
treated crop after use of the plant protection product according to
the proposed conditions of use in comparison, where relevant, with
a suitable reference product or products, where they exist, and/or an
untreated control.
(a) This evaluation will take into consideration the following infor-
mation:
(i) the efficacy data provided for in Annex III;
(ii) other relevant information on the plant protection product
such as nature of the preparation, dose, method of applica-
tion, number and timing of applications;
(iii) all relevant information on the active substance as
provided for in Annex II, including mode of action, vapour
pressure, volatility and water solubility;
(b) This evaluation will include:
(i) the nature, frequency, level and duration of observed
phytotoxic effects and the agricultural, plant health and
environmental (including climatic) conditions that affect
them;
(ii) the differences between main cultivars with regard to their
sensitivity to phytotoxic effects;
(iii) the part of the treated crop or plant products where phyto-
toxic effects are observed;
(iv) the adverse impact on the yield of the treated crop or plant
products in terms of quantity and/or quality;
(v) the adverse impact on treated plants or plant products to
be used for propagation, in terms of viability, germination,
sprouting, rooting and establishment;
(vi) where volatile products are concerned, the adverse impact
on adjacent crops.
2.2.2. Where the available data indicate that the active substance or
significant metabolites, degradation and reaction products persist in
soils and/or in or on plant substances in significant quantities after1991L0414 — EN — 01.07.2003 — 009.001 — 155
▼M10
use of the plant protection product according to the proposed condi-
tions of use, Member States shall evaluate the degree of adverse
effects on subsequent crops. This evaluation will be carried out as
specified in point 2.2.1.
2.2.3. Where the product label includes requirements for use of the plant
protection product withoth er plant protection products or with
adjuvants as a tank mix, the evaluation as specified in point 2.1.1
will be carried out in relation to the information supplied for the
tank mix.
2.3. Impact on vertebrates to be controlled
Where the proposed use of the plant protection product aims to
have an effect on vertebrates, Member States shall evaluate the
mechanism by which this effect is obtained and the observed
effects on the behaviour and health of the target animals; when the
intended effect is to kill the target animal they shall evaluate the
time necessary to obtain the death of the animal and the conditions
under which death occurs.
This evaluation will take into consideration the following informa-
tion:
(i) all relevant information as provided for in Annex II and the
results of the evaluation thereof, including the toxicological
and metabolism studies;
(ii) all relevant information on the plant protection product as
provided for in Annex III, including toxicological studies and
efficacy data.
2.4. Impact on human or animal health
2.4.1. arising from the plant protection product
2.4.1.1. Member States shall evaluate operator exposure to the active
substance and/or to toxicologically relevant compounds in the plant
protection product likely to occur under the proposed conditions of
use (including in particular dose, application method and climatic
conditions) using by preference realistic data on exposure and, if
suchdata are not available, a suitable, validated calculation model.
(a) This evaluation will take into consideration the following infor-
mation:
(i) the toxicological and metabolism studies as provided for in
Annex II and the results of the evaluation thereof
including the acceptable operator exposure level (AOEL).
The acceptable operator exposure level is the maximum
amount of active substance to which the operator may be
exposed without any adverse health effects. The AOEL is
expressed as milligrams of the chemical per kilogram body
weight of the operator. The AOEL is based on the highest
level at which no adverse effect is observed in tests in the
most sensitive relevant animal species or, if appropriate
data are available, in humans;
(ii) other relevant information on the active substances such as
physical and chemical properties;
(iii) the toxicological studies provided for in Annex III,
including where appropriate dermal absorption studies;
(iv) other relevant information as provided for in Annex III
suchas:
— composition of the preparation,
— nature of the preparation,— size, design and type of packaging,
— field of use and nature of crop or target,
— method of application including handling, loading and
mixing of product,
— exposure reduction measures recommended,— protective clothing recommendations,
— maximum application rate,
— minimum spray application volume stated on the label,— number and timing of applications;
(b) This evaluation shall be made for each type of application
method and application equipment proposed for use of the plant1991L0414 — EN — 01.07.2003 — 009.001 — 156
▼M10
protection product as well as for the different types and sizes of
containers to be used, taking account of mixing, loading opera-
tions, application of the plant protection product and cleaning
and routine maintenance of application equipment.
2.4.1.2. Member States shall examine information relating to the nature and
characteristics of the packaging proposed with particular reference
to the following aspects:
— the type of packaging,
— its dimensions and capacity,— the size of the opening,— the type of closure,— its strength, leakproofness and resistance to normal transport
and handling,
— its resistance to and compatibility withth e contents.
2.4.1.3. Member States shall examine the nature and characteristics of the
protective clothing and equipment proposed with particular refer-
ence to the following aspects:
— obtainability and suitability,
— ease of wearing taking into account physical stress and climatic
conditions.
2.4.1.4. Member States shall evaluate the possibility of exposure of other
humans (bystanders or workers exposed after the application of the
plant protection product) or animals to the active substance and/or
to other toxicologically relevant compounds in the plant protection
product under the proposed conditions of use.
This evaluation will take into consideration the following informa-
tion:
(i) the toxicological and metabolism studies on the active
substance as provided for in Annex II and the results of the
evaluation thereof, including the acceptable operator exposure
level;
(ii) the toxicological studies provided for in Annex III, including
where appropriate dermal absorption studies;
(iii) other relevant information on the plant protection product as
provided for in Annex III suchas:
— re-entry periods, necessary waiting periods or other precau-
tions to protect humans and animals,
— method of application, in particular spraying,— maximum application rate,— maximum spray application volume,— composition of the preparation,— excess remaining on plants and plant products after treat-
ment,
— further activities whereby workers are exposed.
2.4.2. Arising from residues
2.4.2.1. Member States shall evaluate the specific information on toxicology
as provided for in Annex II and in particular:
— the determination of an acceptable daily intake (ADI),
— the identification of metabolites, degradation and reaction
products in treated plants or plant products,
— behaviour of residues of the active substance and its metabolites
from the time of application until harvest, or in the case of post-
harvest uses, until outloading of stored plant products.
2.4.2.2. Prior to evaluating the residue levels in the reported trials or in
products of animal origin Member States shall examine the
following information:
— data on the proposed good agricultural practice, including data
on application as provided for in Annex III and proposed pre-
harvest intervals for envisaged uses, or withholding periods or
storage periods, in the case of post-harvest uses,
— nature of the preparation,
— analytical methods and the residue definition.
2.4.2.3. On the basis of suitable statistical models Member States shall eval-
uate the residue levels observed in the reported trials. This1991L0414 — EN — 01.07.2003 — 009.001 — 157
▼M10
evaluation shall be made for each proposed use and shall take into
consideration:
(i) the proposed conditions of use of the plant protection product;
(ii) the specific information on residues in or on treated plants,
plant products, food and feed as provided for in Annex III
and the distribution of residues between edible and non-edible
parts;
(iii) the specific information on residues in or on treated plants,
plant products, food and feed as provided for in Annex II and
the results of the evaluation thereof;
(iv) the realistic possibilities of extrapolating data from one crop to
another.
2.4.2.4. Member States shall evaluate the residue levels observed in
products of animal origin, taking into consideration the information
provided for in Annex III, Part A, point 8.4 and residues resulting
from other uses.
2.4.2.5. Member States shall estimate the potential exposure of consumers
through diet and, where relevant, other ways of exposure, using a
suitable calculation model. This evaluation will take account, where
relevant, of other sources of information such as other authorized
uses of plant protection products containing the same active
substance or which give rise to the same residues.
2.4.2.6. Member States shall, where relevant, estimate the exposure of
animals, taking into account the residue levels observed in treated
plants or plant products intended to be fed to animals.
2.5. Influence on the environment
2.5.1. Fate and distribution in the environment
In the evaluation of the fate and distribution of the plant protection
product in the environment, Member States shall have regard to all
aspects of the environment, including biota, and in particular to the
following:
2.5.1.1. Member States shall evaluate the possibility of the plant protection
product reaching the soil under the proposed conditions of use; if
this possibility exists they shall estimate the rate and the route of
degradation in the soil, the mobility in the soil and the change in
the total concentration (extractable and non-extractable (*)) of the
active substance and of relevant metabolites, degradation and reac-
tion products that could be expected in the soil in the area of
envisaged use after use of the plant protection product according
to the proposed conditions of use.
This evaluation will take into consideration the following informa-
tion:
(i) the specific information on fate and behaviour in soil as
provided for in Annex II and the results of the evaluation
thereof;
(ii) other relevant information on the active substance such as:
— molecular weight,
— solubility in water,— octanol/water partition coefficient,
— vapour pressure,
— volatilization rate,— dissociation constant,
— photodegradation rate and identity of breakdown products,
— hydrolysis rate in relation to pH and identity of breakdown
products;
(iii) all information on the plant protection product as provided for
in Annex III, including the information on distribution and
dissipation in soil;1991L0414 — EN — 01.07.2003 — 009.001 — 158
(*) Non-extractable residues (sometimes referred to as ‘bound’ or ‘non-extracted’ resi-
dues) in plants and soils are defined as chemical species originating from pesticidesused according to good agricultural practice that cannot be extracted by methodswhich do not significantly change the chemical nature of these residues. These non-extractable residues are not considered to include fragments through metabolic path-
ways leading to natural products.
▼M10
(iv) where relevant, other authorized uses of plant protection
products in the area of proposed use containing the same
active substance or which give rise to the same residues.
2.5.1.2. Member States shall evaluate the possibility of the plant protection
product reaching the groundwater under the proposed conditions of
use; if this possibility exists, they shall estimate, using a suitable
calculation model validated at Community level, the concentration
of the active substance and of relevant metabolites, degradation
and reaction products that could be expected in the groundwater in
the area of envisaged use after use of the plant protection product
according to the proposed conditions of use.
As long as there is no validated Community calculation model,
Member States shall base their evaluation especially on the results
of mobility and persistance in soil studies as provided for in
Annexes II and III.
This evaluation will also take into consideration the following
information:
(i) the specific information on fate and behaviour in soil and
water as provided for in Annex II and the results of the
evaluation thereof;
(ii) other relevant information on the active substance such as:
— molecular weight,
— solubility in water,
— octanol/water partition coefficient,
— vapour pressure,— volatilization rate,
— hydrolysis rate in relation to pH and identity of breakdown
products,
— dissociation constant;
(iii) all information on the plant protection product as provided for
in Annex III, including the information on distribution and
dissipation in soil and water;
(iv) where relevant, other authorized uses of plant protection
products in the area of envisaged use containing the same
active substance or which give rise to the same residues;
(v) where relevant, data on dissipation including transformation
and sorption in the saturated zone;
(vi) where relevant, data on the procedures for drinking water
abstraction and treatment in the area of envisaged use;
(vii) where relevant, monitoring data on the presence or absence of
the active substance and relevant metabolites, degradation or
reaction products in groundwater as a result of previous use
of plant protection products containing the same active
substance or which give rise to the same residues; such moni-
toring data shall be interpreted in a consistent scientific way.
2.5.1.3. Member States shall evaluate the possibility of the plant protection
product reaching surface water under the proposed conditions of
use; if this possibility exists they shall estimate, using a suitable
calculation model validated at Community level, the short-term
and long-term predicted concentration of the active substance and
of metabolites, degradation and reaction products that could be
expected in the surface water in the area of envisaged use after
use of the plant protection product according to the proposed condi-
tions of use.
If there is no validated Community calculation model, Member
States shall base their evaluation especially on the results of mobi-
lity and persistence in soil studies and the information on run-off
and drift as provided for in Annexes II and III.
This evaluation will also take into consideration the following
information:
(i) the specific information on fate and behaviour in soil and
water as provided for in Annex II and the results of the evalua-
tion thereof;
(ii) other relevant information on the active substance such as:
— molecular weight,
— solubility in water,— octanol/water partition coefficient,
— vapour pressure,1991L0414 — EN — 01.07.2003 — 009.001 — 159
▼M10
— volatilization rate,
— hydrolysis rate in relation to pH and identity of breakdown
products,
— dissociation constant;
(iii) all relevant information on the plant protection product as
provided for in Annex III, including the information on distri-
bution and dissipation in soil and water;
(iv) possible routes of exposure:
— drift,
— run-off,
— overspray,
— discharge via drains,— leaching,
— deposit in the atmosphere;
(v) where relevant, other authorized uses of plant protection
products in the area of envisaged use containing the same
active substance or which give rise to the same residues;
(vi) where relevant, data on the procedures for drinking water
abstraction and treatment in the area of envisaged use.
2.5.1.4. Member States shall evaluate the possibility of the plant protection
product being dissipated in the air under the proposed conditions of
use; if this possibility exists they shall make the best possible esti-
mation, using where appropriate a suitable, validated calculation
model, of the concentration of the active substance and of relevant
metabolites, degradation and reaction products that could be
expected in the air after use of the plant protection product
according to the proposed conditions of use.
This evaluation will take into consideration the following informa-
tion:
(i) the specific information on fate and behaviour in soil, water
and air as provided for in Annex II and the results of the
evaluation thereof;
(ii) other relevant information on the active substance such as:
— vapour pressure,
— solubility in water,
— hydrolysis rate in relation to pH and identity of breakdown
products,
— photochemical degradation in water and air and identity of
breakdown products,
— octanol/water partition coefficient;
(iii) all relevant information on the plant protection product as
provided for in Annex III, including the information on distri-
bution and dissipation in air.
2.5.1.5. Member States shall evaluate the procedures for destruction or
decontamination of the plant protection product and its packaging.
2.5.2. Impact on non-target species
When calculating toxicity/exposure ratios Member States shall take
into consideration toxicity to the most sensitive relevant organism
used in the tests.
2.5.2.1. Member States shall evaluate the possibility of exposure of birds
and other terrestrial vertebrates to the plant protection product
under the proposed conditions of use; if this possibility exists they
shall evaluate the extent of the short-term and long-term risk to be
expected for these organisms, including their reproduction, after use
of the plant protection product according to the proposed conditions
of use.
(a) This evaluation will take into consideration the following infor-
mation:
(i) the specific information relating to toxicological studies on
mammals and to the effects on birds and other non-target
terrestrial vertebrates, including effects on reproduction,
and other relevant information concerning the active
substance as provided for in Annex II and the results of
the evaluation thereof;1991L0414 — EN — 01.07.2003 — 009.001 — 160
▼M10
(ii) all relevant information on the plant protection product as
provided for in Annex III, including the information on
effects on birds and other non-target terrestrial vertebrates;
(iii) where relevant, other authorized uses of plant protection
products in the area of envisaged use containing the same
active substance or which give rise to the same residues;
(b) This evaluation will include:
(i) the fate and distribution, including persistence and biocon-
centration, of the active substance and of relevant
metabolites, breakdown and reaction products in the
various parts of the environment after application of the
plant protection product;
(ii) the estimated exposure of the species likely to be exposed
at the time of application or during the period that residues
are present, taking into account all relevant routes of expo-
sure suchas ingestion of th e formulated product or treated
food, predation on invertebrates, feeding on vertebrate
prey, contact by overspraying or withtreated vegetation;
(iii) a calculation of the acute, short-term and, where necessary,
long-term toxicity/exposure ratio. The toxicity/exposure
ratios are defined as respectively the quotient of LD50,
LC50or non-observable effects of concentration (NOEC)
expressed on an active substance basis and the estimated
exposure expressed in mg/kg body weight.
2.5.2.2. Member States shall evaluate the possibility of exposure of aquatic
organisms to the plant protection product under the proposed condi-
tions of use; if this possibility exists they shall evaluate the degree
of short-term and long-term risk to be expected for aquatic organ-
isms after use of the plant protection product according to the
proposed conditions of use.
(a) This evaluation will take into consideration the following infor-
mation:
(i) the specific information relating to the effects on aquatic
organisms as provided for in Annex II and the results of
the evaluation thereof;
(ii) other relevant information on the active substance such as:
— solubility in water,
— octanol/water partition coefficient,— vapour pressure,
— volatilization rate,
— KOC,— biodegradation in aquatic systems and in particular the
ready biodegradability,
— photodegradation rate and identity of breakdown
products,
— hydrolysis rate in relation to pH and identity of break-
down products;
(iii) all relevant information on the plant protection product as
provided for in Annex III and in particular the effects on
aquatic organisms;
(iv) where relevant, other authorized uses of plant protection
products in the area of envisaged use, containing the
same active substance or which give rise to the same resi-
dues;
(b) This evaluation will include:
(i) the fate and distribution of residues of the active substance
and of relevant metabolites, breakdown and reaction
products in water, sediment or fish;
(ii) a calculation of the acute toxicity/exposure ratio for fish
and Daphnia. This ratio is defined as the quotient of
respectively acute LC
50or EC50and the predicted short-
term environmental concentration;
(iii) a calculation of the algal growth inhibition/exposure ratio
for algae. This ratio is defined as the quotient of the EC50and the predicted short-term environmental concentration;
(iv) a calculation of the long-term toxicity/exposure ratio for
fish and Daphnia. The long-term toxicity/exposure ratio is
defined as the quotient of the NOEC and the predicted
long-term environmental concentration;1991L0414 — EN — 01.07.2003 — 009.001 — 161
▼M10
(v) where relevant, the bioconcentration in fish and possible
exposure of predators of fish, including humans;
(vi) if the plant protection product is to be applied directly to
surface water, the effect on the change of surface water
quality, suchas pH or dissolved oxygen content.
2.5.2.3. Member States shall evaluate the possibility of exposure of honey-
bees to the plant protection product under the proposed conditions
of use; if this possibility exists they shall evaluate the short-term
and long-term risk to be exptected for honeybees after use of the
plant protection product according to the proposed conditions of
use.
(a) This evaluation will take into consideration the following infor-
mation:
(i) the specific information on toxicity to honeybees as
provided for in Annex II and the results of the evaluation
thereof;
(ii) other relevant information on the active substance such as:
— solubility in water,
— octanol/water partition coefficient,
— vapour pressure,
— photodegradation rate and identity of breakdown
products,
— mode of action (e. g. insect growthregulating activity);
(iii) all relevant information on the plant protection product as
provided for in Annex III, including the toxicity to honey-
bees;
(iv) where relevant, other authorized uses of plant protection
products in the area of envisaged use, containing the
same active substance or which give rise to the same resi-
dues;
(b) This evaluation will include:
(i) the ratio between the maximum application rate expressed
in grammes of active substance per hectare and the contact
and oral LD50expressed in µg of active substance per bee
(hazard quotients) and where necessary the persistence of
residues on or, where relevant, in the treated plants;
(ii) where relevant, the effects on honeybee larvae, honeybee
behaviour, colony survival and development after use of
the plant protection product according to the proposed
conditions of use.
2.5.2.4. Member States shall evaluate the possibility of exposure of benefi-
cial arthropods other than honeybees to the plant protection product
under the proposed conditions of use; if this possibility exists they
will assess the lethal and sublethal effects on these organisms to be
expected and the reduction in their activity after use of the plant
protection product according to the proposed conditions of use.
This evaluation will take into consideration the following informa-
tion:
(i) the specific information on toxicity to honeybees and other
beneficial arthropods as provided for in Annex II and the
results of the evaluation thereof;
(ii) other relevant information on the active substance such as:
— solubility in water,
— octanol/water partition coefficient,
— vapour pressure,
— photodegradation rate and identity of breakdown products,
— mode of action (e. g. insect growthregulating activity);
(iii) all relevant information on the plant protection product as
provided for in Annex III suchas:
— effects on beneficial arthropods other than bees,
— toxicity to honeybees,— available data from biological primary screening,
— maximum application rate,
— maximum number and timetable of applications;
(iv) where relevant, other authorized uses of plant protection
products in the area of envisaged use, containing the same
active substance or which give rise to the same residues.1991L0414 — EN — 01.07.2003 — 009.001 — 162
▼M10
2.5.2.5. Member States shall evaluate the possibility of exposure of earth-
worms and other non-target soil macro-organisms to the plant
protection product under the proposed conditions of use; if this
possibility exists they shall evaluate the degree of short-term and
long-term risk to be expected to these organisms after use of the
plant protection product according to the proposed conditions of
use.
(a) This evaluation will take into consideration the following infor-
mation:
(i) the specific information relating to the toxicity of the
active substance to earthworms and to other non-target
soil macro-organisms as provided for in Annex II and the
results of the evaluation thereof;
(ii) other relevant information on the active substance such as:
— solubility in water,
— octanol/water partition coefficient,— Kd for adsorption,
— vapour pressure,
— hydrolysis rate in relation to pH and identity of break-
down products,
— photodegradation rate and identity of breakdown
products,
—D T
50and DT90for degradation in the soil;
(iii) all relevant information on the plant protection product as
provided for in Annex III, including the effects on earth-
worms and other non-target soil macro-organisms;
(iv) where relevant, other authorized uses of plant protection
products in the area of envisaged use, containing the
same active substance or which give rise to the same resi-
dues;
(b) This evaluation will include:
(i) the lethal and sublethal effects,
(ii) the predicted initial and long-term environmental concen-
tration,
(iii) a calculation of the actue toxicity/exposure ratio (defined
as the quotient of LC50and predicted initial environmental
concentration) and of the long-term toxicity/exposure ratio
(defined as the quotient of the NOEC and predicted long-
term environmental concentration),
(iv) where relevant, the bioconcentration and persistence of
residues in earthworms.
2.5.2.6. Member States shall, where the evaluation carried out under Part B,
point 2.5.1.1, does not exclude the possibility of the plant protec-
tion product reaching the soil under the proposed conditions of
use, evaluate the impact on microbial activity such as the impact
on nitrogen and carbon mineralization processes in the soil after
use of the plant protection product according to the proposed condi-
tions of use.
This evaluation will take into consideration the following informa-
tion:
(i) all relevant information on the active substance, including the
specific information relating to the effects of non-target soil
micro-organisms as provided for in Annex II and the results
of the evaluation thereof;
(ii) all relevant information on the plant protection product as
provided for in Annex III, including the effects on non-target
soil micro-organisms;
(iii) where relevant, other authorized uses of plant protection
products in the area of proposed use, containing the same
active substance or which give rise to the same residues;
(iv) all available information from biological primary screening.
2.6. Analytical methods
Member States shall evaluate the analytical methods proposed for
post-registration control and monitoring purposes, to determine:1991L0414 — EN — 01.07.2003 — 009.001 — 163
▼M10
2.6.1. for formulation analysis:
the nature and quantity of the active substance(s) in the plant
protection product and, where appropriate, any toxicologically,
ecotoxicologically or environmentally significant impurities and
co-formulants.
This evaluation will take into consideration the following informa-
tion:
(i) the data on analytical methods as provided for in Annex II and
the results of the evaluation thereof;
(ii) the data on analytical methods as provided for in Annex III
and in particular:
— the specificity and linearity of the proposed methods,
— the importance of interferences,— the precision of the proposed methods (intra-laboratory
repeatability and inter-laboratory reproducibility);
(iii) the limit of detection and determination of the proposed
methods for impurities.
2.6.2. for residue analysis:
the residues of the active substance, metabolites, breakdown or
reaction products resulting from authorized uses of the plant protec-
tion product and which are of toxicological, ecotoxicological or
environmental significance.
This evaluation will take into consideration the following informa-
tion:
(i) the data on analytical methods as provided for in Annex II and
the results of the evaluation thereof;
(ii) the data on analytical methods as provided for in Annex III
and in particular:
— the specificity of the proposed methods,
— the precision of the proposed methods (intra-laboratory
repeatability and inter-laboratory reproducibility),
— the recovery rate of the proposed methods at appropriate
concentrations;
(iii) the limit of detection of the proposed methods;
(iv) the limit of determination of the proposed methods.
2.7. Physical and chemical properties
2.7.1. Member States shall evaluate the actual active substance content of
the plant protection product and its stability during storage.
2.7.2. Member States shall evaluate the physical and chemical properties
of the plant protection product and in particular:
— where a suitable FAO specification exists, the physical and
chemical properties addressed in that specification,
— where no suitable FAO specification exists, all the relevant
physical and chemical properties for the formulation as referred
to in the ‘Manual on the development and use of FAO specifi-
cations for plant protection products’.
This evaluation will take into consideration the following informa-
tion:
(i) the data on the physical and chemical properties of the active
substance as provided for in Annex II and the results of the
evaluation thereof;
(ii) the data on the physical and chemical properties of the plant
protection product as provided for in Annex III.
2.7.3. Where proposed label claims include requirements or recommenda-
tions for use of the plant protection product with other plant
protection products or adjuvants as a tank mix, the physical and
chemical compatibility of the products in the mixture must be eval-
uated.1991L0414 — EN — 01.07.2003 — 009.001 — 164
▼M10
C.DECISION-MAKING
1.Generalprinciples
1. Where appropriate, Member States shall impose conditions or
restrictions with the authorizations they grant. The nature and
severity of these measures must be selected on the basis of, and
be appropriate to, the nature and extent of the expected advan-
tages and the risks likely to arise.
2. Member States shall ensure that, where necessary, decisions
taken with respect to the granting of authorizations take account
of the agricultural, plant health or environmental (including
climatic) conditions in the areas of envisaged use. Such consid-
erations may result in specific conditions and restrictions of use,
and, where necessary, in authorization being granted for some
but not other areas within the Member State in question.
3. Member States shall ensure that the authorized amounts, in
terms of rates and number of applications, are the minimum
necessary to achieve the desired effect even where higher
amounts would not result in unacceptable risks to human or
animal health or to the environment. The authorized amounts
must be differentiated according to, and be appropriate to, the
agricultural, plant health or environmental (including climatic)
conditions in the various areas for which an authorization is
granted. However, the rates and the number of applications
may not give rise to undesirable effects suchas th e development
of resistance.
4. Member States shall ensure that decisions respect the principles
of integrated control if the product is intended to be used in
conditions where these principles are relied on.
5. Since the evaluation is to be based on data concerning a limited
number of representative species, Member States shall ensure
that use of plant protection products does not have any long-
term repercussions for the abundance and diversity of non-target
species.
6. Before issuing an authorization, Member States shall ensure that
the label of the product:
— fulfils the requirements of Article 16 of this Directive,
— also contains the information on protection of users required
by Community legislation on worker protection,
— specifies in particular the conditions or restrictions under
which the plant protection product may or may not be used
as referred to in points 1, 2, 3, 4 and 5 above.
The authorization shall mention the particulars indicated in
Article 6 (2) (g) and (h), (3) and (4) of Council Directive 78/
631/EEC of 26 June 1978 on the approximation of the laws of
the Member States relating to the classification, packaging and
labelling of dangerous preparations (pesticides) (1) and in Article
16 (g) and (h) of Directive 91/414/EEC.
7. Before issuing authorizations, Member States shall:
(a) ensure that the proposed packaging is in accordance with the
provisions of Directive 78/631/EEC;
(b) ensure that:
— the procedures for destruction of the plant protection
product,
— the procedures for neutralization of the adverse effects of
the product if it is accidentally dispersed, and
— the procedures for the decontamination and destruction
of the packagings,
are in accordance withth e relevant regulatory provisions.1991L0414 — EN — 01.07.2003 — 009.001 — 165
(1) OJ L 206, 29. 7. 1978, p. 13. Directive as last amended by Directive 92/32/EEC (OJ L
154, 5. 6. 1992, p. 1).
▼M10
8. No authorization shall be granted unless all the requirements
referred to in Section 2 are satisfied. However:
(a) when one or more of the specific decision-making require-
ments referred to in Part C, points 2.1, 2.2, 2.3 or 2.7, are
not fully satisfied, authorizations shall be granted only
where the advantages of the use of the plant protection
product under the proposed conditions of use outweight the
possible adverse effects of its use. Any restrictions on use of
the product relating to non-compliance with some of the
aforementioned requirements must be mentioned on the
label, and non-compliance withth e requirements referred to
in point 2.7 must not compromise proper use of the product.
These advantages can be in terms of:
— advantages for and compatibility withintegrated control
measures or organic farming,
— facilitating strategies to minimize the risk of develop-
ment of resistance,
— the need for a greater diversity of types of active
substances or biochemical modes of action, e.g. for use
in strategies to avoid accelerated breakdown in the soil,
— reduced risk for operators and consumers,— reduced contamination of the environment and reduced
impact on non-target species;
(b) where the criteria referred to in Part C, point 2.6, are not
fully satisfied because of limitations in current analytical
science and technology, authorization shall be granted for a
limited period if the methods submitted prove adequate for
the purposes intended. In this case the applicant shall be
given a time limit in which to develop and submit analyticalmethods that are in accordance with the criteria referred to
above. The authorization will be reviewed on expiry of the
time limit accorded to the applicant;
(c) where the reproducibility of the submitted analytical
methods referred to in Part C, point 2.6, has only been veri-
fied in two laboratories, an authorization shall be granted for
one year to permit the applicant to demonstrate the reprodu-
cibility of those methods in accordance with agreed criteria.
9. Where an authorization has been granted according to the
requirements provided for in this Annex, Member States may,
by virtue of Article 4 (6):
(a) define, where possible, preferably in close co-operation with
the applicant, measures to improve the performance of the
plant protection product, and/or
(b) define, where possible, in close co-operation with the appli-
cant, measures to reduce further the exposure that could
occur during and after use of the plant protection product.
Member States shall inform applicants of any measures identi-
fied under (a) or (b) and shall invite applicants to provide any
supplementary data and information necessary to demonstrate
peformance or potential risks arising under the changed condi-
tions.
2.Specificprinciples
The specific principles shall apply without prejudice to the general
principles referred to in Section 1.
2.1. Efficacy
2.1.1. Where the proposed uses include recommendations for the control
of or protection against organisms which are not considered to be
harmful on the basis of experience acquired or scientific evidence
under normal agricultural, plant health and environmental
(including climatic) conditions in the areas of proposed use or
where the other intended effects are not considered to be beneficial
under those conditions, no authorization shall be granted for those
uses.
2.1.2. The level, consistency and duration of control or protection or other
intended effects must be similar to those resulting from the use of
suitable reference products. If no suitable reference product exists,
the plant protection product must be shown to give a defined1991L0414 — EN — 01.07.2003 — 009.001 — 166
▼M10
benefit in terms of the level, consistency and duration of control or
protection or other intended effects under the agricultural, plant
health and environmental (including climatic) conditions in the
area of proposed use.
2.1.3. Where relevant, yield response when the product is used and reduc-
tion of loss in storage must be quantitatively and/or qualitatively
similar to those resulting from the use of suitable reference
products. If no suitable reference product exists, the plant protection
product must be shown to give a consistent and defined quantitative
and/or qualitative benefit in terms of yield response and reduction
of loss in storage under the agricultural, plant health and environ-
mental (including climatic) conditions in the area of proposed use.
2.1.4. Conclusions as to the performance of the preparation must be valid
for all areas of the Member State in which it is to be authorized,
and must hold for all conditions under which its use is proposed,
except where the proposed label specifies that the preparation is
intended for use in certain specified circumstances (e.g. light infes-
tations, particular soil types or particular growing conditions).
2.1.5. Where proposed label claims include requirements for use of the
preparation withoth er specified plant protection products or adju-
vants as a tank mix, the mixture must achieve the desired effect
and comply withth e principles referred to in points 2.1.1 to 2.1.4.
Where proposed label claims include recommendations for use of
the preparation with specified plant protection products or adjuvants
as a tank mix, Member States shall not accept the recommendations
unless they are justified.
2.2. Absence of unacceptable effects on plants or plant products
2.2.1. There must be no relevant phytotoxic effects on treated plants or
plant products except where the proposed label indicates appro-
priate limitations of use.
2.2.2. There must be no reduction of yield at harvest due to phytotoxic
effects below that which could be obtained without the use of the
plant protection product, unless this reduction is compensated for
by other advantages such as an enhancement of the quality of the
treated plants or plant products.
2.2.3. There must be no unacceptable adverse effects on the quality of
treated plants or plant products, except in the case of adverse
effects on processing where proposed label claims specify that the
preparation should not be applied to crops to be used for processing
purposes.
2.2.4. There must be no unacceptable adverse effects on treated plants or
plant products used for propagation or reproduction, suchas effects
on viability, germination, sprouting, rooting and establishment,
except where proposed label claims specify that the preparation
should not be applied to plants or plant products to be used for
propagation or reproduction.
2.2.5. There must be no unacceptable impact on succeeding crops, except
where proposed label claims specify that particular crops, which
would be affected, should not be grown following the treated crop.
2.2.6. There must be no unacceptable impact on adjacent crops, except
where proposed label claims specify that the preparation should
not be applied when particular sensitive adjacent crops are present.
2.2.7. Where proposed label claims include requirements for use of the
preparation withoth er plant protection products or adjuvants, as a
tank mix, the mixture must comply with the principles referred to
in points 2.2.1 to 2.2.6.
2.2.8. The proposed instructions for cleaning the application equipment
must be both practical and effective so that they can be applied
with ease so as to ensure the removal of residual traces of the plant
protection product which could subsequently cause damage.
2.3. Impact on vertebrates to be controlled
An authorization for a plant protection product intended to elimi-
nate vertebrates shall be granted only when:
— death is synchronous with the extinction of consciousness, or
— deathoccurs immediately, or1991L0414 — EN — 01.07.2003 — 009.001 — 167
▼M10
— vital functions are reduced gradually without signs of obvious
suffering.
For repellant products, the intended effect shall be obtained without
unnecessary suffering and pain for the target animals.
2.4. Impact on human or animal health
2.4.1. arising from the plant protection product
2.4.1.1. No authorization shall be granted if the extent of operator exposure
in handling and using the plant protection product under the
proposed conditions of use, including dose and application method,
exceeds the AOEL.
Moreover, the conditions of the authorization shall be in compli-
ance with the limit value established for the active substance and/
or toxicologically relevant compound(s) of the product in accor-
dance withCouncil Directive 80/1107/EEC of 27 November 1980
on the protection of workers from the risks related to exposure to
chemical, physical and biological agents at work(1) and in accor-
dance withCouncil Directive 90/394/EEC of 28 June 1990 on th e
protection of workers from the risks related to exposure to carcino-
gens at work (sixth special directive within the meaning of Article
16 (2) of Directive 89/39/EEC) (2).
2.4.1.2. Where the proposed conditions of use require use of items of
protective clothing and equipment, no authorization shall be granted
unless those items are effective and in accordance with the relevant
Community provisions and are readily obtainable by the user andunless it is feasible to use them under the circumstances of use of
the plant protection product, taking into account climatic conditions
in particular.
2.4.1.3. Plant protection products which because of particular properties or
if mishandled or misused could lead to a high degree of risk must
be subject to particular restrictions suchas restrictions on th e size
of packaging, formulation type, distribution, use or manner of use.
Moreover, plant protection products which are classified as very
toxic may not be authorized for use by non-professional users.
2.4.1.4. Waiting and re-entry safety periods or other precautions must be
such that the exposure of bystanders or workers exposed after the
application of the plant protection product does not exceed the
AOEL levels established for the active substance or toxicologically
relevant compound(s) in the plant protection product nor any limit
values established for those compounds in accordance with the
Community provisions referred to in point 2.4.1.1.
2.4.1.5. Waiting and re-entry safety periods or other precautions must be
established in such a way that no adverse impact on animals occurs.
2.4.1.6. Waiting and re-entry periods or other precautions to ensure that the
AOEL levels and limit values are respected must be realistic; if
necessary special precautionary measures must be prescribed.
2.4.2. arising from residues
2.4.2.1. Authorizations must ensure that residues occurring reflect the
minimum quantities of the plant protection product necessary to
achieve adequate control corresponding to good agricultural prac-
tice, applied in sucha manner (including pre-h arvest intervals or
withholding periods or storage periods) that the residues at harvest,
slaughter or after storage, as appropriate, are reduced to a
minimum.1991L0414 — EN — 01.07.2003 — 009.001 — 168
(1) OJ L 327, 3. 12. 1980, p. 8. Directive as last amended by Directive 88/642/EEC (OJ L
356, 24. 12. 1988, p. 74).
(2) OJ L 196, 26. 7. 1990, p. 1. Directive as amended by Directive 97/42/EC (OJ L 179, 8.
7. 1997, p. 4).
▼M10
2.4.2.2. Where no Community maximum residue limit (MRL)(*) or provi-
sional MRL (at national or at Community level) exists, Member
States shall establish a provisional MRL in accordance with Article
4 (1) (f) of this Directive; conclusions as to the levels fixed must be
valid for all circumstances which could influence the residue levels
in the crop such as timing of application, application rate and
frequency or manner of use.
2.4.2.3. Where the new circumstances under which the plant protection
product is to be used do not correspond to those under which a
provisional MRL (at national or at Community level) was estab-
lished previously, Member States shall not grant an authorization
for the plant protection product unless the applicant can provide
evidence that its recommended use will not exceed that MRL or
unless a new provisional MRL has been established by the Member
State or the Commission in accordance with Article 4 (1) (f) of this
Directive.
2.4.2.4. Where a Community MRL exists Member States shall not grant an
authorization for the plant protection product unless the applicant
can provide evidence that its recommended use will not exceed
that MRL, or unless a new Community MRL has been established
in accordance with the procedure provided for in the relevant
Community legislation.
2.4.2.5. In the cases referred to in points 2.4.2.2 and 2.4.2.3, each applica-
tion for an authorization must be accompanied by a risk assessment
taking into account worst-case potential exposure of consumers in
the Member State concerned on the basis of good agricultural prac-
tice.
Taking into account all registered uses, the proposed use cannot be
authorized if the best possible estimate of dietary exposure exceeds
the ADI.
2.4.2.6. Where the nature of residues is affected during processing, a sepa-
rate risk assessment may need to be carried out under the
conditions provided for in point 2.4.2.5.
2.4.2.7. Where the treated plants or plant products are intended to be fed to
animals, residues occurring shall not have an adverse effect onanimal health.
2.5. Influence on the environment
2.5.1. Fate and distribution in the environment
2.5.1.1. No authorization shall be granted if the active substance and, where
they are of significance from the toxicological, ecotoxicological or
environmental point of view, metabolites and breakdown or reac-
tion products, after use of the plant protection product under the
proposed conditions of use:
— during tests in the field, persist in soil for more than one year
(i.e. DT
90> 1 year and DT50> 3 months), or1991L0414 — EN — 01.07.2003 — 009.001 — 169
(*) A Community MRL will mean an MRL established pursuant to Council Directive 76/
895/EEC of 23 November 1976 relating to the fixing of maximum levels for pesticideresidues in and on fruit and vegetables (
1), Council Directive 86/362/EEC of 24 July
1986 on the fixing of maximum levels for pesticide residues in and on cereals (2),
Council Directive 86/363/EEC of 24 July 1986 on the fixing of maximum levels for
pesticide residues in and on foodstuffs of animal origin (3), Council Regulation (EEC)
No 2377/90 of 26 June 1990 laying down a Community procedure for the establish-ment of maximum residue limits of veterinary medicinal products in foodstuffs ofanimal orgin (
4), Council Directive 90/642/EEC of 27 November 1990 on the fixing
of maximum levels for pesticide residues in and on certain products of plant origin,
including fruit and vegetables (5) or Council Directive 91/132/EEC of 4 March1991
amending Directive 74/63/EEC on undesirable substances and products in feeding-stuffs (
6).
(1) OJ L 340, 9. 12. 1976, p. 26. Directive as last amended by Directive 97/41/EC (OJ
L 184, 12. 7. 1997, p. 33).
(2) OJ L 221, 7. 8. 1986, p. 37. Directive as last amended by Directive 97/41/EC (OJ
L 184, 12. 7. 1997, p. 33).
(3) OJ L 221, 7. 8. 1986, p. 43. Directive as last amended by Directive 97/41/EC (OJ
L 184, 12. 7. 1997, p. 33).
(4) OJ L 224, 18. 8. 1990, p. 1. Regulation as last amended by Commission Regula-
tion (EC) No 749/97 (OJ L 110, 26. 4. 1997, p. 24).
(5) OJ L 350, 14. 12. 1990, p. 71. Directive as amended by Directive 97/41/EC (OJ L
184, 12. 7. 1997, p. 33).
(6) OJ L 66, 13. 3. 1991, p. 16.
▼M10
— during laboratory tests, form non-extractable residues in
amounts exceeding 70 % of the initial dose after 100 days
witha mineralization rate of less th an 5 % in 100 days,
unless it is scientifically demonstrated that under field conditions
there is no accumulation in soil at such levels that unacceptable
residues in succeeding crops occur and/or that unacceptable phyto-
toxic effects on succeeding crops occur and/or that there is an
unacceptable impact on the environment, according to the relevant
requirements provided for in points 2.5.1.2, 2.5.1.3, 2.5.1.4 and
2.5.2.
2.5.1.2. No authorization shall be granted if the concentration of the active
substance or of relevant metabolites, degradation or reaction
products in groundwater, may be expected to exceed, as a result of
use of the plant protection product under the proposed conditions of
use, the lower of the following limit values:
(i) the maximum permissible concentration laid down by Council
Directive 80/778/EEC (1) of 15 July 1980 relating to the quality
of water intended for human consumption, or
(ii) the maximum concentration laid down by the Commission
when including the active substance in Annex I, on the basis
of appropriate data, in particular toxicological data, or, where
that concentration has not been laid down, the concentration
corresponding to one tenth of the ADI laid down when the
active substance was included in Annex I
unless it is scientifically demonstrated that under relevant field
conditions the lower concentration is not exceeded.
2.5.1.3. No authorization shall be granted if the concentration of the active
substance or of relevant metabolites, breakdown or reaction
products to be expected after use of the plant protection product
under the proposed conditions of use in surface water:
— exceeds, where the surface water in or from the area of envi-
saged use is intended for the abstraction of drinking water, the
values fixed by Council Directive 75/440/EEC of 16 June 1975
concerning the quality required of surface water intended for the
abstraction of drinking water in the Member States (2), or
— has an impact deemed unacceptable on non-target species,
including animals, according to the relevant requirements
provided for in point 2.5.2.
The proposed instructions for use of the plant protection product,
including procedures for cleaning application equipment, must be
such that the likelihood of accidental contamination of surface
water is reduced to a minimum.
2.5.1.4. No authorization shall be granted if the airborne concentration of
the active substance under the proposed conditions of use is such
that either the AOEL or the limit values for operators, bystanders
or workers as referred to in Part C, point 2.4.1, are exceeded.
2.5.2. Impact on non-target species
2.5.2.1. Where there is a possibility of birds and other non-target terrestrial
vertebrates being exposed, no authorization shall be granted if:
— the acute and short-term toxicity/exposure ratio for birds and
other non-target terrestrial vertebrates is less than 10 on the
basis of LD50or the long-term toxicity/exposure ratio is less
than 5, unless it is clearly established through an appropriate
risk assessment that under field conditions no unacceptable
impact occurs after use of the plant protection product
according to the proposed conditions of use;
— the bioconcentration factor (BCF, related to fat tissue) is greater
than 1, unless it is clearly established through an appropriate
risk assessment that under field conditions no unacceptable
effects occur — directly or indirectly — after use of the plant
protection product according to the proposed conditions of use.1991L0414 — EN — 01.07.2003 — 009.001 — 170
(1) OJ L 229, 30. 8. 1980, p. 11. Directive as last amended by Directive 91/692/EEC (OJ L
377, 31. 12. 1991, p. 48).
(2) OJ No L 194, 25. 7. 1975, p. 34. Directive as last amended by Directive 91/692/EEC
(OJ No L 377, 31. 12. 1991, p. 48).
▼M10
2.5.2.2. Where there is a possibility of aquatic organisms being exposed, no
authorization shall be granted if:
— the toxicity/exposure ratio for fish and Daphnia is less than 100
for acute exposure and less than 10 for long-term exposure, or
— the algal growth inhibition/exposure ratio is less than 10, or
— the maximum bioconcentration factor (BCF) is greater than
1 000 for plant protection products containing active substances
which are readily biodegradable or greater than 100 for those
which are not readily biodegradable,
unless it is clearly established through an appropriate risk assess-
ment that under field conditions no unacceptable impact on the
viability of exposed species (predators) occurs — directly or indir-
ectly — after use of the plant protection product according to the
proposed conditions of use.
2.5.2.3. Where there is a possibility of honeybees being exposed, no author-
ization shall be granted if the hazard quotients for oral or contact
exposure of honeybees are greater than 50, unless it is clearly estab-
lished through an appropriate risk assessment that under field
conditions there are no unacceptable effects on honeybee larvae,
honeybee behaviour, or colony survival and development after use
of the plant protection product according to the proposed conditions
of use.
2.5.2.4. Where there is a possibility of beneficial arthropods other than
honeybees being exposed, no authorization shall be granted if
more than 30 % of the test organisms are affected in lethal or
sublethal laboratory tests conducted at the maximum proposed
application rate, unless it is clearly established through an appro-
priate risk assessment that under field conditions there is no
unacceptable impact on those organisms after use of the plant
protection product according to the proposed conditions of use.
Any claims for selectivity and proposals for use in integrated pest
management systems shall be substantiated by appropriate data.
2.5.2.5. Where there is a possibility of earthworms being exposed, no
authorization shall be granted if the acute toxicity/exposure ratio
for earthworms is less than 10 or the long-term toxicity/exposure
ratio is less than 5, unless it is clearly established through an appro-
priate risk assessment that under field conditions earthworm
populations are not at risk after use of the plant protection product
according to the proposed conditions of use.
2.5.2.6. Where there is a possibility of non-target soil micro-organisms
being exposed, no authorization shall be granted if the nitrogen or
carbon mineralization processes in laboratory studies are affected
by more than 25 % after 100 days, unless it is clearly established
through an appropriate risk assessment that under field conditions
there is no unacceptable impact on microbial activity after use of
the plant protection product according to the proposed conditions
of use, taking account of the ability of micro-organisms to multiply.
2.6. Analytical methods
The methods proposed must reflect the state of the art. The
following criteria must be met in order to permit validation of the
analytical methods proposed for post-registration control and moni-
toring purposes:
2.6.1. for formulation analysis:
the method must be able to determine and to identify the active
substance(s) and where appropriate any toxicologically, ecotoxico-
logically or environmentally significant impurities and co-
formulants;
2.6.2. for residue analysis:
(i) the method must be able to determine and confirm residues of
toxicological, ecotoxicological or environmental significance;
(ii) the mean recovery rates should be between 70 % and 110 %
witha relative standard deviation of ≤20 %;
(iii) the repeatability must be less than the following values for
residues in foodstuffs:1991L0414 — EN — 01.07.2003 — 009.001 — 171
▼M10
Residue level
mg/kgDifference
mg/kgDifference
in %
0,01 0,005 50
0,1 0,025 25
1 0,125 12,5
> 1 12,5
Intermediate values are determined by interpolation from a
log-log graph;
(iv) the reproducibility must be less than the following values for
residues in foodstuffs:
Residue level
mg/kgDifference
mg/kgDifference
in %
0,01 0,01 100
0,1 0,05 501 0,25 25
>1 2 5
Intermediate values are determined by interpolation from a
log-log graph;
(v) in the case of residue analysis in treated plants, plant products,
foodstuffs, feedingstuffs or products of animal origin, except
where the MRL or the proposed MRL is at the limit of deter-
mination, the sensitivity of the methods proposed must satisfy
the following criteria:
Limit of determination in relation to the proposed provisional
or Community MRL:
MRL (mg/kg)limit of determination
(mg/kg)
>0,5 0,1
0,5 − 0,05 0,1 − 0,02
<0,05 LMR × 0,5
2.7. Physical and chemical properties
2.7.1. Where an appropriate FAO specification exists, that specification
must be met.
2.7.2. Where no appropriate FAO specification exists, the physical and
chemical properties of the product must meet the following require-
ments
(a) Chemical properties:
Throughout the shelf-life period, the difference between the
stated and the actual content of the active substance in the plant
protection product must not exceed the following values:
Declared content in g/kg or g/l at 20 ºC Tolerance
up to 25 ± 15 % homogeneous formulation
± 25 % non-homogeneous formulation
more than 25 up to 100 ± 10 %
more than 100 up to 250 ± 6 %
more than 250 up to 500 ± 5 %
more than 500 ± 25 g/kg or ± 25 g/l1991L0414 — EN — 01.07.2003 — 009.001 — 172
▼M10
(b) Physical properties:
The plant protection product must fulfil the physical criteria
(including storage stability) specified for the relevant formula-
tion type in the ‘Manual on the development and use of FAO
specifications for plant protection products’.
2.7.3. Where the proposed label claims include requirements or recom-
mendations for use of the preparation with other plant protection
products or adjuvants as a tank mix and/or where the proposed
label includes indications on the compatibility of the preparation
with other plant protection products as a tank mix, those products
or adjuvants must be physically and chemically compatible in the
tank mix.1991L0414 — EN — 01.07.2003 — 009.001 — 173