HET COLLEGE VOOR DE TOELATING VAN GEWASBESCHERMINGSMIDDELEN EN BIOCIDEN

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HET COLLEGE VOOR DE TOELATING VAN GEWASBESCHERMINGSMIDDELEN EN BIOCIDEN

1 BESLUIT

Op 29 mei 2013 is van

SUMITOMO CHEMICAL AGRO EUROPE S.A.S.

2 RUE CLAUDE CHAPPE,

69771 SAINT DIDIER AU MONT, D'OR FRANKRIJK

een aanvraag ontvangen tot herregistratie van de toelating van het gewasbeschermingsmiddel MaxCel

op basis van de werkzame stof 6-benzyladenine.

HET COLLEGE BESLUIT tot toelating van bovenstaand middel.

With the reregistration the authorization will be transferred from registration holder VALENT BIOSCIENCES, A DIVISION OF SUMITOMO CHEMICAL AGRO EUROPE S.A. to registration holder SUMITOMO CHEMICAL AGRO EUROPE S.A.S.

Alle bijlagen vormen een onlosmakelijk onderdeel van dit besluit.

Voor nadere gegevens over deze toelating wordt verwezen naar de bijlagen:

- Bijlage I voor details van de aanvraag en toelating.

- Bijlage II voor de etikettering.

- Bijlage III voor wettelijk gebruik.

- Bijlage IV voor de onderbouwing.

1.1 Samenstelling, vorm en verpakking

De toelating geldt uitsluitend voor het middel in de samenstelling, vorm en de verpakking als waarvoor de toelating is verleend.

1.2 Gebruik

Het middel mag slechts worden gebruikt met inachtneming van hetgeen in bijlage III bij dit besluit is voorgeschreven.

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Mede gelet op de onder “wettelijke grondslag” vermelde wetsartikelen, dienen alle volgende aanduidingen en vermeldingen op de verpakking te worden vermeld:

- De aanduidingen, letterlijk en zonder enige aanvulling, zoals vermeld onder

“verpakkingsinformatie” in bijlage I bij dit besluit.

- Het toelatingsnummer met een cirkel met daarin de aanduiding van de W-codering zoals vermeld onder “toelatingsinformatie” in bijlage I bij dit besluit.

- De etikettering zoals opgenomen in bijlage II bij dit besluit.

- Het wettelijk gebruiksvoorschrift, letterlijk en zonder enige aanvulling, zoals opgenomen in bijlage III bij dit besluit.

- Overige bij wettelijk voorschrift voorgeschreven aanduidingen en vermeldingen.

1.4 Aflever- en opgebruiktermijn (respijtperiode)

Bij de herregistratie wordt het etiket uitgebreid met de claim voor stimulering vruchtdunning in peer, maar tevens ingeperkt door het voorschrijven van nieuwe restrictiezinnen met betrekking tot

driftbeperking en een veiligheidstermijn van 90 dagen. Daarom wordt de W-codering van het etiket bij de herregistratie opgehoogd van W.0 naar W.1.

Inperking van het etiket betekent ook dat voor het oude etiket een respijtperiode dient te worden vastgesteld. De nieuwe restricties houden verband met het wegnemen van mogelijke risico’s.

Daarom wordt de respijtperiode beperkt tot het eerstvolgende gebruiksseizoen in 2016.

De nieuwe etikettering met W-codering W.1. dient bij de eerstvolgende aanmaak op de verpakking te worden aangebracht. Oude verpakkingen zonder W-codering (W.0) mogen worden afgeleverd tot 1 juni 2016 en worden opgebruikt en afgevoerd tot 1 september 2016.

2 WETTELIJKE GRONDSLAG

Besluit artikel 80, vijfde lid Verordening (EG) 1107/2009 juncto artikel 28, eerste lid, Wet gewasbeschermingsmiddelen en biociden

Classificatie en etikettering artikel 31 en artikel 65 van de Verordening (EG) 1107/2009 Gebruikt toetsingskader Rgb d.d. 13 juni 2011 en Evaluation Manual 1.1

3 BEOORDELINGEN

3.1 Fysische en chemische eigenschappen

De aard en de hoeveelheid van de werkzame stoffen en de in humaan-toxicologisch en

ecotoxicologisch opzicht belangrijke onzuiverheden in de werkzame stof en de hulpstoffen zijn bepaald. De identiteit van het middel is vastgesteld. De fysische en chemische eigenschappen van het middel zijn vastgesteld en voor juist gebruik en adequate opslag van het middel aanvaardbaar

geacht.

3.2 Analysemethoden

De geleverde analysemethoden voldoen aan de vereisten om de residuen te kunnen bepalen die vanuit humaan-toxicologisch en ecotoxicologisch oogpunt van belang zijn, volgend uit geoorloofd gebruik.

3.3 Risico voor de mens

Van het middel wordt voor de toegelaten toepassingen volgens de voorschriften geen onaanvaardbaar risico voor de mens verwacht.

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Van het middel wordt voor de toegelaten toepassingen volgens de voorschriften geen onaanvaardbaar risico voor het milieu verwacht.

3.5 Werkzaamheid

Van het middel wordt voor de toegelaten toepassingen volgens de voorschriften verwacht dat het werkzaam is.

Bezwaarmogelijkheid

Degene wiens belang rechtstreeks bij dit besluit is betrokken kan gelet op artikel 4 van Bijlage 2 bij de Algemene wet bestuursrecht en artikel 7:1, eerste lid, van de Algemene wet bestuursrecht, binnen zes weken na de dag waarop dit besluit bekend is gemaakt een bezwaarschrift indienen bij: het College voor de toelating van gewasbeschermingsmiddelen en biociden (Ctgb), Postbus 8030, 6710 AA, EDE.

Het Ctgb heeft niet de mogelijkheid van het elektronisch indienen van een bezwaarschrift opengesteld.

Ede, 4 december 2015

HET COLLEGE VOOR DE TOELATING VAN

GEWASBESCHERMINGSMIDDELEN EN BIOCIDEN,

Ir. J.F. de Leeuw Voorzitter

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BIJLAGE I DETAILS VAN DE AANVRAAG EN TOELATING 1 Aanvraaginformatie

Aanvraagnummer: 20130744 THG

Type aanvraag: aanvraag tot herregistratie van

de toelating van het gewasbeschermingsmiddel

Middelnaam: MaxCel

Formele registratiedatum: * 31 mei 2013

Datum in behandeling name:

Datum compliance check: 11 November 2011

* Datum waarop zowel de aanvraag is ontvangen als de aanvraagkosten zijn voldaan.

2 Stofinformatie

Werkzame stof Gehalte

6-benzyladenine 1,93%

De stof 6-benzyladenine is per 1 juni 2011 geplaatst op Annex I van Richtlijn 91/414/EEG (Dir 2011/1/EC, d.d. 3 januari 2011) en vervolgens bij Uitvoeringsverordening (EU) 540/2011 d.d. 25 mei 2011 goedgekeurd. De goedkeuring van deze werkzame stof expireert op 31 mei 2021.

3 Toelatingsinformatie

Toelatingsnummer: 13147 N

Expiratiedatum: 1 december 2025

Afgeleide of parallel: n.v.t.

Biocide, gewasbeschermingsmiddel of toevoegingsstof:

Gewasbeschermingsmiddel

Gebruikers: Professioneel

W-codering professioneel gebruik: 1

4 Aflever- en opgebruiktermijnen voor oude etiket Vorige W-codering professioneel gebruik: 0

Aflevertermijn professioneel gebruik: 1 juni 2016 Opgebruiktermijn professioneel gebruik: 1 september 2016 5 Verpakkingsinformatie

Aard van het preparaat: Met water mengbaar concentraat

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BIJLAGE II Etikettering van het middel MaxCel

Professioneel gebruik

de identiteit van alle stoffen in het mengsel die bijdragen tot de indeling van het mengsel:

-

Pictogram ^-

Signaalwoord ^-

Gevarenaanduidingen ^-

Voorzorgsmaatregelen P280C Beschermende handschoenen en beschermende kleding dragen.

SP 1 Zorg ervoor dat u met het product of zijn verpakking geen water verontreinigt.

Aanvullende etiketelementen

EUH208 Bevat propylgallaat. Kan een allergische reactie veroorzaken.

EUH210 Veiligheidsinformatieblad op verzoek verkrijgbaar.

EUH401 Volg de gebruiksaanwijzing om gevaar voor de menselijke gezondheid en het milieu te voorkomen.

Kinderveilige sluiting verplicht Nee Voelbare gevaarsaanduiding verplicht Nee

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HET COLLEGE VOOR DE TOELATING VAN GEWASBESCHERMINGSMIDDELEN EN BIOCIDEN BIJLAGE III WG van het middel

Wettelijk Gebruiksvoorschrift

Toegestaan is uitsluitend het professionele gebruik als groeiregulator door middel van een gewasbehandeling in de volgende toepassingsgebieden (volgens Definitielijst toepassingsgebieden versie 2.0, Ctgb juni 2011) onder de vermelde toepassingsvoorwaarden

Toepassingsgebied Doel groeiregulatie Dosering (middel) per toepassing Maximale dosering (middel) per toepassing

Maximaal aantal toepassingen per 12 maanden

Veiligheidstermijn in dagen

Appel Vruchtdunning 0,375 -0,75 % (375 - 750 ml per 100

liter water)

11,25 l/ha 1 90

Peer Vruchtdunning 0,75 - 1 % (750 tot 1000 ml per 100

liter water)

10 l/ha 1 90

Toepassingsvoorwaarden

Maak geen pre-mix van MaxCel. Vul de tank half met water en activeer de roerinstallatie. Voeg de noodzakelijke hoeveelheid MaxCel toe. Het product dispergeert beter door voorzichtig te roeren. Te hard roeren kan leiden tot overmatige schuimvorming. Vul voorzichtig roerend de tank aan tot het noodzakelijke volume.

Om in het water levende organismen te beschermen is toepassing in de teelt van appels en peren in percelen die grenzen aan oppervlaktewater uitsluitend toegestaan wanneer gebruik wordt gemaakt van één van de volgende maatregelen:

- een windhaag op de rand van het rijpad in combinatie met éénzijdige bespuiting van de laatste bomenrij in de richting van het perceel met inachtneming van een teeltvrije zone van tenminste 3 meter;

- een tunnelspuit met inachtneming van een teeltvrije zone van tenminste 3 meter;

- een Wannerspuit met reflectieschermen en standaard spuitdoppen met inachtneming van een teeltvrije zone van tenminste 3 meter;

- minimaal 50 % driftreducerende spuitdoppen in combinatie met éénzijdige bespuiting van de laatste bomenrij in de richting van het perceel met inachtneming van een teeltvrije zone van tenminste 3 meter;

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- een KWH k1500-3R2 VLOS 3-rijenspuit met variabele luchtondersteuning en standaard spuitdoppen in de eerste 20 meter grenzend aan het oppervlaktewater met inachtneming van een teeltvrije zone van tenminste 3 meter

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HET COLLEGE VOOR DE TOELATING VAN GEWASBESCHERMINGSMIDDELEN EN BIOCIDEN BIJLAGE IV

Contents Page

1. Identity of the plant protection product ... 2

2. Physical and chemical properties ... 3

3. Methods of analysis ... 8

4. Mammalian toxicology ... 10

5. Residues ... 18

6. Environmental fate and behaviour ... 23

7. Ecotoxicology ... 34

8. Efficacy ... 49

9. Conclusion ... 54

10. Classification and labelling... 54

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1. Identity of the plant protection product

1.1 Applicant

SUMITOMO CHEMICAL AGRO EUROPE S.A.S.

2 RUE CLAUDE CHAPPE,

69771 SAINT DIDIER AU MONT, D'OR FRANKRIJK

1.2 Identity of the active substance

Common name 6-benzyladenine (non-ISO) Name in Dutch 6-benzyladenine

Chemical name N⁶-benzyladenine

CAS no 1214-39-7

EC no 214-927-5

The active substance was included in Annex I of Directive 91/414/EEC on 1 June 2011.

From 14 June 2011 forward, according to Reg. (EU) No 540/2011 the substance is approved under Reg. (EC) No 1107/2009, repealing Directive 91/414/EEC.

1.3 Identity of the plant protection product

Name MaxCel

Formulation type SL

Content active substance 20 g/L 6-benzyladenine

The formulation was not part of the assessment of the active substance for inclusion in Annex I of Directive 91/414/EEC. Although the product name is the same, the formulation composition was changed.

1.4 Function Plant growth regulator.

1.5 Uses applied for

See GAP in Appendix 1 with proposed uses.

1.6 Background to the application

It concerns the re-registration of MaxCel as a fruit thinning agent in apple and a label extension of MaxCel as a fruit thinning agent in pear.

1.7 Packaging details

1.7.1 Packaging description

Material: Professional use:

HDPE/F

Capacity: Professional use:

5L Type of closure and size of opening:

PP cap with induction seal or foil seal.

Other information UN/ADR compliant

Packed 2x5L in corrugated cardboard boxes.

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1.7.2 Detailed instructions for safe disposal No particular recommendations.

2. Physical and chemical properties

2.1 Active substance: 6-benzyladenine

The final List of Endpoints presented below is taken from the EFSA Journal 2010; 8(10):1716, also taking into account the final review report (SANCO/12667/2010 – final, d.d. 4 January 2011). Where relevant, some additional remarks/information are given in italics.

Identity

Active substance (ISO Common Name) N⁶-benzyladenine

Note: There is no ISO common name for this substance;

the name “6-benzyladenine” has been used in the literature but has no official status

Chemical name (IUPAC) N⁶-benzyladenine

Chemical name (CA) N-(phenylmethyl)-1H-purin-6-amino

CIPAC No 829

CAS No 1214-39-7

EEC No (EINECS or ELINCS) 214-927-5 FAO Specification (including year of publication)

None Minimum purity of the active substance

as manufactured (g/kg)

973 g/kg (combined task force specification) Identity of relevant impurities (of

toxicological, environmental and/or other significance) in the active substance as manufactured (g/kg)

None

Molecular formula C12H11N5

Molecular mass 225.26

Structural formula

Physical-chemical properties

Melting point (state purity) 229°C to 230.5°C (99%)

Boiling point (state purity) No boiling point observed up to a temperature of 360°C (98.6%)

Temperature of decomposition Decomposition observed following melting, at temperatures above ~ 245°C (98.6%)

Appearance (state purity) white powder with no detectable odour (99.9%)

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Surface tension at 90% saturated solution and at 20°C : 70.0 mN/m (Not surface active)

Vapour pressure (in Pa, state temperature)

6 x 10^-7 Pa (98.5%) at 25°C

Henry’s law constant (in Pa·m³·mol^-1) 1.77 x 10^-6 Pa.m³.mol^-1 at 25 °C (QSAR)

Calculated to be 2.98 x 10^-6 Pa.m³.mol^-1 at 20 °C Solubility in water (in g/l or mg/l, state

temperature)

at 20°C (99%)

pH Solubility (g/L)

Pure water 65.7 mg/L pH 4.0 Buffer 116 mg/L pH 7.0 Buffer 64.5 mg/L pH 9.0 Buffer 77.8 mg/L Solubility in organic solvents (in g/l or

mg/l, state temperature)

at 20°C (99%)

Solvent Solubility (mg/L)

n-heptan 0.15 mg/L

xylene 9.78 mg/L

1,2-dichloro-ethane 96.9 mg/L

methanol 5820 mg/L

acetone 1130 mg/L

Ethyl acetate 493 mg/L Partition co-efficient (log Pow) (state pH

and temperature)

at 20°C (99%).

Tested solution Log Pow PH 4.0 buffer solution : 1.86 PH 7.0 buffer solution : 2.16 PH 9.0 buffer solution : 2.13 Dissociation constant pKa1 = 9.4 (99%)

pKa2 = 7.3 (99%) UV/VIS absorption (max.) (if absorption

>290 nm state ε at wavelength)

Purity 99 %

The molar extinction coefficients were determined to be:

In methanol/water 9/1

λmax ε (dm³/mol/cm) 207 (maximum) 20800

270 (maximum) 18800

290 10800 *

In methanol/ HCl 1M 9/1

270 (maximum) 19000

290 1000 *

In methanol/ NaOH 1M 9/1

276 (maximum) 18600 284 (shoulder) 14000

290 2000 *

Flammability not highly flammable (99%)

Oxidising properties no oxidising properties (99%) Explosive properties no explosive properties (99%)

*Graphically estimated by RMS

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Plant protection product: MaxCel

Data on the plant protection product is taken from the studies reports submitted by the applicant.

The range of the application concentration of the plant protection product is 0.375 - 1%.

Section (Annex point)

Study Guidelines

and GLP

Findings Evaluation and

conclusion B.2.2.1

(IIIA 2.1)

Appearance:

physical state

GLP Visual

Liquid Acceptable

B.2.2.2 (IIIA 2.1)

Appearance:

colour

GLP Visual

Clear colourless to hazy white Acceptable B.2.2.3

(IIIA 2.1)

Appearance:

odour

GLP Olfactory

No discernible odour Acceptable B.2.2.4

(IIIA 2.2)

Explosive properties

GLP EC A14

Not explosive Acceptable

B.2.2.5 (IIIA 2.2)

Oxidising properties

GLP EC A21

Not oxidising Acceptable

B.2.2.6 (IIIA 2.3)

Flammability Not applicable

B.2.2.7 (IIIA 2.3)

Auto- flammability

GLP EC A15

>400°C Acceptable

B.2.2.8 (IIIA 2.3)

Flash point GLP EC A9

103°C Acceptable

B.2.2.9 (IIIA 2.4)

Acidity / alkalinity

GLP CIPAC MT31.2.3

Acidity: 1.5% as H2SO4 Acceptable

B.2.2.10 (IIIA 2.4)

pH GLP

CIPAC MT75.3

1%w/v in water: 3.5 Neat: 3.4

Acceptable

B.2.2.11 (IIIA 2.5)

Surface tension

GLP OECD 115

0.375%v/v: 43.5 mN/m 0.75%v/v: 43.0 mN/m At 20°C

Acceptable

The surface tension should be

determined at 25°C using the undiluted formulation.

Considering this information is not used in the risk assessment nor relevant for classification and labelling, the data is accepted.

B.2.2.12 (IIIA 2.5)

Viscosity GLP OECD 114 (Ubbelohde)

Kinematic viscosity:

20°C 115 mm²/s 40°C 25.0 mm²/s Dynamic viscosity:

20°C 120 mPa.s 40°C 26.2 mPa.s

Acceptable Shear rate

dependency was not investigated.

Considering the composition of the

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and GLP

conclusion product, this is considered acceptable (the product contains no hydrocarbons).

B.2.2.13 (IIIA 2.6)

Relative density

GLP EC A3

D420

= 1.05 Acceptable

B.2.2.14 (IIIA 2.6)

Bulk (tap) density

Not applicable B.2.2.15

(IIIA 2.7)

Storage stability

GLP

CIPAC MT46

Stable for 2 weeks at 54°C in 1L HDPE bottles.

Properties determined before and after storage: appearance, a.s. content, dilution stability, foam persistence, pH, acidity, packaging stability, weight change.

No significant changes occured

Acceptable

GLP CIPAC MT39.3

Stable for 7 days at 0°C. Acceptable

B.2.2.16 (IIIA 2.7)

Shelf life GLP Stable for 24 months at 20°C and 30°C in 1L HDPE bottles.

Properties determined before and after storage: appearance, a.s. substance content, dilution stability, foam persistence, pH, free acidity, packaging stability.

No significant changes occured

Acceptable Results are taken from an interim study. The study will be continued for up to 3 years.

Considering the interim results were audited, the GLP claim is considered valid.

B.2.2.17 (IIIA 2.8)

Wettability Not applicable

B.2.2.18 (IIIA 2.8)

Persistent foaming

GLP CIPAC MT47.2

0.375%v/v in CIPAC D water:

54 mL

64 mL

Acceptable The highest proposed in-use concentration (1%) was not tested.

Considering the product produces foam above the 60 mL threshold at 0.75%v/v, this is

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and GLP

conclusion case at 1%v/v as well. Measures to reduce foaming are included on the product label.

B.2.2.19 (IIIA 2.8)

Suspensibility Not applicable

B.2.2.20 (IIIA 2.8)

Spontaneity of dispersion

(IIIA 2.8)

Dilution stability

GLP

CIPAC MT41

Clear homogeneous

Acceptable The highest proposed in-use concentration (1%) was not tested.

Considering

measures to ensure a homogeneous spray fluid are included on the product label, this is considered

acceptable.

B.2.2.22 (IIIA 2.8)

Dry sieve test Not applicable

B.2.2.23 (IIIA 2.8)

Wet sieve test Not applicable

B.2.2.24 (IIIA 2.8)

Particle size distribution

(IIIA 2.8)

Content of dust/fines

(IIIA 2.8)

Attrition and friability

(IIIA 2.8)

Emulsifiability, re-

emulsifiability and emulsion stability

Not applicable

B.2.2.28 (IIIA 2.8)

Stability of dilute emulsion

Not applicable

B.2.2.29 (IIIA 2.8)

Flowability Not applicable

B.2.2.30 (IIIA 2.8)

Pourability (rinsibility)

(IIIA 2.8)

Dustability Not applicable

B.2.2.32 Adherence Not applicable

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and GLP

conclusion (IIIA 2.8) and

distribution to seeds

2.9.1 Physical compatibility with other products

Not applicable

2.9.2 Chemical compatibility with other products

Not applicable

Conclusion

The physical and chemical properties of the active substance and the plant protection product are sufficiently described by the available data. Neither the active substance nor the product has any physical or chemical properties, which would adversely affect the use according to the proposed use and label instructions.

To reduce foaming formed during preparation of the spray fluid, measures are included in the intended use.

The shelf-life of the product is 2 years in HDPE

In the GAP/instructions for use the following has to be stated:

Maak geen pre-mix van MaxCel. Vul de tank half met water en activeer de roerinstallatie. Voeg de noodzakelijke hoeveelheid MaxCel toe. Het product dispergeert beter door voorzichtig te roeren. Te hard roeren kan leiden tot overmatige schuimvorming. Vul voorzichtig roerend de tank aan tot het noodzakelijke volume.

2.3 Data requirements None.

3. Methods of analysis

The final List of Endpoints presented below is taken from the EFSA Journal 2010; 8(10):1716. Where relevant, some additional remarks/information are given in italics.

3.1 Analytical methods in technical material and plant protection product

Technical as (principle of method) Fine Agrochemical : HPLC-UV (validated) Valent : HPLC-UV (validated)

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Impurities in technical as (principle of method)

Fine Agrochemical :

- HPLC-UV (fully validated). No other data required - CIPAC MT 17.4, loss in weight (validated)

Valent :

- HPLC-UV (fully validated). No other data required

- ion chromatography (fully validated). No other data required - method (STM 0328200) similar to CIPAC MT17.2 (loss in weight) (validated)

Preparation (principle of method) HPLC-UV at 204 nm.

Conclusion

The analytical methods regarding the technical active substance have been assessed in the DAR and are considered to be acceptable.

For the formulation, an acceptable method with corresponding validation was provided. The method and validation are the same as included in the DAR. The formulation’s composition change is

sufficiently minor to allow extrapolation.

3.2 Residue analytical methods Food/feed of plant origin (principle of method and LOQ for methods for monitoring purposes)

Open for apples In maize : no MRL

LC-MS/MS (fully validated).

LOQ : 0.01 mg/kg in maize

ILV: for tomato, cucumber and olive

No ILV required as no MRL has been set on Maize Due to the nature of the compound the suitability of a multi-residue method has not been assessed

GC-MS

LOQ 0.005 mg/kg in apple

Confirmatory method: 3 mass fragments ILV: apple

Food/feed of animal origin (principle of method and LOQ for methods for monitoring purposes)

No MRL. No method required

Soil (principle of method and LOQ) HPLC-MS/MS ( validated) LOQ : 0.01 mg/kg in soil Water (principle of method and LOQ) HPLC-MS/MS (validated)

LOQ : 0.05 μg/L in drinking and surface water Air (principle of method and LOQ) HPLC-MS/MS ( validated)

LOQ : 22.5 ng/m3 in air Body fluids and tissues (principle of

method and LOQ)

No method required as 6-BA is not classified as toxic or very toxic.

Based on the proposed use of the plant protection product analytical methods for determination of residues in food/feed of plant origin are required for matrices with a high water (apple, pear).

Definition of the residue and MRLs for 6-benzyladenine

Matrix Definition of the residue for monitoring MRL

Food/feed of plant 6-Benzyladenine 0.01 mg/kg (default MRL)

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origin

Food/feed of animal origin

Not relevant

Required LOQ

Soil 6-Benzyladenine 0.05 mg/kg (default)

Drinking water 6-Benzyladenine 0.1 µg/L (drinking water

guideline)

Surface water 6-Benzyladenine 0.1 µg/L

Air 6-Benzyladenine 9 µg/m³ (derived from the

AOEL (0.03 mg/kg bw/day) according to SANCO/825/00) Body fluids and tissues Not applicable (non-toxic compound) 0.05 mg/l (blood)

0.1 mg/kg (tissues; meat or liver)

The residue analytical methods, included in the abovementioned List of Endpoints, are suitable for monitoring of the MRLs.

The method for apples and pears was submitted by the applicant and is considered sufficiently validated. The GC-MS method provided is based on a published method. The primary validation does not comply with the requirements of SANCO/825/00 as only three single recovery determinations were performed at three fortification levels. The ILV was performed on apple and included 6

determinations at 3 fortification levels. Confirmation of analyte identity was achieved by monitoring of 3 mass fragments. Considering the overall good results achieved throughout both studies, the method is considered acceptable. The applicant has indicated that they are developing a more state of art method, based on a multi-residue approach, but an ILV for this method is not yet available. The residue analytical methods should be further assessed when the active substance’s approval is to be renewed.

The residue analytical methods for water, soil and air, evaluated in the DAR, are acceptable and suitable for monitoring of residues in the environment.

Conclusion

The submitted analytical methods meet the requirements. The methods are specific and sufficiently sensitive to enable their use for enforcement of the MRLs and for monitoring of residues in the environment.

3.3 Data requirements None.

4. Mammalian toxicology List of Endpoints

The final List of Endpoints presented below is taken from the EFSA Conclusion on 6-benzyladenine (EFSA Journal 2010;8(10):1716).

Absorption, distribution, excretion and metabolism (toxicokinetics) (Annex IIA, point 5.1)

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Distribution ‡ Rats

Highest concentration was found in stomach wall.

Greater levels than that associated with whole blood were intestine wall, liver kidneys, lungs and ovaries.

Potential for accumulation ‡ No potential for accumulation

Rate and extent of excretion ‡ 80-95% within 24 h mainly via urine (60%)

Metabolism in animals ‡ The major component found in urine was hippuric acid;

the monohydroxylated metabolite of 6BA was also present as a major component in urine.

Other minor components identified in urine were the hydrated adduct of monohydroxylated 6BA,

dihydroxylated 6BA, and the glucuronide conjugates of both the mono and dihydroxylated 6BA.

Parent 6BA was also detected in urine, but was very close to the limit of quantification.

The major identified components in the faecal extracts were hippuric acid and isomers of both mono and dihydroxylated 6BA.

The major identified component in bile was the glutathione conjugate of monohydroxylated 6BA.

Toxicologically relevant compounds ‡ (animals and plants)

6-Benzyladenine

Toxicologically relevant compounds ‡ (environment)

6-Benzyladenine

Acute toxicity (Annex IIA, point 5.2)

Rat LD₅₀ oral ‡ 2094 and 814 mg/kg bw in males and females

respectively and 1584 mg/kg bw (combined) R22

Rat LD50 dermal ‡ >2000 mg/kg bw in both sexes

Rat LC50 inhalation ‡ >5.0 mg/L in both sexes

Skin irritation ‡ Non-irritant

Eye irritation ‡ Non-irritant

Skin sensitisation ‡ Not sensitizing

Short term toxicity (Annex IIA, point 5.3)

Target / critical effect ‡ Rat:

Lower body weight, lower blood glucose level, kidney changes: dilated renal pelvises, mineralised semifluid material within the pelvises and secondary

inflammation.

Limited information on other species (mice and dogs)

Relevant oral NOAEL ‡ 13-week rat: 41 mg/kg bw/day (F)

Relevant dermal NOAEL ‡ No data/ not required

Relevant inhalation NOAEL ‡ No data/ not required

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Genotoxicity ‡ (Annex IIA, point 5.4)

No genotoxic potential.

Long term toxicity and carcinogenicity (Annex IIA, point 5.5)

Target/critical effect ‡ No valid data, not required because of the representative uses

Relevant NOAEL ‡ Not available

Carcinogenicity ‡ No valid data/ not required because of the

representative uses.

Reproductive toxicity (Annex IIA, point 5.6) Reproduction toxicity

Reproduction target / critical effect ‡ Rat:

Lower body weight and food consumption (F0 and F1 parents).

Lower weight gain in pup and delay in sexual maturation

Relevant parental NOAEL ‡ M/F: 30/45 mg/kg bw/day

Relevant reproductive NOAEL ‡ M/F: > 115/170 mg/kg bw /day Relevant offspring NOAEL ‡ M/F: 30/45 mg/kg bw /day Developmental toxicity

Developmental target / critical effect ‡ Rat:

Lower body weight and food consumption in dams.

Lower body weight in foetuses, increased incidence of hydrocephalus and skeletal effects.

Rabbit

Lower mean foetal body weights.

R63

Relevant maternal NOAEL ‡ Rat: 50 mg/kg bw/day

Rabbit <10 mg/kg bw/day Relevant developmental NOAEL ‡ Rat: 50 mg/kg bw/day

Rabbit 20 mg/kg bw/day

Neurotoxicity (Annex IIA, point 5.7)

Acute neurotoxicity ‡ No data/ not required

Repeated neurotoxicity ‡ No data/ not required

Delayed neurotoxicity ‡ No data/ not required

Other toxicological studies (Annex IIA, point 5.8)

Mechanism studies ‡ No data/ not required

Studies performed on metabolites or impurities ‡ No data/ not required

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Medical data ‡ (Annex IIA, point 5.9)

No evidence of toxicological concern from medical surveillance of manufacturing plant personnel

Summary (Annex IIA, point 5.10) Value Study Safety factor

ADI ‡ Not allocate, not

necessary^{o o}

AOEL ‡ 0.03 mg/kg bw/day Developmental

toxicity study in rabbit

300*

ARfD ‡ Not allocate, not

necessary^o

* an additional safety factor of 3 to account for the LOAEL;

o During the preparation of the EFSA conclusion, a data gap was identified by the residue experts for further quantitative evidence that 6-benzyladenine is a naturally occurring compound, hence the consumer risk assessment could not be finalised. It is noted that the setting of ADI and ARfD might be needed once the clarification on the natural occurrence of 6- benzyladenine is provided;

o o The Review Report for the active substance 6-benzyladenine, in contrast to the EFSA Conclusion, contained an ADI for 6- benzyladenine (0.01 mg/kg bw/day).

Dermal absorption ‡ (Annex IIIA, point 7.3)

MAXCEL formulation (SL, 20 g/L 6-benzyladenine) Concentrate:13 % Spray dilutions:7 %

In vivo dermal absorption study in rats.

Classification and proposed labelling with regard to toxicological data (Annex IIA, point 10)

RMS/peer review proposal Substance classified (6-Benzyladenine) Xn; (Harmful)

R22: Harmful if swallowed

Repr. Cat3; R63: Possible risk of harm to the unborn child

Data requirements active substance

No additional data requirements are identified.

4.1 Toxicity of the formulated product (IIIA 7.1)

The formulation MaxCel does not need to be classified on the basis of its acute oral (LD50 rat >5000 mg/kg bw), dermal (LD50 rat >5000 mg/kg bw) and inhalation toxicology (LC50 rat >4.99 mg/L (4 hr)).

The formulation MaxCel is considered not irritating to skin and eyes.

The formulation MaxCel does not have sensitising properties in a Maximisation test.

4.1.1 Data requirements formulated product No additional data requirements are identified.

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4.2 Dermal absorption (IIIA 7.3)

The applicant provided an in vivo dermal absorption study (rat skin) and an in vitro dermal absorption study (human and rat skin). The in vivo dermal absorption study is already agreed at EU level (see List of Endpoints). The dermal absorption values in the List of Endpoints for MAXCEL formulation (SL, 20 g/L 6-BA) are:

- Absorption from undiluted concentrate: 13% (tested concentrate: 17.6 g/L);

- Absorption from diluted spray solution: 7% (tested spray dilution: 0.16 g/L).

In the in vitro study provided by the applicant a concentrate concentration of 1.9% w/w (19 g/kg) and spray dilutions of 0.2 g/L and 0.01 g/L were tested. The in vitro study shows that rat skin is more permeable compared to human skin. The applicant performed a triple pack approach to refine the dermal absorption values in the List of Endpoints.

The concentrations tested in the in vivo study and the in vitro study are not similar. However, as the concentrations are comparable it is considered acceptable to perform a triple pack approach.

The results of the in vitro study show that the ratio between human and rat skin is 1:4.5, 1:4.7 and 1:5.3 for the high, intermediate and low dose, respectively. In the Table below the in vivo rat dermal absorption values are corrected using the ratios between human and rat skin for a prediction of the in vivo human dermal absorption values.

High dose (1.9% w/w)

Intermediate dose (0.16-0.20 g a.s./L)

Low dose (0.01 g a.s./L) In vivo rat dermal absorption

value (%)

13 (12.7) 7 (7.46) n.t.

In vitro human/rat skin ratio 1:4.5 1:4.7 1:5.3

Predicted in vivo human dermal absorption value (%)

2.8 1.6 -

n.t.: not tested.

The predicted in vivo absorption based on the triple pack approach is 2.8% for the high dose and 1.6% for the intermediate dose. For the low dose no triple pack approach can be performed as the low dose was not tested in vivo. The highest intended spray dilution described on the GAP results in a spray concentration of 0.075 g a.s./L. The low dose in the in vitro study is considered a representative spray concentration for the highest intended spray dilution described on the GAP.

The in vitro study shows for both the human and rat skin that the potentially absorbed dose is comparable for the high, intermediate and low dose, i.e., 7.37%, 8.01% and 6.70% for human skin respectively and 33.40%, 37.49% and 35.46% for rat skin respectively. Furthermore, the in vitro study shows that the ratio between human and rat skin is comparable for the high, intermediate and low dose (even somewhat higher for the low dose). Therefore, it is considered acceptable to use the predicted human in vivo dermal absorption value of the intermediate dose in the risk assessment for MaxCel for the spray dilution.

According to the EFSA guidance on dermal absorption (EFSA Journal 2012;10(4):2665), dermal absorption values between 1% and 9% should be rounded to one significant figure. In conclusion, in the risk assessment of MaxCel a dermal absorption value of 3% is used for the concentrate and a dermal absorption value of 2% is used for the spray dilution.

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4.3 Available toxicological data relating to non-active substances (IIIA 7.4)

The available toxicological data relating to non-active substances will be taken into account in the classification and labelling of the formulated product.

4.4 Exposure/risk assessments 4.4.1 Operator exposure/risk

Calculation of the EU-AOEL / Tolerable Limit Value (TLV)

For 6-benzyladenine no TLV has been set. The AOEL will be used for the risk assessment.

Since the formulation is applied once during the cultivation season, a semi-chronic exposure duration is applicable for the operator (including contract workers). A semi-chronic AOEL is therefore derived.

6-Benzyladenine is included in Annex I of 91/414/EEC and subsequently approved under Regulation (EC) 1107/2009 and therefore the semi-chronic EU-AOEL of 0.03 mg/kg bw/d (= 2.10 mg/day for a person of 70 kg), based on the developmental toxicity study in rabbits, is applied (see List of Endpoints).

Exposure/risk

Exposure to 6-benzyladenine during mixing and loading and application of MaxCel is estimated with models. The exposure is estimated for the unprotected operator. In general, mixing and loading and application is performed by the same person. Therefore, for the total exposure, the respiratory and dermal exposure during mixing/loading and application have to be combined.

In the Table below the estimated internal exposure is compared with the systemic EU-AOEL.

Table T.1 Internal operator exposure to 6-benzyladenine and risk assessment for the use of MaxCel

Route Estimated internal

exposure ^a(mg/day)

Systemic EU-AOEL (mg/day)

% AOEL ^b

Mechanical upward spraying on apple and pear (uncovered, 11.25 L/ha) Mixing/

Loading^c

Respiratory < 0.01 2.10 <1

Dermal 0.81 2.10 39

Application^c Respiratory 0.04 2.10 2

Dermal 1.15 2.10 55

Total 2.00 2.10 96

Manual upward spraying on apple and pear (uncovered, 11.25 L/ha) Mixing/

Loading

Respiratory^d < 0.01 2.10 <1

Dermal^c 0.81 2.10 39

Application^e Respiratory 0.27 2.10 13

Dermal 2.50 2.10 119

Total 3.59 2.10 171

a Internal exposure was calculated with:

 biological availability via the dermal route: 3% (concentrate) and 2% (spray dilution) (see 4.2)

 biological availability via the respiratory route: 100% (worst case)

b The risk-index is calculated by dividing the internal exposure by the systemic AOEL.

c External exposure is estimated with EUROPOEM.

d External exposure is estimated with the NL-model.

e External exposure is estimated with the German model (90^th percentile).

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Since the EU-AOEL is exceeded without the use of PPE for manual upward spraying, an assessment with the use of PPE has to be performed for manual upward spraying.

Table T.2 Internal operator exposure to 6-benzyladenine and risk assessment for the use of MaxCel Route Estimated internal

% AOEL ^b

without PPE

with PPE

without PPE

with PPE Manual upward spraying on apple and pear (uncovered, 11.25 L/ha)

Mixing/

Loading

Respiratory^d < 0.01 (< 0.01) 2.10 <1 (<1)

Dermal^c 0.81 (0.81) 2.10 39 (39)

Application^e Respiratory 0.27 (0.27) 2.10 13 (13)

Dermal 2.50 0.51 2.10 119 24

Total 3.59 1.59 2.10 171 76^f

a Internal exposure was calculated with:

 biological availability via the dermal route: 3% (concentrate) and 2% (spray dilution) (see 4.2)

c External exposure is estimated with EUROPOEM.

d External exposure is estimated with the NL-model.

e External exposure is estimated with the German model (90^th percentile).

f PPE: gloves and coverall during application.

4.4.2 Bystander exposure/risk

The exposure is estimated for the professional unprotected bystander. In Table T.3 the estimated internal exposure is compared with the systemic EU-AOEL.

Table T.3 Internal bystander exposure to 6-benzyladenine and risk assessment during application of MaxCel

% AOEL ^b

Bystander exposure during application in apple and pear

Respiratory 0.02 2.10 1

Dermal 0.05 2.10 2

Total 0.06 2.10 3

a External exposure was estimated with EUROPOEM II. Internal exposure was calculated with:

 biological availability via the dermal route: 2% (see 4.2)

Non-professional bystanders and residents may be exposed via the dermal route to spray drift deposits or by inhalation of vapour drift within or directly adjacent to an application area (bystander), or in the vicinity of the application (resident). The internal bystander and resident exposure is calculated in addition to the internal bystander exposure and risk assessment calculated with EUROPOEM II above, which is intended to estimate the work-related bystander exposure. Two different methods are used: 1) the German model which calculates the total exposure for adults and

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transfer; and 2) the UK method which calculates the total bystander exposure for adults, and separately the respiratory and dermal/oral route for resident children. In the Table below the estimated internal exposure values from these methods are compared with the systemic AEL.

Table T.4 Internal bystander and resident exposure to 6-benzyladenine and risk assessment for the application of MaxCel

Systemic AEL (mg/day)^b

% AOEL ^c

Bystander exposure during application in representative uses according to the German model

Child Total 0.01 0.48 2

Adult Total 0.02 1.80 1

Resident exposure during application in all representative uses according to the German model

Child Total 0.01 0.48 2

Bystander exposure during application in representative uses according to the UK method

Resident exposure during application in representative uses according to the UK method

Child Respiratory 0.12 0.45 28

Dermal+Oral 0.01 0.45 2

a External exposure was estimated according to 1) the German guidance paper for exposure and risk assessment for bystanders and residents (Martin et al. 2008, J. Verbr. Lebensm. 3: 272-281), and 2) the UK method. Internal exposure was calculated with:

 biological availability via the dermal route: 2% (see 4.2)

 biological availability via the oral route: 100% (see List of Endpoints)

b From the systemic AOEL of 0.03 mg/kg bw/day a specific AEL is derived assuming a body weight of 16.15 or 15 kg for children in the German model or UK method, respectively, and of 60 kg for adults.

c The risk-index is calculated by dividing the internal exposure by the systemic AEL.

4.4.3 Worker exposure/risk

Shortly after application it is possible to perform re-entry activities during which intensive contact with the treated crop will occur. Therefore, worker exposure is calculated. The exposure is estimated for the unprotected worker. In Table T.5 the estimated internal exposure is compared with the systemic EU-AOEL.

Table T.5 Internal worker exposure to 6-benzyladenine and risk assessment after application of MaxCel

% AOEL ^b

Re-entry activities in apple and pear

Respiratory -^c 2.10 -^c

Dermal 0.55 2.10 26

Total 0.55 2.10 26

a External exposure was estimated with EUROPOEM II. Internal exposure was calculated with:

 biological availability via the dermal route: 3% (spray dilution) (see 4.2)

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c No model is available to calculate the respiratory internal exposure. However, the respiratory internal exposure can be considered negligible in view of the fact that the uses concern field activities (outdoors) and no spraying of the product occurs during re-entry activities.

4.4.4 Re-entry

See 4.4.3 Worker exposure/risk.

Overall conclusion of the exposure/risk assessments of operator, bystander, and worker The product complies with the Uniform Principles.

Operator exposure

For the unprotected operator, adverse health effects after dermal exposure to 6-benzyladenine as a result of the application of MaxCel in apple and pear cannot be excluded. Correct use of personal protective equipment will reduce the dermal exposure and results in a sufficient reduction of the exposure to 6-benzyladenine for the application of MaxCel in apple and pear.

Bystander exposure

Based on the risk assessment, it can be concluded that no adverse health effects are expected for the unprotected bystander due to exposure to 6-benzyladenine during application of MaxCel in apple and pear.

Based on the risk assessment, it can be concluded that no adverse health effects are expected for the non-professional bystander and resident (children and adults close to the application or living next to a field treated) due to exposure to 6-benzyladenine during and after application of MaxCel in apple and pear.

Worker exposure

Based on the risk assessment, it can be concluded that no adverse health effects are expected for the unprotected worker after respiratory and dermal exposure during re-entry activities in apple and pear due to exposure to 6-benzyladenine after application of MaxCel.

4.5 Appropriate mammalian toxicology and operator exposure end-points relating to the product and approved uses

See List of Endpoints.

4.6 Data requirements

Based on this evaluation, no additional data requirements are identified.

4.7 Combination toxicology

MaxCel contains only one active substance and it is not described that it should be used in combination with other formulations.

5. Residues

List of Endpoints

The List of Endpoints presented below is taken from the EFSA Conclusion on the peer review of the pesticide risk assessment of the active substance 6-benzyladenine (EFSA Journal 2010; 8(10):1716).

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Metabolism in plants (Annex IIA, point 6.1 and 6.7, Annex IIIA, point 8.1 and 8.6)

Plant groups covered Metabolism study in apple submitted together with scientific review reports on roots vegetables, cereals and pulses and oilseeds

Rotational crops No data available, not required.

Metabolism in rotational crops similar to metabolism in primary crops?

Not applicable

Processed commodities Not required although a processing study has been evaluated for apple pomace.

Residue pattern in processed commodities similar to residue pattern in raw commodities?

No concentration of residues during processing

Plant residue definition for monitoring 6-Benzyladenine Plant residue definition for risk assessment 6-Benzyladenine Conversion factor (monitoring to risk assessment) None

Metabolism in livestock (Annex IIA, point 6.2 and 6.7, Annex IIIA, point 8.1 and 8.6)

Animals covered No data available, not required.

Time needed to reach a plateau concentration in milk and eggs

Not applicable

Animal residue definition for monitoring Not applicable Animal residue definition for risk assessment Not applicable Conversion factor (monitoring to risk assessment) None

Metabolism in rat and ruminant similar (yes/no) Not applicable Fat soluble residue: (yes/no) Not applicable

Residues in succeeding crops (Annex IIA, point 6.6, Annex IIIA, point 8.5)

No study available. Not required, because only uses in seed production and permanent crops are intended.

Furthermore 6-BA rapidly degrades in soil (DT50 1 - 1.2 days).

Stability of residues (Annex IIA, point 6 introduction, Annex IIIA, point 8 Introduction)

Apples at – 18°C:

12 months at 0.025 mg/kg level 18 months at 0.25 mg/kg level

Residues from livestock feeding studies (Annex IIA, point 6.4, Annex IIIA, point 8.3)

Ruminant: Poultry: Pig:

Conditions of requirement of feeding studies Expected intakes by livestock  0.1 mg/kg diet (dry

weight basis) (yes/no - If yes, specify the level)

No No No

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Potential for accumulation (yes/no): N/A N/A N/A Metabolism studies indicate potential level of

residues ≥ 0.01 mg/kg in edible tissues (yes/no)

N/A N/A N/A

Feeding studies (Specify the feeding rate in cattle and poultry studies considered as relevant)

Residue levels in matrices : Mean (max) mg/kg

Muscle N/A N/A N/A

Liver N/A N/A N/A

Kidney N/A N/A N/A

Fat N/A N/A N/A

Milk N/A

Eggs N/A

5.1 Summary of residue data

The residue assessment of 6-benzyladenine is based on the Draft Assessment Report (DAR) prepared by France, dated September 2007, the Additional report to the original DAR prepared by UK in October 2009, the EFSA Conclusion on the peer review of the pesticide risk assessment of the active substance 6-benzyladenine (EFSA Journal 2010; 8(10):1716), TNO report (CTB-2006-016-RES-NL, d.d.

June 2006) and Ctgb reports 20040057-sava-res-V01and 20130744-Evaluation report natural background levels of 6-benzyladenine.

5.1.1 Metabolism in plants

Metabolism of [¹⁴C]-6-benzyladenine (6-BA) was studied in apple following a foliar application of 0.014 kg as/ha. The application was performed on apples when the fruit was <15 mm in diameter (BBCH 71). Apple samples were collected 0, 7, 50 and 90 Days After Treatment (DAT); leave samples were collected 0, 7 and 90 DAT.

The Total Radioactive Residue (TRR) in leaves and fruit declined rapidly after application. The extractable residues (surface wash and solvent extraction) liberated >79% of the TRR in apple fruit and >67% in leaves. The surface wash TRR decreased extensively with time, indicating: incorporation, growth dilution or rinsing off residue during growth.

In fruit samples taken close to the time of application (0 & 7 DAT), 6-BA was the major component.

One metabolite (M14) was found 7 DAT at levels above 10 % TRR and 0.05 mg/kg. This metabolite was not found at levels above 10 % TRR and 0.05 mg/kg 50 DAT or at commercial harvest (90 DAT).

Metabolism in the fruit samples 50 DAT was more extensive: apart from 6-BA, 10 other components were detected. Only M10 was above 10% TRR (0.011 mg/kg). At 90 DAT no 6-BA was detected. The two components M5 and M10 were detected above 10% TRR. Nonetheless, the absolute quantities were very low (0.005 mg/kg and 0.007 mg/kg for M5 and M10, respectively) and therefore these metabolites are not considered of toxicological concern.

Significant metabolites found in leaves were also present in fruit suggesting that metabolism was similar in both tissues.

5.1.2 Metabolism in livestock

Based on the available residue data, no significant residues in animal feed (>0.1 mg/kg dry diet) are expected as a result of the intended use, so a livestock metabolism study is not required.

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5.1.3 Residue definition (plant and animal) Residue definition in plant and plant products

The metabolism study on apple fruit shows that the TRR is very low at commercial harvest/90 DAT (0.021 mg/kg). The magnitude of the five individual metabolites is <0.01 mg/kg. The TRR of two metabolites is above 10% (21.61% and 30.61% for M5 and M10, respectively). Since the absolute magnitude of both metabolites is very low (0.007 mg/kg), they are considered not relevant for the definition of the residue and further characterisation is considered not necessary.

No significant residue is expected at commercial harvest. Parent 6-BA is the major residue when the application of 6-BA is closer to harvest. Therefore, the residue definition is parent only.

Residue definition in animal products

Based on the available residue data, no significant residues in animal feed (>0.1 mg/kg diet) are expected as a result of the intended use, so a residue definition in animal products is not required.

5.1.4 Stability of residues See List of Endpoints.

5.1.5 Residue data Apple

(cGAP-NL: 1x 0.015 kg as/hL, maximum 0.225 kg as/ha.)

For the application of authorisation, 8 supervised residue trials in apple in Northern Europe have been submitted. Trials were performed under field conditions and GLP. In all trials, the used total dose was substantially higher than the proposed cGAP-NL (two applications at 0.004 kg as/hL and two applications at 0.020 kg as/hL using a spraying volume of 1000 L/ha at an application interval of 7 days). However, none of the trials showed residue levels of parent 6-benzyladenine above the LOQ (0.005 mg/kg) in any sample at harvest time. Therefore, the trials are considered acceptable and a sufficient number of residue trials are available.

During the review of the active substance 6-benzyladenine it was decided to set a PHI of 90 days for the defended uses in apples.

Pear

(cGAP-NL: 1x 0.020 kg as/hL, maximum 0.2 g as/ha)

Residue data in apple can be extrapolated to pear. The PHI of 90 days also applies to pears.

A 90-day PHI is required for the uses of 6-benzyladenine on apples and pears.

“Veiligheidstermijn:

De termijn tussen de laatste toepassing en de oogst mag niet korter zijn dan 90 dagen voor appels en peren.”

5.1.6 Residues in succeeding crops

The intended use for this application for authorisation does concern use in an orchard, where rotational crops are not relevant. Furthermore, there is no risk of significant residues of 6-

benzyladenine in succeeding crops given the rapid degradation of this substance in soil. The DT50 range in soil is between 1 and 1.2 days. Therefore, a rotational crop study is not required.

5.1.7 Residues from livestock feeding studies

Based on the available residue data, no significant residues in animal feed (>0.1 mg/kg diet) are expected as a result of the intended use, so a livestock feeding study is not required.

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5.1.8 Processing factors

The available residue data show that no analytically determinable residues (<0.005 mg/kg) occur in the plant product to be processed and the Theoretical Maximum Daily Intake is less than 10 % of the ADI. Thus, a processing study is not required.

5.1.9 Calculation of the ADI and the ARfD

During the EFSA Peer Review of the pesticide risk assessment of the active substance 6-

benzyladenine, it was initially proposed that 6-benzyladenine is a naturally occurring plant hormone.

In view of this, and given that the available data indicated that residues would be expected to be low, it was proposed that consumer exposure would not be significant. However, during the writing of the EFSA conclusion it was questioned by EFSA whether 6-benzyladenine is naturally occurring, at least in edible crops. A data gap was identified for further quantitative evidence that 6-benzyladenine is a naturally occurring compound and the consumer risk assessment could not be finalized.

In spite of the data gap, 6-Benzyladenine was voted for inclusion on Annex I of 91/414/EEC on 23 November 2010 by the SCFCAH and an ADI of 0.01 was finalised as proposed by the RMS UK in the Additional report to the original DAR. The ADI is based on the NOAEL of 1 mg/kg bw/day in the developmental toxicity study in rabbits. Application of a safety factor for inter- and intraspecies differences of 100 and a safety margin of 10 (taking into account a 2-year dog study and the weak toxicity database including absence of long-term toxicity study in rodents) resulted in an ADI of 0.01 mg/kg bw/day. No Acute Reference Dose (ARfD) value was considered necessary since no consumer exposure was expected for the representative uses.

With particular regard to residues, the review has established that the residues arising from the proposed uses, consequent on application consistent with good plant protection practice, have no harmful effects on human or animal health. Although there were no critical areas of concern in the residues section, the applicant provided a literature study on the natural occurrence of 6-BA

(Heiman, D., B. Baldi and M. Herrero, 2011) to address the data gap identified by EFSA. This literature study was evaluated in Ctgb report 20130744-Evaluation report natural background levels of 6- benzyladenine. The literature study adds little to the data already evaluated in the DAR (September 2007) and in the Additional report (November 2009). Although exact quantitative data on 6-BA levels in food items are limited, the review of the published literature indicate that the aromatic cytokinins, and specifically 6-BA and its conjugates, are naturally present in a multitude of different plants that are utilized as food by humans and many different animals. In addition, in the course of preliminary work toward development of a residue method for 6-BA, Valent BioSciences has found evidence that 6-BA is present in food items that are normal components of European diets. Given that the available data indicate that levels of 6-BA in plant products arising from the approved plant protection product uses would be low, it is not expected that the levels of 6-BA will be higher than the levels which occur naturally.

5.2 Maximum Residue Levels

6-BA is not currently listed in Regulation 396/2005 and therefore the default 0.01 mg/kg value on apple applies. Residue levels arising from the intended use of the product comply with the default MRL of 0.01 mg/kg. Based on the conclusion that 6-BA is proposed as a naturally-occurring

compound, the origin of residues may not be conclusively attributed to the authorised use of 6-BA as a plant growth regulator and fruit thinner. Consideration could be given to inclusion of 6-BA in Annex IV of Directive 396/2005, in which case the compound would be exempted from MRL-setting.

5.3 Consumer risk assessment

6-benzyladenine is a naturally occurring plant hormone and no additional consumer exposure is

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with good plant protection practice, have no harmful effects on human or animal health. The Theoretical Maximum Daily Intake (TMDI, UK diet for toddlers) is less than 6 % of the Acceptable Daily Intake (ADI), (calculated according to the EFSA PRIMO model).

Estimates of acute dietary exposure of adults and children have not been conducted since no ARfD value was considered necessary.

Overall, 6-benzyladenine is a chemical analogue of a naturally occurring substance and the levels of 6-BA are not expected to be higher than the levels which occur naturally. In view of this, consumer exposure is not significant.

Conclusion

Based on the assessment for residues, no risk for the consumer due to the exposure to 6-

benzyladenine is expected, provided that the product is applied according to the proposed GAP and the PHI is set at 90 days. The product complies with the Uniform Principles.

5.4 Data requirements No additional data required.

6. Environmental fate and behaviour

The underlying risk assessment is based on the final List of Endpoints (LoEP) from the EFSA Conclusion (EFSA Journal 2010; 8(10):1716).

List of Endpoints Fate/behaviour

Route of degradation (aerobic) in soil (Annex IIA, point 7.1.1.1.1)

Mineralization after 100 days ‡ 67.81-86.61 % after 120 d, [¹⁴C-benzyl] and [¹⁴C-purine]

label mixed (n= 4)

Non-extractable residues after 100 days ‡ 11.98-20.96 % after 120 d, [¹⁴C-benzyl] and [¹⁴C-purine]

label mixed (n= 4) Metabolites requiring further consideration ‡

- name and/or code, % of applied (range and maximum)

None

Route of degradation in soil - Supplemental studies (Annex IIA, point 7.1.1.1.2) Anaerobic degradation ‡

Mineralization after 100 days Not required.

Non-extractable residues after 100 days Not required.

Metabolites that may require further consideration for risk assessment - name and/or code, % of applied (range and maximum)

Not required.

Soil photolysis ‡

Metabolites that may require further consideration Unidentified metabolite code ‘component 1a’, 5.1% at