Toelatingsnummer 12975 N

Spyrale  

 

12975 N

 

 

 

 

 

 

 

 

HET COLLEGE VOOR DE TOELATING VAN

GEWASBESCHERMINGSMIDDELEN EN BIOCIDEN

 

1 TOELATING

 

Gelet op de aanvraag d.d. 25 november 2005 (20050417 TG) van

 

Syngenta Crop Protection B.V.

Jacob Obrechtlaan 3 a

4611 AP  BERGEN OP ZOOM

 

 

 

tot verkrijging van een toelating voor het gewasbeschermingsmiddel op basis van de werkzame stoffen difenoconazool en fenpropidin

 

Spyrale

 

gelet op artikel 121, eerste lid, jo. artikel 23, eerste lid, Wet gewasbeschermingsmiddelen en biociden (Stb. 2007, 125),

 

BESLUIT HET COLLEGE als volgt:

 

§ I  Toelating

1.      Het middel Spyrale is met ingang van datum dezes toegelaten voor de in bijlage 1 genoemde toepassingen onder nummer 12975 N. Voor de gronden van dit besluit wordt verwezen naar bijlage II bij dit besluit.

2.      De toelating geldt tot 1 januari 2018.

 

§ II  Samenstelling, vorm en verpakking

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

 

§ III  Gebruik

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

 


§ IV Classificatie en etikettering

 

1.    De aanduidingen, die ingevolge artikel 36 van de Wet milieugevaarlijke stoffen en artikelen 14, 15a, 15b, 15c en 15d van de Nadere regels verpakking en aanduiding milieugevaarlijke stoffen en preparaten op de verpakking moeten worden vermeld, worden hierbij vastgesteld als volgt:

 

aard van het preparaat: Emulgeerbaar concentraat

 

werkzame stof:

gehalte:

difenoconazool

100 g/l

fenpropidin

375 g/l

 

 

op verpakkingen die (mede) bestemd zijn voor huishoudelijk gebruik: het kca-logo

(het kca-logo is het logo voor klein chemisch afval bestaande uit een afvalbak met een kruis erdoor als opgenomen in bijlage III bij de genoemde Nadere regels)         

 

letterlijk en zonder enige aanvulling:

 

andere zeer giftige, giftige, bijtende of schadelijke stoffen:  

-

 

gevaarsymbool:

aanduiding:

Xn

Schadelijk

N

Milieugevaarlijk

 

 

Waarschuwingszinnen: 

 

Schadelijk bij opname door de mond.

Irriterend voor de ogen, de ademhalingswegen en de huid.

Kan overgevoeligheid veroorzaken bij contact met de huid.

Schadelijk: gevaar voor ernstige schade aan de gezondheid bij langdurige blootstelling bij opname door de mond.

Zeer vergiftig voor in het water levende organismen; kan in het aquatisch milieu op lange termijn schadelijke effecten veroorzaken.

 

 

Veiligheidsaanbevelingen:

 

Niet roken tijdens gebruik.

Spuitnevel niet inademen.

Draag geschikte handschoenen en beschermende kleding.

In geval van inslikken onmiddellijk een arts raadplegen en verpakking of etiket tonen.

Deze stof en de verpakking als gevaarlijk afval afvoeren. (Deze zin hoeft niet te worden vermeld op het etiket indien u deelneemt aan het verpakkingenconvenant, en op het etiket het STORL-vignet voert, en ingevolge dit convenant de toepasselijke zin uit de volgende verwijderingszinnen op het etiket vermeldt:

1)      Deze verpakking is bedrijfsafval, mits deze is schoongespoeld, zoals wettelijk is voorgeschreven.

2)      Deze verpakking is bedrijfsafval, nadat deze volledig is geleegd.

3)      Deze verpakking dient nadat deze volledig is geleegd te worden ingeleverd bij een KCA-depot. Informeer bij uw gemeente.)

Voorkom lozing in het milieu. Vraag om speciale instructies / veiligheidsgegevenskaart.

 

Specifieke vermeldingen:

 

                        Volg de gebruiksaanwijzing om gevaar voor mens en milieu te voorkomen.

 

 

2.    Behalve de onder 1. bedoelde en de overige bij de Wet Milieugevaarlijke Stoffen en Nadere regels verpakking en aanduiding milieugevaarlijke stoffen en preparaten voorge­schreven aanduidingen en vermeldingen moeten op de verpakking voorkomen:

 

a.       letterlijk en zonder enige aanvulling:
het wettelijk gebruiksvoorschrift
De tekst van het wettelijk gebruiksvoorschrift is opgenomen in Bijlage I, onder A.

 

b.      hetzij letterlijk, hetzij naar zakelijke inhoud:
de gebruiksaanwijzing
De tekst van de gebruiksaanwijzing is opgenomen in Bijlage I, onder B.
De tekst mag worden aangevuld met technische aanwijzingen voor een goede bestrijding mits deze niet met die tekst in strijd zijn
.

 

 - 

 

2 DETAILS VAN DE AANVRAAG

 

2.1 Aanvraag

Het betreft een aanvraag tot toelating van het middel Spyrale (12975 N), een middel op basis van de werkzame stoffen difenoconazool en fenpropidin. Het middel wordt aangevraagd als schimmelbestrijdingsmiddel toegepast door middel van een gewasbehandeling in de teelt van suikerbieten en voederbieten.

 

2.2 Informatie met betrekking tot de stof

Er zijn in Nederland reeds andere middelen op basis van de werkzame stoffen difenoconazool en fenpropidin toegelaten.

 

De werkzame stof fenpropidin en difenoconazool zijn genotificeerd en worden door Zweden  beoordeeld. Van fenpropidin is een concept van de Europese beoordeling beschikbaar.

Er is nog geen besluit genomen tot plaatsing van de werkzame stoffen op bijlage 1 van de gewasbeschermingsrichtlijn 91/414/EEG.

 

2.3 Karakterisering van het middel

Spyrale is een 475 g/L emulsifeerbaar concentraat (EC) dat 375 g/l fenpropidin en 100 g/l difenoconazole bevat.

 

Difenoconazool is een breedspectrum, systemisch difenyl-ether-triazool-fungicide met preventieve en curatieve werking. Het wordt opgenomen door de bladeren waarna het zich acropetaal en translaminair door de plant verplaatst. Difenoconazool is werkzaam tegen Ascomyceten, Basidiomyceten en Deuteromyceten en diverse zaadschimmels.

De stof remt de ergosterolbiosynthese, waardoor de groei en ontwikkeling van de schimmel gestopt wordt. Ergosterol is het belangrijkste sterol in het celmembraan van schimmels. De belangrijkste werking is de remming (inhibitie) van de C-14 demethylering gedurende de ergosterolbiosynthese, vandaar de naam DMI-fungiciden. Laboratoriumstudies hebben aangetoond dat het de subcuticulaire groei van het mycelium remt en zo de ontwikkeling van ziektesymptomen onderdrukt.

 

Fenpropidin is een systemisch, curatief en beschermend piperidine (morfolinen) fungicide dat met name ingezet wordt voor de bestrijding van bladziektes. Het heeft een goede werking tegen echte meeldauw en roest. De stof heeft een vergelijkbare werking als de triazolen, maar verstoort de ergosterolbiosynthese door remming van andere enzymen. Dit betekent dat ook triazool-resistente schimmelstammen bestreden kunnen worden door fenpropidin.

 

Middelen op basis van een van beide werkzame stoffen afzonderlijk zijn in Nederland toegelaten of toegelaten geweest.

 

2.4 Voorgeschiedenis

De aanvraag is op 1 december 2005 ontvangen; op 2 december 2005 zijn de verschuldigde aanvraagkosten ontvangen. Bij brief d.d. 15 augustus 2006 is de aanvraag in behandeling genomen.

 

3  RISICOBEOORDELINGEN

 

Het gebruikte toetsingskader voor de beoordeling van deze aanvraag is de Handleiding toelating bestrijdingsmiddelen (HTB) versie 0.2.

 

3.1  Fysische en chemische eigenschappen

De aard en de hoeveelheid van de werkzame stoffen en de in toxicologisch en ecotoxicologisch opzicht belangrijke onzuiverheden in de werkzame stof en de hulpstoffen zijn bepaald. De identiteit van het middel is vastgesteld. De fysisiche en chemische eigenschappen van het middel zijn vastgesteld en voor juist gebruik en adequate opslag van het middel aanvaardbaar geacht (artikel 28, eerste lid, sub c en e, Wet gewasbeschermingsmiddelen en biociden).

De beoordeling van de evaluatie van het middel en de stof staat beschreven in Hoofdstuk 2, Physical and Chemical Properties, in Bijlage II bij dit besluit.

 

3.2  Analysemethoden

De geleverde analysemethoden voldoen aan de vereisten. De residuen die het gevolg zijn van geoorloofd gebruik die in toxicologisch opzicht of vanuit milieu oogpunt van belang zijn, kunnen worden bepaald met algemeen gebruikte passende methoden (artikel 28, eerste lid, sub d, Wet gewasbeschermingsmiddelen en biociden).

De beoordeling van de evaluatie van de analysemethoden staat beschreven in Hoofdstuk 3, Methods of Analysis, in Bijlage II bij dit besluit.

 

3.3  Risico volksgezondheid

Het middel voldoet aan de voorwaarde dat het, rekening houdend met alle normale omstandigheden waaronder het middel kan worden gebruikt en de gevolgen van het gebruik, geen directe of indirecte schadelijke uitwerking heeft op de gezondheid van de mens. De voorlopige vastgestelde maximum residugehalten op landbouwproducten zijn aanvaardbaar (artikel 28, eerste lid, sub b, onderdeel 4 en sub f, Wet gewasbeschermingsmiddelen en biociden).
Het profiel humane toxicologie inclusief de beoordeling van het risico voor de toepasser staat beschreven in Hoofdstuk 4 Mammalian Toxicology, in Bijlage II bij dit besluit.

Het residuprofiel, de vastgestelde maximum residugehalten en de beoordeling van het risico voor de volksgezondheid staan beschreven in Hoofdstuk 5, Residues in bijlage II behorende bij dit besluit.

 

3.4  Risico voor het milieu

Het middel voldoet aan de voorwaarde dat het, rekening houdend met alle normale omstandigheden waaronder het middel kan worden gebruikt en de gevolgen van het gebruik, geen voor het milieu onaanvaardbaar effect heeft, waarbij in het bijzonder rekening wordt gehouden met de volgende aspecten:

-          de plaats waar het middel in het milieu terechtkomt en wordt verspreid, met name voor wat betreft besmetting van het water, waaronder drinkwater en grondwater,

-          de gevolgen voor niet-doelsoorten.

(artikel 28, eerste lid, sub b, onderdeel 5, Wet gewasbeschermingsmiddelen en biociden).

De beoordeling van het risico voor het milieu staat beschreven in Hoofdstuk 6, Environmental Fate and Behaviour, en Hoofdstuk 7, Ecotoxicology, in Bijlage II bij dit besluit.

Het profiel gedrag en lotgevallen staat beschreven in Hoofdstuk 6 in Bijlage II bij dit besluit. Het profiel Ecotoxicology staat beschreven in Hoofdstuk 7 in Bijlage II bij dit besluit.

 

3.5  Werkzaamheid

Het middel voldoet aan de voorwaarde dat het, rekening houdend met alle normale omstandigheden waaronder het middel kan worden gebruikt en de gevolgen van het gebruik, voldoende werkzaam is en geen onaanvaardbare uitwerking heeft op planten of plantaardige producten (artikel 28, eerste lid, sub b, onderdelen 1 en 2, Wet gewasbeschermingsmiddelen en biociden).

De beoordeling van het aspect werkzaamheid staat beschreven in Hoofdstuk 8, Efficacy, in Bijlage II bij dit besluit.

 

3.6  Eindconclusie

Bij gebruik volgens het Wettelijk Gebruiksvoorschrift/Gebruiksaanwijzing is het middel Spyrale op basis van de werkzame stoffen difenoconazool en fenpropidin voldoende werkzaam en heeft het geen schadelijke uitwerking op de gezondheid van de mens en het milieu (artikel 28, Wet gewasbeschermingsmiddelen en biociden).

 

 

 

Degene wiens belang rechtstreeks bij dit besluit is betrokken kan gelet op artikel 119, eerste lid, Wet gewasbeschermingsmiddelen en biociden 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 217, 6700 AE WAGENINGEN. Het Ctgb heeft niet de mogelijkheid van het elektronisch indienen van een bezwaarschrift opengesteld.

 

 

Wageningen, 21 december 2007

 

 

HET COLLEGE VOOR DE TOELATING VAN  GEWASBESCHERMINGSMIDDELEN EN  BIOCIDEN,





(voorzitter)

 

 



HET COLLEGE VOOR DE TOELATING VAN GEWASBESCHERMINGSMIDDELEN EN BIOCIDEN

 

BIJLAGE I bij het besluit d.d. 21 december 2007 tot toelating van het middel Spyrale, toelatingnummer 12975 N

 

 

A.

WETTELIJK GEBRUIKSVOORSCHRIFT

 

Toegestaan is uitsluitend het gebruik als schimmelbestrijdingsmiddel toegepast door middel van een gewasbehandeling in de teelt van suikerbieten en voederbieten.

 

Veiligheidstermijn

De termijn tussen de laatste toepassing en de oogst mag niet korter zijn dan:

- 28 dagen voor suikerbieten en voederbieten.

 

Dit middel is uitsluitend bestemd voor beroepsmatig gebruik.

 

Om in het water levende organismen te beschermen is de toepassing middels een luchtvaartuig niet toegestaan op percelen die grenzen aan oppervlaktewater.

 

B.

GEBRUIKSAANWIJZING

 

Algemeen

Spyrale is een schimmelbestrijdingsmiddel op basis van de werkzame stoffen difenoconazool en fenpropidin. Beide werkzame stoffen werken systemisch en bezitten zowel een preventieve als een curatieve werking.

 

Toepassingen

Suikerbieten en voederbieten, ter bestrijding van bladvlekkenziekte (Cercospora beticola), meeldauw (Erysiphe betae), Ramularia beticola en roest (Uromyces betae).

Een behandeling uitvoeren zodra aantasting wordt waargenomen. Indien nodig kan de toepassing worden herhaald.

 

Dosering: 1 liter middel per ha.

 



HET COLLEGE VOOR DE TOELATING VAN GEWASBESCHERMINGSMIDDELEN EN BIOCIDEN

 

BIJLAGE II bij het besluit d.d. 21 december 2007 tot toelating van het middel Spyrale, toelatingnummer 12975 N

 

Contents                                                                  Page

 

 

1.   Identity of the plant protection product          2

 

2.   Physical and chemical properties                    3

 

3.   Methods of analysis                                           10

 

4.   Mammalian toxicology                                       13

 

5.   Residues                                                             23

 

6.   Environmental fate and behaviour                  33

 

7.   Ecotoxicology                                                     53

 

8.   Efficacy                                                                87

 

9.   Conclusion                                                          90

 

10. Classification and labelling                              90

 


1.         Identity of the plant protection product

 

1.1       Applicant

Syngenta Crop Protection B.V.

Jacob Obrechtlaan 3a

4600 AM Bergen op Zoom

Nederland

 

1.2       Identity of the active substance

Common name

Fenpropidin

Name in Dutch

Fenpropidin

Chemical name

(R,S)-1-[3-(4-tert-butylphenyl)-2-methylpropyl]-piperidine [IUPAC]

CAS no

67306-00-7

EEG no

Not allocated

 

The active substance is not included in the Annex 1 of Directive 91/414/EEC. A draft assessment report (DAR) of fenpropidin is available (RMS: Sweden).

 

Common name

Difenoconazole

Name in Dutch

Difenoconazool

Chemical name

3-chloro-4-[(2RS,4RS;2RS,4SR)-4-methyl-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-2-yl]phenyl 4-chlorophenyl ether [IUPAC]

CAS no

119446-68-3

EEG no

Not allocated

 

The active substance is not included in the Annex 1 of Directive 91/414/EEC. A draft assessment report (DAR) of difenoconazole is not yet available (RMS: Sweden).

 

1.3       Identity of the plant protection product

Name

Spyrale

Formulation type

EC

Content active substance

Fenpropidin (pure):         375 g/L (37.69%w/w)

Difenoconazole (pure):   100 g/L (10.05%w/w)

 

 

The formulation is not part of the assessment of the active substances for inclusion in Annex 1 of 91/414/EEC.

 

1.4       Function

Spyrale is a fungicide.

 

1.5       Uses applied for

Uses

Dose a.s.

 

 

fenpropidin

(g a.s./ha)

 

 

difenoconazole

Number of applications

Interval between applications

Application time (growth stage and season)

Sugarbeet and fodder beet

375

100

1-2

14-21

Aug-Sept

 

1.6       Background to the application

The application is an authorization of Spyrale for the use in sugar- and fodderbeet.

 

The Rapporteur Member State Sweden assessed the active substance fenpropidin within the framework of placement on Annex I of Directive 91/414/EEG and wrote a Draft Assessment Report (DAR), which was evaluated and commented on by the CTB. The CTB assessed the present application using the Dutch comments, typed in italics in the List of Endpoints underneath.

 

1.7       Packaging details

1.7.1    Packaging description

Material:

Fluorinated HDPE

Or

Co-extruded PE/PA

Capacity:

5L

Type of closure and size of opening:

Screw cap closure with induction heat seal or compression wad and tamper evident ring. Size of the opening: 63mm.

Other information

UN/ADR compliant

 

1.7.2    Detailed instructions for safe disposal

See application form and MSDS

 

 

2.      Physical and chemical properties

 

2.1              Active substance: fenpropidin and difenoconazole

 

Identity (fenpropidin)

Data regarding the identity and the physical and chemical properties are taken from the List of Endpoints (DAR, November 2006). Changes and/or additions are taken up in italics.

Active substance (ISO Common Name)

Fenpropidin

Chemical name (IUPAC)

(R,S)-1-[3-(4-tert-butylphenyl)-2-methylpropyl]-piperidine

Chemical name (CA)

1-[3-[4-(1,1-dimethylethyl)phenyl]-2-methylpropyl]-piperidine

CIPAC No

520

CAS No

67306-00-7

EEC No (EINECS or ELINCS)

Not allocated

FAO Specification (including year of                                publication)

No FAO specification available.

Minimum purity of the active substance as manufactured (g/kg)

940

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

Fenpropidin as manufactured contains no relevant impurities.

Molecular formula

C19H31N

Molecular mass

273.5

Structural formula

 


 


Physical-chemical properties

Melting point (state purity)

-64.6°C ± 0.3°C, purity 99.5 %

Boiling point (state purity)

Not relevant at atmospheric pressure as decomposition occurs.

70.2°C at 1.1 Pa, purity 99.3 %

Temperature of decomposition

Oxidative decomposition: 93°C-155°C

Thermal decomposition: 243°C-288°C (under N2-atmosphere)

Appearance (state purity)

Pale yellow liquid with a weak-amine like odour, purity 96.7 % 

Pale yellow liquid with a weak aromatic odour, purity 99.5 %

Relative density (state purity)

0.913, purity 99.5 %

Surface tension

51.6-52.1 mN/m at 20°C (saturated solution at a pH of approximately 8.6)

Vapour pressure (in Pa, state temperature)

1.7 x10-2­ at 25°C (extrapolated)

Henry’s law constant (in Pa·m3·mol-1)

10.7 Pa m3/mol at 25 °C

 

Solubility in water (in g/l or mg/l, state                                   temperature)

pH 6.0: 130 g/l (acetate buffer) at 25°C

pH 7.0: 0.530 g/l (phosphate buffer) at 25°C

pH 9.0: 6.2 mg/l (borax buffer) at 25°C

Solubility in organic solvents (in g/l or

 mg/l, state temperature)

>250 g/l at 25°C in all the tested solvents (acetone, dichloromethane, ethyl acetate, hexane, methanol, octanol and toluene).

Partition co-efficient (log Pow) (state pH and temperature)

pH 4.2: 0.83 at 25°C **

pH 7.0: 2.9 at 25°C **

pH 9.0: 4.5 at 25°C **

6.42 (KOWWIN calculation; non-dissociated form)

Hydrolytic stability (DT50) (state pH and temperature)

pH 3: Stable at 50°C

pH 7: Stable at 50°C

pH 9: Stable at 50°C

Dissociation constant

10.13 (estimation)

UV/VIS absorption (max.) (if absorption >290 nm state ε at wavelength)

 

Neutral media:

 

Acidic media:

 

Alkaline media:

λmax [nm]

218.2

263.7

217.9

262.9

219.2

263.9

 

No absorption maxima > 290 nm

Photostability (DT50) (aqueous, sunlight,  state pH)

No photodecomposition occurred (pH 5.0, seven days)

Quantum yield of direct photo-

transformation in water at λ > 290 nm

Not relevant since there is no absorption maxima at wavelength > 290 nm.

Photochemical oxidative degradation in air

Overall OH Rate Constant= 112.8567 x 10-12 cm3/molecule.sec

Half-life=1.14 hours

Flashpoint

Flash-point: 156°C (1013 mbar)

Auto-flammability

Auto-ignition temperature: 265°C

Oxidative properties

Not oxidising, purity 97.0%

Explosive properties

Not explosive, purity 96.7%

* The surface tension is to be determined at 90% of its saturation level in purified water.

** The log Pow was determined with the shake flask method. It is unknown whether phase separation was influenced by surface active behaviour of the active substance. Reliability of the log Pow determinations is therefore questionable.

Identity (difenoconazole)

Data regarding the identity and the physical and chemical properties are taken from the List of Endpoints (DAR, December 2006). Changes and/or additions are taken up in italics.

Active substance (ISO Common Name)

Difenoconazole

 

Chemical name (IUPAC)

1-[2-[2-chloro-4-(4-chloro-phenoxy)-phenyl]-4-methyl[1,3]dioxolan-2-ylmethyl]-1H-[1,2,4] triazole

Chemical name (CA)

1-[[2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole

CIPAC No

Not allocated

CAS No

119446-68-3

EEC No (EINECS or ELINCS)

Not allocated

FAO Specification (including year of                                publication)

No FAO specification available.

Minimum purity of the active substance as manufactured (g/kg)

940 g/kg

 

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

Difenoconacole as manufactured does not contain any relevant impurities.

 

Molecular formula

C19H17Cl2N3O3

Molecular mass

406.3 g/mol

Structural formula

 

 

 

Physical-chemical properties

Melting point (state purity)

            82.0-83.0°C (99.3%)

Boiling point (state purity)

Not relevant at atmospheric pressure as decomposition occurs.         

100.8°C at 3.7 mPa (99.3%)

Temperature of decomposition

Decomposition starts at about 337°C (99.3%)

Appearance (state purity)

Technical material: Off-white powder with a slightly sweetish odour, purity not stated.

Purified material: White fine odourless crystalline powder, purity 99.3 % 

Relative density (state purity)

Density: 1.40 g/ml (94.9%)

Density: 1.39 g/ml (99.3)

Surface tension

62.8 mN/m at 20°C (90 % saturated solution)(94.6%)

Vapour pressure (in Pa, state temperature)

3.32 x 10-8­ Pa at 25°C (99.0%)

Henry’s law constant (in Pa·m3·mol-1)

9.0 x 10-7 Pa m3 mol -1

 

Solubility in water (in g/l or mg/l, state                                   temperature)

15 mg/l ± 1.3 mg/l at pH 7.2 and 25 °C

No pH effect is anticipated at environmentally relevant pH

Solubility in organic solvents (in g/l or

 mg/l, state temperature)

Solubility at 25°C in g/L (94.6%):

acetone:          >500 g/l
dichloromethane:       >500 g/l
ethyl acetate:  >500 g/l
hexane:           3.0 g/l
methanol:        >500 g/l
octanol:           110 g/l
toluene            >500 g/l

 

Partition co-efficient (log Pow) (state pH and temperature)

log PO/W = 4.36 ± 0.02 at  25 °C and a pH of approx. 8 (99.3%)

No pH effect is anticipated at environmentally relevant pH.

Hydrolytic stability (DT50) (state pH and temperature)

Stable at pH 5, 7, 9 for 25 days at 25°C

Dissociation constant

 

pKa1 = 1.07 ± 0.18 for the corresponding acid (i.e the neutral species is predominantly present at pH > 1.1) (99.3%)

UV/VIS absorption (max.) (if absorption >290 nm state ε at wavelength)

                          λmax [nm]

                            215

neutral media:     235

                            275

 

                             215

acidic media:        235

                             275

 

                             220

alkaline media:     235

                             275

No absorption maxima between 300 nm and 700 nm at any pH.

Photostability (DT50) (aqueous, sunlight,  state pH)

Not applicable (no absorption above 290 nm)

Quantum yield of direct photo-

transformation in water at λ > 290 nm

Not applicable (no absorption above 290 nm)

Photochemical oxidative degradation in air

DT50 = 4.87 hours (26.3762 x 10-12 cm3/molecule.sec)

Flammability

Not highly flammable

Auto-flammability

No self-ignition below the melting point

Oxidative properties

Not oxidising (91.8%)

Explosive properties

Not explosive(91.8%)

 

2.2              Plant protection product: Spyrale

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

 

The range of the application concentration of the plant protection product is 0.19 - 0.5 %

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

Brown

Acceptable

B.2.2.3 (IIIA 2.1)

Appearance: odour

GLP

Olfactory

Weak, solvent like

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

UN O.2

Not oxidising

 

EC A21 is based on UN method O.2. Therefore this test method is accepted.

Acceptable

B.2.2.6 (IIIA 2.3)

Flammability

 

Not applicable

 

B.2.2.7 (IIIA 2.3)

Auto-flammability

GLP

EC A15

370 oC

Acceptable

B.2.2.8 (IIIA 2.3)

Flash point

GLP

EC A9

103 oC

Acceptable

B.2.2.9 (IIIA 2.4)

Acidity / alkalinity

 

Not applicable

 

B.2.2.10 (IIIA 2.4)

pH

GLP

CIPAC MT75.3

1% in deionised water at 25 oC: 9.9

pH of the neat formulation was not determined and is not required (oil based).

Acceptable

B.2.2.11 (IIIA 2.5)

Surface tension

GLP

EC A5

 

GLP

EC A5

26.2 mN/m (undiluted; 25 oC)

 

 

32.3 mN/m (0.7% in purified water at 20 oC)

32.1 mN/m (0.1% in purified water at 20 oC)

Acceptable

 

 

Acceptable as supplementary information

B.2.2.12 (IIIA 2.5)

Viscosity

GLP

OECD 114

20 oC: 39.6 mPa.s

40 oC: 15.2 mPa.s

(100 s-1; no shear-rate dependence; undiluted product)

Acceptable

B.2.2.13 (IIIA 2.6)

Relative density

GLP

OECD 109

Density: 0.995 g/cm3 (20 oC)

Acceptable

B.2.2.14

(IIIA 2.6)

Bulk (tap) density

 

Not applicable

 

B.2.2.15 (IIIA 2.7)

Storage stability

GLP

OECD 113

Stable for 2 weeks at 54 oC in glass

 

Properties determined before and after storage: a.i. content, density.

Acceptable

GLP

CIPAC MT39.1

Stable for 7 dats at 0 oC (0.2 ml separation)

Acceptable

B.2.2.16 (IIIA 2.7)

Shelf life

GLP

Analytical method AF-1154/1

CIPAC MT75.2, 173

OECD 109

Stable for 2 years at ambient temperatures (20 oC) in fluorinated HDPE.

 

Properties determined before and after storage: a.i. content, pH, density, emulsion properties, packaging stability.

Acceptable

GLP

Analytical method AF-1154/1

CIPAC MT75.2, 173

OECD 109

Stable for 2 years at ambient temperatures (20 oC) in coex PE/PA.

 

Properties determined before and after storage: a.i. content, pH, density, emulsion properties, packaging stability.

Acceptable

B.2.2.17

(IIIA 2.8)

Wettability

 

Not applicable

 

B.2.2.18 (IIIA 2.8)

Persistent foaming

GLP

CIPAC MT47.2

0.7% in CIPAC C water:

10 ml foam after 1 minute

 

Although foam persistence may increase in CIPAC D water, it is unlikely foam persistence will exceed the limit of 60 ml foam after 1 minute.

Acceptable

B.2.2.19

(IIIA 2.8)

Suspensibility

 

Not applicable

 

B.2.2.20

(IIIA 2.8)

Spontaneity of dispersion

 

Not applicable

 

B.2.2.21

(IIIA 2.8)

Dilution stability

 

Not applicable

 

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

 

Not applicable

 

B.2.2.25

(IIIA 2.8)

Content of dust/fines

 

Not applicable

 

B.2.2.26

(IIIA 2.8)

Attrition and friability

 

Not applicable

 

B.2.2.27 (IIIA 2.8)

Emulsifiability, re-emulsifiability and emulsion stability

GLP

CIPAC MT173

Tests performed:

0.7% in CIPAC A

0.7% in CIPAC C

0.1% in CIPAC A

0.1% in CIPAC C

Spontaneity of the emulsion was not spontaneous for all tests.

Stability was acceptable after 0.5, 2 and 24 hours for all tests (96 – 101%).

Re-emulsification was complete and stability after re-emulsification was also acceptable for all tests.

 

The test should be performed in CIPAC D instead of CIPAC C water. However, test results indicate very good emulsion properties and therefore additional tests are not considered required.

Acceptable

B.2.2.28

(IIIA 2.8)

Stability of dilute emulsion

 

See B.2.2.26.

 

B.2.2.29

(IIIA 2.8)

Flowability

 

Not applicable

 

B.2.2.30

(IIIA 2.8)

Pourability (rinsibility)

 

Not applicable

 

B.2.2.31

(IIIA 2.8)

Dustability

 

Not applicable

 

B.2.2.32

(IIIA 2.8)

Adherence and distribution to seeds

 

Not applicable

 

2.9.1

Physical compatibility with other products

 

Not applicable

 

2.9.2

Chemical compatibility with other products

 

Not applicable

 

 

No mixing with other plant protection products or adjuvants is proposed. No information is available on the behaviour of this product when mixed. Mixing with another product or adjuvant can therefore result in unexpected behaviour.

 


Conclusion

The physical and chemical properties of the plant protection product are sufficiently described by the available data. The product does not have physical or chemical properties, which would adversely affect the use according to the proposed use and label instructions.

 

2.3              Data requirements

No data requirements.

 

 

3.         Methods of analysis

 

Description and data concerning the analytical methods for fenpropidin are taken from the List of Endpoints (DAR, May 2005). Changes and/or additions are taken up in italics.

 

Description and data concerning the analytical methods for difenoconazole are taken from the List of Endpoints (DAR, December 2006). Changes and/or additions are taken up in italics.

 

3.1.      Analytical methods in technical material and plant protection product

Technical as (principle of method)

Fenpropidin

GC-FID

Difenoconazole

GC-FID

Impurities in technical as (principle of method)

Fenpropidin

GC-FID and HPLC-UV

Difenoconazole

GC-FID

Confirmation by GC-MS

Preparation (principle of method)

AF-1154/1. GC-FID method for determination of fenpropidin and difenoconazole in formulations.

 

Conclusion

The analytical methods regarding the technical material of fenpropidin and difenoconazole are addressed in the DARs, which are acceptable for both active substances.

 

3.2       Residue analytical methods

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

Fenpropidin

Not required

Difenoconazole

Not required

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

Fenpropidin

Not required

Difenoconazole

LCMSMS method REM 147.07 (difenoconazole and CGA205375). LOQ = 0.01 mg/kg (milk, liver, egg, fat, kidney, muscle)

ILV: yes

Soil (principle of method and LOQ)

Fenpropidin

LC-MSMS method nr. CGA 114900

LOQ: 0.01 mg/kg

Confirmatory method:not required

Difenoconazole

LC-MS/MS

LOQ: 0.01 mg/kg

Confirmatory method:not required

Water (principle of method and LOQ)

Fenpropidin

LC-MS/MS method nr. GRM 024.03A for determination of fenpropidin and CGA289267 in soil.

LOQ = 0.05 µg/l

Confirmatory method:not required

Difenoconazole

GC-ECD method REM 147.05 for determination of difenoconazole in potable and surface water.

LOQ = 0.05 µg/l (drinking water)

LOQ = 0.1 µg/l (surface water)

Confirmatory method: HPLC-UV

Air (principle of method and LOQ)

Fenpropidin

GC with nitrogen phosphorus detector (NPD) for determination of fenpropidin only

LOQ = 1 µg/m3

Confirmatory method: method for water

Difenoconazole

GC-ECD method REM 147.02 for determination of difeconazole in air.

LOQ = 2 μg/m3

Confirmatory method: method for water

Body fluids and tissues (principle of method and LOQ)

Fenpropidin

Not required, non toxic compound

Difenoconazole

Not required, non toxic compound

 

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 a crop specific matrix (sugar beet). However, no residues are expected in food/feed of plant origin, because processing of sugar beets involves thorough purification. Furthermore, because residue levels for fenpropidin are very low (see residue section), no residues in food/feed of animal origin are expected either.

 

Definition of the residue and proposed MRL’s for fenpropidin

Matrix

Proposed definition of the residue for monitoring

Proposed MRL

Food/feed of plant origin

No residues are expected (see residue section). No MRL is set.

Food/feed of animal origin

 

Required LOQ

Soil

Fenpropidin

0.05 mg/kg (default)

Drinking water

Fenpropidin

0.1 µg/L (Dutch drinking water guideline)

Surface water

Fenpropidin

0.1 µg/L

Air

Fenpropidin *

6 µg/m3 (derived from the AOEL (0.02 mg/kg bw/day) according to SANCO/825/00)

Body fluids and tissues

The active substance is not classified as (very) toxic thus no definition of the residue is proposed.

* The DAR states no definition of the residue is proposed. A method for determination of residues in air is considered a requirement and therefore a residue definition of fenpropidin only is considered appropriate.

 

Definition of the residue and proposed MRL’s for difenoconazole

Matrix

Proposed definition of the residue for monitoring

Proposed MRL

Food/feed of plant origin

No definition of the residue is proposed (see residue section). No MRL is set.

Food/feed of animal origin

Sum of difenoconazole and 1-[2-[2-chloro-4-(4-chloro-phenoxy)-phenyl]-2-hydroxy-1-ethyl]-1H-1,2,4-triazole

Liver: 0.2 mg/kg

Other: 0.1 mg/kg

 

Required LOQ

Soil

Difenoconazole *

0.05 mg/kg (default)

Drinking water

Difenoconazole *

0.1 µg/L (Dutch drinking water guideline)

Surface water

Difenoconazole *

5.6 µg/L (NOEC for Daphnia Magna)

Air

Difenoconazole

0.006 mg/m3 (derived from the AOEL (0.02 mg/kg bw/day) according to SANCO/825/00)

Body fluids and tissues

The active substance is not classified as (very) toxic thus no definition of the residue is proposed.

* The 1,2,4-triazole metabolite is left out of the definition of the residue, because this metabolite is not specific for difenoconazole.

 

For fenpropidin no residues are expected in food/feed of plant or animal origin. Residue analytical methods are therefore not required.

 

Conclusion

The residue analytical methods are addressed in the DAR, which are acceptable for both active substances.

 

3.3       Data requirements

No further data requirements.

 

3.4       Physical-chemical classification and labelling

 

Proposal for the classification of fenpropidin (symbols and R phrases)
(EU classification) concerning physical chemical properties

 

Symbol(s):

-

Indication(s) of danger: -

 

Risk phrase(s)

-

-

 

Proposal for the classification of difenoconazole (symbols and R phrases)
(EU classification) concerning physical chemical properties

 

Symbol(s):

-

Indication(s) of danger: -

 

Risk phrase(s)

-

-

 

Proposal for the classification and labelling of Spyrale concerning physical chemical properties

 

Regarding the physical and chemical properties of the formulation, the method of application and the further information on the plant protection product, the following labelling of the preparation is proposed:

 

Substances, present in the formulation, which should be mentioned on the label by their chemical name (other very toxic, toxic, corrosive or harmful substances):

-

Symbol:

-

Indication of danger:

-

R phrases

-

-

 

 

 

S phrases

21

When using do not smoke

 

 

 

Special provisions:
DPD-phrases

-

-

 

 

 

Child-resistant fastening obligatory?

Not applicable

Tactile warning of danger obligatory?

Not applicable

 

Explanation:

Hazard symbol:

-

Risk phrases:

-

Safety phrases:

-

Other:

-

 

 

4.                  Mammalian toxicology

 

List of Endpoints

Fenpropidin

Fenpropidin is an existing active substance. The toxicological profile presented below is based on the Draft Assessment Report (DAR) prepared by the RMS Sweden. The Dutch comments on the DAR and some additional information, when relevant, are also presented (in italic). Since the active substance is still in the process of evaluation/discussion, the toxicological profile below should be regarded as provisional. The process of evaluation just started; Member States commented on the DAR in May 2006 and fenpropidin has not yet been discussed in an Expert Meeting. Based on the comments from the Member States on the DAR, the List of Endpoints is already amended accordingly by the RMS (Nov. 2006).

 



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

Rate and extent of oral absorption

Oral absorption > 80% (excretion within 48 h, 79% in urine, 12% via bile) 1

Distribution

Widely distributed

Potential for accumulation

No evidence for accumulation.

Rate and extent of excretion

Rapid and extensive (82-102%) within 48h, mainly via urine (77-86%) within 24h.

Metabolism in animals

Extensively metabolised (>95%) main metabolite 2-methyl-2-[4-(2-methyl-3-piperidin-1-yl-propyl)-phenyl]-propionic acid; oxidation reactions and sulphate conjugation.

Toxicologically significant compounds
(animals, plants and environment)

Parent compound

1 Intravenous administration showed that at the low dose level 14% was excreted in the faeces (females). It can be concluded that fenpropidin was completely absorbed.

 

Acute toxicity (Annex IIA, point 5.2)

Rat LD50 oral

1452 mg/kg bw

R22

Rat LD50 dermal

>2000 mg/kg bw

----

Rat LC50 inhalation

1.22 mg/l air /4 h

R20

Skin irritation

Irritant

R38

Eye irritation

Irritant

R41

Skin sensitization (test method used and result)

Sensitiser (Maximization, Buehler)

R43

 

Short term toxicity (Annex IIA, point 5.3)

Target / critical effect

Local irritation, body weight, liver (hypertrophy), spinal chord demyelinisation, corneal opacity.

Relevant oral  NOAEL

1 yr dog 2 mg/kg bw/day 2

 

Relevant dermal NOAEL

>1-2 mg/kg bw/day

 

Relevant inhalation NOAEL

Not evaluated for systemic toxicity, study inclonclusive for systemic toxicity but sufficient to show local irritation of nose and upper respiratory tract.

R37

2 In the DAR a NOAEL of 5 mg/kg bw/day was derived. NL proposed a systemic NOAEL of 2 mg/kg bw/d, based on the dose-related liver effects at 5 mg/kg bw/d; relative liver weights were increased 16%, the same two animals showed hepatocyte hypertrophy and AP is also dose related increased at 5 mg/kg bw/d. Based on the NL comment on the DAR, the RMS amended the List of Endpoints.

 

Genotoxicity (Annex IIA, point 5.4)

No genotoxic potential. 3

 

3 The genotoxic potential of fenpropidin was investigated in four in vitro studies (Ames test, chromosome aberration test in Chinese hamster ovary cells CHO-K1, V79/HGPRT mutation test in Chinese hamster cells, UDS test in primary rat hepatocytes) and in one in vivo study (micronucleus test in mouse bone marrow).

 

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

Target/critical effect

Body weight; rats

Relevant NOAEL

50 ppm (2.27 mg/kg bw/day in females)

Carcinogenicity

No carcinogenic potential.

 

 

Reproductive toxicity (Annex IIA, point 5.6)

Reproduction target / critical effect

Reproductive toxicity: Body weights, decreased number of F2 pups delivered and implantations at maternally toxic doses. Parental toxicity (-17% bw, F1 females)

 

Relevant reproductive parental NOAEL

100 ppm (8-18 mg/kg bw/day)

 

Relevant reproductive offspring NOAEL

100 ppm (9-18 mg/kg bw/day)

 

Developmental target / critical effect

Incompletely ossified and split neural arches at maternally toxic doses.

 

Relevant developmental maternal NOAEL

Rat: 19.5 mg/kg bw/day

 

Relevant developmental offspring NOAEL

Rat: 47.5 mg/kg bw/day

 

 

Neurotoxicity (Annex IIA, point 5.7)

Acute and repeated neurotoxicity

No data, no study required

 

Delayed neurotoxicity

No data, no study required

 

Other studies

Spinal chord demyelination

90 day rat

NOAEL: 10.1 mg/kg bw/day 

1-year dog

NOAEL: 5 mg/kg bw/day

R48

 

Other toxicological studies (Annex IIA, point 5.8) 

Mechanism studies

No data, no study required

Studies performed on metabolites or impurities

No data, no study required

 

Human data (Annex IIA, point 5.9)

 

 

Limited - no detrimental effects on health in manufacturing personnel (one incident of eye and skin irritations reported) or in a farmer survey of 65 farmers in the UK.

 

 

Summary (Annex IIA, point 5.10)

Value

Study

Safety factor

ADI

0.02 mg/kg bw/d 4

rat, 2-yr study

dog, 1-yr study

100

AOEL

0.02 mg/kg bw/d

dog, 1-yr study

100

(100%*)

ARfD (acute reference dose)

0.05 mg/kg bw

dog 28-day and 26 weeks studies

100

* Correction for oral absorption

4 In the DAR an ADI of 0.023 mg/kg bw/day was derived. NL proposed a slight adjustment of the ADI: 0.02 mg/kg bw/d based on the NOAEL of 2.23 mg/kg bw/d in the 2y rat study and the NOAEL of 2 mg/kg bw/d in the 1y dog study. Based on the NL comment on the DAR, the RMS amended the List of Endpoints.

 

Dermal absorption (Annex IIIA, point 7.3)

Product information: TERN 750 EC (A-7516 B, 750 g ai/l, 82% w/w): tested in vivo and in vitro at 0.4% in water and undiluted EC formulation

 

Concentrate: 2.5%

Spray dilution: 6.4%

Rat in vivo and comparative in vitro (human/rat skin).

 

Difenoconazole

Difenoconazole is an existing active substance. The EU-dossier is complete, however the Draft Assessment Report (DAR) is not yet available. Sweden is RMS. The most recent risk assessment of difenoconazole was performed in 2004 (for the registration of Score 250 EC), see the decision of September 10, 2004 (based on the Board meeting C-148.3.2, d.d. August 11, 2004). The toxicological profile presented below is based on TNO report nr. 261050-162, d.d. 26-04-1993, TNO report nr. 257767-162, d.d. 27-01-1998 and RIVM report nr. 08663A00, d.d. 12-09-2002. Since the active substance is still in the process of evaluation/discussion, the toxicological profile below should be regarded as provisional.

 

Toxicokinetiek

Er zijn geen exacte gegevens overlegd t.a.v. de absorptie van difenoconazool in proefdieren. In C-32.3.2 is op basis van de hoeveelheid ongemetaboliseerd difenoconazool in de faeces van de rat (17%) en het feit dat enig metabolisme in de darm plaats kan vinden de orale absorptie op ongeveer 75% gesteld. Difenoconazool wordt snel uitgescheiden zoals bleek uit proeven waarbij 0,5 en 300 mg/kg lg 14C-difenoconazool oraal werd toegediend aan ratten. De meeste activiteit (70-85%) werd teruggevonden in de faeces. Er werd geen verschil gevonden in route en snelheid van uitscheiding tussen de verschillende dosisgroepen. Bij ratten worden dezelfde metabolieten gevormd als bij geiten en kippen. De belangrijkste metabolieten zijn: mA, mB, mC en mD. Metaboliet mA wordt gevormd door het openbreken van de dioxolangroep van difenoconazool. Vervolgens vindt er een reductie van het keton plaats en ontstaat er een hydroxylgroep (mB). Door afsplitsing van de triazolring (mC) ontstaat de metaboliet mD. De snelheid waarmee deze metabolieten gevormd worden verschilt echter per diersoort.

 

Toxicodynamiek

Acute toxiciteit

Difenoconazool dient voor orale toxiciteit als schadelijk geclassificeerd te worden (R22). Difenoconazool hoeft niet geclassificeerd te worden voor dermale toxiciteit. Difenoconazool dient bij inhalatoire blootstelling volgens de EG-criteria als schadelijk geclassificeerd te worden (R20). Difenoconazool is niet irriterend voor de huid of ogen. Difenoconazool is niet sensibiliserend voor de huid.

 

Kortdurende en chronische toxiciteit/Carcinogeniteit

In subacute en semi-chronische studies met ratten en honden bleek de lever na orale blootstelling een van de doelorganen van difenoconazool, naast nieren en rode bloedcellen. Veranderingen die werden waargenomen betroffen een toename in levergewicht, lever-gerelateerde afwijkingen in klinische chemische parameters en hypertrofie van hepatocyten. Uit de 28-dagen dermale studie met de rat werd een NOAEL afgeleid van 100 mg/kg lg/d, gebaseerd op verhoogde levergewichten en hypertrofie van levercellen en hypertrofie van folliculaire cellen van de schildklier bij de naast hogere dosis groep.

 

Ook in een chronische studie bij de rat werden na twee jaar orale toediening van difenoconazool verhoogde levergewichten en hypertrofie van levercellen gevonden. Lever­tumoren werden gevonden in een chronische toxiciteits/carcinogeniteitsstudie met de muis. In deze studie werden muizen gedurende 18 maanden oraal blootgesteld aan doseringen difenoconazool van 0, 10, 30, 300, 2500 en 4500 mg/kg lg/d. Vanaf 300 mg/kg lg/d werden hepatotoxische effecten gevonden in de vorm van verhoogde levergewichten, lever ­gerela­teerde afwijkingen in klinische chemie en leverpathologie (hypertrofie en necrose van levercellen, galstuwing en vettige degeneratie). Bij 2500 en 4500 mg/kg gl/d neemt het aantal hepatocellulaire adenomen en carcinomen toe.

 

Het feit dat difenoconazool geen genotoxische eigenschappen heeft, gecombineerd met het gegeven dat de lever een toxicologisch doelorgaan van deze stof is in diverse diersoorten en het feit dat toename van levertumoren alleen gevonden werd in muizen bij doseringen die ruim boven de NOAEL voor levereffecten in deze diersoort liggen rechtvaardigt het gebruik van grenswaarden voor het beoordelen van het risico voor de mens (toepasser/volksgezondheid) als gevolg van blootstelling aan difenoconazool.

 

In de chronische studie met de rat werd in alle testdoseringen een niet dosisgerelateerde toename van pancreastumoren gevonden. Vergelijking met historische controlewaarden voor dit soort tumoren in deze rattenstam leidt tot de conclusie dat deze toename van de frequentie van deze tumoren in de onderhavige studie niet gerelateerd is aan blootstelling aan difenoconazool.

Genotoxiciteit

Difenoconazool was negatief in een puntmutatietest met bacteriën (Ames test) en in een genmutatietest met zoogdieren in vitro. Difenoconazool induceerde geen micronucleď in het beenmerg en geen kernafwijkingen in vivo in respectievelijk de muis en hamster. Difenoconazool veroorzaakt geen “unscheduled DNA synthesis” in rattenhepatocyten in vitro. In afwezigheid van een metabole activator bleek deze stof ook geen “unscheduled DNA synthesis” te veroorzaken in humane fibroblasten (maar dit is niet getest in aanwezigheid van S9-mix).

Er zijn geen aanwijzingen dat difenoconazool genotoxische eigenschappen bezit.

Reproductie- en ontwikkelingstoxiciteit

Gebaseerd op de embryotoxiciteit/teratogeniteitsstudies bij ratten en konijnen en de
2-generatie reproductiestudie bij ratten, is de NOAEL voor reproductie- en ontwikkelings-stoornissen 13-16 mg/kg lg/dag. Er werden geen teratogene effecten van difenoconazool gevonden. De waargenomen ontwikkelingsstoornissen traden alleen op bij doseringen die maternale toxiciteit veroorzaken.

Specifiek onderzoek

Difenoconazool induceert lenscataracten bij hoge doseringen bij kippen en (minder consistent) bij honden. De laagste dosering waarbij dit is opgetreden, bedraagt 96 mg/kg lg/dag (hond).

 

Data requirements active substances

Fenpropidin and difenoconazole: The data requirements identified in the EU-assessment are also applicable to the Dutch assessment.

 

4.1       Toxicity of the formulated product (IIIA 7.1)

The formulation Spyrale needs to be classified as R22 ‘Harmful if swallowed’, based on the acute oral toxicity (LD50 rat between 1500 and 2000 mg/kg bw).  

The formulation Spyrale does not need to be classified on the basis of its acute dermal (LD50 rat > 4000 mg/kg bw), and inhalation toxicology (no study available; not necessary).

The formulation is considered irritating to skin and needs to be classified as R38 ‘Irritating to skin’.

The formulation is considered irritating to eyes and needs to be classified as R36 ‘Irritating to eyes’.

The submitted maximisation test for skin sensitisation had several shortcomings. Based on the amount of fenpropidin, the formulation Spyrale needs to be classified as R43 ‘May cause sensitisation by skin contact’, according to the classification and labelling Directive.

 

4.1.1    Data requirements formulated product

No additional data requirements are identified.

 

4.2       Dermal absorption (IIIA 7.3)

Fenpropidin

The area doses in the dermal absorption studies in the DAR were 0.03 mg/cm2 and 7.5 mg/cm2. The amount of fenpropidin in Spyrale is 375 g/L and the tested formulation TERN 750 EC contains 750 g/L. This means that the dermal absorption of fenpropidin from the concentrated formulation Spyrale (resulting in an area dose <7.5 mg/cm2) might be somewhat higher than from the concentrated formulation TERN 750 EC. Furthermore, the composition of the formulations is not comparable. For example, Spyrale has a higher content of organic solvent, which might slightly increase dermal absorption of fenpropidin. For the current risk assessment, a worst-case dermal absorption value of 6.4% (see List of Endpoints) will therefore be used for the concentrate and the spray dilution.

 


Difenoconazole

Two dermal absorption studies are available: an in vivo study in rats and an in vitro study with rat and human skin membranes, both performed with difenoconazole formulated as Score 250 EC. The results of the in vivo study show a dermal absorption of 30, 12, and 8% for an area dose of 0.5 µg/cm2, 12.5 µg/cm2 and 2500 µg/cm2, respectively. From the in vitro study, flux ratios (human/rat skin) of 0.1, 0.08, and 0.03 were derived. For the risk assessment this results in 0.3% for the concentrate (2.5 mg/cm2) and 3% for the spray dilution (0.5 µg/cm2) (these are rounded values because of the wide variation in the study results). These area doses are also relevant for the current application (the area dose for the spray dilution of Spyrale is 1 µg/cm2, based on the GAP). Score 250 EC and Spyrale are both EC formulations and the compositions of the formulations are comparable. In conclusion, for the current risk assessment a dermal absorption value of 0.3% for the concentrate and 3% for the spray dilution will be used.

 

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

Other formulants: no reason for toxicological concern.

 

4.4       Exposure/risk assessments

 

Overview of the intended uses

An application has been submitted for the authorisation of the plant protection product Spyrale, a fungicide based on the active substances fenpropidin and difenoconazole, in sugar and fodder beet.

Spyrale is an EC formulation and contains 375 g/L fenpropidin and 100 g/L difenoconazole.

The formulation Spyrale is applied by mechanical downward spraying in sugar and fodder beet. The formulation is applied 1-2 times (with a spray interval of 21 days) during the period July – September with a maximum dose of 1 L formulation / ha. Therefore, a semi-chronic exposure duration is applicable for the operator (including contract workers).

 

Calculation of the AOEL

 

Fenpropidin

Fenpropidin is not yet included in Annex I of 91/414/EEC. This means that the Netherlands may calculate the AOEL according to the Dutch method. This method takes into account the caloric need of the species studied and results in a more specific value than the EU-AOEL for which a standard factor of 100 is applied.

The calculation of the systemic AOEL for semi-chronic exposure is based on the NOAEL of 2 mg/kg bw/day in the 1-year study with the dog. Calculations from other studies result in higher AOELs.

Safety factors are used to compensate for the uncertainties, which arise, for example, from extrapolation from the tested species to humans and the differences between experimental circumstances, and to ensure that at the acceptable exposure level no adverse health effects will occur.

 

Used factors are:

·       extrapolation dog® man on basis of caloric need:                                             1.4

·       other interspecies differences:                                                                            3

·       intraspecies differences (professional use):                                                       3

·       biological availability via oral route:                                                                      100%

·       weight of professional operator/worker:                                                              70 kg

 

AOELsystemic: 2 x 1 x 70 / (1.4 x 3 x 3) = 11 mg/day

 

Difenoconazole

Difenoconazole is not yet included in Annex I of 91/414/EEC. This means that the Netherlands may calculate the AOEL according to the Dutch method. This method takes into account the caloric need of the species studied and results in a more specific value than the EU-AOEL for which a standard factor of 100 is applied.

The calculation of the systemic AOEL for semi-chronic exposure is based on the NOAEL of 2.3 mg/kg bw/day in the 13-week study with the rat. Calculations from other studies result in higher AOELs.

Safety factors are used to compensate for the uncertainties, which arise, for example, from extrapolation from the tested species to humans and the differences between experimental circumstances, and to ensure that at the acceptable exposure level no adverse health effects will occur.

 

Used factors are:

·       extrapolation rat® man on basis of caloric need:                                              4

·       other interspecies differences:                                                                            3

·       intraspecies differences (professional use):                                                       3

·       biological availability via oral route:                                                                      75%

·       weight of professional operator/worker:                                                              70 kg

 

AOELsystemic: 2.3 x 0.75 x 70 / (4 x 3 x 3) = 3.4 mg/day

 

4.4.1    Operator exposure/risk

 

Fenpropidin

Exposure to fenpropidin during mixing and loading and application of Spyrale is estimated with models. The exposure is estimated for the unprotected operator. In Table T.1 the estimated internal exposure is compared with the systemic AOEL. 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.

 

Table T.1 Internal operator exposure to fenpropidin and risk assessment for the use of Spyrale

 

Route

Estimated internal exposure a (mg /day)

Systemic

AOEL

(mg/day)

Risk-index b

Mechanical downward spraying on sugar and fodder beet

Mixing/

Loading

Respiratory

0.019

11

<0.01

Dermal

4.80

11

0.4

Application

Respiratory

0.03

11

<0.01

Dermal

0.72

11

0.1

 

Total

5.6

11

0.5

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

·       biological availability via the dermal route:   6.4% (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.

 

Difenoconazole

Exposure to difenoconazole during mixing and loading and application of Spyrale is estimated with models. The exposure is estimated for the unprotected operator. In Table T.2 the estimated internal exposure is compared with the systemic AOEL. 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.

 

Table T.2 Internal operator exposure to difenoconazole and risk assessment for the use of Spyrale

 

Route

Estimated internal exposure a (mg /day)

Systemic

AOEL

(mg/day)

Risk-index b

Mechanical downward spraying on sugar and fodder beet

Mixing/

Loading

Respiratory

0.005

3.4

<0.01

Dermal

0.06

3.4

0.02

Application

Respiratory

0.008

3.4

<0.01

Dermal

0.09

3.4

0.03

 

Total

0.2

3.4

0.05

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

·       biological availability via the dermal route:   0.3% for the concentrate and 3% for the 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.

 

The applicant also submitted three operator exposure studies with three other herbicides (SC and EC formulations), containing other active substances and applied by tractor in different crops. Evaluation of the studies showed that the studies had several drawbacks and that the three studies as such should not overrule the results with appropriate exposure modelling as with EUROPOEM for handling liquids and downward spraying when potential dermal and inhalation exposure is concerned. The submitted operator exposure studies were therefore not used for the current risk-assessment.

 

4.4.2    Bystander exposure/risk

 

Fenpropidin and difenoconazole

The bystander exposure is only a fraction of the operator exposure. Based on the low risk-indices for the operator, no exposure calculations are performed for bystanders.

 

4.4.3    Worker exposure/risk

 

Fenpropidin and difenoconazole

Shortly after application it is not necessary to perform any re-entry activities during which intensive contact with the treated crop will occur. Therefore no worker exposure is calculated.

 

4.4.4    Re-entry

 

Fenpropidin and difenoconazole

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

Based on the risk assessment, it can be concluded that no adverse health effects are expected for the unprotected operator after dermal and respiratory exposure to fenpropidin and difenoconazole as a result of the application of Spyrale in sugar and fodder beet. No additional risks are expected of the simultaneous exposure to fenpropidin and difenoconazole.

It should be noted that because of the local and sensibilisation effects of the formulation PPE will be prescribed on the label.

 


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 fenpropidin and difenoconazole during application of Spyrale in sugar and fodder beet.

 

Worker exposure

Based on the risk assessment, it can be concluded that no adverse health effects are expected for the unprotected worker after dermal and respiratory exposure during re-entry activities in sugar and fodder beet due to exposure to fenpropidin and difenoconazole after application of Spyrale.

 

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

The formulation Spyrale is a mixture of two active substances. The combined toxicological effect of these two active substances has not been investigated with regard to repeated dose toxicity. Possibly, the combined exposure to these active substances may lead to a different toxicological profile than the profile(s) based on the individual substances.

 

Both substances have effects on the liver, resulting in hypertrophy. A combined exposure to these substances could therefore induce an additive effect. However, since the estimated exposure to these substances is, especially for difenoconazole, only a small fraction of the AOEL, no risks are expected even if an additive effect will be induced by the simultaneous exposure to both substances.

 

4.8       Mammalian toxicology classification and labelling

 

Proposal for the classification of the active ingredients (symbols and R phrases)
(EU classification)

 

Fenpropidin

Symbol:

Xn

Indication of danger: Harmful

 

Risk phrases

R20/22

R37/38

R41

R43

R48/22

Harmful by inhalation and if swallowed

Irritating to respiratory system and skin

Risk of serious damage to eyes

May cause sensitization by skin contact

Harmful: danger of serious damage to health by prolonged exposure if swallowed

 

Difenoconazole

Symbol:

Xn

Indication of danger: Harmful

 

Risk phrases

R20/22

Harmful by inhalation and if swallowed

 

 


Proposal for the classification and labelling of the formulation concerning health

 

Based on the profile of the substance, the provided toxicology of the preparation, the characteristics of the co-formulants, the method of application and the risk assessment for the operator, as mentioned above, the following labelling of the preparation is proposed:

 

Substances, present in the formulation, which should be mentioned on the label by their chemical name (other very toxic, toxic, corrosive or harmful substances):

-

Symbol:

Xn

Indication of danger:

Harmful

R phrases

22

Harmful if swallowed.

 

36/37/38

Irritating to eyes, respiratory system and skin.

 

43

May cause sensitisation by skin contact.

 

48/22

Harmful: danger of serious damage to health by prolonged exposure if swallowed.

 

 

 

S phrases

23

Do not breathe gas/fumes/vapour/spray (appropriate wording to be specified by the manufacturer).

 

36/37

Wear suitable protective clothing and gloves.

 

46

If swallowed, seek medical advice immediately and show this container or label.

 

 

 

Special provisions:
DPD-phrases

-

-

 

 

 

Plant protection products phrase:
DPD-phrase

DPD01

To avoid risk for man and the environment, comply with the instructions for use

Child-resistant fastening obligatory?

n.a.

Tactile warning of danger obligatory?

n.a.

 

Explanation:

Hazard symbol:

-

Risk phrases:

R43 is assigned as the available maximisation test for skin sensitisation was not performed correctly. Therefore, the negative result of the test is considered questionable. The active substance fenpropidin is a skin-sensitiser and is present in the formulation in a concentration greater than it’s limit value for classification with R43. The formulation therefore needs to be classified as: R43: May cause sensitisation by skin contact.

R48/22 is assigned based on the evaluation of the RMS in the DAR of fenpropidin and the comments of MSs.

Safety phrases:

S2, S13 and S20 are no longer invariably assigned to formulations intended for professional use only. The CTB only assigns S35 to preparations with hazard-symbol T+, T, or C with respect to the toxicological aspect of the preparation in question.

S23 is assigned based on R37.

S36/37 is invariably assigned by the CTB to all formulations labelled with Xi, R43.

S46 is invariably assigned to formulations assigned with the mentioned R-phrase(s), intended for professional use only when this does not lead to more than six safety-phrases.

Other:

-

 

 

5.                  Residues

 

Spyrale is an EC formulation and containing 100 g/l difenoconazole and 375 g/l fenpropidin. The application for authorisation in the cultivation of sugar and fodder beets was submitted. The intended use is: a maximum of 2 applications of 100 g difenoconazole /ha and 375 g fenpropidin/ha with an interval of 14-21 days and a pre-harvest interval (PHI) of 28 days.

 

Overview of intended use fenpropidin

 

Use

Application rate

 

Frequency

Interval

[days]

PHI

[days]

Time of application

Kg ai/ha

L water/ha

Kg ai/hL

sugar and fodder beets

375

200-600

0.063-0.188

1-2

14-21

28

August-September

 

Overview of intended use difenoconazole

 

Use

Application rate

 

Frequency

Interval

[days]

PHI

[days]

Time of application

Kg ai/ha

L water/ha

Kg ai/hL

sugar and fodder beets

100

200-600

0.017-0.050

1-2

14-21

28

August-September

 

List of Endpoints

Fenpropidin

Fenpropidin is an existing active substance. The residue profile presented below is based on the Draft assessment report (DAR) prepared by the RMS Sweden. The Dutch comments on the Draft assessment report (DAR), when relevant, are also presented (in italic). Since the active substance is still in the process of evaluation/discussion, the residue profile below should be regarded as provisional. The List of Endpoints below is the most recent available (November 2006).

 

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

Plant groups covered

Cereals (wheat), root vegetables (sugar beet), fruits (grapes, banana). Foliar application.

Rotational crops

Leafy vegetables (lettuce), root vegetables (radish), cereals (spring and winter wheat)

Metabolism in rotational crops similar to metabolism in primary crops

Yes. No new metabolites were observed.

Processed commodities

Fenpropidin is stable under conditions representative of pasteurisation, baking/brewing/boiling and sterilisation. (96.1 to 97.1% of the applied radioactivity consisted of parent fenpropidin).

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

Residue levels were similar to the unprocessed commodities.

Plant residue definition for monitoring

Parent Fenpropidin

Plant residue definition for risk assessment

Parent Fenpropidin

Conversion factor (monitoring to risk assessment)

N/A

 

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

Animals covered

Ruminant (goat), poultry (hen)

Time needed to reach plateau concentration in milk and eggs

48 hours in milk

72 hours in eggs

Animal residue definition for monitoring

Parent Fenpropidin and CGA 289267*

Animal residue definition for risk assessment

Parent Fenpropidin*

Conversion factor (monitoring to risk assessment)

N/A*

Metabolism in rat and ruminant similar (yes/no)

Yes

Fat soluble residue: (yes/no)

No

* Metabolite CGA 289267 was added to the animal residue definition for monitoring after comments on the DAR from EFSA and Member States. The residue definition for monitoring is now different from the residue definition for risk assessment. A conversion factor should therefore be derived.

 

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

 

 

Maximum residues of fenpropidin in human food commodities of succeeding crops (lettuce, radish roots) grown in rotation after cereals are not expected to exceed 0.01 mg/kg.

 

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

 

 

Wheat grain, wheat straw, grapes, banana, sugar beets and wine: stable at ‑18°C for at least 24 months.

Muscle, liver, kidney, fat: stable at 18°C for at least 3 months.*

Milk: stable at 18°C for at least 2 months.*

Blood: stable at 18°C for at least 1 month.*

* stability of metabolites CGA 289267 and CGA 289268 was studies in Muscle, liver, kidney, fat, milk and blood. These metabolites were proven to be stable in these matrices for at least 24 weeks for CGA 289267 en 30 months for CGA 289268.

 

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

Intakes by livestock ł 0.1 mg/kg diet/day:

Ruminant:

 

Poultry:

 

Pig:

          

Metabolism studies indicate potential level of residues ≥ 0.01 mg/kg in edible tissues (yes/no)

yes

no

no

 

Residue levels in feeding studies (dose level: mg/kg)

Mean (max) mg/kg

Muscle

*

N/R

N/R

Liver

*

N/R

N/R

Kidney

*

N/R

N/R

Fat

*

N/R

N/R

Milk

*

N/R

N/R

Eggs

*

N/R

N/R

*Dietary burden based on representative crops not carried out, as this is not representative of the true dietary burden based on all registered crops. Calculation of the actual dietary burden and proposals for MRLs in products of animal origin will be included in the EU MRL submission.

N/R=Not required

 

Processing factors (Annex IIA, point 6.5, Annex IIIA, point 8.4)

Crop/processed crop

Number of studies

Transfer factor

% Transference *

Barley – malt

2

1.1

 

Barley – wort

2

0.7

 

Barley – beer

2

0.4

 

Wheat – bran

4

4.2

 

Wheat – flour (Type 550)

4

0.2

 

Wheat – wholemeal flour

4

1.1

 

Wheat – wholegrain bread

4

1.0

 

* Calculated on the basis of distribution in the different portions, parts or products as determined through balance studies.

 

Difenoconazole

Difenoconazole is an existing active substance. The EU-dossier is complete, however the Draft assessment report (DAR) is not yet available. Sweden is RMS. The residual profile presented below is based on the RIVM reports 08653A00 (September 2002) and 09042A00 (March 2003) and TNO report CTB-2007-003-RES (February 2007) and on the decision of the board of September 3rd 2004 (as discussed in board meeting C-148.3.3, of August 11th 2004). Since the active substance is still in the process of evaluation/discussion, the residue profile below should be regarded as provisional.

 

Comments on/additions to List of Endpoints

Fenpropidin: see List of Endpoints and summary below for additional remarks. Remarks in the List of Endpoints are given in italics.

 

5.1       Summary of residue data

 

5.1.1    Metabolism in plants

Fenpropidin

see List of Endpoints

 

Difenoconazole

In previous assessments it was concluded that the major residue component in plant parts directly treated is parent difenoconazole.

The major residue component in plant parts, which have not been treated directly, is triazolyl-alanine (mH) or triazolyl-acetic acid (mJ).

The metabolites, which are formed in plants, are also present in the rat, except triazolalanine and triazole acetic acid.

Metabolism studies in four different crop groups are available: root and tuber vegetables, fruit, cereals and pulses/oilseeds.

Sugar and fodder beets belong to the category “root and tuber vegetables”.

As metabolism studies showed that the metabolism of difenoconazole is similar in more than three crop groups, it is concluded that the results from the metabolism studies cover all crop groups.

 

5.1.2    Metabolism in livestock

Fenpropidin

See List of Endpoints.

 

Difenoconazole

In previous assessments it was concluded that the same difenoconazole metabolites are formed in hens and goats.

The major residue components were the alcohol derivative (mB) in liver and kidney and free triazole (mC) in milk and eggs.

Furthermore, small amount of parent substance, mA and mD were detected, as well as hydroxy-difenoconazole (mE) en hydroxy-mB (mF), where in both cases the hydrolysis of the phenyl-ring is concerned.

The main metabolic pathway as well as the less important pathway in livestock is similar to the metabolic pathway in plants, with the exception that in animals no triazole bonds with serine or acetic acid could be demonstrated.

The metabolism of difenoconazole in livestock is similar with the metabolism in the rat.

 

5.1.3    Residue definition (plant and animal)

Fenpropidin

No residue definition for fenpropidin is present in the Dutch residue directive “Regeling Residuen”. The residue definition in the List of Endpoints will be adopted.

 

Difenoconazole

 

Plant products

The residue definition in the Dutch residue directive “Regeling Residuen” for products of plant origin is parent difenoconazole, with an LOD of 0.05 mg/kg, for monitoring as well as risk assessment.

 

Animal products

The residue definition for monitoring in the Dutch residue directive “Regeling Residuen” for products for animal products is the sum of difenoconazole and 1-[2-[2-chloro-4-(4-chloro-phenoxy)-phenyl]‑2-hydroxy-1‑ethyl]-1H-1,2,4-triazole, expressed as difenoconazole, with an LOD of 0.1 mg/kg.

The residue definition for risk assessment in the Dutch residue directive “Regeling Residuen” for milk and eggs is 1H-1,2,4-triazole, expressed as difenoconazole.

The residue definition for risk assessment for all other animal products is the same as the residue definition for monitoring in animal products.

 

5.1.4    Stability of residues

Fenpropidin

Fenpropidin was proven to be stable in wheat grain and wheat straw (dry matrix), and in grapes, banana and wine (watery matrix) and in sugar beets (sugar beet specific matrix)..

Fenpropidin was proven to be stable in various matrices (water, dry, and sugar beets), the stability of fenpropidin was demonstrated sufficiently.

 

Difenoconazole

Difenoconazole was proven to be stable in various products of plant products (lettuce, soy beans, wheat grain and straw, cottonseed, cottonseed oil, cotton seed cake, apples and grapes) and metabolite mB was proven to be stable in apples and grapes, both substances for 2-years when stored at –20°C. In animal products (tissues, milk and eggs) difenoconazole is stable for at least 1-year and mB is stable for at least 1-year in tissues and stable for at least 9-months in milk, all when stored at –20°C.

 

Sugar beets are considered to have a separate matrix, storage stability studies for this specific matrix should be submitted. However, since difenoconazole was proven to be stable in various matrices (fat, water, dry), the stability of difenoconazole was demonstrated sufficiently.

 

5.1.5    Residue data

Fenpropidin

Five residue trials performed in Northern Europe with fenpropidin in sugar beets were submitted. Two trials were performed in accordance with the cGAP-NL (2x 0.28-0.47 kg as/ha, interval 16-26 days and PHI 21-35 days), three trials were performed with too long an interval (29-36 days). As the residue levels in these studies are of the same order of magnitude as the results in the correctly performed studies, the results from all five studies are used in this assessment.

 

Residue levels detected in the acceptable trials are:

Roots:             <0.01, <0.05 (4x) mg/kg

Leaves/tops:   0.881, 1.034, 1.3, 1.858, 2.379 mg/kg (not analysed in one study)

 

With the results, the following values can be calculated:

Roots:             STMR: <0.05 mg/kg, HR: <0.05 mg/kg, MRL: <0.05 mg/kg

Leaves/tops:   STMR: 1.3 mg/kg, HR: 2.4 mg/kg, MRL: 5 mg/kg

 

Difenoconazole

Five residue trials performed in Northern Europe with difenoconazole in sugarbeets were submitted. Two trials were performed in accordance with the cGAP-NL (2x 0.75-1.25 kg as/ha, interval 16-26 days and PHI 21-35 days), three trials were performed with too long an interval (29-36 days). As the residue levels in these studies are of the same order of magnitude as the results in the correctly performed studies, the results from all five studies are used in this assessment.

 

Residue levels detected in the acceptable trials are:

Roots:             0.01, <0.02 (3x), 0.033 mg/kg.

Leaves/tops:   0.084, 0.087, 0.09, 0.204, 0.247 mg/kg.

 

Twenty supervised residue trials have been previously evaluated.  In two trials, samples were taken only at PHI = 40 or 47 days; in one trial, only one application of 0.125 kg as/ha was made; in four trials 3 applications of 0.1 kg as/ha or 4x 0.125 kg as/ha were made. Results from these 7 trials will not be used.

Six trials were performed with intervals that were too long (32-36 days) or too short (11-14 days). As the residue levels in these studies are of the same order of magnitude as the results in the correctly performed studies, the results from these six trials are used in this assessment.

Nine trails are therefore performed in accordance with the cGAP. In several trials, higher residue levels were detected at sampling times later than PHI=28 days, in these cases, the residue levels at later time points were used and are marked below with #.

Roots:             <0.02 (4x), 0.02, 0.02#, 0.06 (3x), 0.08 (2x), 0.10 (2x) mg/kg

Leaves/tops:   0.06, 0.25 (2x), 0.26, 0.41, 0.43 (2x), 0.47, 0.49, 0.53, 0.60# (2x), 0.62, 0.74 mg/kg

 

With the results, the following values can be calculated:

Roots:             STMR: <0.02 mg/kg, HR: 0.1 mg/kg, MRL: 0.1 mg/kg

Leaves/tops:   STMR: 0.41 mg/kg, HR: 0.74 mg/kg, MRL: 1 mg/kg

 

5.1.6    Residues in succeeding crops

Fenpropidin

In the DAR, residues in rotational crops have been studied. Maximum residues of fenpropidin in human food commodities of succeeding crops (lettuce, radish roots) grown in rotation after cereals are not expected to exceed 0.01 mg/kg.

The intended use in the DAR for cereals is max. 2 applications of 750 g as/ha, with an interval of 21 days and a PHI = 28 days.

The total applied dose in cereal is therefore double the total dose for sugar and fodder beets. No residues above the limit of detection are expected in rotational crops grown in rotation after sugar and fodder beets.

 

Difenoconazole

In succeeding crops, mainly water soluble metabolites (73-90%) were detected: triazolyl-alanine (mH), triazolyl- acetic acid (mJ), and a newly identified metabolite: OH‑triazolyl-propane acid (mK).

These three metabolites together form 67-82% of the total recovered (TRR) residue in lettuce, winter wheat, maize and sugar beet. For mH as well as for mJ, it was already concluded that they are not of toxicological relevance.

Metabolite mK is very similar in appearance to mH, the location of the nitro-group in the alanine part of mH is an OH-group in the mK metabolite. As mH is at least as polar as mH, it is as rapidly excreted as mH. MK too is considered to be of no toxicological relevance.

MH, mJ and mK residues in succeeding crops are not considered to be any risk for the public health.

 

Small amounts  (0.3-2.3%) of organically soluble residues were detected; these organically soluble residues are of toxicological relevance.

In the study, the correct dose level was applied, but the plant-back date was longer than 30-days (98-369 days). The level of parent substance, metabolites mA, mB and mD in the soil were therefore possibly lower in the study than in the worst-case situation. However, when it is assumed that 30 days after treatment still 100% of the residue in the soil would have been organically soluble and available, theoretically, still no residues of organically soluble residues above the limit of detection of 0.05* mg/kg could be detected in any plant part.

 

It is therefore concluded, that residues in succeeding crops exists mainly of the non-toxicological metabolites mH, mJ and mK.

A small amount exists of organically soluble residues, but even when this would all be parent difenoconazole, the amount would still be below the LOD of 0.05 mg/kg in all plant parts tested. Therefore, no risk for the public health is expected and no difficulties at monitoring (as no residues of difenoconazole are present, which is the residue definition), due to residues in succeeding crops.

Supplemental studies in succeeding crops with difenoconazole are therefore not required.

 

5.1.7    Residues from livestock feeding studies

Fenpropidin

In the DAR on fenpropidin, a feeding study in dairy cows is available; this study was evaluated previously by CTB. See the comment in the List of Endpoints, a calculation of the actual dietary burden and proposals for MRLs in products of animal origin will be included in the EU-MRL submission.

The dietary intake by livestock is calculated for this national authorisation. Fenpropidin is authorised in cereals nationally. As no individual residue levels are available for fenpropidin in cereals, the STMR and HR values from the DAR are used.

The estimated exposure to difenoconazole of livestock is 6.3, 6.3, 0.4, and 1.0 mg/kg dry feed for dairy cow, meat cow, chicken and pig, respectively.

The feeding study with cattle was performed with 3.15, 15.75 and 31.5 mg/kg dry feed. The study therefore covers the estimated intake by ruminants and pigs.

 

A feeding study for chickens is not available. In the metabolism study in hen, performed at 25N, significant residue levels were detected in all tissues, i.e. kidney, liver, eggs, fat and meat (0.62, 0.52, 0.04, 0.03-0.05 and 0.07 mg/kg, respectively). Residues in poultry tissues and eggs after exposure to fenpropidin through feed can therefore not be excluded.

Since the residue levels seen in the overdosed metabolism study do not lead to an exceedance of the ADI or the ARfD, a feeding study in chicken is not deemed necessary (see point 5.3). No residues above the LOD in chicken products are expected.

 

Difenoconazole

Sugar beets, sugar beet leaves and fodder beets are used as livestock feed.

Cabbage and pome fruit, in which difenoconazole is already authorised, are also used as livestock feed.

In a maximum theoretical intake calculation for livestock with the MRLs for these crops, the exposure of livestock to difenoconazole residues in sugar and fodder beets, apples and pears was calculated. The HRs from the supervised residue trials in sugar beet, apple and head cabbage were used in this calculation. The transfer factor for dried sugar beet leaves (see 5.1.8) is not taken into account, as the calculation has default factor for raw agricultural product to dry matter.

The estimated exposure to difenoconazole of livestock is 1.8, 2.0, 0.14, and 1.6 mg/kg dry feed for dairy cow, meat cow, chicken and pig, respectively.

A feeding study with cattle with an intake of 3 mg/kg feed showed plateau values of 0.16, 0.03, 0.04, 0.02 en < 0.005 mg/kg in liver, kidney, fat, meat and milk, respectively.

 

The residue in meat consists mostly of the alcohol derivative. The parent substance is not or hardly present. Both the parent substance as the alcohol derivative are fat-soluble, therefore, the MRL for meat is expressed in mg/kg fat.

 

No triazole residues were detected in milk. When the triazole levels found in the metabolism study in goat, which was performed with an overdose of 3N, are used in the dietary intake calculations, no exceedance of the ADI or the ARfD occurs.

 

A feeding study in chicken is not available. Based on the data from the chicken metabolism study, this is not necessary. When the amounts of radioactively labelled residue found in this study, performed at 30N, are taken into account in a dietary intake calculation, no risk for the public health is calculated. No residues above the LOD of 0.02* mg/kg in chicken products are expected. No residues above the LOD of 0.02* mg/kg in chicken products are expected.

 

5.1.8    Processing factors

Fenpropidin

Two studies were conducted to investigate the impact of processing on the content of the residue in sugar beets, treated with difenoconazole and fenpropidin. Samples were frozen and within 10 months, samples were processed to sliced dry leaves, raw juice, pulp after pressing, water after pressing, lime sludge, thin juice, thick juice, sugar and molasses (syrup).

The residue levels and the respective transfer factors for the sugar beets from two trials in Northern Europe are presented in tables below.

Table R.1 Fenpropidin levels in sugar beet samples collected during the processing and concomitant transfer factors

 

Product

 

Total residue (mg/kg)

 

Transfer factor

Sugar beet leaves (RAC)

Sliced dried leaves

Roots (RAC)

Raw juice

Pulp after pressing

Water after pressing

Lime sludge

Thin juice

Thick juice

Sugar

Molasses (syrup)

0.722

1.091

<0.05

<0.05

<0.05

<0.05

<0.05

<0.05

<0.05

<0.05

<0.05

-

1.5

-

1

1

1

1

1

1

1

1

Sugar beet leaves (RAC)

Sliced dried leaves

Roots (RAC)

Raw juice

Pulp after pressing

Water after pressing

Lime sludge

Thin juice

Thick juice

Sugar

Molasses (syrup)

0.781

2.219

<0.05

<0.05

<0.05

<0.05

<0.05

<0.05

<0.05

<0.05

<0.05

-

2.8

-

1

1

1

1

1

1

1

1

RAC = raw agricultural commodity

 

No concentration of residues occurred during processing of sugar beets into the commodities analysed. Concentration of residues occurred during processing of sugar beet leaves into sliced dried leaves. This can have an influence on the intake assessment for livestock feeding.

 

Difenoconazole

Residues of difenoconazole in processed products were analysed in three studies with apples and in one study with pears. In two of the studies with apples, no detectable residues were present in the samples at the start of the trials. As the method of analysis in the study with pears was considered to be unacceptable, the results from this study were considered unreliable.

The processing factors in the remaining study with apple were based on the amount of parent substance, are 1.0, < 0.33, 6.0, 0.83 and 1.8 for washing, juice, pommace, sauce and dried apple slices, respectively.

 

The intake of difenoconazole through the consumption of sugar takes up 1% en 4% of the ADI for the general population and for children, respectively. Therefore, processing studies with sugar beets are not required, but were submitted.

 

Two studies were conducted to investigate the impact of processing on the content of the residue in sugar beets, treated with difenoconazole and fenpropidin. Samples were frozen and within 10 months, samples were processed to sliced dry leaves, raw juice, pulp after pressing, water after pressing, lime sludge, thin juice, thick juice, sugar and molasses (syrup).

The residue levels and the respective transfer factors for the sugar beets from two trials in Northern Europe are presented in tables below.

Table R.2 Difenoconazole levels in sugar beet samples collected during the processing and concomitant transfer factors

 

Product

 

Total residue (mg/kg)

 

Transfer factor

Sugar beet leaves (RAC)

Sliced dried leaves

Roots (RAC)

Raw juice

Pulp after pressing

Water after pressing

Lime sludge

Thin juice

Thick juice

Sugar

Molasses (syrup)

0.063

0.201

<0.02

<0.02

<0.02

<0.02

<0.02

<0.02

<0.02

<0.02

<0.02

-

3

-

1

1

1

1

1

1

1

1

Sugar beet leaves (RAC)

Sliced dried leaves

Roots (RAC)

Raw juice

Pulp after pressing

Water after pressing

Lime sludge

Thin juice

Thick juice

Sugar

Molasses (syrup)

0.115

0.083

<0.02

<0.02

<0.02

<0.02

<0.02

<0.02

<0.02

<0.02

<0.02

-

1.4

-

1

1

1

1

1

1

1

1

RAC = raw agricultural commodity

 

5.1.9    Calculation of the ADI and the ARfD

Fenpropidin

Calculation of the ADI

The ADI is based on the NOAEL of 2.27 mg/kg bw/day in females in the 2-year oral rat study. Application of a safety factor for inter- and intraspecies differences of 100 results in an ADI of 0.02 mg/kg bw/day (see the List of Endpoints for mammalian toxicology).

 

Calculation of the ARfD

The ARfD is based on the NOAEL of 5 mg/kg bw/d in the 28-day and 26-weeks dog study. Application of a safety factor for inter- and intraspecies differences of 100 results in an ARfD of 0.05 mg/kg bw/day (see the List of Endpoints for mammalian toxicology).

 

Difenoconazole

Calculation of the ADI

The ADI is based on the NOAEL of 1 mg/kg bw/d in the 2-year chronic rat study. Application of a safety factor for inter- and intraspecies differences of 100 results in an ADI of 0.01 mg/kg bw/day (see the List of Endpoints for mammalian toxicology).

 

Calculation of the ARfD

The ARfD is based on the NOAEL of 25 mg/kg bw/d in the rabbit teratogenicity study. Application of a safety factor for inter- and intraspecies differences of 100 results in an ARfD of 0.25 mg/kg bw/day (see the List of Endpoints for mammalian toxicology).

 


5.2       Maximum Residue Levels

Fenpropidin

Only MRLs for products of animal origin and cereals have been established nationally. No harmonised EU-MRLs are available.

 

Commodity

MRLs

(mg/kg)

Milk

0.005*

Liver   

0.02

Kidney, meat, fat       

0.01*

Wheat

0.1

Barley

0.2

           

Currently no MRLs for products solely used as livestock feed or for sugar beets are established. In the future, when the regulation 396/2005 will be in force, MRLs for these commodities will be necessary.

The product complies with the MRL Directives.

Notification of the MRL is not necessary.

 

Difenoconazole

No harmonised EU-MRLs for difenoconazole are available. National MRLs have been established:

Commodity

MRLs

(mg/kg)

Pome fruit

0.5

Banana

0.1

Carrot

1

Celeriac

0.5

Celery Leaves, parsley

3

Head cabbage

0.2

Celery

0.2

Milk, eggs, honey, fat, meat

0.1*

Liver of ruminant/pig  

0.2

Liver of poultry           

0.1*

Kidney ruminant/pig  

0.1*

The LOD is 0.05* mg/kg for products of plant origin.

The product complies with the MRL Directives/Regulation.

Notification of the MRL is not necessary.

 

5.3       Consumer risk assessment

Fenpropidin

Risk assessment for chronic exposure through diet

Based on the proposed residue tolerances, a calculation of the National Theoretical Maximum Daily Intake (NTMDI) was carried out using the National Dutch diet, the national MRLs and the highest residue levels found in the hen metabolism study. Calculation of the NTMDI shows that 2.0 % and 4.0 % of the ADI is used for the general population and for children, respectively.

 

Risk assessment for acute exposure through diet

A calculation of the National Estimated Short Term Intake (NESTI) was carried out using the National Dutch diet (‘large portion sizes’; 97.5 percentile from dietary data), the UK ‘unit weights’ and previously mentioned national MRLs and the highest residue levels found in the hen metabolism study. The NESTI uses 6.4 % and 4.4 % of the ARfD for the general population [wheat] and for children [wheat], respectively.

 

Difenoconazole

Risk assessment for chronic exposure through diet

Based on the proposed residue tolerances, a calculation of the National Theoretical Maximum Daily Intake (NTMDI) was carried out using the National Dutch diet and the national MRLs. Calculation of the NTMDI shows that 19.1 % and 76 % of the ADI is used for the general population and for children, respectively.

 

Risk assessment for acute exposure through diet

A calculation of the National Estimated Short Term Intake (NESTI) was carried out using the National Dutch diet (‘large portion sizes’; 97.5 percentile from dietary data), the UK ‘unit weights’ and previously mentioned national MRLs. The NESTI uses 1.6 % and 5.2 % of the ARfD for the general population and for children, respectively, both by apples.

 

Conclusion

The product complies with the Uniform Principles.

 

5.4       Data requirements

No additional data required.

 

 

6.                  Environmental fate and behaviour

 

The Order Uniform Principles Plant Protection Products came into effect on 23 December 2005 by publication of the implementation decision in the Bulletin of Acts and Decrees (Staatsblad) 663 of 22 December 2005, while repealing the Order Environmental Authorisation Criteria Pesticides (Staatsblad 413).

The Regulation elaborating the uniform principles for plant protection products published in the Government Gazette (Staatscourant) 248 of 21 December 2005 took effect at the same time, while repealing the Regulation implementation environmental authorisation criteria for pesticides 2000. A transitional provision has not been laid down. This means that the regulation takes immediate effect. All applications for authorisation of plant protection products should be evaluated in compliance with the new regulation.

 

List of Endpoints Fate/behaviour 

 

Active substance Difenoconazole

Difenoconazole is an existing substance. The decision to place it on Annex I hasn’t been taken yet. The EU dossier is complete, but the DAR is not yet available. RMS is Sweden. The applicant requested to use the available data for difenoconazole, which was submitted for the formulation Score 250 EC (CSR Adviesrapport 08650a00, 29 maart 2002). This list of data is only available in Dutch.

 

Gedrag in grond

 

Omzettingssnelheid en omzettingsroute in grond

 

Omzettingssnelheid

Difenoconazool is op basis van omzettingsgegevens in vijf grondsoorten slecht afbreekbaar. In alle studies ontbreken gegevens omtrent de historie van de bodem en de recovery van de analysemethode.

Tabel M.2 Overzicht van halfwaardetijden voor omzetting in grond (laboratoriumstudies)

Grondsoort

Conditie

Dosering

 

[mg w.s./kg]

T

 

[°C]

pH

DT50

 

[d]

DT50

(20°C)

[d]

Opmerkingen

 

 

 

 

 

 

 

 

Loamy sand

Aeroob

0,1

20

5

140

140

 

Silty loam

Aeroob

0,1

20

7,2

129

129

 

Loam

Aeroob

0,19

20

7,2

104

104

Triazool label

Loam

Aeroob

0,19

20

7,2

118

118

Chloorfenyl label

Sandy loam

Aeroob

0,257

20

7,4

149

149

Chloorfenyl label

Loamy sand

Aeroob

0,257

20

7,5

186

186

Chloorfenyl label

Silty clay loam

Aeroob

0,257

20

6,7

187

187

Chloorfenyl label

Silty loam

Aeroob

1,0

20

7,2

368

368

gem. van 355 en 381 d.

Silty loam

Aeroob

1,0

10

7,2

654

-

Geen betrouwbare extrapolatie mogelijk

Silty loam

Aeroob

1,0

30

7,2

197

-

Geen betrouwbare extrapolatie mogelijk

Sandy loam

Aeroob

9,68

25

8,5

495

738

gem. van 470 en 520 d (25 şC).

Loam

Aeroob

10

25

6,5

520

775

Dosering te hoog

Loam

Aeroob

10

20

6,8

470

470

Dosering te hoog

Sandy loam

Anaeroob

9,68

25

8,5

805

1200

gem. van 470 en 1140 d (25 şC).

Loam

Anaeroob

10

25

6,5

950

1400

 

Loam

Anaeroob

10

20

6,8

820

820

 

 

De DT50-waarden bij 10 en 30 ˚C worden niet gebruikt voor de beoordeling omdat deze temperaturen buiten de range vallen waarbinnen een betrouwbare omrekening naar 20 ˚C mogelijk is. In de eerdere beoordelingen is verder nog gebruik gemaakt van een DT50 van 630 dagen, bepaald bij 20 ˚C in silty loam. Deze grond was echter te droog geďncubeerd (pF 4). In dezelfde grond werd met dezelfde dosering bij pF 3 en 20 ˚C een DT50 van 368 dagen gevonden (zie Tabel M.2). Het is waarschijnlijk dat de relatief hoge DT50 van 630 dagen is veroorzaakt door het te lage vochtgehalte. Deze waarde wordt dan ook niet betrouwbaar geacht en is in de huidige beoordeling niet opgenomen. Studies met concentraties ≥ 1 mg/kg worden eveneens niet representatief geacht voor de huidige toepassing en de DT50-waarden uit deze studies worden niet meegenomen in het gemiddelde.

De omzetting van difenoconazool in deze studies vond plaats door biodegradatie, er is geen omzetting onder steriele omstandigheden. Er zijn geen aanwijzingen dat de twee isomeren (cis en trans) duidelijk verschillende omzettingssnelheden hebben.

In één laboratoriumstudie werden twee transformatieproducten gevonden in gehalten >10% (11 en 13%), maar deze zijn niet geďdentificeerd. In een andere studie werd 1,2,4-triazool (mB) aangetroffen in een hoeveelheid van 21% na 190 d.

·       difenoconazool: 140, 129, 104, 118, 149, 186 en 187 dagen (gemiddelde:145 dagen, range 104 -187 dagen).

 

Mineralisatie en grondgebonden residuen

In minder betrouwbare laboratoriumomzettingsstudies bij 20-25 °C en pF 3 bereikten de gebonden residuen en CO2 de volgende waarden (Tabel M.3):

Tabel M.3 Overzicht van grondgebonden residu en mineralisatie

Conditie

grondgebonden residu

 

% na 100 dagen

CO2

 

% na 100 dagen

Overschrijding limiet

grondgebonden residu

 >70% en CO2 <5%

Opmerkingen

 

 

 

 

 

Aeroob

35

22

Nee

0,1 mg/kg

Aeroob

14

7

Nee

1,0 mg/kg

Aeroob

15

0,25

Nee

1,0 mg/kg

Aeroob

<20

<1

Nee

10 mg/kg

Aeroob

<25

<2

Nee

10 mg/kg

Aeroob

<17

<2

Nee

10 mg/kg

Aeroob

<9

<1

Nee

9,68 mg/kg

Aeroob

<9

<1

Nee

9,68 mg/kg

 

 

 

 

 

 

Fotochemische omzetting in grond

In een tweetal fotodegradatie experimenten met natuurlijk zonlicht werden DT50-waarden van 17 en 55 dagen gevonden (39° NB). Bij kunstmatig zonlicht werden DT50-waarden van 5 - 13 dagen gevonden. Difenoconazool is gevoelig voor fotodegradatie, met name in vergelijking tot de biotransformatiesnelheid.

Omzetting onder veldomstandigheden

Er zijn diverse veldstudies naar de verdwijning van difenoconazool beschikbaar, zie Tabel M.4.

 

Tabel M.4 Overzicht van halfwaardetijden voor omzetting in grond (veldstudies)

Teststof

Grond-soort

Locatie

Dose-ring

[kg w.s./ha]

Dose-ring

[mg w.s./kg]

o.s.

 

[%]

pH

DT50

veld

[d]

DT90

 

Opmerkingen

 

 

 

 

 

 

 

 

 

 

14C difeno-conazool

Loam

Zwitserland

0,8

1,06

2,6

6,8

 

>1 jaar

SCORE 250 EC

14C difeno-conazool

Sandy loam

Zwitserland

0,125

0,17

3,9

7,3

139

>1 jaar

SCORE 250 EC

14C difeno-conazool

Clay

Engeland

0,375

0,50

3,4

7,6

158

>1 jaar

SCORE 250 EC

14C difeno-conazool

Clay

Engeland

0,125

0,17

3,4

7,6

182

>1 jaar

SCORE 250 EC

14C difeno-conazool

Sandy clay

Engeland

0,375

0,50

3,1

8,2

186

>1 jaar

SCORE 250 EC

14C difeno-conazool

Sandy clay

Engeland

0,125

0,17

3,1

8,2

 

>1 jaar

SCORE 250 EC

14C difeno-conazool

Silty loam

Duitsland

0,5

0,67

2,1

6,6

27

124 d.

*

14C difeno-conazool

Loamy sand

Duitsland

0,5

0,67

1,8

6,2

93

124 d.

*

14C difeno-conazool

Silty loam

Duitsland

0,5

0,67

2,3

6,8

72

>152 d.

*

14C difeno-conazool

Silty loam

Frankrijk

0,15

0,20

 

 

331

>1 jaar

SCORE 250 EC

14C difeno-conazool

Loamy sand

VS

0,13

0,17

 

 

133

 

gemiddelde van 148 en 117 dagen

* Verdwijning snel in eerste maand, daarna langzamer.

 

Metabolieten

De metaboliet mA: 1-{2-[2-chloor-4-(4-chloorfenoxy)fenyl]-2-hydroxy-ethyl}-1H-1,2,4-triazool werd in een veldexperiment aangetroffen na 182 dagen met een maximum van 11% van het aanwezige residu in de 0-10 cm laag, overeenkomend met 8% van de opgebrachte hoeveelheid difenoconazool. Na 369 dagen was het gehalte mA gehalveerd tot 4% van de opgebrachte hoeveelheid difenoconazool. mA is geen belangrijke (major) metaboliet.

In een laboratoriumstudie waarbij de omzettingssnelheid van mA werd bepaald onder aërobe omstandigheden werd in een sandy loam, een loamy sand en een silt loam bij 20 °C een DT50 gevonden van respectievelijk 93 d, 83 d en 151 d.

 

De metaboliet mB (1,2,4-triazool) werd aangetroffen in een veldlysimeterstudie met een maximum van 11% van de opgebrachte hoeveelheid difenoconazool (label in de triazool ring) 182 dagen na toediening. Na 369 dagen was dit gehalte 8%. 1,2,4-Triazool werd ook aangetroffen in  een laboratoriumstudie in een hoeveelheid van 21% na 190 d.

 

In studies naar residuen van difenoconazool na herhaalde toepassing van 0,075 - 0,150 kg/ha op kale grond of op tarwe (Engeland, 1991-1993) waren de gemeten gehalten na de toepassing in het derde jaar niet hoger dan na de toepassing in het eerste jaar.

 

De beschikbare DT50-waarden voor 1,2,4-triazool zijn in Tabel M.5 weergegeven.

Tabel M.5 Overzicht van halfwaardetijden voor omzetting van 1,2,4-triazool in grond (laboratoriumstudies)

Teststof

Grondsoort

Conditie

Dosering

 

[mg w.s./kg]

T

 

[°C]

o.s.

 

[%]

pH

pF

DT50

 

[d]

DT50

(20°C)

[d]

Opmerkingen

1,2,4-triazool

loamy sand

Aeroob

50

22

4,3

6,0

2,5

190

222

 

1,2,4-triazool

sandy loam

Aeroob

50

22

1,2

5,5

2,5

164

192

 

1,2,4-triazool

silty loam

Aeroob

1

25

2,3

7,6

3

155

231

 

1,2,4-triazool

sandy loam

Aeroob

0,06

20

2,4

6,9

2,5-3

60

  60

Door CTB herberekende waarde

1,2,4-triazool

loamy sand

Aeroob

0,06

20

3,4

6,2

2-2,5

244

244

Door CTB herberekende waarde

1,2,4-triazool

silt loam

Aeroob

0,06

20

1,7

7,9

3,5-4

19

  19

Door CTB herberekende waarde

 

Uit deze gegevens ontstaat in eerste instantie geen eenduidig beeld over de afbraaksnelheid van 1,2,4-triazool; het is niet duidelijk waardoor de grote verschillen in afbraaksnelheid worden veroorzaakt. Er lijkt geen sprake te zijn van een concentratie-afhankelijke afbraak: bij 0,06 mg/kg worden zowel hoge als lage waarden gevonden en de DT50 van 244 dagen (een door het RIVM herberekende waarde) is vergelijkbaar met de waarden die bij 1 en 50 mg/kg worden gevonden. Ook de verschillen in extractiemethode kunnen geen verklaring zijn voor de verschillende uitkomsten. Bij de studie met 0,06 mg/kg bestaan wel twijfels over de doelmatigheid van de extractie. De recovery van 1,2,4-triazool is echter 85-94%, hetgeen voldoende kan worden geacht.

De aanvrager heeft beargumenteerd dat de experimenten uitgevoerd met concentraties ≥ 1 mg 1,2,4-triazool/kg niet meegenomen mogen worden in het gemiddelde aangezien de concentraties te sterk afwijken van de werkelijk in de grond te verwachten concentratie (0,004 mg/kg). Mede gelet op het gestelde in de Regeling uitvoering milieutoelatingseisen bestrijdingsmiddelen kan met deze argumentatie akkoord worden gegaan. Overigens werd op 8 september 1999 reeds met Novartis (tegenwoordig Syngenta) overeengekomen dat uitsluitend studies met concentraties < 1 mg/kg relevant worden geacht voor de beoordeling.

De aanvrager heeft tevens bezwaar gemaakt tegen de wijze waarop door het CTB de herberekening van de DT50-waarden van de degradatie studies met de 0,06 mg/kg concentraties zijn uitgevoerd. Het CTB is het echter niet eens met de aanvrager dat de DT50-waarde van 1,2,4-triazool in de orde van 12-15 d ligt. Derhalve is een nadere analyse gemaakt van de gegevens uit de studie met een dosering van 0,06 mg/kg van Slangen (2000).

 

Sandy loam

1,2,4-Triazool wordt in deze grond duidelijk bifasisch afgebroken. Gezien de extreem korte duur van de 1e fase (3 dagen) is het redelijk deze fase niet mee te nemen in de bepaling van de DT50. De DT50-waarde is bepaald met de meetpunten 7-120 dagen d.m.v. een 1e-orde kinetisch model en niet-lineaire regressie. De berekende DT50-waarde is 60 d. Er werd een uitstekende fit gevonden op alle meetpunten indien het FOMC-model werd toegepast (Gustafson & Holden) met een DT50 van 3,5 dagen. DT50-waarden verkregen met dit model zijn echter niet geschikt om als invoer voor PEARL te dienen.

Loamy sand

In deze studie is duidelijk een afname van de biomassa in de loop van het experiment opgetreden. Derhalve zijn de meetpunten > 30 dagen niet meegenomen bij de bepaling van de DT50. Vermoedelijk is ook in dit geval de afbraak bifasisch of multicompartimentaal, maar gezien het geringe aantal meetpunten in de 2e fase is afgezien van een DT50 bepaling in de 2e fase. Derhalve werd de DT50 berekend over alle meetpunten ≤ 30 dagen m.b.v. niet-lineaire regressie en een 1e-orde model: DT50 = 14,4 d (r2 = 0,79).

 

Silt

1,2,4-Triazool wordt in deze grond duidelijk bifasisch afgebroken. Gezien de extreem korte duur van de 1e fase (3 dagen) is het redelijk deze fase niet mee te nemen in de bepaling van de DT50. De DT50 werd bepaald uit de meetpunten 7-120 d en bedraagt 19 d. De DT50 op basis van alle meetpunten, niet-lineaire regressie en een 1e-orde model is bepaald op14 d. Gezien het betrekkelijk geringe verschil tussen deze DT50-waarden wordt de laatste waarde als worst case waarde gebruikt voor de beoordeling.

 

1,2,4-Triazool is ook een bodemmetaboliet van propiconazool. Propiconazool is recent geplaatst op Annex I. Voor 1,2,4-triazool zijn de volgende DT50 -waarden vastgesteld in de eindpuntenlijst van propiconazool: 2-12 d. Deze waarden kunnen echter niet worden gebruikt bij de huidige beoordeling aangezien sprake is van andere toepassingen en andere vormingspercentages van triazool, en derhalve van een ander risico.

 

In veldstudies met 4 gronden werden voor de dissipatie van de triazoolgroep uit de bovenste 5 cm indicatieve DT50-waarden van 2,7-3,2 dagen gevonden.

 

Voor de berekening van uitspoeling en accumulatie is uitgegaan van de volgende DT50-waarden:

·       werkzame stof: 140, 129, 104, 118, 149, 186 en 187 dagen (gemiddelde:145 dagen, range 104 -187 dagen).

·       mB: 60, 14 en 19 dagen (gemiddeld 31 dagen, range 14 – 60 dagen).

 

Mobiliteit

 

Adsorptiestudies

De volgende Kom-waarden zijn beschikbaar voor difenoconazool: 233, 1150, 1830, 1850, 2040, 2060, 3500 en 4070 L/kg.

Voor 1,2,4-triazool (mB) zijn de volgende Kom-waarden beschikbaar uit schudproeven: 14, 20, 22, 25, 52, 60 en 69 L/kg.

De aanvrager heeft een uitvoerige argumentatie gegeven waarom de Kom-waarden van 1,2,4-triazool van 14, 20 en 22 L/kg verkregen uit de studie van Keller (1983) niet gebruikt zouden moeten worden. In essentie is de argumentatie:

·       Er is methanol toegevoegd aan het medium, terwijl dit gezien de oplosbaarheid van 1,2,4-triazool niet nodig was. De methanol zou een competitie kunnen aangaan met 1,2,4-triazool op beschikbare adsorptie sites op het oppervlak van de bodemdeeltjes.

·       Het experiment is uitgevoerd in water i.p.v. in een oplossing van een calciumzout.

Er is echter niet aangetoond of aannemelijk gemaakt door de aanvrager dat de adsorptie sites van methanol en 1,2,4- triazool dezelfde zijn. Het is ook mogelijk dat triazool specifieke adsorptie sites heeft, bijv. ijzerionen  in de organische stof. 1,2,4-Triazool kan waarschijnlijk complexen vormen met overgangsmetalen. De aanvrager dient experimenteel aan te tonen dat bij toenemende concentraties methanol 1,2,4-triazool van de adsorptie sites verdreven wordt.

Vooralsnog worden de waarden 14, 20 en 22 L/kg meegenomen in de beoordeling.

 

Voor mA  zijn de volgende Kom-waarden beschikbaar uit schudproeven: 5437, 3921, 1677, 1929, 1933 en 2979 L/kg, gemiddeld 2979 L/kg (range 1677 – 5437 L/kg).

 

Kolomstudies

In kolomstudies werden Kom waarden van >90 - >3540 L/kg gevonden voor difenoconazool.

In een veldlysimeterstudie werd vanaf 95 dagen na toediening van 0,13 kg w.s./ha maximaal 1,8 μg/L radioactiviteit (r.a.) teruggevonden in het percolaat. De kolom bestond uit een loamy sand met slechts 0,1% o.m. en was 91 cm diep. In totaal spoelde max. 0,5% r.a. uit in 363 dagen, maar de r.a. is niet geďdentificeerd. In dit jaar werd ca. 1000 mm water opgebracht en spoelde ca. 100 mm water uit. Gezien de geringe hoeveelheid eluaat en het feit dat de radioactiviteit niet is geďdentificeerd wordt deze studie niet bruikbaar geacht.

 

In een kolomstudie met een loamy sand was na 353 dagen veroudering (label in de fenylring) slechts 6% aanwezig als extraheerbare (onbekende) metabolieten. Na uitspoeling bevond zich maximaal 1,27% van de opgebrachte hoeveelheid r.a. in het percolaat. Een onbekende metaboliet spoelde uit met een maximum van 0,8%. In een kolom met loam was na uitspoeling slechts 0,83 (triazool-label) en 0,06% (fenyl-label) van de opgebrachte hoeveelheid r.a. aanwezig. Deze residuen werden verder niet onderzocht. Deze studie geeft onvoldoende informatie omtrent de uitspoeling van metabolieten van difenoconazool.

 

Voor de berekening van accumulatie en uitspoeling zijn de volgende Kom-waarden beschikbaar:

·       werkzame stof: 233, 1150, 1830, 1850, 2040, 2060, 3500, en 4070 L/kg (gemiddelde: 2090 L/kg, range 233 – 4070 L/kg).

·       mB: 14, 20, 22, 25, 52, 60 en 69 L/kg (gemiddelde 37 L/kg; range 14 – 69 L/kg).

 

Gedrag in water

 

Omzettingssnelheid en omzettingsroute in water

 

Bioafbreekbaarheid

Difenoconazool is niet “readily biodegradable”.

 

Hydrolyse

Difenoconazool hydrolyseert niet in water.

 

Fotolyse

De DT50 van difenoconazool bedraagt in water onder kunstlicht 6 dagen. Bij belichting met natuurlijk zonlicht werd een DT50 van 145 dagen gevonden.

 

Omzetting in water-sedimentsystemen

De omzetting van difenoconazool in water/sedimentsystemen verloopt langzaam, de systeem- DT50 kan niet worden berekend maar bedraagt >800 dagen. Uit een inverse modellering met TOXSWA blijkt dat de volgende waarden voor TOXSWA bruikbaar zijn: DT50 water 469 d; DT50 sediment 10.000 d. Er zijn geen metabolieten ≥ 10% aangetroffen. Uit een separaat experiment bleek de systeem-DT50 van mA 301 d in een rivier systeem en 630 d in een vijversysteem.

 

Gedrag in lucht

 

Omzettingssnelheid en omzettingsroute in lucht

Difenoconazool is weinig vluchtig. De dampspanning van difenoconazool bedraagt 1,2 x 10-8 Pa bij 20°C. Difenoconazool is weinig vluchtig uit water: de lucht-water verdelingscoëfficiënt bedraagt  6 x 10-10 L/L. Gegevens over vervluchtiging en omzetting van de werkzame stof in de atmosfeer zijn niet beschikbaar.

Metabolite 1,2,4-triazole

For metabolite 1,2,4-triazole a concept List of Endpoints is available. This list has been evaluated in the PRAPeR expertmeeting 12 (January 2007).

 

Agreed end point

1,2,4-triazole

Aerobic conditions

Soil type (USDA)

 

 

pH

(CaCl2)

t. oC / % MWHC

DT50/ DT90
(d)

 f. f.    kdp/kf

DT50 (d)

20°C pF2/10kPa

St.

(r2)

Method of calculation

Sandy loam

 

6.4

20oC / 40 % MWHC

6.32 / 21.0

 

5.0

0.75

SFO

Loamy sand

 

5.8

20oC / 40 % MWHC

9.91 / 33.0

 

9.9

0.81

SFO

Silt loam

 

6.7

20oC / 40 % MWHC

12.27 / 40.8

 

8.2

0.95

SFO

Geometric mean

 

 

 

7.4

 

 

 

 

Agreed End-point for calculating PEC soil for EU assessments 12 days (Not normalised).

Geomean for FOCUS modelling 7.4 days

 

Agreed end point

Metabolite 1,2-4 triazole

Soil Type(USDA)

OC %

Soil pH

(CaCl2)

Kd (mL/g)

Koc

(mL/g)

Kf

(mL/g)

Kfoc

(mL/g)

1/n

Silty clay

0.70

8.8

 

 

0.833

120

0.897

Clay loam

1.74

6.9

 

 

0.748

43

0.827

Sand

0.12

4.8

 

 

0.234

202

0.8851

Silty clay loam

0.70

7.0

 

 

0.722

104

0.922

Sandy loam

0.81

6.9

 

 

0.720

59

1.016

Arithmetic mean (of 4 values excluding the very low OC sand that was considered not representative of agricultural soils)

0.756

89

0.9155

pH dependence (yes or no)

No

 

Agreed End-point for calculating FOCUS modelling arithmetic mean Kfoc of 89 days, 1/1 0.92 excluding results of the sand soil.

 

In NL an additional study is available (Keller 1984). This study has not been available for EU assessment yet, but will be included in the Dutch assessment. Additional data: Kom: 14, 20 en 22 L/kg.

 

This gives a mean Kom of 38.4 L/kg.

 

Active substance fenpropidin

Fenpropidin is an existing substance, not yet placed on Annex I. A DAR is available, RMS is Sweden. For the risk assessment, the most recent List of Endpoints of November 2006 is used. Comments are inserted in italic.

 

Fate and Behaviour in the Environment

 


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

Mineralization after 100 days

16-32 % after 90/92 d, 22°C

(14C-label in benzylic carbon)

Non-extractable residues after 100 days

8.9-19% after 90/92 d, 22°C

(14C-label in benzylic carbon)

Metabolites requiring further consideration-

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

None

(CGA289267[1] max. 4.6% of AR day 62 at 22°C;

max. 10.6% of AR day 184 at 8°C)

 

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

Anaerobic degradation

Mineralization after 100 days

Stable

0.0% of AR after 59/60 days, 22°C

Metabolites requiring further consideration-

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

None

Soil photolysis

 

Insignificant

Metabolites requiring further consideration-

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

None

 

Rate of degradation in soil (Annex IIA, point 7.1.1.2, Annex IIIA, point 9.1.1)

 

Laboratory studies

Parent

Aerobic conditions

Soil type

appl. rate, mg/kg

pH

t. oC / % MWHC

DT50 /DT90 (d)

DT50 (d)

20°C pF2/10kPa

St.

(r2)*

Method of calculation

sandy loam

1.4

6.9

22 / 75% 1/3 bar

84 / 278

68

0.98

SFO

sandy loam

10.0

6.9

22 / 75% 1/3 bar

103 / 342

84

0.99

SFO

loam

1.4

7.5

22 / 75% 1/3 bar

58 / 192

49

0.99

SFO

loam

10.0

7.5

22 / 75% 1/3 bar

82 / 271

69

0.998

SFO

sandy loam

0.9

7.4

22 / 40% MWC

98 / >275

77

0.98

SFO

sandy loam

9.4

7.4

22 / 40% MWC

68 / 226

54

0.99

SFO

sandy loam

9.4

7.4

8 / 40% MWC

217 / >275

-

0.96

SFO

sandy loam

9.4

7.4

22 / 20% MWC

165 / >365

-

0.95

SFO

 

 

 

 

 

 

 

 

Geometric mean

 

85.7 ** / 251 ***

66**