Toelatingsnummer 13185 N

Powertwin

 

13185 N

 

 

 

 

 

 

 

 

HET COLLEGE VOOR DE TOELATING VAN

GEWASBESCHERMINGSMIDDELEN EN BIOCIDEN

 

1 TOELATING

 

Gelet op de aanvraag d.d. 29 juni 2006 (20060440 TG) van

 

MAKHTESHIM-AGAN HOLLAND B.V.

Arnhemseweg 87

3832 GK LEUSDEN

 

 

tot verkrijging van een toelating van het gewasbescehrmingsmiddelop basis van de werkzame stoffenethofumesaat en fenmedifam,

 

Powertwin

 

gelet opartikel 121, eerste lid, jo. artikel 23, eerste lid, Wet gewasbeschermingsmiddelen en biociden,

 

BESLUIT HET COLLEGE als volgt:

 

1.1 Toelating

1.      Het middel Powertwin is toegelaten voor de in bijlage I genoemde toepassingen onder nummer 13185 N met ingang van datum dezes. Voor de gronden van dit besluit wordt verwezen naar bijlage II bij dit besluit.

2.      De toelating geldt tot 1 mei 2019.

 

1.2 Samenstelling, vorm en verpakking

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

 

1.3 Gebruik

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

 

1.4 Classificatie en etikettering

Gelet op artikel 29, eerste lid, sub d, Wet gewasbeschermingsmiddelen en biociden,

 

1.                     De aanduidingen, welke ingevolge artikel 36 van de Wet milieugevaarlijke stoffen en artikelen 14, 15a, 15b, 15c en 15e 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: Suspensie concentraat

 

werkzame stof:

gehalte:

ethofumesaat

200 g/l

fenmedifam

200 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 stof(fen):

-

 

gevaarsymbool:

aanduiding:

Xi

Irriterend

N

Milieugevaarlijk

 

 

Waarschuwingszinnen:

Kan overgevoeligheid veroorzaken bij contact met de huid.

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

 

 

Veiligheidsaanbevelingen:

Was alle beschermende kleding na gebruik.

Draag geschikte handschoenen en beschermende kleding.

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.

Middel niet onverdund met metaal in aanraking brengen.

 

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

 

Het betreft een aanvraag tot verkrijging van een toelating van het middel Powertwin (13185 N), een middel op basis van de werkzame stofethofumesaat en fenmedifam. Het middel wordt aangevraagd als onkruidbestrijdingsmiddel in de teelt van suiker- en voederbieten voor de toepassing na opkomst van de bieten.

 

2.2 Informatie met betrekking tot de stof

Er zijn in Nederland reeds andere middelen op basis van de werkzame stoffenethofumesaat en fenmedifam toegelaten.

Beide werkzame stoffen zijn opgenomen in Annex I van de gewasbeschermingsrichtlijn 91/414/EEG, ethofumesaat per 1 maart 2003 en fenmedifam per 1 maart 2005.

 

2.3 Karakterisering van het middel

Powertwin is een als Suspensie Concentraat geformuleerd herbicide op basis van de werkzame stoffen ethofumesaat (200 g/l) en fenmedifam (200 g/l).

Ethofumesaat behoort tot de groep der benzofuranen. Het is een selectief herbicide, dat zowel door de spruiten (grasachtigen) als door het blad (breedbladigen) opgenomen wordt, waarna het door het blad getransporteerd wordt. Ethofumesaat remt de meristematische groei door in te grijpen op de celdeling en vorming van de waslaag op de bladeren.

Fenmediam behoort tot de groep der fenyl-carbamaten. Het is een selectief systemisch herbicide, dat opgenomen wordt door het blad, waarna het apoplastisch getransporteerd wordt (naar de groeipunten toe). Fenmedifam blokkeert het electronentransport in de fotosynthese. Het heeft geen bodemwerking en voornamelijk breedbladige onkruiden worden bestreden.

 

2.4 Voorgeschiedenis

De aanvraag is op 4 juli 2006 ontvangen; op 5 juli 2006 zijn de verschuldigde aanvraagkosten ontvangen. Bij brief d.d. 27 februari 2007 is de aanvraag in behandeling genomen.

 

3 RISICOBEOORDELINGEN

Het gebruikte toetsingskader voor de beoordeling van deze aanvraag is weergegeven in de RGB (Hoofdstuk 2); te weten de werkinstructies RGB (voor toxicologie en milieu) en de in de RGB aangeduide (delen van de) toepasselijke versie van de HTB (in dit geval versie 1.0).

 

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 fysische 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 voor de mens

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 4 en 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.

 

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 Powertwin op basis van de werkzame stoffenethofumesaat en fenmedifam 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, 29 april 2009

 

 

HET COLLEGE VOOR DE TOELATING VAN GEWASBESCHERMINGSMIDDELEN EN BIOCIDEN,





dr. D. K. J. Tommel

voorzitter

 

 



HET COLLEGE VOOR DE TOELATING VAN GEWASBESCHERMINGSMIDDELEN EN BIOCIDEN

 

BIJLAGE I bij het besluit d.d. 29 april 2009 tot toelating van het middel Powertwin, toelatingnummer 13185 N

 

 

A.

WETTELIJK GEBRUIKSVOORSCHRIFT

 

Toegestaan is uitsluitend het gebruik als onkruidbestrijdingsmiddel in de teelt van suiker- en voederbieten.

 

Ethofumesaat mag slechts om de 3 jaar worden toegepast.

De totale dosering in n seizoen mag niet hoger zijn dan 1,0 kg ethofumesaat per hectare.

 

Het is verboden dit middel met een luchtvaartuig toe te passen.

 

Het middel is uitsluitend bestemd voor professioneel gebruik.

 

B.

GEBRUIKSAANWIJZING

 

Algemeen

Powertwin is een herbicide voor toepassing na opkomst van de bieten. Het middel heeft een systemische werking via ondergrondse delen en contactwerking op bovengrondse delen. Het geeft een goede bestrijding van de meeste njarige onkruiden, waaronder veelknopigen en kleefkruid. Powertwin dient verspoten te worden in 250 liter water per hectare bij een druk van minimaal 3 bar.

 

Toepassingen

Daar onkruiden nooit gelijktijdig kiemen, verdient een gesplitste toepassing de voorkeur. De behandelingen dienen op jonge onkruiden te worden uitgevoerd. Naarmate de onkruiden kleiner zijn kan lager gedoseerd worden.

 

Toepassing in het Lage Dosering Systeem

Eerste toepassing

Na-opkomst in het kiembladstadium van de bieten

Vervolg toepassing(en)

Uitvoeren afhankelijk van de onkruiddruk in het kiembladstadium van het onkruid

 

Dosering: 0,5 l/ha Powertwin + 0,5 l/ha Goltix SC + 0,5 l/ha minerale of plantaardige olie. Zonodig wekelijks herhalen en eventueel de doseringen opvoeren naar 0,75 of 1 l/ha van alle genoemde middelen afhankelijk van de grootte van de onkruiden en het gewas.

Per teeltseizoen mag niet meer dan 5 liter Powertwin (= 1,0 kg ethofumesaat) per hectare worden toegepast.

 

Restricties

Spuit op een gezond en droog bietengewas, dat niet is verzwakt door insecten, nachtvorst of voorafgaande bespuitingen met herbiciden of insecticiden. Spuit bij voorkeur niet bij scherp zonnig weer en niet bij een dagtemperatuur hoger dan 18 C.

 

Indien na bieten wintergranen worden geteeld, dient voor het zaaien eerst geploegd te worden om schade als gevolg van eventuele residuen in de grond te voorkomen.



HET COLLEGE VOOR DE TOELATING VAN GEWASBESCHERMINGSMIDDELEN EN BIOCIDEN

 

BIJLAGE II bij het besluit d.d. 29 april 2009 tot toelating van het middel Powertwin, toelatingnummer 13185 N

 

RISKMANAGEMENT

 

 

 

Contents Page

 

 

1. Identity of the plant protection product 2

 

2. Physical and chemical properties 3

 

3. Methods of analysis 11

 

4. Mammalian toxicology 15

 

5. Residues 23

 

6. Environmental fate and behaviour 29

 

7. Ecotoxicology 49

 

8. Efficacy 86

 

9. Conclusion 89

 

10. Classification and labelling 89

 


1. Identity of the plant protection product

 

1.1 Applicant

Makhteshim Agan Holland B.V.

Arnhemseweg 87

3832 GK Leusden

 

1.2 Identity of the active substance

Common name

ethofumesate

Name in Dutch

ethofumesaat

Chemical name

()-2-ethoxy-2,3-dihydro-3,3-dimethylbenzofuran-5-ylmethanesulfonate

CAS nr

26225-79-6

EEG nr

247-525-3

 

The active substance ethofumesate is considered to be equivalent to the active substance as included on March 1st 2003 in Annex I of directive 91/414/EEC.

 

Common name

phenmedipham

Name in Dutch

fenmedifam

Chemical name

methyl 3-(3-methylcarbaniloyloxy)carbanilate;
3-methoxycarbonylaminophenyl 3-methylcarbanilate [IUPAC]

CAS nr

13684-63-4

EEG nr

237-199-0

 

The active substance phenmedipham was included on March 1st 2005 in Annex I of directive 91/414/EEC.

 

1.3 Identity of the plant protection product

Name

Powertwin

Formulation type

SC

Content active substance

200 g/L ethofumesate and 200 g/L phenmedipham

 

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

 

1.4 Function

Herbicide.

 

1.5 Uses applied for

Uses

F= Field

G= Greenhouse

Dose (g a.s./ha)

phenmedipham

 

ethofumesate

Number of applications

Interval between applications

Application time (growth stage and season)

Sugar beet and fodder beet*)

100-200

100-200

6

7-14

post-emergence up to BBCH 38-39 in combination with other herbicides in a low dose system (March-June)

 

 

 

 

 

 

*) Use restricted to 1 kg in one season per ha per 3 years.

 

 

 

1.6 Background to the application

The product Powertwin is a new product. The active ingredients are well-known and authorized in several herbicides in the Netherlands.

 

1.7 Packaging details

1.7.1 Packaging description

Material:

HDPE

Capacity:

5 L

Type of closure and size of opening:

Screw cap, 62.7 mm opening

Other information

ADR compliant

 

1.7.2 Detailed instructions for safe disposal

See MSDS.

 

 

2.            Physical and chemical properties

 

Active substance: Ethofumesate

Data about the identity and the physical and chemical properties are taken from the List of Endpoints (25 January 2002). Changes and/or additions are taken up in italics.

 

Identity

Active substance (ISO Common Name)

Ethofumesate

Chemical name (IUPAC)

()-2-ethoxy-2,3-dihydro-3,3-dimethylbenzofuran-5-ylmethanesulfonate

Chemical name (CA)

5-Benzofuranol, 2-ethoxy-2,3-dihydro-3,3-dimethyl-, methanesulfonate, (.+-.)-

CIPAC No

233

CAS No

26225-79-6

EEC No (EINECS or ELINCS)

247 525-3

FAO Specification (including year of publication)

not available

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

960

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

none

Molecular formula

C13H18O5S

Molecular mass

286.3

Structural formula

 

 

 

 

Physical-chemical properties

Melting point (state purity)

69.6-70.7 C (99.9 %)

Boiling point (state purity)

ethofumesate decomposes before reaching the boiling point

Temperature of decomposition

(DSC), 285 C

(TGA), 224C

Appearance (state purity)

white crystalline solid

Relative density (state purity)

1.3 (20 C/96.9 %)

Surface tension

not applicable

Vapour pressure (in Pa, state temperature)

6.5 x 10-4 at 25 C

 

Henrys law constant (in Pam3mol-1)

3.72 x 10-3 at 25 C

6.8 x 10-4 at 25 C (technical grade)

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

pH 3 -11: 39 - 44 mg/l (tech. material) at 20.00.5C

pH 7.7: 50 mg/l at 25.00.5C

pH 7.7: 57 mg/l at 30.00.5C

Solubility in organic solvents (in g/l or

mg/l, state temperature)

acetone, dichloromethane, dimethylsulphoxide,

ethyl acetate > 600 g/l at 25C

toluene and p-xylene 300-600 g/l at 25C

methanol 120-150 g/l at 25C

ethanol 60-75 g/l at 25C

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

2.7 (pH 6.4 at 25 C)

2.7 (pH 6.4 at 20 C)

Hydrolytic stability (DT50) (state pH and temperature)

-pH 5 (35C): 2.68% of NC 8493 were detected after 36 days. Half-life is 940 days. Ethofumesate is stable to hydrolysis.

-pH 5 (25 C): 1.57% of NC 8493 were detected after 36 days. Half-life is 2050 days. Ethofumesate is stable to hydrolysis.

-pH 7 (35C and 36 days): stable to hydrolysis

-pH 9 (25C and 36 days): stable to hydrolysis

Dissociation constant

according to the chemical structure ethofumesate is not expected to dissociate in water

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

e at 230 nm: 6650

e at 282 nm: 2520

e at 228 nm: 7090

e at 282 nm: 2790

Abs. max at 230 nm and 282 nm, with a tailing

of low absorbance between 290 and 300 nm.

Absorption of sunlight is only expected at a narrow range between 290 and 300 nm. No absorption > 300 nm.

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

8 - 13 d: 12 h of sunlight exposure per day

37 - 62 d: during summer at 40N to 60N in Europe

 

4.6 d: whole year - central Europe

2.6 d: for month May

 

DT50 was calculated as 7 days and DT90 as 23 days assuming first order kinetics. (new study 2000)

Quantum yield of direct photo-

transformation in water at λ > 290 nm

9.5 11 x 10-5

Photochemical oxidative degradation in air

2.1 h Atkinson

4.1 h Atkinson

Flammability

Not flammable (method A10 and A12)

Auto-flammability

Not auto-flammable (method A16)

Does not self-ignite at RT (method A13)

Oxidatising properties

Not oxidising (statement based on chemical structure)

Explosive properties

Not explosive (method A14)

 

Active substance: Phenmedipham

Data about the identity and the physical and chemical properties are taken from the List of Endpoints (DAR, October 2003). Changes and/or additions are taken up in italics.

 

Identity

Active substance (ISO Common Name)

Phenmedipham

Chemical name (IUPAC)

methyl 3-(3-methylcarbaniloyloxy)carbanilate;
3-methoxycarbonylaminophenyl 3-methylcarbanilate

Chemical name (CA)

3-[(methoxycarbonyl)amino]phenyl (3-methylphenyl) carbamate

CIPAC No

77

CAS No

13684-63-4

EEC No (EINECS or ELINCS)

EINECS: 237-199-0

FAO Specification (including year of publication)

AGP: CP/90, (1980); min. 97.0 1 %

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

min. 970 g/kg

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

None

Molecular formula

C16H16N2O4

Molecular mass

300.3

Structural formula

 

 

 

Physical-chemical properties

Melting point (state purity)

142.7 C (99.2 % pure)

Boiling point (state purity)

No boiling point, decomposition begins at 147 C.

Temperature of decomposition

147 C (97 % tech.)

Appearance (state purity)

Colourless, crystalline powder, odourless. (99.6% pure)

Relative density (state purity)

1.359 g/cm3 at 20 C (99.3 % pure)

Surface tension

71.2 mN/m at 20 C (98.5 % tech.)

Vapour pressure (in Pa, state temperature)

7 10 -10 Pa at 25 C (99.3 % pure)

Henrys law constant (in Pam3mol-1)

5 10 -8 Pa m3 mol 1 at 20C

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

pH 3,4: 1,8 mg/l at 20 C (99.0 % pure)

Phenmedipham decomposes at neutral or basic pH.

Solubility in organic solvents (in g/l or

mg/l, state temperature)

All in g/l at 20 C: toluene: 0.97; dichloromethane: 16.7; methanol: 36.2; acetone: 165; ethyl acetate: 56.3: isooctane 0.16

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

3.59 at 22 C and pH 4

No pH dependence

Hydrolytic stability (DT50) (state pH and temperature)

pH 5: DT50 = 119.5 h at 25 C;
pH 7: DT50 = 14.5 h at 25 C;
pH 9: DT50 = 0.16 h at 25 C;

Dissociation constant

Phenmedipham does not dissociate.

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

lmax: 205 nm, emax: 59646 l mol-1 cm-1
lmax: 237 nm, emax: 37848 l mol-1 cm-1
lmax: 274 nm, emax: 2761 l mol-1 cm-1 at pH 6.2

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

Photochemically stable.

Quantum yield of direct photo-

transformation in water at λ > 290 nm

Photochemically stable.

Photochemical oxidative degradation in air

DT50 = 6.7h

Flammability

Not to be considered as highly flammable.

Auto-flammability

148 oC

Oxidising properties

Not oxidising

Explosive properties

Not to be considered as explosive.

 

2.1              Plant protection product: Powertwin

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

 

The range of application concentrations of the plant protection product is 0.2-1.0%.

 

Section

(Annex point)

Study

Guidelines and GLP

Findings

Evaluation and conclusion

B.2.2.1 (IIIA 2.1)

Appearance: physical state

Visual

GLP: Y

Suspension

Acceptable

B.2.2.2 (IIIA 2.1)

Appearance: colour

Visual

GLP: Y

White

Acceptable

B.2.2.3 (IIIA 2.1)

Appearance: odour

Organoleptic

GLP: Y

Weak characteristic odour

Acceptable

B.2.2.4 (IIIA 2.2)

Explosive properties

EEC A14

Statement

Not explosive based on the individual properties of the products components.

Acceptable

B.2.2.5 (IIIA 2.2)

Oxidising properties

EEC A17

Statement

Not oxidising based on individual properties of the products components.

Acceptable

B.2.2.6 (IIIA 2.3)

Flammability

 

Not applicable

 

B.2.2.7 (IIIA 2.3)

Auto-flammability

EEC A15

GLP: Y

495 oC

Acceptable

B.2.2.8 (IIIA 2.3)

Flash point

EEC A9

GLP: Y

>102oC

Acceptable

B.2.2.9 (IIIA 2.4)

Acidity / alkalinity

CIPAC MT31.2

GLP: Y

Acidity 0.04% H2SO4

 

Acceptable

B.2.2.10 (IIIA 2.4)

pH

CIPAC MT75.3

GLP : Y

pH of the undiluted product: 2.9

Acceptable

B.2.2.10 (IIIA 2.4)

pH

CIPAC MT75.3

GLP : Y

pH of 1% dilution: 4.3

Acceptable

B.2.2.11 (IIIA 2.5)

Surface tension

EEC A5
GLP

Undiluted, 20C:

37.0 mN/m

Acceptable

B.2.2.12 (IIIA 2.5)

Viscosity

OECD 114 equivalent

GLP: Y

20 oC, shear stress 50 s-1:

Dynamic viscosity 114 mPa.s, kinematic viscosity

1.0E-04 m2/s

Acceptable

B.2.2.13 (IIIA 2.6)

Relative density

A3 equivalent

GLP: Y

Density : 1.1124 g/mL

D204 = 1.112

Acceptable

B.2.2.14

(IIIA 2.6)

Bulk (tap) density

 

Not applicable

 

B.2.2.15 (IIIA 2.7)

Storage stability

GLP: Y

CIPAC MT 46, GIFAP 17, 75.3, 31.2, 184, 160, 47.2 & 148

Analytical method was that included in List of Endpoints.

 

 

 

CIPAC MT39.3

GLP: Y

The product was found to be physically and chemically stable in HDPE for 14 days at 54oC.

 

All relevant physical properties were determined. The suspensibility and foam stability were determined at 0.67% and 1% concentrations, whereas the in-use concentration is 0.2-1.0%. This is accepted (see B.2.2.17 and B.2.2.18, test results represent day 0 value of stability tests).

 

 

Stable for 7 days at 0 oC. After storage appearance, pH, acidity, suspensibility and wet sieve residue were determined.

Acceptable

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Acceptable

B.2.2.16 (IIIA 2.7)

Shelf life

GLP: Y

CIPAC MT 46, GIFAP 17, 75.3, 31.2, 184, 160, 47.2 & 148

Analytical method was that included in List of Endpoints.

 

The product was found to be physically and chemically stable in HDPE after storage for 2 years at ambient temperature.

 

All relevant physical properties were determined. The suspensibility and foam stability were determined at 0.67% and 1% concentrations, whereas the in-use concentration is 0.2-1.0%. This is accepted (see B.2.2.17 and B.2.2.18, test results represent day 0 value of stability tests).

 

Packaging

The packaging proved suitable to its contents. The original containers as described in the test report were made of HDPE, which gives sufficient reason to believe the proposed packaging for the Dutch market is suitable for storage of the product.

Acceptable

B.2.2.17

(IIIA 2.8)

Wettability

 

Not applicable

 

B.2.2.18 (IIIA 2.8)

Persistent foaming

CIPAC MT47.2

GLP: Y

 

 

 

 

 

 

 

0.67% v/v dilution in CIPAC C water :

10 s 20 mL foam

1 min 18 mL foam

3 min 16 mL foam

12 min 14 mL foam

 

1.0% v/v dilution in CIPAC C water :

10 s 20 mL foam

1 min 16 mL foam

3 min 16 mL foam

12 min 14 mL foam

Acceptable

B.2.2.19

(IIIA 2.8)

Suspensibility

CIPAC MT184

GLP: Y

In CIPAC D water for phenmedipham/ethofumesate at product concentrations:

0.67% v/v: 99.5/98.9%

1.0% v/v: 99.6/99.0%.

 

The suspension stability was not determined at the lowest in-use concentration of 0.2%. This is accepted since the results at 0.67-1.0% were very comparable (hence no concentration dependence in this range) and excellent.

Acceptable

B.2.2.20

(IIIA 2.8)

Spontaneity of dispersion

CIPAC MT160

GLP: Y

In CIPAC C water after 5 minutes

at product concentration 5% v/v: 94.4% (phenmedipham)

93.8% (ethofumesate)

Acceptable

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

CIPAC MT185

GLP: Y

0.01% w/w residue on a 75 micron sieve.

Acceptable

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

 

Not applicable

 

B.2.2.28

(IIIA 2.8)

Stability of dilute emulsion

 

Not applicable

 

B.2.2.29

(IIIA 2.8)

Flowability

 

Not applicable

 

B.2.2.30

(IIIA 2.8)

Pourability (rinsibility)

CIPAC MT148

GLP: Y

Residue: 2.9%

Rinsed residue: 0.27%

Acceptable

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

Testing method of product physical compatibility (ASTM E 1518-99)

Mixing with the product Goltix and mineral oil is proposed for the LDS(A) in order to increase efficacy.

 

In order to prove that these mixes do not give any stability problems during application, laboratory tests were performed with mixes of Powertwin, Goltix 700 SC and mineral oil (determination of dispersion stability (visual) and screen residue (160 m)).

 

Mixes of Powertwin and Goltix (0.5% v/v each) and of Powertwin (0.5% v/v), Goltix (0.5% v/v) and oil (0.2% v/v) formed stable mixtures.

 

The tested concentration of Powertwin (0.5%) is considered to be worst-case (in-use concentrations are lower, 0.2-0.4%). The proportion of oil in the tested mix was lower than recommended. Problems with compatibility are however not anticipated, since also 6 other mixes containing Powertwin, Goltix and one or two other products, 4 other mixes containing Powertwin, oil and one or two other products, and 4 mixes containing Powertwin and two products other than Goltix or oil were tested, and all found to be compatible.

Acceptable

2.9.2

Chemical compatibility with other products

 

See 2.9.1

 

(A) LDS = Low Dosage System, a tankmix of Powertwin with Goltix SC and mineral oil in a volume ratio of 1:1:1.

 

Conclusion

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

 

2.2              Data requirements

None.

 

 

3.            Methods of analysis

 

3.1.            Analytical methods in technical material and plant protection product

 

Active substance: Ethofumesate

Data on analytical methods were submitted by the applicant.

 

Technical as (principle of method)

GC/FID

Impurities in technical as (principle of method)

GC/FID / GCMS

Preparation (principle of method)

HPLC/DAD

 

Conclusion

These analytical methods are considered to be acceptable.

 

Active substance: Phenmedipham

Data on analytical methods are taken from the List of Endpoints (DAR, October 2003). Changes and/or additions are taken up in italics.

 

Technical as (principle of method)

HPLC, reversed phase (RP-18 ) column, UV detection at 238 nm, mobile phase: acetonitrile/water/dioxane.
(Corresponds CIPAC method 77/TC/M/3.2 (revised))

Impurities in technical as (principle of method)

HPLC, reversed phase (RP-18 ) column, UV detection at 238 nm, mobile phase: acetonitrile/0.005 M pentanesulfonic acid Na-salt/dioxane.
Residual toluene by capillary GC-FID.
Residual water by Karl Fischer titration.

Preparation (principle of method)

HPLC/DAD

 

Conclusion

The analytical methods for the technical active substance and impurities have been assessed in the DAR and are considered to be acceptable. The method submitted by the applicant for determination of the active ingredient in the preparation was considered to be acceptable.

 

3.2              Residue analytical methods

 

Active substance: Ethofumesate

Data on analytical methods are taken from the last available List of Endpoints with analytical methods (1999). Changes and/or additions are taken up in italics.

 

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

Samples were extracted with acetone/water, filtered and re-extracted with dichloromethane. After clean-up on Florisil, ethofumesate was determined by GC-FPD/NPD. LoQ = 0.01-0.05 mg/kg.

Samples were extracted with ethylacetate/hexane. A silica gel cartridge and a C18 cartridge were used to clean up the combined extracts. Residues of ethofumesate and NC 9607 were determined by GC-MSD Multi-residue analysis. LoQ = 0.05 mg/kg.

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

Samples were extracted with acetonitrile, concentrated to dryness, re-dissolved, followed by clean-up on HPLC and solid phase, concentrated to dryness, re-dissolved, and analysed by GC-MS. LoQ = 0.1 mg/kg.

Soil (principle of method and LOQ)

Residues of ethofumesate in soil samples were extracted with acetone, concentrated, extracted with dichloromethane, concentrated to dryness, re-dissolved, cleaned-up on silica or Florisil, and analysed by HPLC-UV or GC-MS. LoQ = 0.01-0.05 mg/kg.

Water (principle of method and LOQ)

Samples were extracted with dichloromethane, concentrated to dryness, re-dissolved in cyclohexane and analysed by GC-FPD. LoQ = 0.05-0.1 mg/l.

Air (principle of method and LOQ)

A volume of air was drawn through a RP-18 cartridge. Ethofumesate was eluted with isopropanol, concentrated to dryness, re-dissolved, and analysed by GC-MS. LoQ = 0.02-0.1 mg/m3.

Body fluids and tissues (principle of method and LOQ)

Not required, non toxic compound, however the following method was submitted:

Samples of dog plasma were extracted with ethyl acetate, concentrated to dryness, re-dissolved, and analysed by HPLC-UV. LoQ = 0.1 mg/ml.

 

The proposed use of the plant protection product involves treatment of sugar and fodder beet. No residues of ethofumesate above the LOQ are anticipated in food of plant and animal origin.

 

Definition of the residue and proposed MRLs for ethofumesate

Matrix

definition of the residue for monitoring

EU MRL

Food/feed of plant origin

ethofumesate (sum of ethofumesate and the metabolite 2,3-dihydro-3,3-dimethyl-2-oxobenzofuran-5-yl methane sulphonate expressed as ethofumesate)

not applicable

Food/feed of animal origin

ethofumesate (sum of ethofumesate and the metabolite 2,3-dihydro-3,3-dimethyl-2-oxobenzofuran-5-yl methane sulphonate expressed as ethofumesate)

0.1* mg/kg (provisional)

 

Required LOQ

Soil

Ethofumesate

0.05 mg/kg (default)

Drinking water

Ethofumesate

0.1 g/L (Dutch drinking water guideline)

Surface water

Ethofumesate

0.3 mg/L (NOEC for Daphnia magna)

Air

Ethofumesate

0.75 mg/m3 (derived from the AOELsys of 2.5 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 residue analytical methods, included in the above List of Endpoints, are suitable for monitoring of the MRLs.

 

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

 

Active substance: Phenmedipham

Data on analytical methods are taken from the List of Endpoints (DAR, October 2003). Changes and/or additions are taken up in italics.

 

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

HPLC-MS/MS; LOQ: 0.05 mg/kg (phenmedipham) in sugar beets

Confirmatory method: not required for LC-MS/MS

ILV: no; DFG S19 method is fully validated

 

DFG S19 multi residue method GLC/MSD; LOQ: 0.02 mg/kg (phenmedipham) in sugar beets

Confirmatory method: DFG multi method S 6-A

ILV: yes

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

HPLC-MS/MS; LOQ: PMP 0.05 mg/kg (all products)
(and MHPC metabolite LOQ: 0.05 mg/kg (all products))
Confirmatory method: not required for LC-MS/MS

ILV: yes

Soil (principle of method and LOQ)

HPLC-MS/MS; LOQ: PMP 0.01 mg/kg, MHPC metabolite LOQ: 0.01 mg/kg)

Confirmatory method: not required for LC-MS/MS

Water (principle of method and LOQ)

HPLC- MS/MS; LOQ: PMP 0.01 mg/l, MHPC metabolite LOQ: 0.01 mg/l in both surface and drinking water

Confirmatory method: not required for LC-MS/MS

Air (principle of method and LOQ)

HPLC-UV; LOQ: 10 g/m (phenmedipham)

Confirmatory method: HPLC-MS/MS method for water

Body fluids and tissues (principle of method and LOQ)

not required not toxic or very toxic

 

The proposed use of the plant protection product involves treatment of sugar and fodder beet. No residues of ethofumesate above the LOQ are anticipated in food of plant and animal origin.

 

Definition of the residue and proposed MRLs for phenmedipham

Matrix

Definition of the residue for monitoring

EU MRL

Food/feed of plant origin

phenmedipham

not applicable

Food/feed of animal origin

phenmedipham

0.05* mg/kg

 

Required LOQ

Soil

phenmedipham and MHPC

0.05 mg/kg (default)

Drinking water

phenmedipham and MHPC

0.1 g/L (Dutch drinking water guideline)

Surface water

phenmedipham and MHPC

25 g/L (NOEC for Daphnia Magna)

Air

phenmedipham

0.039 mg/m3 (derived from the AOEL (0.13 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.

Not applicable

 

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

 

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

 

Conclusion

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

 

3.3 Data requirements

None.

 

3.4 Physical-chemical classification and labelling

 

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

 

Active substance: Ethofumesate

 

Symbol(s):

-

Indication(s) of danger: -

Risk phrase(s)

-

-

 

Active substance: Phenmedipham

 

Symbol(s):

-

Indication(s) of danger: -

 

Risk phrase(s)

-

-

 

Proposal for the classification and labelling of the formulation 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):

none

Symbol:

none

Indication of danger:

none

R phrases

none

none

 

 

 

S phrases

none

none

 

 

 

Special provisions:
DPD-phrases

V33-NL

Do not bring undiluted product into contact with metal

 

 

 

Child-resistant fastening obligatory

no

Tactile warning of danger obligatory

no

 

 

Explanation:

Hazard symbol:

none

Risk phrases:

none

Safety phrases:

none

Other:

pH is low. As a consequence the product may be corrosive to metal.

 

 

4.            Mammalian toxicology

 

List of Endpoints

 

Ethofumesate

Ethofumesate is an existing active substance, included in Annex I of 91/414/EEC. The final List of Endpoints presented below is taken from the final review report on ethofumesate (SANCO/6503/VI/99-final, 15 May 2002). Where relevant, some additional remarks/information are given in italics.

 

Absorption, distribution, excretion and metabolism in mammals

Rate and extent of absorption:

Up to 100 % absorbed. Value based on oral and iv. dosing.

Distribution:

Widely distributed.

Potential for accumulation:

No evidence of accumulation

Rate and extent of excretion:

Rapid and almost complete within 24 h. Mainly via urine (approximately 90 %)

Toxicologically significant compounds:

Parent compound and metabolites

Metabolism in animals:

Extensively metabolised. Hydrolysis, oxidation and ring opening.

 

 

Acute toxicity

Rat LD50 oral:

> 5 000 mg/kg bw

Rat LD50 dermal:

> 2 000 mg/kg bw

Rat LC50 inhalation:

> 0.3 mg/l (whole-body exposure, dust aerosol) 1

Skin irritation:

Non-irritant.

Eye irritation:

Non-irritant.

Skin sensitization (test method used and result):

Non-sensitising (M&K, Buehler).

1 In the DAR for ethofumesate another acute inhalation study is summarized with an LC50 of > 3.97 mg/L (4 h nose only, highest attainable concentration). Based on this study ethofumesate does not classify for acute inhalation toxicity.

 

Short term toxicity

Target / critical effect:

Increased liver and kidney weights

Lowest relevant oral NOAEL / NOEL:

250 mg/kg bw/d (90-day oral study in dog)

Lowest relevant dermal NOAEL / NOEL:

1000 mg/kg bw/d (21-day dermal study in rabbit)

Lowest relevant inhalation NOAEL / NOEL:

Data not required.

 

 

Genotoxicity

No genotoxic potential. One test was positive but was not done according to OECD Guidelines. All other tests were negative (15 tests).

 

 

Long term toxicity and carcinogenicity

Target / critical effect:

Liver

Lowest relevant NOAEL:

7 mg/kg bw/d; 2-year feeding study in rat

Carcinogenicity:

No carcinogenic potential

 

Reproductive toxicity

Target / critical effect - Reproduction:

Decreased pup weight at parental toxic dose levels

Lowest relevant reproductive NOAEL / NOEL:

78 mg/kg bw/d; multigeneration study in rat (Tesh-1980) 2

Target / critical effect - Developmental toxicity:

Foetotoxicity.
Increased incidences of resorption at maternal toxic dose levels.
Increase in the delayed ossification is not significant at litter toxic dose levels.

Lowest relevant developmental NOAEL / NOEL:

300 mg/kg bw/d (developmental study in rabbit) 3

2 Also parental NOAEL

3 Also maternal NOAEL

 

Delayed neurotoxicity

Data not required. No indication from other studies.

 

 

Other toxicological studies

Data not required.

 

 

Medical data

General survey of accessible literature: no adverse effects in humans exposed.

 

Summary

 

 

Value

Study

Safety factor

ADI:

0.07 mg/kg bw/d

2-y rat (Suresh‑95)

100

AOEL systemic:

2.5 mg/kg bw/d

90-d dog (Brownlie-94)

100

ARfD (acute reference dose):

Not required

 

 

 

 

Dermal absorption

No data. Default value of 10% is used for calculations. 4

4 See 4.2 for comment on dermal absorption

 

A few of the studies in the EU-dossier have data protection. The applicant of Powertwin has a Letter of Access from the ethofumesate beta taskforce which submitted new studies, equivalent to the protected studies. The results of these studies are comparable or within the margins prescribed to accept the data in the EU-List of Endpoints. Therefore the EU-List of Endpoints is used without adaptations.

 

Phenmedipham

Phenmedipham is an existing active substance, included in Annex I of 91/414/EEC. The final List of Endpoints presented below is taken from the final review report on phenmedipham (SANCO/4060/2001 final, d.d. 13 February 2004). Where relevant, some additional remarks/information are given in italics.

 



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

Rate and extent of absorption:

Rapid. 85%, based on urinary excretion in 24 30 h

Distribution:

Widely distributed, highest residues in blood (methylphenyl ring label)

Potential for accumulation:

Low potential for accumulation

Rate and extent of excretion:

Rapid. Over 90% within 24- 30 h

Toxicologically significant compounds:

Parent compound and metabolites. 3-aminophenol and 3-aminotoluene may be of special toxicological concern

Metabolism in animals:

Extensively metabolised. Oxidative/hydrolytic cleavage of parent molecule, hydroxylation of aromatic ring structures, acetylation of amino groups and further oxidation of methyl groups

 

Acute toxicity (Annex IIA, point 5.2)

Rat LD50 oral

>8000 mg/kg

Rat LD50 dermal

>2000 mg/kg

Rat LC50 inhalation

>7.0 mg/l (nose only)

Skin irritation

Non irritant

Eye irritation

Non irritant

Skin sensitization (test method used and result)

Not sensitising (M & K)

 

Short term toxicity (Annex IIA, point 5.3)

Target / critical effect

Effects on red blood cells (methemoglobinemia and hemolytic anemia) and related effects (hemosiderin deposition in spleen, liver and kidneys)

Lowest relevant oral NOAEL / NOEL

150 ppm (13 mg/kg bw/day) (90-day, rat)

Lowest relevant dermal NOAEL / NOEL

No data. Not required

Lowest relevant inhalation NOAEL / NOEL

No data. Not required

 

Genotoxicity (Annex IIA, point 5.4)

Clastogenic in vitro. Non-genotoxic in vivo (mouse bone marrow: negative for chromosome aberrations and micronuclei induction; mouse spermatogonial cells: negative for induction of chromosomal aberrations) 1

1 The genotoxic potential of phenmedipham was investigated in 13 in vitro studies (Ames test, mammalian cell gene mutation test in Chinese hamster lung fibroblasts V79 and mouse lymphoma cells, mammalian cytogenetic test in Chinese hamster ovary cells) and 5 in vivo studies (micronucleus test in mouse bone marrow and chromosome aberration test in NMRI mouse spermatogonial cells).

 


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

Target/critical effect

Effects on red blood cells (methemoglobinemia and hemolytic anemia) and related histophatological effects in spleen, liver and kidneys (increased weight, hemosiderosis, extramedullar hematopoiesis)

Lowest relevant NOAEL / NOEL

60 ppm (3 mg/kg bw/day) 2-year, rat)

Carcinogenicity

No carcinogenic potential

 

Reproductive toxicity (Annex IIA, point 5.6)

Target / critical effect Reproduction:

Reduced pup weight at parentally toxic dose levels

Lowest relevant reproductive NOAEL / NOEL

25 mg/kg bw/day (two-generation, rat) 2

Target / critical effect Developmental

Retarded ossification in rats and rabbits at maternally toxic dose levels

Lowest relevant developmental NOAEL / NOEL

Rabbit: 225 mg/kg bw/day 3

2 The NOAELs for paternal and maternal toxicity were respectively 75 and 25 mg/kg bw/day based on reduced bodyweight.

3 Also maternal NOAEL

 

Delayed neurotoxicity (Annex IIA, point 5.7)

 

No data. Not required.

 

Other toxicological studies (Annex IIA, point 5.8)

 

No data. Not required.

 

Medical data (Annex IIA, point 5.9)

 

Four different studies were supplied which reported cases of allergic dermatitis, photoallergic dermatosis, allergic rhinitis and toxic hepatitis in pesticide operators and field workers who had applied Betanal or Betamix formulations of phenmedipham.

 


Summary (Annex IIA, point 5.10)

Value

Study

Safety factor

ADI:

0.03 mg/kg bw/day

2-year rat study

100

AOEL systemic:

0.13 mg/kg bw/day

90-day rat study

100

ARfD (acute reference dose)

Not allocated, not necessary

 

Dermal absorption (Annex IIIA, point 7.3)

 

1% (based on an absorption study in vivo in rat, and comparative in vitro penetration studies with rat and human skin). 4

4 The dermal absorption study is performed with a OF (oil flowable) formulation with 75 g/L phenmedipham. From the available studies it can be concluded that there was hardly no difference between the dermal absorption of the undiluted formulation (0.9%) and the 1:50 spray dilution (0.2%). Therefore, the dermal absorption will be considered 1% (worst case).

 

Data requirements active substances

Ethofumesate and phenmedipham: None.

 

4.1 Toxicity of the formulated product (IIIA 7.1)

The formulation Powertwin does not need to be classified on the basis of its acute oral (LD50 rat >5000 mg/kg bw), dermal (LD50 rat >2000 mg/kg bw), and inhalation toxicology (LC50 rat >0.725 mg/L; maximum attainable concentration).

The formulation Powertwin does not need to be classified for dermal irritation or eye irritation.

The formulation Powertwin is positive in a Maximisation test for skin sensitisation and needs to be classified as R43 May cause sensitisation by skin contact.

 

4.1.1 Data requirements formulated product

None.

 

4.2 Dermal absorption (IIIA 7.3)

Ethofumesate

NL commented on dermal absorption for ECCO76, WG-Evaluation and WG-Legislation. Based on physical chemical parameters (Mol. Weight 286, log Pow 2.7) and the almost complete oral absorption, the value for dermal absorption might be much higher. In the absence of data, a default value of 100% should be used according to the EU Guidance document on Dermal Absorption (Rev. 7). Since the dermal absorption is a formulation related property, NL can deviate from the value in the List of Endpoints. For the risk assessment a value of 100% will be used.

 

Phenmedipham

It is assumed that the dermal absorption of phenmedipham formulated as Powertwin (SC formulation with 200 g/L phenmedipham) will not be higher than the dermal absorption of the oil flowable (OF) formulation used in the dermal absorption studies in the DAR. In the available studies the undiluted formulation and spray dilution (1:50) were tested. For the current application diverse spray dilutions are prescribed (1:100 - 1:600). Since the dermal absorption of the spray dilution (0.2%) was lower than of the undiluted formulation (0.9%), a dermal absorption of 1% (see List of Endpoints) is considered relevant for the present risk assessment.

 

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 Powertwin, a herbicide based on the active substances ethofumesate and phenmedipham, in sugar and fodder beets.

 

Powertwin is a SC formulation and contains 200 g/L ethofumesate and 200 g/L phenmedipham.

 

The formulation Powertwin is applied by mechanical downward spraying. Application is once every 3 years and the formulation is applied 1-6 times (0.1-0.2 kg a.s./ha). The period of application is in spring and is less than 3 months. Therefore, a semi-chronic exposure duration is applicable for the operator (including contract workers).

 

Calculation of the AOEL

 

Ethofumesate

Since ethofumesate is included in Annex I of 91/414/EEC, the semi-chronic EU-AOEL of 2.5 mg/kg bw/day (= 175 mg/day for a 70-kg operator), based on the 90 day study in dogs, is applied (see List of Endpoints).

 

 


Phenmedipham

Since phenmedipham is included in Annex I of 91/414/EEC, the semi-chronic EU-AOEL of
0.13 mg/kg bw/day (= 9.1 mg/day for a 70-kg operator), based on the 90-day oral toxicity study in dogs, is applied (see List of Endpoints).

 

4.4.1 Operator exposure/risk

Ethofumesate

Exposure to ethofumesate during mixing and loading and application of Powertwin 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.

The maximum dose in the field is 0.2 kg/ha ethofumesate.

Table T.1 Internal operator exposure to ethofumesate and risk assessment for the use of Powertwin

 

Route

Estimated internal exposure a (mg /day)

Systemic

AOEL

(mg/day)

Risk-index b

Mechanical downward spraying on sugar and fodder beets

Mixing/

Loading

Respiratory

0.01

175

<0.01

Dermal

40

175

0.23

Application

Respiratory

0.016

175

<0.01

Dermal

6

175

0.03

 

Total

46

175

0.3

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

       biological availability via the dermal route: 100% (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.

 

Phenmedipham

Exposure to phenmedipham during mixing and loading and application of Powertwin 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.

The maximum dose in the field is 0.2 kg/ha phenmedipham.

Table T.2 Internal operator exposure to phenmedipham and risk assessment for the use of Powertwin

 

Route

Estimated internal exposure a (mg /day)

Systemic

AOEL

(mg/day)

Risk-index b

Mechanical downward spraying on sugar and fodder beets

Mixing/

Loading

Respiratory

0.01

9.1

<0.01

Dermal

0.40

9.1

0.04

Application

Respiratory

0.016

9.1

<0.01

Dermal

0.06

9.1

0.01

 

Total

0.5

9.1

0.05

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

       biological availability via the dermal route: 1% (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.

 

4.4.2 Bystander exposure/risk

Ethofumesate and phenmedipham

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

 

4.4.3 Worker exposure/risk

Ethofumesate and phenmedipham

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

Ethofumesate and phenmedipham

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 ethofumesate and phenmedipham as a result of the application of Powertwin in sugar and fodder beets.

 

Bystander exposure

Based on the risk assessment it can be concluded that no adverse health effects are expected for the bystander after dermal and respiratory exposure to ethofumesate and phenmedipham as a result of the application of Powertwin in sugar and fodder beets.

 

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 to ethofumesate and phenmedipham as a result of the application of Powertwin in sugar and fodder beets.

 

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

See Lists of Endpoints.

 

4.6 Data requirements

None.

 

4.7 Combination toxicology

The formulation Powertwin is a mixture of two active substances. Furthermore, for application in a low dose system, a tank mixture of 0,5 L/ha Powertwin + 0,5 L/ha Goltix SC (based on the active substance metamitron; 700 g/L) + 0,5 L/ha mineral or vegetable oil is prescribed on the label (when necessary the doses can be increased to 0.75 or 1 L/ha of all formulations). The combined toxicological effect of these active substances has not been investigated.

Possibly, the combined exposure to these active substances may lead to a different toxicological profile than the profile(s) based on the individual substances.

 

Ethofumesate and metamitron induce effects on the liver. The critical effect of phenmedipham is haemolytic anaemia. Based on the differences in toxicological profile, no additional risk is expected for the combined exposure to ethofumesate and phenmedipham or to metamitron and phenmedipham.

 

Metamitron and ethofumesate both induce effects on the liver. These effects could possibly be correlated to the induction of biotransformation enzymes. In that case these substances could in principle influence the toxicological effects of each other (induce or deduce).

The estimated combined exposure to metamitron (risk-index = 0.45, based on the recent risk assessment of Goltix Super in C-173.3.13; risk-index is adjusted for the dose/ha (=maximum of 1 L formulation/ha) as described on the label for Powertwin) and ethofumesate (risk-index=0.26 for a maximum of 1 L formulation/ha) results in a risk-index of 0.7. Therefore, no extra risk is expected for the combined exposure to metamitron and ethofumesate, 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)

 

Ethofumesate

Symbol:

-

Indication of danger: -

 

Risk phrases

-

-

 

Phenmedipham

Symbol:

-

Indication of danger: -

 

Risk phrases

-

-

 

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:

Xi

Indication of danger:

irritant

R phrases

R43

May cause sensitisation by skin contact.

S phrases

S36/37

Wear suitable protective clothing and gloves.

 

SPo2

Wash all protective clothing after use.

Special provisions:
DPD-phrases3

-

-

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:

Xi is obligatory when R43 is assigned.

Risk phrases:

The sensitisation study in the guinea pig showed that the formulation should be classified as sensitising, R43.

Safety phrases:

S2, S13 and S20 are no longer invariably assigned to formulations intended for professional use only. S36/37 is assigned to formulations labelled with Xi, R43. SPo2 is invariably assigned to formulations to which S36/37 is assigned and containing active substances complying with re-registration.

Other:

-

 

 

5.            Residues

 

Powertwin is a suspension concentrate (SC) based on 200 g/L ethofumesate and 200 g/l phenmedipham.

Ethofumesate is an existing active substance included in Annex I of directive 91/414/EEC. The dossier is owned by the ethofumesate alpha task force.

Phenmedipham is also an existing active substance included in Annex I of directive 91/414/EEC.

The applicant has letters of access to both dossiers.

 

Ethofumesate

 

Lists of Endpoints (January 25th, 2002)

 

Residues

 

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

Plant groups covered

Sugar beet (root crops), rye grass (cereals), onion (root crops), tobacco (leafy vegetables), wheat (cereals), radish (root crops) and cabbage (leafy vegetables).

Rotational crops

Root and tuber vegetables (radish, carrots, cabbage), leaf vegetables (spinach, cabbage) and cereals (wheat, grain, corn)

Plant residue definition for monitoring

Ethofumesate and the metabolites 2,3-dihydro-3,3-dimethyl-2-oxo-benzofuran-5-yl methane sulphonate (AE C509607) and 2-(2-hydroxy-5-methane sulphonyloxyphenyl)-2-methyl-propionic acid (AE C520645; free and conjugated)

Plant residue definition for risk assessment

Ethofumesate and the metabolites 2,3-dihydro-3,3-dimethyl-2-oxo-benzofuran-5-yl methane sulphonate (AE C509607) and 2-(2-hydroxy-5-methane sulphonyloxyphenyl)-2-methyl-propionic acid (AE C520645; free and conjugated).

Conversion factor (monitoring to risk assessment)

None

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

 

 

Root and tuber vegetables (radish, carrots, cabbage), leaf vegetables (spinach) and cereals (wheat, grain, corn)

 

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

Animals covered

Cow and hen (parent compound only)

Animal residue definition for monitoring

Ethofumesate (2-Ethoxy-2,3-dihydro-3,3-dimethyl-benzofuran-5-yl-methane sulphonate) and the metabolites 2,3-dihydro-3,3-dimethyl-2-oxo-benzofuran-5-yl methane sulphonate ( AE C509607) and 2-(2-hydroxy-5-methane sulphonyloxyphenyl)-2-methylpropionic acid (AE C520645; in free form only).

 

Animal residue definition for risk assessment

Ethofumesate (2-Ethoxy-2,3-dihydro-3,3-dimethyl-benzofuran-5-yl-methane sulphonate) and the metabolites 2,3-dihydro-3,3-dimethyl-2-oxo-benzofuran-5-yl methane sulphonate ( AE C509607) and 2-(2-hydroxy-5-methane sulphonyloxyphenyl)-2-methylpropionic acid (AE C520645; in free form only).

 

Conversion factor (monitoring to risk assessment)

-

Metabolism in rat and ruminant similar (yes/no)

Yes

Fat soluble residue: (yes/no)

Log Pow parent compound: 2.7

Log Pow NC 20 645: Data not available.

 

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

 

 

Root and tuber vegetables (radish, carrots, cabbage), leaf vegetables (spinach) and cereals (wheat, grain, corn)

 

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

 

 

Ethofumesate and the two conjugated metabolites NC 9607 and conjugated NC 8493 were not degraded during prolonged storage (maximum 54 weeks) of frozen samples of sugar beet plants.

Ethofumesate and NC 9607 residues in fortified samples of sugar beet tops, and ethofumesate residues in fortified samples of sugar beet roots did not significantly decline after storage at -20 C for up to 24 months. But, NC 9607 residues in fortified samples of sugar beet roots gave a mean recovery of 77 % after 24 months storage at -20 C.
Studies on cereals, leafy vegetables and root crops will not be evaluated for the time being.

 

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

 

Not required as the notifier has announced that there is no intended use in grassland. According to extrapolation from a new metabolism study (C 003362) all residues in a dairy cow, all tissues (including liver and kidney) and milk would be below LOQ. A new estimation of ethofumesate intake (1x) via fodder crops by RMS (17 December 1999) resulted in a total intake of 0.91 ppm in dairy cows and 0.89 ppm in beef cows (will be included in the addendum to the DAR). According to 7031/VI/95 rev 4, livestock feeding studies are however, only required when total diet is: 0.1 ppm and metabolism studies indicate that significant residues (0.01 ppm or above the LOQ) may occur in edible animal tissue when taking account of the potential 1x dose rate. If current uses in fodder crops (sugar beet tops and roots (molasses), fodder beet tops, mangold tops and roots and pulses) also are the only intended uses, there seems to be no need for a new livestock feeding study.

 

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

Crop/processed crop

 

Number of studies

Transfer factor

% Transference

Sugarbeet/Sugar

 

4

0.1-0.3

Not possible to calculate

Sugarbeet/Molasses

 

4

6-24

Not possible to calculate

Sugarbeet/Wet pulp

 

3*

0.2-0.4

Not possible to calculate

Sugarbeet/Thick juice

 

5

4-5

Not possible to calculate

Sugarbeet/Thin (raw) juice

 

5

0.5-1.9

Not possible to calculate

* Substrates in studies R19 and R41 were not analysed

 

Phenmedipham (October 22nd, 2003)

 

List of Endpoints

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

Plant groups covered

Root vegetables (sugar beet), leafy crops (spinach), fruits (strawberry), pulses (pea)

Rotational crops

-

Plant residue definition for monitoring

phenmedipham

Plant residue definition for risk assessment

phenmedipham

Conversion factor (monitoring to risk assessment)

-

 

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

Animals covered

Cow and hen

Animal residue definition for monitoring

MHPC expressed as phenmedipham

Animal residue definition for risk assessment

phenmedipham and MHPC

Conversion factor (monitoring to risk assessment)

1*

Metabolism in rat and ruminant similar (yes/no)

Yes

Fat soluble residue: (yes/no)

potential to accumulate

* Phenmedipham was included in the residue definition for unclear reasons since it was not found in animal tissue. A conversion factor of 1 is used in the EU.

 

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

 

-

 

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

 

Parent compound is stable at 10 oC for at least 5 months in processed commodities of sugar beets (cosettes, dry pulp and molasses).

Parent compound is stable at 20 oC for at least 24 months in sugar beets.

 

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

Intakes by livestock 0.1 mg/kg diet/day:

Ruminant:

Yes

Poultry:

Yes

Pig:

no studies

Muscle

-

4 ng/g (skeletal muscle)

3 ng/g (skeletal muscle/ breast)

-

Liver

112 ng/g (MPC label)

150 ng/g (PC label)

16 ng/g

-

Kidney

140 g/g (MPC label)

150 ng/g (PC label)

-

-

Fat

-

7 ng/g (peritoneal fat)

-

Milk

8 ng/g (MPC label)

18 ng/g (PC label)

-

-

Eggs

-

16 ng/g

-

 

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

Crop/processed crop

 

Number of studies

Transfer factor

% Transference

Sugar beet/ sugar

4

 

 

Sugar beet/ molasses

1

 

 

Sugar beet/ wet pulp

2

 

 

Sugar beet/ dry pulp

2

 

 

Sugar beet/ pulp

2

 

 

Sugar beet/ thick juice

2

 

 

Sugar beet/ thin juice

2

 

 

Sugar beet/ diffusion juice

2

 

 

Sugar beet/ lime cake

2

 

 

Sugar beet/ cosettes

1

 

 

Sugar beet/ mother lye

1

 

 

Sugar beet/ cuts

1

 

 

Strawberry/ jam

1

 

 

 

 

Comments on/additions to List of Endpoints

Ethofumesate: in the evaluation table (Doc. 6487/VI/99 rev. 6 (05.02.2001)), a data requirement to be dealt with at member state level was identified. As this data requirement concerned the use on beans with pods in Southern Europe, it is not of importance for this application for authorisation

Phenmedipham: in the evaluation table (Doc. 4082/2001 rev. 1-2 (13.11.2003)), data requirements to be dealt with at member state level were identified. As these data requirements concerned the use on strawberry and peas, they are not of importance for this application for authorisation

 

5.1 Summary of residue data

Only points that need clarification to the data in the List of Endpoints or that are not covered in the List of Endpoints, are discussed below.

 

5.1.3 Residue definition (plant and animal)

Ethofumesate

The residue definition for monitoring and risk assessment of plant and animal products is ethofumesate (sum of ethofumesate and the metabolite 2,3-dihydro-3,3-dimethyl-2-oxobenzofuran-5-yl methane sulphonate expressed as ethofumesate)

 

This residue definition is different from the residue definition in the List of Endpoints, which also contains metabolite 2-(2-hydroxy-5-methane sulphonyloxyphenyl)-2-methyl-propionic acid. During MRL harmonisation it was concluded that due to analytical difficulties, this metabolite could not be measured. A conversion factor for risk assessment to include this metabolite was not considered necessary.

 

Phenmedipham

The residue definition for monitoring and risk assessment of plant products is phenmedipham.

 

The residue definition for monitoring of animal products is Phenmedipham (Methyl-N-(3-hydroxyphenyl) carbamate (MHPC) expressed as phenmedipham). The residue definition for risk assessment is phenmedipham and MHPC, however, it is unclear why phenmedipham is included, as it is not found in animal tissue. A conversion factor of 1 is therefore used in the EU.

 

5.1.5 Residue data

Ethofumesate

Eight residue trials are provided by the beta task force performed in Northern Europe in 2000 and 2001. In all studies the dose level was 2 applications of 748-804 g ai/ha, which is ca. 1.8 times overdosed compared to cGAP-NL. However, since residues accounted for 8x < 0.05 mg/kg (both shoots and roots), the studies were considered acceptable.

 

Phenmedipham

In the DAR for phenmedipham, 154 supervised residue trials in sugar beet and 30 in fodder beet in Northern Europe are available. The intended use for this application (1 kg ai/ha) is similar to the supported use in the DAR (maximally 960 g as/ha/season). A sufficient number of residue trials is available.

For sugar beet the analysed residue values range from <0.01 to 0.3 mg/kg and from <0.01 to 1.2 mg/kg for roots and leaves, respectively. For fodder beet the analysed residue values range from <0.02 to <0.1 mg/kg and from <0.02 to <0.05 mg/kg for roots and leaves, respectively.

 

5.1.6 Residues in succeeding crops

Ethofumesate

Due to persistence of ethofumesate for Annex I inclusion the following restriction was set: the dose level of ethofumesate must not exceed 1.0 kg ai/ha every 3 years. With the current application request and normal crop rotation, this restriction will be honoured and no detectable residue levels are expected in rotational crops.

 

Phenmedipham

Due to fast degradation and strong adsorption in soil, no detectable residues are present in succeeding crops.

 

5.1.8 Processing factors

Ethofumesate

See List of Endpoints.

 

Phenmedipham

Processing studies with sugar beet are available in the DAR on phenmedipham. As no detectable residue levels (<0.02-<0.1 mg/kg) were present at harvest, no processing factor could be derived.

 

5.1.9 Calculation of the ADI and the ARfD

Ethofumesate

Calculation of the ADI

The ADI was based on the NOAEL of 7 mg/kg bw/d from the 2-year oral rat study. Using a safety factor of 100, the ADI was established at 0.07 mg/kg bw/d.

 

Calculation of the ARfD

The ARfD was not allocated, since ethofumesate shows no acute toxic properties at the expected exposure level.

 

Phenmedipham

Calculation of the ADI

The ADI is based on the NOAEL of 3 mg/kg bw/d in the 2-year rat study. Application of a safety factor for inter- and intraspecies differences of 100 results in an ADI of 0.03 mg/kg bw/day (see the List of Endpoints for mammalian toxicology).

 

Calculation of the ARfD

No ARfD is derived since phenmedipham shows no acute toxic properties.

 

5.2 Maximum Residue Levels

Ethofumesate

EU-MRLs have been established by means of Regulation (EC) 396/2005 for:

product

MRL (mg/kg)

Sugar beet

0.5

Beetroot

0.1

Fresh Herbs

1

Oilseeds, oil fruits, coffee beans, cocoa, kapok, tea, hops

0.1*

Herbal infusions, spices

0.5

All other plant commodities, including cereals

0.05*

All animal commodities

0.1*

 

The product complies with the MRL Regulation. Notification of the MRL is not necessary.

 

Phenmedipham

EU-MRLs have been established by means of Regulation (EC) 396/2005 for:

product

MRL (mg/kg)

Strawberries

0.1 (p)

Beetroot

0.1 (p)

Spinach and similar

0.5 (p)

Fresh Herbs

7

Globe artichokes

0.2 (p)

Oilseeds, Tea, Hops, Oil fruits, Spices

0.1* (p)

All other plant commodities

0.05* (p)

All animal commodities

0.05* (p)

 

The product complies with the MRL Regulation. Notification of the MRL is not necessary.

 

5.3 Consumer risk assessment

Ethofumesate

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 EU-MRLs. Calculation of the NTMDI shows that < 1% of the ADI is used for both the general population and for children.

 

Risk assessment for acute exposure through diet

Since no ARfD is derived, a calculation of the National Estimated Short Term Intake (NESTI) is not necessary.

 

Phenmedipham

Risk assessment for chronic exposure through diet

A calculation of the National Theoretical Maximum Daily Intake (NTMDI) was carried out using the National Dutch diet and the harmonised EU-MRLs . Calculation of the NTMDI shows that 2.0 % and 6.9 % of the ADI is used for the general population and for children, respectively.

 

Risk assessment for acute exposure through diet

Since no ARfD is derived, a calculation of the National Estimated Short Term Intake (NESTI) is not necessary.

 

Conclusion

Based on the assessment for residues, no risk for the consumer due to the exposure to phenmedipham and ethofumesate is currently expected. The product complies with the Uniform Principles.

 

5.4 Data requirements

None.

 

 

6.            Environmental fate and behaviour

 

Powertwin has been assessed in C-187.3.1 d.d. 14th November 2007. Additional questions were raised for eco-toxicology. Additional data were received on 12th August 2008. Only the use in beets with the LDS system is applied for. For this application a tank mix with metamitron (Goltix SC or Goltix WG) has to be used.

 

List of Endpoints Fate/behaviour

Ethofumesate

 

Ethofumesate is an existing substance, placed on Annex I. For the risk assessment the final List of Endpoints is used.

 

List of Endpoints Fate/behaviour in the environment

 

Fate and behaviour in soil

Route of degradation

 

Aerobic:

 

Mineralization after 100 days:

Range 6 - 13%; median 8.7%; n=5

Non-extractable residues after 100 days:

Range 16 - 34%; median 31%; n=5

Major metabolites above 10 % of applied active substance: name and/or code
% of applied rate (range and maximum)

All less than 6%

 

 

Supplemental studies

 

Anaerobic:

Not relevant because of very slow transformation

 

 

Soil photolysis:

DT50 two studies :

14 d; =290nm, 24 h light, 1.5 kg a.s./ha

65 days; 300-800 nm, light 12h per day, 15 mg as/kg.

 

 

Remarks:

None

 

Rate of degradation

 

Laboratory studies

 

DT50lab (20 C, aerobic):

40 - 75% WHC:

range 47 211 d; mean 97 d; median 84 d; n=10

DT90lab (20 C, aerobic):

40 - 75% WHC:

range 210 701 d; median 331 d; n=10

DT50lab (10 C, aerobic):

No study.

Calculation of DT50, 10C carried out on eight DT50 laboratory tests (20-21C, aerobic) using Q10=2.2.

Result: DT50, (10C, aerobic) (calc.) = 198 d

DT50lab (20 C, anaerobic):

Very slow transformation: 90-100% unaltered

after 60 d; n=2

 

Field studies (country or region)

 

DT50f from soil dissipation studies:

Germany: One dose range 0.8 - 6.5 kg as/ha: range 15 - 250 d; median 65 d; n=10. Not dose related

UK: One dose 1.5 kg as/ha: 36 and 56 d; mean 46 d; n=2

California, USA: 2.1 kg as/ha: 75 d. n=1

Calculated mean of all = 77 d; median = 56 d;

n=13

After standardization of the relevant studies:

mean 39.1 days

DT90f from soil dissipation studies:

Germany: One dose range 0.8 - 6.5 kg as/ha: range 3 months - >3 years; median ca.11 months; n=11.

UK: One dose 1.5 kg as/ha: 4 and 4.6 months, mean 4.3 months; n=2

Soil accumulation studies:

No relevant data.

Calculated based on a field DT50 = 119 days

a) Application of 1.0 kg as/ha and year, a plateau concentration of 114% of maximum PECsoil reached after 3 years. Plateau concentration 1.5 mg as/kg soil.

b) Application 1.0 kg as/ha each third year. There was no significant accumulation.

Three years after applic. 0.1% of dose remained.

Soil residue studies:

Data not required.

 

 

Remarks:
e.g. effect of soil pH on degradation rate

 

None.

 


Adsorption/desorption

 

Kf / Koc:

 

Kd

 

pH dependence:

Koc: range 97 - 245; mean = 147; median 132; n=11

 

Kd: range 0.73 6.2; mean = 2.7; median 2.3; n=11

 

Not pH dependent.

 

Mobility

 

Laboratory studies:

 

Column leaching:

According to BBA Guideline (200 mm over 2 d): n.d.-2.9% as; n=9

Other method (508 mm over 15 - 20 d): 4.2-67% of applied radioactivity; n=4

Aged residue leaching:

Three different methods: n.d.-4.2% of applied initial radioactivity; n=5

 

 

Field studies:

 

Lysimeter/Field leaching studies:

Two studies according to BBA guideline:

 

Three lysimeters with loamy sand soil. Lysimeter with a surface area of 0.5 m2 and a depth of 1.0 m. One dose of 1.25 kg as/ha applied pre-emergence to sugar beet on silty sand in April 1992. An approximate mean rainfall of 857 mm/year. Terminated after 2 years.
LOD = 0.1 g/L

Two lysimeters with a sandy soil. Lysimeter with a surface area of 1.0 m2 and a depth of 1.2m. One dose of 1.5 kg as/ha applied to fodder beet on sandy soil in both lysimeters in May year 1 and additionally to one soil in May year 2. Total rainfall (4 years) 3280 mm. Terminated after 3 years.
LOD = 0.01 g/L

Results: No detected active substance or metabolite in leachate in any of the lysimeters.

 

 

Remarks:

None.

 

Fate and behaviour in water

Abiotic degradation

 

Hydrolytic degradation:

pH 5.0, 7.0, 9.2: Negligible

Major metabolites:

None.

Photolytic degradation:

Artificial light: (greatly variable results)
37-62 d (summer, 40-60
N)
4.6 d (on a year basis) / 2.6 d (for month May)

Major metabolites:

None identified.

 

 

Biological degradation

 

Readily biodegradable:

Not readily biodegradable; n=3

Water/sediment study:

Calculations: 3 out of 5 according to first order kinetics, 2 out of 5 according to 1.5th order kinetics

DT50 water:

Study 1: 13 days, n=1 (1st order)

Study 2: 11 and 19 days, n=2 (1st and 1.5th order)

Study 3: 7 and 50 days, n=2 (root of 1st order)

DT90 water:

Study 1: -

Study 2: 121 and 212 days, n=2

Study 3: -

DT50 whole system:

Study 1: 125 days, n=1, (1st order)

Study 2: 105 and 153 days, n=2 (1st and 1.5th
order)

Study 3: 242 and 285 days, n=2 (root of 1st
order)

DT90 whole system:

Study 1: -

Study 2: 507 and 550 days, n=2

Study 3: -

Distribution in water / sediment systems
(active substance)

Study 1: After 84 days, 14% of applied radioactivity as parent compound in water / 51% in sediment, n=1. Maximum 53% parent compound in the sediment after 63 days of incubation. No DT50 calculated for the sediment.

Study 2: After 103 days, 13-18% of applied radioactivity as parent compound in water / 37-41% in sediment. Maximum 48 49 % of applied as parent compound in the sediment after 30 days of incubation. Thereafter DT50 in the sediment 170 270 days.

Study 3: After 225 and 234 days, 21 and 1.5% of applied radioactivity as parent compound in water / 30 and 53% in sediment. No DT50 calculated for the sediment.

Distribution in water / sediment systems
(metabolites)

Maximum of 4 unknown metabolites,
altogether up to 17% of applied radioactivity.

Accumulation in water and/or sediment:

Considered not relevant since active substance is applied every third year.

Rate of mineralisation

 

Non-extractable residues

6-9%

 

27%

Degradation in the saturated zone

Degradation in the saturated zone: No study. Not required.

 

 

Remarks:

None.

 

Fate and behaviour in air

Volatility

 

Vapour pressure:

6.5 x 10-4 Pa (25 C)

Henry's law constant:

6.8 x 10-4 Pam3mol -1 (25 C)

 

 

Photolytic degradation

 

Direct photolysis in air:

Data not required.

Photochemical oxidative degradation in air

DT50:

2.1 h, calc. according to Meyland and Howard (AOP)

4.1 h, calc. According to Atkinson

Volatilisation:

From plant surfaces:

22% lost from plant surface during 24 hours

From soil:

15% lost from soil surface during the first 24 hours

 

 

Remarks:

No remarks.

 

Phenmedipham

Phenmedipham is an existing substance, placed on Annex I since April 2004. For the risk assessment the final List of Endpoints (February 2004) is used. Additions are placed in italic.

 

List of Endpoints Fate/behaviour

 

Fate and Behaviour in the Environment

 


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

PMP: Mineralization after 100 days

 

CO2 evolved:

13.3 16.5 % of AR within 120 days, AP 14C-labelled, low temperature/low moisture (n=1)

9.7 11.3 % of AR within 120 days, phenoxy ring U-14C labelled (n=3)

PMP: Non-extractable residues after 100 days

 

63.6 64.1 % of AR within 120 days, AP 14C-labelled, low temperature/low moisture (n=1)

71.3 73.8 % of AR within 120 days

phenoxy ring U-14C labelled (n=3)

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

MHPC max 14 % of AR at day 14 (n=1)

APMP max 4 % of AR after 56 days (n=1)

(label position AP)

MHPC max 54 % at day 5 (n=1, ring-U-labelled)

MHPC: Mineralization after 100 days

From MHPC: ca. 10 % CO2 within 7 days (n=3)

MHPC: Non-extractable residues after 100 days

From MHPC: 80-83 % within 7 days (n=3)

 

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

Anaerobic degradation

 

CO2 evolved 6.6 % of AR,

NER 74.3 % of AR after 97 days,

MHPC max 19 % of AR after 32 days

(label position AP, n=1)

Soil photolysis

 

DT50 79 hours on irradiated soil

photochemical products:

3-aminophenol and 3-methoxycarbonylaminophenol

max 17.8 % of AR (sum of all polar products)

after 105 hours of irradiation

(n=1)

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

Method of calculation

laboratory: 1st order kinetics

computer program by Timme

 

Laboratory studies (range or median, with n value, with r2 value)

 

 

PMP

DT50lab (22C, aerobic): 14.1 days (n=1, r2 = 0.934)

Normalised to 20 C by using Q10 of 2.2: 16.4 days

DT50lab (20C, aerobic): 26, 42, 43 d, mean=37 days (n=3, r2 = 0.932 - 0.953)

 

DT90lab (22C, aerobic): 47 days (n=1, r2 = 0.934)

Normalised to 20 C by using Q10 of 2.2: 55 days

DT90lab (20C, aerobic): 85, 138, 143 days (n=3, r2 = 0.932 0.953)

 

DT50lab (11C, aerobic): 25 days,

DT90lab (11C, aerobic): 105 days

 

PMP

DT50lab (22C, anaerobic): 12.5 days (n=1, r2 = 0.934)

DT90lab (22C, anaerobic): 42 days (n=1, r2 = 0.934)

Metabolites:

MHPC

DT50lab (22C, aerobic): 12 days (n=1, r2 = 0.748)

DT90lab (22C, aerobic): 38 days (n=1, r2 = 0.748)

DT50lab (20C, aerobic): 0.1, 0.2, 0.3 days (n=3,

r2 = 0.992 - 0.999)

DT90lab (20C, aerobic): 1.2, 2.3, 2.9 days (n=3,

r2 = 0.992 - 0.999)

MHPC

DT50lab (20C, anaerobic): 49 days (n=1, r2 = 0.930)

DT90lab (20C, anaerobic): 161 days (n=1, r2 = 0.930)

APMP

DT50lab (22C, aerobic): 16.7 days (n=1, r2 = 0.993)

DT90lab (22C, aerobic): 55.5 days (n=1, r2 = 0.993)

APMP

DT50lab (20C, anaerobic): 70 days (n=1, r2 = 0.982)

DT90lab (20C, anaerobic): 231 days (n=1, r2 =0.982)

Degradation in the saturated zone

no data submitted nor required

Field studies (state location, range or median with n value)

first order kinetics, DT50f:

Germany, bare soil, four sites:

5.8 days at pH 5.0,

9.0 days at pH 6.9,

15.7 days at pH 7.1,

39.9 days at pH 6.0,

mean 17.6 days (n=4, r2 not available, 1st order)

USA, California, one site:

sandy loam, on red beet stage 4-6 leaf:

13.3 days at pH 7.0 (n=1, r2 not available, 1st order)

 

metabolites: no DT50 values calculated in the field studies

 

DT90f: Germany, sites described above:

range 30 - 133 days, mean 82 days (n=4 , r2 not available, 1st order)

 

For PECsoil calculation the median DT50f of 15.5 days from the German field studies was used.

 

For FOCUS gw modelling the DT50lab of 25 days was used for PMP, and 7 days for MHPC.

Soil accumulation and plateau concentration

no data submitted nor required

 

Soil adsorption/desorption (Annex IIA, point 7.1.2)

Kf /Koc

PMP

 

 

 

 

 

 

MHPC

 

 

 

 

 

 

 

pH dependence (yes / no) (if yes type of

dependence)

Koc:

PMP:

657, 934, 1072, mean = 888, 1/n = 0.821, 0.865, 0.854

(soil samples, n = 3, equilibrium time 2.5 hours)

469, 728, mean = 599, 1/n = 0.82, 0.84

(sediments, n=2, equilibrium time 3 hours)

 

Koc:

MHPC: 212, 138, 58, 470, mean = 220, 1/n = 0.515, 0.699, 0.949, 0.805 (n = 4, one outlier excluded)

 

Kd:

MHPC: 0.57 - 4.8

 

Yes, due to the hydrolysis processes which indirect affect the adsorption of parent. No dependence for the metabolites.

 

For FOCUS gw modelling with FOCUS_PEARL v. 1.1.1 following median Kom values were used:

PMP: 422, 1/n = 0.84

MHPC: 101, 1/n = 0.752

 

Mobility in soil (Annex IIA, point 7.1.3, Annex IIIA, point 9.1.2)

Column leaching

PMP:

 

 

 

 

 

 

 

 

 

 

 

 

 

PMP:

 

 

 

 

 

 

 

 

 

 

PMP:

 

 

 

 

 

 

 

 

MHPC:

 

1) Guideline: US EPA subdiv. N, para 163.1

Precipitation: 920 ml corresponding to 50.8 cm rainfall in 10 days (92 ml/d)

Soils: 2 soils, label positions AP and T

Use rate: 0.825 kg/ha (AP) and 1.1 kg/ha (T)

Leachate: total residue 0.33 - 0.45 % of AR in leachates, not characterized further

Soil columns: total residue 88.1 92.6 % of AR in soil columns (mainly in the top 5 cm), NER 43.1 53.1 % and 34.9 60.4 % extractable of it

Volatiles 3.72 7.27 % of AR during the leaching period.

 

2) Guideline: US EPA subdiv. N, para 163.1

Precipitation: 560 mm in 5 days

Soil: 2 soils, label positions AP and T

Use rate 1.65 kg/ha

Leachate: total residue 0.6 - 2.3 % of AR in leachates, not characterized further

Soil columns: total residue 89.5 95.4 % of AR in soil columns (mainly in the top 10 cm), extractable 26 64 % of it, mainly unchanged parent

Volatiles not trapped.

 

3) Guideline: BBA

Precipitation: 200 ml/day for 2 days

Soils: 3 soils, label position AP

Use rate: 1.5 kg/ha

Leachate: total residue <0.5 % of AR in leachates, not characterized further

Soil columns: total residue > 93 % of AR, mainly in the top 5 cm.

 

Guideline: TNO in-house method

Precipitation: 140 ml/day for 3 days, corresponding to 30 cm of rainfall in 3 days

Soils: 2 soils, humic sand and loam

Use rate: 0.5 mg MHPC/column

Leachate: 47.2 - 47.7 % of AR in leachates in the loam soil, not detected in the humic sand soil

Soil columns: In the humic sand the main part of the activity remained in the soil layers 12-24 cm, in the loam soil the activity was evenly distributed to the layers 6-30 cm, and only traces were located in the top 5 cm.

Aged residues leaching

 

1) Guideline: BBA

Soils: 1 soil, German standard soil 2.1

Use rate: 960 g/ha, label position T

Aged at 20 degrees C, 40 % MWHC, for 33 days

Precipitation: 2 days irrigation of 200 mm

Leachate: 0.48 % of AR was found in the leachate, not characterized further

Soil column: 96.2 % of AR remained in soil, mainly in the top 10 cm

Volatiles: 5.7 % of AR.

 

2) Guideline: EPA Vol 40, No 123, Part II, 1975

Soils: 2 soils, German standard soils 2.2 and 2.3

Use rate: 1.25 kg/ha, label position AP

Aged at 25-30 degrees C, 70 % MWHC, for 30 days

Precipitation: 45 days irrigation of 125 mm/day

Leachate: 0.58 and 1.66 % of AR was found in the leachates, not characterized further

Soil column: 99.1 112.9 % of AR remained in the soil, mainly in the top 6 cm. The aged soil was not analysed further for the metabolites.

 

3) Guideline: EPA Vol 40, No 123, Part II, 1975

Soils: 2 soils, German standard soils 2.2 and 2.3

Use rate: 1.65 kg/ha on soil 2.2 and 1.25 kg/ha on soil 2.3, label position T

Aged at 25-30 degrees C, 75 % MWHC, for 30 days

Precipitation: 45 days irrigation of 125 mm/day

Leachate: 1.37 - 1.83 % of AR was found in the leachates, not characterized further

Soil column: 72.9 88.7 % of AR remained in the soil, mainly in the top 5 cm. The aged soil was not characterized further for the metabolites.

Lysimeter/ field leaching studies

 

1) Location: UK

Study type: lysimeter

Soils: loamy sand, low content of organic matter

Number of applications: one single application of 0.942 kg/ha in the first year, study continued over 2 years

Crops: sugar beet + wheat

Average annual rainfall: 757 mm (1st year), 948 mm (2nd year)

Average annual leachate volume: 200 mm/ first year (25 % of the precipitation), 445 mm/ second year (47 % of the precipitation)

% radioactivity in the leachate (max/year): after 2 years totally 0.8 - 1.1 % of AR was leached

Peak annual average concentrations: total radioactive residues 1.28 1.9 mg/l in the first year, 1.1 1.33 mg/l in the second year (40 % of AR in leachate attributed to humic acid type fragments and up to 27 % incorporated with naturally occurring compounds), MHPC 0.006 mg/l, PMP could not be detected in any of the samples (LOD = 0.03 mg/l as a.s.equivalents).

 

2) Location: Germany

Study type: lysimeter

Soils: loamy sand with low organic matter content

Number of applications: 1.0 kg/ha either once or in two successive years, study continued for up to 3 years

Crops: sugar beet (1 or 2 successive years) + wheat

Average annual rainfall: 860 mm/year (cumulative sum of 2582 mm within 3 years)

Average annual leachate volume: 428 mm

% radioactivity in the leachate (max/year): after 2 years totally 0.22 - 0.32 % of AR was leached

Peak annual average concentrations: total radioactive residues 0.314 0.805 mg/l (water soluble humic acid-type components, due to the low radioactivity the further characterization was not possible). MHPC was calculated as <0.01 mg as equivalents/l. (LOQ = 0.017 mg/l for PMP and 0.010 mg/l for MHPC).

 

Route and rate of degradation in water (Annex IIA, point 7.2.1)

Hydrolysis of active substance and relevant metabolites (DT50) (state pH and temperature)

DT50 DT90 r2

pH 4: 259 d 861 d -0.9726

pH 5: 47 d 156 d -0.9958

pH 7: 12 h 39 h -0.9922

pH 9: 7 min 24 min -0.9860

(25 oC, 1st order kinetics)

Hydrolysis products:

MHPC formed:

pH 4: max 8.0 % of AR after 672 h

pH 5: max 38.0 % of AR after 720 h

pH 7: completely after 72 h

pH 9: completely after 30 min

 

MHPC is hydrolytically stable at pH 4, 5, 7, 9 under sterile conditions and at 50 oC over 120 h.

Photolytic degradation of active substance and relevant metabolites

no degradation (artificial light source, λ > 290 nm)

Readily biodegradable (yes/no)

no

Degradation in - DT50 water

water/sediment - DT90 water

 

- DT50 whole system

- DT90 whole system

 

 

MHPC: - DT50 water

- DT90 water

- DT50 whole system

- DT90 whole system

 

 

Mineralisation

NER in sediment

 

 

 

 

Distribution in water / sediment systems (active

substance)

 

 

 

 

 

 

Distribution in water / sediment systems

(metabolites)

0.1 0.3 days (t/1st order, r2 = 0.989, 0.544, n=2 )

0.6 3.4 days (t/1st order, r2 = 0.989, 0.544, n=2 )

 

0.11, 0.12, 0.18 days (1st order kinetics, r2 = 0.942 0.978, n=3)

0.38, 0.40, 0.60 days (1st order kinetics, r2 = 0.942 0.978, n=3)

 

10-21 days (apparent DT50 determined visually)

not available

 

10.6, 23.9, 24.9 days (1st order kinetics, r2 = 0.942 0.978, n=3)

35.3, 79.4, 82.8 days (1st order kinetics, r2 = 0.942 0.978, n=3)

 

CO2: 14 - 30 % of AR at study end after 126 days (n=2)

NER in sediment: max.55 - 78 % of AR after 70/35 days,

50 % at study end after 126 days, n=2)

 

1 - 2 % of AR in water phase and

51 - 55 % in sediment after 126 days

(non-sterilised samples, 2 label positions, 2 systems),

44 - 51 % of AR in water and

39 - 44 % in sediment after 126 days (sterilised samples, 1 label position, 2 systems).

 

MHPC: 60 - 70 % of AR within 1 - 2 days

1 % of AR after 126 days

 

Fate and behaviour in air (Annex IIA, point 7.2.2, Annex III, point 9.3)

Direct photolysis in air

not studied, no data required

Photochemical oxidative degradation in air (DT50)

6.7 hours derived by the Atkinson method of calculation

Volatilization

from plant surfaces: no data

 

from soil: no data

 

Major Components of the Environmental Residue (Annex IIA, point 7.3)

Relevant to the environment

 

 

Soil: phenmedipham, MHPC

Water: phenmedipham, MHPC

Air: phenmedipham

 

Monitoring data, if available (Annex IIA, point 7.4)

Soil (indicate location and type of study)

no data submitted nor required

Surface water (indicate location and type of study)

no data submitted nor required

Ground water (indicate location and type of study)

no data submitted nor required

Air (indicate location and type of study)

no data submitted nor required

 

Powertwin

An additional study for the formulated product Powertwin (= 200 g/L ethofumesate + 200 g/L phenmedipham) was submitted. This was summarized and evaluated by Notox (report 177282/485435, July, 2007).

 

Column leaching

Formulation was applied at 800 g ethofumesate + 800 g/L phenmedipham. No ethofumesate or phenmedipham was detected in the leachate (< 5 g/L; < 2% of applied). The study is considered acceptable, but will not be used in risk assessment.

 

Metamitron

 

Endpoints Metamitron

For the use in beets in LDS, a tankmix with Goltix SC (= 700 g/L metamitron) is proposed. Therefore, combination effects are assessed for each aspect.

Metamitron is an existing active substance, decided to be listed on Annex I of Guideline 91/414/EEC per 1st September 2009 (directive 2008/125/EEC d.d. 19th December 2008). For the risk assessment data from the final List of Endpoints (dated September 2008) is used.

 

Compartment

Endpoint

Metamitron