1991L0414—EN—01.01.2002—004.001—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)
(OJL230,19.8.1991,p.1)
Amendedby:
OfficialJournal
No page date
►M1CommissionDirective93/71/EECof27July1993 L221 27 31.8.1993
►M2CommissionDirective94/37/ECof22July1994 L194 65 29.7.1994
►M3CouncilDirective94/43/ECof27July1994 L227 31 1.9.1994
►M4CommissionDirective94/79/ECof21December1994 L354 16 31.12.1994
►M5CommissionDirective95/35/ECof14July1995 L172 6 22.7.1995
►M6CommissionDirective95/36/ECof14July1995 L172 8 22.7.1995
►M7CommissionDirective96/12/ECof8March1996 L65 20 15.3.1996
►M8CommissionDirective96/46/ECof16July1996 L214 18 23.8.1996
►M9CommissionDirective96/68/ECof21October1996 L277 25 30.10.1996
►M10CouncilDirective97/57/ECof22September1997 L265 87 27.9.1997
►M11CommissionDirective97/73/ECof15December1997 L353 26 24.12.1997
►M12CommissionDirective98/47/ECof25June1998 L191 50 7.7.1998
►M13CommissionDirective1999/1/ECof21January1999 L21 21 28.1.1999
►M14CommissionDirective1999/73/ECof19July1999 L206 16 5.8.1999
►M15CommissionDirective1999/80/ECof28July1999 L210 13 10.8.1999
►M16CommissionDirective2000/10/ECof1March2000 L57 28 2.3.2000
►M17CommissionDirective2000/49/ECof26July2000 L197 32 3.8.2000
►M18CommissionDirective2000/50/ECof26July2000 L198 39 4.8.2000
►M19CommissionDirective2000/66/ECof23October2000 L276 35 28.10.2000
►M20CommissionDirective2000/67/ECof23October2000 L276 38 28.10.2000
►M21CommissionDirective2000/68/ECof23October2000 L276 41 28.10.2000
►M22CommissionDirective2000/80/ECof4December2000 L309 14 9.12.2000
►M23CommissionDirective2001/21/ECof5March2001 L69 17 10.3.2001
►M24CommissionDirective2001/28/ECof20April2001 L113 5 24.4.2001
►M25CommissionDirective2001/36/ECof16May2001 L164 1 20.6.2001
►M26CommissionDirective2001/47/ECof25June2001 L175 21 28.6.2001
►M27CommissionDirective2001/49/ECof28June2001 L176 61 29.6.2001
►M28CommissionDirective2001/87/ECof12October2001 L276 17 19.10.2001
1991L0414—EN—01.01.2002—004.001—2
Correctedby:
►C1Corrigendum,OJL170,25.6.1992,p.40(91/414/EEC)
►C2Corrigendum,OJL4,6.1.1996,p.16(93/71/EEC)
►C3Corrigendum,OJL280,23.11.1995,p.58(94/79/EC)
►C4Corrigendum,OJL221,21.8.1999,p.19(1999/73/EC)
▼B
COUNCILDIRECTIVE
of15July1991
concerningtheplacingofplantprotectionproductsonthemarket
(91/414/EEC)
THECOUNCILOFTHEEUROPEANCOMMUNITIES,
Having regard to the Treaty establishing the European Economic
Community,andinparticularArticle43thereof,
HavingregardtotheproposalfromtheCommission(1),
HavingregardtotheopinionoftheEuropeanParliament(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
organismsincludingweeds;whereasitisabsolutelyessentialtoprotectplants against these risksto prevent a decline in yields and to help toensuresecurityofsupplies;
Whereasoneofthemostimportantwaysofprotectingplantsandplant
products and of improving agricultural production is to use plantprotectionproducts;
Whereastheseplantprotectionproductscanhavenon-beneficialeffects
uponplantproduction;whereastheirusemayinvolverisksandhazardsfor humans, animals and the environment, especially if placed on themarket without having been officially tested and authorized and ifincorrectlyused;
Whereas,inviewofthehazards,therearerulesinmostMemberStates
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-
nizingtheprovisionslaiddownintheMemberStates;
Whereasuniformrulesontheconditionsandproceduresfortheauthor-
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
standardofprotection,which,inparticular,mustpreventtheauthoriza-
tion of plant protection products whose risks to health, groundwater
andtheenvironmentandhumanandanimalhealthshouldtakepriorityovertheobjectiveofimprovingplantproduction;
Whereasitisnecessary,atthetimewhenplantprotectionproductsare
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 ingeneral and,inparticular, noharmfuleffect onhumanoranimalhealthorongroundwater;1991L0414—EN—01.01.2002—004.001—3
(1) OJNoC89,10.4.1989,p.22.
(2) OJNoC72,18.3.1991,p.33.
(3) OJNoC56,7.3.1990,p.3.
▼B
Whereas authorization should be limited to plant protection products
containing certain active substances specified at Community level onthebasisoftheirtoxicologicalandecotoxicological properties;
Whereas it is therefore necessary to establish a Community list of
authorizedactivesubstances;
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 aviewtoadmissionofasubstancetothelistshouldbespecified;
Whereas theCommunity procedureshouldnotprevent MemberStates
fromauthorizing for use in their territory for a lim ited period plantprotection products containing an active substance not yet entered onthe Community list,providedthat theinterested party hassubmitted 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
ofplantprotectionproductscontainingthesaidsubstances;
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 with a view to authorization,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
theregionsconcerned;whereastothisendthereisaneedtoharmonize
the methods of experimentation and control applied by the MemberStatesforthepurposeofgrantingauthorization;
Whereasitisthereforedesirablethatasystemforthemutualsupplyof
informationshouldbeestablishedandthatMemberStatesshouldmakeavailable to each other on request the particulars and scientific docu-mentation submitted in connection with applications for authorization
ofplantprotectionproducts;
Whereas, however, Member States must be enabled to authorize plant
protectionproductsnotcomplyingwiththeabovementionedconditions
whenitisnecessarytodosobecauseofanunforeseeabledangerthrea-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
StandingCommitteeonPlantHealth;
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;
WhereasitisnecessarytomaintainconsistencybetweenthisDirective
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 improvestheprotectionofconsumersofplantsandplantproducts;1991L0414—EN—01.01.2002—004.001—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
repetitionoftestsonanimals;
Whereas, inorder toensure that the requirements laid downare satis-
fied, Member States must make provision for appropriate control andinspection arrangements withregardtothemarketing anduseofplant
protectionproducts;
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
correspondinprincipletothoselaiddowninDirective90/220/EECof23April1990onthedeliberatereleaseintotheenvironmentofgeneti-cally modified organisms(
2); whereas in future however the supply of
data in accordance with Part B of Annexes II and III is likely to be
subject to specific requirements, provision should be made to amend
thisDirectiveaccordingly;
Whereastheimplementation ofthisDirectiveandtheadaptationofits
Annexestoadvances intechnical andscientific knowledge necessitate
closecooperationbetweentheCommissionandtheMemberStates,andwhereas the procedure of the Standing Committee on Plant Healthoffersasuitablebasisforthiscooperation,
HASADOPTEDTHISDIRECTIVE:
Scope
Article 1
1. ThisDirective concernstheauthorization,placingonthemarket,
use and control within the Community of plant protection products in
commercialformandtheplacingonthemarketandcontrolwithintheCommunityofactivesubstancesintendedforausespecifiedinArticle2(1).
2. ThisDirectiveshallapplywithoutprejudicetoCouncilDirective
78/631/EEC of 26June1978 onthe approximation of the lawsof theMemberStatesrelatingtotheclassification,packagingandlabellingofdangerous 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),aslastamendedbyDirective90/517/EEC(6).
3. ThisDirectiveappliestotheauthorizationtoplaceonthemarket
plantprotection productscontaining orcomposedofgenetically 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 with the provisions of Parts A, B and DandtherelevantprovisionsofPartCofDirective90/220/EEC.
TheCommissionshallsubmittotheCouncil,insufficienttimeforthe
lattertobeabletoactnotlaterthantwoyearsafterthedateofnotifi-cation of this Directive, a proposal for an amendment with a view to1991L0414—EN—01.01.2002—004.001—5
(1) OJNoL358,18.12.1986,p.1.
(2) OJNoL117,8.5.1990,p.15.
(3) OJNoL206,29.7.1978,p.13.
(4) OJNoL144,30.5.1984,p.1.
(5) OJNo196,16.8.1967,p.1.
(6) OJNoL287,19.10.1990,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
withtheprocedurelaiddowninthesaidArticle10.
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 operationofthearrangementsdescribedinthefirstandsecondsubparagraphs.
4. This Directive shall apply without prejudice to Council Regula-
tion (EEC) No 1734/88 of 16 June 1988 concerning export fromandimportintotheCommunityofcertaindangerouschemicals(
2).
Definitions
Article 2
ForthepurposesofthisDirectivethefollowingdefinitionsshallapply:1.‘plant protection products’
active substances and preparations containing one or more active
substances, put up in the formin which they are supplied to theuser,intendedto:
1.1. protect plants or plant products against all harmful organisms or
preventtheactionofsuchorganisms,insofarassuchsubstancesorpreparationsarenototherwisedefinedbelow;
1.2. influencethelifeprocessesofplants,otherthanasanutrient,(e.g.
growthregulators);
1.3. preserve plant products, in so far as such substances or products
are not subject to special Council of Commission provisions onpreservatives;
1.4. destroyundesiredplants;or1.5. destroy parts of plants, check or prevent undesired growth of
plants;
2.‘residues of plant protection products’
oneormoresubstancespresentinoronplantsorproductsofplant
origin,edibleanimalproductsorelsewhereintheenvironmentandresultingfromtheuseofaplantprotectionproduct,includingtheirmetabolites andproductsresultingfromtheirdegradation orreac-tion;
3.‘substances’
chemicalelementsandtheircompounds,astheyoccurnaturallyor
by manufacture, including any impurity inevitable resulting from
themanufacturingprocess;
4.‘active substances’
substances or micro-organisms including viruses, having general
orspecificaction:
4.1. againstharmfulorganisms;or4.2. onplants,partsofplantsorplantproducts;5.‘preparations’
mixtures or solutions composed of two or more substances of
whichatleastoneisanactivesubstance,intendedforuseasplant
protectionproducts;
6.‘plants’
liveplantsandlivepartsofplants,includingfreshfruitandseeds;
7.‘plant products’1991L0414—EN—01.01.2002—004.001—6
(1) ThisDirectivewasnotifiedtotheMemberStateson26July1991.
(2) OJNoL155,22.6.1988,p.2.
▼B
productsintheunprocessedstateorhavingundergoneonlysimple
preparation such as milling, drying or pressing, derived fromplants,butexcludingplantsthemselvesasdefinedinpoint6;
8.‘harmful organisms’
pestsof 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
byman;
10.‘placing on the market’
anysupply,whetherinreturnforpaymentorfreeofcharge,other
thanforstoragefollowedbyconsignmentfromtheterritoryoftheCommunity ordisposal. Importation ofaplant protection product
intotheterritory oftheCommunity shall bedeemed toconstitute
placingonthemarketforthepurposesofthisDirective;
11.‘authorization of a plant protection product’
administrative actbywhichthecompetent authorityofaMember
State authorizes, following an application submitted by an appli-
cant, the placing on the market of a plant protection product in
itsterritoryorinapartthereof;
12.‘environment’
water,air,land,wildspeciesoffaunaandflora,andanyinterrela-
tionship between them, as well as any relationship with livingorganisms;
13.‘integrated control’
therationalapplication ofacombinationofbiological,biotechno-
logical,chemical,culturalorplant-breedingmeasureswherebytheuse of chemical plant protection products is limited to the strictminimum necessary to maintain the pest population at levelsbelowthosecausingeconomicallyunacceptabledamageorloss.
General provisions
Article 3
1. MemberStatesshallprescribethatplantprotectionproductsmay
notbeplacedonthemarketandusedintheirterritoryunlesstheyhaveauthorizedtheproductinaccordancewiththisDirective,exceptwheretheintendeduseiscoveredbyArticle22.
2. Member States shall not, on the grounds that a plant protection
productisnotauthorized foruseintheirterritory,impedetheproduc-tion,storageormovementofsuchproductsintendedforuseinanotherMemberState,providedthat:
— theproductisauthorizedinanotherMemberState,and
— the inspection requirements laid down by the Member States in
ordertoensurecompliancewithparagraph1aresatisfied.
3. MemberStatesshallprescribethatplantprotectionproductsmust
be usedproperly. Properuseshall include compliance withthe condi-tions established in accordance with Article 4 and specified on the
labelling,andtheapplicationoftheprinciplesofgoodplantprotection
practice as well as, whenever possible, the principles of integratedcontrol.
4. Member States shall prescribe that active substances may not be
placedonthemarketunless:
— theyareclassified,packagedandlabelledinaccordancewithDirec-
tive67/548/EEC,and
— where the active substance was not on the market two years after
notification of this Directive, a dossier has been forwarded to theMemberStates andtothe Commission, inaccordance withArticle6, with the declaration that the active substance is intended for a1991L0414—EN—01.01.2002—004.001—7
▼B
use specified in Article 2 (1). This condition shall not apply to
activesubstancesintendedforauseunderArticle22.
Granting,reviewandwithdrawalofauthorizationsofplantprotec-
tionproducts
Article 4
1. MemberStatesshallensurethataplantprotection productisnot
authorizedunless:
(a) its active substances are listed in Annex I and any conditions laid
downthereinarefulfilled,
and, with regard to the following points (b), (c), (d) and (e),
pursuant to the uniformprinciples provided for in Annex VI,
unless:
(b) it is established, in the light of current scientific and technical
kowledgeandshownfromappraisal ofthedossierprovidedforinAnnex III, that when used in accordance with Article 3 (3), andhaving regard to all normal conditions under which it may beused,andtotheconsequencesofitsuse:
(i) itissufficientlyeffective;
(ii) ithasnounacceptableeffectonplantsorplantproducts;
(iii) itdoesnotcauseunnecessarysufferingandpaintovertebrates
tobecontrolled;
(iv) ithasnoharmfuleffectonhumanoranimalhealth,directlyor
indirectly (e.g. through drinking water, food or feed) or ongroundwater;
(v) it has no unacceptable influence on the environment, having
particularregardtothefollowingconsiderations:
— its fate and distribution in the environment, particularly
contamination of water including drinking water andgroundwater,
— itsimpactonnon-targetspecies;
(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) itsresidues,resultingfromauthorizeduses,andwhichareoftoxi-
cological or environmental significance, can be determined by
appropriatemethodsingeneraluse;
(e) its physical and chemical properties have been determined and
deemed acceptable for the purposes of the appropriate use andstorageoftheproduct;
(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 subparagraph of Article 1 (1) of Directive 90/462/EEC(
1)
and in Article 11 of Directive 86/362/EEC(2), as amended by
Directive88/298/EEC(3).1991L0414—EN—01.01.2002—004.001—8
(1) OJNoL350,14.12.1990,p.71.
(2) OJNoL221,7.8.1986,p.36.
(3) OJNoL126,20.5.1988,p.53.
▼B
Inparticular:
(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
maximumlevelssetinaccordancewiththefirstsubparagraph;
(ii) MemberStatesmustensurethattheconditionsforapprovalare
appliedinsuchawaythattheprovisionalmaximumlevelsare
notexceeded.
2. The authorization must stipulate the requirements relating to the
placing on the market and use of the product or at least those aimed
atensuringcompliancewiththeprovisionsofparagraph1(b).
3. Member States shall ensure that compliance with the require-
ments set out in paragraph 1 (b) to (f) is established 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
MemberStateconcerned.
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
MemberStates;theymayberenewedafterverification thatthecondi-tions imposed in paragraph 1 are still satisfied. Renewal may begranted for the period necessary to the competent authorities of theMemberStates,forsuchverification,whereanapplicationforrenewalhasbeenmade.
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 forauthorization or party to whoman extension of the fieldof application was granted in accordance with Article 9 to submitfurther information necessary for the review. The authorization may,where necessary, be extended for the period necessary to complete areviewandprovidesuchfurtherinformation.
6. Without prejudice to Decisions already taken pursuant to Article
10,anauthorizationshallbecancelledifitisestablishedthat:
(a) the requirements for obtaining the authorization are not or are no
longersatisfied;
(b) false or misleading particulars were supplied concerning the facts
onthebasisofwhichtheauthorizationwasgranted;
ormodifiedifitisestablishedthat:
(c) onthebasisofdevelopmentsinscientificandtechnicalknowledge
themannerofuseandamountsusedcanbemodified.
Itmayalsobecancelledormodifiedattherequestoftheholderofthe
authorization,whoshallstatethereasonstherefor;amendmentscanbegranted only if it is established that the requirements of Article 4 (1)
continuetobesatisfied.
Where a Member State withdraws an authorization, it shall immedi-
ately inform the holder of the authorization; moreover, it may grant a
periodofgraceforthedisposal,storage,placingonthemarketanduse
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
thisDirective.1991L0414—EN—01.01.2002—004.001—9
(1) OJNoL33,8.2.1979,p.36.
(2) OJNoL296,27.10.1990,p.63.
▼B
InclusionofactivesubstancesinAnnexI
Article 5
1. In the light of current scientific and technical knowledge, an
active substance shall be included inAnnexIforan initial period not
exceeding10years,ifitmaybeexpectedthatplantprotectionproducts
containingtheactivesubstancewillfulfilthefollowingconditions:
(a) theirresidues,consequentonapplicationconsistentwithgoodplant
protection practice, do not have any harmful effects on human oranimal healthorongroundwateroranyunacceptable influence ontheenvironment,andthesaidresidues,insofarastheyareoftoxi-
cological or environmental significance, can be measured by
methodsingeneraluse;
(b) their use, consequent on application consistent with good plant
protection practice, does not have any harmful effects on human
oranimalhealthoranyanacceptableinfluenceontheenvironmentasprovidedforinArticle4(1)(b)(iv)and(v).
2. For inclusion of an active substance in Annex I, the following
shallbetakenintoparticularaccount:
(a) whererelevant,anacceptabledailyintake(ADI)forman;
(b) anacceptableoperatorexposurelevelifnecessary;
(c) whererelevant,anestimateofitsfateanddistributionintheenvir-
onmentaswellasitsimpactonnon-targetspecies.
3. For the first inclusion of an active substance which was not yet
onthemarkettwoyearsafternotificationofthisDirective,therequire-ments shall be deemed to be satisfied where this has been establishedforatleastonepreparationcontaingingthesaidactivesubstance.
4. Inclusion of an active substance in Annex I may be subject to
requirementssuchas:
— theminimumdegreeofpurityoftheactivesubstance,
— thenatureandmaximumcontentofcertainimpurities,— restrictionsarisingfromevaluationoftheinformationreferredtoin
Article6,takingaccountoftheagricultural,planthealthandenvir-onmental(includingclimatic)conditionsinquestion,
— typeofpreparation,— mannerofuse.
5. On request, the inclusion of a substance in Annex I may be
renewedonceormoreforperiodsnotexceeding 10years;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,whereanapplicationhasbeenmadeforsuchrenewalinsuffi-cient time,andinanycasenotlessthantwoyearsbeforetheentryisdue to lapse, and shall be granted for the period necessary to provide
informationrequestedinaccordancewithArticle6(4).
Article 6
1. Inclusion of an active substance in Annex I shall be decided in
accordancewiththeprocedurelaiddowninArticle19.
Thefollowingshallalsobedecidedinaccordancewiththatprocedure:
— anyconditionsforinclusion,
— amendementstoAnnexI,wherenecessary,
— removal of an active substance form Annex I if it no longer satis-
fiestherequirementsofArticle5(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 together with a dossier complying with Annex III on at1991L0414—EN—01.01.2002—004.001—10
▼B
leastonepreparationcontainingthatactivesubstance.TheCommission
shall refer the dossier to the Standing Committee on Plant HealthreferredtoinArticle19forexamination.
3. Withoutprejudicetotheprovisionsofparagraph4,attherequest
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 dossierhasbeensubmittedinaccordancewiththerequirementsofAnnexesII
andIII.
4. Iftheassessmentofthedossierreferredtoinparagraph2shows
that further information is necessary, the Commission may ask theapplicant to submit such information. The applicant or his authorizedrepresentativemaybeaskedbytheCommissiontosubmithisremarks
toit,inparticularwheneveranunfavourabledecisionisenvisaged.
These provisions shall also apply if, after inclusion of an active
substance in Annex I, facts emerge that cast doubt on its conformitywith the requirements indicated in Article 5 (1)and (2), orif renewalinaccordancewithArticle5(5)isbeingconsidered.
5. The procedure concerning the submissionandappraisal ofappli-
cations forinclusion inAnnexIandsetting orvarying anyconditions
for inclusion shall be adopted in accordance with the procedure laiddowninArticle21.
Informationonpotentiallyharmfuleffects
Article 7
Member States shall prescribe that the holder of an authorization or
thosetowhomanextensionofthefieldofapplicationhasbeengranted
in accordance with Article 9 (1) must immediately notify the 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 dangerouseffectsontheenvironment. MemberStatesshall
ensurethatthepartiesconcernedimmediatelynotifythisinformationto
theotherMemberStatesandtotheCommission,whichshallrefertheinformationtothecommitteereferredtoinArticle19.
Transitionalmeasuresandderogations
Article 8
1. By way of derogation from Article 4, a Member State may, to
enableagradualassessmenttobemadeofthepropertiesofnewactive
substancesandtomakeiteasierfornewpreparationstobemadeavail-
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,providedthat:
(a) following application of Article 6 (2) and (3) it is found that the
dossier on the active substance satisfies the requirements ofAnnexesIIandIIIinrelationtotheprojecteduses;
(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 informationprovidedforinArticle12(1).
FollowingtheevaluationofthedossierasprovidedforinArticle6(3),
it may be decided, in accordance with the procedure laid down inArticle 19, that the active substance does not satisfy the requirements1991L0414—EN—01.01.2002—004.001—11
▼B
specifiedinArticle5(1).InsuchcasestheMemberStatesshallensure
thattheauthorizationsmustbewithdrawn.
By way of derogation fromArticle 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 bemadeofthedossierand,whereappropriate,ofanyadditionalinforma-tionrequestedinaccordancewithArticle6(3)and(4).
TheprovisionsofArticle4(2),(3),(5)and(6)shallapplytoauthori-
zations granted underthe terms ofthisparagraph withoutprejudice totheforegoingsubparagraphs.
2. By way of derogation fromArticle 4 and without prejudice to
paragraph 3ortoDirective 79/117/EEC, aMemberState 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.
AftertheadoptionofthisDirective,theCommissionshallcommencea
programme of work for the gradual examination of these active
substances within the 12-year period referred to in the foregoingsubparagraph.Thisprogrammemayrequireinterestedpartiestosubmitall requisite data to the Commission and the Member States within aperiod provided for in the programme. A Regulation, adoptedaccordingtotheprocedurelaiddowninArticle19,willsetoutallthe
provisionsnecessaryfortheimplementationoftheprogramme.
TenyearsfollowingnotificationofthisDirectivetheCommissionshall
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
firstsubparagraphistobeextendedforaperiodtobedetermined.
Duringthe12-yearperiodreferredtointhefirstsubparagraphitmay,
following examination by the Committee referred to in Article 19 ofsuch active substance, be decided by the procedure laid down in thatArticlethatthesubstancecanbeincludedinAnnexIandunderwhich
conditions, or, in cases where the requirements of Article 5 are not
satisfiedortherequisiteinformationanddatahavenotbeensubmittedwithin the prescribed period, that such active substance will not beincludedinAnnexI.TheMemberStatesshallensurethattherelevantauthorizations are granted, withdrawn orvaried, asappropriate, within
aprescribedperiod.
3. Wheretheyreviewplantprotectionproductscontaininganactive
substanceinaccordance withparagraph2,andbeforesuchreviewhastaken place, Member States shall apply the requirementslaid down inArticle 4 (1) (b) (i) to (v), and (c) to (f) in accordance with nationalprovisionsconcerningthedatatobeprovided.
4. By way of further derogation fromArticle 4, in special circum -
stancesaMemberStatemayauthorize foraperiodnotexceeding 120days the placing on the market of plant protection products notcomplying with Article 4 for a limited and controlled use if such ameasure 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 beextendedforagivenperiod,repeated,orrevoked.1991L0414—EN—01.01.2002—004.001—12
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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
onthemarket inaMemberState tothecompetent authorities ofeach
Member State where the plant protection product is intended to beplacedonthemarket.
Officialorscientificbodiesinvolvedinagriculturalactivitiesorprofes-
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
otherthanthosecoveredbythisauthorization.
MemberStatesshallgrantanextensionofthefieldofapplicationofan
authorized plant protection product and shall be obliged to grant suchanextensionwhenitisinthepublicinteresttotheextentthat:
— the documentation and information to support an extension of the
fieldofapplicationhasbeensubmittedbytheapplicant,
— theyhaveestablishedthattheconditionsreferredtoinArticle4(1)
(b)(iii),(iv)and(v)aresatisfied,
— theintendeduseisminorinnature,— usersare fully and specifically informed as to instructions for use,
bymeans of an addition to the labelling or,failing that, bymeansofanofficialpublication.
2. Every applicant shall be required to have a permanent office
withintheCommunity.
3. MemberStatesmayrequirethatapplicationsforauthorization be
submitted in their national or official languages or one of those
languages. They may also require that samples of the preparation and
ofitsingredientsbeprovided.
4. Each Member State shall agree to consider any application for
authorization made to it and shall decide thereon within a reasonableperiod,providedthatithasthenecessaryscientificandtechnicalstruc-turesatitsdisposal.
5. MemberStatesshallensurethatafileiscompiledoneachappli-
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 laiddowninArticle 13(1)together withasummaryofthelatter. Member States shall on request make available to the other
Member States and to the Commission the files provided for in this
paragraph; theyshallsupplytothemonrequestallinformation neces-saryforfullcomprehension ofapplications, andshallwhererequestedensure that applicants provide a copy of the technical documentationlaiddowninArticle13(1)(a).
Mutualrecognitionofauthorizations
Article 10
1. At the request of the applicant, who must substantiate the claim
tocomparabilitywithdocumentaryevidence,aMemberStatetowhich
an application is made for the authorization of a plant protection
productalreadyauthorizedinanotherMemberStatemust:
— refrain fromrequiring 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 theuseoftheproductarecomparableintheregionsconcerned,and
— to the extent that the uniformprinciples have been adopted in
accordance withArticle23,wheretheproductcontainsonlyactivesubstances listed in Annex I, also authorize the placing of thatproductonthemarketinitsterritory,totheextentthatagricultural,1991L0414—EN—01.01.2002—004.001—13
▼B
planthealthandenvironmental(includingclimatic)conditionsrele-
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
workersconcerned.
Subject to compliance with the Treaty, authorization may also be
accompanied by restrictions onuse 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
acceptabledailyintakeoftheresiduesconcerned.
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. MemberStatesshallinformtheCommissionofcaseswherethey
haverequiredrepetitionofatestandofcaseswheretheyhaverefused
to authorize a plant protection product already authorized in another
Member State, in respect of which the applicant had claimed that theagricultural,planthealthandenvironmental(includingclimatic)condi-tions relevant to use of the product in the regions concerned in theMemberStatewherethetestwascarriedoutorforwhichauthorization
wasgrantedwerecomparabletothoseintheirownterritory.Theyshall
notify the Commission of the grounds on which repetition of the testwasrequiredorauthorizationwasrefused.
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,oftheseriousecological vulnerability problemsthatmayarisein
certainCommunityregionsorzonestherebyrequiring,iftheydoarise,specific protection measures. The Member State shall without delayaccept the tests and analyses or authorize the placing of the plantprotectionproductonthemarket,subjectinthelattercasetoanyterms
whichtheabovedecisionmayset.
Article 11
1. Where a Member State has valid reasons to consider that a
productwhichithasauthorizedorisboundtoauthorize underArticle
10constitutes arisktohuman oranimal health orthe environment, itmayprovisionallyrestrictorprohibittheuseand/orsaleofthatproducton its territory. It shall immediately inform the Commission and theotherMemberStatesofsuchactionandgivereasonsforitsdecision.
2. A decision shall be taken on the matter within three months in
accordancewiththeprocedurelaiddowninArticle19.
Exchangeofinformation
Article 12
1. Withinaperiodofonemonthattheendofeachquarteratleast,
MemberStatesshallinformeachotherandtheCommissioninwritingof any plant protection products authorized or withdrawn, in accor-dancewiththeprovisionsofthisDirective,indicatingatleast:
— thenameorbusinessnameoftheholderoftheauthorization,
— thetradenameoftheplantprotectionproduct,— thetypeofpreparation,1991L0414—EN—01.01.2002—004.001—14
▼B
— thenameandamountofeachactivesubstancewhichitcontains,
— theuseorusesforwhichitisintended,
— the maximum residue levels provisionally established where they
havenotalreadybeensetbyCommunityrules,
— whererelevant,thereasonsforwithdrawalofanauthorization,
— thedossierneededfortheevaluationofthemaximumresiduelevels
provisionallyestablished.
2. Each Member State shall draw up an annual list of the plant
protection products authorized in its territory and shall communicate
thatlisttotheotherMemberStatesandtheCommission.
In accordance with the procedure laid down in Article 21 a standar-
dized information system shall be set up to facilitate the application
ofparagraphs1and2.
Datarequirements, dataprotectionandconfidentiality
Article 13
1. WithoutprejudicetoArticle10,MemberStatesshallrequirethat
applicants for authorization of a plant protection product submit withtheirapplication:
(a) a dossier satisfying, in the light of current scientific and technical
knowledge,therequirementssetoutinAnnexIII;and
(b) foreachactive substanceintheplantprotectionproduct,adossier
satisfying, in the light of current scientific and technical knowl-edge,therequirementssetoutinAnnexII.
2. Bywayofderogationfromparagraph1,andwithoutprejudiceto
the provisions of paragraphs 3 and 4, applicants shall be exemptedfromsupplying the inform ation 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 purityandnatureofimpurities,fromthecompositionregisteredinthedossieraccompanyingtheoriginalapplication.
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) unlesstheapplicanthasagreedwiththefirstapplicantthatusemay
bemadeofsuchinformation;or
(b) foraperiodof10yearsfromfirstinclusioninAnnexIofanactive
substancenotonthemarkettwoyearsafterthedateofnotificationofthisDirective;or
(c) forperiodsnotexceeding10yearsfromthedateofthedecisionin
each Member State and provided for in existing national rules,concerning an active substance on the market two years after the
dateofnotificationofthisDirective;and
(d) for a period of five years fromthe date of a decision, following
receiptoffurtherinformationnecessaryforfirstinclusioninAnnexI, 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 periodprovided forinparagraphs 3(b)and(c),inwhichcasethe period of five years shall be extended so as to expire on thesamedateasthoseperiods.1991L0414—EN—01.01.2002—004.001—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) unlesstheapplicanthasagreedwiththefirstapplicantthatusemay
bemadeofsuchinformation;or
(b) foraperiodof10yearsfromfirstauthorizationoftheplantprotec-
tionproductinanyMemberState,whereauthorizationfollowstheinclusion 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 precedesinclusion in Annex I of any active substance contained in theproduct.
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
producedbyapersonormanufacturingprocessotherthanthosespeci-fiedinthedossieronthebasisofwhichtheactivesubstancewasfirstincluded in Annex I. They shall transmit to it all data regarding theidentifyandimpuritiesoftheactivesubstance.
6. By way of derogation fromparagraph 1, for active substances
already on the market two years after notification of this Directive,
Member States may, with due regard forthe provisionsof the Treaty,
continuetoapplypreviousnationalrulesconcerningdatarequirementsaslongassuchsubstancesarenotincludedinAnnexI.
7. Notwithstandingparagraph1,andwithoutprejudicetoArticle10,
wheretheactivesubstanceislistedinAnnexI:
(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 whichtheyintendmakingapplication:
— whethertheplantprotectionproductforwhichanapplicationis
tobemadeisthesameasaplantprotectionproductforwhichauthorizationhasbeengranted,and
— as to the name and address of the holder or holders of the
authorizationorauthorizations.
The enquiry shall be supported by evidence that the prospective
applicant intendstoapply forauthorization onhisownbehalf and
thattheotherinformationspecifiedinparagraph1isavailable;
(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 shallatthetimeinformtheholdersoftheauthorizationsofthenameand
addressoftheapplicant.
Theholderorholdersofpreviousauthorizationsandtheapplicantshall
takeallreasonablestepstoreachagreementonthesharingofinforma-tionsoastoavoidtheduplicationoftestingonvertebrateanimals.
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 requesteddata, with a view to limiting the duplication of testing on vertebrate
animals.
If,nevertheless,theapplicantandholdersofpreviousauthorizationsof
the same product can still not reach an agreement on the sharing ofdata, Member States may introduce national measures obliging theapplicant and holders of previous authorizations located within theirterritory to share the data with a view to avoiding duplicative testingon vertebrate animals and determine both the procedure for utilizing1991L0414—EN—01.01.2002—004.001—16
▼B
information, and the reasonable balance of the interests of the parties
concerned.
Article 14
MemberStatesandtheCommissionshall,withoutprejudicetoCouncil
Directive 90/313/EEC of 7 June 1990 on the freedomof access to
information on the environment(1), ensure that information submitted
byapplicants involving industrial andcommercial secrets istreated asconfidential if the applicant wishing to have an active substanceincludedinAnnexIortheapplicantforauthorizationofaplantprotec-tion product so requests, and if the Member State or the Commission
acceptsthattheapplicant'srequestiswarranted.
Confidentialityshallnotapplyto:
— thenamesandcontentoftheactivesubstanceorsubstancesandthe
nameoftheplantprotectionproduct,
— the name of other substances which are regarded as dangerous
underDirectives67/548/EECand78/631/EEC,
— physico-chemical data concerning the active substance and plant
protectionproduct,
— any ways of rendering the active substance or plant protection
productharmless,
— asummaryoftheresultsoftheteststoestablishthesubstance'sor
product'sefficacy andharmlessnesstohumans,animals,plantsandtheenvironment,
— recommendedmethodsandprecautionstoreducehandling,storage,
transport,fireorotherhazards,
— methods of analysis referred to in Articles 4 (1) (c) and (d) and 5
(1),
— methodsofdisposaloftheproductandofitspackaging,
— decontamination procedures to be followed in the case of acciden-
tialspillageorleakage,
— firstaidandmedical treatment tobegiveninthecaseofinjuryto
persons.
Iftheapplicantsubsequentlydisclosespreviouslyconfidentialinforma-
tion, he shall be required to informthe com petent authority
accordingly.
Packagingandlabelling ofplantprotectionproducts
Article 15
Article5(1)ofDirective78/631/EECshallapplytoallplantprotection
productsnotcoveredbyDirective78/631/EEC.
Article 16
Member States shall take all necessary measures to ensure that the
packaging of plant protection products satisfies the following require-mentsastolabelling.
1. Allpackagingmustshowclearlyandindeliblythefollowing:
(a) thetradenameordesignationoftheplantprotectionproduct;
(b) thenameandaddressoftheholderoftheauthorizationandthe
authorization number of the plant protection product and, if
different, the name and address of the person responsible forthe final packaging and labelling or for the final labelling oftheplantprotectionproductonthemarket;
►
C1(c) thenameandamountofeachactivesubstanceexpressed
asprovidedforinArticle6ofDirective78/631/EECand ◄in
particularparagraph(2)(d)ofthatArticle.1991L0414—EN—01.01.2002—004.001—17
(1) OJNoL158,23.6.1990,p.56.
▼B
Thenamemustbeasgiveninthelistcontained inAnnexIto
Directive 67/548/EEC or, if not included therein, its ISOcommon name. If the latter is not available, the active
substance shall be designated by its chemical designation
accordingtoIUPACrules;
(d) thenetquantityofplantprotectionproductgiveninlegalunits
ofmeasurement;
(e) theformulationbatchnumberorsomemeansofidentifyingit;
(f) the particulars required under Article 6 of Directive 78/631/
EEC, inparticular thosementioned inparagraph 2(d),(g),(h)and(i),andparagraphs3and4ofthatArticleandinformationonfirstaid;
(g) thenatureofanyspecialrisksforhumans,animalsortheenvir-
onment, by means of standard phrases selected as appropriatefromthosegiveninAnnexIV;
(h) safetyprecautionsfortheprotection ofhumans,animals orthe
environment,intheformofstandardphrasesselectedasappro-
priatefromthosegiveninAnnexV;
(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) theusesforwhichtheplantprotectionproducthasbeenauthor-
ized and any specific agricultural, plant health andenvironmental conditions under which the product may beusedorshouldnotbeused;
(l) directions for use and the dose rate, expressed in metric units,
foreachuseprovidedforunderthetermsoftheauthorization;
(m) wherenecessary,thesafetyintervalforeachusebetweenappli-
cationand:
— sowingorplantingofthecroptobeprotected,
— sowingorplantingofsucceedingcrops,— accessbyhumansoranimals,— harvesting,— useorconsumption;
(n) particularsofpossiblephytotoxicity, varietal susceptibility, and
any other direct or indirect adverse side effects on plants orproducts of plant origin together with the intervals to be
observedbetweenapplicationandsowingorplantingof:
— thecropinquestion,or
— subsequentcrops;
(o) ifaccompaniedbyaleaflet,asprovidedforinparagraph2,the
sentence‘Readaccompanyinginstructionsbeforeuse’;
(p) directions for safe disposal of the plant protection product and
ofthepackaging;and
(q) the expiry date relevant to normal conditions of storage where
theshelflifeoftheproductislimitedtolessthantwoyears.
2. MemberStatesmaypermittherequirementsinparagraph1(l),(m)
and (n) to be indicated on a separate leaflet accompanying thepackage if the space available on the package is too small. Such aleafletshallberegardedaspartofthelabelforthepurposesofthisDirective.
3. Takingaccountoftherulesinforcewithintheirterritoriesregarding
the supply of certain plant protection products to certain categoriesof users, pending Community harmonization, the Member Statesshall require that it be indicated on the label whether a product is
restrictedtocertaincategoriesofusers.
4. In no circumstances may the label of the packaging of a plant
protection product bear the indications ‘non-toxic’, ‘harmless’, orsimilarindications.However,informationtotheeffectthattheplant1991L0414—EN—01.01.2002—004.001—18
▼B
protection product may be used when bees or other non-target
species are active, or when crops or weeds are in flower or othersuch phrases to protect bees or other non-target species may be
given on the label, if the authorization relates explicitly to use
duringtheseasonforbeesorotherspecifiedorganismsandpresentsminimalhazardtothem.
5. Member States may make the placing of plant protection products
on the market in their territories subject to their being labelled in
theirnationallanguageorlanguages,andmayrequirethatsamples,
models ordrafts ofthe packaging, labelling and leaflets referred tointhisArticlebesubmitted.
Bywayofderogationfromparagraph1(g)and(h),MemberStates
mayrequireadditionalphrasestobeclearlyandindeliblymarkedon
packagingwheretheyaredeemedtobenecessaryfortheprotection
of human beings, animals or the environment; in that event theyshallnotifytheotherMemberStatesandtheCommissionforthwithof each derogation granted and shall forward the additional phraseorphrasesandthereasonsfortheserequirements.
InaccordancewiththeprocedurelaiddowninArticle19,adecision
shallbetakenthattheadditionalphraseorphrasesisorarejustifiedandhencethatAnnexesIVandVmustbeamendedaccordingly,orthat the Member States concerned must no longer require suchphrase(s). The Member State shall be entitled to maintain itsrequirementuntilsuchtimeasadecisionhasbeentaken.
Controlmeasures
Article 17
MemberStatesshallmakethenecessaryarrangementsforplantprotec-
tion products which have been placed onthe market and fortheir useto be officially checked to see whether they comply with the require-ments of this Directive and in particular with the requirements of theauthorizationandinformationappearingonthelabel.
TheMember Statesshall report annually before 1Augusttothe other
Member States and the Commission on the results of the inspection
measurestakeninthepreviousyear.
Administrativeprovisions
Article 18
1. The Council, acting by a qualified majority on a proposal from
the Commission, shall adopt the ‘uniform principles’ referred to inAnnexVI.
2. In accordance with the procedure laid down in Article 19 and
havingregardtocurrentscientificandtechnicalknowledge,theneces-saryamendmentstoAnnexesII,III,IV,VandVIshallbeadopted.
Article 19
Where the procedure laid down in this Article is to be followed,
matters shall be referred without delay by the chairman, either on hisown initiative or at the request of a Member State, to the StandingCommittee onPlantHealth,setupbyDecision76/894/EEC(
1),herin-
afterreferredtoas‘theCommittee’.
Therepresentative oftheCommissionshallsubmittothecommittee a
draft of the measures to be taken. The committee shall deliver itsopinion on the draft within a time limit which the chairman may laydown according to the urgency of the matter. The opinion shall bedelivered by the majority laid down in Article 148 (2) of the Treaty.The votes of the representatives of the Member States within the1991L0414—EN—01.01.2002—004.001—19
(1) OJNoL340,9.12.1976,p.25.
▼B
committeeshallbeweightedinthemannersetoutinthatArticle.The
chairmanshallnotvote.
The Commission shall adopt the measures envisaged if they are in
accordancewiththeopinionofthecommittee.
Ifthemeasuresenvisagedarenotinaccordancewiththeopinionofthe
committee,orifnoopinionisdelivered,theCommissionshall,without
delay, submittotheCouncil aproposalrelating tothemeasurestobe
taken.TheCouncilshallactbyaqualifiedmajority.
If,ontheexpiryofaperiodofthreemonthsfromthedateofreferralto
theCouncil,theCouncilhasnotacted,theproposedmeasuresshallbeadoptedbytheCommission.
Article 20
Where the procedure laid down in this Article is to be followed,
matters shall be referred by the chairman, either on his own initiativeorattherequestofaMemberState,tothecommittee.
TherepresentativeoftheCommissionshallsubmittotheCommitteea
draft of the measures to be taken. The Committee shall deliver itsopiniononthe draft, within atime limit whichthe Chairman maylay
down according to the urgency of the matter. The opinion shall be
delivered by the majority laid down in Article 148 (2) of the Treaty.The votes of the representatives of the Member States within theCommittee shall be weighted in the manner set out in that Article.TheChairmanshallnotvote.
The Commission shall adopt the measures envisaged if they are in
accordancewiththeopinionofthecommittee.
Ifthemeasuresenvisagedarenotinaccordancewiththeopinionofthe
committee,orifnoopinionisdelivered,theCommissionshall,withoutdelay, submittotheCouncil aproposalrelating tothemeasurestobetaken.TheCouncilshallactbyaqualifiedmajority.
If,ontheexpiryofaperiodof15daysfromthedateofreferraltothe
Council, the Council has not acted, the proposed measures shall be
adoptedbytheCommission.
Article 21
Where the procedure laid down in this Article is to be followed,
matters shallbereferred bytheChairman, either onhisowninitiative
orattherequestofaMemberState,tothecommittee.
Therepresentative oftheCommissionshallsubmittothecommittee a
draft of the measures to be taken. The committee shall deliver itsopinion on the draft, within a time limit which the chairman may lay
downaccording totheurgency ofthematter, ifnecessarybytaking a
vote.
Theopinionshallberecordedintheminutes;inaddition,eachMember
State shall have the right to ask to have its position recorded in theminutes.
TheCommissionshalltaketheutmostaccountoftheopiniondelivered
by the committee. It shall inform the committee of the manner inwhichitsopinionhasbeentakenintoaccount.
Researchanddevelopment
Article 22
1. TheMemberStatesshallprescribethatanyexperimentortestfor
researchordevelopment purposesinvolvingtherelease intotheenvir-onment of an unauthorized plant protection product may only becarried out after authorization for trial purposes has been granted andundercontrolledconditionsandforlimitedquantitiesandareas.1991L0414—EN—01.01.2002—004.001—20
▼C1
▼B
▼B
2. Thepersonsconcernedshallsubmitanapplication tothecompe-
tentauthorityoftheMemberStateinwhoseterritorytheexperimentortestistobeconducted,withintimeperiodsprescribedbytheMember
Statebeforethecommencementoftheexperimentortest,togetherwith
adossiercontainingalltheavailabledatatopermitanassessmenttobemade of possible effects on human or animal health or the possibleimpactontheenvironment.
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 Member
State concerned may either prohibit them or permit them subject tosuch conditions as it considers necessary to prevent those conse-quences.
3. Paragraph 2shall not apply if the Member State hasgranted the
person concerned the right to undertake certain experiments and tests
and has determined the conditions under which the experiments and
testshavetobeundertaken.
4. Common conditions for the application of this Article, in parti-
cular the maximum quantities of pesticides that may be releasedduring experiments covered byparagraph 1,andthe minimum data tobe submitted in accordance with paragraph 2, shall be adopted inaccordancewiththeprocedurelaiddowninArticle19.
5. This Article shall not apply to experiments or tests covered by
PartBofDirective90/220/EEC.
ImplementationoftheDirective
Article 23
1. Member States shall bring into force the laws, regulations and
administrative provisions necessary to comply with this Directive
withintwoyearsfollowingnotificationthereof.Theyshallimmediatelyinform the Commission thereof. The uniform principles shall beadoptedoneyearafterthedateofnotification.
WhenMemberStatesadoptthesemeasures,theyshallcontainarefer-
encetothisDirectiveorshallbeaccompaniedbysuchreferenceontheoccasion of their official publication. The methods of making such a
referenceshallbelaiddownbytheMemberStates.
2. Paragraph 1 notwithstanding, Member States need not bring into
force laws, regulations and administrative provisions implementingArticle 10 (1), second indent, until one year at the latest followingadoptionoftheuniformprinciples,andonlyinrelationtotherequire-ments of Article 4 (1) (b) to (e) which are covered by the uniform
principlesthusadopted.
Article 24
ThisDirectiveisaddressedtotheMemberStates.1991L0414—EN—01.01.2002—004.001—21
ANNEX I
ACTIVESUBSTANCESAUTHORISEDFORUSEINPLANTPROTECTIONPRODUCTS
GeneralprovisionsapplyingtoallsubstanceslistedinthisAnnex:
Fortheimplementation oftheuniformprinciplesofAnnexVIinrelationtoeachsubstance,theconclusionsofthe
reviewreportonit,andinparticulartheAppendicesIandIIthereof,asfinalisedintheStandingCommitteeonPlant
Healthonthedateindicatedunder‘specificprovisions’forthatsubstanceshallbetakenintoaccount.
Member States shall keep available all review reports (except for confidential information within the meaning of
Article14oftheDirective)forconsultationbyanyinterestedpartiesorshallmakeitavailable tothemonspecific
request.
Numb-
erCommonname,identifi-
cationnumbersIUPACname Purity(1)Entryinto
forceExpirationof
inclusionSpecificprovisions
1 Imazalil
CASNo73790-28-0,
35554-44-0
CIPACNo335(±)-1-( β-allyloxy-2,4-
dichlorophenylethyl)imi-
dazole
or
(±)-allyl1-(2,4-dichloro-
phenyl)-2-imidazol-1-
ylethylether975g/kg 1.1.1999 31.12.2008 Onlyusesasfungicidemaybeauthorised
Forthefollowingusesthefollowingparticularconditionsapply:
— post harvest fruit, vegetable and potato treatments may only be authorised when an
appropriatedecontamination systemisavailable orariskassessmenthasdemonstrated
to the authorising Member State that the discharge of the treatment solution does not
haveanunacceptablerisktotheenvironmentandinparticulartoaquaticorganisms,
— postharvesttreatment ofpotatoes mayonlybeauthorisedwhenariskassessmenthas
demonstrated to the authorising Member State that the discharge of the processing
wastefromtreatedpotatoesdoesnothaveanunacceptablerisktoaquaticorganisms,
— outdoorfoliarusesmayonlybeauthorisedwhenariskassessmenthasdemonstratedto
the authorising Member State that the use has no unacceptable effects on human and
animalhealthandtheenvironment
Date of Standing Committee on Plant Health at which the review report was finalised:
11.7.1997.
2 Azoxystrobin
CASNo131860-33-8CIPACNo571Methyl(E)-2-{2[6-(2-
cyanophenoxy)pyri-
midin-4-yloxy]phenyl}-
3-methoxyacrylate930g/kg(Z
isomermax.
25g/kg)1.7.1998 1.7.2008 Onlyusesasfungicidemaybeauthorised
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-
priateriskmitigationmeasures
Date of Standing Committee on Plant Health at which the review report was finalised:
22.4.1998▼M221991L0414—EN—01.01.2002—004.001—22
Numb-
erCommonname,identifi-
cationnumbersIUPACname Purity(1)Entryinto
forceExpirationof
inclusionSpecificprovisions
3 Kresoxim-methyl
CASNo143390-89-0
CIPACNo568Methyl(E)-2-methoxyi-
mino-2-[2-(o-tolyloxy-
methyl)phenyl]acetate910g/kg 1.2.1999 31.1.2009 Onlyusedasfungicidemaybeauthorised
In their decision-making according to the uniform principles, Member States shall pay
particularattentiontotheprotectionofgroundwaterundervulnerableconditions
Date of Standing Committee on Plant Health at which the review report was finalised:
16.10.1998
4 Spiroxamine
CASNo1181134-30-8CIPACNo572(8-tert-Butyl-1,4-dioxa-
spiro[4.5]decan-2-
ylmethyl)-ethyl-propyla-
mine940g/kg
(diastereo-
mersAand
Bcombined)1.9.1999 1.9.2009 Onlyusesasafungicidemaybeauthorised
Intheirdecision-makingaccordingtotheuniformprinciples,MemberStates:— mustpayparticular attention tooperator safety andmustensurethat theconditions of
authorisationincludeappropriateprotectivemeasures,and
— mustpayparticular attention totheimpact onaquatic organismsandmustensurethat
theconditionsofauthorisationinclude,whereappropriate,riskmitigationmeasures
Date of Standing Committee on Plant Health at which the review report was finalised:
12.5.1999
5 Azimsulfuron
CASNo120162-55-2
CIPACNo5841-(4,6-dimethoxypyri-
midin-2-yl)-3-[1-methyl-
4-(2-methyl-2H-tetrazol-
5-yl)-pyrazol-5-ylsul-
fonyl]-urea.980g/kg 1.10.1999 1.10.2009 Onlyusesasherbicidemaybeauthorised
Aerialapplicationmaynotbeauthorised
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
andmustensurethat theconditionsofauthorisation include,whereappropriate, riskmiti-
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
CASNo69377-81-7
CIPACNo4314-amino-3,5-dichloro-6-
fluoro-2-pyridyloxyacetic
acid950g/kg 1.12.2000 30.11.2010 Onlyusesasherbicidemaybeauthorised
Intheirdecision-makingaccordingtotheuniformprinciples,MemberStates:
— shall take into account the additional information requested in point 7 of the review
report,
— mustpayparticularattentiontotheprotectionofgroundwater,— mustpayparticular attention totheimpact onaquatic organismsandmustensurethat
theconditionsofauthorisationinclude,whereappropriate,riskmitigationmeasures
MemberStatesshallinformtheCommissioniftherequestedadditionaltrialsandinforma-
tionasoutlinedinpoint7ofthereviewreportwerenotsubmittedby1.12.2000
Date of Standing Committee on Plant Health at which the review report was finalised:
30.11.1999▼M221991L0414—EN—01.01.2002—004.001—23
Numb-
erCommonname,identifi-
cationnumbersIUPACname Purity(1)Entryinto
forceExpirationof
inclusionSpecificprovisions
7 Metsulfuron-methyl
CASNo74223-64-6
EECNo441Methyl-2-(4-methoxy-6-
methyl-1,3,5,-triazin-2-
ylcarbamoylsulfamoyl)-
benzoate960g/kg 1.7.2001 30.6.2011 Onlyusesasherbicidemaybeauthorised
Intheirdecisionmakingaccordingtotheuniformprinciples,MemberStates:
— mustpayparticularattentiontotheprotectionofgroundwater,
— mustpayparticular attention totheimpact onaquatic organismsandmustensurethat
theconditionsofauthorisationinclude,whereappropriate,riskmitigationmeasures
Date of Standing Committee on Plant Health at which the review report was finalised:
16.6.2000
8 Prohexadione-calcium
CASNo127277-53-6
CIPACNo567Calcium3,5-dioxo-4-
propionylcyclohexane-
carboxylate890g/kg 1.10.2000 1.10.2010 Onlyusesasplantgrowthregulatormaybeauthorised
Date of Standing Committee on Plant Health at which the review report was finalised:
16.6.2000
9 Triasulfuron
CASNo82097-50-5CIPACNo4801-[2-(2-chloroethoxy)-
phenylsulfonyl]-3-(4-
methoxy-6-methyl-1,3,5-
triazin-2-yl)urea940g/kg 1.8.2001 31.7.2011 Onlyusesasherbicidemaybeauthorised
Intheirdecisionmakingaccordingtotheuniformprinciples,MemberStates:— mustpayparticularattentiontotheprotectionofgroundwater,
— mustpayparticular attention totheimpact onaquatic organismsandmustensurethat
theconditionsofauthorisationinclude,whereappropriate,riskmitigationmeasures
Date of Standing Committee on Plant Health at which the review report was finalised:
13.7.2000
10 Esfenvalerate
CASNo66230-04-4CIPACNo481(S)-α-Cyano-3-phenoxy-
benzyl-(S)-2-(4-chloro-
phenyl)-3-methylbutyrate830g/kg 1.8.2001 31.7.2011 Onlyusesasinsecticidemaybeauthorised
Intheirdecisionmakingaccordingtotheuniformprinciples,MemberStates:— 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,riskmitigationmeasures
Date of Standing Committee on Plant Health at which the review report was finalised:
13.7.2000
11 Bentazone
CASNo25057-89-0
CIPACNo3663-isopropyl-(1H)-2,1,3-
benzothiadiazin-4-(3H)-
one-2,2-dioxide960g/kg 1.8.2001 31.7.2011 Onlyusesasherbicidemaybeauthorised
In their decision-making according to the uniform principles, Member States must pay
particularattentiontotheprotectionofgroundwater
Date of Standing Committee on Plant Health at which the review report was finalised:
13.7.2000▼M221991L0414—EN—01.01.2002—004.001—24
Numb-
erCommonname,identifi-
cationnumbersIUPACname Purity(1)Entryinto
forceExpirationof
inclusionSpecificprovisions
12 Lambda-cyhalothrin
CASNo91465-08-6
CIPACNo463A1:1mixtureof:
(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-
clopropanecarboxylate810g/kg 1.1.2002 31.12.2011 Onlyusesasinsecticidemaybeauthorised
Intheirdecision-makingaccordingtotheuniformprinciples,MemberStates:
— mustpayparticularattentiontooperatorsafety,
— 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,whereappropriate,riskmitigationmeasures,
— 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
CASNo126833-17-8
CIPACNo603N-(2,3-dichloro-4-hydro-
xyphenyl)-1-methylcy-
clohexanecarboxamide≥950g/
kg(
2)1June2001 31May2011 Onlyusesasafungicidemaybeauthorised.
IndecisionmakingaccordingtotheUniformPrinciplesMemberStatesmustpayparticular
attentiontothepotentialimpactonaquaticorganismsandmustensurethattheconditions
ofauthorisationinclude,whereappropriate,riskmitigationmeasures.
DateofStandingCommitteeonPlantHealthatwhichthereviewreportwasfinalised: 19
October2000
14 Amitrole
CASNo61-82-5
CIPACNo90H-[1,2,4]-triazole-3-
ylamine900g/kg 1.1.2002 31.12.2011 Onlyusesasherbicidemaybeauthorised
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
theStandingCommitteeonPlantHealthon12December2000shallbetakenintoaccount.
InthisoverallassessmentMemberStates:
— mustpayparticularattentiontotheprotectionofoperators
— mustpayparticularattentiontotheprotectionofthegroundwaterinvulnerableareas,in
particularwithrespecttonon-cropuses
— mustpayparticularattentiontotheprotectionofbeneficialarthropods— 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
assessmenthasdemonstratedthatthereisnounacceptableimpactandwhenthecondi-
tionsofauthorisationinclude,whereappropriate,riskmitigationmeasures▼M221991L0414—EN—01.01.2002—004.001—25▼M24
▼M23
Numb-
erCommonname,identifi-
cationnumbersIUPACname Purity(1)Entryinto
forceExpirationof
inclusionSpecificprovisions
15 Diquat
CASNo2764-72-9
(ion),85-00-7(dibro-
mide)
CIPACNo559,10-Dihydro-8a,10a-
diazoniaphenanthreneion
(dibromide)950g/kg 1.1.2002 31.12.2011 Onthebasisofcurrentlyavailableinformation,onlyusesasterrestrialherbicideanddesic-
cantmaybeauthorised.Usesinaquaticweedcontrolshallnotbeauthorised
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
StandingCommitteeonPlantHealthon12December2000shallbetakenintoaccount.In
thisoverallassessmentMemberStates:
— 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
mustensurethattheconditionsofauthorisationinclude,whereappropriate,riskmitiga-
tionmeasures
16 Pyridate
CASNo55512-33.9CIPACNo4476-Chloro-3-phenylpyri-
dazin-4-ylS-octylthio-
carbonate900g/kg 1.1.2002 31.12.2011 Onlyusesasherbicidemaybeauthorised
FortheimplementationoftheuniformpriciplesofAnnexVI,theconclusionsofthereview
report on pyridate, 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.
InthisoverallassessmentMemberStates:
— mustpayparticularattentiontotheprotectionofgroundwater
— 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
CASNo148-79-8
CIPACNo3232-Thiazol-4-yl-1H-benzi-
midazole985g/kg 1.1.2002 31.12.2011 Onlyusesasfungicidemaybeauthorised.Foliarsprayapplicationsshallnotbeauthorised
FortheimplementationoftheuniformpriciplesofAnnexVI,theconclusionsofthereview
report on thiabendazole, 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.
InthisoverallassessmentMemberStates:
— mustpayparticularattentiontotheprotectionofaquaticandsediment-dwellingorgan-
isms and must ensure that the conditions of authorisation include, where appropriate,
riskmitigationmeasures
Suitable risk mitigation measures (e.g. depuration with diatom earth or activated carbon)
have to be implemented to protect surface watersfrom unacceptable levels of contamina-
tionviawastewater▼M231991L0414—EN—01.01.2002—004.001—26
Numb-
erCommonname,identifi-
cationnumbersIUPACname Purity(1)Entryinto
forceExpirationof
inclusionSpecificprovisions
18 Paecilomycesfumo-
soroseus
Apopkastrain97,PFR
97orCG170,
ATCC20874Notapplicable Theabsence
ofsecondary
metabolites
shouldbe
checkedin
eachfermen-
tationbroth
byHPLC1July2001 30June2011 Onlyusesasaninsecticidemaybeauthorised
EachfermentationbrothshouldbecheckedbyHPLCtoensurethatnosecondarymetabo-
litesarepresent
DateofStandingCommitteeonPlantHealthatwhichthereviewreportwasfinalised: 27
April2001
19 DPXKE459(flupyr-
sulfuron-methyl)
CASNo144740-54-5
CIPACNo5772-(4,6-dimethoxypyri-
midin-2-ylcarbamoylsul-
famoyl)-6-trifluromethyl-
nicotinatemonosodium
salt903g/kg(3) 1July2001 30June2011 Onlyusesasaherbicidemaybeauthorised.
Indecision-makingaccordingtotheUniformPrinciplesMemberStatesmustpayparticular
attentiontotheprotectionofgroundwater.
DateofStandingCommitteeonPlantHealthatwhichthereviewreportwasfinalised: 27
April2001.
20 Acibenzolar-s-methyl
CASNo135158-54-2
CIPACNo597Benzo[1,2,3]thiadiazole-
7-carbothioicacidS-
methylester970g/kg 1November
200131October
2011Onlyusesasaplantactivatormaybeauthorised.
DateofStandingCommitteeonPlantHealthatwhichthereviewreportwasfinalised: 29
June2001.
21 Cyclanilide
CASNo113136-77-9
CIPACNo586Notavailable 960g/kg 1November
200131October
2011Onlyusesasaplantgrowthregulatormaybeauthorised.
The maximum content of the impurity 2,4-dichloroaniline (2,4-DCA) in the active
substanceasmanufacturedshouldbe1g/kg.
DateofStandingCommitteeonPlantHealthatwhichthereviewreportwasfinalised: 29
June2001.
22 Ferricphosphate
CASNo10045-86-0CIPACNo629Ferricphosphate 990g/kg 1November
200131October
2011Onlyusesasamolluscicidemaybeauthorised.
DateofStandingCommitteeonPlantHealthatwhichthereviewreportwasfinalised: 29
June2001
23 Pymetrozine
CASNo123312-89-0CIPACNo593(E)-6-methyl-4-[(pyridin-
3-ylmetylene)amino]-4,5-
dihydro-2H-[1,2,4]-
triazin-3one950g/kg 1November
200131October
2011Onlyusesasaninsecticidemaybeauthorised.
Indecision-makingaccordingtotheuniformprinciplesMemberStatesmustpayparticular
attentiontotheprotectionofaquaticorganisms.
DateofStandingCommitteeonPlantHealthatwhichthereviewreportwasfinalised: 29
June2001.▼M231991L0414—EN—01.01.2002—004.001—27▼M26
▼M27
▼M28
Numb-
erCommonname,identifi-
cationnumbersIUPACname Purity(1)Entryinto
forceExpirationof
inclusionSpecificprovisions
24 Pyraflufen-ethyl
CASNo129630-19-9
CIPACNo605Ethyl-2-chloro-5-(4-
chloro-5-difluoro-
methoxy-1-mhypyrazol-
3-yl)-4-fluorophenoxya-
cetate956g/kg 1November
200131October
2011Onlyusesasaherbicidemaybeauthorised.
Indecision-makingaccordingtotheuniformprinciplesMemberStatesmustpayparticular
attentiontotheprotectionofalgaeandaquaticplantsandshouldapply,whereappropriate,
riskmitigationmeasures.
DateofStandingCommitteeonPlantHealthatwhichthereviewreportwasfinalised: 29
June2001.
(1) Furtherdetailsonidentityandspecificationofactivesubstancesareprovidedintheirreviewreports.
►M24(2) Furtherdetailsonidentityandspecificationofactivesubstanceareprovidedinthereviewreport(doc.6797/VI/99rev.2). ◄
►M27(3) FurtherdetailsonidentityandspecificationofactivesubstancesareprovidedinthereviewreportforDPXKE459(flupyrsulfuron-methyl)(5050/ VI/97).◄▼M281991L0414—EN—01.01.2002—004.001—28▼M22
▼B
ANNEX II
REQUIREMENTS FOR THE DOSSIER TO BE SUBMITTED FOR THE
INCLUSIONOFANACTIVESUBSTANCEINANNEXI
INTRODUCTION
Theinformationrequiredshall:
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,theinformation shallbegenerated usingsuitableinternationally or
nationally validated test guidelines or, in the absence thereof, test guide-
linesacceptedbythecompetentauthority;
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
Methodhasnotyetbeenupdated; ◄
1.4. include,whenrequiredbythecompetentauthority,afulldescriptionoftest
guidelines used, except if they are referred to or described in this Annex,
andafulldescriptionofanydeviationsfromthemincludingajustification,
whichisacceptabletothecompetentauthority,forthesedeviations;
1.5. include a full and unbiased report of the studies conducted as well as full
descriptionofthemorajustification,whichisacceptabletothecompetent
authoritywhere:
— particulardataandinformationwhichwouldnotbenecessaryowingto
thenatureoftheproductoritsproposeduses,arenotprovided,
or
— itisnotscientificallynecessary,ortechnicallypossibletosupplyinfor-
mationanddata;
1.6. where relevant, have been generated in accordance with the requirements
ofDirective86/609/EEC.
2.1. Tests and analyses must be conducted in accordance with the 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
theenvironment.
2.2. Bywayofderogationfrompoint2.1,MemberStatesmayprovidethattests
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
beneficialarthropodsotherthanbeesshallbeconductedbyofficialoroffi-
cially-recognizedtestingfacilitiesororganizationswhichsatisfyatleastthe
requirements as set out under points 2.2 and 2.3 of the introduction to
AnnexIII.
Thisderogationappliestotrialsactuallystartedonorbefore31December
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
themarket twoyearsafternotification oftheDirective shallbeconducted1991L0414—EN—01.01.2002—004.001—29
(1) OJNoL15,17.1.1987,p.29.▼M1
▼M4
▼M1
▼M5
▼M5
byofficial orofficially-recognized testingfacilities ororganizations which
satisfyatleasttherequirementsunderpoints2.2and2.3oftheintroduction
toAnnexIII.
This derogation applies for supervised residue trials actually started on or
before31December1997.
2.4. By way of derogation frompoint 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,
mayhavebeen conducted byofficial orofficially recognisedtesting facil-
ities or organisations which satisfy at least the requirements under points
2.2and2.3oftheintroductionofAnnexIII.
PARTA
Chemicalsubstances (1)
1.Identityoftheactive substance
Theinformationprovidedmustbesufficienttoidentifywithprecision
eachactivesubstance,todefineitintermsofitsspecificationandto
characterize it as to its nature. The information and data referred to,
unlessotherwisespecified,arerequiredforallactivesubstances.
1.1. Applicant (name, address, etc.)
The name and address of the applicant (permanent Community
address)mustbeprovidedasmustthename,position,telephoneand
telefaxnumberoftheappropriatepersontocontact.
Where,inaddition,theapplicanthasanoffice,agentorrepresentative
intheMemberStatetowhichtheapplicationforinclusioninAnnexI
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,
mustbeprovided.
1.4. Chemical name (IUPAC and CA nomenclature)
TheChemicalnameasgiveninAnnexItoDirective67/548/EEC,or,
ifnotincludedinthisDirective,inaccordancewithbothIUPACand
CAnomenclature,mustbeprovided.
1.5. Manufacturer's development code number(s)
Codenumbersusedtoidentifytheactivesubstance,andwhereavail-
able, formulations containing the active substance, during
developmentwork,mustbereported.Foreachcodenumberreported,1991L0414—EN—01.01.2002—004.001—30
(1) SubstancewithinthemeaningofthedefinitionofArticle2,point3.▼M25
▼B
▼M2
▼M2
thematerialtowhichitrelates,theperiodforwhichitwasused,and
the Member States or other countries in which it was used and is
beingused,mustbestated.
1.6. CAS, EEC and CIPAC numbers (if available)
Chemical Abstracts, EEC (EINECS or ELINCS), and CIPAC
numbers,wheretheyexist,mustbereported.
1.7. Molecular and structural formula, molecular mass
Themolecularformula,molecularmassandstructuralformulaofthe
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-
productsandimpuritiespresentinthefinalproduct,mustbeprovided,
foreachmanufacturingplant.Generallyprocessengineeringinforma-
tionisnotrequired.
Where the information provided relates to a pilot plant production
system,theinformation requiredmustagainbeprovidedonceindus-
trialscaleproductionmethodsandprocedureshavestabilized.
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
offormulatedproducts,mustbereported.
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
inachangedspecificationofpurity.
1.10. Identity of isomers, impurities and additives (e.g. stabilizers), together
with the structural formula and the content expressed as g/kg
Themaximumcontenting/kgofinactiveisomersaswellastheratio
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
mustbeprovided.
For each component, present in quantities of 1 g/kg or more, the
followinginformation,whererelevant,mustbeprovided:
— chemicalnameaccordingtoIUPACandCAnomenclature,
— ISOcommonnameorproposedcommonnameifavailable,— CAS number, EEC (EINECS or ELINCS) number, and CIPAC
numberifavailable,
— molecularandstructuralformula,— molecularmass,and
— maximumcontenting/kg.
Where the manufacturing process is such that impurities and by-
productswhichareparticularlyundesirablebecauseoftheirtoxicolo-
gical,ecotoxicologicalorenvironmentalpropertiescouldbepresentin
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
each compound of concern, must be reported. Additionally the
followinginformation,whererelevant,mustbeprovided:
— chemicalnameaccordingtoIUPACandCAnomenclature,
— ISOcommonnameorproposedcommonnameifavailable,
— CAS number, EEC (EINECS or ELINCS) number, and CIPAC
numberifavailable,
— molecularandstructuralformula,— molecularmass,and— maximumcontenting/kg.1991L0414—EN—01.01.2002—004.001—31
▼M2
Where the information provided relates to a pilot plant production
system,theinformation requiredmustagainbeprovidedonceindus-
trial scale production methods and procedures have stabilized, if
productionchangesresultinachangedspecificationofpurity.
Where the information provided does not fully identify a component
viz. condensates, detailed information on the composition must be
providedforeachsuchcomponent.
Thetradenameofcomponentsaddedtotheactivesubstance,priorto
manufactureofformulatedproduct,topreservestabilityandfacilitate
ease of handling, wherethey are used, mustalso be provided. Addi-
tionally the following information, where relevant, must be provided
forsuchadditives:
— chemicalnameaccordingtoIUPACandCAnomenclature,
— ISOcommonnameorproposedcommonnameifavailable,
— CAS number, EEC (EINECS or ELINCS) number, and CIPAC
numberifavailable,
— molecularandstructuralformula,
— molecularmass,and
— maximumcontenting/kg.
For added components, other than active substance and other than
impurities resulting from the manufacturing process, the function of
thecomponent(additive)mustbegiven:
— antifoamingagent,
— antifreeze,— binder,
— other(specify),
— buffer,— dispersingagent,
— 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,asappropriate.Theanalyticalresultsreportedmustinclude
quantitativedata,intermsofg/kgcontent,forallcomponentspresent
inquantities ofmorethan1g/kgandtypically shouldaccountforat
least98%ofthematerialanalysed.Theactualcontentofcomponents
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 each relevant compo-
nent,asappropriate.
Where an active substance is produced in different plants this infor-
mationmustbeprovidedforeachoftheplantsseparately.
In addition, where available and relevant, samples of the active
substance produced in laboratory scale or pilot production systems,
must be analyzed, if such material was used in generating toxicolo-
gicalorecotoxicologicaldata.
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,
theinformationprovidedmustpermit:
— physical, chemical, and technical hazards associated with
activesubstances,tobeidentified,
— classificationofactivesubstanceastoharzard,— appropriate restrictions and conditions to be associated with
inclusionsinAnnexItobeselected,and
— appropriateriskandsafetyphrasestobespecified.The information and data referred to are required for all active
substances,exceptwhereotherwisespecified.
(ii) The information provided, taken together with that provided for
relevantpreparations,mustpermitthephysical,chemicalhazards
associatedwithpreparations,tobeidentified,permitpreparations
to be classified, and permit establishment that preparations can1991L0414—EN—01.01.2002—004.001—32
▼M2
be used without unnecessary difficulty, and be such that expo-
sureofman,animals, andtheenvironment isminimized, taking
accountofmannerofuse.
(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
describedindetail,andjustified.
(iv) Incertainspecifiedinstances,testsmustbeconductedusingpuri-
fied active substance of stated specification. In such cases the
principles of the method(s) of purification must be reported.
The purity of such test material, which must be as high as can
be achieved using the best available technology, must be
reported. A reasoned justification must be provided in cases
wherethedegreeofpurityachievedislessthan980g/kg.
Such justification must demonstrate that all technically feasible
andreasonablepossibilitiesfortheproductionofthepureactive
substancehavebeenexhausted.
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 toEEC method A1.Measurements shouldbetaken up to
360ºC.
2.1.2. Whereappropriatetheboilingpointofpurifiedactivesubstancesmust
bedeterminedandreportedaccordingtoEECmethodA2.Measure-
mentsshouldbetakenupto360ºC.
2.1.3. Where melting point and/or boiling point cannot be determined
because of decomposition or sublimation, the temperature at which
decompositionorsublimationoccurs,mustbereported.
2.2. Relative density
Inthecaseofactive substanceswhichareliquidsorsolids,therela-
tive density of the purified active substance must be determined and
reportedaccordingtoEECmethodA3.
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
vapourpressurecurve.
2.3.2. Inthecaseofactivesubstanceswhicharesolidsorliquids,volatility
(Henry's law constant) of purified active substance must be deter-
mined or calculated from its water solubility and vapour pressure
andbereported(inPa×m3×mol−1).
2.4. Appearance (physical state, colour and odour; if known)
2.4.1. Adescriptionofboththecolour,ifany,andthephysicalstateofboth
the active substance as manufactured and purified active substance,
mustbeprovided.
2.4.2. A description of any odour associated with the active substance as
manufactured and purfied active substance, noted when handling the
materialsinlaboratoriesorproductionplants,mustbereported.
2.5. Spectra (UV/VIS, IR, NMR, MS), molecular extinction at relevant
wavelengths
2.5.1. Thefollowingspectaincludingatableofsignalcharacteristicaneeded
forinterpretationmustbedeterminedandreported:Ultraviolet/Visible
(UV/VIS),infrared(R),nuclearmagneticresonance(NMR),andmass
spectra(MS)ofpurifiedactivesubstanceandmolecularextinctionat
relevantwavelengths,mustbedeterminedandreported.
ThewavelengthsatwhichUV/visiblemolecularextinctionoccursare
to be determined and reported and mustinclude whereappropriate a
wavelengthatthehighestabsorptionvalueabove290nm.
In the case of active substances which are resolved optical isomers
theiropticalpuritymustbemeasuredandreported.
2.5.2. The UV/visible absorption spectra, IR, NMRand MS spectra, where
necessary for the identification of the impurities considered to be of1991L0414—EN—01.01.2002—004.001—33
▼M2
toxicological, ecotoxicological orenvironmental significance mustbe
determinedandreported.
2.6. Solubility in water including effect of pH (4 to 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 equilibriumwith atm ospheric
carbon dioxide). Where the active substance is capable of forming
ions, determinations must also be made in the acidic range (pH4 to
6)andinthealkalinerange(pH8to10),andbereported.Wherethe
stability of the active substance in aqueous media is such that water
solubilitycannotbedetermined,ajustificationbasedontestdatamust
beprovided.
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
reportediflessthan250g/kg;thetemperatureappliedmustbespeci-
fied:
— Aliphatichydrocarbon:preferablyn-heptane,
— Aromatichydrocarbon:preferablyxylene,— Halogenatedhydrocarbon:preferably1,2-dichlorethane,— Alcohol:preferablymethanolorisopropylalcohol,— Ketone:preferablyacetone,— Ester:preferablyethylacetate.
If for a particular active substance, one or more of these solvents is
unsuitable (e.g. reacts with test material), alternative solvents can be
used instead. In such cases, choices made must be justified in terms
oftheirstructureandpolarity.
2.8. Partition coefficient n-octanol/water including effect of pH (4 to 10)
The n-octanol/water partition coefficient of purified active substance
mustbedeterminedandreportedaccordingtoEECmethodA8.The
effect of pH (4 to 10) must be investigated when the substance is
acidic or basic as defined by its pKa value (< 12 for acids, > 2 for
bases).
2.9. Stability in water, hydrolysis rate, photochemical degradation,
quantum yield and identity of breakdown product(s), dissociation
constant including effect of pH (4 to 9)
2.9.1. The hydrolysis rate of purified active substances (usually radiola-
belledactivesubstance,>95%purity),foreachofthepHvalues4,
7 and 9, under sterile conditions, in the absence of light, must be
determinedandreportaccordingtoEECmethodC7.Forsubstances
withalowrateofhydrolysis,theratecanbedeterminedat50ºC,or
anotherappropriatetemperature.
If degradation is observed at 50 ºC, degradation rate at another
temperature must be determined, and an Arrhenius plot must be
constructedtopermit anestimate tobemadeofhydrolysisat20ºC.
The identity of hydrolysis products formed and the rate constantly
observed,mustbereported.TheestimatedDT50valuemustalsobe
reported.
2.9.2. Forcompoundswithamolar(decadic)absorptioncoefficient( ε)>10
(1×mol
−1×cm−1)atawavelength λ≥290nm,directphototrans-
formationinpurified (e.g.distilled) waterat20to25ºC,ofpurified
active substance usually radio labelled using artificial light under
sterileconditions,ifnecessaryusingasolubilizer,mustbedetermined
andreported.Sensitizerssuchasacetonemustnotbeusedasacosol-
vent or solubilizer. The light source must simulate sunlight and be
equippedwithfilterstoexcluderadiationatwavelengths λ<290nm.
Theidentityofbreakdownproductsformedwhichatanytimeduring
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,aswellasphotochemicalhalflifemustbereported.
2.9.3. Where necessary to investigate direct phototrans-formation, the
quantum yield of direct photodegradation in water must be deter-
minedandreported,togetherwithcalculationstoestimate theoretical1991L0414—EN—01.01.2002—004.001—34
▼M2
lifetime of the active substance in the top layer of aqueous systems
andthereallifetimeofthesubstance.
ThemethodisdescribedintheFAORevisedGuidelinesonEnviron-
mentalCriteriafortheRegistrationofPesticides.
2.9.4. Wheredissociationinwateroccurs,thedissociationconstant(s)(pKa
values) of the purified active substance must be determined and
reported according toOECDTest Guideline 112.The identity ofthe
dissociated species formed, based on theoretical considerations, must
be reported. If the active, substance is a salt, the pKa value of the
activeprinciplemustbegiven.
2.10. Stability in air, photochemical degradation, identity of breakdown
product(s)
An estimation of the photochemical oxidative degradation (indirect
hototransformation)oftheactivesubstance,mustbesubmitted.
2.11. Flammability including auto-flammability
2.11.1. The flammability of active substances as manufactured, which are
solids,gases,oraresubstanceswhichevolvehighlyflammablegases,
mustbe determined and reported according toEEC method A10,A
11orA12asasappropriate.
2.11.2. The auto-flamability of active substances as manufactured must be
determined and reported according to EEC method A15 or A16 as
appropriate, and/or, where necessary according to the UN-Bowes-
Cameron-Cage-Test (UN-Recommendations on the Transport of
DangerousGoods,Chapter14,No14.3.4).
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
EECmethodA9;onlyclosedcupmethodsshouldbeused.
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
EECmethodA5.
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
exothermicallywithacombustiblematerial.Insuchcases,itissuffi-
cient to provide that information as justification for not determining
theoxidizingpropertiesofthesubstance.
3.Furtherinformationontheactivesubstance
(i) The information provided must describe the intended purposes
forwhich preparations containing the active substance are used,
or are to be used and the dose and manner of their use or
proposeduse.
(ii) The information provided must specify the normal methods and
precautionstobefollowed,inthehandling,storageandtransport
oftheactivesubstance.
(iii) Thestudies,dataandinformationsubmitted,togetherwithother
relevant studies, data and information, must both specify and
justify the methods and precautions to be followed in the event
offire.Thepossibleproductsofcombustionintheeventoffire
should be estimated, based on the chemical structure and the
chemicalandphysicalpropertiesoftheactivesubstance.
(iv) Thestudies,dataandinformationsubmitted,togetherwithother
relevantstudies,dataandinformation,mustdemonstratethesuit-
abilityofmeasuresproposedforuseinemergencysituations.1991L0414—EN—01.01.2002—004.001—35
▼M2
(v) The informaton and data referred to are reqired for all active
substances,exceptwhereotherwisespecified.
3.1. Function, e.g. fungicide, herbicide, insecticide, repellant, growth
regulator
Thefunctionmustbespecifiedfromamongthefollowing:
— acaricide
— bactericide
— fungicide
— herbicide
— insecticide— molluscicide
— nematicide
— plantgrowthregulator
— repellant
— rodenticide— semio-chemicals
— talpicide
— viricide
— other(mustbespecified)
3.2. Effects on harmful organisms, e.g. contact poison, inhalation poison,
stomach poison, fungitoxic, etc. systematic or not in plants
3.2.1. Thenatureoftheeffectsonharmfulorganismsmustbestated:
— contactaction
— stomachaction
— inhalationaction— fungitoxicaction
— fungistaticaction
— desiccant
— reproductioninhibitor
— other(mustbespecified)
3.2.2. Itmustbestatedwhetherornottheactivesubstanceistranslocatedin
plants and where relevant whether such translocation is apoplastic,
symplasticorboth.
3.3. Field of use envisaged, e.g. field, protected crops, storage of plant
products, home gardening
Thefield(s)ofuse,existingandproposed,forpreparationscontaining
theactivesubstancemustbespecifiedfromamongthefollowing:
— Fielduse,suchasagriculture,horticulture,forestryandviticulture
— Protectedcrops
— Amenity
— Weedcontrolonnon-cultivatedareas— Homegardening
— Houseplants
— Plantproductsstoragepractice
— Other(specify)
3.4. Harmful organisms controlled and crops or products protected or
treated
3.4.1. Details of existing and the intended usein terms of crops,groupsof
crops, plants, or plant products treated and where relevant protected,
mustbeprovided.
3.4.2. Whererelevant,detailsofharmfulorganismsagainstwhichprotection
isafforded,mustbeprovided.
3.4.3 Where relevant, effects achieved e.g. sprout suppression, retardation
of ripening, reduction in stemlength, enhanced fertilization etc.,
mustbereported.
3.5. Mode of action
3.5.1. Totheextentthatishaselucidated, astatementmustbeprovidedas
tothemodeofactionoftheactivesubstanceinterms,whererelevant,1991L0414—EN—01.01.2002—004.001—36
▼M2
of the biochemical and physiological mechanism(s) and biochemical
pathway(s) involved. Where availble, the results of relevant experi-
mentalstudiesmustbereported.
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,
7.1,7.2and9,whererelevant,mustbeprovidedforactivemetabolite
ordegradationproduct:
— chemicalnameaccordingtoIUPACandCAnomenclature,
— ISOcommonnameorporposedcommonname,— CAS EEC-number EEC (EINECS or ELINCS) number, and
CIPACnumberifavailable,
— empiricalandstructuralformula,and— molecularmass.
3.5.3. Available information relating to the formation of active metabolites
anddegradationproducts,mustbeprovided,toinclude:
— theprocesses,mechanismsandreactionsinvolved,
— kinetic and other data concerning the rate of conversion and if
knowntheratelimitingstep,
— 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-
mentofresistanceorcross-resistancemustbeprovided.
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)mustbeprovidedforallactivesubstances.
3.8. Procedures for destruction or decontamination
3.8.1. Controlled incineration
Inmanycasesthepreferredorsolemeanstosafelydisposeofactive
substances, contaminated materials, or contaminated packaging, is
throughcontrolledincinerationinalicensedincinerator.
Wherethecontentofhalogensoftheactivesubstanceisgreaterthan
60%,thepyrolyticbehaviouroftheactivesubstanceundercontrolled
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
forsafedisposal.
3.8.2. Others
Other methods to dispose of the active substance, contaminated
packagingandcontaminatedmaterials,whereproposed,mustbefully
described.Datamustbeprovidedforsuchmethods,toestablishtheir
effectivenessandsafety.
3.9. Emergency measures in case of an accident
Procedures for the decontamination of water in case of an accident
mustbeprovided.1991L0414—EN—01.01.2002—004.001—37
(1) OJNoL196,16.8.1967,p.1.
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4.Analyticalmethods
Introduction
Theprovisionsofthissectiononlycoveranalyticalmethodsrequired
forpost-registrationcontrolandmonitoringpurposes.
Foranalyticalmethodsusedforgenerationofdataasrequiredinthis
Directive orforotherpurposesthe applicant hastoprovideajustifi-
cationforthemethodused;wherenecessaryseparateguidancewillbe
developedforsuchmethodsonthebasisofthesamerequirementsas
defined for methods for post-registration control and monitoring
purposes.
Descriptions of methods must be provided and include details of
equipment,materialsandconditionsused.
As far as practicable these methods must employ the simplest
approach,involvetheminimumcost,andrequirecommonlyavailable
equipment.
Forthissectionthefollowingapplies:
Impurities Anycomponentotherthanthepureactive
substancewhichispresentintheactive
substanceasmanufactured(includingnon-
activeisomers)originatingfromthemanu-
facturingprocessorfromdegradationduring
storage,
Relevantimpurities Impuritiesoftoxicologicaland/orecotoxico-
logicalorenvironmentalconcern,
Significantimpurities Impuritieswithacontentof ≥1g/kginthe
activesubstanceasmanufactured,
Metabolites Metabolitesincludeproductsresultingfrom
degradationorreactionoftheactive
substance,
Relevantmetabolites Metabolitesoftoxicologicaland/orecotoxi-
cologicalorenvironmentalconcern.
Onrequestthefollowingsamplesmustbeprovided:
(i) analyticalstandardsofthepureactivesubstance;
(ii) samplesoftheactivesubstanceasmanufactured;
(iii) analyticalstandardsofrelevantmetabolitesandallothercompo-
nentsincludedintheresiduedefinition;
(iv) if available, samples of reference substances for the relevant
impurities.
4.1.Methodsfortheanalysisoftheactivesubstanceasmanufactured
Forthispointthefollowingdefinitionsapply:
(i)Specificity
Specificity is the ability of a method to distinguish between the
analytebeingmeasuredandothersubstances.
(ii)Linearity
Linearity is defined as the ability of the method, within a given
range, to obtain an acceptable linear correlation between the
resultsandtheconcentrationofanalyteinsamples.
(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
acceptedreferencevalue(forexampleISO5725).
(iv)Precision
Precisionisdefinedastheclosenessofagreementbetweeninde-
pendenttestresultsobtainedunderprescribedconditions.1991L0414—EN—01.01.2002—004.001—38
▼M8
Repeatability:Precisionunderrepeatabilityconditions,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
oftime.
The reproducibility is not required for the active substance as
manufactured(fordefinitionofreproducibilityseeISO5725).
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
manufacturedasspecifiedinthedossiersubmittedinsupportofinclu-
sion in Annex I to Directive 91/414/EEC. The applicability of
existingCipacmethodsmustbereported.
4.1.2. Methods must also be provided for the determination of significant
and/orrelevantimpuritiesandadditives(e.g.stabilizers)intheactive
substanceasmanufactured.
4.1.3. Specificity,linearity,accuracyandrepeatability4.1.3.1. Specificityofmethodssubmitted,mustbedemonstratedandreported.
In addition the extent of interference by other substances present in
theactivesubstanceasmanufactured(e.g.isomers,impuritiesoraddi-
tives),mustbedetermined.
While interferences due to other components may be identified as
systematic errors in the assessment of the accuracy of methods
proposedforthedetermination ofpureactive substanceintheactive
substance as manufactured, an explanation must be provided for any
interferenceoccurringwhichcontributesmorethan±3%tothetotal
quantity determined. The degree of interference for methods for the
determinationofimpuritiesmustalsobedemonstrated.
4.1.3.2. Thelinearityofproposedmethodsoveranappropriaterangemustbe
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 ormore concentrations. Alternatively, five concentrations, each
as single measurements, are acceptable. Reports submitted must
includetheequationofthecalibrationlineandthecorrelationcoeffi-
cientandrepresentativeandproperlylabelleddocumentationfromthe
analysis,e.g.chromatograms.
4.1.3.3. Accuracyisrequiredformethodsforthedeterminationofpureactive
substance and significant and/or relevant impurities in the active
substanceasmanufactured.
4.1.3.4. Fortherepeatabilityinthedeterminationofthepureactivesubstance
in principle a minimum of five determinations must be made. The
relative standarddeviation (%RSD)mustbereported.Outliersiden-
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
occurrenceofindividualoutliers,mustbeattempted.
4.2.Methodsforthedeterminationofresidues
The methods must be capable of determining the active substance
and/or relevant metabolites. For each method and for each relevant
representative matrix, the specificity, precision, recovery, and limit
ofdeterminationmustbeexperimentallydeterminedandreported.
In principle, residue methods proposed should be multi-residue
methods; a standard multi-residue method must be assessed and
reportedastoitssuitability forresiduedetermination. Whereresidue
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
forindividualcompounds,a‘commonmoietymethod’maybeaccep-
table.
Forthissectionthefollowingdefinitionsapply:
(i)Specificity
Specificity is the ability of a method to distinguish between the
analytebeingmeasuredandothersubstances.1991L0414—EN—01.01.2002—004.001—39
▼M8
(ii)Precision
Precisionisdefinedastheclosenessofagreementbetweeninde-
pendenttestresultsobtainedunderprescribedconditions.
Repeatability:Precisionunderrepeatabilityconditions,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
oftime.
Reproducibility: As the definition of reproducibility in relevant
publications(forexample,inISO5725)isingeneralnotpractic-
ableforresidueanalyticalmethods,reproducibilityinthecontext
of this Directive is defined as a validation of repeatability of
recovery, fromrepresentative m atrices and at representative
levels,byatleast onelaboratory whichisindependent fromthat
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
metaboliteoriginallyaddedtoasampleoftheappropriatematrix
whichcontainsnodetectableleveloftheanalyte.
(iv)Limit of determination
Thelimit ofdetermination (oftenreferredtoaslimitofquantifi-
cation)isdefinedasthelowestconcentration tested,atwhichan
acceptablemeanrecoveryisobtained(normally70to110%with
a relative standard deviation of preferably ≤20 %; in certain
justified cases lower or higher mean recovery rates as well as
higherrelativestandarddeviationsmaybeacceptable).
4.2.1. Residuesinand/oronplants,plantproducts,foodstuffs(ofplantand
animalorigin),feedingstuffs
Methods submitted must be suitable for the determination of all
componentsincludedintheresiduedefinitionassubmittedaccording
to the provisions of section 6, points 6.1 and 6.2 in order to enable
Member States to determine compliance with established MRL's or
todeterminedislodgeableresidues.
The specificity of the methods must enable all components included
intheresiduedefinitiontobedetermined,usinganadditionalconfir-
matorymethodifappropriate.
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
untreatedsamplewithaliquotsfortifiedattherequiredlevel(s).
The results froman independent laboratory validation m ust be
reported.
The limit of determination including the individual and mean
recovery mustbe determined and reported. The overall relative stan-
dard deviation, as well as the relative standard deviation for each
fortificationlevelmustbeexperimentallydeterminedandreported.
4.2.2. Residuesinsoil
Methods for analysis of soil for parent compound and/or relevant
metabolitesmustbesubmitted.
Thespecificityofthemethodsmustenabletheparentcompoundand/
or relevant metabolites to be determined, using an additional confir-
matorymethodifappropriate.
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 each fortification level must be experimentally
determinedandreported.
Theproposedlimitofdeterminationmustnotexceedaconcentration
whichisofconcern withregard toexposureofnon-target organisms
or because of phytotoxic effects. Normally the proposed limit of
determinationshouldnotexceed0,05mg/kg.1991L0414—EN—01.01.2002—004.001—40
▼M8
4.2.3. Residuesinwater(includingdrinkingwater,groundwaterandsurface
water)
Methods for analysis in water for parent compound and/or relevant
metabolitesmustbesubmitted.
Thespecificityofthemethodsmustenabletheparentcompoundand/
or relevant metabolites to be determined, using an additional confir-
matorymethodifappropriate.
The repeatability, recovery and the limit of determination including
theindividual andmeanrecovvery mustbedetermined andreported.
The overall relative standard deviation, as well as the relative stan-
dard deviation for each fortification level must be experimentally
determinedandreported.
For drinking water the proposed limit of determination must not
exceed0,1µg/l.Forsurfacewatertheproposedlimitofdetermination
must not exceed a concentration which has an impact on non-target
organisms deemed to be unacceptable according to the requirements
ofAnnexVI.
4.2.4. Residuesinair
Methodsfortheanalysisinairoftheactivesubstanceand/orrelevant
metabolites formed during or shortly after application must be
submitted unless it can be justified that exposure of operators,
workersorbystandersisnotlikelytooccur.
Thespecificityofthemethodsmustenabletheparentcompoundand/
or relevant metabolites to be determined, using an additional confir-
matorymethodifappropriate.
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 each fortification level must be experimentally
determinedandreported.
The proposed limit of determination must take into account relevant
healthbasedlimitvaluesorrelevantexposurelevels.
4.2.5. Residuesinbodyfluidsandtissues
Whereanactivesubstanceisclassifiedastoxicorhighlytoxicappro-
priateanalyticalmethodsmustbesubmitted.
Thespecificityofthemethodsmustenabletheparentcompoundand/
or relevant metabolites to be determined, using an additional confir-
matorymethodifappropriate.
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 each fortification level must be experimentally
determinedandreported.
5. Toxicologicalandmetabolismstudies
Introduction
(i) Theinformationprovided,takentogetherwiththatprovidedfor
oneormorepreparationscontainingtheactive substance,must
besufficienttopermitanevaluationtobemadeastotherisks
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.
Inaddition,theinformationprovidedmustbesufficientto:
— permit a decision to be made as to whether, or not, the
activesubstancecanbeincludedinAnnexI,
— specify appropriate conditions or restrictions to be asso-
ciatedwithanyinclusioninAnnexI,
— classifytheactivesubstanceastohazard,— establish a relevant acceptable daily intake (ADI) level for
man,
— establishacceptableoperatorexposurelevel(s)(AOEL),— specify the hazard symbols, the indications of danger, and
the risk and safety phrases for the protection of man,1991L0414—EN—01.01.2002—004.001—41
▼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
eventofpoisoninginman,and
— permitanevaluationtobemadeastothenatureandextent
oftherisksforman,animals(speciesnormallyfedandkept
or consumed by man) and of the risks for other non-target
vertebratespecies.
(ii) Thereisaneedtoinvestigateandreportallpotentiallyadverse
effects found during routine toxicological investigations
(includingeffectsonorgansandspecialsystemssuchasimmu-
notoxicity and neurotoxicity) and to undertake and report such
additional studies which may be necessary to investigate the
probablemechanisminvolved,toestablishNoaels(noobserved
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
substancetested,mustbereported.
(iii) Inthecontextoftheinfluencethatimpuritiescanhaveontoxi-
cologicalbehaviour,itisessentialthatforeachstudysubmitted,
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
usedinthemanufactureofpreparationstobeauthorized,except
whereradiolabelledmaterialisrequiredorpermitted.
(iv) Where studies are conducted using an active substance
producedinthelaboratoryorinapilotplantproductionsystem,
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
decisionastothepossibleneedforrepetitionofthestudies.
(v) In the case of studies in which dosing extends over a period,
dosingshouldpreferablybedoneusingasinglebatchofactive
substanceifstabilitypermits.
(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
distributeduniformlyinthediet.
(vii) Where, as a result of metabolism or other processes in or on
treated plants, or as a result of processing of treated products,
theterminalresidue(towhichconsumersorworkersasdefined
inAnnexIII,point7.2.3willbeexposed)containsasubstance
whichisnottheactivesubstanceitselfandisnotidentifiedasa
metabolite in mammals, it will be necessary to carry out toxi-
citystudiesonthesecomponentsoftheterminalresidueunless
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
findingsofthemetabolite cannotbeevaluatedbytheavailable
resultsrelatingtotheactivesubstance.
(viii) Thewayofadministrationofthetestsubstancedependsonthe
mainexposureroutes.Incaseswhereexposureismainlybythe
gas phase, it can be more appropriate to perform inhalation
studiesinsteadoforalstudies.
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.Thesedatacanprovideinformationusefulinthedesignandinterpre-
tation of subsequent toxicity tests. However, it must be remembered
thatinformationoninterspeciesdifferencesmaybecrucialinextrapo-
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—01.01.2002—004.001—42
▼M4
Aimofthetest:
Thetestsshouldprovidesufficientdatatopermit:
— anevaluationoftherateandextentofabsorption,
— the tissue distribution and the rate and extent of excretion of the
testsubstanceandtherelevantmetabolites,
— theidentificationofmetabolitesandthemetabolicpathway.
The effect of doselevel on these parameters and whether results are
different after single versus repeated doses, should also be investi-
gated.
Circumstancesinwhichrequired
Asingledosetoxicokineticstudyinrats(oralrouteofadministration)
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 performadditional studies on another species (such as goat or
chicken).
Testguideline
CommissionDirective87/302/EECof18November1987adaptingto
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
dangeroussubstances(1),partB,Toxicokinetics.
5.2.Acutetoxicity
Thestudies,dataandinformation tobeprovidedandevaluated must
besufficient topermit theidentification ofeffectsfollowingasingle
exposure to the active substance, and in particular to establish, or
indicate:
— thetoxicityoftheactivesubstance;
— the time courseand characteristics of the effects withfull details
ofbehaviouralchangesandpossiblegrosspathologicalfindingsat
post-mortem;
— wherepossiblemodeoftoxicaction;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 with Council Directive 67/
548/EEC.Theinformationgenerated throughacutetoxicitytestingis
of particular value in assessing hazards likely to arise in accident
situations.
5.2.1. Oral
CircumtancesinwhichrequiredThe acute oral toxicity of the active substance must always be
reported.
TestguidelineThe 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
dangeroussubstances(
2),MethodB1orB1bis.
5.2.2. Percutaneous
CircumstancesinwhichrequiredThe acute percutaneous toxicity of the active substance must always
bereported.1991L0414—EN—01.01.2002—004.001—43
(1) OJNoL133,30.5.1988,p.1.
(2) OJNoL383A,29.12.1992,p.1.
▼M4
Testguideline
Bothlocalandsystemiceffectsmustbeinvestigated.Thetestmustbe
carriedoutinaccordancewithDirective92/69/EECmethodB3.
5.2.3. Inhalation
Circumstancesinwhichrequired
Theinhalationtoxicityoftheactivesubstancemustbereportedwhere
theactivesubstanceis:
— agasorliquifiedgas,
— istobeusedasafumigant,
— is to be included in a smoke generating, aerosol or vapour
releasingpreparation,
— istobeusedwithfoggingequipment,
— hasavapourpressure>1×10&minus;2Paandistobeincludedin
preparationstobeusedinenclosedspacessuchaswarehousesor
glasshouses,
— is to be included in preparations which are powderscontaining a
significant proportion of particles of diameter ►C3< 50µm ◄
(>1%onaweightbasis),or
— istobeincludedinpreparationstobeappliedinamannerwhich
generates a significant proportion of particles or droplets of
diameter<50µm(>1%onaweightbasis).
TestguidelineThetestmustbecarriedoutinaccordancewithDirective92/69/EEC
MethodB2.
5.2.4. Skin irritation
Aimofthetest
The test will provide the potential of skin irritancy of the active
substanceincludingthepotentialreversibilityoftheeffectsobserved.
Circumstancesinwhichrequired
Theskinirritancyoftheactivesubstancemustbedeterminedexcept
where it is likely, as indicated in the test guideline, that severe skin
effectsmaybeproducedorthateffectscanbeexcluded.
Testguideline
The acute skin irritation must be carried out in accordance with
Directive92/69/EECMethodB4.
5.2.5. Eye irritation
Aimoftest
The test will provide the potential of eye irritancy of the active
substanceincludingthepotentialreversibilityoftheeffectsobserved.
Circumstancesinwhichrequired
Eye irritation tests must be conducted except where it is likely, as
indicatedinthetestguideline,thatsevereeffectsontheeyesmaybe
produced.
Testguidelines
TheacuteeyeirritationmustbedeterminedinaccordancewithDirec-
tive92/69/EECMethodB5.
5.2.6. Skin sensitization
Aimoftest
Thetest will providesufficient information toassessthepotential of
theactivesubstancetoprovokeskinsensitizationreactions.
Circumstancesinwhichrequired
The test must always be carried out except where the substance is a
knownsensitizer.1991L0414—EN—01.01.2002—004.001—44
▼M4
Testguideline
ThetestmustbecarriedoutinaccordancewithDirective92/69/EEC
MethodB6.
5.3.Short-termtoxicity
Short-term toxicity studies must be designed to provide information
astotheamountoftheactivesubstancethatcanbetoleratedwithout
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-termstudies
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-termstudiesprovide inform ation useful in
thedesignofchronictoxicitystudies.
Thestudies,dataandinformationtobeprovidedandevaluated,must
besufficienttopermittheidentificationofeffectsfollowingrepeated
exposuretotheactivesubstance,andinparticulartofurtherestablish,
orindicate:
— therelationshipbetweendoseandadverseeffects,
— toxicity of the active substance including where possible the
Noael,
— targetorgans,whererelevant,— thetimecourseandcharacteristicsofpoisoningwithfulldetailsof
behavioural changes and possible pathological findings at post-
mortem,
— specifictoxiceffectsandpathologicalchangesproduced,
— where relevant the persistence and reversibility of certain toxic
effectsobserved,followingdiscontinuationofdosing,
— wherepossible,themodeoftoxicaction,and— the relative hazard associated with the different routes of expo-
sure.
5.3.1. Oral 28-day study
Circumstancesinwhichrequired
Although it is not mandatory to perform 28-day short term studies,
they can be useful as range finding tests. Where conducted they
mustbereported,sincetheresultscouldbeofparticularvalueinthe
identification of adaptive responses which can be masked in chronic
toxicitystudies.
Testguideline
ThetestmustbecarriedoutinaccordancewithDirective92/69/EEC
MethodB7.
5.3.2. Oral 90-day study
Circumstancesinwhichrequired
The short-termoral toxicity (90 day) of the active substance to both
rat and dog, must always be reported. Where there is evidence that
thedogissignificantlymoresensitiveandwheresuchdataarelikely
to be of value in extrapolating results obtained to man, a 12-month
toxicitystudyindogsmustbeconductedandreported.
Testguidelines
Directive87/302/EEC,PartB,sub-chronicoraltoxicitytest.
5.3.3. Other routes
Circumstancesinwhichrequired
For the assessment of operator exposure additional percutaneous
studiesmaybeuseful.
For volatile substances (vapour pressure >10
−2Pascal) expert judg-
ment isrequired to decide whether the shortterm studieshave to be
performedbyoralorinhalationexposure.
Testguidelines— 28-daydermal:Directive92/69/EECMethodB9,1991L0414—EN—01.01.2002—004.001—45
▼M4
— 90-daydermal:Directive87/302/EEC,PartB,sub-chronicdermal
toxicitystudy,
— 28-dayinhalation:Directive92/69/EECMethodB8,
— 90-day inhalation: Directive 87/302/EEC, Part B, sub-chronic
inhalationtoxicitystudy.
5.4.Genotoxicitytesting
Aimofthetest
Thesestudiesareofvaluein:
— thepredictionofgenotoxicpotential
— theearlyidentificationofgenotoxiccarcinogens
— theelucidationofthemechanismofactionofsomecarcinogens
To avoid responses that are artifacts of the test system, excessively
toxic doses must not be used in either in vitroorin vivoassays for
mutagenicity. Thisapproachshouldberegarded asgeneralguidance.
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
CircumstancesinwhichrequiredIn vitromutagenicitytests(bacterialassayforgenemutation,testfor
clastogenicity in mammalian cells and test for gene mutation in
mammaliancells)mustalwaysbeperformed.
TestguidelinesAcceptabletestguidelinesare:Directive 92/69/EEC Method B14 — Salmonella Typhimurium
reversemutationassay
Directive92/69/EECMethodB10— in vitromammaliancytogenetic
test
Directive87/302/EEC,PartB— in vitromammaliancellgenemuta-
tiontest
5.4.2. In vivo studies in somatic cells
CircumstancesinwhichrequiredIf all the results of the in vitrostudies are negative further resting
must be done with consideration of other relevant information avail-
able (including toxicokinetic, toxicodynamic and physico-chemical
data and data on analogous substances). The test can be an in vivo
studyoran in vitrostudyusingadifferentmetabolizingsystemfrom
that/thosepreviouslyused.
Ifthein vitrocytogenetictestispositive,an in vivotestusingsomatic
cells(metaphaseanalysisinrodentbonemarrowormicronucleustest
inrodents)mustbeconducted.
Ifeitherofthe in vitrogenemutationtestsarepositive,an in vivotest
to investigate unscheduled DNAsynthesisor a mouse spottest must
beconducted.
TestguidelinesAcceptabletestguidelinesare:Directive92/69/EECMethodB12—Micronucleustest,Directive87/302/EECPartB—Mousespottest,Directive 92/69/EEC Method B11 — In vivoMammalian Bone-
Marrowcytogenetictest,Chromosomalanalysis.
5.4.3. In vivo studies in germ cells
CircumstancesinwhichrequiredWhen any result of an in vivostudy in somatic cells is positive, in
vivotesting for germcell effects m ay 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—01.01.2002—004.001—46
▼M4
andanticipatedexposure.Suitabletestswouldneedtoexamineinter-
action with DNA (such as the dominant lethal assay), to look at the
potentialforinheritedeffectsandpossiblymakeaquantitativeassess-
ment of heritable effects. It is recognized that in view of their
complexity,theuseofquantitativestudieswouldrequirestrongjusti-
fication.
5.5.Longtermtoxicityandcarcinogenicity
Aimofthetest
The long-termstudies 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
exposuretothe active substance,andinparticular mustbesufficient
to:
— identify adverse effects resulting fromexposure to the active
substance,
— identifytargetorgans,whererelevant,
— establishthedose-responserelationship,
— identifychangesintoxicsignsandmanifestationsobserved,and— establishtheNoael.
Similarly, the carcinogenicity studies taken together with other rele-
vantdataandinformationontheactivesubstance,mustbesufficient
topermitthehazardsforhumans,followingrepeatedexposuretothe
activesubstance,tobeassessed,andinparticularmustbesufficient:
— to identify carcinogenic effects resulting fromexposure to the
activesubstance,
— toestablishthespeciesandorganspecificityoftumoursinduced,
— toestablishthedose-responserelationship,and
— for non-genotoxic carcinogens, to identify the maximum dose
elicitingnoadverseeffect(thresholddose).
Circumstancesinwhichrequired
The long-termtoxicity and carcinogenicity of all active substances
must be determined. If in exceptional circumstances, it is claimed
that such testing is unnecessary, that claimm ust be fully justified,
viz.toxicokinetic data demonstrates that absorption of the active
substance does not occur fromthe gut, through the skin or via the
pulmonarysystem.
Testconditions
Along-termoraltoxicityandcarcinogenicitystudy(twoyears)ofthe
activesubstancemustbeconductedusingtheratastestspecies;these
studiescanbecombined.
A carcinogenicity study of the active substance must be conducted
usingthemouseastestspecies.
Whereanon-genotoxicmechanismforcarcinogenicityissuggested,a
well argued case, supported with relevant experimental data,
including that necessary to elucidate the possible mechanism
involved,mustbeprovided.
While the standard reference points for treatment responses are
concurrentcontroldata,historicalcontroldata,maybehelpfulinthe
interpretation of particular carcinogenicity studies. Where submitted,
historical control data should be fromthe sam e species and strain,
maintainedundersimilarconditionsandshouldbefromcontempora-
neous studies. The information on historical control data provided
mustinclude:
— identification of species and strain, name of the supplier, and
specific colony identification, if the supplier has more than one
geographicallocation,
— 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,theamountconsumed,
— approximate age,indays,ofthecontrolanimalsatthebeginning
ofthestudyandatthetimeofkillingordeath,1991L0414—EN—01.01.2002—004.001—47
▼M4
— descriptionofthecontrolgroupmortalitypatternobservedduring
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 fromthe
study,and
— a statement of the nature of the tumours that may have been
combinedtoproduceanyoftheincidencedata.
The doses tested, including the highest dosetested, must be selected
onthebasisoftheresultsofshort-termtestingandwhereavailableat
the time of planning the studies concerned, on the basis of metabo-
lismand 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-termtoxicity 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
consideredrelevanttoevaluationstobemade.
In the collection of data and compilation of reports, incidence of
benignandmalignanttumoursmustnotbecombined,unlessthereis
clear evidence of benign tumours becoming malignant with time.
Similarly,dissimilar,un-associatedtumours,whetherbenignormalig-
nant, occurring in the same organ, must not be combined, for
reportingpurposes.Intheinterestsofavoidingconfusion,terminology
suchasthatdeveloped byAmerican SocietyofToxicologic Patholo-
gists(1),ortheHannoverTumourRegistry(RENI)shouldbeusedin
thenomenclatureandreportingoftumours.Thesystemusedmustbe
identified.
It is essential that biological material selected for histopathological
examination includesmaterial selectedtoprovidefurtherinformation
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.
Testguideline
ThestudiesmustbecarriedoutinaccordancewithDirective87/302/
EEC, part B, Chronic toxicity test, Carcinogenicity test or combined
chronictoxicity/carcinogenicity test.
5.6.Reproductivetoxicity
Adversereproductiveeffectsareoftwomaintypes:
— impairmentofmaleorfemalefertility,and
— impacts on the normal development of progeny (developmental
toxicity).
Possible effects on all aspects of reproductive physiology in both
males andfemales, as wellaspossibleeffects onpre-natal andpost-
natal development, must be investigated and reported. If in excep-
tional circumstances, it is claimed that such testing is unnecessary,
thatclaimmustbefullyjustified.
Whilethestandardreferencepointfortreatmentresponsesareconcur-
rent control data, historical control data may be helpful in the
interpretation of particular reproductive studies. Where submitted,
historical control data should be fromthe sam e species and strain,
maintainedundersimilarconditionsandshouldbefromcontempora-
neous studies. The information on historical control data provided
mustinclude:
— identification of species and strain, name of the supplier, and
specific colony identification, if the supplier has more than one
geographicallocation,
— name of the laboratory and the dates when the study was
performed,1991L0414—EN—01.01.2002—004.001—48
(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,theamountconsumed,
— approximate age,indays,ofthecontrolanimalsatthebeginning
ofthestudyandatthetimeofkillingordeath,
— descriptionofthecontrolgroupmortalitypatternobservedduring
or at the end of the study, and other pertinent observations (e.g.
diseases,infections),and
— nameofthelaboratoryandtheexaminingscientistresponsiblefor
gatheringandinterpretingthetoxicologicaldatafromthestudy.
5.6.1. Multi-generation studies
Aimofthetest
The studies reported, taken together with other relevant data and
information on the active substance, mustbe sufficient to permit the
identificationofeffectsforreproduction,followingrepeatedexposure
totheactivesubstance,andinparticularmustbesufficient:
— to identify direct and indirect effects on reproduction resulting
fromexposuretotheactivesubstance,
— toidentifyanyenhancementofgeneraltoxiceffects(notedduring
short-termandchronictoxicitytesting),
— to establish the dose-response relationship, to identify changes in
toxicsignsandmanifestationsobserved,and
— toestablishtheNoael.
CircumstancesinwhichrequiredA reproduction toxicity study in rats over at least two generations
mustalwaysbereported.
Testguideline
The tests must be carried out in accordance with Directive 87/302/
EEC, Part B, two-generation reproduction toxicity test. In addition
organweightofreproductiveorgansmustbereported.
SupplementarystudiesWherenecessaryforabetterinterpretationoftheeffectsonreproduc-
tion and as far as this information is not yet available it could be
necessary to performsupplem entary studies in order to provide the
followinginformation:
— separatemaleandfemalestudies,
— threesegmentdesigns,
— dominantlethalassayformalefertility,— cross-matings of treated males with untreated females and vice
versa,
— effectsonspermatogenesis,
— effectsonoogenesis,
— spermmotility,mobilityandmorphology,and— investigationofhormonalactivity.
5.6.2. Developmental toxicity studies
Aimofthetest
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
mustbesufficient:
— to identify direct and indirect effects on embryonic and foetal
developmentresultingfromexposuretotheactivesubstance,
— toidentifyanymaternaltoxicity,— toestablishtherelationshipbetweenobservedresponsesanddose
inbothdamandoffspring,
— to identify changes in toxic signs and manifestations observed,
and
— toestablishtheNoael.
Furthermore, the tests will give additional information on any
enhancementofgeneraltoxiceffectsofpregnantanimals.1991L0414—EN—01.01.2002—004.001—49
▼M4
Circumstancesinwhichrequired
Thetestsmustalwaysbecarriedout.TestconditionsDevelopmental toxicitymustbedeterminedbothtoratandrabbitby
theoralroute.Malformationsandvariationsshouldbereportedsepa-
rately. A glossary of terminology and diagnostic principles for
malformationsandvariationsmustbegiveninthereport.
TestguidelineThe tests must be carried out in accordance with Directive 87/302/
EEC,PartB,teratogenicitytest—rodentandnon-rodent.
5.7.Delayedneurotoxicitystudies
Aimofthetest
The test shall provide sufficient data to evaluate if the active
substancecouldprovokedelayedneurotoxicityafteracuteexposure.
Circumstancesinwhichrequired
These studies have to be performed for substances of similar or
related structures to those capable of inducing delayed neurotoxicity
suchasorganophosphates.
Testguidelines
ThetestmustbecarriedoutinaccordancewithOECDGuideline418.
5.8.Othertoxicological studies
5.8.1. Toxicity studies of metabolites as referred to in the introduction point
(vii)
Supplementarystudies,wheretheyrelatetosubstancesotherthanthe
activesubstance,arenotaroutinerequirement.
Decisionsastotheneedforsupplementarystudiesmustbemadeona
casebycasebasis.
5.8.2. Supplementary studies on the active substance
Incertaincasesitcanbenecessarytocarryoutsupplementarystudies
tofurtherclarifyobservedeffects.Thesestudiescouldinclude:
— studiesonabsorption,distribution,excretionandmetabolism,
— studiesontheneurotoxicpotential,— studiesontheimmunotoxicologicalpotential,— studiesonotherroutesofadministration.
Decisionsastotheneedforsupplementarystudiesmustbemadeona
case by case basis, taking into account the results of the available
toxicologicalandmetabolismstudiesandthemostimportantexposure
routes.
Studiesrequiredmustbedesignedonanindividualbasis,inthelight
oftheparticularparameterstobeinvestigatedandtheobjectivestobe
achieved.
5.9.Medicaldata
Whereavailable,andwithoutprejudicetotheprovisionsofArticle5
of Council Directive 80/1107/EEC of 27 November 1980 on the
protection of workers fromthe risks related to chem ical, physical
andbiologicalagentsatwork(
1),practical dataandinformationrele-
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
topoisoning,shouldbeinvestigatedandreported.1991L0414—EN—01.01.2002—004.001—50
(1) OJNoL327,3.12.1980,p.8.
▼M4
Data and information relevant to the effects of human exposure,
whereavailable and ofthe 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
followingaccidentaloroccupationalexposure.
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-
suretotheactivesubstanceandexposuretootherchemicals,mustbe
submitted. Such reports should, where feasible, include data relevant
to the mechanism of action of the active substance. These reports
shall,whereavailable,includedatafrompersonsexposedinmanufac-
turing plants or after application of the active substance (e.g.: in
efficacytrials).
Available information on the sensitization including allergenic
responseofworkersandothersexposedtotheactivesubstance,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
otherrelevantclinicalinformation.
5.9.2. Direct observation, e.g.: clinical cases and poisoning incidents
Available reports fromthe open literature, relating to clinical cases
andpoisoningincidents,wheretheyarefromrefereedjournalsoroffi-
cialreports,mustbesubmittedtogetherwithreportsofanyfollow-up
studiesundertaken.Suchreportsshouldcontaincompletedescriptions
of the nature, level and duration of exposure, as well as the clinical
symptoms observed, first aid and therapeutic measures applied and
measurementsandobservationsmade.Summaryandabstractinforma-
tionisnotofvalue.
Wheresupportedwiththenecessarylevel ofdetail, suchdocumenta-
tion can be of particular value in confirming the validity of
extrapolationsfromanimaldatatomanandinidentifyingunexpected
adverseeffectswhicharespecifictohumans.
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,andconductedinaccordance withrecognized standards(1),
epidemiologicalstudiesareofparticularvalueandmustbesubmitted.
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,includingtheearlysignsandsymptomsandfulldetailsof
clinicaltestsusefulfordiagnosticpurposes,whereavailable,mustbe
providedandincludefulldetailsofthetimecoursesinvolvedrelevant
totheingestion,dermalexposureorinhalationofvaryingamountsof
theactivesubstance.
5.9.5. Proposed treatment: first aid measures, antidotes, medical treatment
Thefirstaidmeasurestobeusedintheeventofpoisoning(actualand
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 useof antidotes, must be
describedinfull.Informationbasedonpractical experience, whereit
existsandisavailable,inothercasesontheoreticalgrounds,astothe
effectiveness of alternative treatment regimes, where relevant, must
be provided. Contraindications associated with particular regimes,
particularly those relating to ‘general medical problems’ and condi-
tions,mustbedescribed.1991L0414—EN—01.01.2002—004.001—51
(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
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5.9.6. Expected effects of poisoning
Where known, the expected effects and the duration of these effects
followingpoisoningmustbedescribedandincludetheimpactof:
— thetype,levelanddurationofexposure,oringestion,and
— varying time periods between exposure, or ingestion, and
commencementoftreatment.
5.10.Summaryofmammaliantoxicity andoverallevaluation
Asummaryofalldataandinformationprovidedunderparagraphs5.1
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, with particular reference to
the risks for man and animals that may or do arise, and the extent,
qualityandreliabilityofthedatabase.
Whererelevant,inthelightoffindingswithrespecttotheanalytical
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
theactivesubstanceasmanufactured,mustbeargued.
Onthebasisofanassessmentofthedatabase,andtherelevantdeci-
sion making criteria and guidelines, justifications must be submitted
fortheNoaelsproposedforeachrelevantstudy.
On the basis of these data scientifically reasoned proposals for the
establishment of ADIand AOEL(s)for the active substance must be
submitted.
6. Residuesinorontreatedproducts,foodandfeed
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
infood.Inaddition,theinformationprovidedmustbesufficient
to:
— permitadecisiontobemadeastowhether,ornot,theactive
substancecanbeincludedinAnnexI,
— specifyappropriateconditionsorrestrictionstobeassociated
withanyinclusioninAnnexI.
(ii) A detailed description (specification) of the material used, as
providedunderSection1,point11mustbeprovided.
(iii) Studiesshouldbeperformedaccordingtotheguidanceavailable
on regulatory testing procedures for residues of plant protection
productsinfood(1).
(iv) Whererelevant,datashouldbeanalyzedusingappropriatestatis-
tical methods. Full details of the statistical analysis should be
reported.
(v) Stabilityofresiduesduringstorage.
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).
Studieswithnon-radio-labelled substancesshouldbecarriedout
with representative substratets and preferably on samples from
treated cropsoranimals withincurred residues.Alternatively, if
this is not possible, aliquots of prepared control samples should
bespikedwithaknownamountofchemicalbeforestorageunder
normalstorageconditions.
Where the degradation during storage is significant (more than
30 %) it may be necessary to change the storage conditions or1991L0414—EN—01.01.2002—004.001—52
(1) Guidanceunderdevelopment.▼M9
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nottostorethesamplesprior toanalysisand repeat andstudies
wheretheunsatisfactorystorageconditionswereused.
Detailed information withrespect to the sample preparation and
storage conditions (temperature and duration) of samples and
extracts must be submitted. Storage stability data using sample
extractswillalsoberequiredunlesssamplesareanalysedwithin
24hoursofextraction.
6.1.Metabolism,distributionandexpressionofresidueinplants
Aim of the tests
Theobjectivesofthesestudiesare:
— to provide an estimate of total terminal residues in the relevant
portionofcropsatharvestfollowingtreatmentasproposed,
— toidentifythemajorcomponentsofthetotalterminalresidue,— to indicate the distribution of residues between relevant crops
parts,
— to quantify the major components of the residue and to establish
theefficiencyofextractionproceduresforthesecomponents,
— todecideonthedefinitionandexpressionofaresidue.
Circumstances in which required
Thesestudiesmustalwaysbeperformedunlessitcanbejustifiedthat
no residues will remain on plants/plant products which are used as
foodorfeedingstuffs.
Test conditions
Metabolismstudies have to involve crops or categories of crops in
which plant protection products containing the active substance in
questionwouldbeused.Ifawiderangeofusesindifferentcropcate-
goriesorinthecategoryfruitsisenvisaged,studieshavetobecarried
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
fallingintooneoffivecategories:rootvegetables,leafycrops,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
differentmetabolismwilloccur.Themetabolismstudieshavealsoto
take into account the different properties ofthe active substance and
theintendedmethodofapplication.
Anevaluationoftheresultsfromdifferentstudieshastobesubmitted
onthepointandpathofuptake(e.g.vialeavesorroots),andonthe
distribution of residues between relevant parts of the crop at harvest
(with particular emphasis on edible parts for man or animals). If the
activesubstanceorrelevantmetabolitesarenottakenupbythecrop,
this must be explained. Information on the mode of action and the
physico-chemical properties of the active substance may be helpful
inassessingtrialdata.
6.2.Metabolism,distributionandexpressionofresidueinlivestock
Aim of tests
Theobjectivesofthesestudiesare:
— to identify the major components of the total terminal residue in
edibleanimalproducts,
— to quantify the rate of degradation and excretion of the total
residueincertainanimalproducts(milkoreggs)andexcreta,
— to indicate the distribution of residues between relevant edible
animalproducts,
— toquantify the major componentsoftheresidueandtoshowthe
efficiencyofextractionproceduresforthesecomponents,
— to generate data fromwhich a decision on the need for livestock
feedingstudiesasprovidedforinpoint6.4canbemade,
— todecideonthedefinitionandexpressionofaresidue.1991L0414—EN—01.01.2002—004.001—53
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Circumstances in which required
Metabolismstudiesonanimals,suchaslactatingruminants(e.g.goat
or cow)or laying poultry, are onlyrequired whenpesticide usemay
leadtosignificantresiduesinlivestockfeed( ≥0,1mg/kgofthetotal
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
Theobjectivesofthesestudiesare:
— to quantify the highest likely residue levels in treated crops at
harvest or outloading fromstore following the propopsed good
agriculturalpractice(GAP),
and
— todetermine,whenappropriate,therateofdeclineofplantprotec-
tionproductdeposits.
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 fromsoil or other substrates
can be taken up by such plants except where extrapolation from
adequatedataonanothercropispossible.
ResiduetrialdatashallbesubmittedintheAnnexIIdossierforthose
usesofplantprotectionproductsforwhichauthorization issoughtat
the moment of introduction of a dossier for inclusion of the active
substanceinAnnexI.
Test conditions
SupervisedtrialsshouldcorrspondtoproposedcriticalGAP.Thetest
conditions must take into account the highest residues which may
reasonably arise (e.g. maximum number of proposed applications,
useofthemaximumenvisagedquantity,shortestpre-harvestintervals,
withholdingperiodsorstorageperiods)butwhichremainrepresenta-
tive of the realistic worst case conditions in which the active
substancewouldbeused.
Sufficient data must be generated and submitted to confirm that
patternsdetermined holdfortheregionsandtherangeofconditions,
likelytobeencounteredintheregionsconcernedforwhichitsuseis
toberecommended.
When establishing a supervised trial programme, normally factors
suchasclimaticdifferencesexistingbetweenproductionareas,differ-
ences in production methods (e.g. outdoor versus glasshouse uses),
seasonsofproduction,typeofformulations,etc.shouldbetakeninto
account.
Ingeneral,foracomparablesetofconditions,trialsshouldbecarried
out over a minimum of two growing seasons. All exceptions should
befullyjustified.
The precise number of trials necessary is difficult to determine in
advance of a preliminary evaluation of the trial results. Minimum
datarequirements onlyapplywherecomparability canbeestablished
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
growingareaarerequired.
Duetotheinherentlyhigherlevelofhomogeneityinresiduesarising
frompost-harvest treatm ents or protected crops, trials fromone
growing season will be acceptable. For post-harvest treatments, in
principleaminimumoffourtrialsarerequired,carriedoutpreferably
atdifferentlocationswithdifferentcultivars.Asetoftrialshastobe
carried out for each application method and store type unless the
worstcaseresiduesituationcanbeclearlyidentified.1991L0414—EN—01.01.2002—004.001—54
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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
productswillbelowerthanthelimitofdetermination.
Whereasignificantpartoftheconsumablecropispresentatthetime
of application, half of the supervised residue trials reported should
includedatatoshowtheeffectoftimeonthelevelofresiduepresent
(residuedeclinestudies)unlessitcanbejustifiedthattheconsumable
cropisnotaffectedbytheapplicationoftheplantprotectionproduct
undertheproposedconditionsofuse.
6.4.Livestockfeedingstudies
Aim of the tests
Theobjectiveofthesestudiesistodeterminetheresidueinproducts
of animal origin which will result from residues in feedingstuffs or
foddercrops.
Circumstances in which required
Feedingstudiesareonlyrequired:
— when significant residues ( ≥0,1 mg/kg of the total diet as
received, except special cases, such as active substances which
accumulate) occur in crops or part of the crop (e.g. trimmings,
waste)fedtoanimals,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
obtainedatthe1×doserate.
Whereappropriateseparatefeedingstudiesforlactatingruminantand/
or laying poultry should be submitted. Where it appears from the
metabolism studies submitted in accordance with the provisions of
point 6.2 that metabolic pathways differ significantly in the pig as
comparedtoruminants,apigfeedingstudymustbeconductedunless
theexpectedintakebypigsisnotsignificant.
Test conditions
Ingeneral,thefeedisadministeredinthreedosages(expectedresidue
level, three to five times, and 10 times the expected residue level).
Whensettingthe1×dose,atheoreticalfeedrationmustbecompiled.
6.5.Effectsofindustrialprocessingand/orhouseholdpreparations
Circumstances in which required
The decision as to whether it is necessary to carry out processing
studieswilldependon:
— the importance of a processed product in the human or animal
diet,
— thelevelofresidueintheplantorplantproducttobeprocessed,— thephysico-chemicalpropertiesoftheactivesubstanceorrelevant
metabolites,and
— the possibility that degradation products of toxicological signifi-
cancemaybefoundafterprocessingoftheplantorplantproduct.
Processingstudies are not normally necessary if no significant or no
analytically determinable residuesoccurintheplantorplantproduct
whichwouldbe processed,or ifthe total theoretical maximum daily
intake (TMDI)islessthan 10%ofthe ADI.Inaddition, 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/pulpmayberequired.
‘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
determinableresiduesbelow0,1mg/kg.
Studies on the effects on the nature of the residue are not normally
required where only simple physical operations, not involving a1991L0414—EN—01.01.2002—004.001—55
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changeintemperature oftheplantortheplantproduct,areinvolved
suchaswashing,trimmingorpressing.
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 fromresidues in the raw products
duringprocessingwhichmayrequireaseparateriskassessment.
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,
whereappropriate. The effects of processother 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 with a radio-labelled form of the
activesubstance.
6.5.2. Effects on the residue levels
Aim of the testsThemainobjectivesofthesestudiesare:
— todeterminethequantitativedistributionofresiduesinthevarious
intermediateandendproducts,andtoestimatetransferfactors,
— toenableamorerealisticestimatetobemadeofdietaryintakeof
residues.
Test conditionsProcessing studies should represent household processing and/or
actualindustrialprocesses.
Inthefirstinstanceitisusuallyonlynecessarytocarryoutacoreset
of ‘balance studies’ representative of the common processesrelevant
totheplantsorplantproductscontainingsignificantresidues.Justifi-
cationshouldbegivenfortheselection madeoftheserepresentative
process(es). The technology to be used in processing studies should
alwayscorrespondascloselyaspossibletotheactualconditionsthat
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 such a balance sheet any
concentrationsorreductionsinresiduesinindividualproductscanbe
recognized and the corresponding transfer factors can also be deter-
mined.
Iftheprocessedplantproductsplayanimportantpartinthediet,and
if the ‘balance study’ indicates that a significant transfer of residue
intotheprocessedproductscouldoccur,thenthree‘follow-upstudies’
todetermineresidueconcentrationordilutionfactorsmustbecarried
out.
6.6.Residuesinsucceedingcrops
Aim of the test
The objective of these studies is to permit an evaluation of possible
residuesinsucceedingcrops.
Circumstances in which required
Where data generated in accordance with Annex II, Section 7, point
7.1orAnnexIII,Section9,point9.1,showsthatsignificantresidues
(>10%oftheappliedactivesubstanceasatotalofunchangedactive
substanceanditsrelevantmetabolitesordegradationproducts)remain
in soil or in plant materials, such as straw or organic material up to
sowing or planting time of possible succeeding crops, and which
couldleadtoresiduesabovethelimitofdeterminationinsucceeding
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
studiesshouldbecarriedout,ifnecessaryfollowedbyfieldtrials.1991L0414—EN—01.01.2002—004.001—56
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Test conditions
Ifatheoreticalestimationofresiduesinsucceedingcropsisdone,full
detailsandajustificationshallbebegiven.
Metabolismanddistributionstudiesandfieldtrials,ifnecessary,shall
be carried out on representative crops chosen to represent normal
agriculturalpractice.
6.7.Proposedmaximumresiduelevels(MRLs)andresiduedefiniton
A full justification for the propsoed MRLs must be provided,
including,whererelevant,fulldetailsofthestatisticalanalysisused.
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
monitoringpurposes.
6.8.Proposedpre-harvest intervals for envisaged uses,or withholding
periodsorstorageperiods,inthecaseofpost-harvestuses
Afulljustificationfortheproposalsmustbeprovided.
6.9.Estimation of the potential and actual exposure through diet and
othermeans
Considerationwillbegiventothecalculationofarealisticprediction
ofdietaryintake.Thismaybedoneinastep-wisefashionleadingto
an increasingly realistic predictions of intake. Where relevant, other
sources of exposure such as residues arising fromthe use of m edi-
cinesorveterinarydrugshavetobetakenintoacocunt.
6.10.Summaryandevaluationofresiduebehaviour
AsummaryandevaluationofalldatapresentedinthisSectionshould
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, with particular reference to
the risks for man and animals that may or do arise, and the extent,
qualityandreliablityofthedatabase.
In particular, the toxicological significance of any non-mammalian
metabolitesmustbeaddressed.
Aschematicdiagramshouldbepreparedofthemetabolicpathwayin
plants and animals with a brief explanation of the distribution and
chemicalchangesinvolved.
7.Fateandbehaviourintheenvironment
Introduction
(i) The information provided, taken together with that for one or
morepreparationscontainingtheactivesubstance,mustbesuffi-
cient to pemit an assessment of the fate and behaviour of the
active substance in the environment, and of the non-target
specieslikelytobeatriskfromexposuretotheactivesubstance,
its metabolites, degradation and reaction products, where they
areoftoxicologicalorenvironmentalsignificance.
(ii) In particular, the information provided for the active substance,
together with other relevant information, and that provided for
oneormorepreparationscontainingit,shouldbesufficientto:
— decide whether, ornot,the active substance can beincluded
inAnnexI,
— specifyappropriateconditionsorrestrictionstobeassociated
withanyinclusioninAnnexI,
— classifytheactivesubstanceastohazard;
— 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—01.01.2002—004.001—57
▼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
coursesinvolved,
— identifynon-targetspeciesandpopulationsforwhichhazards
arisebecauseofpotentialexposure,and
— identifymeasuresnecesarytominimizecontaminationofthe
environmentandimpactonnon-targetspecies.
(iii) A detailed description (specification) of the material used, as
providedforunderSection1,point11mustbeprovided.Where
testingisdoneusingactivesubstancethematerialusedshouldbe
of that specification that will be used in the manufacture of
preparations to be authorized except where radio-labelled mate-
rialisused.
Wherestudiesareconductedusingactivesubstanceproducedin
the laboratory or in a pilot plant production system, the studies
mustberepeatedusingactivesubstanceasmanufactured,unless
it can be justified that the test material used is essentially the
sameforthepurposesofenvironmentaltestingandassessment.
(iv) Whereradio-labelledtestmaterialisused,radio-labelsshouldbe
positionedatsites(oneormoreasnecessary),tofacilitateeluci-
dation of metabolic and degradative pathways and to facilitate
investigation of the distribution of the active substance and of
itsmetabolite, reaction anddegradation productsintheenviron-
ment.
(v) Itmay be necessary to conduct separate studies formetabolites,
degradation or reaction products, where these products can
constitutearelevantrisktonon-targetorganismsortothequality
ofwater,soilandairandwheretheireffectscannotbeevaluated
by the available results relating to the active substance. Before
such studies are performed the information from the Sections 5
and6hastobetakenintoaccount.
(vi) Whererelevant,testsshouldbedesignedanddataanalysedusing
appropriatestatisticalmethods.
Fulldetailsofthestatistical anaylsisshouldbereported(e.g.all
point estimates should begiven withconfidence 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
otherinternationalstandards.
Themicrobialbiomassofsoilsusedforlaboratorydegradationstudies
mustbedeterminedjustpriortothecommencementandattheendof
thestudy.
It is recommended to use as much as possible the same soils
throughoutalllaboratorysoilstudies.
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
besuchthat:
— they cover arange oforganic carbon content, particle size distri-
butionandpHvalues;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:
— 4,5to5,5
— 6to7,and
— 8(approximately).
Soils used must, wherever possible, be freshly sampled. If use of
storedsoilsisunavoidable,storageshouldbeproperlycarriedoutfor
alimitedtimeunderdefinedandreportedconditions.Soilsstoredfor
longer periods of time can only be used for adsorption/desorption
studies.1991L0414—EN—01.01.2002—004.001—58
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Thesoilchosentobeginstudyingshouldnothaveextremecharacter-
istics with respect to parameters such as particle size distribution,
organiccarboncontentandpH.
SoilsshouldbecollectedandhandledinaccordancewithISO10381-
6(Soil quality — Sampling — Guidance on the collection, handling
and storage of soil for the assessment of microbial processes in the
laboratory).Anydeviationsmustbereportedandjustified.
Field studies should be carried out in conditions as close to normal
agriculturalpractice aspossibleonarangeofsoiltypesandclimatic
conditions representative of the area(s) of use. Weather conditions
shallbereportedincaseswherefieldstudiesareconducted.
7.1.1. Route and rate of degradation
7.1.1.1. Routeofdegradation
Aimofthetests
The data and information provided, together withother relevant data
andinformation,shouldbesufficientto:
— identify, where feasable, the relative importance of the types of
processinvolved(balancebetweenchemicalandbiologicaldegra-
dation),
— identify the individual components present which at any time
account for more than 10 % of the amount of active substance
added,including,wherefeasible,non-extractableresidues,
— identifywherepossiblealsoindividualcomponentspresentwhich
account for less than 10 % of the amount of active substance
added,
— establishtherelativeproportionsofthecomponentspresent(mass
balance),and
— permitthesoilresidueofconcernandtowhichnon-targetspecies
areormaybeexposed,tobedefined.
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. Aerobicdegradation
Circumstancesinwhichrequired
Thedegradationpathwayorpathwaysmustalwaysbereportedexcept
where the nature and manner of use of preparations containing the
active substance, preclude soil contamination such as uses on stored
productsorwoundhealingtreatmentsfortrees.
Testconditions
Thedegradationpathwayorpathwaysmustbereportedforonesoil.Resultsobtainedmustbepresentedintheformofschematicdrawings
showing the pathways involved, and in the formof balance sheets
which show the distribution of radio-label as a function of time, as
between:
— activesubstance,
—C O
2,
— volatilecompoundsotherthanCO2,
— individualidentifiedtransformationproducts,— extractablesubstancesnotidentified,and— non-extractableresiduesinsoil.
The investigation of degradation pathways must include all feasible
steps to characterise and quantify non-extractable residues formed
after100dayswhenexceeding70%oftheapplieddoseoftheactive
substance. The techniques and methodologies applied are best
selected on a case-by-case basis. A justification must be provided
wherethecompoundsinvolvedarenotcharacterized.
Thedurationofthestudyisnormally120days,exceptwhereaftera
shorterperiodthelevelsofnon-extractableresiduesandCO
2aresuch
thattheycanbeextrapolatedinareliablewayto100days.1991L0414—EN—01.01.2002—004.001—59
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Testguideline
Setac—Proceduresforassessingtheenvironmentalfateandecotoxi-
cityofpesticides(1).
7.1.1.1.2. Supplementarystudies
— Anaerobicdegradation
Circumstancesinwhichrequired
Ananaerobicdegradationstudymustbereportedunlessitcanbe
justified thatexposureoftheplantprotection productscontaining
theactivesubstancetoanaerobicconditionsisunlikelytooccur.
Testconditionsandtestguideline
The same provisions as provided for under the corresponding
paragraphofpoint7.1.1.1.1apply.
— Soilphotolysis
Circumstancesinwhichrequired
Asoilphotolysisstudymustbereportedunlessitcanbejustified
that deposition of the active substance at the soil surface is unli-
kelytooccur.
Testguideline
Setac — Procedures for assessing the Environmental fate and
ecotoxicityofpesticides.
7.1.1.2. Rateofdegradation
7.1.1.2.1. Laboratorystudies
AimofthetestsThesoildegradationstudiesshouldprovidebestpossibleestimatesof
thetimetakenfordegradationof50%and90%(DT
50labandDT90lab),
of the active substance, and of relevant metabolites, degradation and
reactionproductsunderlaboratoryconditions.
— Aerobicdegradation
Circumstancesinwhichrequired
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
asusesonstoredproductsorwoundhealingtreatmentsfortrees.
Testconditions
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.
mustbereported.
In order to investigate the influence of temperature on degrada-
tion,oneadditionalstudyat10ºChastobeperformedononeof
thesoilsusedfortheinvestigationofdegradationat20ºCuntila
validated Community calculation model for the extrapolation of
degradationratesatlowtemperaturesisavailable.
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
morethan10%oftheamountofactive substanceadded,except
where their DT50values were able to be determined from the
resultsofthedegradationstudieswiththeactivesubstance.
Testguideline
Setac — Procedures for assessing the environmental fate and
ecotoxicityofpesticides.
— Anaerobicdegradation
Circumstancesinwhichrequired
Therateofanaerobicdegradationoftheactivesubstancemustbe
reportedwhereananaerobicstudyhastobeperformedaccording
topoint7.1.1.1.2.
Testconditions1991L0414—EN—01.01.2002—004.001—60
(1) Society of Environmental Toxicology and Chemistry (SETAC), 1995. Procedures for
assessingtheenvironmentalfateandecotoxicityofpesticides,ISBN90-5607-002-9.
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Therateofanaerobicdegradationoftheactivesubstancemustbe
carried out in the soil used in the anaerobic study performed
accordingtopoint7.1.1.1.2.
The duration of the study is normally 120 days except if more
than 90 % of the active substance is degraded before that period
expires.
Similarstudiesforonesoilmustbereportedforallrelevantmeto-
bolites,degradationandreactionproductswhichoccurinsoiland
whichatanytimeduringthestudiesaccountformorethan10%
oftheamountofactivesubstanceadded,exceptwheretheirDT50valueswereabletobedeterminedfromtheresultsofthedegrada-tionstudieswiththeactivesubstance.
Testguideline
Setac — Procedures for assessing the environmental fate and
ecotoxicityofpesticides.
7.1.1.2.2. Fieldstudies
— Soildissipationstudies
Aimofthetest
The soil dissipation studies should provide estimates of the time
taken for dissipation of 50% and 90 %(DT
50fand DT90f),ofthe
active substance under field conditions. Where relevant, informa-
tion on relevant metabolites, degradation and reaction products
mustbereported.
CircumstancesinwhichrequiredThe tests have to be conducted in those conditions where DT
50labdetermined at 20 ºC and at a moisture content of the soil related
toapFvalueof2to2,5(suctionpressure)isgreaterthan60days.
Where plant protection products containing the active substance
areintendedtobeusedincoldclimaticconditions,thetestshave
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
(suctionpressure)isgreaterthan90days.
Testconditions
Individualstudiesonarangeofrepresentativesoils(normallyfour
different types) must be continued until > 90 % of the amount
applied have dissipated. The maximum duration of the studies is
24months.
Testguideline
SETAC — Procedures for assessing the environmental fate and
ecotoxicityofpesticides.
— Soilresiduestudies
Aimofthetest
Soil residue studies should provide estimates of the soil residue
levels at harvest or at time of cowing or planting succeeding
crops.
Circumstancesinwhichrequired
SoilresiduestudiesmustbereportedwhereDT50labisgreaterthan
one-third of the period between the application and harvest and
whereabsorptionbythesucceedingcropispossible,exceptwhere
soil residues at sowing or planting of a succeeding crop can be
reliably estimated from the data of the soil dissipation studies or
whereitcanbejustifiedthattheseresiduescannotbephytotoxic
toorleaveunacceptableresiduesinrotationalcrops.
Testconditions
Individual studies must be continued until harvest or time of
sowingorplantingsucceedingcrops,unless>90%oftheamount
appliedhavedissipated.
TestguidelineSETAC — Procedures for assessing the environmental fate and
ecotoxicityofpesticides.
— Soilaccumulationstudies
Aimofthetests
Thetestsshouldprovidesufficientdatatoevaluatethepossibility
ofaccumulationofresiduesoftheactivesubstanceandofrelevant
metabolites,degradationandreactionproducts.
Circumstancesinwhichrequired
Whereonthebasisofsoildissipationstudiesitisestablishedthat
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—01.01.2002—004.001—61
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which a plateau concentration is achieved must be investigated
except where reliable information can be provided by a model
calculationoranotherappropriateassessment.
Testconditions
Long termfield studies m ust be done on two relevant soils and
involvemultipleapplications.
Beforeperformingthesestudiestheapplicantshallseektheagree-
ment of the competent authorities on the type of study to be
performed.
7.1.2. Adsorption and desorption
Aimofthetest
The data and information provided, together withother relevant data
andinformation,shouldbesufficienttoestablishtheabsorptioncoef-
ficient of the active substance and of relevant metabolites,
degradationandreactionproducts.
Circumstancesinwhichrequired
The studies must always be reported except where the nature and
manner of use of preparations containing the active substance,
precludesoilcontaminationsuchasusesonstoredproductsorwound
healingtrees.
Testoconditions
Studiesontheactivesubstancemustbereportedforfoursoiltypes.Similar studies, for at least three soil types, must be reported for all
relevant metabolites, degradation and reaction products whichinsoil
degradation studies account at any time for more than 10 % of the
amountofactivesubstanceadded.
TestguidelineOECDmethod106
7.1.3. Mobility in the soil
7.1.3.1. Columnleachingstudies
Aimofthetest
The test should provide sufficient data to evaluate the mobility and
leaching potential of the active substance and if possible of relevant
metabolities,degradationandreactionproducts.
CircumstancesinwhichrequiredStudiesinfoursoilsmustbecarriedoutwhereintheabsorptionand
desorptionstudiesprovidedforunderpoint7.1.2itisnotpossibleto
obtainreliableabsorptioncoefficientvalues.
Testguideline
SETAC — Procedures for assessing the environmental fate and
ecotoxicityofpesticides.
7.1.3.2. Agedresiduecolumnleaching
AimofthetestThe test should provide sufficient data to estimate the mobility and
leaching potential of relevant metabolites, degradation and reaction
products.
Circumstancesinwhichrequired
Thestudiesmustbeperformedexcept:
— wherethenatureandmannerofuseofpreparationscontainingthe
active substance, preclude soil contamination such as uses on
storedproductsorwoundhealingtreatmentsfortrees,or
— whereaseparatestudyforthemetabolite,degradationorreaction
productinaccordancetopoint7.1.2or7.1.3.1wasperformed.
Testconditions
Theperiod(s)ofageing shouldbedetermined frominspection ofthe
degradationpatternsofactivesubstanceandmetabolitestoensurethat
arelevantspectrumofmetabolitesispresentatthetimeofleaching.1991L0414—EN—01.01.2002—004.001—62
▼M6
Testguideline
SETAC — Procedures for assessing the environmental fate and
ecotoxicityofpesticides.
7.1.3.3. Lysimeterstudiesorfieldleachingstudies
AimofthetestsThetestshouldprovidedataon:
— themobilityinsoil,
— thepotentialforleachingtogroundwater,
— Thepotentialdistributioninsoil.
CircumstancesinwhichrequriedExpert judgement will be necessary to decide whether lysimeter
studies or field leaching studies should be carried out, taking into
account the resultsofdegradation andother mobility studiesandthe
predicted environmental concentrations in groundwater (PEC
GW),
calculated inaccordancewiththeprovisionsofAnnexIII,Section9.
The type and conditions of the study to be conducted should be
discussedwiththecompetentauthorities.
Testconditions
Great care is necessary in design of both experimental installations
andindividualstudies,toensurethatresultsobtainedcanbeusedfor
assessment purposes. Studies should cover the realistic worst case
situation, taking into account the soil type, climatic conditions, the
applicationrateandthefrequencyandperiodofapplication.
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
influencestheleachingprocess.
Precipitation,soilandairtemperatureshavetoberecordedatregular
intervals(atleastonaweeklybase).
—Lysimeterstudies
Testconditions
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
whichauthorizationissought.Whenduringthestudythesoilhas
to be disturbed for agricultural reasons it must not be disturbed
deeperthan25cm.
— Fieldleachingstudies
Testconditions
Information on the groundwater table in the experimental fields
must be submitted. If soil cracking is observed during the study
thismustbefullydescribed.
Greatattentionshouldbegiventothenumberandthelocationof
water collection devices. The placement of these devices in the
soilshouldnotresultinpreferentialflowpaths.
TestguidelineSETAC — Procedures for assessing the environmental fate and
ecotoxicityofpesticides.
7.2.Fateandbehaviourinwaterandair
Aimofthetests
Theinformationanddataprovided,takentogetherwiththatprovided
for one or more preparations containing the active substance, and
otherrelevantinformation,shouldbesufficienttoestablish,orpermit
estimationof:
— persistence in water systems (bottom sediment and water,
includingsuspendedparticles),
— theextenttowhichwater,sedimentorganismsandairareatrisk,
— potentialforcontaminationofsurfacewaterandgroundwater.1991L0414—EN—01.01.2002—004.001—63
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7.2.1. Route and rate of degradation in aquatic systemes (as far as not
covered by point 2.9)
AimofthetestsThe data and information provided, together withother relevant data
andinformation,shouldbesufficientto:
— identifytherelativeimportanceofthetypesofprocessesinvolved
(balancebetweenchemicalandbiologicaldegradation),
— wherepossible,identifytheindividualcomponentspresent,— establish the relative proportions of the components present and
theirdistributionasbetweenwater,includingsuspendedparticles,
andsediment,and
— permittheresidueofconcernandtowhichnon-targetspeciesare
ormaybeexposed,tobedefined.
7.2.1.1. Hydrolyticdegradation
Circumstancesinwhichrequired
Thetestmustalwaysbeperformedforrelevantmetabolites,degrada-
tion and reaction products which account at any time for more than
10%oftheamountofactivesubstanceaddedunlesssufficientinfor-
mation on their degradation is available from the test performed in
accordancewithpoint2.9.1.
TestconditionsandtestguidelineThesameprovisionsasprovidedunderthecorrespondingparagraphs
ofpoint2.9.1apply.
7.2.1.2. Photochemicaldegradation
CircumstancesinwhichrequiredThetestmustalwaysbeperformedforrelevantmetabolites,degrada-
tion and reaction products which account at any time for more than
10%oftheamountofactivesubstanceaddedunlesssufficientinfor-
mation on their degradation is available from the test performed in
accordancewithpoints2.9.2and2.9.3.
TestconditionsandtestguidelineThesameprovisionsasprovidedunderthecorrespondingparagraphs
ofpoints2.9.2and2.9.3apply.
7.2.1.3. Biologicaldegradation7.2.1.3.1. ‘Readybiodegradability’
CircumstancesinwhichrequiredThetestmustalwaysbeperformedunlessitisnotrequiredunderthe
provisionsofAnnexVItoDirective67/548/EECfortheclassification
oftheactivesubstance.
TestguidelineEECmethodC4.
7.2.1.3.2. Water/sedimentstudy
CircumstancesinwhichrequiredThetestmustbereportedunlessitcanbejustifiedthatcontamination
ofsurfacewaterwillnotoccur.
TestguidelineSETAC — Procedures for assessing the environmental fate and
ecotoxicityofpesticides.
7.2.1.4. Degradationinthesaturatedzone
CircumstancesinwhichrequiredTransformationratesinthesaturatedzoneofactivesubstancesandof
relevant metabolites, degradation and reaction products can provide
usefulinformationonthefateofthesesubstancesinthegroundwater.
TestconditionsExpert judgement is required to decide whether this information is
necessary. Before performing these studies the applicant shall seek1991L0414—EN—01.01.2002—004.001—64
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theagreementofthecompetentauthoritiesonthetypeofstudytobe
performed.
7.2.2. Route and rate of degradation in air (as far as not covered by point
2.10)
Guidanceunderdevelopment.
7.3.Definitionoftheresidue
Inthelightofthechemicalcompositionofresiduesoccurringinsoil,
waterorair,resultingfromuse,orproposeduse,ofaplantprotection
product containing the active substance a proposal for the definition
of the residue must be submitted, taking account of both the levels
foundandtheirtoxicologicalandenvironmentalsignificance.
7.4.Monitoringdata
Availablemonitoringdataconcerningfateandbehaviouroftheactive
substanceandrelevantmetabolites,degradationandreactionproducts
mustbereported.
8.Ecotoxicological studies
Introduction
(i) The information provided, taken together with that for one or
morepreparationscontainingtheactivesubstance,mustbesuffi-
cienttopermitanassessmentoftheimpactonnon-targetspecies
(floraandfauna),likelytobeatriskfromexposuretotheactive
substance, its metabolites, degradation and reaction products,
where they are of environmental significance. Impact can result
fromsingle, prolonged or repeated exposure and can be rever-
sibleorirreversible.
(ii) In particular, the information provided for the active substance,
together with other relevant information, and that provided for
oneormorepreparationscontainingit,shouldbesufficientto:
— decide whether, ornot,the active substance can beincluded
inAnnexI,
— specifyappropriateconditionsorrestrictionstobeassociated
withanyinclusioninAnnexI,
— permit an evaluation of short- and long-term risks for non-
target species — populations, communities, and processes
—asappropriate,
— classifytheactivesubstanceastohazard,
— specify the precautions necessary for the protection of non-
targetspecies,and
— specify the hazard symbols, the indications of danger, and
relevant risk and safety phrases for the protection of the
environment,tobementionedonpackaging(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
theseeffects.Allavailablebiologicaldataandinformationwhich
is relevant to the assessment of the ecotoxicological profile of
theactivesubstancemustbereported.
(iv) The information on fate and behaviour in the environment,
generated and submitted in accordance with points 7.1 to 7.4,
andonresiduelevelsinplantsgeneratedandsubmittedinaccor-
dancewithpoint6iscentraltotheassessmentofimpactonnon-
targetspecies,inthattogetherwithinformationonthenatureof
the preparation and its manner of use, it defines the nature and
extentofpotentialexposure.Thetoxicokinetic andtoxicological
studiesandinformation submitted inaccordance withpoints5.1
to 5.8 provide essential information as to toxicity to vertebrate
speciesandthemechanismsinvolved.
(v) Whererelevant,testsshouldbedesignedanddataanalysedusing
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
ratherthanstatingsignificant/nonsignificant).1991L0414—EN—01.01.2002—004.001—65
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Testsubstance
(vi) A detailed description (specification) of the material used, as
providedforunderpoint1.11mustbeprovided.Wheretesting
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-
rialisused.
(vii) Wherestudiesareconductedusingactivesubstanceproducedin
thelaboratoryorinapilotplantproductionsystem,thestudies
must be repeated using active substance as manufactured,
unlessitcanbejustifiedthatthetestmaterialusedisessentially
the same, for the purposes of ecotoxicological testing and
assessment.Incasesofuncertainty,appropriatebridgingstudies
must be submitted to serve as a basis for a decision as to the
possibleneedforrepetitionofthestudies.
(viii) In the case of studies in which dosing extends over a period,
dosingshouldpreferablybedoneusingasinglebatchofactive
substanceifstabilitypermits.
Whenever a study implies the use of different doses, the rela-
tionshipbetweendoseandadverseeffectmustbereported.
(ix) Forallfeedingstudies,averageachieveddosemustbereported,
including where possible the dose in mg/kg body weight.
Where dosing via the diet is utilized the test compound must
bedistributeduniformlyinthediet.
(x) Itmaybenecessarytoconductseparatestudiesformetabolites,
degradation or reaction products, where these products can
constitute a relevant risk to non-target organisms and where
theireffectscannotbeevaluatedbytheavailableresultsrelating
to the active substance. Before such studies are performed the
informationfrompoints5,6and7hastobetakenintoaccount.
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
inthevarioustoxicitytestsspecified.
8.1.Effectsonbirds
8.1.1. Acuteoraltoxicity
Aim of the test
The test should provide, where possible, LD50values, the lethal
threshold dose, time courses of response and recovery and the
NOEL,andmustincluderelevantgrosspathologicalfindings.
Circumstances in which requiredThepossibleeffectsoftheactivesubstanceonbirdsmustbeinvesti-
gated except where the active substance is intended solely to be
included inpreparationsforexclusive useinenclosed spaces(e.g. inglasshousesorinfoodstoragepractice).
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 2000 mg/kg
bodyweight.
Test guidelineSetac—Proceduresforassessingtheenvironmentalfateandecotoxi-
cityofpesticides(
1).
8.1.2. Short-termdietarytoxicity
Aim of the testThe test should provide the short termdietary toxicity (LC
50values,
lowestlethal concentration (LLC),wherepossiblenoobservedeffect1991L0414—EN—01.01.2002—004.001—66
(1) Society of Environmental Toxicology and Chemistry (Setac), 1995. Procedures for
Assessing the Environmental Fate and Ecotoxicity of Pesticides, ISBN90-5607-002-9.
▼M7
concentrations (NOEC), time courses of response and recovery) and
includerelevantgrosspathologicalfindings.
Circumstances in which required
The dietary (five-day) toxicity of the active substance to birds must
alwaysbeinvestigatedononespeciesexceptwhereastudyinaccor-
dance with the provisionsof 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
relatedtothefirstspeciestested.
Test guideline
ThetestmustbecarriedoutinaccordancewithOECDMethod205.
8.1.3. Subchronictoxicityandreproduction
Aim of the test
Thetestshouldprovidethesubchronictoxicityandreproductivetoxi-
cityoftheactivesubstancetobirds.
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
breedingseasonisunlikelytooccur.
Test guideline
ThetestmustbecarriedoutinaccordancewithOECDMethod206.
8.2.Effectsonaquaticorganisms
Thedataofthetestsreferred toinpoints8.2.1,8.2.4and8.2.6have
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/
EECfortheclassificationoftheactivesubstance.
Data reported must be supported with analytical data on concentra-
tionsofthetestsubstanceinthetestmedia.
8.2.1. Acutetoxicitytofish
Aim of the test
The test should provide the acute toxicity (LC50), and details of
observedeffects.
Circumstances in which required
Thetestmustalwaysbecarriedout.
Test conditions
The acute toxicity of the active substance must be determined for
rainbow trout (Oncorhynchus mykiss) and for a warmwater fish
species. Where tests with metabolites, degradation or reaction
products have to be performed the species used must be the more
sensitiveofthetwospeciestestedwiththeactivesubstance.
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,regulationsandadministrativeprovisionsrelatingtotheclassifi-
cationandlabellingofdangerous,substances,MethodC1.
8.2.2. Chronictoxicitytofish1991L0414—EN—01.01.2002—004.001—67
(1) OJNoL383,29.12.1992,p.113.
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Circumstances in which required
Achronictoxicitystudymustbecarriedoutunlessitcanbejustified
that continued or repeated exposure of fish is unlikely to occur or
unlessasuitablemicrosomormesocosmstudyisavailable.
Expertjudgmentisrequiredtodecidewhichtesthastobeperformed.
In particular for active substance for which there are indications of
particularconcerns(relatedtothetoxicityoftheactivesubstancefor
fishorthepotential exposure)theapplicant shallseektheagreement
ofthecompetentauthoritiesonthetypeoftesttobeperformed.
A fish early life stage toxicity test might be appropriate where
bioconcentration factors (BCF) are between 100 and 1000 or where
EC50oftheactivesubstance<0,1mg/l.
Afishlifecycletestmightbeappropriateincaseswhere
— thebioconcentrationfactorisgreatertan1000andtheelimination
of the active substance during a depuration phase of 14 days is
lowerthan95%,
or
— thesubstanceisstableinwaterorsediment(DT90>100days).
Itisnot necessary toperformachronic toxicity test onjuvenile fish
when a fish early life stage toxicity test or a fish life cycle test has
been performed; it is likewise not necessary to perform a fish early
lifestagetoxicitytestwhenafishlifecycletesthasbeenperformed.
8.2.2.1. Chronictoxicitytestonjuvenilefish
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
observedeffects.
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
growthandbehaviourmustbegenerated.
8.2.2.2. Fishearlylifestagetoxicitytest
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 guidelineThetestmustbecarriedoutinaccordancewithOECDMethod210.
8.2.2.3. Fishlifecycletest
Aim of the testThe test will provide effects on reproduction of the parental and the
viabilityofthefilialgeneration.
Test conditionsBefore performing these studies the applicant shall seek the agree-
ment of the competent authorities on the type and conditions of the
studytobeperformed.
8.2.3. Bioconcentrationinfish
Aim of the testThe test should provide the steady-state bioconcentration factors,
uptake rate constants and depuration rate constants, calculated for
eachtestcompound,aswellasrelevantconfidencelimits.
Circumstances in which requiredThe bioconcentration potential of active substances, of metabolites
andofdegradationandreactionproducts,likelytopartitionintofatty
tissues(suchaslogp
ow≥3—seepoint2.8orotherrelevantindica-
tions of bioconcentration), must be investigated and be reported,
unlessitcanbejustified thatexposureleadingtobioconcentration is
notlikelytooccur.1991L0414—EN—01.01.2002—004.001—68
▼M7
Test guideline
ThetestmustbecarriedoutinaccordancewithOECDMethod305E.
8.2.4. Acutetoxicitytoaquaticinvertebrates
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-
tioncausingnoimmobilization.
Circumstances in which required
The acute toxicity must always be determined for Daphnia(prefer-
ablyDaphnia magna) . Where plant protection products containing
theactivesubstanceareintendedtobeuseddirectlyonsurfacewater
additional data have to be reported on at least one representative
species fromeach of the following groups: aquatic insects, aqautic
crustaceans (on a species not related to Daphnia)and aquatic
gastropodmolluscs.
Test guidelineThetestmustbecarriedoutinaccordancewithDirective92/69/EEC,
MethodC2.
8.2.5. Chronictoxicitytoaquaticinvertebrates
Aim of the testThetestshouldprovidewherepossibleEC
50valuesforeffectssuchas
immobilization and reproduction and the highest concentration at
whichnoeffect suchasonmartality orreproductionoccurs(NOEC)
anddetailsofobservedeffects.
Circumstances in which requiredA test on Daphniaand on at least one representative aquatic insect
speciesandanaquaticgastropodmolluscspeciesmustbecarriedout
unless it can be justified that continued or repeated exposure is notlikelytooccur.
Test conditionsThetestwith Daphniamustbecontinuedfor21days.
Test guidelineThetestmustbecarried outinaccordance withOECDMethod202,
PartII.
8.2.6. Effectsonalgalgrowth
Aim of the testThe test should procide EC
50values for growth and growth rate,
NOECvalues,anddetailsofobservedeffects.
Circumstances in which requiredPossibleeffects onalgal growthofactive substancesmustalwaysbe
reported.
Forherbicides atestonasecondspeciesfromadifferent taxonom ic
grouphastobeperformed.
Test guidelineThetestmustbecarriedoutinaccordancewithDirective92/69/EEC,
MethodC3.
8.2.7. Effectsonsedimentdwellingorganisms
Aim of testThetestwillmeasureeffectsonsurvivalanddevelopment(including
effects on emergence of adults for Chironomus), the relevant EC
50valuesandtheNOECvalues.
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
aquaticsediments,expertjudgementshouldbeusedtodecidewhether
an acute or a chronic sediment toxicity test in required. Such expert1991L0414—EN—01.01.2002—004.001—69
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judgement should take into account whether effects on sediment
dwelling invertebrates are likely by comparing the aquatic inverte-
brate toxicity EC50data frompoints 8.2.4 and 8.2.5 with the
predicted levels of the active substances in sediment from data in
AnnexIII,point9.
Test conditionsBefore performing these studies the applicant shall seek the agree-
ment of the competent authorities on the type and conditions of the
studytobeperformed.
8.2.8. Aquaticplants
Atestonaquaticplantshastobeperformedforherbicides.
Before performing these studies the applicant shall seek the agree-
ment of the competent authorities on the type and conditions of the
studytobeperformed.
8.3.Effectonarthropods
8.3.1. Bees
8.3.1.1. Acutetoxicity
Aim of the testThe test shouldprovide the acute oral and contact LD
50value of the
activesubstance.
Circumstances in which requiredPotentialimpactonbeesmustbeinvestigated,exceptwhereprepara-
tions containing the active substance are for exclusive use in
situationswherebeesarenotlikelytobeexposedsuchas:
— foodstorageinenclosedspaces,
— non-systemicseeddressings,
— non-systemicpreparationsforapplicationtosoil,
— non-systemicdippingtreatmentsfortransplantedcropsandbulbs,
— woundsealingandhealingtreatments,
— rodenticidalbaits,
— useinglasshouseswithoutpollinators.
Test guideline
ThetestmustbecarriedoutinaccordancewithEPPOGuideline170.
8.3.1.2. Beebroodfeedingtest
Aim of the testThe test should provide sufficient information to evaluate possible
risksfromtheplantprotectionproductonhoneybeelarvae.
Circumstances in which requiredThetestmustbecarriedoutwhentheactivesubstancemayactasan
insect growth regulator unless it can be justified that it is not likely
thatbeebroodwouldbeexposedtoit.
Test guideline
ThetestmustbecarriedoutinaccordancewithICPBRMethod(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, Volume22,pp613to616,1992.)
8.3.2. Otherarethropods
Aim of the testThetestshouldprovidesufficientinformationtoevaluatethetoxicity
(mortality and sublethal effects) of the active substance to selected
arthropodspecies.
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—01.01.2002—004.001—70
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where preparations containing the active substance are for exclusive
useinsituationswherenon-targetarthropodsarenotexposedsuchas:
— foodstorageinenclosedspaces,
— woundsealingandhealingtreatments,— rodenticidalbaits.
Test conditionsThetestmustbeperformedinitially inthelaboratoryonanartificial
substrate (i.e. glass plate or quartz sand, as appropriate) unless
adverse effects can be clearly predicted fromother studies. In these
cases,morerealisticsubstratesmaybeused.
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
possibleandifappropriate,theyshouldrepresenttheothertwomajorfunctional groups, ground dwelling predators and foliage dwelling
predators. Where effects are observed with species relevant to the
proposeduseoftheproduct,furthertestingmaybecarriedoutatthe
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 with non-
target arthropods(
1). Testing must be conducted at rates equivalent
tothehighestrateoffieldapplicationtoberecommended.
Test guidelineWhere relevant, testing should be done according to appropriate
guidelines which satisfy at least the requirements for testing as
includedinSetac—Guidancedocumentonregulatorytestingproce-
duresforpesticideswithnon-targetarthropods.
8.4.Effectsonearthworms
8.4.1. Acutetoxicity
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
mustincludeobservedmorphologicalandbehaviouraleffects.
Circumstances in which requiredEffects on earthworms must be investigated, where preparations
containingtheactivesubstanceareappliedtosoil,orcancontaminate
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 ontheapproximation oflaws,regula-tions and administrative provisions relating to the classification,
packaging and labelling of dangerous substances, Part C, Toxicity
forearthworms:Artificialsoiltest.
8.4.2. Sublethaleffects
Aim of the testThe test shouldprovidethe NOECandthe effects ongrowth,repro-
ductionandbehaviour.
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
beuseful.1991L0414—EN—01.01.2002—004.001—71
(1) Fromthe Workshop European Standard Characteristics of beneficials Regulatory
Testing(Escort),28to30March1994,ISBN0-95-22535-2-6.
(2) OJNoL133,30.5.1988,p.1.
▼M7
Test conditions
Thetestmustbecarriedouton Eisenia foetida.
8.5.Effectsonsoilnon-targetmicro-organisms
Aim of the test
The test should provide sufficient data to evaluate the impact of the
activesubstanceonsoilmicrobialactivity,intermsofnitrogentrans-
formationandcarbonmineralization.
Circumstances in which required
Thetestmustbecarriedoutwherepreparationscontainingtheactive
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
measureratesofrecoveryfollowingtreatment.
Test conditions
Soilsusedmust be freshly sampled agricultural soils.The sitesfrom
which soil is taken must not have been treated during the previous
twoyearswithanysubstancethatcouldsubstantially alter thediver-
sity and levels of microbial populations present, other than in a
transitorymanner.
Test guideline
Setac—Proceduresforassessingtheenvironmentalfateandecotoxi-
cityofpesticides.
8.6.Effects on other non-target organisms (flora and fauna) believed
tobeatrisk
Asummaryofavailabledatafrompreliminarytestsusedtoassessthe
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
impactonnon-targetspecies.
8.7.Effectsonbiological methodsforsewagetreatment
Effectsonbiologicalmethodsforsewagetreatment mustbereported
where the use of plant protection products containing the active
substancecangiverisetoadverseeffectsonsewagetreatmentplants.
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
— Hazardsymbol(s)
— Indicationsofdanger— Riskphrases
— Safetyphrases
11. A dossier as referred to in Annex III, part A, for a representative
plant protection product
PARTB
Introduction
(i) Active substances are defined in Article 2(4) and include chemical
substancesandmicro-organismsincludingviruses.
This Part provides data requirements for active substances consisting of
micro-organisms,includingviruses.1991L0414—EN—01.01.2002—004.001—72
▼B
▼M25
▼M25
For the purposesof Annex II, Part B, the term ‘micro-organism’ is used
and is defined as follows: ‘A microbiological entity, cellular or non-
cellular,capableofreplicationoroftransferringgeneticmaterial’.
The definition applies to, but is not limited to, bacteria, fungi, protozoa,
virusesandviroids.
(ii) For all micro-organisms that are subject to application all available rele-
vantknowledgeandinformationinliteratureshouldbeprovided.
The mostimportant andinformative information isobtained bythechar-
acterisation and identification of a micro-organism. Such information is
foundin sections1 to3(identity, biological properties and further infor-
mation) which form the basis for an assessment of human health and
environmentaleffects.
Newlygenerateddatafromconventionaltoxicologicaland/orpathological
experimentsonlaboratoryanimalsarenormallyrequiredunlesstheappli-
cant can justify, onthebasisofthe previousinformation, that theuseof
the micro-organism, undertheproposedconditions ofuse,doesnot have
anyharmfuleffectsonhumanandanimalhealthorongroundwaterorany
unacceptableinfluenceontheenvironment.
(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.
Testingshouldincludeviableand,ifappropriate,non-viablemicro-organ-
isms,andablankcontrol.
(iv) Wheretestingisdone,adetaileddescription(specification)ofthematerial
usedanditsimpurities,accordingtotheprovisionsofsection1,point1.4,
must be provided. The material used should be of that specification that
willbeusedinthemanufactureofpreparationstobeauthorised.
Where studies are conducted using micro-organisms produced in the
laboratory or in a pilot plant production system, the studies must be
repeatedusingmicro-organismsasmanufactured,unlessitcanbedemon-
stratedthatthetestmaterial usedisessentiallythesameforthepurposes
ofthetestingandassessment.
(v) Where the micro-organism has been genetically modified, as defined in
CouncilDirective90/220/EECof23April1990onthedeliberate release
intotheenvironmentofgenetically modifiedorganisms(2),acopyofthe
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-
valuesshouldbegivenratherthanstatingsignificant/nonsignificant).
(vii) In the case of studies in which dosing extends over a period, dosing
should preferably be done usinga single batch of the micro-organism, if
stabilitypermits.
If the studies are not performed using a single batch of the micro-
organism,thesimilarityofthedifferentbatcheshastobestated.
Whenever a study implies the use of different doses, the relationship
betweendoseandadverseeffectmustbereported.
(viii) Iftheplantprotectionactionisknowntobeduetotheresidualeffectofa
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-
mentsofAnnexII,PartA.
1. IDENTITYOFTHEMICRO-ORGANISM
The identification together with the characterisation of the micro-
organismprovidesthemostimportantinformationandisakeypoint
fordecision-making.
1.1.Applicant
The name and address of the applicant (permanent community
address) must be provided, as must the name, position, telephone
andfaxnumberoftheappropriatepersontocontact.1991L0414—EN—01.01.2002—004.001—73
(1)USEPA Microbial Pesticide Test Guidelines, OPPTS Series 885, February 1996
(http://www.epa.gov/oppbppd1/biopesticides/guidelines/series885.htm).
(2) OJL117,8.5.1990,p.15.
▼M25
Where,inaddition,theapplicanthasanoffice,agentorrepresentative
intheMemberStatetowhichtheapplicationforinclusioninAnnexI
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, with a 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
numberofproducers,theinformationrequiredmustagainbenotified
totheCommissionandtheMemberStates.
1.3.Nameandspeciesdescription,straincharacterisation
(i) The micro-organism should be deposited at an internationally
recognisedculturecollection andgivenanaccessionnumberand
thesedetailsmustbesubmitted.
(ii) Each micro-organism that is subject to the application should be
identifiedandnamedatthespecieslevel.Thescientificnameand
taxonomic grouping, i.e. family, genus, species, strain, serotype,
pathovar or any other denomination relevant to the micro-
organism,mustbestated.
Itmustbeindicatedwhetherthemicro-organism:
— is indigenous or non-indigenous at the species level to the
intendedareaofapplication,
— isawildtype,
— isaspontaneousorinducedmutant,
— has been modified, using techniques described in Annex IA,
Part2,andAnnexIBtoDirective90/220/EEC.
Inthe latter twocases, all knowndifferences between the modi-
fiedmicro-organismandtheparentwildstrainmustbeprovided.
iii) Bestavailable technologyshouldbeusedtoidentify andcharac-
terisethemicro-organismatthestrainlevel.Theappropriatetest
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
namesusedduringthedevelopment,ifany,mustbeprovided.
(v) Relationshipstoknownpathogensshouldbeindicated.
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.Thecontent shouldbeexpressedinappropriate terms,such
asnumberofactive unitspervolumeorweightoranyothermanner
thatisrelevanttothemicro-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
inachangedspecificationofpurity.
1.4.2. Identity and content of impurities, additives, contaminating micro-
organisms
Itisdesirabletohaveaplantprotectionproductwithoutcontaminants
(includingcontaminatingmicro-organisms),ifpossible.Theleveland
nature of acceptable contaminants should be judged from a risk
assessmentpointofview,bythecompetentauthority.1991L0414—EN—01.01.2002—004.001—74
▼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
wherepossibleasoutlinedinAnnexII,PartB,section1,point1.3.
Relevant metabolites (i.e. if expected to be of concern to human
health and/or the environment) known to be formed by the micro-
organismshould be identified and characterised at different states or
growth stages of the micro-organism (see Annex IIB, Introduction,
(viii)).
Where relevant detailed information on all components such as
condensates,culturemedium,etc.mustbeprovided.
Inthecaseofchemical impuritiesthatarerelevant forhumanhealth
and/ortheenvironment,theidentityandmaximumcontent,expressed
inappropriateterms,mustbeprovided.
In the case of additives, the identity and content in g/kg must be
provided.
Theinformationonidentity ofchemical substancessuchasadditives
must be provided as outlined in Annex II, Part A, section 1, point
1.10.
1.4.3. Analytical profile of batches
Whererelevant,thesamedataasoutlinedinAnnexII,PartA,section
1,point1.11,havetobereported,usingtheappropriateunits.
2. BIOLOGICALPROPERTIESOFTHEMICRO-ORGANISM2.1.History of the micro-organism and its uses. Natural occurrence
andgeographicaldistribution
Familiarity, interpreted as the availability of relevant knowledge of
themicro-organism,shouldbepresented.
2.1.1. Historical background
The historical background of the micro-organism and its use (tests/
researchprojectsorcommercialuse)mustbeprovided.
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-
organismshould be reported. The natural occurrence of the m icro-organismin the relevant environm ent shall be given if possible at
strainlevel.
Inthecaseofamutant,orageneticallymodifiedmicro-organism(as
definedinAnnexIA,Part2,andAnnexIBtoDirective90/220/EEC),
detailed information should be provided on its production and isola-
tionandonthemeans bywhichitcanbeclearly distinguished from
theparentwildstrain.
2.2.Informationontargetorganism(s)
2.2.1. Description of the target organism(s)
Whererelevant,detailsofharmfulorganismsagainstwhichprotection
isafforded,mustbeprovided.
2.2.2. Mode of action
Theprincipalmodeofactionshouldbeindicated.Inconnectionwith
the mode of action it should also be stated if the micro-organism
produces a toxin with a residual effect on the target organism. In
thatcase,themodeofactionofthistoxinshouldbedescribed.
Ifrelevant,informationonthesiteofinfectionandmodeofentryinto
the target organismand its susceptible stages should be given. The
resultsofanyexperimentalstudiesmustbereported.
Itshouldbestatedbywhichwayanuptakeofthemicro-organism,or
its metabolites (especially toxins) may occur (e.g. contact, stomach,
inhalation). Itmustalsobestatedwhetherornotthemicro-organism1991L0414—EN—01.01.2002—004.001—75
▼M25
oritsmetabolites aretranslocated inplantsand,whererelevant, how
thistranslocationtakesplace.
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
proposedconditionofuseshallbeindicated.
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
relatedtothetargetspeciesorbeingespeciallyexposedshallbeindi-
cated.
Anyexperienceofthetoxiceffectoftheactivesubstanceoritsmeta-
bolic products on humans or animals, of whether the organism is
capable of colonising or invading humans or animals (including
immunosuppressedindividuals) and whether itis pathogenic shall be
stated.Anyexperienceofwhethertheactivesubstanceoritsproducts
mayirritateskin,eyesorrespiratoryorgansofhumansoranimalsand
whetheritisallergenic incontactwithskinorwheninhaledshallbe
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,aswellasvectorsforviruses,mustbepresented.
The generation time and the type of reproduction of the micro-
organismmustbestated.
Information on the occurrence of resting stages and their survival
time,theirvirulenceandinfectionpotentialmustbeprovided.
Thepotentialofthemicro-organismtoproducemetabolites,including
toxinsthatareofconcernforhumanhealthand/ortheenvironment,in
itsdifferentdevelopmentstagesaftertherelease,mustbeindicated.
2.5.Infectiveness,dispersalandcolonisationability
The persistence of the micro-organism and information on its life
cycleunderthetypicalenvironmentalconditionsofusemustbeindi-
cated.Inaddition,anyparticular sensitivityofthemicro-organism to
certain compartments of the environment (e.g. UV light, soil, water)
mustbestated.
Theenvironmentalrequirements(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
ofeffectsonhumanhealth(section5).
Thepossibleeffectoffactorssuchastemperature,UVlight,pH,and
the presence of certain substances on the stability of relevant toxins
mustalsobestated.
Information on possible dispersal routes of the micro-organism (via
airasdustparticlesoraerosols,withhostorganismsasvectors,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
tobepathogenictohumans,animals,cropsorothernon-targetspecies
andthetypeofdiseasecausedbythemshallbeindicated.Itshallbe
stated whether it is possible, and if so, by which means to clearly
distinguishtheactivemicro-organismfromthepathogenicspecies.1991L0414—EN—01.01.2002—004.001—76
▼M25
2.7.Geneticstabilityandfactorsaffectingit
Whereappropriate,informationongeneticstability(e.g.mutationrate
oftraitsrelatedtothemodeofactionoruptakeofexogenousgenetic
material)undertheenvironmentalconditionsofproposedusemustbe
provided.
Information must also be provided on the micro-organism's capacity
totransfergeneticmaterial tootherorganismsaswellasitscapacity
tobeingpathogenicforplants,animalsorman.Ifthemicro-organism
carries relevant additional genetic elements, the stability of the
encodedtraitsshouldbeindicated.
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
thissubstance,itspresenceinsideoroutsidethecellanditsstability,
its mode of action (including external and internal factors of the
micro-organism necessary to action) as well as its effect on humans,
animalsorothernon-targetspeciesshallbeprovided.
Theconditionsunderwhichthemicro-organismproducesthemetabo-
lite(s)(especiallytoxin(s))mustbedescribed.
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-
litesonthemicro-organism'smodeofactionshouldbeprovided.
2.9.Antibioticsandotheranti-microbialagents
Many micro-organisms produce some antibiotic substances. Interfer-
ence with the use of antibiotics in human or veterinary medicine
mustbeavoidedatanystageofthedevelopmentofamicrobialplant
protectionproduct.
Information on the micro-organism's resistance or sensitivity to anti-
biotics or other anti-microbial agents must be provided, in particular
thestabilityofthegenescodingforantibioticresistance,unlessitcan
bejustifiedthatthemicro-organismhasnoharmfuleffectsonhuman
oranimalhealth,orthatitcannottransferitsresistancetoantibiotics
orotheranti-microbialagents.
3. FURTHERINFORMATIONONTHEMICRO-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
proposeduse.
(ii) The information provided must specify the normal methods and
precautionstobefollowedinthehandling,storageandtransport
ofthemicro-organism.
(iii) The studies, data and information submitted, must demonstrate
thesuitability ofmeasuresproposedforuseinemergency situa-
tions.
(iv) Theinformationanddatareferredtoarerequiredforeachmicro-
organism,exceptwhereotherwisespecified.
3.1.Function
Thebiologicalfunctionmustbespecifiedfromamongthefollowing:
— controlofbacteria,
— controloffungi,— controlofinsects,— controlofmites,— controlofmolluscs,— controlofnematodes,— controlofweeds,
— other(mustbespecified).1991L0414—EN—01.01.2002—004.001—77
▼M25
3.2.Fieldofuseenvisaged
Thefield(s)ofuse,existingandproposed,forpreparationscontaining
themicro-organismmustbespecifiedfromamongthefollowing:
— fielduse,suchasagriculture,horticulture,forestry,andviticulture,
— protectedcrops(e.g.ingreenhouses),— amenity,— weedcontrolonnon-cultivatedareas,— homegardening,
— houseplants,
— storedproducts,— other(specify).
3.3.Cropsorproductsprotectedortreated
Details of existing and intended use in terms of crops, groups of
crops,plants,orplantproductsprotected,mustbeprovided.
3.4.Methodofproductionandqualitycontrol
Fullinformationonhowthemicro-organismisproducedinbulkmust
beprovided.
Both production method/process and product must be subject to a
continuous quality control by the applicant. In particular, the occur-
rence ofspontaneouschanging ofmajor characteristics ofthe micro-
organismand of the absence/presence of significant contam inants
shouldbemonitored.Thequalityassurancecriteriafortheproduction
shouldbesubmitted.
The techniques used to ensure a uniformproduct, and the assay
methodsforitsstandardisation,maintenance andpurityofthemicro-
organismmustbedescribedandspecified(e.g.HACCP).
3.5.Information on the occurrence or possible occurrence of the
developmentofresistanceofthetargetorganism(s)
Availableinformationonthepossibleoccurrenceofthedevelopment
of resistance or cross-resistance of the target organism(s) must be
provided. Where possible, appropriate management strategies should
bedescribed.
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-
organismfromlosing its effects on the target species m ust be
described.
3.7.Recommended methods and precautions concerning handling,
storage,transportorfire
A safety data sheet similar to that required for chemical active
substancesinArticle27ofDirective67/548/EEC(
1)mustbeprovided
foreachmicro-organism.
3.8.Proceduresfordestructionordecontamination
Inmanycasesthepreferredorsolemeansofsafedisposalofmicro-
organisms, contaminated materials, or contaminated packaging, is
throughcontrolledincinerationinalicensedincinerator.
Methodstodisposesafelyofthemicro-organismor,wherenecessary,
to kill it prior to disposal, and methods to dispose of contaminated
packaging and contaminated materials, mustbefully described. Data
mustbeprovidedforsuchmethodstoestablishtheireffectivenessand
safety.1991L0414—EN—01.01.2002—004.001—78
(1) Seedoc.6853/VI/98,Conciseoutlinereportofthefirstpeerreviewmeetingonmicro-
organisms.
▼M25
3.9.Measuresincaseofanaccident
Informationonproceduresforrenderingthemicro-organismharmless
intheenvironment(e.g.waterorsoil)incaseofanaccidentmustbe
provided.
4. ANALYTICALMETHODS
Introduction
Theprovisionsofthissectiononlycoveranalyticalmethodsrequired
forpost-registrationcontrolandmonitoringpurposes.
Post-approval monitoring might be considered for all areas of risk
assessment. This is particularly the case when (strains of) micro-
organismsthatarenon-indigenoustotheintendedareaofapplication
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 such methods on
the basis of the same requirements as defined for methods for post-
registrationcontrolandmonitoringpurposes.
Descriptions of methods must be provided and include details of
equipment, materials and conditions used. The applicability of any
internationallyrecognisedmethodmustbereported.
As far as practicable these methods must employ the simplest
approach,involvetheminimumcost,andrequirecommonlyavailable
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
usedtoanalysemicro-organismsandtheirresidues.
Forthissectionthefollowingapplies:
Impurities Any component (including contaminating
micro-organisms and/or chemical substances)
otherthanthespecifiedmicro-organism,origi-
natingfromthemanufacturingprocessorfrom
degradationduringstorage
Relevantimpurities Impurities, as defined above, that are of
concern for human or animal health and/or
theenvironment
Metabolites Metabolites include products resulting from
degradative and biosynthetic reactions taking
place within the micro-organism or other
organismsusedtoproducethemicro-organism
ofinterest
Relevantmetabolites Metabolites that are of concern for human or
animalhealthand/ortheenvironment
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
theenvironment.
Onrequestthefollowingsamplesmustbeprovided:
(i) samplesofthemicro-organismasmanufactured;
(ii) analytical standards of relevant metabolites (especially toxins)
andallothercomponentsincludedintheresiduedefinition;
(iii) if available, samples of reference substances for the relevant
impurities.
4.1.Methodsfortheanalysisofthemicro-organismasmanufactured
— Methodsfortheidentificationofthemicro-organism.
— Methodsforprovidinginformationonpossiblevariability ofseed
stock/activemicro-organism.
— Methodstodifferentiateamutantofthemicro-organismfromthe
parentwildstrain.
— Methodsfortheestablishmentofpurityofseedstockfromwhich
batchesareproducedandmethodstocontrolthatpurity.1991L0414—EN—01.01.2002—004.001—79
▼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-
ismsarecontrolledtoanacceptablelevel.
— Methodsforthedeterminationofrelevantimpuritiesinthemanu-
facturedmaterial.
— Methodstocontrol the absence and to quantify (withappropriate
limits of determination) the possible presence of any human and
mammalianpathogens.
— Methods to determine storage stability, shelf-life of the micro-
organism,ifappropriate.
4.2.Methodstodetermineandquantifyresidues(viableornon-viable)
of:
— theactivemicro-organism(s),
— relevantmetabolites(especiallytoxins),
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,groundwaterandsurfacewater)andinairwhererelevant.
Analytical methods for amount or activity of proteinaceous products
should also be included, e.g. by testing exponential cultures and
culturesupernatantsinananimalcellbioassay.
5. EFFECTSONHUMANHEALTH
Introduction
(i) Available information based on the properties of the micro-
organismand corresponding organism s (sections 1 to 3),
includinghealthandmedicalreportsmaybesufficientforadeci-
sion whether the micro-organism would cause health effects
(infectious/pathogenic/toxic) inhumansornot.
(ii) The information provided, taken together with that provided for
oneormorepreparationscontainingthemicro-organism,mustbe
sufficient topermit anevaluation to bemade as tothe risksfor
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
sufficientto:
— permit a decision to be made as to whether, or not, the
micro-organismcanbeincludedinAnnexI,
— specifyappropriateconditionsorrestrictionstobeassociated
withanyinclusioninAnnexI,
— specify risk and safety phrases (once introduced) for the
protection of man, animals and the environment to be
includedonpackaging(containers),
— identify relevant first aid measures as well as appropriate
diagnostic and therapeutic measures to be followed in the
eventofinfectionoranotheradverseeffectinman.
(iii) Alleffectsfoundduringinvestigationsshouldbereported.Inves-
tigations which may be necessary in order to evaluate the
probable mechanism involved, and to assess the significance of
theseeffects,mustalsobeperformed.
(iv) Forall studiesactual achieved doseincolonyformingunitsper
kg body weight (cfu/kg), as well as in other appropriate units,
mustbereported.
(v) Evaluationofthemicro-organismshouldbecarriedoutinatier-
wisemanner.
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 fromconventional 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
onhumanandanimalhealth.Pendingtheacceptanceofspecific
guidelinesatinternationallevel,theinformationrequiredshallbe1991L0414—EN—01.01.2002—004.001—80
▼M25
generated using available test guidelines (e.g. USEPA OPPTS
Guidelines).
Tier II studies must be conducted if tests under Tier I have
shownadversehealtheffects.Thetypeofstudytobeperformed
depends on the effects observed in the Tier I studies. Before
performing such studies, the applicant shall seek agreement of
thecompetentauthoritiesonthetypeofstudytobeperformed.
TIERI
5.1.Basicinformation
Basicinformation isrequired about themicro-organism's potential to
causeadverseeffectssuchasabilitytocolonise,tocausedamageand
toproducetoxinsandotherrelevantmetabolites.
5.1.1. Medical data
Whereavailable,andwithoutprejudicetotheprovisionsofArticle5
of Council Directive 80/1107/EEC of 27 November 1980 on the
protection of workers fromthe risks related to chem ical, 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 fromthe 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,theeffectivenessofpotentialantagonists,shouldbeinvestigated
and reported. Where relevant, methods to kill or render the micro-
organismuninfectivemustbeindicated(seesection3,point3.8).
Data and information relevant to the effects of human exposure,
whereavailable and ofthe 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
ofadverseeffects.Suchdatacanbegeneratedfollowingaccidentalor
occupationalexposure.
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
reportsshould,wherefeasible,includedatarelevanttothemechanism
ofactionofthemicro-organism.Thesereportsshall,whereavailable,
include data frompersons exposed in m anufacturing plants or after
applicationofthemicro-organism(e.g.inefficacytrials).
Specialattentionshouldbedevotedtothosewhosesusceptibilitymay
be affected, e.g. pre-existing disease, medication, compromised
immunity,pregnancyorbreastfeeding.
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
anyallergytestsorinterviewedaboutallergenicsymptoms.
5.1.4. Direct observation, e.g. clinical cases
Available reports fromthe open literature on the m icro-organismor
closely related members of the taxonomic group (relating to clinical
cases), where they are fromreference journals or official reports,
must be submitted together with reports of any follow-up studies
undertaken. Such reports are of particular value and should contain
complete descriptions of the nature, level and duration of exposure,
as well as the clinical symptoms observed, first aid and therapeutic1991L0414—EN—01.01.2002—004.001—81
(1) OJL327,3.12.1980,p.8.
(2) OJL374,31.12.1990,p.1.
▼M25
measures applied and measurements and observations made.
Summaryandabstractinformationisoflimitedvalue.
Ifthereareanimalstudiesperformed,reportsrelatingtoclinicalcases
canbeofparticularvalueinconfirmingthevalidityofinterpretations
from animal data to man and in identifying unexpected adverse
effectswhicharespecifictohumans.
5.2.Basicstudies
Inordertomakeitpossibletocorrectlyinterprettheobtainedresults,
it is of greatest importance that the suggested test methods are rele-
vant regarding species sensitivity, administration route, etc., and
relevant froma biological and toxicological point of view. The way
of administration of the test micro-organism depends on the main
exposureroutestohumans.
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 with a recovery period (after which full macro-
scopic and microscopic pathology is to be performed, including an
explorationformicro-organismsinthetissuesandorgans).Thisfacil-
itates theinterpretation ofcertain effects and providesthepossibility
to recognise infectiveness and/or pathogenicity, which in turn helps
taking decisions on other issues such as the necessity to perform
long-termstudies (carcinogenicity etc., see point 5.3), and whether
ornottoperformresiduestudies(seepoint6.2).
5.2.1. Sensitisation(1)
Aimofthetest
Thetest will providesufficient information toassessthepotential of
themicro-organismtoprovokesensitisationreactionsbyinhalationas
wellaswithdermalexposure.Amaximisedtesthastobeperformed.
Circumstancesinwhichrequired(2)
Informationonsensitisationmustbereported.
5.2.2. Acute toxicity, pathogenicity and infectiveness
Thestudies,dataandinformation tobeprovidedandevaluated must
besufficient topermit theidentification ofeffectsfollowingasingle
exposuretothemicro-organism,andinparticulartoestablish,orindi-
cate:
— the toxicity, pathogenicity and infectiveness of the micro-
organism,
— the time courseand characteristics of the effects withfull details
ofbehaviouralchangesandpossiblegrosspathologicalfindingsat
post-mortem,
— wherepossiblemodeoftoxicaction,— the relative hazards associated with the different routes of expo-
sure,and
— blood analyses throughout the studies in order to evaluate the
clearanceofthemicro-organism.
Acute toxic/pathogenic effects may be accompanied by infectiveness
and/ormorelong-termeffectswhichcannotbeobservedimmediately.
Withaviewtohealthevaluation,itisthereforenecessarytocarryout
studiesontheabilitytoinfectinconnectionwithoralintake,inhala-
tionandintraperitoneal/subcutaneousinjectionbytestmammals.1991L0414—EN—01.01.2002—004.001—82
(1) The available methods for testing dermal sensitisation are not suitable for testing
micro-organisms. Sensitisation by inhalation is most probably a greater problemcompared with dermal exposure to micro-organisms but so far, there are no validatedtestmethods.Developmentofthesekindsofmethodsisthereforeofgreatimportance.Until then, all micro-organisms should be regarded as potential sensitisers. This
approach alsotakesintoconsiderationimmuno-compromisedorother sensitive indivi-
dualsinthepopulation(e.g.pregnantwomen,new-bornchildrenorelderly).
(
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
regardedasnotobligatorybutoptional,onaprovisionalbase.
▼M25
Duringthe acute toxicity, pathogenicity and infectiveness studies, an
estimationofthemicro-organismand/ortheactivetoxinclearance in
the organs deemed to be relevant for microbial examination (e.g.
liver, kidneys, spleen, lungs, brain, blood and site of administration)
mustbeperformed.
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, thymusgland andlesionsatthe 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 isofparticular value inassessinghazards likely
toarise inaccident situations and consumer risksdue to exposure to
possibleresidues.
5.2.2.1. Acute oral toxicity, pathogenicity and infectiveness
Circumstancesinwhichrequired
Theacuteoraltoxicity,pathogenicityandinfectivenessofthemicro-
organismmustbereported.
5.2.2.2. Acute inhalation toxicity, pat hogenicityandinfectiveness
Circumstancesinwhichrequired
The inhalation toxicity(
1), pathogenicity and infectiveness of the
micro-organismmustbereported.
5.2.2.3. Intraperitoneal/subcutaneous single dose
The intraperitoneal/subcutaneous test is considered a highly sensitive
assaytoelicitinparticularinfectiveness.
Circumstancesinwhichrequired
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
injectionifthemaximumtemperatureforgrowthandmultiplicationis
lowerthan37oC.
5.2.3. Genotoxicity testing
Circumstancesinwhichrequired
Ifthemicro-organismproducesexotoxinsaccordingtopoint2.8,then
thesetoxinsandanyotherrelevantmetabolitesintheculturemedium
mustalsobetestedforgenotoxicity.Suchtestsontoxinsandmetabo-
litesshouldbeperformedusingthepurifiedchemicalifpossible.
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.
Inthe case ofa virusthe riskofinsertional mutagenesis in mammal
cellsortheriskofcarcinogenicityhastobediscussed.
Aimofthetest
Thesestudiesareofvaluein:
— thepredictionofgenotoxicpotential,
— theearlyidentificationofgenotoxiccarcinogens,— theelucidationofthemechanismofactionofsomecarcinogens.1991L0414—EN—01.01.2002—004.001—83
(1) Aninhalationstudymaybereplacedbyanintratrachealstudy.
▼M25
It is important that a flexible approach is adopted, with selection of
further tests being dependent upon interpretation of results at each
stage.
Testconditions(1)
Genotoxicity of cellular micro-organisms will be studied after
breaking of the cells, wherever possible. Justification should be
providedonthemethodofsamplepreparationused.
Genotoxicityofvirusesshouldbestudiedoninfectiousisolates.
5.2.3.1. In vitrostudies
Circumstancesinwhichrequired
Results of in vitromutagenicity tests (bacterial assay for gene muta-
tion, test for clastogenicity in mammalian cells and test for gene
mutationinmammaliancells)mustbeprovided.
5.2.4. Cell culture study
Thisinformation mustbereportedforintracellular replicating micro-
organisms, suchas viruses, viroidsor specific bacteria and protozoa,
unlesstheinformation fromsections1to3clearly demonstrates that
themicro-organismdoesnotreplicateinwarm-bloodedorganisms.A
cell culture study should be performed in human cell or tissue
culturesofdifferentorgans.Selectioncanbebasedonexpectedtarget
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
isakeyconsideration.
5.2.5. Information on short-term toxicity and pathogenicity
Aimofthetest
Short-term toxicity studies must be designed to provide information
astotheamountofthemicro-organismthatcanbetolerated 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-termstudiesprovide inform ation useful in
thedesignofchronictoxicitystudies.
Thestudies,dataandinformationtobeprovidedandevaluated,must
besufficienttopermittheidentificationofeffectsfollowingrepeated
exposuretothemicro-organism,andinparticulartofurtherestablish,
orindicate:
— therelationshipbetweendoseandadverseeffects,
— toxicity of the micro-organism including where necessary the
NOAELfortoxins,
— targetorgans,whererelevant,— the time courseand characteristics of the effects withfull details
ofbehaviouralchangesandpossiblegrosspathologicalfindingsat
post-mortem,
— specifictoxiceffectsandpathologicalchangesproduced,— where relevant the persistence and reversibility of certain toxic
effectsobserved,followingdiscontinuationofdosing,
— wherepossible,themodeoftoxicaction,and— the relative hazard associated with the different routes of expo-
sure.
During the short-term toxicity study, an estimation of the micro-
organismclearanceinthemainorgansmustbeperformed.
Investigations should be included for pathogenicity and infectiveness
endpoints.1991L0414—EN—01.01.2002—004.001—84
(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
Circumstancesinwhichrequired
The short-term toxicity (minimum 28 days) of the micro-organism
mustbereported.
The choice of test species has to be justified. The choice of study
lengthdependsonacutetoxicityandclearancedata.
Expertjudgementisrequiredtodecidewhatrouteofadministrationis
preferable.
5.2.5.1. Health effects after repeated inhalatory exposure
Informationonthehealtheffectsafterrepeatedinhalatoryexposureis
considerednecessary,particularlyfortheriskassessmentoftheoccu-
pational setting. Repeated exposure might influence the clearance
capacity(e.g.resistance)ofthehost(human).Furthermore,forproper
risk assessment the toxicity after repeated exposure to contaminants,
growth medium, co-formulants and the micro-organism needs to be
addressed.It shouldbe kept in mind that the formulants inthe plant
protection product can influence the toxicity and infectiveness of a
micro-organism.
Circumstancesinwhichrequired
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.Thiscanbethecaseifitisdemonstratedthatthetestmaterial
hasnoinhalablefractionand/orrepeatedexposureisnotexpected.
5.2.6. Proposed treatment: first aid measures, medical treatment
Thefirstaidmeasurestobeusedintheeventofinfectionandinthe
eventofcontaminationofeyesmustbeprovided.
Therapeuticregimesforuseintheeventofingestionorcontamination
ofeyesandskinmustbedescribedinfull.Informationbasedonprac-
tical experience, where it exists and is available, in other cases on
theoretical grounds, as to the effectiveness of alternative treatment
regimes,whererelevant,mustbeprovided.
Informationonresistancetoantibioticsmustbeprovided.
(ENDOFTIERI)
TIERII
5.3.Specifictoxicity,pathogenicityandinfectivenessstudies
In certain cases, it can be necessary to carry out supplementary
studiestofurtherclarifytheadversehumaneffects.
In particular, if results fromearlier studies indicate that the m icro-
organismmaycauselong-termhealtheffects,studiesonchronictoxi-
city,pathogenicityandinfectiveness,carcinogenicityandreproductive
toxicitymustbecarriedout.Furthermore,whereatoxinisproduced,
kineticstudiesmustbeperformed.
Studiesrequiredmustbedesignedonanindividualbasis,inthelight
oftheparticularparameterstobeinvestigatedandtheobjectivestobe
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
Circumstancesinwhichrequired
If all the results of the in vitrostudies are negative further testing
must be done with consideration of other relevant information avail-
able. The test can be an in vivostudy or an in vitrostudy using a
differentmetabolisingsystemfromthat/thosepreviouslyused.
Ifthein vitrocytogenetictestispositive,an in vivotestusingsomatic
cells(metaphaseanalysisinrodentbonemarrowormicronucleustest
inrodents)mustbeconducted.1991L0414—EN—01.01.2002—004.001—85
▼M25
Ifeitherofthe in vitrogenemutationtestsarepositive,an in vivotest
to investigate unscheduled DNAsynthesisor a mouse spottest must
beconducted.
5.5.Genotoxicity— In vivostudiesingermcells
Aimofthetestandtestconditions
Seepoint5.4.
Circumstancesinwhichrequired
When any result of an in vivostudy in somatic cells is positive, in
vitrotesting forgermcell effects m ay bejustified. Thenecessity 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),
tolookatthepotentialforinheritedeffectsandpossiblymakeaquan-
titativeassessmentofheritableeffects.Itisrecognisedthatinviewof
theircomplexity, theuseofquantitative studieswouldrequirestrong
justification.
(ENDOFTIERII)
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, with particular reference to
the risks for man and animals that may or do arise, and the extent,
qualityandreliabilityofthedatabase.
Itmustbeexplainedwhetherexposureofanimalsorhumanshasany
implicationsforvaccinationorserologicalmonitoring.
6. RESIDUESINORONTREATEDPRODUCTS,FOODANDFEED
Introduction
(i) The information provided, taken together with that for one or
morepreparationscontainingthemicro-organism,mustbesuffi-
cient to permit an evaluation to be made as to the riskfor man
and/oranimals,arisingfromexposuretothemicro-organismand
its residual traces and metabolites (toxins) remaining in or on
plantsorplantproducts.
(ii) Inaddition,theinformationprovidedmustbesufficientto:
— permitadecisiontobemadeastowhetherornotthemicro-
organismcan be included in Annex I to Directive 91/414/
EEC,
— specifyappropriateconditionsorrestrictionstobeassociated
withanyinclusioninAnnexItoDirective91/414/EEC,
— whererelevant,setmaximumresiduelevels,preharvestinter-
vals to protect consumers and waiting periods, to protect
workershandlingthetreatedcropsandproducts.
(iii) For the evaluation of risk arising fromresidues, experim ental
data on levels of exposure to the residue may not be required
whereitcanbejustified,thatthemicro-organismanditsmetabo-
litesarenothazardoustohumansintheconcentrationsthatcould
occur as a result of authorised use. This justification can be
basedonopenliterature,onpracticalexperienceandoninforma-
tionsubmittedinsections1through3andsection5.
6.1.Persistance and likelihood of multiplication in or on crops,
feedingstuffsorfoodstuffs
A substantiated estimation of persistance/competitiveness of the
micro-organismandrelevantsecondarymetabolites(especiallytoxins)
inoronthecropundertheenvironmentalconditionsprevailingatand
after the intended use, taking into account in particular the informa-
tionprovidedinsection2,hastobedelivered.
Moreover, the application shall state to which extent and on which
basisitisconsideredthatthemicro-organismcan(orcannot)multiply1991L0414—EN—01.01.2002—004.001—86
▼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,
suchastheADI,canbeestablishedforriskmanagement.
6.2.1. Non-viable residues
Anonviablemicro-organismisamicro-organismthatisnotcapable
ofreplicationoroftransferringgeneticmaterial.
If relevant quantities of the micro-organism or of produced metabo-
lites,especiallytoxins,havebeenfoundtobepersistantinsection2,
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
undernaturalconditionsorinadifferentphenotypicstate.
In agreement with Directive 91/414/EEC, the conclusion concerning
thedifferencebetweennaturalconcentrationsandanelevatedconcen-
tration due to treatment with the micro-organism, is to be based on
experimentally obtained data, and not on extrapolations or calcula-
tionsusingmodels.
Beforeperformingsuchstudies,theapplicantshallseekagreementof
thecompetentauthoritiesonthetypeofstudytobeperformed.
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
thatcouldoccurasaresultofauthoriseduse.
In agreement with Directive 91/414/EEC, the conclusion concerning
thedifferencebetweennaturalconcentrationsandanelevatedconcen-
tration due to treatment with the micro-organism, is to be based on
experimentally obtained data, and not on extrapolations or calcula-
tionsusingmodels.
Thepersistenceofviableresiduesneedsspecialattentionifinfective-
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
requirestudiessimilartothoseprovidedforinPartA.
Beforeperformingsuchstudies,theapplicantshallseekagreementof
thecompetentauthoritiesonthetypeofstudytobeperformed.
6.3.Summaryandevaluationofresiduebehaviourresultingfromdata
submittedunderpoints6.1and6.2
7. FATEANDBEHAVIOURINTHEENVIRONMENT
Introduction
(i) Informationontheorigin,theproperties,andthesurvivalofthe
micro-organism and its residual metabolites as well as its
intended use form the basis for an assessment of environmental
fateandbehaviour.
Experimentaldataarenormallyrequiredunlessitcanbejustified
that an assessment of its fate and behaviour in the environment
can be performed with the information already available. This
justificationcanbebasedonopenliterature,onpracticalexperi-
enceand,oninformationsubmittedinsections1through6.The
function of the micro-organism in environmental processes (as
definedinsection2,point2.1.2)isofparticularinterest.1991L0414—EN—01.01.2002—004.001—87
▼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/ortheenvironment.
(iii) Inparticular,theinformationprovidedshouldbesufficientto:
— decide whether, or not, the micro-organism can be included
inAnnexI,
— specifyappropriateconditionsorrestrictionstobeassociated
withanyinclusioninAnnexI,
— specifythehazardsymbols(onceintroduced),theindications
ofdanger,andrelevantriskandsafetyphrasesfortheprotec-
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
thetimecoursesinvolved,
— identifymeasuresnecessarytominimisecontaminationofthe
environmentandimpactonnon-targetspecies.
(iv) Anyrelevant metabolites (i.e. of concern for human health and/
ortheenvironment)formedbythetestorganismunderanyrele-
vant environmental conditions should be characterised. If
relevant metabolites are present in or produced by the micro-
organism,data asoutlined underAnnexII,Part A,point 7may
berequired,ifallofthefollowingconditionsaremet:
— the relevant metabolite is stable outside the micro-organism,
seepoint2.8,and
— atoxiceffectoftherelevantmetaboliteisindependentofthe
presenceofthemicro-organism,and
— the relevant metabolite is expected to occur in the environ-
ment in concentrations considerably higher than under
naturalconditions.
(v) Available information on the relationship with naturally occur-
ringwildtyperelativesshouldbetakenintoaccount.
(vi) Before performing studies as referred to below, the applicant
shall seek agreement of the competent authorities on whether
studiesneed tobe performed and,if so,the type ofstudy tobe
conducted.Theinformation fromtheothersectionshas,also,to
betakenintoaccount.
7.1.Persistence andmultiplication
Whererelevant,appropriateinformationonthepersistenceandmulti-
plication of the micro-organism, in all environmental compartments
has to be given, unless it can be justified that exposure of the parti-
cularenvironmentalcompartmenttothemicro-organismisunlikelyto
occur.Specialattentionshallbegivento
— competitiveness under the environmental conditions prevailing at
andaftertheintendeduse,and
— population dynamicsinseasonally orregionally extreme climates
(particularlyhotsummer,coldwinterandrainfall)andtoagricul-
turalpracticesappliedafterintendeduse.
Estimated levels of the specified micro-organism in a time course
after use of the product under the proposed conditions of use shall
begiven.
7.1.1. Soil
Information on viability/population dynamics should be reported in
severalcultivatedanduncultivatedsoilsrepresentativeofsoilstypical
ofthevariousCommunityregionswhereuseexistsorisanticipated.
The provisions on choice of soil and its collection and handling, as
referred toinPartA,point7.1,Introduction, havetobefollowed. If
the test organismis to be used in association with other m edia, e.g.
rockwool,thismustbeincludedinthetestrange.
7.1.2. Water
Information should be reported on viability/population dynamics in
natural sediment/water systems under both dark and illuminated
conditions.1991L0414—EN—01.01.2002—004.001—88
▼M25
7.1.3. Air
Incaseofparticularconcernsforoperator,workerorbystanderexpo-
sure,informationontheconcentrationsinairmightbenecessary.
7.2.Mobility
The possible spread of the micro-organism and its degradation
productsinrelevantenvironmentalcompartmentshastobeevaluated,
unlessitcanbejustifiedthatexposureoftheparticularenvironmental
compartments to the micro-organism is unlikely to occur. In this
context,theintendeduse(e.g.fieldorgreenhouse,applicationtosoil
ortocrops),lifecyclestages,includingoccurrenceofvectors,persis-
tenceandtheabilityoftheorganismtocoloniseadjacenthabitatsare
ofparticularinterest.
Thespread,thepersistenceandprobabletransportrangesneedspecial
attentioniftoxicity,infectivenessorpathogenicityhavebeenreported
or if any other information suggests possible hazard to humans,
animals ortotheenvironment. Inthiscase thecompetent authorities
may require studies similar to those provided for in Part A. Before
performing such studies, the applicant shall seek agreement of the
competentauthoritiesonthetypeofstudytobeperformed.
8. EFFECTSONNON-TARGETORGANISMS
Introduction
(i) The information on identity, biological properties and further
informationinsections1to3and7iscentraltotheassessment
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.Theinformationsubmittedinaccordancewithsection
5 will provide essential information as to effects to mammals
andthemechanismsinvolved.
Experimentaldataarenormallyrequired,unlessitcanbejusti-
fied that an assessment of effects on non-target organisms can
beperformedwiththeinformationalreadyavailable.
(ii) The choice of the appropriate non-target organisms for testing
ofenvironmental effectsshouldbebasedontheidentityofthe
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
organismscloselyrelatedtothetargetorganism.
(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 riskfromexposure to
the micro-organism, where they are of environmental signifi-
cance. Impact can result from single, prolonged or repeated
exposureandcanbereversibleorirreversible.
(iv) In particular, the information provided for the micro-organism,
together with other relevant information, and that provided for
oneormorepreparationscontainingit,shouldbesufficientto:
— decidewhether,ornot,themicro-organismcanbeincluded
inAnnexI,
— specify appropriate conditions or restrictions to be asso-
ciatedwithanyinclusioninAnnexI,
— permit an evaluation of short- and long-term risks for non-
target species — populations, communities, and processes
—asappropriate,
— classifythemicro-organismastobiologicalhazard,— specifytheprecautionsnecessaryfortheprotectionofnon-
targetspecies,and
— specify the hazard symbols (once introduced), the indica-
tionsofdanger,andrelevantriskandsafetyphrasesforthe
protection of the environment, to be mentioned on packa-
ging(containers).
(v) There is a need to report all potentially adverse effects found
duringroutineinvestigationsonenvironmentaleffects,tounder-
take and report, where required by the competent authorities,
such additional studies which may be necessary to investigate1991L0414—EN—01.01.2002—004.001—89
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the probable mechanisms involved and to assess the signifi-
cance of these effects. All available biological data and
information which isrelevant tothe assessmentofthe ecology
profileofthemicro-organismmustbereported.
(vi) Forallstudies,averageachieveddoseincfu/kgbodyweightas
wellasinotherappropriateunitsmustbereported.
(vii) It may be necessary to conduct separate studies for relevant
metabolites(especiallytoxins),wheretheseproductscanconsti-
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
whethersuchstudiesneed tobeperformedand,ifso,thetype
of study to be conducted. The information from sections 5, 6
and7hastobetakenintoaccount.
(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,wherepossible, be usedin the various
testsspecified.
(ix) Testsmustbeperformedunlessitcanbejustifiedthatthenon-
targetorganismwillnotbeexposedtothemicro-organism.Ifit
isjustifiedthatthemicro-organismdoesnotcausetoxiceffects
or is not pathogenic or infective to vertebrates or plants, only
reaction to appropriate non-target organisms must be investi-
gated.
8.1.Effectsonbirds
Aimofthetest
Informationontoxicity,infectivenessandpathogenicitytobirdsmust
bereported.
8.2.Effectsonaquaticorganisms
Aimofthetest
Information on toxicity, infectiveness and pathogenicity to aquatic
organismsmustbereported.
8.2.1. Effects on fish
Aimofthetest
Information on toxicity, infectiveness and pathogenicity to fish must
bereported.
8.2.2. Effects on freshwater invertebrates
Aimofthetest
Informationontoxicity,infectivenessandpathogenicitytofreshwater
invertebratesmustbereported.
8.2.3. Effects on algae growth
Aimofthetest
Information on effects on algal growth, growth rate and capacity to
recovermustbereported.
8.2.4. Effects on plants other than algae
Aimofthetest
Informationoneffectsonplantsotherthanalgaemustbereported.
8.3.Effectsonbees
Aimofthetest
Informationontoxicity,infectiveness andpathogenicity tobeesmust
bereported.1991L0414—EN—01.01.2002—004.001—90
▼M25
8.4.Effectsonarthropodsotherthanbees
Aimofthetest
Informationontoxicity,infectivenessandpathogenicitytoarthropods
other than bees must be reported. The selection of the test species
shouldberelatedtothepotentialuseoftheplantprotectionproducts
(e.g. foliar or soil application). Special attention should be given to
organisms used for biological control and organisms playing an
importantroleinintegratedpestmanagement.
8.5.Effectsonearthworms
Aimofthetest
Information on toxicity, infectiveness and pathogenicity to earth-
wormsmustbereported.
8.6.Effectsonnon-targetsoilmicro-organisms
Impactonrelevantnon-targetmicro-organismsandontheirpredators
(e.g. protozoa for bacterial inoculants) should be reported. Expert
judgementisrequiredtodecidewhetheradditionalstudiesareneces-
sary. Such decision will take into consideration the available
informationinthisandothersections,inparticulardataonthespeci-
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
usedinintegratedcropmanagement(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
studiessuchaschronic,sub-lethalorreproductivestudiesonselected
non-targetorganisms.
Beforeperformingsuchstudies,theapplicantshallseekagreementof
thecompetentauthoritiesonthetypeofstudytobeperformed.
9. SUMMARY AND EVALUATION OF ENVIRONMENTAL
IMPACT
A summary and evaluation of all data relevant to the environmental
impact,shouldbecarriedoutaccordingtotheguidancegivenbythe
competentauthoritiesoftheMemberStatesconcerningtheformatof
such summaries and evaluations. It should include a detailed and
critical assessmentofthosedatainthecontextofrelevantevaluative
anddecisionmakingcriteriaandguidelines,withparticularreference
totherisksfortheenvironmentandnon-targetspeciesthatmayordo
arise,andtheextent,qualityandreliabilityofthedatabase.Inparti-
cularthefollowingissuesshouldbeaddressed:
— distribution and fate in the environment, and the time courses
involved,
— identificationofnon-targetspeciesandpopulationsatrisk,andthe
extentoftheirpotentialexposure,
— identification of precautions necessary to avoid or minimise
contamination of the environment, and for the protection of non-
targetspecies.1991L0414—EN—01.01.2002—004.001—91
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ANNEX III
REQUIREMENTS FOR THE DOSSIER TO BE SUBMITTED FOR THE
AUTHORIZATIONOFAPLANTPROTECTIONPRODUCT
INTRODUCTION
Theinformationrequiredshall:
1.1. include a technical dossier supplying the information necessary for evalu-
ating efficacy and the foreseeable risks, whether immediate or delayed,
whichtheplantprotectionproductmayentailforhumans,animalsandthe
environment and containing at least the information and results of the
studiesreferredtobelow;
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,theinformation shallbegenerated usingsuitableinternationally or
nationally validated test guidelines or, in the absence thereof, test guide-
linesacceptedbythecompetentauthority;
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
Methodhasnotyetbeenupdated; ◄
1.4. includewhenrequiredbythecompetentauthority,afulldescriptionoftest
guidelines used, except if they are referred to or described in this Annex,
andafulldescriptionofanydeviationsfromthemincludingajustification,
whichisacceptabletothecompetentauthority,forthesedeviations;
1.5. includeafullandunbiasedreportofthestudiesconductedaswellasafull
descriptionofthemorajustification,whichisacceptabletothecompetent
authoritywhere:
— particulardataandinformationwhichwouldnotbenecessaryowingto
thenatureoftheproductoritsproposeduses,arenotprovided,
or
— itisnotscientificallynecessary,ortechnicallypossibletosupplyinfor-
mationanddata.
1.6. where relevant, have been generated in accordance with the requirements
ofDirective86/609/EEC.
2.1. Tests and analyses must be conducted in accordance with the principles
laid downinDirective 87/18/EEC wheretesting isdone toobtain data on
theproperties and/or safety withrespect tohumanoranimal health orthe
environment.
2.2. Testsandanalyses,requiredundertheprovisionsofSection6points6.2to
6.7 of this Annex, shall be conducted by official or officially recognized
testing facilites or organizations which satisfy at least the following
requirements:
— haveattheirdisposalsufficientscientificandtechnicalstaff,havingthe
necessary education, training, technical knowledge and experience for
theirassignedfunctions,
— 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
thereafteraccordingtoanestablishedprogramme,
— haveattheirdisposalappropriateexperimentalfieldsand,whereneces-
saryglasshouses,growthcabinetsorstoragerooms.Theenvironmentin
whichthetestsareundertakenshallnotinvalideitsresultsoradversely
effecttherequiredaccuracyofmeasurement,
— make available to all relevant personnel operating procedures and
protocolsusedforthetrials,1991L0414—EN—01.01.2002—004.001—92
▼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
leastitslocationandtheplantprotectionproductsincludedinit,
— ensurethatthequalityoftheworkperformedisappropriatetoitstype,
range,volumeandintendedpurpose,
—►C2maintain records of all original observations, calculations and
deriveddata, ◄calibration recordsandthefinaltestreportaslongas
theproductconcernedauthorizedintheCommunity.
2.3. MemberStatesshallrequirethatofficiallyrecognizedtestingfacilitiesand
organizations,and,whererequested,officialfacilitiesandorganizations:
— report to the relevant national authority all detailed information neces-
sarytodemonstratethattheycansatisfytherequirements providedfor
inpoint2.2,
— accept at any time the inspections, which each Member State shall
regularly organize on its territory in order to verify the compliance
withtherequirementaslaiddowninpoint2.2.
2.4. Bywayofderogationfrompoint2.1,MemberStatesmayapplytheprovi-
sions of points 2.2 and 2.3, by extension, to tests and analyses performed
ontheir territory inorderto obtain data ontheproperties and/or safety of
thepreparationswithrespecttohoney-beesandbeneficialarthropodsother
thanbeesandactuallystartedonorbefore31December1999.
2.5. Bywayofderogationfrompoint2.1,MemberStatesmayapplytheprovi-
sions of points 2.2 and 2.3, by extension, to supervised residue trials
performedontheirterritoryinaccordancewiththeprovisionsofSection8
‘Residues in or on treated products, food and feed’ with plant protection
productscontainingactivesubstancesalreadyonthemarkettwoyearsafter
notificationoftheDirectiveandactuallystartedonorbefore31December
1997.
2.6. By way of derogation frompoint 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,
mayhavebeen conducted byofficial orofficially recognisedtesting facil-
ities or organisations which satisfy at least the requirements under points
2.2and2.3oftheintroductionofAnnexIII.
3. The information required shall include the proposed classification and
labelling of the plant protection product in accordance with relevant
CommunityDirectives.
4. In individial cases it may be necessary to require certain information as
provided for in Annex II,Part A,for formulants. Before suchinformation
willberequiredandbeforepossiblenewstudieshavetobeperformed,all
information on the formulant, made available to the competent authority,
willbeconsidered,inparticularwhen:
— the use of the formulant is permitted in food, animal feeding stuffs,
medicinesorcosmeticsinaccordancewithCommunitylegislation,
or
— asafetydatasheethasbeensubmittedfortheformulantinaccordance
withCouncilDirective67/548/EEC.
PARTA
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 themin term s of their specification and nature. The
information and data referred to, unless otherwise specified, are
requiredforallplantprotectionproducts.
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
telefaxnumberoftheappropriatepersontocontact.1991L0414—EN—01.01.2002—004.001—93
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▼B
▼M2
▼M2
Whereinaddition,theapplicanthasanoffice,agentorrepresentative
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
numberoftheappropriatepersontocontact.
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
each active substance in the preparation must be provided as must
the name and address of each manufacturing plant in which the
preparationandactivesubstancearemanufactured.
A contact point (preferable a central contact point, to include name,
telephoneandtelefaxnumbers)mustbeprovidedforeach.
Iftheactivesubstanceoriginatesfromamanufacturerfromwhichdata
accordingtoAnnexIIhadnotbeensubmittedpreviously,astatement
ofpurityanddetailed informationontheimpuritiesinAnnexIIhave
tobeprovided.
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
tradenameofalreadyregisteredplantprotectionproducts.)
1.4. Detailed quantitative and qualitative information on the composition
of the preparation (active substance(s), and formulants)
1.4.1. Forpreparationsthefollowinginformationmustbereported:
— the content of both technical active substance(s) and pure active
substance(s);
— thecontentofformulants.
The concentrations should be expressed in terms as provided for in
Article6(2)ofDirective78/631/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-
vantitmustbestatedwhichsalt,ester,anionorcationispresent.
1.4.3. Formulants mustwherepossible,beidentified bothbytheir chemical
nameasgiveninAnnexItoDirective67/548/EEC,or,ifnotincluded
in this Directive, inaccordance withbothIUPACand CAnomencla-
ture.Theirstructure orstructural formula mustbeprovided.Foreach
componentoftheformulantstherelevantEEC(EINECSorELINCS)
numberandCASnumberwheretheyexist,mustbeprovided. Where
theinformationprovideddoesnotfullyidentifyaformulant,anappro-
priate specification must be provided. The trade name of formulants,
wheretheyexist,mustalsobeprovided.
1.4.4. Forformulantsthefunctionmustbegiven:
— adhesive(sticker),
— antifoamingagent,
— antifreeze,
— binder,— buffer,
— carrier,
— deodorant,— dispersingagent,— dye,
— emetic,
— emulsifier,— fertilizer,
— preservative,
— odourant,— perfume,1991L0414—EN—01.01.2002—004.001—94
▼M2
— propellant,
— repellent,
— safener,— solvent,— stabilizer,
— synergist,
— thickener,— wettingagent,— miscellaneous(specify).
1.5. Physical state and nature of the preparation (emulsifiable concentrate,
wettable powder, solution etc).
1.5.1. Thetypeandcodeofpreparationmustbedesignatedaccordingtothe
‘Catalogue of pesticide formulation types and international coding
system(GIFAPTechnicalMonographNo2.1989)’.
Whereaparticularpreparationisnotdefinedpreciselyinthispublica-
tion a full description of the physical nature and state of the
preparation must be provided, together with a proposal for a suitable
descriptionofthetypeofpreparationandaproposalforitsdefinition.
1.6. Function (herbicide, insecticide, etc.)
Thefunctionmustbespecifiedfromamongthefollowing:
— acaricide,
— bactericide,
— fungicide,— herbicide— insecticide,
— molluscicide,
— nematicide,— plantgrowthregulator,— repellant,
— rodenticide,
— semio-chemicals,— talpicide,— viricide,
— other(mustbespecified).
2.Physical,chemicalandtechnicalpropertiesoftheplantprotection
product
Theextenttowhichplantprotectionproductsforwhichauthorization
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
ApplicationStandards,mustbestated.DivergencesfromFAOspecifi-
cationsmustbedescribedindetail,andjustified.
2.1. Appearance (colour and odour)
A description of both the colour and odour, if any, and the physical
stateofthepreparation,mustbeprovided.
2.2. Explosivity and oxidizing properties
2.2.1. Theexplosivepropertiesofpreparationsmustbereportedaccordingto
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
preparationsthemethodusedmustbejustified.Theoxidizingproper-
ties do not have to be determined if it can be shown without
reasonabledoubtonthebasisofthermodynamic information,thatthe
preparation is incapable of reacting exothermically with combustible
materials.1991L0414—EN—01.01.2002—004.001—95
▼M2
2.3. Flash point and other indications of flammability or spontaneous igni-
tion
Theflashpointofliquidswhichcontainflammable solvents,mustbe
determined and reported according to EEC Method A9. 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. Theauto-flammability ofpreparationsmustbedetermined and
reported in accordance with EEC methods 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
DangerousGoods,Chapter14,No14.3.4).
2.4. Acidity/alkalinity and if necessary pH value
2.4.1. Inthecaseofpreparationswhichareacidic (pH<4)oralkaline (pH
> 10) the acidity or alkalinity and the pH value must be determined
andreportedaccordingtoCIPACMethodMT31andMT75respec-
tively.
2.4.2. Whererelevant(iftobeappliedasaqueousdilution)thepHofa1%
aqueous dilution, emulsion or dispersion of the preparation, must bedeterminedandreportedaccordingtoCIPACMethodMT75.
2.5. Viscosity and surface tension
2.5.1. In the case of liquid preparations for Ultra Low Volume use (ULV)
thekinematic viscositymustbedeterminedandreportedaccordingto
OECDTestGuideline114.
2.5.2. For non newtonian liquids the viscosity must be determined and
reportedtogetherwiththetestconditions.
2.5.3. In the case of liquid preparations the surface tension hasto be deter-
minedandreportedaccordingtoEECmethodA5.
2.6. Relative density and bulk density
2.6.1. The relative density of liquid preparations must be determined and
reportedaccordingtoEECMethodA3.
2.6.2. Thebulk(tap)densityofpreparationswhicharepowdersorgranules,
must be determined and reported according to CIPAC Methods MT
33,MT159orMT169asappropriate.
2.7. Storage — stability and shelf-life: Effects of light, temperature and
humidity on technical characteristics of the plant protection product
2.7.1. Thestabilityofthepreparationafterstoragefor14daysat54ºCmust
bedeterminedandreportedaccordingtoCIPACMethodMT46.
Other times and/or temperatures may be needed (e.g. eight weeks at
40 ºCor 12weeks at 35ºC or18 weeksat 30 ºC) ifthe preparation
isheatsensitive.
If the active substance content after the heat stability test has
decreased by more than 5 % of the initially found content, the
minimumcontentshallbedeclaredandinformationonthedegradation
productsshallbesupplied.
2.7.2. Additionally in the case of liquid preparations, the effect of low
temperatures on stability, must be determined and reported according
toCIPACMethodsMT39,MT48,MT51orMT54asappropriate.
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,withappropriatetemperaturespecifications,mustbereported.
UsefulinformationisgiveninGIFAPMonographNo.17.
2.8. Technical characteristics of the plant protection product
Thetechnicalcharacteristicsofthepreparationmustbedeterminedto
permitadecisiontobemadeastoitsacceptability.
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
accordingtoCIPACMethodMT53.3.1991L0414—EN—01.01.2002—004.001—96
▼M2
2.8.2. Persistent foaming
The persistence of foaming of preparations to be diluted with water,
mustbedeterminedandreportedaccordingtoCIPACMethodMT47.
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
MT15,MT161orMT168asappropriate.
— The spontaneity of dispersion of water dispersible products (e.g.
suspension concentrates and water dispersible granules) must be
determinedandreportedaccordingtoCIPACMethodsMT160or
MT174asappropriate.
2.8.4. Dilution stability
The dilution stability of water soluble products must be determined
andreportedaccordingtoCIPACMethodMT41.
2.8.5. Dry sieve test and wet sieve test
In order to ensure that dustable powders have a suitable particle size
distributionforeaseofapplication,adrysievetestmustbeconducted
andreportedaccordingtoCIPACMethodMT59.1.
In the case of water dispersible products, a wet sieve test must be
conductedandreportedaccordingtoCIPACMethodMT59.3orMT
167asappropriate.
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
determinedandreportedaccordingtoOECDMethod110.
The nominal size range of granules for direct application must be
determined and reported in accordance with CIPAC MT 58.3, for
waterdispersiblegranulesinaccordancewithCIPACMT170.
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
accordingtoOECDMethod110.
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
togetherwiththemethodused.
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
accordingtoCIPACMethodsMT36orMT173asappropriate.
2.8.7.2. Thestabilityofdiluteemulsionsandofpreparationswhichareemul-
sions, must be determined and reported according to CIPAC Method
MT20orMT173.
2.8.8. Flowability, pourability (rinsability) and dustability
2.8.8.1. The flowability of granular preparations must be determined and
reportedaccordingtoCIPACMehtodMT172.
2.8.8.2. Thepourability(includingrinsedresidue)ofsuspensions(e.g.suspen-
sionconcentrates, suspo-emulsions),mustbedetermined andreported
accordingtoCIPACMethodMT148.
2.8.8.3. The dustability of dustable powders following accelerated storage
according2.7.1mustbedeterminedandreportedaccordingtoCIPAC
MethodMT34oranothersuitablemethod.1991L0414—EN—01.01.2002—004.001—97
▼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-housetestmethods.Apracticaltestwouldbeanacceptablealterna-tive.
2.9.2. The chemical compatibility of tank mixes must be determined and
reported except whereexamination oftheindividual propertiesofthe
preparationswouldestablishbeyondreasonabledoubtthatthereisno
possibility of reaction taking place. In such cases it is sufficient to
providethatinformationasjustificationfornotpracticallydetermining
thechemicalcompatibility.
2.10. Adherence and distribution to seeds
In the case of preparations for seed treatment, both distribution and
adhesionmustbeinvestigatedandreported;inthecaseofdistribution
accordingtoCIPACMethodMT175.
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
Thefield(s)ofuse,existingandproposed,forpreparationscontaining
theactivesubstancemustbespecifiedfromamongthefollowing:
— fielduse,suchasagriculture,horticulture,forestryandviticulture,
— protectedcrops,
— amenity,
— weedcontrolonnon-cultivatedareas,
— homegardening,
— houseplants,— plantproductsstoragepractice,
— other(specify).
3.2. Effects on harmful organisms, e.g. contact, inhalation or stomach
poison, fungitoxic or fungistatic, etc., systemic or not in plants
Thenatureoftheeffectsonharmfulorganismsmustbestated:
— contactaction,
— stomachaction,— inhalationaction,
— fungitoxicaction,
— fungistaticaction,
— desiccant,
— reproductioninhibitor,
— other(mustbespecified).
Itmustbestatedwhetherornottheproductistranslocatedinplants.
3.3. Details of intended use e.g. types of harmful organisms controlled and/
or plants or plant products to be protected
Detailsoftheintendedusemustbeprovided.Whererelevant,effectsachievede.g.sproutsuppression,retardationof
ripening,reduction instemlength,enhancedfertilization etc.mustbe
reported.
3.4. Application rate
For each method of application and each use, the rate of application
per unit (ha, m
2,m3) treated, in terms of g or kg of both preparation
andactivesubstance,mustbeprovided.
Applicationratesshallnormallybeexpressedingorkg/haorinkg/m3
andwhereappropriateingorkg/tonne;forprotectedcropsandhome
gardeninguseratesshallbeexpressedingorkg/100m2orgorkg/m3.1991L0414—EN—01.01.2002—004.001—98
▼M2
3.5. Concentration of active substance in material used (e.g. in the diluted
spray, baits or treated seed)
Thecontentofactivesubstanceshallbereported,asappropriate,ing/
l,g/kg,mg/kgoring/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
andvolumeofdiluenttobeusedperunitofareaorvolume.
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,indays,mustbestated.
The duration of protection afforded both by each application and by
themaximumnumberofapplicationstobeused,mustbeindicated.
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
followfromthedataprovidedunderparagraph6.6.
Limitationsonchoiceofsucceedingcrops,ifany,mustbestated.
3.9. Proposed instructions for use
Theproposedinstructionsforuseofthepreparation, tobeprinted on
labelsandleaflets,mustbeprovided.
4.Furtherinformationontheplantprotectionproduct
4.1. Packaging (type, materials, size etc.), compatibility of the preparation
with proposed packaging materials
4.1.1. Packagingtobeusedmustbefullydescribedandspecifiedintermsof
thematerialsused,mannerofconstruction(e.g.extruded,weldedetc.),
sizeandcapacity,sizeofopening,typeofclosureandseals.Itmustbe
designedinaccordancewiththecriteriaandguidelinesspecifiedinthe
FAO‘GuidelinesforthePackagingofPesticides’.
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
Methodsforintermediate bulkcontainers,and,wherefortheprepara-
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
reportedaccordingtoGIFAPMonographNo17.
4.2. Procedures for cleaning application equipment
Cleaning procedures for both application equipment and protective
clothingmustbedescribedindetail.Theeffectivenessofthecleaning
procedure,mustbefullyinvestigatedandreported.
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
sections7and8.
4.3.1. Where relevant pre-harvest intervals, re-entry periods or withholding
periodsnecessarytominimizethepresenceofresiduesinoroncrops,
plantsandplantproducts,orintreatedareasorspaces,withaviewto
protectingmanorlivestock,mustbespecifiede.g.:
— pre-harvestinterval(indays)foreachrelevantcrop,1991L0414—EN—01.01.2002—004.001—99
▼M2
— re-entryperiod(indays)forlivestock,toareastobegrazed,
— re-entry period (in hours or days) for man to crops, buildings or
spacestreated,
— withholdingperiod(indays)foranimalfeedingstuffs,— waitingperiod(indays),betweenapplicationandhandlingtreated
products,or
— waiting period (in days), between last application and sowing or
plantingsucceedingcrops.
4.3.2. Where necessary, in the light of the test results, information on any
specific agricultural, plant health or environmental conditions under
whichthepreparationmayormaynotbeusedmustbeprovided.
4.4. Recommended methods and precautions concerning: handling,
storage, transport or fire
The recommended methods and precautions concerning handling
procedures(detailed)forthestorage,atbothwarehouseanduserlevel
ofplantprotectionproducts,fortheirtransportandintheeventoffire
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-
oversmustbeprovided.
Where relevant assessment has to be done according to ISO — TR
9122.
Whereappropriatethenatureandcharacteristicsofprotectiveclothing
andequipmentproposedmustbeprovided.Thedataprovidedmustbe
sufficient to evaluate the suitability and effectiveness under realistic
conditionsofuse(e.g.fieldorglasshousecircumstances).
4.5. Emergency measures in the case of an accident
Whetherarisingduringtransport,storageoruse,detailedproceduresto
be followed in the event of an emergency, must be provided; and
include:
— containmentofspillages,
— decontaminationofareas,vehiclesandbuildings,— disposalofdamagedpackaging,adsorbentsandothermaterials,
— protectionofemergencyworkersandbystanders,
— firstaidmeasures.
4.6. Procedures for destruction or decontamination of the plant protection
product and its packaging
Proceduresfordestructionanddecontaminationmustbedevelopedfor
both small quantities (user level) and large quantities (warehouse
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
disposalfeasible.
4.6.1. Possibility of neutralization
Neutralization procedures (e.g by reaction with alkali to formless
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
Inmanycasesthepreferredorsolemeanstosafelydisposeofactive
substancesaswellasplantprotectionproductscontainingit,contami-
nated materials, or contaminated packaging, is through controlled
incinerationinalincensedincinerator.
Where the content of halogens of the active substance(s) in the
preparationisgreaterthan60%,thepyrolyticbehaviouroftheactive
substanceundercontrolledconditions(includingwhererelevantsupply
of oxygen and defined residence time) at 800 ºC and the content of
polyhalogenateddibenzo-p-dioxinsanddibenzo-furansintheproducts1991L0414—EN—01.01.2002—004.001—100
▼M2
of pyrolysis must be reported. The applicant must provide detailed
instructionsforsafedisposal.
4.6.3. Others
Othermethodstodisposeofplantprotectionproducts,packagingand
contaminatedmaterials,whereproposed,mustbefullydescribed.Data
mustbeprovidedforsuchmethods,toestablishtheireffectivenessand
safety.
5.Analyticalmethods
Introduction
The provisionsof this section onlycover analytical methods required
forpost-registrationcontrolandmonitoringpurposes.
Foranalytical methodsusedforgeneration ofdataasrequired inthis
Directiveorforotherpurposestheapplicanthastoprovideajustifica-
tion for the method used; where necessary separate guidance will be
developedforsuchmethodsonthebasisofthesamerequirements as
defined for methods for post-registration control and monitoring
purposes.
Descriptions of methods must be provided and include details of
equipment,materialsandconditionsused.
As far as practicable these methods must employ the simplest
approach,involvetheminimumcost,andrequirecommonlyavailable
equipment.
Forthissectionthefollowingapplies:
Impurities Anycomponentotherthanthepureactive
substancewhichispresentintheactive
substanceasmanufactured(includingnon-
activeisomers)originatingfromthemanu-
facturingprocessorfromdegradationduring
storage
Relevantimpurities Impuritiesoftoxicologicaland/orecotoxico-
logicalorenvironmentalconcern
Metabolites Metabolitesincludeproductsresultingfrom
degradationorreactionoftheactive
substance
Relevantmetabolites Metabolitesoftoxicologicaland/orecotoxi-
cologicalorenvironmentalconcern
Onrequestthefollowingsamplesmustbeprovided:
(i) samplesofthepreparation;
(ii) analyticalstandardsofthepureactivesubstance;
(iii) samplesoftheactivesubstanceasmanufactured;
(iv) analytical standardsofrelevant metabolites andall othercompo-
nentsincludedintheresiduedefinition;
(v) if available, samples of reference substances for the relevant
impurities.
FordefinitionsseeAnnexII,Section4,points4.1and4.2.
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.Ifacombinedmethodisnotsubmitted,thetechnicalreasons
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
suchthat—onthebasisoftheoretical consideration—suchimpuri-
tiesmaybeformedbyitsmanufacturing processorfromdegradation
duringstorage.1991L0414—EN—01.01.2002—004.001—101
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If required, methods for the determination of formulants or constitu-
entsofformulantsinthepreparationmustbesubmitted.
5.1.3. Specificity,linearity,accuracyandrepeatability5.1.3.1. Specificityofmethodssubmitted,mustbedemonstratedandreported.
Inadditiontheextentofinterferencebyothersubstancespresentinthe
preparationmustbedetermined.
While interferences due to other components may be identified as
systematic errors in the assessment of the accuracy of methods
proposed,anexplanationmustbeprovidedforanyinterferenceoccur-
ring which contribute more than ± 3 % to the total quantity
determined.
5.1.3.2. Thelinearityofproposedmethodsoveranappropriaterange,mustbe
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
determinationsmustbemadeatthreeormoreconcentrations.Alterna-
tively, five concentrations, each as single measurements, are
acceptable.Reportssubmittedmustincludetheequationofthecalibra-
tion line and the correlation coefficient and representative and
properly labelled documentation from the analysis, e.g. chromato-
grams.
5.1.3.3. Accuracywillnormallyonlyberequiredformethodsforthedetermi-
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
thereasonfortheoccurrenceofindividualoutliers,mustbeattempted.
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
beapplied.
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 mustbe possible
toevaluatethenatureandextentofbenefitsthataccruefollowinguse
of the preparation, where they exist in comparison to suitable refer-
ence products and damage thresholds, and to define its conditions of
use.
Thenumberoftrialstobeconductedandreporteddependsmainlyon
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
typeofplantprotectionproduct.
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
istoberecommended.Whereanapplicantclaimsthattestsinoneor
more of the proposed regions of use are unnecessary because condi-
tions are comparable with those in other regions where tests have
beencarriedout,theapplicantmustsubstantiatetheclaimforcompar-
abilitywithdocumentaryevidence.
Inordertoassessseasonaldifferences,ifany,sufficientdatamustbe
generated and submitted to confirm the performance of the plant
protection product in each agronomically and climatically different
region for each particular crop (or commodity)/harmful organism1991L0414—EN—01.01.2002—004.001—102
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combination. Normally trials on effectiveness or phytotoxicity, where
relevant,inatleasttwogrowingseasonsmustbereported.
If to the opinion of the applicant the trials fromthe first season
adequately confirm thevalidity ofclaimsmadeonthebasisofextra-
polationofresultsfromothercrops,commoditiesorsituationsorfrom
testswithcloselysimilarpreparations, ajustification, whichisaccep-
tabletothecompetentauthorityfornotcarryingoutasecondseaons's
work must be provided. Conversely, where, because of climatic or
planthealthconditionsorotherreasonsthedataobtainedinanyparti-
cular season are of limited value for the assessment of performance,
trialsinoneormorefurtherseasonsmustbeconductedandreported.
6.1. Preliminary tests
Reports in summary form of preliminary tests, including glasshouse
andfieldstudies,usedtoassessthebiologicalactivityanddoserange
findingoftheplantprotectionproductandoftheactivesubstance(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.
Wherethisinformationisnotsubmittedajustificationwhichisaccep-
tabletothecompetentauthoritymustbeprovided.
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
suitablereferenceproducts,wheretheyexist.
Test conditions
Normally a trial consists of three components: test product, reference
productanduntreatedcontrol.
Theperformance oftheplantprotection productmustbeinvestigated
inrelationtosuitablereferenceproducts,wheretheyexist.Asuitable
reference productisdefinedasanauthorized plantprotection product
whichhasprovedasufficientperformance inpractice undertheagri-
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
levelcausingorknowntocauseadverseeffects(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
productcanbemade.
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
forwhichclaimsaremade.Trialsmustincludethedifferentstagesof
growthoflifecycleoftheharmfulspecies,wherethisisrelevantand
thedifferent strainsorraces,wheretheseare likely toshowdifferent
degreesofsusceptibility.
Similarly,trialstoprovidedataonplantprotectionproductswhichare
plantgrowthregulators,musthowthelevelofeffectsonthespeciesto
betreated,andincludeinvestigationofdifferencesintheresponseofa
representative sample of the range of cultivars on which its use is
proposed.
Inordertoclarifythedoseresponse,doserateslowerthantherecom-
mended one must be included in some trials in order to enable to
assess whether the recommended rate is the minimum necessary to
achievethedesiredeffect.
The duration of the effects of treatment must be investigated in rela-
tiontothecontrolofthetargetorganismoreffectonthetreatedplants
or plant products, as appropriate. When more than one application is
recommended, trials mustbereported whichestablishthe duration of1991L0414—EN—01.01.2002—004.001—103
▼M1
theeffectsofanapplication,thenumberofapplicationsnecessaryand
thedesiredintervalsbetweenthem.
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
tobeencounteredinpracticaluse.
Unless there are clear indications that the performance of the plant
protectionproductionisunlikelytobeaffectedtoasignificantdegree
by environemental factors, such as 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
chemicallyrelatedproductsossoaffected.
Where proposedlabel claims include recommendations fortheuseof
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
Trialsmustbedesignedtoinvestigatespecifiedissues,tominimizethe
effectsofrandomvariationbetweendifferentpartsofeachsiteandto
enable statistical analysis to be applied to results amenable to such
analysis.Thedesign,analysisandreportingoftrialsmustbeinaccor-
dancewithEuropeanandMediterraneanPlantProtectionOrganization
(EPPO) guidelines 152 and 181. The report shall include a detailed
andcriticalassessmentofthedata.
The trials mustbe carried out in accordance to specific EPPOguide-
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
therequirementsofthecorrespondingEPPOguideline.
A statistical analysis of results amenable to such analysis must be
carried out; where necessary the test guideline used must be adapted
toenablesuchanalysis.
6.3. Information on the occurrence or possible occurrence of
thedevelopmentofresistance
Laboratory data and where it exists, field information relating to the
occurrenceanddevelopmentofresistanceorcross-resistanceinpopu-
lations of harmful organisms to the active substance(s), or to related
actived substances, must be provided. Where such information is not
directly relevant totheusesforwhichauthorization isoughtortobe
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.
Wherethereisevidenceorinformationtosuggestthat,incommercial
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
termsofquantityand/orquality
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
possibleoccurrenceoftaintorodourorotherqualityaspectsofplants
orplantproductsaftertreatmentwiththeplantprotectionproduct.
Circumstances in which requiredThepossibilityoftheoccurrenceoftaintorodourinfoodcropsmust
beinvestigatedandbereportedwhere:
— the nature of the products or its use is such that a risk of occur-
renceoftaintorodourmightbeexpected,
or1991L0414—EN—01.01.2002—004.001—104
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— otherproductsbasedonthesameoracloselysimilaractiveingre-
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
adverseinfluenceonotherqualityaspects(forexampleinthecase
ofuseofplantgrowthregulatorscloseorharvest),or
— otherproductsbasedonthesameoracloselysimilaractiveingre-
dienthavebeenshowntohaveanadverseinfluenceonthequality.
Testingshouldbeconductedinitially onthemaincropsonwhichthe
plant protection product is to be used, at twice the normal rates of
applicationandusing,whererelevant,themainmethodsofprocessing.
Where effects are observed it is necessary to performtesting at the
normalrateofapplication.
The extent of investigation necessary on other crops will depend on
theirdegreeofsimilarityofthemaincropsalreadytested,thequantity
and quality of data available on those main crops and how far the
mannerofuseoftheplantprotectionproductandmethodsofproces-
singthecrops,aresimilar.Itisgenerallysufficienttoperformthetest
withthemainformulationtypetobeauthorized.
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 with the plant
protection product on transformation processes or on the quality of
theirproducts.
Circumstances in which requiredWhen the treated plants or plant products are normally intended for
useintransformationprocesssuchaswinemaking,brewingorbread
makingandwhenatharvestsignificantresiduesarepresent,thepossi-bility of the occurrence of adverse effects must be investigated and
reportedwhere:
— 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
toharvest),
or
— otherproductsbasedonthesameoracloselysimilaractiveingre-
dient have been shown to have an adverse influence on these
processesoritsproducts.
Itisgenerallysufficienttoperformthetestwiththemainformulation
typetobeauthorized.
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
performanceoftheplantprotectionproductandofpossibleoccurrence
ofyieldreductionorlossinstorageoftreatedplantsorplantproducts.
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.
Whentreatedplantsorplantproductsarelikelytobestoredtheeffect
ontheyieldafterstorage,includingdataonstaragelifemustbedeter-
minedwhererelevant.
This information will normally be available from the tests required
undertheprovisionsofpoint6.2.1991L0414—EN—01.01.2002—004.001—105
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6.5. Phytotoxicity to target plants (including different culti-
vars),ortotargetplantproducts
Aim of the tests
The test shall provide sufficient data to permit an evaluation of the
performanceoftheplantprotectionproductandofthepossibleoccur-
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-
mediateapplicationratemustalsobeinvestigated.
Where adverse effects occur, but are claimed to be unimportant in
comparison with the 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,
includingeffectsofcropgrowhstage,vigour,andotherfactorswhich
mayinfluencesuspectibilitytodamageorinjury.
The extent of investigation necessary on other crops will depend on
theirdegreeofsimilaritytothemaincropsalreadytested,thequantity
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.
Itisgenerallysufficienttoperformthetestwiththemainformulation
typetobeauthorized.
Where proposedlabel claims include recommendations fortheuseof
theplantprotectionproductwithotherplantprotectionproduct(s),the
provisionsofthepreviousparagraphsapplyforthemixture.
Test guideline
Observationsconcerning phytotoxicity mustbeperformed inthetests
providedforunderpoint6.2.
Where phytotoxic effects are seen, they must be accurately assessed
and recorded in accordance with EPPO guideline 135 or when a
MemberStaterequiressoandwhenthetestiscarriedoutontheterri-
tory of this Member State, with guidelines satisfying at least the
requirementsofthisEPPOguideline.
A statistical analysis of results amenable to such analysis must be
carried out, where necessary the test guideline used must be adapted
toenablesuchanalysis.
6.6. Observations on undesirableorunintendedside-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 with the plant protection product on
succeedingcrops.
Circumstances in which required
Wheredata,generatedinaccordancewithSection9,point9.1,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, such as straw
or organic material up to sowing or planting time of possible
succeeding crops, observations must be submitted on effects on the
normalrangeofsucceedingscrops.1991L0414—EN—01.01.2002—004.001—106
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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 with the plant protection product on
otherplants,includingadjacentcrops.
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
vapourdrift.
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 with the plant protection product on
plantsorplantproductsotbeusedforpropagation.
Circumstances in which requiredObservations must be submitted on the impact of plant protection
products on plant parts used for propagation except where the
proposedusesprecludeuseoncropsintendedforproductionofseeds,
cuttings,runnersortubersforplanting,asappropriate.
(i) forseeds—viability,germinationandvigour;
(ii) cuttings—rootingandgrowthrates;
(iii) runners—establishmentandgrowthrates;
(iv) tubers—sproutingandnormalgrowth.
Test guideline
SeedstestingshallbedoneaccordingtoISTAMethods(
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 therequirementsofthissection,shallbereported.Anyobservedenviron-
mental effects must also be reported, especially effects on wildlife
and/orbeneficialorganisms.
6.7. Summary and evaluation of data presented under 6.1 to 6.6
Asummaryofall dataandinformations providedunderpoints6.1to
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
andmeasuresnecessarytoavoidorminimizeadverseeffects.
7. Toxicologicalstudies
For proper evaluation of the toxicity of preparations sufficient infor-
mation should be available on acute toxicity, irritation and
sensitizationoftheactivesubstance.Ifpossible,additionalinformation
on mode of toxic action, toxicological profile and all other known
toxicologicalaspectsoftheactivesubstanceshouldbesubmitted.
In the context of the influence that impurities and other components
canhaveontoxicologicalbehaviour,itisessentialthatforeachstudy
submitted, a detailed description (specification) of the material used,
be provided. Tests must be conducted using the plant protection
producttobeauthorized.
7.1.Acutetoxicity
Thestudies,dataandinformation tobeprovidedandevaluated, must
be sufficient to permit the identification of effects following a single1991L0414—EN—01.01.2002—004.001—107
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Association, Seed Science and Technology ,Volume13,No2,1985.▼M4
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exposureto theplant protection product, tobe assessed,andin parti-
culartoestablish,orindicate:
— thetoxicityoftheplantprotectionproducts,
— toxicity of the plant protection product relative to the active
substance,
— thetimecourseandcharacteristicsoftheeffectwithfulldetailsof
behavioural changes and possible gross pathological findings at
post-mortem,
— wherepossiblethemodeoftoxicaction,and
— therelativehazardassociatedwiththedifferentroutesofexposure.
While the emphasis must be on estimating the toxicity ranges
involved,theinformationgeneratedmustalsopermittheplantprotec-
tionproducttobeclassifiedinaccordancewithCouncilDirective78/
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
Circumstancesinwhichrequired
An acute oral test should always be carried out unless the applicant
can justify to the satisfaction of the competent authority that Article
3.2ofCouncilDirective78/631/EECcanbeinvoked.
Testguidelines
Thetestmustbecarried outinaccordance withDirective 92/69/EEC
MethodB1orB1bis.
7.1.2. Percutaneous
CircumstancesinwhichrequiredAn acute percutaneous test should always be carried out unless the
applicant can justify to the satisfaction of the competent authority
thatArticle3.2ofCouncilDirective78/631/EECcanbeinvoked.
Testguideline
Thetestmustbecarried outinaccordance withDirective 92/69/EEC
MethodB3.
7.1.3. Inhalation
Aimofthetest
Thetestwillprovidetheinhalationtoxicitytoratsoftheplantprotec-
tionproductorofthesmokeitgenerates.
Circumstancesinwhichrequired
Thetestmustbecarriedoutwheretheplantprotectionproduct:
— isagasorliquifiedgas,
— isasmokegeneratingformulationorfumigant,— isusedwithfoggingequipment,— isavapourreleasingpreparation,
— isanaerosol,
— is a powder containing a significant proportion of particles of
diameter<50µm(>1%onaweightbasis),
— istobeappliedfromaircraftincaseswhereinhalationexposureis
relevant,
— containsanactivesubstancewithavapourpressure>1×10
−2Pa
andistobeusedinenclosedspacessuchaswarehousesorglass-
houses,
— istobeappliedinamannerwhichgeneratesasignificantpropor-
tion of particles or droplets of diameter <50 µm (> 1 % on a
weightbasis).
Testguideline
Thetestmustbecarried outinaccordance withDirective 92/69/EEC
MethodB2.1991L0414—EN—01.01.2002—004.001—108
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7.1.4. Skin irritation
Aimofthetest
Thetestwillprovidethepotentialofskinirritancyoftheplantprotec-
tion product including the potential reversibility of the effects
observed.
Circumstancesinwhichrequired
Theskinirritancyoftheplantprotection productmustbedetermined
exceptwhereitislikely,asindicatedinthetestguideline,thatsevere
skineffectsmaybeproducedorthateffectscanbeexcluded.
Testguideline
Thetestmustbecarried outinaccordance withDirective 92/69/EEC
MethodB4.
7.1.5. Eye irritation
Aimofthetest
The test will provide the protential for eye irritation of the plant
protection product, including the potential reversibility of the effects
observed.
Circumstancesinwhichrequired
Eye irritation tests must be conducted except where it is likely, as
indicated inthetestguideline,thatsevereeffectsontheeyesmaybe
produced.
Testguideline
TheeyeirritationmustbedeterminedinaccordancewithDirective92/
69/EECMethodB5.
7.1.6. Skin sensitization
Aimofthetest
The test will provide sufficient information to assess the potential of
theplantprotectionproducttoprovokeskinsensitizationreactions.
Circumstancesinwhichrequired
The tests must always be carried out except where the active
substance(s)orco-formulantsareknowntohavesensitizingproperties.
TestguidelineThe tests have to be carried out in accordance with Directive 92/69/
EECMethodB6.
7.1.7. Supplementary studies for combinations of plant protection products
Aimofthetest
Incertaincasesitmaybenecessarytocarryoutthestudiesasreferred
to under points 7.1.1 to 7.1.6 for a combination of plant protection
productswheretheproductlabelincludesrequirements foruseofthe
plant protection product with other plant protection products and/or
withadjuvantsasatankmix.Decisionsastotheneedforsupplemen-
tarystudiesmustbemadeonacasebycasebasis,takingintoaccount
theresultsoftheacute toxicitystudiesoftheindividual plantprotec-
tion products, the possibility for exposure to the combination of the
products concerned and available information or practical experience
withtheproductsconcernedorsimilarproducts.
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 of27 November 1980on the protec-
tion of workers fromthe risks related to exposure to chem ical,
physical and biological agents at work(
1) have to be taken into
account.1991L0414—EN—01.01.2002—004.001—109
(1) OJNoL327,3.12.1980,p.8.▼M9
▼M4
7.2.1. Operator exposure
The risks for those using plant protection products depend on the
physical,chemicalandtoxicological propertiesoftheplantprotection
product aswell asthe type ofthe product (undiluted/diluted), and on
theroute,thedegreeanddurationofexposure.Sufficientinformation
and data must be generated and reported to permit an assessment of
theextentofexposuretotheactivesubstance(s)and/ortoxicologically
relevant compounds in the plant protection product likely to occur
undertheproposedconditionsofuse.Itmustalsoprovideabasisfor
theselectionoftheappropriateprotectivemeasuresincludingpersonal
protective equipment to be used by operators and to be specified on
thelabel.
7.2.1.1. Estimation of operator exposure
AimoftheestimationAnestimationshallbemade,usingwhereavailableasuitablecalcula-
tion model, inorder topermit anevaluation ofthe operator exposure
likelytoariseundertheproposedconditionsofuse.
Circumstancesinwhichrequired
Anestimationofoperatorexposuremustalwaysbecompleted.
EstimationconditionsAnestimation shallbemadeforeachtypeofapplication methodand
applicationequipmentproposedforuseoftheplantprotectionproduct
taking account ofthe requirements resultingfrom the implementation
oftheclassification andlabellingprovisionsofDirective78/631/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
andcleaningandroutinemaintenanceofapplicationequipment.
At first an estimation shall be made with the assumption that the
operatorisnotusinganypersonalprotectiveequipment.
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
willtaketheseintoaccount.
7.2.1.2. Measurement of operator exposure
AimofthetestThe test shall provide sufficient data to permit an evaluation of the
operatorexposurelikelytoariseundertheproposedconditionsofuse.
Circumstancesinwhichrequired
Actual exposure data for the relevant exposure route(s) must be
reported where the risk assessment indicates that a health-based limit
valueisexceeded.Thiswill,forexample,bethecasewhentheresults
oftheestimationofoperatorexposureprovidedforunderpoint7.2.1.1
indicatethat:
— theAcceptableOperatorExposureLevel(s)(AOEL)establishedin
thecontextofinclusionoftheactivesubstance(s)inAnnexI,and/
or
— theLimitValuesestablishedfortheactivesubstanceand/ortoxico-
logically relevant compound(s) of the plant protection product in
accordance with Council Directive 80/1107/EEC and Council
Directive 90/394/EEC of 28 June 1990 on the protection of
workers fromthe risks related to exposure to carcinogens at
work(
1),
maybeexceeded.Actual exposure data must also be reported when no appropriate
calculation model or no appropriate data are available to do the esti-
mationprovidedforunderpoint7.2.1.1.1991L0414—EN—01.01.2002—004.001—110
(1) OJNoL196,26.7.1990,p.1.
▼M4
Incaseswheredermalexposureisthemostimportantexposureroute,
adermal absorptiontestortheresultsofasub-acutedermal study,if
notalready available, maybeausefulalternative testtoprovidedata
inordertorefinetheestimateprovidedforunderpoint7.2.1.1.
Testconditions
The test mustbe done underrealistic exposure conditions taking into
accounttheproposedconditionsofuse.
7.2.2. Bystander exposure
Bystanders can be exposed during the application of plant protection
products.Sufficient information anddatamustbereported toprovide
abasisfortheselectionofappropriateconditionsofuse,includingthe
exclusionofbystandersfromtreatmentareasandseparationdistances.
Aimoftheestimation
Anestimationshallbemade,usingwhereavailableasuitablecalcula-
tionmodelinordertopermitanevaluationofthebystanderexposure
likelytoariseundertheproposedconditionsofuse.
Circumstancesinwhichrequired
Anestimationofbystanderexposuremustalwaysbecompleted.
EstimationconditionsAn estimation of bystander exposure must be made for each type of
applicationmethod.Theestimationshallbemadewiththeassumption
thatbystandersdonotuseanypersonalprotectiveequipment.
Measurement of bystander exposure may be required when estimates
indicateacauseforconcern.
7.2.3. Worker exposure
Workers can be exposed following application of plant protection
products,whenentering treated fieldsorpremisesorhandlingtreated
plantsorplantproductsonwhichresiduesremain.Sufficientinforma-
tion anddata mustbereported toprovideabasisforthe selection of
appropriate protective measures, including waiting and re-entry
periods.
7.2.3.1. Estimation of worker exposure
AimoftheestimationAnestimationshallbemadeusingwhereavailableasuitablecalcula-
tion model, in order to permit an evaluation of the worker exposure
likelytoariseundertheproposedconditionsofuse.
Circumstancesinwhichrequired
Theestimationofworkerexposuremustalwaysbecompleted.Estimationconditions
An estimation of worker exposure must be made for each crop and
tasktobecarriedout.
Atfirsttheestimationshallbemadeusingavailabledataontheexpo-
sure to be expected with the assumption that the worker is not using
anypersonalprotectiveequipment.
Where appropriate, a second estimation shall be made with the
assumption that the worker is using effective and readily obtainable
protectiveequipmentwhichisfeasibletobeused.
Where appropriate, a further estimation shall be made using data
generated on the amount ofdislodgeable residues underthe proposed
conditionsofuse.
7.2.3.2. Measurement of worker exposure
AimofthetestThe test shall provide sufficient data to permit an evaluation of the
workerexposurelikelytoariseundertheproposedconditionsofuse.
CircumstancesinwhichrequiredActual 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—01.01.2002—004.001—111
▼M4
resultsoftheestimation ofworkerexposureprovidedforunderpoint
7.2.3.1indicatethat:
— the AOEL(s) established in the context of inclusion of the active
substance(s)inAnnexI,
and/or
— theLimitValuesestablishedfortheactivesubstanceand/ortoxico-
logically relevant compound(s) of the plant protection product in
accordance with Council Directives 80/1107/EEC and 90/394/
EEC,
maybeexceeded.Actual exposure data must also be reported when no appropriate
calculation model or no appropriate data are available to do the esti-
mationprovidedforunderpoint7.2.3.1.
Wheredermalexposureisthemostimportantexposureroute,adermal
absorption test, if not already available, may be a useful alternative
testtoprovidedatainordertorefinetheestimate providedforunder
point7.1.3.1.
Testconditions
The test mustbe done underrealistic exposure conditions taking into
accounttheproposedconditionsofuse.
7.3.Dermalabsorption
Aimofthetest
The test shall provide a measurement of the absorption of the active
substanceandtoxicologicallyrelevantcompoundsthroughtheskin.
CircumstancesinwhichrequiredThe 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
wheretheresultsoftheestimation ormeasurement ofoperator expo-
sureprovidedforunderpoints7.2.1.1or7.2.1.2indicatethat:
— the AOEL(s) established in the context of inclusion of the active
substance(s)inAnnexI,
and/or
— thelimitvaluesestablishedfortheactivesubstanceand/ortoxico-
logically relevant compound(s) of the plant protection product in
accordance with Council Directives 80/1107/EEC and 90/394/
EECmaybeexceeded.
Testconditions
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
performan in vivocomparative absorption study on rat and human
skin.
Testguideline
Appropriateelements ofOECDguideline 417aretobeused.Forthe
design of the studies it may be necessary to take into account the
resultsoftheskinabsorptionstudieswiththeactivesubstance(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
Directive91/155/EECof5March1991definingandlayingdownthe
detailed arrangements for the system of specific information relating
todangerouspreparations inimplementation ofArticle 10ofCouncil
Directive 88/379/EEC(
1) must be submitted for each formulant. All
otheravailableinformationshouldbesubmitted.1991L0414—EN—01.01.2002—004.001—112
(1) OJNoL76,22.3.1991,p.35.
▼M9
8. Residuesinorontreatedproducts,foodandfeed
Introduction
TheprovisionsofAnnexII,Section6,Introductionapply.
8.1.Metabolism, distribution and expression of residue in plants or
livestock
Aim of the tests
Theobjectivesofthesestudiesare:
— to provide an estimate of total terminal residues in the relevant
portionofcropsatharvestfollowingtreatmentasproposed,
— to quantify the rate of degradation and excretion of the total
residueincertainanimalproducts(milkoreggs)andexcreta,
— to identify the major components of the total terminal residue in
cropsandinedibleanimalproductsrespectively,
— toindicatethedistributionofresiduesbetweenrelevantcropparts
andbetweenrelevantedibleanimalproductsrespectively,
— to quantify the major components of the residue and to show the
efficiencyofextractionproceduresforthesecomponents,
— to generate data fromwhich a decision on the need for livestock
feedingstudiesasprovidedforinpoint8.3canbemade,
— todecideonthedefinitionandexpressionofaresidue.
Circumstances in which requiredSupplementarymetabolismstudiesonlyneedtobeperformedwhereit
is not possible to extrapolate fromdata 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
expectedthatadifferentmetabolismwilloccur.
Test conditionsThe same provisions as provided under the corresponding paragraphs
ofAnnexII,Section6,points6.1and6.2apply.
8.2.Residuetrials
Aim of the tests
Theobjectivesofthesestudiesare:
— to quantify the highest likely residue levels in treated crops at
harvestoroutloadingfromstorefollowingtheproposedgoodagri-
culturalpractice(GAP),
and
— to determine, when appropriate, the rate of decline of pesticide
deposits.
Circumstances in which required
Supplementaryresiduetrialsonlyneedtobeperformedwhereitisnot
possible to extrapolate fromdata obtained on the active substance in
accordance to the requirements of Annex II, Section 6, point 6.3.
Thismightbethecaseforspecialformulations,forspecialapplication
methodsorforcropsforwhichdatawerenotsubmittedintheframe-
work of inclusion of the active substance in Annex I or were not
necessaryforamendingtheconditionsofitsinclusioninAnnexI.
Test conditionsThe same provisions as provided under the corresponding paragraphs
ofAnnexII,Section6,point6.3apply.
8.3.Livestockfeedingstudies
Aim of the tests
The objective of these studies isto determine the residue in products
of animal origin which will result from residues in feedingstuffs or
foddercrops.1991L0414—EN—01.01.2002—004.001—113
▼M9
Circumstances in which required
Supplementaryfeedingstudiesforthepurposeofassessingmaximum
residuelevelsforproductsofanimaloriginareonlyrequiredwhereit
is not possible to extrapolate fromdata 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
tobeauthorizedwhichleadstoanincreasedintakeofresiduesoflive-
stockforwhichdatawerenotsubmittedintheframeworkofinclusion
oftheactivesubstanceinAnnexIorwerenotnecessaryforamending
theconditionsofitsinclusioninAnnexI.
Test conditions
The same provisions as provided under the corresponding paragraphs
ofAnnexII,Section6,point6.4apply.
8.4.Effectsofindustrialprocessingand/orhouseholdpreparations
Aim of the testsThemainobjectivesofthesestudiesare:
— to establish whether or not breakdown or reaction products arise
fromresidues in the raw products during processing which m ay
requireaseparateriskassessment,
— todeterminethequantitativedistributionofresiduesinthevarious
intermediateandendproducts,andtoestimatetransferfactors,
— toenableamorerealisticestimatetobemadeofdietaryintakeof
residues.
Circumstances in which requiredSupplementary studies only need to be performed where it is not
possible to extrapolate fromdata 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
AnnexI.
Test conditions
The same provisions as provided under the corresponding paragraphs
ofAnnexII,Section6,point6.5apply.
8.5.Residuesinsucceedingcrops
Aim of the test
The objective of these studies is to permit an evaluation of possible
residuesinsucceedingcrops.
Circumstances in which required
Supplementary studies are only required where it is not possible to
extrapolate fromdata 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
forcropsforwhichdatawerenotsubmittedintheframeworkofinclu-
sion of the active substance in Annex I or were not necessary for
amendingtheconditionsofitsinclusioninAnnexI.
Test conditions
The same provisions as provided under the corresponding paragraphs
ofAnnexII,Section6,point6.6apply.
8.6.Proposedmaximumresiduelevels(MRLs)andresiduedefinition
A full justification for the proposed MRLs must be provided,
including,whererelevant,fulldetailsofthestatisticalanalysisused.
Ifthemetabolismstudiessubmittedinaccordancewiththeprovisions
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
benecessary.1991L0414—EN—01.01.2002—004.001—114
▼M9
8.7.Proposed pre-harvest intervals for envisaged uses, or withholding
periodsorstorageperiods,inthecaseofpost-harvestuses.
Afulljustificationfortheproposalsmustbeprovided.
8.8.Estimation of the potential and actual exposure through diet and
othermeans
Considerationwillbegiventothecalculation ofarealistic prediction
ofdietary intake. Thismaybedoneinastep-wisefashionleading to
an increasingly realistic prediction of intake. Where relevant, other
sourcesofexposuresuchasresiduesarisingfromtheuseofmedicines
orveterinarydrugshavetobetakenintoaccount.
8.9.Summaryandevaluationofresiduebehaviour
AsummaryandevaluationofalldatapresentedinthisSectionshould
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
assessmentofthosedatainthecontextofrelevantevaluativeanddeci-
sion-making criteria and guidelines, with particular reference to the
risksformanandanimalsthatmayordoarise,andtheextent,quality
andreliabilityofthedatabase.
Wheremetabolismdatahavebeensubmittedthetoxicologicalsignifi-
canceofanynon-mammalianmetabolitesmustbeaddressed.
Aschematicdiagramshouldbepreparedofthemetabolic pathwayin
plants and animals with a brief explanation of the distribution and
chemicalchangesinvolvedifmetabolismdatahavebeensubmitted.
9.Fateandbehaviourintheenvironment
Introduction
(i) Theinformationprovided,takentogetherwiththatfortheactive
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
specieslikelytobeatriskfromexposuretoit.
(ii) In particular, the information provided for the plant protection
product, together with other relevant information, and that
providedfortheactivesubstance,shouldbesufficientto:
— specify the hazard symbols, the indications of danger, and
relevantriskandsafetyphrasesfortheprotectionoftheenvir-
onment,whicharetobeincludedonpackaging(containers),
— predict the distribution, fate, and behaviour in the environ-
mentaswellasthetimecoursesinvolved,
— identifynon-targetspeciesandpopulationsforwhichhazards
arisebecauseofpotentialexposure,and
— identifymeasuresnecessarytominimizecontaminationofthe
environmentandimpactonnon-targetspecies.
(iii) Where radio-labelled test material is used, the provisions of
AnnexII,Chapter7,introduction,point(iv)apply.
(iv) Whererelevanttestsshouldbedesignedanddataanalysedusing
appropriatestatisticalmethods.
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
(PECSWandPECGW)andair(PECA).
Justified estimates must be made of the expected concentrations
oftheactivesubstanceandrelevantmetabolites,degradationand
reaction products, in soil, groundwater, surface water and air,
following use as proposed or already occurring. In addition a
realisticworst-caseestimationmustbemade.
For the purposes of the estimation of such concentrations the
followingdefinitionsapply:
—Predicted environmental concentration in soil (PECS)
Thelevelofresiduesinthetoplayerofthesoilandtowhich
non-targetsoilorganismsmaybeexposed(acuteandchronic
exposure).1991L0414—EN—01.01.2002—004.001—115
▼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)
Thelevelofresiduesingroundwater.
—Predicted environmental concentration in air (PECA)
Thelevelofresiduesinair,towhichman,animalsandother
non-target organisms may be exposed (acute and chronic
exposure).
Fortheestimationoftheseconcentrationsallrelevantinformation
ontheplantprotectionproductandontheactive substancemust
betakenintoaccount.Ausefulapproachfortheseestimationsis
provided in the EPPO schemes for environmental risk assess-
ment(1). Where relevant the parameters provided for in this
sectionshouldbeused.
Whenmodelsareusedforestimationofpredictedenvironmental
concentrationstheymust:
— make a best-possible estimation of all relevant processes
involvedtakingintoaccountrealisticparametersandassump-
tions,
— where possible be reliably validated with measurements
carried out under circumstances relevant for the use of the
model,
— berelevanttotheconditionsintheareaofuse.
The information provided must, where relevant, include that referred
toinAnnexII,PartA,point7:and
9.1Fateandbehaviourinsoil
Where appropriate, the same provisionsrelating to theinformation to
beprovidedonthesoilusedandonitsselectionapplyasprovidedfor
underAnnexII,point7.1.
9.1.1. Rate of degradation in soil
9.1.1.1. Laboratorystudies
AimofthetestThesoildegradationstudiesshouldprovidebestpossibleestimatesof
thetimetakenfordegradationof50and90%(DT
50labandDT90lab)of
theactivesubstanceunderlaboratoryconditions.
CircumstancesinwhichrequiredThe persistence and behaviour of plant protection products in soil
must be investigated unless it is possible to extrapolate from data
obtainedontheactivesubstanceandrelevantmetabolites,degradation
and reaction products in accordance to the requirements of Annex II,
point7.1.1.2.Thisextrapolationis,forexample,notpossibleforslow
releaseformulations.
TestconditionsThe 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%oftheactivesubstanceisdegradedbeforethatperiodexpires.
TestguidelineSETAC — Procedures for assessing the environmental fate and
ecotoxicityofpesticides.
9.1.1.2. Fieldstudies
— Soildissipationstudies
Aimofthetest1991L0414—EN—01.01.2002—004.001—116
(1) OEPP/EPPO (1993). Decision-making schemes for the environmental risk assessment
ofplant protection products.Bulletin OEPP/EPPOBulletin23,1-154andBulletin 24,
1-87.
▼M6
Thesoil dissipationstudiesshouldprovidebest-possibleestimates
ofthetimetakenfordissipationof50and90%(DT50fandDT90f),
of the active substance under field conditions. Where relevant,
information on relevant metabolites, degradation and reaction
productsmustbecollected.
Circumstancesinwhichrequired
The dissipation and behaviour of plant protection products in soil
mustbe investigated unlessit is possible toextrapolate from data
obtainedontheactivesubstanceandrelevantmetabolites,degrada-
tion and reaction products in accordance to the requirements of
Annex II, point 7.1.1.2. This extrapolation is, for example, not
possibleforslow-releaseformulations.
Testconditionsandtestguideline
The same provisions as provided under the corresponding para-
graphofAnnexII,point7.1.1.2.2.apply.
— Soilresiduestudies
Aimofthetest
Soil residue studies should provide estimates of the soil residue
levelsatharvestorattimeofsowingorplantingsucceedingcrops.
Circumstancesinwhichrequired
Soilresiduestudiesmustbereportedunlessitispossibletoextra-
polate fromdata obtained on the active substance and relevant
metabolites, degradation andreaction productsinaccordance with
therequirementsofAnnexII,point7.1.1.2.2.Thisextrapolationis,
forexample,notpossibleforslow-releaseformulations.
TestconditionsThe same provisions as provided under the corresponding para-
graphofAnnexII,point7.1.1.2.2.apply.
Testguideline
SETAC — Procedures for assessing the environmental fate and
ecotoxicityofpesticides.
— Soilaccumulationstudies
Aimofthetests
Thetestsshouldprovidesufficient datatoevaluate thepossibility
ofaccumulationofresiduesoftheactivesubstanceandofrelevant
metabolites,degradationandreactionproducts.
CircumstancesinwhichrequiredSoilaccumulationstudiesmustbereportedunlessitispossibleto
extrapolatefromdataobtainedontheactivesubstanceandrelevant
metabolites, degradation andreaction productsinaccordance with
therequirementsofAnnexII,point7.1.1.2.2.Thisextrapolationis,
forexample,notpossibleforslow-releaseformulations.
Testconditions
The same provisions as provided under the corresponding para-
graphofAnnexII,point7.1.1.2.2.apply.
Testguideline
SETAC — Procedures for assessing the environmental fate and
ecotoxicityofpesticides.
9.1.2. Mobility in the soil
Aimofthetest
The test should provide sufficient data to evaluate the mobility and
leaching potential of the active substance and relevant metabolites,
degradationandreactionproducts.
9.1.2.1. Laboratorystudies
Circumstancesinwhichrequired
Themobilityofplantprotectionproductsinsoilmustbeinvestigated
unless it is possible to extrapolate fromdata obtained in accordance
withtherequirementsofAnnexII,points7.1.2and7.1.3.1.Thisextra-
polationis,forexample,notpossibleforslow-releaseformulations.
TestguidelineSETAC — Procedures for assessing the environmental fate and
ecotoxicityofpesticides.
9.1.2.2. Lysimeterstudiesorfieldleachingstudies
Aimofthetests1991L0414—EN—01.01.2002—004.001—117
▼M6
Thetestshouldprovidedataon:
— themobilityoftheplantprotectionproductinsoil,
— thepotentialforleachingtogroundwater,— thepotentialdistributioninsoils.
Circumstancesinwhichrequired
Expert judgement will be necessary to decide whether field leaching
studiesorlysimeter studiesshouldbecarried out,takingintoaccount
the results of degradation and mobility studies and the calculated
PEC
s. The type of study to be conducted should be discussed with
thecompetentauthorities.
These studies must be performed unless it is possible to extrapolate
fromdata obtained on the active substance and relevant m etabolites,
degradationandreactionproductsinaccordancewiththerequirements
of Annex II, point 7.1.3. This extrapolation is, for example, not
possibleforslowreleaseformulations.
Testconditions
The same provisions as provided for under the corresponding para-
graphofAnnexII,point7.1.3.3apply.
9.1.3. Estimation of expected concentrations in soil
PECsestimationsmustrelatebothtoasingleapplicationatthehighest
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
termsofmgofactivesubstanceandofrelevantmetabolites,degrada-
tionandreactionproductsperkgofsoil.
The factors to be considered in making PECsestimations relate to
direct and indirect application to soil,drift,runoff,andleaching and
includeprocessessuchasvolatilization,adsorption,hydrolysis,photo-
lysis, aerobic and anaerobic degradation. For the purposes of PECscalculations,thebulkdensityofsoilscanbeassumedtobe1,5g/cm3
dryweight,whilethedepthofthesoillayerisassumedtobe5cmfor
applications at the soil surface and 20 cmwhen incorporation in the
soilisinvolved.Wheregroundcoverispresentattimeofapplication,
itistobeassumedthat50%(minimum)oftheapplieddosereaches
the soil surface unless actual experimental data give more specific
information.
Initial, short-termand long-termPECscalculations (time weighted
averages)mustbeprovided:
— initial:immediatelyafterapplication,
— short-term:24hours,2daysand4daysafterlastapplication,— 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
(includingclimatic)conditions.
Suitableestimations(calculations)ofpredictedenvironmentalconcen-
tration in groundwater PEC
GW, of active substance and relevant
metabolites,degradationandreactionproducts,mustbesubmitted.
PECestimationsmustrelatetothemaximumnumberandhighestrates
ofapplication,forwhichauthorizationissought.
Expert judgment is required to decide if additional field tests could
provideusefulinformation.Beforeperformingthesestudiestheappli-
cantshallseektheagreementofthecompetentauthoritiesonthetypeofstudytobeperformed.
9.2.2. Impact on water treatment procedures
In cases where this information is necessary in the framework of a
conditional authorization asmeant inAnnexVI,PartC,point 2.5.1.2
(b),theinformationprovidedshouldpermittoestablishortoestimate
effectiveness of water treatment procedures (drinking water and1991L0414—EN—01.01.2002—004.001—118
▼M6
sewagetreatment),andimpactonsuchprocedures.Beforeperforming
any studies the applicant shall seek the agreement of the competent
authoritiesonthetypeofinformationtobeprovided.
9.2.3. Estimation of concentrations in surface water
Thesurfacewatercontaminationrouteshavetobedefinedtakinginto
account relevant agricultural, plant health, and environmental
(includingclimatic)conditions.
Suitableestimations(calculations)ofpredictedenvironmentalconcen-
tration in surface water PECsw, of active substance and relevant
metabolites,degradationandreactionproducts,mustbesubmitted.
PECestimationsmustrelatetothemaximumnumberandhighestrates
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-
tationandre-suspension.
Initial, short-termand long-termPECswcalculations relevant to static
and slow moving water bodies (time weighted averages) must be
provided:
— initial:immediatelyafterapplication,
— short-term:24hours,2daysand4daysafterlastapplication,
— long-term:7,14,21,28,and42daysafterlastapplication, where
relevant.
Expert judgment is required to decide if additional field tests could
provideusefulinformation.Beforeperformingthesestudiestheappli-
cantshallseektheagreementofthecompetentauthoritiesonthetype
ofstudytobeperformed.
9.3.Fateandbehaviourinair
Guidanceunderdevelopment.
10.Ecotoxicological studies
Introduction
(i) Theinformationprovided,takentogetherwiththatfortheactive
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
fromsingle, prolonged or repeated exposure, and can be rever-
sible,orirreversible.
(ii) In particular, the information provided for the plant protection
product, together with other relevant information, and that
providedfortheactivesubstance,shouldbesufficientto:
— specify the hazard symbols, the indications of danger, and
relevant risk and safety phrases for the protection of the
environment,tobementionedonpackaging(containers),
— permit an evaluation of the short- and long-term risks for
non-target species — populations, communities, and
processesasappropriate,
— permit an evaluation of whether special precautions are
necessaryfortheprotectionofnon-targetspecies.
(iii) There is a need to report all potentially adverse effects found
during routine ecotoxicological investigations and to undertake
and report such additional studies which may be necessary to
investigatethemechanismsinvolvedandassessthesignificance
oftheseeffects.
(iv) In general, much of the data relating to impact on non-target
species, required for authorization of plant protection products,
willhavebeensubmittedandevaluated fortheinclusionofthe
active substance(s) in Annex I. The information on fate and
behaviourintheenvironment,generatedandsubmittedinaccor-
dance with points 9.1 to 9.3, and on residue levels in plants
generated and submitted in accordance with point 8 is central1991L0414—EN—01.01.2002—004.001—119
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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 with point 7.1 provide essential information as to
toxicitytovertebratespecies.
(v) Where relevant, tests should be designed and data analysed
using appropriate statistical methods. Full details of the statis-
ticalanalysisshouldbereported(e.g.allpointestimatesshould
be given with confidence intervals, exact p-values should be
givenratherthanstatingsignificant/nonsignificant).
(vi) Whenever a study implies the use of different doses, the rela-
tionshipbetweendoseandadverseeffectmustbereported.
(vii) Where exposure data are necessary to decide whether a study
has to be performed, the data obtained in accordance with the
provisionsofAnnexIII,point9shouldbeused.
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 approach for
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 fromavailable data that the plant protection
product is more toxic as the active substance, the toxicity data
of the plant protection product have to be usedfor the calcula-
tionofrelevanttoxicity/exposureratios.
(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
usedasprovidedforunderpoint1.4,beprovided.
(ix) In order to facilitate the assessment of the significance of test
resultsobtained the samestrain ofeach relevant species should
wherepossiblebeusedinthevarioustoxicitytestsspecified.
10.1.Effectsonbirds
Possibleeffectsonbirdsmustbeinvestigatedexceptwherethepossi-
bilitythatbirdswillbeexposed,directlyorindirectly,canberuledout
suchasforuseinenclosedspacesorwoundhealingtreatments.
The acute toxicity/exposure ratio (TERa), the short termdietary toxi-
city/exposure ratio (TERst) and the long termdietary toxicity/
exposureratio(TERlt)mustbereported,where:
TERa=LD50(mga.s./kgbodyweight)/ETE(mga.s./kgbodyweight)
TERst=LC50(mga.s./kgfood)/ETE(mga.s./kgfood)
TERlt=NOEC(mga.s./kgfood)/ETE(mga.s./kgfood)
whereETE=estimatedtheoreticalexposure.In the case of pellets, granules or treated seeds the amount of a.s. in
eachpellet,granuleorseedmustbereportedaswellastheproportion
oftheLD
50forthea.s.in100particlesandpergramofparticles.The
sizeandshapeofpelletsorgranulesmustbereported.
Inthecaseofbaitstheconcentration ofa.s.inthebait(mg/kg)must
bereported.
10.1.1. Acuteoraltoxicity
Aim of the test
The test should provide, where possible, LD50values, the lethal
threshold dose, time courses of response and recovery, the NOEL,
andmustincluderelevantgrosspathologicalfindings.
Circumstances in which requiredTheacute oral toxicity ofpreparations mustbereported,whereTER
aor TERstfor the active substance(s) in birds are between 10 and 1001991L0414—EN—01.01.2002—004.001—120
(1) OEPP/EPPO (1993). Decision-making schemes for the environmental risk assessment
ofplantprotection products. Bulletin OEPP/EPPO Bulletin 23, 1-154and Bulletin 24,
1-87.
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orwhereresultsfrommammaltestinggiveevidenceofasignificantly
higher toxicity of the prepration compared to the active substance
unlessitcanbejustifiedthatitisnotlikelythatbirdsareexposedto
theplantprotectionproductitself.
Test conditionsThe studymustbeconducted onthe mostsensitive species identified
inthestudiesprovidedforinAnnexII,point8.1.1or8.1.2.
10.1.2. Supervisedcageorfieldtrials
Aim of the testThe test will provide sufficient data to evaluate the nature and the
extentoftheriskinpracticalconditionsofuse.
Circumstances in which requiredWheretheTER
aandTERstare>100andwhenthereisnoevidenceof
riskfromanyfurtherstudyontheactive substance(e.g.reproduction
study) no further testing isrequired. In the other cases, expert judge-
mentisnecessarytodecidewhetherthereisaneedtocarryoutfurther
studies.Thisexpertjudgementwilltakeintoaccount,whererelevant,
foragingbehaviour,repellency,alternativefood,actualresiduecontent
in the food, persistence of the compound in the vegetation, degrada-
tion of the formulated product or treated produce, the amount of
predationofthefood,acceptanceofbait,granulesortreatedseedand
thepossibilityforbioconcentration.
WhereTERaandTERst≤10orTERlt≤5,cageorfieldtrialsmust
beconductedandreportedunlessafinalassessmentispossibleonthe
basisofstudiesaccordingtopoint10.1.3.
Test conditions
Before performing these studies the applicant should seek the agree-
ment of the competent authorities on the type and conditions of the
studytobeperformed.
10.1.3. Acceptanceofbait,granulesortreatedseedsbybirds
Aim of the testThe test will provide sufficient data to evaluate the possibility of
consumptionoftheprotectionproductorplantproductstreatedwithit.
Circumstances in which requiredInthecaseofseeddressings,pellets,baitsandpreparationswhichare
granulesandwhereTER
a≤10,acceptability (palatability) testsmust
beconducted.
10.1.4. Effectsofsecondarypoisoning
Expertjudgmentisrequiredtodecidewhethertheeffectsofsecondary
poisoningshouldbeinvestigated.
10.2.Effectsonaquaticorganisms
Possibleeffectsonaquatic speciesmustbeinvestigated exceptwhere
thepossibilitythataquaticspecieswillbeexposedcanberuledout.
TERaandTERltmustbereported,where:
TERa= acute LC50(mg a.s./l)/realistic worst case PECsw(initial or
short-term,inmga.s./l)
TERlt=chronicNOEC(mga.s./l)/longtermPECsw(mga.s./l)
10.2.1. Acutetoxicitytofish,aquaticinvertebratesoreffectsonalgalgrowth
Circumstances in which requiredInprincipletestsshouldbecarriedoutononespeciesfromeachofthe
threegroupsofaquaticorganismsasreferredtoinAnnexII,point8.2
(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
moresensitive,testsononlythemostsensitivespeciesoftherelevant
grouphavetobeperformed.
Thetestmustbeperformedwhere:
— the acute toxicity of the plant protection product can not be
predicted on the basis of the data for the active substance which1991L0414—EN—01.01.2002—004.001—121
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is especially the case if the formulation contains two or more
active substances or formulants such as solvents, emulgators,
surfactants, dispersants, fertilizers which are able to increase the
toxicityincomparisonwiththeactivesubstance,or
— theintendeduseincludesdirectapplicationonwater
unlesssuitablestudiesreferredtounderpoint10.2.4areavailable.
Test conditions and test guidelines
The relevant provisions as under the corresponding paragraphs of
AnnexII,points8.2.1,8.2.4and8.2.6apply.
10.2.2. Microcosmormesocomstudy
Aim of the test
Thetestsmustprovidesufficientdatatoevaluatetheessentialimpact
onaquaticorganismsunderfieldconditions.
Circumstances in which required
Where TERa≤100 or where TERlt≤10, expert judgment must be
usedtodecidewhetheramicrocosmormesocomstudyisappropriate.
Thisjudgmentwilltakeintoaccounttheresultsofanyadditionaldata
overandabovethoserequiredbytheprovisionsofAnnexII,point8.2
andofpoint10.2.1.
Test conditions
Beforeperformingthesestudiestheapplicantshallseektheagreement
of the competent authorities on the specific aims of the study to be
performed and consequently on the type and conditions of the study
tobeperformed.
The study should include at least the highest likely exposure rate,
whether fromdirect applicaiton, drift, drainage or run-off. The dura-
tionofthestudymustbesufficienttopermitevaluationofalleffects.
Test guideline
Appropriateguidelinesareincludedin:
Setac — Guidance document on testing procedures for pesticides in
freshwatermesocosms/WorkshopHuntingdon,3and4July1991
or
Freshwaterfieldtestsforhazardassessmentofchemicals—European
WorkshoponFreshwaterFieldTests(EWOFFT).
10.2.3. Residuedatainfish
Aim of the testThetestwillprovidesufficientdatatoevaluatethepotentialforoccur-
renceofresiduesinfish.
Circumstances in which required
Ingeneraldataareavailablefrombioconcentrationstudiesinfish.
Where bioconcentration has been observed in the study performed in
accordancewithAnnexII,point8.2.3expertjudgementisrequiredto
decide whether a long-term microcosm or mesocosm study has to be
carried out in order to establish the maximum residues likely to be
encountered.
Test guideline
Setac — Guidance document on testing procedures for pesticides in
freshwatermesocosms/WorkshopHuntingdon,3and4July1991.
10.2.4. Additionalstudies
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
possibletoextrapolatefromdataobtainedinthecorrespondingstudies
ontheactivesubstance.
10.3.Effectsonterrestrial vertebratesotherthanbirds
Possibleeffectsonwildvertebratespeciesmustbeinvestigatedexcept
whereitcanbejustifiedthatitisnotlikelythatterrestrialvertebrates1991L0414—EN—01.01.2002—004.001—122
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other than birds are exposed, directly or indirectly. TERa, TERstand
TERltmustbereported,where:
TERa=LD50(mga.s./kgbodyweight)/ETE(mga.s./kgbodyweight)
TERst=subchronicNOEL(mga.s./kgfood)/ETE(mga.s./kgfood)
TERlt=chronicNOEL(mga.s./kgfood)/ETE(mga.s./kgfood)
whereETE=estimatedtheoreticalexposure.
Inprincipletheevaluationsequencefortheassessmentofriskstosuch
speciesissimilartothatforbirds.Inpracticeitisnotoftennecessary
toperformfurthertestingasthestudiesconductedinaccordancewith
the requirements of Annex II, point 5 and Annex III, point 7 would
providetherequiredinformation.
Aimofthetest
Thetestwillprovidesufficientinformationtoevaluatethenatureand
the extent of risks for terrestrial vertebrates other than birds in prac-
ticalconditionsofuse.
Circumstancesinwhichrequired
Where TERaandTERst>100andwherethereisnoevidence ofrisk
fromany further study no further testing is required. In the other
cases,expertjudgment isnecessarytodecide whetherthereisaneed
to carry out further studies. This expert judgment will take into
account, where relevant, foraging behaviour, repellency, alternative
food,actual residue content inthefood,persistence ofthecompound
in the vegetation, degradation of the formulated product or treated
produce,theamountofpredationofthefood,acceptanceofbait,gran-
ulesortreatedseedandthepossibilityforbioconcentration.
Where TERaand TERst≤10 or TERlt≤5 cage or field trials or
otherappropriatestudiesmustbereported.
Testconditions
Beforeperformingthesestudiestheapplicantshallseektheagreement
ofthecompetentauthoritiesonthetypeandconditionsofthestudyto
be performed and whether the effects of secondary poisoning should
beinvestigated.
10.4.Effectsonbees
The possible effects on bees must be investigated except where the
productisforexclusive useinsituationswherebeesarenotlikely to
beexposedsuchas:
— foodstorageinenclosedspaces,
— non-systemicseeddressings,
— non-systemicpreparationsforapplicationtosoil,— non-systemicdippingtreatmentsfortransplantedcropsandbulbs,
— woundsealingandhealingtreatments,
— rodenticidalbaits,— useinglasshouseswithoutpollinators.
The hazard quotients for oral and contact exposure (Q
HOand QHC),
mustbereported:
QHO=dose/oralLD50(µga.s.perbee)
QHC=dose/contactLD50(µga.s.perbee)
where
dose = the maximum application rate, for which authorization is
sought,ingofactivesubstanceperhectare.
10.4.1. Acuteoralandcontacttoxicity
Aim of the test
The test should provide the LD50values (by oral and contact expo-
sure).
Circumstances in which requiredTestingisrequiredif:
— theproductcontainsmorethanoneactivesubstance;1991L0414—EN—01.01.2002—004.001—123
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— thetoxicityofanewformulationcannotbereliablypredictedtobe
eitherthesameorlowerthanaformulationtestedaccordingtothe
provisionsofAnnexII,point8.3.1.1orofthispoint.
Test guidelineThetestmustbecarriedoutaccordingtoEPPOGuideline170.
10.4.2. Residuetest
Aim of the testThe test should provide sufficient information to evaluate possible
riskstoforagingbeesfromresidualtracesofplantprotectionproducts
remainingoncrops.
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
therearenosignificantresidualtracesremainingoncropswhichcould
affect foragingbeesorunlesssufficient information isavailable from
cage,tunnelorfieldtests.
Test conditionsThe median lethal time (LT
50) (in hours) following 24-hour exposure
to residues on leaves aged during eight hours must be determined,
andreported.WhereLT50ismorethaneighthours,nofurthertesting
isrequired.
10.4.3. Cagetests
Aim of the test
The test should provide sufficient information to evaluate possible
risksfromtheplantprotectionproductforbeesurvivalandbehaviour.
Circumstances in which requiredWhereQ
HOandQHCare<50,furthertestingisnotrequiredexcept if
significanteffectsareobservedinthebeebroodfeedingtestorifthere
areindicationsforindirecteffectssuchasdelayedactionormodifica-
tion of bee behaviour, in those cases cage and/or field tests shall be
carriedout.
WhereQHOandQHCare>50,cageand/orfieldtestingisrequired.
Wherefieldtestingisconductedandreportedinaccordancewithpoint
10.4.4, it is not necessary to conduct cage tests. However, cage tests
whereconducted,mustbereported.
Test conditionsThe test should be carried out using healthy bees. If bees have been
treated, e.g. with a varroacide, it is necessary to wait for four weeks
beforeusingthecolony.
Test guidelineThetestsmustbeconductedinaccordancewithEPPOGuideline170.
10.4.4. Fieldtests
Aim of the test
The test should provide sufficient information to evaluate possible
risks fromthe plant protection product on bee behaviour, colony
survivalanddevelopment.
Circumstances in which requiredFieldtestsmustbeconductedwhereonthebasisofexpertjudgement,
takingintoaccounttheproposedmannerofuseandthefateandbeha-
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 naturalstrength.Ifbeeshavebeentreated, e.g.withavarroa-
cide, it is necessary to wait for four weeks before using the colony.
The tests shall be conducted under conditions reasonably representa-
tiveoftheproposeduse.1991L0414—EN—01.01.2002—004.001—124
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Specialeffects(larvaltoxicity,longresidualeffect,disorientingeffects
onbees)identifiedbythefieldtestsmayrequirefurtherinvestigation
usingspecificmethods.
Test guideline
ThetestsmustbeconductedinaccordancewithEPPOGuideline170.
10.4.5. Tunneltests
Aim of the test
The test should provide sufficient information to evaluate the impact
onbeesresultingfromfeedingoncontaminatedhoneydeworflowers.
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. with a varroacide, it is necessary to wait for four weeks
beforeusingthecolony.
Test guideline
ThetestmustbecarriedoutinaccordancewithEPPOGuideline170.
10.5.Effectsonarthropodsotherthanbees
Theeffectsofplantprotectionproductsonnon-targetterrestrialarthro-
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-
bitingthesameenvironment.
10.5.1. Laboratory,extendedlaboratoryandsemi-fieldtests
Aim of the test
Thetestshouldprovidesufficientinformation toevaluate thetoxicity
of the plant protection productfor selected arthropod species that are
relevanttotheintendeduseoftheproduct.
Circumstances in which required
Testing is not required where severe toxicity (> 99 % effect on the
organismscompared tocontrol) canbepredicted fromrelevant avail-
abledataorwheretheplantprotectionproductisforexclusiveusein
situationswherenon-targetarthropodsarenotexposedsuchas:
— foodstorageinenclosedspaces,
— woundsealingandhealingtreatments,— rodenticidalbaits.
Testing is required when significant effects on the organisms in
comparisonwiththecontrolarereportedinthelaboratorytestsatthe
maximum recommended dose, conducted in accordance with the
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
definedintherespectivetestguidelines.
Testingisalsorequiredif:
— theproductcontainsmorethanoneactivesubstance,
— thetoxicityofanewformulationcannotbereliablypredictedtobe
eitherthesameorlowerthanaformulationtestedaccordingtothe
provisionsofAnnexII,point8.3.2orofthispoint,
— onthebasisoftheproposedmannerofuseoronthebasisofthe
fate and behaviour continued or repeated exposure can be antici-
pated,
— thereisasignificant change intheproposeduse,e.g.fromarable
crops to orchards, and species relevant to the new use have not
previouslybeentested,
— there is an increase in the recommended application rate, above
thatpreviouslytestedunderAnnexII.1991L0414—EN—01.01.2002—004.001—125
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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
AnnexII,point8.3.2.
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 %. Thiswill enable a comparison to be
made; if it significantly more toxic two species relevant to its
proposedusemustbetested.
Testingmustbeconductedatarateequivalenttothemaximumrateof
application for which authorization is sought. A sequential testing
approachshouldbeadopted,i.e.laboratory,andifnecessaryextended
laboratoryand/orsemi-field.
Wheretherewillbemorethanoneapplicationperseason,theproduct
should be applied at twice the recommended application rate unless
thisinformation isalreadyavailable fromstudiesperformedinaccor-
dancewithAnnexII,point8.3.2.
Where onthebasisoftheproposedmanner ofuseoronthebasisof
the fate and behaviour continued or repeated exposure can be antici-
pated(suchastheproductistobeapplied more thanthreetimesper
season with a re-application of 14 days or less), expert judgment is
requiredtoexaminewhetherfurthertestingisrequired,beyondinitial
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
such as plant material or a natural soil should be used. However it
maybemoreappropriatetocarryoutfieldtests.
Test guideline
Whererelevanttestingshouldbedoneaccordingtoappropriateguide-
lineswhichsatisfyasleasttherequirementsfortestingasincludedin
Setac-Guidancedocumentonregulatorytestingproceduresforpesti-
cideswithnon-targetarthropods.
10.5.2. Fieldtests
Aim of the test
Thetestsshouldprovidesufficientinformationtoevaluate theriskof
theplantprotectionproductforarthropodsunderfieldconditions.
Circumstances in which requiredWheresignificanteffectsareseenfollowinglaboratoryandsemi-field
exposure,orwhereonthebasisoftheproposedmannerofuseoron
thebasisofthefateandbehaviourcontinuedorrepeatedexposurecan
be anticipated expert judgment is required to examine whether more
extensivetestingisnecessarytopermitanaccurateriskassessment.
Test conditions
The tests must be conducted under representative agricultural condi-
tions and in accordance with the proposed recommendations for use,
resultinginarealisticworstcasestudy.
Atoxicstandardshouldbeincludedinalltests.Test guidelineWhererelevanttestingshouldbedoneaccordingtoappropriateguide-
lineswhichsatisfyatleasttherequirements fortestingasincludedin
Setac — Guidance document on regulatory testing procedures for
pesticideswithnon-targetarthropods.
10.6.Effectsonearthwormsandothersoilnon-targetmacro-organisms,
believed tobeatrisk
10.6.1. Effectsonearthworms
The possibleimpact onearthworms mustbereported except whereit
can be justified that it is not likely that earthworms are exposed,
directlyorindirectly.1991L0414—EN—01.01.2002—004.001—126
▼M7
TERaandTERltmustbereportedwhere:
TERa=L C50(mg a.s./kg)/realistic worst case PECs(initial or short-
term,inmga.s./kg)
TERlt=NOEC(mga.s./kg)/longtermPECs(mga.s./kg).
10.6.1.1. Acutetoxicitytests
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 mustinclude observed morphological and beha-
viouraleffects.
Circumstances in which requiredThesestudiesareonlyrequiredwhere
— theproductcontainsmorethanoneactivesubstance,
— thetoxicityofanewformulationcannotbereliablypredictedfrom
the formulation tested according to the provisions of Annex II,
point8.4orofthispoint.
Test guidelineThetestsmustbeconductedinaccordancetoOECDMethod207.
10.6.1.2. Testsforsublethaleffects
Aim of the testThe test should provide the NOEC and the effects on growth, repro-
ductionandbehaviour.
Circumstances in which requiredThesestudiesareonlyrequiredwhere
— theproductcontainsmorethanoneactivesubstance,
— thetoxicityofanewformulationcannotbereliablypredictedfrom
the formulation tested according to the provisions of Annex II,
point8.4orofthispoint,
— there is an increase in the recommended application rate, above
thatpreviouslytested.
Test conditionsThesameprovisionsasunderthecorrespondingparagraphsofAnnex
II,point8.4.2apply.
10.6.1.3. Fieldstudies
Aim of the test
Thetestshouldprovidesufficientdatatoevaluatetheeffectsonearth-
wormsinfieldconditions.
Circumstances in which required
Where TER
lt< 5 a field study to determine effects under practical
fieldconditionsmustbeconductedandreported.
Expert judgment is required to decide whether residue contents of
earthwormsshouldbeinvestigated.
Test conditions
Fieldsselectedshallhaveareasonableearthwormpopulation.
The test must be carried out at the maximum proposed application
rate.Atoxicreferenceproductmustbeincludedinthetest.
10.6.2. Effectsonothersoilnon-targetmacro-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
breakdownofdeadplantandanimalorganicmatter.
Circumstances in which required
TestingisnotrequiredwhereinaccordancewithAnnexIII,point9.1,
itisevidentthatDT
90valuesarelessthan100days,orthenatureand
manner of use of the plant protection product are such that exposure
does not occur or when data fromstudies on the active substance1991L0414—EN—01.01.2002—004.001—127
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performedinaccordancewiththeprovisionsofAnnexII,points8.3.2,
8.4 and 8.5 indicate that there is no risk for soil macrofauna, earth-
wormsorsoilmicroflora.
Impact on organic matter breakdown must be investigated and
reported,wheretheDT90fvaluesdeterminedinfielddissipationstudies
(point9.1)are>365days.
10.7.Effectsonsoilnon-targetmicro-organisms
10.7.1. Laboratorytesting
Aim of the test
The test should provide sufficient data to evaluate the impact of the
plantprotectionproductonsoilmicrobialactivityintermsofnitrogen
transformationandcarbonmineralization.
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
requiredifinthestudiesperformedinaccordancewiththeprovisions
ofAnnexII,point8.5deviationsfromcontrolvaluesintermsofmeta-
bolicactivity ofthemicrobial biomassafter100daysis<25%,and
suchdata are relevant tothe uses,nature,and propertiesofthe parti-
cularpreparationtobeauthorized.
Test guidelineSetac—Proceduresforassessingtheenvironmentalfateandecotoxi-
cityofpesticides.
10.7.2. Additionaltesting
Aim of the test
The test should provide sufficient data to evaluate the impact of the
plantprotectionproductunderfieldconditionsonmicrobialactivitiy.
Circumstances in which required
Where at the end of 100 days, measured activity deviates by more
than 25 % fromthe control, in the laboratory testing further testing
inthelaboratory,underglassand/orinthefieldmaybenecessary.
10.8.Available data from biological primary screening in summary
form
Asummaryofavailabledatafrompreliminarytestsusedtoassessthe
biological activity and dose range finding whether positive or nega-
tive, which provides information with respect to possible impact on
non/target species, both flora and fauna, must be provided, together
with a critical assessment as to its relevance to potential impact on
non-targetspecies.
11. Summary and evaluation of points 9 and 10
A summary and evaluation of all data presented in points 9 and 10
shouldbe carried out according to the guidance given bythe compe-
tent authorities of the Member States concerning the format of such
summaries and evaluations. It should include a detailed and critical
assessmentofthosedatainthecontextofrelevantevaluativeanddeci-
sion making criteria and guidelines, with particular reference to the
risksfortheenvironmentandnon-targetspeciesthatmayordoarise,
andtheextent,qualityandreliabilityofthedatabase.Inparticularthe
followingissuesshouldbeaddressed:
— predicting distribution and fate in the environment, and the time
coursesinvolved,
— identifying non-target species and populations at risk, and
predictingtheextentofpotentialexposure,
— evaluation as to the short- and long-termrisks for non-target
species — populations, communities, and processes — as appro-
priate,
— evaluation asto theriskoffishkills,and fatalities inlarge verte-
brates,orterrestrialpredators,regardlessofeffectsatpopulationor
communitylevel,and1991L0414—EN—01.01.2002—004.001—128
▼M7
— identification of precautions necessary to avoid or minimize
contamination of the environment, and for the protection of non-
targetspecies.
12. Further information
12.1. Informationonauthorizationsinothercountries
12.2. Information on established maximum residue limits (MRL) in other
countries
12.3. Proposals including justification for the classification and labelling
proposedinaccordance withDirective 67/548/EEC and Directive 78/
631/EEC
— Hazardsymbol(s)
— Indicationsofdanger— Riskphrases— Safetyphrases
12.4. ProposalsforriskandsafetyphrasesinaccordancewithArticle15(1),
(g)and(h)andproposedlabel
12.5. Specimensofproposedpackaging
PARTB
Introduction
(i) ThisPartprovidesdatarequirementsfortheauthorisationofaplantprotec-
tionproductbasedonpreparationsofmicro-organismsincludingviruses.
Theterm‘micro-organism’asdefinedintheintroductionofAnnexII,Part
B,alsoappliestoAnnexIII,PartB.
(ii) Where relevant, data should be analysed using appropriate statistical
methods. Fulldetails of the statistical analysis shouldbe reported (e.g. all
point estimates should be given with confidence intervals, exact p-values
shouldbegivenratherthanstatingsignificant/nonsignificant).
(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.USEPAguideline(
1));whereappropriate test
guidelines as described in Annex II, Part A, should be adapted in such a
waythat they areappropriate formicro-organisms. Testing shouldinclude
viableand,ifappropriate,non-viablemicro-organisms,andablankcontrol.
(iv) Whenever a study implies the use of different doses, the relationship
betweendoseandadverseeffectmustbereported.
(v) Wheretestingisdone,adetaileddescription(specification)ofthematerial
usedanditsimpurities,accordingtotheprovisionsofsection1,point1.4,
mustbeprovided.
(vi) In cases where a new preparation is to be dealt with, extrapolation from
AnnexII,PartB,couldbeacceptable,providedthatallthepossibleeffects
of the formulants and other components, especially on pathogenicity and
infectiveness,arealsoevaluated.
1. IDENTITYOFTHEPLANTPROTECTIONPRODUCT
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
Directive91/414/EEC.
1.1.Applicant
The name and address of the applicant (permanent community
address) must be provided as must the name, position, telephone and
faxnumberoftheappropriatepersontocontact.1991L0414—EN—01.01.2002—004.001—129
(1)USEPA Microbial Pesticide Test Guidelines, OPPTS Series 885, February 1996
(http://www.epa.gov/oppbppd1/biopesticides/guidelines/series885.htm).▼B
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Where,inaddition,theapplicanthasanoffice,agentorrepresentative
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
oftheappropriatepersontocontact.
1.2.Manufacturerofthepreparationandthemicro-organism(s)
The name and address of the manufacturer of the preparation and of
eachmicro-organisminthepreparation mustbeprovidedasmustthe
name and address of each manufacturing plant in which the prepara-
tionandmicro-organismaremanufactured.
A contact point (preferable a central contact point, to include name,
telephoneandfaxnumbers)mustbeprovidedforeachmanufacturer.
If the m icro-organismoriginates froma producer fromwhich data
according to Annex II, Part B, had not been submitted previously,
detailed information onthe name andspecies description, asrequired
in Annex II, Part B, section 1.3, and on impurities, as required in
AnnexII,PartB,section1.4,havetobeprovided.
1.3.Tradenameorproposedtradename,andmanufacturer'sdevelop-
mentcodenumberofthepreparationifappropriate
All former and current trade names and proposed trade names and
developmentcodenumbersofthepreparationreferredtointhedossier
as well as the current names and numbers must be provided. Full
detailofanydifferencesmustbeprovided.(Theproposedtradename
must not give rise to confusion with the trade name of already
authorisedplantprotectionproducts.)
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
anaccessionnumber.Thescientificnamemustbestated,aswell
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)inthemarketedproductshallbestated.
(ii) Forpreparationsthefollowinginformationmustbereported:
— the content of the micro-organism(s) in the plant protection
productandthecontentofthemicro-organisminthematerial
used for manufacturing of plant protection products. These
must include the maximum, minimum and nominal content
oftheviableandnon-viablematerial,
— thecontentofformulants,
— the content of other components (such as by-products,
condensates, culture medium, etc.) and contaminating micro-
organisms,derivedfromproductionprocess.
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
chemicalnameasgiveninAnnexItoDirective67/548/EEC,or,
ifnotincludedinthisDirective,inaccordancewithbothIUPAC
andCAnomenclature. Their structureorstructural formulamust
be provided. For each component of the formulants the relevant
EC(EinecsorElincs)numberandCASnumberwheretheyexist,
mustbeprovided.Wheretheinformationprovideddoesnotfully
identify a formulant, an appropriate specification must be
provided. The trade name of formulants, where they exist, must
alsobeprovided.
(iv) Forformulantsthefunctionmustbegiven:
— adhesive(sticker)
— antifoamingagent
— antifreeze
— binder— buffer
— carrier1991L0414—EN—01.01.2002—004.001—130
▼M25
— deodorant
— dispersingagent— dye— emetic
— emulsifier
— fertiliser— odorant— parfume— preservative
— propellant
— repellent— safener— solvent
— stabiliser
— synergist— thickener— wettingagent— miscellaneous(specify).
(v) Identification of contaminating micro-organisms and other
componentsderivedfromproductionprocess.
Contaminating micro-organismsmustbeidentified asoutlinedin
AnnexII,PartB,section1,point1.3.
Chemicals (inert components, by-products, etc.) must be identi-
fiedasoutlinedinAnnexII,PartA,section1,point1.10.
Wheretheinformationprovideddoesnotfullyidentifyacompo-
nent, such as condensate, culture medium, etc., detailed
information on the composition must be provided for each such
component.
1.5.Physicalstateandnatureofthepreparation
Thetypeandcodeofpreparationmustbedesignatedaccordingtothe
‘Catalogue of pesticide formulation types and international coding
system(GIFAPTechnicalMonographNo2,1989)’.
Whereaparticularpreparationisnotdefinedpreciselyinthispublica-
tion a full description of the physical nature and state of the
preparation must be provided, together with a proposal for a suitable
descriptionofthetypeofpreparationandaproposalforitsdefinition.
1.6.Function
Thebiologicalfunctionmustbespecifiedfromamongthefollowing:
— controlofbacteria,
— controloffungi,
— controlofinsects,
— controlofmites,— controlofmolluscs,— controlofnematodes,
— controlofweeds,
— other(mustbespecified).
2. PHYSICAL, CHEMICAL AND TECHNICAL PROPERTIES OF
THEPLANTPROTECTIONPRODUCT
Theextent towhichplantprotection productsforwhichauthorisation
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
ApplicationStandards,mustbestated.DivergencesfromFAOspecifi-
cationsmustbedescribedindetail,andjustified.
2.1.Appearance(colourandodour)
A description of both the colour and odour, if any, and the physical
stateofthepreparation,mustbeprovided.1991L0414—EN—01.01.2002—004.001—131
▼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
growth of contaminating micro-organisms must be determined
and reported. The conditions under which the test has been
performedmustbejustified.
(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
51orMT54asappropriate.
(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)MonographNo17.
2.2.2. Other factors affecting stability
Effectofexposuretoair,packaging,etc.,ontheproductstabilitymust
beexplored.
2.3.Explosivityandoxidisingproperties
Explosivity and oxidising properties will be determined as defined in
AnnexIII,PartA,section2,point2.2,unlessitcanbejustifiedthatit
istechnicallyorscientificallynotnecessarytoperformsuchstudies.
2.4.Flash point and other indications of flammability or spontaneous
ignition
Flashpointandflammabilitymustbedetermined,asdefinedinAnnex
III,PartA,section2,point2.3,unlessitcanbejustifiedthatitistech-
nicallyorscientificallynotnecessarytoperformsuchstudies.
2.5.Acidity,alkalinityandifnecessarypHvalue
Acidity,alkalinityandpHwillbedeterminedasdefinedinAnnexIII,
PartA,section2,point2.4,unlessitcanbejustifiedthatitistechni-
callyorscientificallynotnecessarytoperformsuchstudies.
2.6.Viscosityandsurfacetension
ViscosityandsurfacetensionwillbedeterminedasdefinedinAnnex
III,PartA,section2,point2.5,unlessitcanbejustifiedthatitistech-
nicallyorscientificallynotnecessarytoperformsuchstudies.
2.7.Technicalcharacteristics oftheplantprotectionproduct
Thetechnicalcharacteristicsofthepreparationmustbedeterminedto
permitadecisiontobemadeastoitsacceptability.Iftestshavetobe
performed, they must be done at temperatures compatible with
survivalofthemicro-organism.
2.7.1. Wettability
The wettability of solid preparations which are diluted for use (e.g.
wettablepowdersandwaterdispersiblegranules),mustbedetermined
andreportedaccordingtoCIPACMethodMT53.3.
2.7.2. Persistent foaming
The persistence of foaming of preparations to be diluted with water,
mustbedeterminedandreportedaccordingtoCIPACMethodMT47.
2.7.3. Suspensibility and suspension stability
— The suspensibility of water dispersible products (e.g. wettable
powders, water dispersible granules, suspension concentrates)1991L0414—EN—01.01.2002—004.001—132
(1) CollaborativeInternationalPesticidesAnalyticalCouncil.
(2) International GroupofNationalPesticideManufacturers'Associations.
▼M25
mustbedeterminedandreportedaccordingtoCIPACMethodMT
15,MT161orMT168asappropriate.
— The spontaneity of dispersion of water dispersible products (e.g.
suspension concentrates and water dispersible granules) must be
determinedandreportedaccordingtoCIPACMethodsMT160or
MT174asappropriate.
2.7.4. Dry sieve test and wet sieve test
In order to ensure that dustable powders have a suitable particle size
distributionforeaseofapplication,adrysievetestmustbeconducted
andreportedaccordingtoCIPACMethodMT59.1.
In the case of water dispersible products, a wet sieve test must be
conductedandreportedaccordingtoCIPACMethodMT59.3orMT
167asappropriate.
2.7.5. Particle size distribution (dustable and wettable powders, granules),
content of dust/fines (granules), attrition and friability (granules)
(i) Thesizedistributionofparticlesinthecaseofpowders,mustbe
determinedandreportedaccordingtoOECDMethod110.
Thenominalsizerangeofgranulesfordirectapplicationmustbe
determinedandreportedinaccordancewithCIPACMT58.3,for
waterdispersiblegranulesinaccordancewithCIPACMT170.
(ii) The dust content of granular preparations, must be determined
and reported according to CIPAC Method MT 171. If relevant
foroperatorexposuretheparticlesizeofdustmustbedetermined
andreportedaccordingtoOECDMethod110.
(iii) The friability and attrition characteristics of granules, must be
determined andreportedonceinternationally agreedmethodsare
available.Wherealreadydataareavailabletheymustbereported
togetherwiththemethodused.
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
reportedaccordingtoCIPACMethodMT36orMT173asappro-
priate.
(ii) The stability of dilute emulsions and of preparations which are
emulsions, mustbe determined and reported according toCIPAC
MethodMT20orMT173.
2.7.7. Flowability, pourability (rinsability) and dustability
(i) Theflowability ofgranular preparationsmustbedetermined and
reportedaccordingtoCIPACMethodMT172.
(ii) The pourability (including rinsed residue) of suspensions (e.g.
suspension concentrates, suspo-emulsions), must be determined
andreportedaccordingtoCIPACMethodMT148.
(iii) The dustability of dustable powders must be determined and
reported according toCIPACMethodMT34oranother 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
Thephysicalcompatibilityofrecommendedtankmixesmustbedeter-
minedandreported.
2.8.2. Chemical compatibility
The chemical compatibility of recommended tank mixes must be
determined and reported except where examination of the individual
propertiesofthepreparationswouldestablishbeyondreasonabledoubt
thatthereisnopossibilityofreactiontakingplace.Insuchcasesitis
sufficienttoprovidethatinformationasjustificationfornotpractically
determiningthechemicalcompatibility.1991L0414—EN—01.01.2002—004.001—133
▼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
beinvestigated,basedontheefficacydata.Intervalsbetweenapplica-
tion of the biological pesticide and chemical pesticides should be
specified,ifappropriate,inordertoavoidlossofefficacy.
2.9.Adherenceanddistributiontoseeds
In the case of preparations for seed treatment, both distribution and
adhesionmustbeinvestigatedandreported;inthecaseofdistribution
accordingtoCIPACMethodMT175.
2.10.Summaryandevaluationofdatapresentedunderpoints2.1to2.9
3. DATAONAPPLICATION
3.1.Fieldofuseenvisaged
Thefield(s)ofuse,existingandproposed,forpreparationscontaining
themicro-organismmustbespecifiedfromamongthefollowing:
— fielduse,suchasagriculture,horticulture,forestryandviticulture,
— protectedcrops(e.g.inglasshouses),
— amenity,
— weedcontrolonnon-cultivatedareas,— homegardening,
— houseplants,
— storedproducts,
— 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-
staticaction,nutrientcompetition,etc.)mustbestated.
It must also be stated whether or not the product is translocated in
plants and, where relevant, if such translocation is apoplastic,
symplasticorboth.
3.3.Detailsofintendeduse
Detailsoftheintendeduse,e.g.typesofharmfulorganismscontrolled
and/orplantsorplantproductstobeprotected,mustbeprovided.
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-
organismsonthesamecrop,shouldalsobeprovided.
3.4.Applicationrate
For each method of application and each use, the rate of application
perunit(ha,m
2,m3)treated,intermsofgorkgorlfortheprepara-
tionandintermsofappropriateunitsforthemicro-organism,mustbe
provided.
Applicationratesshallnormallybeexpressedingorkg/haorinkg/m3
andwhereappropriateingorkg/tonne;forprotectedcropsandhome
gardeninguseratesshallbeexpressedingorkg/100m2orgorkg/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
numberofactiveunit/mlorgoranyotherrelevantunit.1991L0414—EN—01.01.2002—004.001—134
▼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
andvolumeofdiluenttobeusedperunitofareaorvolume.
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
intervalbetweenapplications,indays,mustbestated.
The duration of protection afforded both by each application and by
themaximumnumberofapplicationstobeused,mustbeindicated.
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,
andfollowfromthedataprovidedundersection6,point6.6.
Limitationsonchoiceofsucceedingcrops,ifany,mustbestated.
3.9.Proposedinstructionsforuse
Theproposedinstructionsforuseofthepreparation, tobeprinted on
labelsandleaflets,mustbeprovided.
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
ofclosure and seals. Itmustbe designed inaccordance withthe
criteria and guidelines specified in the FAO ‘Guidelines for the
PackagingofPesticides’.
(ii) The suitability of the packaging, including closures, in terms of
itsstrength,leakproofnessandresistancetonormaltransportand
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,
accordingtoISOstandard8317.
(iii) The resistance of the packaging material to its contents must be
reportedaccordingtoGIFAPMonographNo17.
4.2.Proceduresforcleaningapplicationequipment
Cleaning procedures for both application equipment and protective
clothingmustbedescribedindetail.Theeffectivenessofthecleaning
proceduremustbedetermined,usinge.g.biotests,andreported.
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
sections7and8.
(i) Where relevant pre-harvest intervals, re-entry periods or with-
holdingperiodsnecessarytominimisethepresenceofresiduesin
or on crops, plants and plant products, or in treated areas or
spaces,withaviewtoprotectingmanorlivestock,mustbespeci-
fiede.g.:
— pre-harvestinterval(indays)foreachrelevantcrop,
— re-entryperiod(indays)forlivestock,toareastobegrazed,
— re-entry period (in hoursor days) for man to crops, buildings
orspacestreated,
— withholdingperiod(indays)foranimalfeedingstuffs,1991L0414—EN—01.01.2002—004.001—135
▼M25
— waiting period (in days), between application and handling
treatedproducts.
(ii) Where necessary, in the light of the test results, information on
anyspecificagricultural, planthealthorenvironmentalconditions
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)forthestorage,atbothwarehouseanduserlevel
ofplantprotectionproducts,fortheirtransportandintheeventoffire
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-
oversmustbeprovided.
Whererelevant,assessmenthastobedoneaccordingtoISOTR9122.
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.fieldorglasshousecircumstances).
4.5.Measuresinthecaseofanaccident
Whetherarisingduringtransport,storageoruse,detailedproceduresto
befollowedintheeventofanaccident,mustbeprovidedandinclude:
— containmentofspillages,
— decontaminationofareas,vehiclesandbuildings,
— disposalofdamagedpackaging,adsorbentsandothermaterials,
— protectionofemergencyworkersandbystanders,— firstaidmeasures.
4.6.Proceduresfordestructionordecontaminationoftheplantprotec-
tionproductanditspackaging
Proceduresfordestructionanddecontaminationmustbedevelopedfor
both small quantities (user level) and large quantities (warehouse
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
disposalfeasible.
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
controlledincinerationinalicensedincinerator.
Theapplicantmustprovidedetailedinstructionsforsafedisposal.
4.6.2. Others
Othermethodstodisposeofplantprotectionproducts,packagingand
contaminatedmaterials,whereproposed,mustbefullydescribed.Data
mustbeprovidedforsuchmethods,toestablishtheireffectivenessand
safety.
5. ANALYTICALMETHODS
Introduction
The provisionsof this section onlycover analytical methods required
forpost-registrationcontrolandmonitoringpurposes.
Itisdesirabletohaveaplantprotectionproductwithoutcontaminants,
if possible. The level of acceptable contaminants should be judged
fromariskassessmentpointofview,bythecompetentauthority.
Both production and product must be subject to a continuous quality
control by the applicant. The quality criteria for the product should
besubmitted.1991L0414—EN—01.01.2002—004.001—136
▼M25
Foranalytical methodsusedforgeneration ofdataasrequired inthis
Directiveorforotherpurposestheapplicanthastoprovideajustifica-
tion for the method used; where necessary separate guidance will be
developedforsuchmethodsonthebasisofthesamerequirements as
defined for methods for post-registration control and monitoring
purposes.
Descriptions of methods must be provided and include details of
equipment,materialsandconditionsused.Theapplicabilityofexisting
CIPACmethodsmustbereported.
As far as practicable these methods must employ the simplest
approach,involvetheminimumcost,andrequirecommonlyavailable
equipment.
Forthissectionthefollowingapplies:
Impurities Any component (including contaminating
micro-organisms and/or chemical substances)
other than the specified micro-organism, origi-
natingfromthemanufacturing processorfrom
degradationduringstorage
Relevantimpurities Impurities, as defined above, that are of
concern for humanoranimal 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
ofinterest
Relevantmetabolites Metabolites that are of concern for human or
animalhealthand/ortheenvironment
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 humanoranimal health and/or the
environment.
Onrequestthefollowingsamplesmustbeprovided:
(i) samplesofthepreparation;
(ii) samplesofthemicro-organismasmanufactured;
(iii) analyticalstandardsofthepuremicro-organism;
(iv) analytical standardsofrelevant metabolites andall othercompo-
nentsincludedintheresiduedefinition;
(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.
— Methodstoestablishregularcontrol ofthefinalproduct(prepara-
tion)inordertoshowthatitdoesnotcontainotherorganismsthan
theindicatedonesandtoestablishitsuniformity.
— Methods to identify any contaminating micro-organisms of the
preparation.
— Methods used to determine the storage stability and shelf life of
thepreparationmustbeprovided.
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
requirementsofAnnexII,PartB,section4,point4.2,issufficient.1991L0414—EN—01.01.2002—004.001—137
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6. EFFICACYDATA
The provisions for efficacy data have already been adopted under
CommissionDirective93/71/EEC(1).
7. EFFECTSONHUMANHEALTH
Forproperevaluationofthetoxicityincludingpotentialforpathogeni-
cityandinfectivenessofpreparationssufficientinformationshouldbe
available on acute toxicity, irritation and sensitisation of the micro-
organism.Ifpossible,additionalinformationonmodeoftoxicaction,
toxicological profile and all other known toxicological aspects of the
micro-organismshouldbesubmitted.Specialattentionshouldbegiven
toco-formulants.
While performing toxicology studies, all signs of infection or patho-
genicityshouldbenoted.Toxicologystudiesshouldincludeclearance
studies.
In the context of the influence that impurities and other components
canhaveontoxicologicalbehaviour,itisessentialthatforeachstudy
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
culturingit,arethesameforwhichinformationanddataaresubmitted
inthecontextofAnnexII,PartB.
Atieredtestingsystemwillbeappliedtothestudyoftheplantprotec-
tionproduct.
7.1.Basicacutetoxicity studies
Thestudies,dataandinformation tobeprovidedandevaluated, must
be sufficient to permit the identification of effects following a single
exposuretotheplantprotectionproduct,andinparticulartoestablish,
orindicate:
— thetoxicityoftheplantprotectionproduct,
— toxicity of the plant protection product relative to the micro-
organism,
— thetimecourseandcharacteristicsoftheeffectwithfulldetailsof
behavioural changes and possible gross pathological findings at
post-mortem,
— wherepossiblethemodeoftoxicaction,and— therelativehazardassociatedwiththedifferentroutesofexposure.
While the emphasis must be on estimating the toxicity ranges
involved,theinformationgeneratedmustalsopermittheplantprotec-
tionproducttobeclassifiedinaccordancewithDirective78/631/EEC.
The information generated through acute toxicity testing is of parti-
cularvalueinassessinghazardslikelytoariseinaccidentsituations.
7.1.1. Acute oral toxicity
Circumstancesinwhichrequired
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)ofDirective78/631/EECcanbeinvoked.
Testguideline
ThetestmustbecarriedoutinaccordancewithMethodB.1orB.1 bis
ofCommissionDirective92/69/EEC(
2).
7.1.2. Acute inhalation toxicity
Aimofthetest
Thetestwillprovidetheinhalationtoxicitytoratsoftheplantprotec-
tionproduct.1991L0414—EN—01.01.2002—004.001—138
(1) OJL221,31.8.1993,p.27.
(2) OJL383,29.12.1992,p.113.
▼M25
Circumstancesinwhichrequired
Thetestmustbecarriedoutwheretheplantprotectionproduct:
— isusedwithfoggingequipment,
— isanaerosol,
— is a powder containing a significant proportion of particles of
diameter<50micrometre(>1%onaweightbasis),
— istobeappliedfromaircraftincaseswhereinhalationexposureis
relevant,
— istobeappliedinamannerwhichgeneratesasignificantpropor-
tion of particles or droplets of diameter < 50 micrometre (> 1 %
onaweightbasis),
— containsavolatilecomponentatgreaterthan10%.
Testguideline
ThetestmustbecarriedoutinaccordancewithMethodB.2ofDirec-
tive92/69/EEC.
7.1.3. Acute percutaneous toxicity
Circumstancesinwhichrequired
An acute percutaneous test should always be carried out unless the
applicant can justify to the satisfaction of the competent authority
thatArticle3(2)ofDirective78/631/EECcanbeinvoked.
Testguideline
ThetestmustbecarriedoutinaccordancewithMethodB.3ofDirec-
tive92/69/EEC.
7.2.Additionalacutetoxicitystudies
7.2.1. Skin irritation
Aimofthetest
Thetestwillprovidethepotentialofskinirritancyoftheplantprotec-
tion product including the potential reversibility of the effects
observed.
Circumstancesinwhichrequired
The skin irritancy of the plant protection product must always be
determined, except where the formulants are not expected to be skin
irritantorthemicro-organismisshownnottobeskinirritantorwhere
it is likely, as indicated in the test guideline, that severe skin effects
canbeexcluded.
Testguideline
ThetestmustbecarriedoutinaccordancewithMethodB.4ofDirec-
tive92/69/EEC.
7.2.2. Eye irritation
Aimofthetest
Thetestwillprovidethepotentialforeyeirritationoftheplantprotec-
tion product, including the potential reversibility of the effects
observed.
Circumstancesinwhichrequired
Theeyeirritancy oftheplantprotection productmustbedetermined,
wheretheformulantsaresuspectedtobeeyeirritant,exceptwherethe
micro-organismiseyeirritantorwhereitislikely,asindicatedinthe
testguideline,thatsevereeffectsontheeyesmaybeproduced.
Testguideline
TheeyeirritationmustbedeterminedinaccordancewithMethodB.5
ofDirective92/69/EEC.1991L0414—EN—01.01.2002—004.001—139
▼M25
7.2.3. Skin sensitisation
Aimofthetest
The test will provide sufficient information to assess the potential of
theplantprotectionproducttoprovokeskinsensitisationreactions.
Circumstancesinwhichrequired
The test must be carried out where the formulants are suspected to
have skin sensitising properties, except where the micro-organism(s)
ortheformulantsareknowntohaveskinsensitisingproperties.
Testguideline
The tests have to be carried out in accordance with Method B.6 of
Directive92/69/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,thedegreeanddurationofexposure.Sufficientinformationand
data must be generated and reported to permit an assessment of the
extentofexposuretotheplantprotectionproductlikelytooccurunder
theproposedconditionsofuse.
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 fromthe inform ation
provided for the preparation in the present section of Annex III, Part
B,furtherdermalabsorptiondatacanbenecessary.
Results fromexposure m onitoring during production or use of the
productmustbesubmitted.
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
specifiedonthelabel.
7.4.Availabletoxicological datarelating tonon-activesubstances
A copy of the notification and the safety data sheet submitted in the
contextofEuropeanParliament andCouncilDirective 1999/45/EC(1)
andCommissionDirective91/155/EECof5March1991definingand
layingdownthedetailedarrangementsforthesystemofspecificinfor-
mationrelatingtodangerouspreparationsinimplementationofArticle
10ofDirective88/379/EEC(2)mustbesubmittedforeachformulant.
Allotheravailableinformationshouldbesubmitted.
7.5.Supplementary studies for combinations of plant protection
products
Aimofthetest
Incertaincasesitmaybenecessarytocarryoutthestudiesasreferred
to under points 7.1 to 7.2.3 for a combination of plant protection
productswheretheproductlabelincludesrequirements foruseofthe
plant protection product with other plant protection products and/or
withadjuvantsasatankmix.Decisionsastotheneedforsupplemen-
tarystudiesmustbemadeonacase-by-casebasis,takingintoaccount
theresultsoftheacute toxicitystudiesoftheindividual plantprotec-
tion products, the possibility for exposure to the combination of the
products concerned and available information or practical experience
withtheproductsconcernedorsimilarproducts.
7.6.Summaryandevaluationofhealtheffects
Asummaryofalldataandinformationprovidedunderparagraphs7.1
through 7.5, must be submitted, and include a detailed and critical1991L0414—EN—01.01.2002—004.001—140
(1) OJL200,30.7.1999,p.1.
(2) OJL76,22.3.1991,p.35.
▼M25
assessmentofthosedatainthecontextofrelevantevaluativeanddeci-
sion-making criteria and guidelines, with particular reference to the
risksformanandanimalsthatmayordoarise,andtheextent,quality
andreliabilityofthedatabase.
8. RESIDUESINORONTREATEDPRODUCTS,FOODANDFEED
ThesameprovisionsasdetailedinAnnexII,PartB,section6,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-
organismanditsmetabolites.
9. FATEANDBEHAVIOURINTHEENVIRONMENT
ThesameprovisionsasdetailedinAnnexII,PartB,section7,apply;
the information required according to this section has to be provided
unlessitispossibletoextrapolate thefateandbehaviouroftheplant
protection product in the environment on the basis of the data avail-
ableinAnnexII,PartB,section7.
10. EFFECTSONNON-TARGETORGANISMS
Introduction
(i) Theinformationprovided,takentogetherwiththatforthemicro-
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
fromsingle, prolonged or repeated exposure, and can be rever-
sible,orirreversible.
(ii) Thechoiceoftheappropriatenon-targetorganismsfortestingof
environmentaleffectsshouldbebasedontheinformationonthe
micro-organism, as required in Annex II, Part B, and on the
informationontheformulantsandothercomponents,asrequired
bysections1to9ofthepresentAnnex.Fromsuchknowledgeit
wouldbepossibletochoosetheappropriatetestorganisms,such
asorganismscloselyrelatedtothetargetorganism.
(iii) In particular, the information provided for the plant protection
product, together with other relevant information, and that
providedforthemicro-organism,shouldbesufficientto:
— specify the hazard symbols, the indications of danger, and
relevant risk and safety phrases for the protection of the
environment,tobementionedonpackaging(containers),
— permit an evaluation of the short- and long-term risks for
non-target species — populations, communities, and
processesasappropriate,
— permit an evaluation whether special precautions are neces-
saryfortheprotectionofnon-targetspecies.
(iv) There is a need to report all potentially adverse effects found
during routine investigations of environmental effects and to
undertake and report such additional studies which may be
necessarytoinvestigate themechanismsinvolvedandassessthe
significanceoftheseeffects.
(v) In general, much of the 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)inAnnexI.
(vi) Whereexposuredataarenecessarytodecidewhetherastudyhas
tobeperformed,thedataobtainedinaccordancewiththeprovi-
sionsofAnnexIII,PartB,section9,shouldbeused.
Fortheestimationofexposureoforganismsallrelevantinforma-
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
fromavailable 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
usedforthecalculationofrelevanteffect/exposureratios.
(vii) In order to facilitate the assessment of the significance of test
resultsobtained, the same strain ofeach relevant species should
where possible be used in the various specified tests for effects
onnontargetorganisms.1991L0414—EN—01.01.2002—004.001—141
▼M25
10.1.Effectsonbirds
ThesameinformationasprovidedinAnnexII,PartB,section8,point
8.1,hastobereportedwhereitisnotpossibletopredicttheeffectsof
the plant protection product onthe basisof thedata available forthe
micro-organism, unless it can be justified that exposure of birds is
unlikelytooccur.
10.2.Effectsonaquaticorganisms
ThesameinformationasprovidedinAnnexII,PartB,section8,point
8.2,hastobereportedwhereitisnotpossibletopredicttheeffectsof
the plant protection product onthe basisof thedata available forthe
micro-organism, unless it can be justified that exposure of aquatic
organismsisunlikelytooccur.
10.3.Effectsonbees
ThesameinformationasprovidedinAnnexII,PartB,section8,point
8.3,hastobereportedwhereitisnotpossibletopredicttheeffectsof
the plant protection product onthe basisof thedata available forthe
micro-organism,unlessitcanbejustifiedthatexposureofbeesisunli-
kelytooccur.
10.4.Effectsonarthropodsotherthanbees
ThesameinformationasprovidedinAnnexII,PartB,section8,point
8.4,hastobereportedwhereitisnotpossibletopredicttheeffectsof
the plant protection product onthe basisof thedata available forthe
micro-organism, unlessitcanbejustified thatexposureofarthropods
otherthanbeesisunlikelytooccur.
10.5.Effectsonearthworms
ThesameinformationasprovidedinAnnexII,PartB,section8,point
8.5,hastobereportedwhereitisnotpossibletopredicttheeffectsof
the plant protection product onthe basisof thedata available forthe
micro-organism,unlessitcanbejustifiedthatexposureofearthworms
isunlikelytooccur.
10.6.Effectsonsoilmicro-organisms
ThesameinformationasprovidedinAnnexII,PartB,section8,point
8.6,hastobereportedwhereitisnotpossibletopredicttheeffectsof
the plant protection product onthe basisof thedata available forthe
micro-organism, unlessit can be justified that exposure of nontarget
soilmicro-organismsisunlikelytooccur.
10.7.Additionalstudies
Expert judgement isrequired todecide whetheradditional studiesare
necessary. Such decision will take into consideration the available
information inthisandothersections,inparticulardataonthespeci-
ficity of the micro-organism, and the expected exposure. Useful
information may also be available from the observations carried out
inefficacytesting.
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
takenintoconsideration.
Additional studies might include further studies on additional species
orhighertierstudiessuchasstudiesonselectednon-targetorganisms.
Beforeperformingsuchstudies,theapplicantshallseekagreementof
thecompetentauthoritiesonthetypeofstudytobeperformed.
11. SUMMARYANDEVALUATIONOFENVIRONMENTALIMPACT
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
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, with particular reference
totherisksfortheenvironmentandnon-targetspeciesthatmayordo1991L0414—EN—01.01.2002—004.001—142
▼M25
arise, and the extent, quality and reliability of the database. In parti-
cularthefollowingissuesshouldbeaddressed:
— predictionofdistributionandfateintheenvironment,andthetime
coursesinvolved,
— identification of non-target species and populations at risk, and
predictionoftheextentofpotentialexposure,
— identification of precautions necessary to avoid or minimise
contamination of the environment, and for the protection of non-
targetspecies.1991L0414—EN—01.01.2002—004.001—143
▼B
ANNEX IV
RISKPHRASES1991L0414—EN—01.01.2002—004.001—144
▼B
ANNEX V
SAFETYPHRASES1991L0414—EN—01.01.2002—004.001—145
▼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. Absenceofunacceptableeffectsonplantsorplantproducts
2.3. Impactonvertebratestobecontrolled2.4. Impactonhumanoranimalhealth2.4.1. arisingfromtheplantprotectionproduct
2.4.2. arisingfromresidues
2.5. Influenceontheenvironment2.5.1. Fateanddistributionintheenvironment
2.5.2. Impactonnon-targetspecies
2.6. Analyticalmethods2.7. Physicalandchemicalproperties
C.DECISION-MAKING
1.General principles
2.Specific principles
2.1. Efficacy
2.2. Absenceofunacceptableeffectsonplantsorplantproducts2.3. Impactonvertebratestobecontrolled
2.4. Impactonhumanoranimalhealth
2.4.1. arisingfromtheplantprotectionproduct2.4.2. arisingfromresidues
2.5. Influenceontheenvironment
2.5.1. Fateanddistributionintheenvironment2.5.2. Impactonnon-targetspecies
2.6. Analyticalmethods
2.7. Physicalandchemicalproperties1991L0414—EN—01.01.2002—004.001—146
▼M10
A.INTRODUCTION
1. The principles developed in this Annexaimtoensure that evalua-
tionsanddecisionswithregardtoauthorization ofplantprotection
products, provided they are chemical preparations, results in the
implementation of the requirements of Article 4 (1) (b), (c), (d)
and(e)ofthisDirectivebyalltheMemberStatesatthehighlevel
ofprotectionofhumanandanimalhealthandtheenvironment.
2. In evaluating applications and granting authorizations Member
Statesshall:
(a) — ensure that the dossier supplied is in accordance with the
requirements ofAnnexIII,atthelatestatthetimeoffina-
lization of the evaluation for the purpose of decision-
making,withoutprejudice,whererelevant,totheprovisions
ofArticle13(1)(a),(4)and(6)ofthisDirective,
— ensure that the data submitted are acceptable in terms of
quantity, quality, consistency and reliability and sufficient
topermitaproperevaluationofthedossier,
— evaluate, where relevant, justifications submitted by the
applicantfornotsupplyingcertaindata;
(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
AnnexI,andtheresultsoftheevaluationofthosedata,without
prejudice, where relevant, to the provisions of Article 13 (1)
(b),(2),(3)and(6)ofthisDirective;
(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
componentsoritsresidues.
3. Whereinthespecificprinciplesonevaluationreferenceismadeto
AnnexIIdata,thisshallbeunderstoodasbeingthedatareferredto
inpoint2(b).
4. Where the data and information provided are sufficient to permit
completionoftheevaluationforoneoftheproposeduses,applica-
tionsmustbeevaluatedandadecisionmadefortheproposeduse.
Taking account of justifications provided and with the 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
oneoftheproposeduses.
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
AnnexorofthisDirective.
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
AnnexIII.
6. ThejudgementsmadebythecompetentauthoritiesoftheMember
States during the evaluation and decision-making process must be
basedonscientificprinciples,preferablyrecognizedatinternational
level(forexample,bytheEPPO),andbemadewiththebenefitof
expertadvice.
B.EVALUATION
1.Generalprinciples
1. Having regard to current scientific and technical knowledge,
MemberStatesshallevaluatetheinformationreferredtoinPart
A,point2,andinparticular:
(a) assess the performance in terms of efficacy and phytotoxi-
city of the plant protection product for each use for which
authorizationissought;and1991L0414—EN—01.01.2002—004.001—147
▼M10
(b) identify the harzards arising, assess their significance and
make a judgment as to the likely risks to humans, animals
ortheenvironment.
2. In accordance with the terms of Article 4 of this Directive,
whichinter aliaspecifies 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
takeintoaccounttheprinciplesofintegratedcontrol.
3. Intheevaluationofapplicationssubmitted,MemberStatesshall
have regard to the agricultural, plant health or environmental
(includingclimatic)conditionsintheareasofuse.
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
thatthechancesoffailingtodetectadverseeffectsorofunder-
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
leadtoafalseclassificationofrisk.
The first evaluation made shall be based on the best available
dataorestimatesreflectingtherealisticconditionsofuseofthe
plantprotectionproduct.
This should be followed by a repeat evaluation, taking account
of potential uncertainties in the critical data and of a range of
useconditionsthatarelikelytooccurandresultinginarealistic
worst-caseapproach,todeterminewhetheritispossiblethatthe
initialevaluationcouldhavebeensignificantlydifferent.
5. Where specific principles of Section 2 provide for the use of
calculation models in the evaluation of a plant protection
product,thosemodelsshall:
— make a best possible estimation of all relevant processes
involved taking into account realistic parameters and
assumptions,
— besubmittedtoananalysisasreferredtoinB,point1.4,
— be reliably validated with measurements carried out under
circumstancesrelevantfortheuseofthemodel,
— berelevanttotheconditionsintheareaofuse.
6. Wheremetabolites,degradationorreactionproductsarereferred
tointhe specific principles, onlythosethat arerelevant forthe
proposedcriterionshallbetakenintoconsideration.
2.Specificpriciples
MemberStatesshall,fortheevaluationofthedataandinformation
submitted in support of applications, and without prejudice to the
generalprinciplesofSection1,implementthefollowingprinciples.
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 organismcould be harm ful under the agricultural, plant
health and environmental (including climatic) conditions in the
areaoftheproposeduse.
2.1.2. Wheretheproposeduseconcernsaneffectotherthanthecontrolof
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)conditionsintheareaofproposeduseiftheplantprotec-
tionproductwerenotused.
2.1.3. MemberStatesshallevaluatetheefficacydataontheplantprotec-
tion product as provided for in Annex III having regard to the
degree of control or the extent of the effect desired and having
regardtotherelevantexperimentalconditionssuchas:
— thechoiceofthecroporcultivar,1991L0414—EN—01.01.2002—004.001—148
▼M10
— the agricultural and environmental (including climatic) condi-
tions,
— thepresenceanddensityoftheharmfulorganism,— thedevelopmentstageofcropandorganism,
— theamountoftheplantprotectionproductused,
— ifrequiredonthelabel,theamountofadjuvantadded,— thefrequencyandtimingoftheapplications,
— thetypeofapplicationequipment.
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-
teredinpracticeintheareaofproposeduseandinparticular:
(i) thelevel,consistencyanddurationoftheeffectsoughtinrela-
tiontothedoseincomparisonwithasuitablereferenceproduct
orproductsandanuntreatedcontrol;
(ii) where relevant, effect on yield or reduction of loss in storage,
in terms of quantity and/or quality, in comparison with a
suitablereferenceproductorproductsandanuntreatedcontrol.
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)
conditionsintheareaofproposeduse.
2.1.5. Wheretheproductlabel includes requirements foruseoftheplant
protectionproductwithotherplantprotection productsand/orwith
adjuvantsasatankmix,MemberStatesshallmaketheevaluations
referred to in points 2.1.1 to 2.1.4 in relation to the information
suppliedforthetankmix.
Where the product label includes recommendations for use of the
plant protection product with other plant protection products and/
or withadjuvants as a tank mix, Member States shall evaluate the
appropriatenessofthemixandofitsconditionsofuse.
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
theproposedconditionsofuseincomparison,whererelevant,with
asuitablereferenceproductorproducts,wheretheyexist,and/oran
untreatedcontrol.
(a) Thisevaluationwilltakeintoconsiderationthefollowinginfor-
mation:
(i) theefficacydataprovidedforinAnnexIII;
(ii) other relevant information on the plant protection product
suchasnatureofthepreparation,dose,methodofapplica-
tion,numberandtimingofapplications;
(iii) all relevant information on the active substance as
providedforinAnnexII,includingmodeofaction,vapour
pressure,volatilityandwatersolubility;
(b) Thisevaluationwillinclude:
(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) thedifferencesbetweenmaincultivarswithregardtotheir
sensitivitytophytotoxiceffects;
(iii) thepartofthetreatedcroporplantproductswherephyto-
toxiceffectsareobserved;
(iv) theadverseimpactontheyieldofthetreatedcroporplant
productsintermsofquantityand/orquality;
(v) the adverse impact on treated plants or plant products to
beusedforpropagation,intermsofviability,germination,
sprouting,rootingandestablishment;
(vi) wherevolatile productsareconcerned,theadverseimpact
onadjacentcrops.
2.2.2. Where the available data indicate that the active substance or
significantmetabolites,degradationandreactionproductspersistin
soilsand/orinoronplantsubstancesinsignificant quantities after1991L0414—EN—01.01.2002—004.001—149
▼M10
useoftheplantprotectionproductaccordingtotheproposedcondi-
tions of use, Member States shall evaluate the degree of adverse
effects on subsequent crops. Thisevaluation will be carried out as
specifiedinpoint2.2.1.
2.2.3. Wheretheproductlabel includes requirements foruseoftheplant
protection product with other 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
tankmix.
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
effectsonthebehaviourandhealthofthetargetanimals;whenthe
intended effect is to kill the target animal they shall evaluate the
timenecessarytoobtainthedeathoftheanimalandtheconditions
underwhichdeathoccurs.
Thisevaluation willtakeintoconsideration thefollowinginforma-
tion:
(i) all relevant information as provided for in Annex II and the
results of the evaluation thereof, including the toxicological
andmetabolismstudies;
(ii) all relevant information on the plant protection product as
provided for in Annex III, including toxicological studies and
efficacydata.
2.4. Impact on human or animal health
2.4.1. arising fromthe plant protection product
2.4.1.1. Member States shall evaluate operator exposure to the active
substanceand/ortotoxicologicallyrelevantcompoundsintheplant
protectionproductlikelytooccurundertheproposedconditionsof
use (including in particular dose, application method and climatic
conditions) using by preference realistic data on exposure and, if
suchdataarenotavailable,asuitable,validatedcalculationmodel.
(a) Thisevaluationwilltakeintoconsiderationthefollowinginfor-
mation:
(i) thetoxicologicalandmetabolismstudiesasprovidedforin
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
exposedwithoutanyadverse health effects.The AOELis
expressedasmilligramsofthechemicalperkilogrambody
weightoftheoperator.TheAOELisbasedonthehighest
levelatwhichnoadverseeffectisobservedintestsinthe
most sensitive relevant animal species or, if appropriate
dataareavailable,inhumans;
(ii) otherrelevantinformationontheactivesubstancessuchas
physicalandchemicalproperties;
(iii) the toxicological studies provided for in Annex III,
includingwhereappropriatedermalabsorptionstudies;
(iv) other relevant information as provided for in Annex III
suchas:
— compositionofthepreparation,
— natureofthepreparation,— size,designandtypeofpackaging,
— fieldofuseandnatureofcroportarget,
— method of application including handling, loading and
mixingofproduct,
— exposurereductionmeasuresrecommended,— protectiveclothingrecommendations,
— maximumapplicationrate,
— minimumsprayapplicationvolumestatedonthelabel,— numberandtimingofapplications;
(b) This evaluation shall be made for each type of application
methodandapplicationequipmentproposedforuseoftheplant1991L0414—EN—01.01.2002—004.001—150
▼M10
protectionproductaswellasforthedifferenttypesandsizesof
containerstobeused,takingaccountofmixing,loadingopera-
tions, application of the plant protection product and cleaning
androutinemaintenanceofapplicationequipment.
2.4.1.2. MemberStatesshallexamineinformationrelatingtothenatureand
characteristics of the packaging proposed with particular reference
tothefollowingaspects:
— thetypeofpackaging,
— itsdimensionsandcapacity,— thesizeoftheopening,— thetypeofclosure,— its strength, leakproofness and resistance to normal transport
andhandling,
— itsresistancetoandcompatibilitywiththecontents.
2.4.1.3. Member States shall examine the nature and characteristics of the
protective clothing and equipment proposed with particular refer-
encetothefollowingaspects:
— obtainabilityandsuitability,
— easeofwearingtakingintoaccountphysicalstressandclimatic
conditions.
2.4.1.4. Member States shall evaluate the possibility of exposure of other
humans(bystandersorworkersexposedaftertheapplicationofthe
plant protection product) or animals to the active substance and/or
toothertoxicologically relevant compoundsintheplant protection
productundertheproposedconditionsofuse.
Thisevaluation willtakeintoconsideration thefollowinginforma-
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
whereappropriatedermalabsorptionstudies;
(iii) other relevant information on the plant protection product as
providedforinAnnexIIIsuchas:
— re-entryperiods,necessarywaitingperiodsorotherprecau-
tionstoprotecthumansandanimals,
— methodofapplication,inparticularspraying,— maximumapplicationrate,— maximumsprayapplicationvolume,— compositionofthepreparation,— excess remaining on plants and plant products after treat-
ment,
— furtheractivitieswherebyworkersareexposed.
2.4.2. Arising fromresidues
2.4.2.1. MemberStatesshallevaluatethespecificinformationontoxicology
asprovidedforinAnnexIIandinparticular:
— thedeterminationofanacceptabledailyintake(ADI),
— the identification of metabolites, degradation and reaction
productsintreatedplantsorplantproducts,
— behaviourofresiduesoftheactivesubstanceanditsmetabolites
fromthetimeofapplicationuntilharvest,orinthecaseofpost-
harvestuses,untiloutloadingofstoredplantproducts.
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
followinginformation:
— 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
storageperiods,inthecaseofpost-harvestuses,
— natureofthepreparation,
— analyticalmethodsandtheresiduedefinition.
2.4.2.3. OnthebasisofsuitablestatisticalmodelsMemberStatesshalleval-
uate the residue levels observed in the reported trials. This1991L0414—EN—01.01.2002—004.001—151
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evaluationshallbemadeforeachproposeduseandshalltakeinto
consideration:
(i) theproposedconditionsofuseoftheplantprotectionproduct;
(ii) the specific information on residues in or on treated plants,
plant products, food and feed as provided for in Annex III
andthedistributionofresiduesbetweenedibleandnon-edible
parts;
(iii) the specific information on residues in or on treated plants,
plantproducts,foodandfeedasprovidedforinAnnexIIand
theresultsoftheevaluationthereof;
(iv) therealisticpossibilitiesofextrapolatingdatafromonecropto
another.
2.4.2.4. Member States shall evaluate the residue levels observed in
productsofanimalorigin,takingintoconsiderationtheinformation
provided for in Annex III,Part A, point 8.4 and residues resulting
fromotheruses.
2.4.2.5. Member States shall estimate the potential exposure of consumers
through diet and, where relevant, other ways of exposure, using a
suitablecalculationmodel.Thisevaluationwilltakeaccount,where
relevant, of other sources of information such as other authorized
uses of plant protection products containing the same active
substanceorwhichgiverisetothesameresidues.
2.4.2.6. Member States shall, where relevant, estimate the exposure of
animals, taking into account the residue levels observed in treated
plantsorplantproductsintendedtobefedtoanimals.
2.5. Influence on the environment
2.5.1. Fate and distribution in the environment
Intheevaluationofthefateanddistributionoftheplantprotection
productintheenvironment,MemberStatesshallhaveregardtoall
aspectsoftheenvironment,includingbiota,andinparticulartothe
following:
2.5.1.1. MemberStatesshallevaluatethepossibilityoftheplantprotection
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
activesubstanceandofrelevantmetabolites, degradationandreac-
tion products that could be expected in the soil in the area of
envisaged use after use of the plant protection product according
totheproposedconditionsofuse.
Thisevaluation willtakeintoconsideration thefollowinginforma-
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) otherrelevantinformationontheactivesubstancesuchas:
— molecularweight,
— solubilityinwater,— octanol/waterpartitioncoefficient,
— vapourpressure,
— volatilizationrate,— dissociationconstant,
— photodegradationrateandidentityofbreakdownproducts,
— hydrolysisrateinrelationtopHandidentityofbreakdown
products;
(iii) allinformationontheplantprotectionproductasprovidedfor
in Annex III, including the information on distribution and
dissipationinsoil;1991L0414—EN—01.01.2002—004.001—152
(*) 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-
waysleadingtonaturalproducts.
▼M10
(iv) where relevant, other authorized uses of plant protection
products in the area of proposed use containing the same
activesubstanceorwhichgiverisetothesameresidues.
2.5.1.2. MemberStatesshallevaluatethepossibilityoftheplantprotection
productreachingthegroundwaterundertheproposedconditionsof
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
andreactionproductsthatcouldbeexpectedinthegroundwaterin
the area of envisaged use after use of the plant protection product
accordingtotheproposedconditionsofuse.
As long as there is no validated Community calculation model,
MemberStates shall base their evaluation especially on the results
of mobility and persistance in soil studies as provided for in
AnnexesIIandIII.
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
evaluationthereof;
(ii) otherrelevantinformationontheactivesubstancesuchas:
— molecularweight,
— solubilityinwater,
— octanol/waterpartitioncoefficient,
— vapourpressure,— volatilizationrate,
— hydrolysisrateinrelationtopHandidentityofbreakdown
products,
— dissociationconstant;
(iii) allinformationontheplantprotectionproductasprovidedfor
in Annex III, including the information on distribution and
dissipationinsoilandwater;
(iv) where relevant, other authorized uses of plant protection
products in the area of envisaged use containing the same
activesubstanceorwhichgiverisetothesameresidues;
(v) where relevant, data on dissipation including transformation
andsorptioninthesaturatedzone;
(vi) where relevant, data on the procedures for drinking water
abstractionandtreatmentintheareaofenvisageduse;
(vii) whererelevant,monitoringdataonthepresenceorabsenceof
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
substanceorwhichgiverisetothesameresidues;suchmoni-
toringdatashallbeinterpretedinaconsistentscientificway.
2.5.1.3. MemberStatesshallevaluatethepossibilityoftheplantprotection
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-termpredicted 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
useoftheplantprotectionproductaccordingtotheproposedcondi-
tionsofuse.
If there is no validated Community calculation model, Member
Statesshallbasetheirevaluationespeciallyontheresultsofmobi-
lity and persistence in soil studies and the information on run-off
anddriftasprovidedforinAnnexesIIandIII.
This evaluation will also take into consideration the following
information:
(i) the specific information on fate and behaviour in soil and
waterasprovidedforinAnnexIIandtheresultsoftheevalua-
tionthereof;
(ii) otherrelevantinformationontheactivesubstancesuchas:
— molecularweight,
— solubilityinwater,— octanol/waterpartitioncoefficient,
— vapourpressure,1991L0414—EN—01.01.2002—004.001—153
▼M10
— volatilizationrate,
— hydrolysisrateinrelationtopHandidentityofbreakdown
products,
— dissociationconstant;
(iii) all relevant information on the plant protection product as
providedforinAnnexIII,includingtheinformationondistri-
butionanddissipationinsoilandwater;
(iv) possibleroutesofexposure:
— drift,
— run-off,
— overspray,
— dischargeviadrains,— leaching,
— depositintheatmosphere;
(v) where relevant, other authorized uses of plant protection
products in the area of envisaged use containing the same
activesubstanceorwhichgiverisetothesameresidues;
(vi) where relevant, data on the procedures for drinking water
abstractionandtreatmentintheareaofenvisageduse.
2.5.1.4. MemberStatesshallevaluatethepossibilityoftheplantprotection
productbeingdissipatedintheairundertheproposedconditionsof
use;ifthispossibilityexiststheyshallmakethebestpossibleesti-
mation, using where appropriate a suitable, validated calculation
model,oftheconcentration oftheactivesubstanceandofrelevant
metabolites, degradation and reaction products that could be
expected in the air after use of the plant protection product
accordingtotheproposedconditionsofuse.
Thisevaluation willtakeintoconsideration thefollowinginforma-
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
evaluationthereof;
(ii) otherrelevantinformationontheactivesubstancesuchas:
— vapourpressure,
— solubilityinwater,
— hydrolysisrateinrelationtopHandidentityofbreakdown
products,
— photochemicaldegradationinwaterandairandidentityof
breakdownproducts,
— octanol/waterpartitioncoefficient;
(iii) all relevant information on the plant protection product as
providedforinAnnexIII,includingtheinformationondistri-
butionanddissipationinair.
2.5.1.5. Member States shall evaluate the procedures for destruction or
decontaminationoftheplantprotectionproductanditspackaging.
2.5.2. Impact on non-target species
Whencalculatingtoxicity/exposureratiosMemberStatesshalltake
into consideration toxicity to the most sensitive relevant organism
usedinthetests.
2.5.2.1. Member States shall evaluate the possibility of exposure of birds
and other terrestrial vertebrates to the plant protection product
undertheproposedconditionsofuse;ifthispossibilityexiststhey
shallevaluatetheextentoftheshort-termandlong-termrisktobe
expectedfortheseorganisms,includingtheirreproduction,afteruse
oftheplantprotectionproductaccordingtotheproposedconditions
ofuse.
(a) Thisevaluationwilltakeintoconsiderationthefollowinginfor-
mation:
(i) thespecificinformationrelatingtotoxicologicalstudieson
mammals and to the effects on birdsand 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
theevaluationthereof;1991L0414—EN—01.01.2002—004.001—154
▼M10
(ii) allrelevantinformation ontheplantprotectionproductas
provided for in Annex III, including the information on
effectsonbirdsandothernon-targetterrestrialvertebrates;
(iii) where relevant, other authorized uses of plant protection
productsintheareaofenvisagedusecontainingthesame
activesubstanceorwhichgiverisetothesameresidues;
(b) Thisevaluationwillinclude:
(i) thefateanddistribution,includingpersistenceandbiocon-
centration, of the active substance and of relevant
metabolites, breakdown and reaction products in the
various parts of the environment after application of the
plantprotectionproduct;
(ii) theestimatedexposureofthespecieslikelytobeexposed
atthetimeofapplicationorduringtheperiodthatresidues
arepresent,takingintoaccountallrelevantroutesofexpo-
suresuchasingestionoftheformulatedproductortreated
food, predation on invertebrates, feeding on vertebrate
prey,contactbyoversprayingorwithtreatedvegetation;
(iii) acalculationoftheacute,short-termand,wherenecessary,
long-termtoxicity/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
exposureexpressedinmg/kgbodyweight.
2.5.2.2. MemberStatesshallevaluatethepossibilityofexposureofaquatic
organismstotheplantprotectionproductundertheproposedcondi-
tionsofuse;ifthispossibilityexiststheyshallevaluatethedegree
of short-termand long-termrisk to be expected for aquatic organ-
isms after use of the plant protection product according to the
proposedconditionsofuse.
(a) Thisevaluationwilltakeintoconsiderationthefollowinginfor-
mation:
(i) the specific information relating to the effects on aquatic
organisms as provided for in Annex II and the results of
theevaluationthereof;
(ii) otherrelevantinformationontheactivesubstancesuchas:
— solubilityinwater,
— octanol/waterpartitioncoefficient,— vapourpressure,
— volatilizationrate,
— KOC,— biodegradationinaquaticsystemsandinparticularthe
readybiodegradability,
— photodegradation rate and identity of breakdown
products,
— hydrolysisrateinrelationtopHandidentityofbreak-
downproducts;
(iii) allrelevantinformation ontheplantprotectionproductas
provided for in Annex III and in particular the effects on
aquaticorganisms;
(iv) where relevant, other authorized uses of plant protection
products in the area of envisaged use, containing the
sameactivesubstanceorwhichgiverisetothesameresi-
dues;
(b) Thisevaluationwillinclude:
(i) thefateanddistributionofresiduesoftheactivesubstance
and of relevant metabolites, breakdown and reaction
productsinwater,sedimentorfish;
(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-
termenvironmentalconcentration;
(iii) a calculation of the algal growth inhibition/exposure ratio
foralgae.ThisratioisdefinedasthequotientoftheEC50andthepredictedshort-termenvironmentalconcentration;
(iv) a calculation of the long-termtoxicity/exposure ratio for
fishandDaphnia.Thelong-termtoxicity/exposureratiois
defined as the quotient of the NOEC and the predicted
long-termenvironmentalconcentration;1991L0414—EN—01.01.2002—004.001—155
▼M10
(v) where relevant, the bioconcentration in fish and possible
exposureofpredatorsoffish,includinghumans;
(vi) if the plant protection product is to be applied directly to
surface water, the effect on the change of surface water
quality,suchaspHordissolvedoxygencontent.
2.5.2.3. MemberStatesshallevaluate thepossibilityofexposureofhoney-
bees to the plant protection product under the proposed conditions
of use; if this possibility exists they shall evaluate the short-term
and long-termrisk to be exptected for honeybees after use of the
plant protection product according to the proposed conditions of
use.
(a) Thisevaluationwilltakeintoconsiderationthefollowinginfor-
mation:
(i) the specific information on toxicity to honeybees as
providedforinAnnexIIandtheresultsoftheevaluation
thereof;
(ii) otherrelevantinformationontheactivesubstancesuchas:
— solubilityinwater,
— octanol/waterpartitioncoefficient,
— vapourpressure,
— photodegradation rate and identity of breakdown
products,
— modeofaction(e.g.insectgrowthregulatingactivity);
(iii) allrelevantinformation ontheplantprotectionproductas
providedforinAnnexIII,includingthetoxicitytohoney-
bees;
(iv) where relevant, other authorized uses of plant protection
products in the area of envisaged use, containing the
sameactivesubstanceorwhichgiverisetothesameresi-
dues;
(b) Thisevaluationwillinclude:
(i) the ratio between the maximum application rate expressed
ingrammesofactivesubstanceperhectareandthecontact
and oral LD50expressed in µg of active substance per bee
(hazard quotients) and where necessary the persistence of
residuesonor,whererelevant,inthetreatedplants;
(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
conditionsofuse.
2.5.2.4. MemberStatesshallevaluatethepossibilityofexposureofbenefi-
cialarthropodsotherthanhoneybeestotheplantprotectionproduct
undertheproposedconditionsofuse;ifthispossibilityexiststhey
willassessthelethalandsublethaleffectsontheseorganismstobe
expected and the reduction in their activity after use of the plant
protectionproductaccordingtotheproposedconditionsofuse.
Thisevaluation willtakeintoconsideration thefollowinginforma-
tion:
(i) the specific information on toxicity to honeybees and other
beneficial arthropods as provided for in Annex II and the
resultsoftheevaluationthereof;
(ii) otherrelevantinformationontheactivesubstancesuchas:
— solubilityinwater,
— octanol/waterpartitioncoefficient,
— vapourpressure,
— photodegradationrateandidentityofbreakdownproducts,
— modeofaction(e.g.insectgrowthregulatingactivity);
(iii) all relevant information on the plant protection product as
providedforinAnnexIIIsuchas:
— effectsonbeneficialarthropodsotherthanbees,
— toxicitytohoneybees,— availabledatafrombiologicalprimaryscreening,
— maximumapplicationrate,
— maximumnumberandtimetableofapplications;
(iv) where relevant, other authorized uses of plant protection
products in the area of envisaged use, containing the same
activesubstanceorwhichgiverisetothesameresidues.1991L0414—EN—01.01.2002—004.001—156
▼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-termand
long-termrisk to be expected to these organism s after use of the
plant protection product according to the proposed conditions of
use.
(a) Thisevaluationwilltakeintoconsiderationthefollowinginfor-
mation:
(i) the specific information relating to the toxicity of the
active substance to earthworms and to other non-target
soilmacro-organismsasprovidedforinAnnexIIandthe
resultsoftheevaluationthereof;
(ii) otherrelevantinformationontheactivesubstancesuchas:
— solubilityinwater,
— octanol/waterpartitioncoefficient,— Kdforadsorption,
— vapourpressure,
— hydrolysisrateinrelationtopHandidentityofbreak-
downproducts,
— photodegradation rate and identity of breakdown
products,
—D T
50andDT90fordegradationinthesoil;
(iii) allrelevantinformation ontheplantprotectionproductas
provided for in Annex III, including the effects on earth-
wormsandothernon-targetsoilmacro-organisms;
(iv) where relevant, other authorized uses of plant protection
products in the area of envisaged use, containing the
sameactivesubstanceorwhichgiverisetothesameresi-
dues;
(b) Thisevaluationwillinclude:
(i) thelethalandsublethaleffects,
(ii) the predicted initial and long-termenvironm ental concen-
tration,
(iii) a calculation of the actue toxicity/exposure ratio (defined
asthequotientofLC50andpredictedinitialenvironmental
concentration)andofthelong-termtoxicity/exposureratio
(defined asthequotient oftheNOECandpredicted long-
termenvironmentalconcentration),
(iv) where relevant, the bioconcentration and persistence of
residuesinearthworms.
2.5.2.6. MemberStatesshall,wheretheevaluationcarriedoutunderPartB,
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
useoftheplantprotectionproductaccordingtotheproposedcondi-
tionsofuse.
Thisevaluation willtakeintoconsideration thefollowinginforma-
tion:
(i) all relevant information onthe 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
oftheevaluationthereof;
(ii) all relevant information on the plant protection product as
provided for in Annex III, including the effects on non-target
soilmicro-organisms;
(iii) where relevant, other authorized uses of plant protection
products in the area of proposed use, containing the same
activesubstanceorwhichgiverisetothesameresidues;
(iv) allavailableinformationfrombiologicalprimaryscreening.
2.6. Analytical methods
Member States shall evaluate the analytical methods proposed for
post-registrationcontrolandmonitoringpurposes,todetermine:1991L0414—EN—01.01.2002—004.001—157
▼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.
Thisevaluation willtakeintoconsideration thefollowinginforma-
tion:
(i) thedataonanalyticalmethodsasprovidedforinAnnexIIand
theresultsoftheevaluationthereof;
(ii) the data on analytical methods as provided for in Annex III
andinparticular:
— thespecificityandlinearityoftheproposedmethods,
— theimportanceofinterferences,— the precision of the proposed methods (intra-laboratory
repeatabilityandinter-laboratoryreproducibility);
(iii) the limit of detection and determination of the proposed
methodsforimpurities.
2.6.2. for residue analysis:
the residues of the active substance, metabolites, breakdown or
reactionproductsresultingfromauthorizedusesoftheplantprotec-
tion product and which are of toxicological, ecotoxicological or
environmentalsignificance.
Thisevaluation willtakeintoconsideration thefollowinginforma-
tion:
(i) thedataonanalyticalmethodsasprovidedforinAnnexIIand
theresultsoftheevaluationthereof;
(ii) the data on analytical methods as provided for in Annex III
andinparticular:
— thespecificityoftheproposedmethods,
— the precision of the proposed methods (intra-laboratory
repeatabilityandinter-laboratoryreproducibility),
— the recovery rate of the proposed methods at appropriate
concentrations;
(iii) thelimitofdetectionoftheproposedmethods;
(iv) thelimitofdeterminationoftheproposedmethods.
2.7. Physical and chemical properties
2.7.1. MemberStatesshallevaluatetheactualactivesubstancecontentof
theplantprotectionproductanditsstabilityduringstorage.
2.7.2. Member States shall evaluate the physical and chemical properties
oftheplantprotectionproductandinparticular:
— where a suitable FAO specification exists, the physical and
chemicalpropertiesaddressedinthatspecification,
— where no suitable FAO specification exists, all the relevant
physicalandchemicalpropertiesfortheformulationasreferred
tointhe‘Manualonthedevelopment anduseofFAOspecifi-
cationsforplantprotectionproducts’.
Thisevaluation willtakeintoconsideration thefollowinginforma-
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
evaluationthereof;
(ii) the data on the physical and chemical properties of the plant
protectionproductasprovidedforinAnnexIII.
2.7.3. Whereproposedlabelclaimsincluderequirementsorrecommenda-
tions for use of the plant protection product with other plant
protection products or adjuvants as a tank mix, the physical and
chemicalcompatibilityoftheproductsinthemixturemustbeeval-
uated.1991L0414—EN—01.01.2002—004.001—158
▼M10
C.DECISION-MAKING
1.Generalprinciples
1. Where appropriate, Member States shall impose conditions or
restrictions with the authorizations they grant. The nature and
severityofthesemeasuresmustbeselectedonthebasisof,and
be appropriate to, the nature and extent of the expected advan-
tagesandtheriskslikelytoarise.
2. Member States shall ensure that, where necessary, decisions
takenwithrespecttothegrantingofauthorizationstakeaccount
of the agricultural, plant health or environmental (including
climatic) conditionsintheareasofenvisageduse.Suchconsid-
erationsmayresultinspecificconditionsandrestrictionsofuse,
and, where necessary, in authorization being granted for some
butnototherareaswithintheMemberStateinquestion.
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
maynotgiverisetoundesirableeffectssuchasthedevelopment
ofresistance.
4. MemberStatesshallensurethatdecisionsrespecttheprinciples
of integrated control if the product is intended to be used in
conditionswheretheseprinciplesarereliedon.
5. Sincetheevaluationistobebasedondataconcerningalimited
number of representative species, Member States shall ensure
that use of plant protection products does not have any long-
termrepercussionsfortheabundanceanddiversityofnon-target
species.
6. Beforeissuinganauthorization,MemberStatesshallensurethat
thelabeloftheproduct:
— fulfilstherequirementsofArticle16ofthisDirective,
— alsocontainstheinformationonprotectionofusersrequired
byCommunitylegislationonworkerprotection,
— specifies in particular the conditions or restrictions under
which the plant protection product may or may not be used
asreferredtoinpoints1,2,3,4and5above.
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
labellingofdangerouspreparations(pesticides)(1)andinArticle
16(g)and(h)ofDirective91/414/EEC.
7. Beforeissuingauthorizations,MemberStatesshall:
(a) ensurethattheproposedpackagingisinaccordancewiththe
provisionsofDirective78/631/EEC;
(b) ensurethat:
— the procedures for destruction of the plant protection
product,
— theproceduresforneutralizationoftheadverseeffectsof
theproductifitisaccidentallydispersed,and
— the procedures for the decontamination and destruction
ofthepackagings,
areinaccordancewiththerelevantregulatoryprovisions.1991L0414—EN—01.01.2002—004.001—159
(1) OJL206,29.7.1978,p.13.DirectiveaslastamendedbyDirective92/32/EEC(OJL
154,5.6.1992,p.1).
▼M10
8. No authorization shall be granted unless all the requirements
referredtoinSection2aresatisfied.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 proposedconditions of useoutweight the
possibleadverseeffectsofitsuse.Anyrestrictionsonuseof
the product relating to non-compliance with some of the
aforementioned requirements must be mentioned on the
label,andnon-compliance withtherequirements referredto
inpoint2.7mustnotcompromiseproperuseoftheproduct.
Theseadvantagescanbeintermsof:
— advantages for and compatibility with integrated control
measuresororganicfarming,
— facilitating strategies to minimize the risk of develop-
mentofresistance,
— the need for a greater diversity of types of active
substances or biochemical modes of action, e.g. for use
instrategiestoavoidacceleratedbreakdowninthesoil,
— reducedriskforoperatorsandconsumers,— reduced contamination of the environment and reduced
impactonnon-targetspecies;
(b) where the criteria referred to in Part C, point 2.6, are not
fully satisfied because of limitations in current analytical
science andtechnology, authorization shallbegranted fora
limited period if the methods submitted prove adequate for
the purposes intended. In this case the applicant shall be
givenatimelimitinwhichtodevelopandsubmitanalyticalmethods that are in accordance with the criteria referred to
above. The authorization will be reviewed on expiry of the
timelimitaccordedtotheapplicant;
(c) where the reproducibility of the submitted analytical
methodsreferredtoinPartC,point2.6,hasonlybeenveri-
fiedintwolaboratories,anauthorizationshallbegrantedfor
oneyeartopermittheapplicanttodemonstratethereprodu-
cibilityofthosemethodsinaccordancewithagreedcriteria.
9. Where an authorization has been granted according to the
requirements provided for in this Annex, Member States may,
byvirtueofArticle4(6):
(a) define,wherepossible,preferablyincloseco-operationwith
the applicant, measures to improve the performance of the
plantprotectionproduct,and/or
(b) define,wherepossible,incloseco-operationwiththeappli-
cant, measures to reduce further the exposure that could
occurduringandafteruseoftheplantprotectionproduct.
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
Thespecificprinciplesshallapplywithoutprejudicetothegeneral
principlesreferredtoinSection1.
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
wheretheotherintendedeffectsarenotconsideredtobebeneficial
under those conditions, no authorization shall be granted for those
uses.
2.1.2. Thelevel,consistencyanddurationofcontrolorprotectionorother
intended effects mustbe similar tothose resulting from the useof
suitable reference products. If no suitable reference product exists,
the plant protection product must be shown to give a defined1991L0414—EN—01.01.2002—004.001—160
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benefitintermsofthelevel,consistencyanddurationofcontrolor
protection or other intended effects under the agricultural, plant
health and environmental (including climatic) conditions in the
areaofproposeduse.
2.1.3. Whererelevant,yieldresponsewhentheproductisusedandreduc-
tion of loss in storage must be quantitatively and/or qualitatively
similar to those resulting from the use of suitable reference
products.Ifnosuitablereferenceproductexists,theplantprotection
productmustbeshowntogiveaconsistentanddefinedquantitative
and/or qualitative benefit in terms of yield response and reduction
of loss in storage under the agricultural, plant health and environ-
mental(includingclimatic)conditionsintheareaofproposeduse.
2.1.4. Conclusionsastotheperformanceofthepreparationmustbevalid
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
intendedforuseincertainspecifiedcircumstances(e.g.lightinfes-
tations,particularsoiltypesorparticulargrowingconditions).
2.1.5. Where proposed label claims include requirements for use of the
preparation with other specified plant protection products or adju-
vants as a tank mix, the mixture must achieve the desired effect
andcomplywiththeprinciplesreferredtoinpoints2.1.1to2.1.4.
Where proposed label claims include recommendations for use of
thepreparationwithspecifiedplantprotectionproductsoradjuvants
asatankmix,MemberStatesshallnotaccepttherecommendations
unlesstheyarejustified.
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-
priatelimitationsofuse.
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
treatedplantsorplantproducts.
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
preparationshouldnotbeappliedtocropstobeusedforprocessing
purposes.
2.2.4. Theremustbenounacceptable adverseeffectsontreatedplantsor
plantproductsusedforpropagationorreproduction,suchaseffects
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
propagationorreproduction.
2.2.5. Theremustbenounacceptableimpactonsucceedingcrops,except
where proposed label claims specify that particular crops, which
wouldbeaffected,shouldnotbegrownfollowingthetreatedcrop.
2.2.6. There must be no unacceptable impact on adjacent crops, except
where proposed label claims specify that the preparation should
notbeappliedwhenparticularsensitiveadjacentcropsarepresent.
2.2.7. Where proposed label claims include requirements for use of the
preparation with other plant protection products or adjuvants, as a
tank mix, the mixture must comply with the principles referred to
inpoints2.2.1to2.2.6.
2.2.8. The proposed instructions for cleaning the application equipment
must be both practical and effective so that they can be applied
witheasesoastoensuretheremovalofresidualtracesoftheplant
protectionproductwhichcouldsubsequentlycausedamage.
2.3. Impact on vertebrates to be controlled
An authorization for a plant protection product intended to elimi-
natevertebratesshallbegrantedonlywhen:
— deathissynchronouswiththeextinctionofconsciousness,or
— deathoccursimmediately,or1991L0414—EN—01.01.2002—004.001—161
▼M10
— vital functions are reduced gradually without signs of obvious
suffering.
Forrepellantproducts,theintendedeffectshallbeobtainedwithout
unnecessarysufferingandpainforthetargetanimals.
2.4. Impact on human or animal health
2.4.1. arising fromthe plant protection product
2.4.1.1. Noauthorizationshallbegrantediftheextentofoperatorexposure
in handling and using the plant protection product under the
proposedconditionsofuse,includingdoseandapplicationmethod,
exceedstheAOEL.
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 with Council Directive 80/1107/EEC of 27 November 1980
on the protection of workers fromthe risks related to exposure to
chemical, physical and biological agents at work(1) and in accor-
dance with Council Directive 90/394/EEC of 28 June 1990 on the
protectionofworkersfromtherisksrelatedtoexposuretocarcino-
gensatwork(sixthspecialdirective withinthemeaningofArticle
16(2)ofDirective89/39/EEC)(2).
2.4.1.2. Where the proposed conditions of use require use of items of
protectiveclothingandequipment,noauthorizationshallbegranted
unlessthoseitemsareeffectiveandinaccordancewiththerelevant
Community provisions and are readily obtainable by the user andunlessit is feasible to usethemunder the circum stances of useof
theplantprotectionproduct,takingintoaccountclimaticconditions
inparticular.
2.4.1.3. Plant protection products whichbecause ofparticular properties or
ifmishandled ormisused could lead toahighdegree ofriskmust
be subject to particular restrictions such as restrictions on the size
ofpackaging, formulation type, distribution, useormanner ofuse.
Moreover, plant protection products which are classified as very
toxicmaynotbeauthorizedforusebynon-professionalusers.
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
AOELlevelsestablishedfortheactivesubstanceortoxicologically
relevant compound(s)in the plant protection product norany limit
values established for those compounds in accordance with the
Communityprovisionsreferredtoinpoint2.4.1.1.
2.4.1.5. Waiting and re-entry safety periods or other precautions must be
establishedinsuchawaythatnoadverseimpactonanimalsoccurs.
2.4.1.6. Waitingandre-entryperiodsorotherprecautionstoensurethatthe
AOEL levels and limit values are respected must be realistic; if
necessaryspecialprecautionarymeasuresmustbeprescribed.
2.4.2. arising fromresidues
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 such a manner (including pre-harvest intervals or
withholdingperiodsorstorageperiods)thattheresiduesatharvest,
slaughter or after storage, as appropriate, are reduced to a
minimum.1991L0414—EN—01.01.2002—004.001—162
(1) OJL327,3.12.1980,p.8.DirectiveaslastamendedbyDirective88/642/EEC(OJL
356,24.12.1988,p.74).
(2) OJL196,26.7.1990,p.1.DirectiveasamendedbyDirective97/42/EC(OJL179,8.
7.1997,p.4).
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2.4.2.2. WherenoCommunitymaximumresiduelimit (MRL)(*)orprovi-
sional MRL (at national or at Community level) exists, Member
StatesshallestablishaprovisionalMRLinaccordancewithArticle
4(1)(f)ofthisDirective;conclusionsastothelevelsfixedmustbe
validforallcircumstanceswhichcouldinfluencetheresiduelevels
in the crop such as timing of application, application rate and
frequencyormannerofuse.
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
unlessanewprovisionalMRLhasbeenestablishedbytheMember
StateortheCommissioninaccordancewithArticle4(1)(f)ofthis
Directive.
2.4.2.4. WhereaCommunityMRLexistsMemberStatesshallnotgrantan
authorization for the plant protection product unless the applicant
can provide evidence that its recommended use will not exceed
thatMRL,orunlessanewCommunity MRLhasbeen established
in accordance with the procedure provided for in the relevant
Communitylegislation.
2.4.2.5. Inthe casesreferred toinpoints2.4.2.2and2.4.2.3,each applica-
tionforanauthorizationmustbeaccompaniedbyariskassessment
taking into account worst-case potential exposure of consumers in
theMemberStateconcernedonthebasisofgoodagriculturalprac-
tice.
Takingintoaccountallregistereduses,theproposedusecannotbe
authorizedifthebestpossibleestimateofdietaryexposureexceeds
theADI.
2.4.2.6. Wherethenatureofresiduesisaffected duringprocessing,asepa-
rate risk assessment may need to be carried out under the
conditionsprovidedforinpoint2.4.2.5.
2.4.2.7. Wherethetreatedplantsorplantproductsareintendedtobefedto
animals, residues occurring shall not have an adverse effect onanimalhealth.
2.5. Influence on the environment
2.5.1. Fate and distribution in the environment
2.5.1.1. Noauthorizationshallbegrantediftheactivesubstanceand,where
theyareofsignificance fromthetoxicological, ecotoxicological or
environmental point of view, metabolites and breakdown or reac-
tion products, after use of the plant protection product under the
proposedconditionsofuse:
— during tests in the field, persist in soil for more than one year
(i.e.DT
90>1yearandDT50>3months),or1991L0414—EN—01.01.2002—004.001—163
(*) ACommunityMRLwillmeananMRLestablishedpursuanttoCouncilDirective76/
895/EECof23November1976relatingtothefixingofmaximumlevelsforpesticideresidues in and on fruit and vegetables(
1), Council Directive 86/362/EECof 24 July
1986 on the fixing of maximum levels for pesticide residues in and on cereals(2),
Council Directive 86/363/EECof 24 July 1986 onthe fixing of maximum levels for
pesticideresiduesinandonfoodstuffsofanimalorigin(3),CouncilRegulation(EEC)
No2377/90 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 March 1991
amending Directive 74/63/EEC on undesirable substances and products in feeding-stuffs(
6).
(1) OJL340,9.12.1976,p.26.DirectiveaslastamendedbyDirective97/41/EC(OJ
L184,12.7.1997,p.33).
(2) OJL221,7.8.1986,p.37.DirectiveaslastamendedbyDirective97/41/EC(OJ
L184,12.7.1997,p.33).
(3) OJL221,7.8.1986,p.43.DirectiveaslastamendedbyDirective97/41/EC(OJ
L184,12.7.1997,p.33).
(4) OJL224,18.8.1990,p.1.Regulation aslastamended byCommissionRegula-
tion(EC)No749/97(OJL110,26.4.1997,p.24).
(5) OJL350,14.12.1990,p.71.DirectiveasamendedbyDirective97/41/EC(OJL
184,12.7.1997,p.33).
(6) OJL66,13.3.1991,p.16.
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— during laboratory tests, formnon-extractable residues in
amounts exceeding 70 % of the initial dose after 100 days
withamineralizationrateoflessthan5%in100days,
unless it is scientifically demonstrated that under field conditions
there is no accumulation in soil at such levels that unacceptable
residuesinsucceeding cropsoccurand/orthatunacceptable 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. Noauthorization shallbegrantediftheconcentration oftheactive
substance or of relevant metabolites, degradation or reaction
productsingroundwater,maybeexpectedtoexceed,asaresultof
useoftheplantprotectionproductundertheproposedconditionsof
use,thelowerofthefollowinglimitvalues:
(i) the maximum permissible concentration laid down by Council
Directive80/778/EEC(1)of15July1980relatingtothequality
ofwaterintendedforhumanconsumption,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
activesubstancewasincludedinAnnexI
unless it is scientifically demonstrated that under relevant field
conditionsthelowerconcentrationisnotexceeded.
2.5.1.3. Noauthorization shallbegrantediftheconcentration oftheactive
substance or of relevant metabolites, breakdown or reaction
products to be expected after use of the plant protection product
undertheproposedconditionsofuseinsurfacewater:
— exceeds, where the surface water in or fromthe area of envi-
sageduseis intended forthe abstraction ofdrinking water, the
valuesfixedbyCouncilDirective75/440/EECof16June1975
concerningthequalityrequiredofsurfacewaterintendedforthe
abstractionofdrinkingwaterintheMemberStates(2),or
— has an impact deemed unacceptable on non-target species,
including animals, according to the relevant requirements
providedforinpoint2.5.2.
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
waterisreducedtoaminimum.
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
orworkersasreferredtoinPartC,point2.4.1,areexceeded.
2.5.2. Impact on non-target species
2.5.2.1. Wherethereisapossibilityofbirdsandothernon-targetterrestrial
vertebratesbeingexposed,noauthorizationshallbegrantedif:
— the acute and short-termtoxicity/exposure ratio for birds and
other non-target terrestrial vertebrates is less than 10 on the
basis of LD50or the long-termtoxicity/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
accordingtotheproposedconditionsofuse;
— thebioconcentrationfactor(BCF,relatedtofattissue)isgreater
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
protectionproductaccordingtotheproposedconditionsofuse.1991L0414—EN—01.01.2002—004.001—164
(1) OJL229,30.8.1980,p.11.DirectiveaslastamendedbyDirective91/692/EEC(OJL
377,31.12.1991,p.48).
(2) OJNoL194,25.7.1975,p.34.Directive aslastamended byDirective91/692/EEC
(OJNoL377,31.12.1991,p.48).
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2.5.2.2. Wherethereisapossibilityofaquaticorganismsbeingexposed,no
authorizationshallbegrantedif:
— thetoxicity/exposureratioforfishandDaphniaislessthan100
foracuteexposureandlessthan10forlong-termexposure,or
— thealgalgrowthinhibition/exposureratioislessthan10,or
— the maximum bioconcentration factor (BCF) is greater than
1000forplantprotectionproductscontainingactivesubstances
which are readily biodegradable or greater than 100 for those
whicharenotreadilybiodegradable,
unless it is clearly established through an appropriate risk assess-
ment that under field conditions no unacceptable impact on the
viabilityofexposedspecies(predators)occurs—directlyorindir-
ectly — after use of the plant protection product according to the
proposedconditionsofuse.
2.5.2.3. Wherethereisapossibilityofhoneybeesbeingexposed,noauthor-
ization shall be granted if the hazard quotients for oral or contact
exposureofhoneybeesaregreaterthan50,unlessitisclearlyestab-
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
oftheplantprotectionproductaccordingtotheproposedconditions
ofuse.
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
managementsystemsshallbesubstantiatedbyappropriatedata.
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
ratioislessthan5,unlessitisclearlyestablishedthroughanappro-
priate risk assessment that under field conditions earthworm
populationsarenotatriskafteruseoftheplantprotectionproduct
accordingtotheproposedconditionsofuse.
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
ofuse,takingaccountoftheabilityofmicro-organismstomultiply.
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
analyticalmethodsproposedforpost-registrationcontrolandmoni-
toringpurposes:
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) themethodmustbeabletodetermineandconfirmresiduesof
toxicological,ecotoxicologicalorenvironmentalsignificance;
(ii) the mean recovery rates should be between 70 % and 110 %
witharelativestandarddeviationof ≤20%;
(iii) the repeatability must be less than the following values for
residuesinfoodstuffs:1991L0414—EN—01.01.2002—004.001—165
▼M10
Residuelevel
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-loggraph;
(iv) the reproducibility must be less than the following values for
residuesinfoodstuffs:
Residuelevel
mg/kgDifference
mg/kgDifference
in%
0,01 0,01 100
0,1 0,05 501 0,25 25
>1 25
Intermediate values are determined by interpolation from a
log-loggraph;
(v) inthecaseofresidueanalysisintreatedplants,plantproducts,
foodstuffs, feedingstuffs or products of animal origin, except
wheretheMRLortheproposedMRLisatthelimitofdeter-
mination,thesensitivityofthemethodsproposedmustsatisfy
thefollowingcriteria:
Limit of determination in relation to the proposed provisional
orCommunityMRL:
MRL(mg/kg)limitofdetermination
(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
mustbemet.
2.7.2. Where no appropriate FAO specification exists, the physical and
chemicalpropertiesoftheproductmustmeetthefollowingrequire-
ments
(a) Chemicalproperties:
Throughout the shelf-life period, the difference between the
statedandtheactualcontentoftheactivesubstanceintheplant
protectionproductmustnotexceedthefollowingvalues:
Declaredcontenting/kgorg/lat20ºC Tolerance
upto25 ±15%homogeneousformulation
±25%non-homogeneousformulation
morethan25upto100 ±10%
morethan100upto250 ±6%
morethan250upto500 ±5%
morethan500 ±25g/kgor±25g/l1991L0414—EN—01.01.2002—004.001—166
▼M10
(b) Physicalproperties:
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
specificationsforplantprotectionproducts’.
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
tankmix.1991L0414—EN—01.01.2002—004.001—167