HET COLLEGE VOOR DE TOELATING VAN GEWASBESCHERMINGSMIDDELEN EN BIOCIDEN

BIJLAGE II bij het besluit d.d. 5 november 2010 tot uitbreiding van de toelating van het middel Primstar, toelatingnummer 12585 N

RISKMANAGEMENT

Contents Page

1. Identity of the plant protection product 2

2. Physical and chemical properties 4

3. Methods of analysis 11

4. Mammalian toxicology 16

5. Residues 26

6. Environmental fate and behaviour 32

7. Ecotoxicology 51

8. Efficacy 75

9. Conclusion 78

10. Classification and labelling 79

1. Identity of the plant protection product

1.1 Applicant

Dow AgroSciences B.V.

Prins Boudewijnlaan 41
B-2650 EDEGEM

BELGIË

1.2 Identity of the active substance

ISO common name	Florasulam
Name in Dutch	Florasulam
Chemical name	IUPAC: 2′,6′,8-trifluoro-5-methoxy[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonanilide CAS: N-(2,6-difluorophenyl)-8-fluoro-5-methoxy[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonamide
CAS nr	145701-23-1
EEG nr	Not allocated

The active substance florasulam was included on October 1^st 2002 in the Annex I of Directive 91/414/EEC.

Common name	Fluroxypyr-meptyl
Name in Dutch	Fluroxypyr-meptyl
Chemical name	Methylheptyl (4-amino-3,5-dichloro-6-fluoro-2-pyridyloxy)acetate [IUPAC]
CAS no	81406-37-3
EEG no	279-752-9

The active substance fluroxypyr was included on December 1^st 2000 in Annex 1 of Directive 91/414/EEC. Fluroxypyr-meptyl was evaluated as part of the evaluation for inclusion of the active substance in Annex I of Directive 91/414/EEC.

1.3 Identity of the plant protection product

Name

Primstar

Formulation type

Content active substance

Fluroxypyr-meptyl: 144 g/L (14.53%w/w)

(equivalent to 100 g/L (10.1%w/w) fluroxypyr)

Florasulam: 2.5 g/L (0.25%w/w)

The formulation was not part of the assessment of the active substance for inclusion in Annex I of Directive 91/414/EEC.

1.4 Function

Herbicide.

1.5 Uses applied for

Extension of use is applied for application in autumn (for grass seed production, newly sown pastures, existing pastures and lawns and sport fields), increase of the maximum dosage for spring and winter cereals, extension of use in grass manure crops, and for non-professional use on lawns, and other types of privately used grass vegetation and in (private) pastures.

Uses (F) = Field, (G) = Greenhouse	Dose a.s. (g a.s./ha)	Number of applications	Interval between applications	Application time (growth stage and season)
Professional use
Winter cereals (F)	4.5 g florasulam per ha and 180 g fluroxypyr per ha	1	-	3-leaf until flag leaf; BBCH 13-39 March-May
Spring cereals (F)	3.75 g florasulam per ha and 150 g fluroxypyr per ha	1	-	3-leaf until flag leaf; BBCH 13-39 March-May
Grass seed production (F)	2.5 g florasulam per ha and 100 g fluroxypyr per ha	1	-	From 3-leaf (from BBCH 13) March-May or Aug-Nov
Grass manure crops (F)	2.5 g florasulam per ha and 100 g fluroxypyr per ha	1	-	from 3-leaf stage onwards August-Nov
Newly sown pastures (F)	2.5 g florasulam per ha and 100 g fluroxypyr per ha	1	-	From 3-leaf (BBCH 13), March-May or Aug-Nov
Existing pastures (F)	4.8 g florasulam per ha and 190 g fluroxypyr per ha	1	-	March-October
Lawns and sport fields (F)	4.8 g florasulam per ha and 190 g fluroxypyr per ha	1	-	March-October
Non-professional
Newly sown pastures (F)	2.5 g florasulam per ha and 100 g fluroxypyr per ha	1	-	From 3-leaf (BBCH 13), March-May or Aug-Nov
Existing pastures (F)	4.8 g florasulam per ha and 190 g fluroxypyr per ha	1	-	March-October
Lawns and sport fields (to be changed to “other types of privately used grass vegetation”) (F)	4.8 g florasulam per ha and 190 g fluroxypyr per ha	1	-	March-October

1.6 Background to the application

It concerns an extension of the authorization.

1.7 Packaging details

1.7.1 Packaging description

Material:	PET (bottle) or HDPE
Capacity:	1, 2 or 5 L PET (professional use) 40 – 125 mL HDPE (non-professional use)
Type of closure and size of opening:	1 and 2L bottles: 45mm opening 5L bottles: 63mm opening Type of closure: HDPE screw cap with induction seal. 40 – 125 mL container: 20mm, child-resistant
Other information	UN/ADR compliant The bottle for non-professional use uses a closed dosing system, to minimise exposure for the user.

1.7.2 Detailed instructions for safe disposal

See application form and MSDS.

2. Physical and chemical properties

2.1 Active substances: florasulam and fluroxypyr

Identity (florasulam)

Data on the identity and the physical and chemical properties is taken from the List of Endpoints (EFSA Review Report (final), September 2002). Changes and/or additions are taken up in italics.

Active substance (ISO Common Name)	Florasulam
Chemical name (IUPAC)	2', 6', 8-Trifluoro-5-methoxy-s-triazolo [1,5-c] pyrimidine-2-sulfonanilide
Chemical name (CA)	N-(2,6-diflurophenyl)-8-fluoro-5 methoxy (1,2,4) triazolo (1,5-c)pyrimidine-2-sulphonamide
CIPAC No	616
CAS No	145701-23-1
EEC No (EINECS or ELINCS)	not available
FAO Specification (including year of publication)	not available
Minimum purity of the active substance as manufactured (g/kg)	970
Identity of relevant impurities (of toxicological, environmental and/or other significance) in the active substance as manufactured (g/kg)	No impurities are considered to be of toxicological, ecotoxicological or environmental significance.
Molecular formula	C₁₂H₈O₃N₅F₃S
Molecular mass	359.3
Structural formula

Physical-chemical properties

Melting point (state purity)	193.5 to 230.5 °C with decomposition (99.7 %)
Boiling point (state purity)	Not required
Temperature of decomposition	approx. 202.5 °C
Appearance (state purity)	Purified a.s. (99.7%): solid at 25°C. Technical material : also solid.
Relative density (state purity)	1.53 at 22°C (99.7%)
Surface tension	71.5 mN/m at 21 °C (99 mg/l solution) (not surface active)
Vapour pressure (in Pa, state temperature)	1 x 10^-5 Pa at 25°C (99.7%)
Henry’s law constant (in Pa·m³·mol^-1)	3.29 x 10^-5 Pa.m³/mol (pH 5) at 20°C 4.35 x 10^-7 Pa.m³/mol (pH 7) at 20°C 2.94 x 10^-8 Pa.m³/mol (pH 9) at 20°C
Solubility in water (in g/l or mg/l, state temperature)	solubility at 20 °C in : purified water (pH 5.6-5.8) : 0.121 g/L pH 5.0 buffer : 0.084 g/L pH 7.0 buffer : 6.36 g/L pH 9.0 buffer : 94.2 g/L
Solubility in organic solvents (in g/l or mg/l, state temperature)	solubility at 20 °C in : n-heptane* 0.019x10^-3 g/L xylene* 0.227 g/L dichloroethane 3.75 g/L methanol 9.81 g/L n-octanol* 0.184 g/L acetone 123 g/L ethyl acetate 15.9 g/L acetonitrile 72.1 g/L * g/L solution (rest : g/L solvent)
Partition co-efficient (log P_ow) (state pH and temperature)	At 20 °C pH 4.0: log P_ow = 1.00 At 20 °C pH 7.0: log P_ow = -1.22 At 20 °C pH 10.0: log P_ow = -2.06
Hydrolytic stability (DT₅₀) (state pH and temperature)	50 °C: pH 4 and 7: less than 5% degradation after 7 d pH 9: k = 0.378 d^-1; t_1/2 = 2 d (triazole-label) 25°C: pH 5: no degradation observed after 30 d pH 7: no degradation observed after 30 d pH 9: k = 0.00692 d^-1; t_1/2 = 100 d (phenyl-label) k = 0.00706 d^-1; t_1/2 = 98 d (triazole-label)
Dissociation constant	pK_a = 4.54 (determined at 22-23°C)
UV/VIS absorption (max.) (if absorption >290 nm state ε at wavelength)	acidic (pH 0.75): λ 259.8 nm; ε 1.22x10⁴L.mol^-1.cm^-1 basic (pH 13.21): λ 262.4 nm; ε 2.36x10⁴L.mol^-1.cm^-1 methanolic (pH 12.60): λ 204.1 nm; ε 2.74x10⁴L.mol^-1.cm^-1 florasulam has no absorption max. above 290 nm, but γ > 10 L.mol^-1.cm^-1.
Photostability (DT₅₀) (aqueous, sunlight, state pH)	pH 5, 25°C, natural sunlight 40°N, June and May; t_1/2= 88-223 d
Quantum yield of direct photo- transformation in water at λ > 290 nm	F = 0.074
Photochemical oxidative degradation in air	Estimated (based on Atkinson method) half-life of florasulam in the atmosphere (by hydroxyl radical oxidation) 1.82 h (calculated with 1.5 x 10⁶ OH-radicals/cm³ and 12 h day)
Flammability	not highly flammable/ not self-heating substance
Auto-flammability	No self-ignition before the onset of melting at 194 °C florasulam is not classified as a self-heating substance
Oxidising properties	Not oxidising
Explosive properties	Not explosive

Identity (fluroxypyr)

Data on the identity and the physical and chemical properties is taken from the List of Endpoints (Draft Review Report, September 1999). Changes and/or additions are taken up in italics.

The information included in the draft assessment report (DAR) and the Listing of Endpoints is incomplete. However, sufficient data is available for evaluation of the active substance fluroxypyr-meptyl. Whether the dossier requires amendment will be looked into during the upcoming re-evaluation of the active substance (inclusion expires on November 30^th 2010).

Common name (ISO)	Fluroxypyr	Fluroxypyr-meptyl
Chemical name (IUPAC)	4-amino-3,5-dichloro-6-fluoro-2-pyridyloxyacetic acid	Methylheptyl (4-amino-3,5-dichloro-6-fluoro-2-pyridyloxy)acetate
Chemical name (CA)	[(4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy]acetic acid	1-methylheptyl [(4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy]acetate
CIPAC No	431	431.214
CAS No	69377-81-7	81406-37-3
EEC No	Not allocated	279-752-9
FAO SPECIFICATION	Not available	Not available
Minimum purity of the active substance as manufactured (g/kg)	950 (as fluroxypyr-meptyl)	950
Identity of relevant impurities (of toxicological, environmental and/or other significance) in the active substance as manufactured (g/kg)	None	None
Molecular formula	C₇H₅Cl₂FN₂O₃	C₁₅H₂₁Cl₂FN₂O₃
Molecular mass	255	367.3
Structural formula

Physical-chemical properties

	Fluroxypyr	Fluroxypyr-meptyl
Melting point	232 - 233 °C (99.7%)	58.2 - 60 °C (99.4%)
Boiling point	No boiling point observed up to 360 °C	No boiling point observed up to 360 °C
Temperature of decomposition	*	312 - 345 ^oC(99,0%)
Appearance	White crystalline solid	White crystalline solid
Relative density	1.09 (99.7%)	1.322 (99.6%)
Surface tension	Not submitted.	Not determined (solubility in water < 1 mg/kg)
Vapour pressure	3.78 · 10^-9 Pa at 20 °C (purity not stated)	1.3 · 10^-6 Pa at 20 °C (99,8%)
Henry's law constant	1.06 · 10^-8 Pa·m³·mol^-1	5.5 · 10^-3 Pa·m³·mol^-1
Solubility in water	pH 5: 5.7 g/l pH 7: - pH 9: 7.3 g/l	pH 5: 0.0813 mg/l pH 7: 0.109 mg/l pH 9: 0.09 mg/l
Solubility in organic solvents	At 25 °C: - hexane: 0.002 g/l - methanol: 35 g/l - 2-propanol: 9 g/l -dichloromethane: 0.15 g/l -ethylacetate: 11 g/l -toluene: 0.77 g/l - xylene: 0.3 g/l acetone: 9.2 g/l	At 25 °C: - hexane: 45 g/l - methanol: 469 g/l - 2-propanol: 288 g/l; - xylene, toluene, dichloromethane, acetone, ethylacetate: >500 g/l
Partition co-efficient (log P_OW)	2.0 (pH unknown)	4.5 in pure water at 25°C
Hydrolytic stability (DT₅₀)	pH 5: stable pH 7: stable pH 9: stable	pH 5: 9.8 d pH 7: 17.5 d pH 9: 10.2 d
Dissociation constant	pKa (25 °C) = 2.94	no dissociation in water
UV/VIS absorption (max.)	Absorption in the range of 210 to 218 nm, only	No maximum between 290 and 900 nm
Photostability (DT₅₀)	*	63 d in water
Quantum yield of direct photo- transformation in water at λ > 290 nm	Not required	Not required
Photochemical oxidative degradation in air	Half-life : 4.5 h	Half-life: 3.3 h
Flammability	*	Non flammable
Auto-flammability	*	> 400°C
Oxidative properties	*	Not oxidising
Explosive properties	*	Non explosive

* Some information appears to be missing. Because the DAR contains limited information regarding these endpoints, it is not possible to amend the Listing of Endpoints. The missing data is not relevant to this assessment because only the meptyl ester variant of fluroxypyr is formulated.

2.2 Plant protection product: Primstar

The spray concentration of Primstar, according to the proposed use, is within the range of 0.24% to 0.96%.

Section

(Annex point)

Study

Guidelines and GLP

Findings

Evaluation and conclusion

B.2.2.1 (IIIA 2.1)

Appearance: physical state

GLP: yes

Thick liquid

Acceptable

B.2.2.2 (IIIA 2.1)

Appearance: colour

GLP: yes

Munsell colour system

White (N9.5/90.0%R)

Acceptable

B.2.2.3 (IIIA 2.1)

Appearance: odour

GLP: yes

Paint-like odour

Acceptable

B.2.2.4 (IIIA 2.2)

Explosive properties

GLP: yes

EEC A14

Not explosive

Acceptable

B.2.2.5 (IIIA 2.2)

Oxidising properties

Theoretical assessment

Not oxidising, based on the classification of the individual components of the formulation.

Acceptable

B.2.2.6 (IIIA 2.3)

Flammability

Not applicable for liquids.

B.2.2.7 (IIIA 2.3)

Auto-flammability

GLP: yes

EEC A15

> 400 ^oC

Acceptable

B.2.2.8 (IIIA 2.3)

Flash point

GLP: yes

EEC A9

61 ^oC

Acceptable

B.2.2.9 (IIIA 2.4)

Acidity / alkalinity

GLP: yes

CIPAC MT31.2.3

Free acidity: 0.03% H₂SO₄

Acceptable

B.2.2.10 (IIIA 2.4)

GLP: yes

CIPAC MT75.2

1%w/v solution: pH = 5.8

Pure water pH: 6.73

Determined before and after storage stability tests.

Acceptable

GLP: yes

CIPAC MT75.2, CIPAC MT75.1

1% dispersion: 6.59

Neat : 5.80

Acceptable

B.2.2.11 (IIIA 2.5)

Surface tension

GLP: yes

EEC A5

0.15% v/v: 37.5 mN/m at 20 ^oC

2.57%v/v: 33.0 mN/m at 20 ^oC

Undiluted 34.5mN/m at 25 ^oC

Acceptable; R65 not triggered.

B.2.2.12 (IIIA 2.5)

Viscosity

GLP: yes

EU-AM-93-2

shear rate

(s^-1)

viscosity at 20°C

(mPa.s)

viscosity at 40°C

(mPa.s)

424

85.8

219

Acceptable

B.2.2.13 (IIIA 2.6)

Relative density

GLP: yes

EEC A3

D₄²² = 0.992

Acceptable

B.2.2.14

(IIIA 2.6)

Bulk (tap) density

Not applicable

B.2.2.15 (IIIA 2.7)

Storage stability

GLP: yes

CIPAC MT39.1

Stable for 6 months at 40 ^oC

Stable for 7 days at 0 ^oC

Acceptable

B.2.2.16 (IIIA 2.7)

Shelf life

GLP

Stable for 2 years at 20 ^oC in PET and HDPE/F

Properties determined before and after storage: packaging stability, appearance, a.i. content, pH (1% and neat), foam persistence, pourability, wet sieve residue, emulsion characteristics.

Study in HDPE commissioned.

Acceptable

A new type of packaging is proposed for non-professional use for which no shelf-life study is available. As both PET and fluorinated HDPE proved suitable, it is considered acceptable that a shelf-life study in HDPE is provided within 3 years.

B.2.2.17

(IIIA 2.8)

Wettability

Not applicable

B.2.2.18 (IIIA 2.8)

Persistent foaming

GLP: yes

CIPAC MT47.2

2.57%v/v emulsion:

4 ml foam after 1 minute

3ml foam after 12 minutes

Also determined after storage stability tests.

Acceptable

GLP: yes

CIPAC MT47.2

5.14%v/v in CIPAC C water: 6 mL

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

GLP: yes

CIPAC MT59.3

0.001%w/w residue on a 75 μm sieve.

Also determined after storage stability tests.

Acceptable

GLP: yes

CIPAC MT59.3

0.01%w/w residue on a 75 μm sieve.

Acceptable

B.2.2.24

(IIIA 2.8)

Particle size distribution

GLP: yes

EU-AM-93-3

D(v,0.5): 0.64

D(v,0.9): 1.10

Acceptable; not required.

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

GLP: yes

CIPAC MT180

5% in CIPAC B and C water.

The product is and forms a stable emulsion under conditions of the test.

The test should be performed at the highest and lowest proposed dose in CIPAC A and D water (0.24% and 0.96%).

An additional test was performed (see below)

GLP

CIPAC MT180

Tested in CIPAC A and D water at concentrations 0.15% and 2.57%.

No sediment or oil was observed in any of the samples.

Acceptable

B.2.2.29

(IIIA 2.8)

Flowability

Not applicable

B.2.2.30

(IIIA 2.8)

Pourability (rinsibility)

GLP: yes

CIPAC MT148

Residue: 3.8%

Rinsed residue: 0.31%

Also determined after storage stability tests.

Acceptable

GLP: yes

CIPAC MT148

Residue: 4.0%

Rinsed residue: 0.118%

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

Not applicable

2.9.2

Chemical compatibility with other products

Not applicable

Conclusion

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

The product Primstar has a shelf-life of 2 years in PET and fluorinated HDPE (HDPE/F).

Provisionally, the non-professional packaging (HDPE) is approved, awaiting a shelf-life study to be submitted within 3 years.

2.3 Data requirements

None.

3. Methods of analysis

3.1. Analytical methods in technical material and plant protection product

For fluroxypyr and florasulam no List of Endpoints is available for the section analytical methods. Therefore, information from volume 3 of the DAR and studies provided by the applicant are used.

Technical as (principle of method)

FLuroxypyr

HPLC with UV detection

GC FID

Florasulam

HPLC with UV detection at 260 nm for determination of florasulam.

Impurities in technical as (principle of method)

FLuroxypyr

HPLC with UV detection

GC FID

Florasulam

HPLC with UV detection at 260 nm.

GC with FID for the determination of the process solvents.

Preparation (principle of method)

HPLC method with UV detection at 260 nm for the determination of fluroxypyr-meptyl and florasulam.

Conclusion

The analytical methods regarding the technical active ingredients have been assessed in the DAR and are considered acceptable. The analytical method for the determination of the active substances in the formulation was provided by the applicant and is fully validated.

3.2 Residue analytical methods

Food/feed of plant origin (principle of method and LOQ for methods for monitoring purposes)	Fluroxypyr: Caustic methanol extraction followed by acid(and base)/MBTE partitioning. Determination with GCMS. LOQ = 0.05 mg/kg (grain) and LOQ = 0.20 mg/kg (straw/grass) ILV: not submitted Various other methods are available, but none comply with guideline SANCO/825/00. LC-MS/MS method for the determination of fluroxypyr-meptyl as acid (fluroxypyr) equivalent in wet, dry, oily and acidic crops. LOQ = 0.01 mg/kg _{Confirmatory method: not required for LC-MS/MS} ILV: available Florasulam ERC 95.6 : HPLC with UV detection at 260 nm. LOQ for wheat grain : 0.01 mg/kg, LOQ for wheat straw and whole plant : 0.05 mg/kg. ILV performed (wheat, barley). GRM 99.17: LC/MS/MS LOQ for maize cob: 0.01 mg/kg, _{LOQ for maize straw and whole plant : 0.05 mg/kg.}
Food/feed of animal origin (principle of method and LOQ for methods for monitoring purposes)	Fluroxypyr: Method GRM 96.03: extraction with diethyl ether and back extraction into diluted sodium hydroxide. Then SPE (C18) en after elution with ACN/water extraction into chlorobutane. For fat an additional clean-up is used. Derivatization in a sulphuric acid/propanol mixture and determination with GCMS. LOQ = 0.01 mg/kg for muscle, kidney, liver, fat and milk. ILV is performed. LC-MS/MS method for the determination of fluroxypyr-meptyl as acid (fluroxypyr) equivalent in bovine products. LOQ = 0.01 mg/kg _{Confirmatory method: not required for LC-MS/MS} ILV: available Florasulam No method required.
Soil (principle of method and LOQ)	Fluroxypyr-meptyl: Acetone extraction and after clean up determination with GCMS. LOQ = 0.01 mg/kg. Fluroxypyr, 3,5-dichloropyridinol, 2-methoxypyridine: Acidic acetone extraction followed by different clean-up steps. Determination with GCMS. LOQ = 0.01 mg/kg Florasulam For determination of extractable residues : -ESP LC-MS/MS – LOQ : 0.05 mg/kg for florasulam and 5-hydroxy metabolite. -ESP LC-MS – LOQ : 0.05 mg/kg for both compounds. -GC-MSD – LOQ : 0.05 mg/kg for florasulam residues. For determination of bioavailable residues : -ESP LC-MS/MS – LOQ : 0.05 mg/kg for florasulam and 5-hydroxy metabolite. _{-A Magnetic Particle-based Immunoassay test kit for DE-570 determination - LOQ : 0.05}_m_{g/kg for florasulam residues.}
Water (principle of method and LOQ)	Fluroxypyr : 1) Method ERC83.11 (GC-ECD) for determination of fluroxypyr-meptyl in drinking water. LOQ = 0.05 mg/L 2) Method ERC83.12 (GC-ECD) for determination of fluroxypyr (acid) in drinking water. LOQ = 0.05 mg/L 3) Method ERC92.17 for determination of the metabolites 3,5-dichloropyridinol (GC-MS, 1 mass fragment) and 2-methoxypyridine (GC-ECD) LOQ = 0.05 mg/L GC-MS Method GRM00.21 for determination of fluroxypyr, fluroxypyr-meptyl, 4-Amino-3,5-dichloro-6-fluoro-2-pyridinol (metabolite II) and 4-Amino-3,5-dichloro-6-fluoro-methoxypyridine (metabolite III) in surface water. LOQ = 5 µg/l Confirmatory method : 3 mass fragments LC-MS/MS method for the determination of fluroxypyr-meptyl, fluroxypyr, fluroxypyr-DCP and fluroxypyr-MP in drinking, ground and surface water. LOQ = 0.05 µg/L Confirmatory: not required for LC-MS/MS Florasulam Drinking water : -HPLC with UV detection at 260 nm for determination of florasulam and 5-hydroxy-metabolite. LOQ of 0.05 mg/L for florasulam and 0.10 mg/L for the metabolite. - HPLC with UV detection at 260 nm involving derivatisation, determining florasulam residues – LOQ : 0.05 mg/L. Surface water : HPLC with UV detection at 260 nm for determination of florasulam and 5-hydroxy-metabolite. LOQ of 0.10 mg/L for florasulam and 0.20 mg/L for the metabolite. Drinking water, surface water and ground water : A Magnetic Particle-based immunoassay test kit for determination of florasulam residues – LOQ : 0.1 mg/L. Method GRM 07.23 using LC-MS/MS for determination of florasulam and its 5-hydroxy metabolite in surface water. LOQ = 0.05 µg/L Confirmatory method: not required for LC-MS/MS
Air (principle of method and LOQ)	Fluroxypyr-meptyl: TENAX sampling, elution with ethyl acetate and determination with GC-ECD. LOQ = 1.7 µg/m³ Florasulam HPLC-UV method involving derivatisation of florasulam – LOQ : 1.5 µg/m³.
Body fluids and tissues (principle of method and LOQ)	Not required; florasulam and fluroxypyr are not classified as (very) toxic.

The residue analytical methods for food/feed of plant material require validation for dry matrices (cereals). For florasulam sufficiently validated methods are available. For fluroxypyr, however, insufficient information is included in the DAR.

Definition of the residue and proposed MRL’s for fluroxypyr-meptyl
Matrix	Definition of the residue for monitoring	MRL
Food/feed of plant origin	Fluroxypyr-meptyl and fluroxypyr expressed as fluroxypyr	According to the Dutch pesticide law: Cereals: 0.1 mg/kg
Food/feed of animal origin	Fluroxypyr	According to the Dutch pesticide law: Kidneys: 0.5 mg/kg Other: 0.05 mg/kg
		Required LOQ
Soil	Fluroxypyr-meptyl, fluroxypyr, metabolite II and III *	0.05 mg/kg (default)
Drinking water	Fluroxypyr-meptyl, fluroxypyr,	0.1 µg/L (Dutch drinking water
Surface water	Fluroxypyr-meptyl, fluroxypyr, metabolite II and III *	0.1 µg/L
Air	Fluroxypyr-meptyl	0.42 mg/m³ (derived from the AOEL 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.

* From the section environmental fate: 4-Amino-3,5-dichloro-6-fluoro-2-pyridinol (metabolite II); 4-Amino-3,5-dichloro-6-fluoro-methoxypyridine (metabolite III);

Definition of the residue and proposed MRL’s for florasulam
Matrix	Definition of the residue for monitoring	MRL
Food/feed of plant origin	Florasulam	According to the Dutch pesticide law: Cereals (other): 0.01 mg/kg
Food/feed of animal origin	Florasulam. Residues are expected to be very low and therefore no MRL was proposed.	Not applicable.
		Required LOQ
Soil	Florasulam and its 5-hydroxy metabolite	0.05 mg/kg (default
Drinking water	Florasulam and its 5-hydroxy metabolite	0.1 µg/L (Dutch drinking water guideline)
Surface water	Florasulam and its 5-hydroxy metabolite	0.1 µg/L
Air	Florasulam	0.015 mg/m³ (derived from the AOEL 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 abovementioned List of Endpoints, are suitable for monitoring of the MRL’s of florasulam, but not for fluroxypyr. The DAR does not include methodology validated according to guideline SANCO/825/00.

A new residue analytical method using LC-MS/MS was provided, validated for all crop types using wheat (hay, grain), whole olives, grapefruit, onion and rape seed. In addition, bovine milk (skim milk, whole milk, cream) was validated. The method showed acceptable accuracy, specificity, repeatability and linearity.

Residue analytical methodology is required to be suitable for detection of residues in surface water at a LOQ of 0.1 µg/L (HTB 1.0 requirement). The residue analytical method, included in the EU dossier, for determination of the 5-hydroxy metabolite of florasulam in surface water is insufficiently validated to comply with this requirement. The applicant provided an additional method, method GRM 07.23, validated for determination of florasulam and its 5-hydroxy metabolite in surface water. The method showed acceptable accuracy, specificity, repeatability and linearity.

For surface water a residue analytical method is available for fluroxypyr-meptyl and the metabolites included in the definition of the residue at a LOQ of 5 µg/L. The LOQ of the method is insufficiently low; a LOQ of 0.1 µg/L is required. As well as for florasulam, the applicant provided additional validation, comprising validation for a method using LC-MS/MS, for determination of fluroxypyr-meptyl, fluroxypyr and major metabolites (fluroxypyr-DCP and –MP) in surface, drinking and ground water with a LOQ of 0.05 µg/L. The method showed acceptable accuracy, specificity, repeatability and linearity.

The residue analytical methods available for soil, water and air are acceptable and suitable for monitoring of residues in the environment. Additionally, residue analytical methods for crops are suitable for monitoring of MRL’s.

Conclusion

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

3.3 Data requirements

None.

3.4 Physico-chemical classification and labelling

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

Symbol(s):

Indication(s) of danger: -

Risk phrase(s)

Proposal for the classification of fluroxypyr-meptyl (symbols and R phrases)
(EU classification)

Symbol(s):

Indication(s) of danger: -

Risk phrase(s)

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

Professional use

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(s):	-	Indication(s) of danger:	-
R-phrases
S-phrases	S21	When using do not smoke.
Plant protection products phrase: DPD-phrase	-	-
Child-resistant fastening obligatory?			Not applicable
Tactile warning of danger obligatory?			Not applicable

Explanation:
Hazard symbol:	-
Risk phrases:	-
Safety phrases:	-
Other:	-

Non professional-use

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(s):	-	Indication(s) of danger:	-
R-phrases
S-phrases	S21	When using do not smoke.
Plant protection products phrase: DPD-phrase	-	-
Child-resistant fastening obligatory?			No
Tactile warning of danger obligatory?			No

Explanation:
Hazard symbol:	-
Risk phrases:	-
Safety phrases:	-
Other:	-

The product Primstar has a shelf-life of 2 years in PET and fluorinated HDPE (HDPE/F).

Provisionally, the non-professional packaging (HDPE) is approved, awaiting a shelf-life study to be submitted within 3 years.

New packaging for non-professional use includes packaging of 125 mL and smaller. In this case, this does not influence the labelling proposal.

4. Mammalian toxicology

List of Endpoints

Florasulam

Florasulam is a new active substance, included in Annex I of 91/414/EEC. The final List of Endpoints presented below is copied from the final review report on florasulam

(SANCO/1406/2001-final, 18 September 2002). Where relevant, some additional remarks/information are given in italics.

Absorption, distribution, excretion and metabolism in mammals
Rate and extent of absorption:	High bioavailability (91%) within 24 h
Distribution:	Uniformly distributed; highest residues in skin and carcass at 168 h
Potential for accumulation:	No evidence for accumulation
Rate and extent of excretion:	Rapid and extensive (approx 91%) within 24 h, mainly via urine (85%) within 24 h
Toxicological significant compounds (animals, plants and environment)	Parent compound and metabolites
Metabolism in animals	Limited; >70% of dose excreted as parent compound; hydroxylation of phenyl moiety and subsequent conjugation to a limited extent

Acute toxicity
Rat LD₅₀ oral	>6000 mg/kg bw
Rat LD₅₀ dermal	>2000 mg/kg bw (rabbit)
Rat LC₅₀ inhalation	>5 mg/l (4 hr; nose only)
Skin irritation	Non irritant
Eye irritation	Non irritant
Skin sensitisation (test method used and result)	Non sensitizer (Buehler and M&K tests)

Short term toxicity
Target / critical effect	Anemia, hepatotoxicity, renal hypertrophy epithelial cells, collecting ducts, adrenal vacuolation (dog)
Lowest relevant oral NOAEL / NOEL	1 y & 90-d dog (oral feed); 5 mg/kg bw/d
Lowest relevant dermal NOAEL / NOEL	28-d rat, systemic toxicity >1000 mg/kg bw/d
Lowest relevant inhalation NOAEL / NOEL	No data – not required

Genotoxicity	No genotoxic potential ¹
¹The genotoxic potential of fluroxypyr was investigated in three in vitro studies (Ames test, mammalian cell gene mutation test in CHO cells (HPRT), chromosome aberration study in rat lymphocytes) and in one in vivo study (mouse micronucleus bone marrow). Long term toxicity and carcinogenicity
Target/critical effect	Kidney collecting duct hypertrophy, papillary mineralisation, necrosis and inflammation (rat and/or mice)
Lowest relevant NOAEL / NOEL	2 yr rat (oral feed): 10 mg/kg bw/d
Carcinogenicity	No carcinogenic potential

Reproductive toxicity ²
Reproduction target / critical effect	No reproductive toxicity at parental toxic doses
Lowest relevant reproductive NOAEL / NOEL	NOAEL >500 mg/kg bw/d
Developmental target / critical effect	No developmental toxicity or teratogenicity
Lowest relevant developmental NOAEL / NOEL	NOAEL rabbit: 500 mg/kg bw/d

² The parental NOAEL in the 2-generation study is 100 mg/kg bw/d. Critical effects: increased kidney weight, necrosis and/or inflammation renal papilla, hemorrhagic cast in urinary bladder.

The maternal NOAEL in the teratogenicity study with rats is 250 mg/kg bw/d. Critical effects: decreased food consumption and body weight, increased kidney weight.

The maternal NOAEL in the teratogenicity study with rabbits is ≥500 mg/kg bw/d (= highest dose tested).

Delayed neurotoxicity

No evidence of neurotoxicity from acute and long-term neurotoxicity studies

Other toxicological studies

Renal cells affected are probably Type A intercalated cells, involved in acid-base regulation

Medical data

Limited; new active substance, no detrimental effects on health in manufacturing personnel

Summary	Value	Study	Safety factor
ADI:	0.05 mg/kg/bw/d	1 year dog study	100
AOEL systemic:	0.05 mg/kg/bw/d	90 day dog study	100
ArfD (acute reference dose):	not allocated – not necessary

Dermal absorption

12% within 24 h, in vivo rat study

Fluroxypyr

Fluroxypyr 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 fluroxypyr (6848/VI/98 – final, d.d. 15 December 1999). Where relevant, some additional remarks/information are given in italics. In the List of Endpoints fluroxypyr (acid) and fluroxypyr-meptyl (MHE) are mentioned.

Absorption, distribution, excretion and metabolism in mammals
Rate and extent of absorption:	~100 %; < 0.5 d; oral [acid, MHE]
Distribution:	Highest residues: Gastro-intestinal-tract and kidneys [acid, MHE]
Potential for accumulation:	No indication of accumulation after repeated administration [MHE]
Rate and extent of excretion:	Efficiently eliminated within 2 days: urine (91 - 94 %); faeces (4 - 6 %) [acid, MHE]
Toxicologically significant compounds:	MHE; rapidly and completely hydrolysed to fluroxypyr; sodium salt; unchanged excreted

Acute toxicity
Rat LD₅₀ oral:	> 2000 mg/kg bw [MHE]
Rat LD₅₀ dermal:	> 2000 mg/kg bw [MHE]
Rat LC₅₀ inhalation:	>1.0 mg/l (highest attainable concentration) [MHE]
Skin irritation:	Not irritating [MHE]
Eye irritation:	Not irritating [MHE]
Sensitization:	Not sensitising [MHE] ¹
¹ results from an M&K and buehler test
Short term toxicity
Target / critical effect:	Kidney [acid, MHE]
Lowest relevant NOAEL:	80 mg/kg bw/d; 13 weeks; oral; mouse and rat [acid] NOEL 300 mg/kg bw/d; dermal [MHE]

Genotoxicity	No evidence of genotoxicity [acid] ²
² The genotoxic potential of fluroxypyr was investigated in five in vitro studies (Ames test, mammalian cell gene mutation test in mouse lymphoma cells, mammalian cell gene mutation test in CHO cells, chromosome aberration study in CHO cells, UDS test) and in one in vivo study (chromosome aberration study in Chinese hamster bone marrow).
Long term toxicity and carcinogenicity
Target / critical effect:	Kidney [acid]
Lowest relevant NOAEL:	80 mg/kg bw/d; 2 y; oral; rat (Wistar) [acid]
Carcinogenicity:	No evidence of carcinogenicity [acid]

Reproductive toxicity
Reproduction:	No conclusive adverse effects [acid] NOAEL 150 mg/kg bw/d for reproductive and maternal toxicity [acid]
Developmental toxicity:	No evidence of teratogenicity in rats or rabbits [acid] ³
³ NOAEL 100 mg/kg bw (rabbit), 250 mg/kg bw (rat)
Delayed neurotoxicity	Not a primary neurotoxin, delayed neurotoxicity studies are not required [acid, MHE]

Other toxicological studies	None of toxicological relevance

Medical data	No reports of adverse effects in humans [acid, MHE]
Summary
ADI:	0.8 mg/kg bw; SF=100; 2 y rat [acid]
AOEL:	0.8 mg/kg bw/d (oral); SF=100; 2 y rat [acid]
ARfD	Not allocated – not necessary

Dermal absorption	Default value of 10% dermal absorption based on the physical chemical properties of this active ingredient [acid, MHE]

Data requirements active substances

Florasulam and fluroxypyr: None.

4.1 Toxicity of the formulated product (IIIA 7.1)

The formulation Primstar does not need to be classified on the basis of its acute oral (LD₅₀ rat >2000 mg/kg bw), dermal (LD₅₀ rat >5000 mg/kg bw), and inhalation toxicology (no study performed; not required).

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

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

Primstar does not have sensitising properties in a Maximisation test, but is positive in a LLNA 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)

Florasulam

The dermal absorption value in the List of Endpoints is based on an in vivo rat study. Rats were exposed for 24 hours to florasulam formulated as Primus SC. The concentrate (530 μg/cm²) and a spray dilution (0.9 μg/cm²) were tested. The absorbed dose was low, 0.2% for the concentrate and 0.4% for the dilution, respectively. There was a relatively large dermal depot and it could not be excluded that the amount in the skin may become systemically available. The dermal depot was therefore regarded as potentially absorbed. This resulted in an average of 12% absorbed, for the concentrate and the spray dilution. This evaluation is however very worst-case, since the data at the 72 h kill show that the amount which was absorbed was not increased compared to the 24 h kill and that the amount in the skin was firmly bound.

The composition of the SE formulation Primstar is comparable to the composition of the SC formulation Primus, except for the amount of organic solvent. The organic solvent in Primstar may increase dermal absorption. The 12% dermal absorption in the List of Endpoints is however sufficiently worst-case for the current risk assessment (because the data actually show that dermal absorption is around 0.5% for the concentrate and spray dilution).

Fluroxypyr

Dermal absorption of fluroxypyr, formulated as Primstar, is 10% (default value) based on physical/chemical properties (see List of Endpoints).

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

The formulation Primstar is applied by mechanical downward spraying by the professional operator and by manual downward spraying by the non-professional. The formulation is applied once a year with a maximum dose of 1.9 L formulation / ha. Therefore, a semi-chronic exposure duration is applicable for the operator (including contract workers).

Calculation of the AOEL

Florasulam

Since florasulam is included in Annex I of 91/414/EEC, the semi-chronic EU-AOEL of 0.05 mg/kg bw/day (= 3.5 mg/day for a 70 kg operator and 3.15 mg/day for a 63 kg non-professional user), based on the 90-day dog study, is applied (See List of Endpoints).

Fluroxypyr

Since fluroxypyr is included in Annex I of 91/414/EEC, the semi-chronic EU-AOEL of 0.8 mg/kg bw/day (= 56 mg/day for a 70 kg operator and 50.4 mg/day for a 63 kg non-professional user), based on the 2-year rat study, is applied (See List of Endpoints).

4.4.1 Operator exposure/risk

Florasulam

Exposure to florasulam during mixing and loading and application of Primstar 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 for the professional operator and in Table T.2 with the systemic AEL for the non-professional. 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 florasulam and risk assessment for the use of Primstar by the professional operator

	Route	Estimated internal exposure ^a(mg /day)	Systemic AOEL (mg/day)	Risk-index ^b
Mechanical downward spraying on winter cereals, spring cereals, grass seed, grass manure crops, newly sown pastures, pasture, lawns and sport fields
Mixing/ Loading	Respiratory	<0.01	3.5	<0.01
Mixing/ Loading	Dermal	0.11	3.5	0.03
Application	Respiratory	<0.01	3.5	<0.01
Application	Dermal	0.02	3.5	<0.01
	Total	0.13	3.5	0.04

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

· biological availability via the dermal route: 12% (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.

Table T.2 Internal operator exposure to florasulam and risk assessment for the use of Primstar by the non-professional

	Route	Estimated internal exposure ^a(mg /day)	Systemic AEL (mg/day)	Risk-index ^b
Manual downward spraying on pasture and lawns
Mixing/ Loading	Respiratory	<0.01	3.15	<0.01
Mixing/ Loading	Dermal	0.01	3.15	<0.01
Application	Respiratory	<0.01	3.15	<0.01
Application	Dermal	0.092	3.15	0.03
	Total	0.1	3.15	0.03

a External exposure was estimated by EUROPOEM (mixing/loading; dermal), Dutch model (mixing/loading; respiratory) and UK-POEM (application). Internal exposure was calculated with:

· biological availability via the dermal route: 12% (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 AEL.

Fluroxypyr

Exposure to fluroxypyr during mixing and loading and application of Primstar is estimated with models. The exposure is estimated for the unprotected operator. In Table T.3 the estimated internal exposure is compared with the systemic AOEL for the professional operator and in Table T.4 with the systemic AEL for the non-professional. 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.3 Internal operator exposure to fluroxypyr and risk assessment for the use of Primstar by the professional operator

	Route	Estimated internal exposure ^a(mg /day)	Systemic AOEL (mg/day)	Risk-index ^b
Mechanical downward spraying on winter cereals, spring cereals, grass seed, grass manure crops, newly sown pastures, pasture, lawns and sport fields
Mixing/ Loading	Respiratory	0.01	56	<0.01
Mixing/ Loading	Dermal	3.80	56	0.07
Application	Respiratory	0.02	56	<0.01
Application	Dermal	0.57	56	0.01
	Total	4.4	56	0.08

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

· biological availability via the dermal route: 10% (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.

Table T.4 Internal operator exposure to fluroxypyr and risk assessment for the use of Primstar by the non-professional

	Route	Estimated internal exposure ^a(mg /day)	Systemic AEL (mg/day)	Risk-index ^b
Manual downward spraying on pasture and lawns
Mixing/ Loading	Respiratory	<0.01	50.4	<0.01
Mixing/ Loading	Dermal	0.25	50.4	<0.01
Application	Respiratory	0.02	50.4	<0.01
Application	Dermal	3.07	50.4	0.06
	Total	3.3	50.4	0.07

a External exposure was estimated by EUROPOEM (mixing/loading; dermal), Dutch model (mixing/loading; respiratory) and UK-POEM (application). Internal exposure was calculated with:

· biological availability via the dermal route: 10% (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 AEL.

4.4.2 Bystander exposure/risk

Florasulam and fluroxypyr

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

4.4.3 Worker exposure/risk

Florasulam and fluroxypyr

Shortly after application it is not necessary to perform any re-entry activities during which intensive contact with the treated crop will occur.

4.4.4 Re-entry

Florasulam

The possible re-entry activities are playing children and sporting. In the table below the estimated internal exposure as a result of dermal exposure is compared with the systemic AEL. There is no model available to estimate respiratory exposure, but it is expected that this will be negligible.

Table T.5 Internal re-entry exposure to florasulam and risk assessment after application of Primstar

	Route	Estimated internal exposure ^a(mg /day)	Systemic AEL (mg/day)	Risk-index ^b
Re-entry sports fields and lawns
Child (10.5 month)	Dermal	0.003	0.44 ^C	0.01
Child (4 year)	Dermal	0.004	0.75 ^C	0.01
Adult (sporting)	Dermal	0.017	3.15 ^C	0.01

a External exposure was estimated by the “RIVM re-entry model” which will become part of the ConsExpo model. Internal exposure was calculated with:

· biological availability via the dermal route: 12% (see 4.2)

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

c From the systemic AOEL of 0.05 mg kg/bw day a specific AEL is derived for children of 10.5 month (8.7 kg bw) and 4 year (15 kg bw) and for adults (63 kg bw).

Fluroxypyr

Table T.6 Internal re-entry exposure to fluroxypyr and risk assessment after application of Primstar

	Route	Estimated internal exposure ^a(mg /day)	Systemic AEL (mg/day)	Risk-index ^b
Re-entry sports fields and lawns
Child (10.5 month)	Dermal	0.10	7.0 ^C	0.01
Child (4 year)	Dermal	0.14	12 ^C	0.01
Adult (sporting)	Dermal	0.57	50 ^C	0.01

a External exposure was estimated by the “RIVM re-entry model” which will become part of the ConsExpo model. Internal exposure was calculated with:

· biological availability via the dermal route: 10% (see 4.2)

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

c From the systemic AOEL of 0.8 mg kg/bw day a specific AEL is derived for children of 10.5 month (8.7 kg bw) and 4 year (15 kg bw) and for adults (63 kg bw).

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 florasulam and fluroxypyr as a result of the application of Primstar in winter cereals, spring cereals, grass seed, grass manure crops, newly sown pastures, pasture, lawns and sport fields.

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 florasulam and fluroxypyr during application of Primstar in winter cereals, spring cereals, grass seed, grass manure crops, newly sown pastures, pasture, lawns and sport fields.

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 winter cereals, spring cereals, grass seed, grass manure crops, newly sown pastures, pasture, lawns and sport fields due to exposure to florasulam and fluroxypyr after application of Primstar.

4.5 Appropriate mammalian toxicology and operator exposure endpoints relating to
the product and approved uses

See Lists of Endpoints.

4.6 Data requirements

None.

4.7 Combination toxicology

The formulation Primstar 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 will lead to a different toxicological profile than the profile that is based on the individual substances.

The toxicological profile of florasulam and fluroxypyr is comparable (effects on kidney). An additive effect can be expected as a result of combined exposure to these substances.

The estimated exposure to florasulam and fluroxypyr is well below the AOEL and AEL, also when the risk-indices are added up. Therefore, it is not expected that a combined exposure to the two active substances in Primstar will result in an additional risk above the estimated risks based on the individual substances, when used according to the proposed use.

4.8 Mammalian toxicology classification and labelling

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

Florasulam

Symbol:

Indication of danger: -

Risk phrases

Fluroxypyr

Symbol:

Indication of danger: -

Risk phrases

Proposal for the classification and labelling of the formulation concerning health for professional use

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 labeling 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	R36/38	Irritating to eyes and skin.
	R43	May cause sensitisation by skin contact.
	R67	Vapours may cause drowsiness and dizziness.
S phrases	S36/37	Wear suitable protective clothing and gloves.
	S46	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?			Not applicable
Tactile warning of danger obligatory?			Not applicable

Explanation:
Hazard symbol:	-
Risk phrases:	Primstar is positive in an LLNA test for skin sensitisation and needs to be classified as R43 ‘May cause sensitisation by skin contact’.
Safety phrases:	-
Other:	-

Proposal for the classification and labelling of the formulation concerning health for non-professional use

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	R36/38	Irritating to eyes and skin.
	R43	May cause sensitisation by skin contact.
	R67	Vapours may cause drowsiness and dizziness.
S phrases	S2	Keep out of the reach of children.
	S36/37	Wear suitable protective clothing and gloves.
	S46	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?			Not applicable
Tactile warning of danger obligatory?			Not applicable

Explanation:
Hazard symbol:	-
Risk phrases:	Primstar is positive in an LLNA test for skin sensitisation and needs to be classified as R43 ‘May cause sensitisation by skin contact’.
Safety phrases:	S2 is assigned to formulations intended for non professional use in combination with the assigned risk-phrases.
Other:	-

5. Residues

List of Endpoints (florasulam)

The List of Endpoints with regard to residues is taken from the Conclusions of the Working Group Plant Protection Products, d.d. October 3^rd-4^th 2000. Information and questions answered later on in the evaluation process has been taken into account.

Metabolism in plants
Plant groups covered	Cereals (winter wheat)
Rotational crops	Cereals (spring wheat), pulses and oilseeds (sunflower), Leafy vegetables (cabbage), root vegetables (carrot)
Plant residue definition for monitoring	Parent compound
Plant residue definition for risk assessment	Parent compound
Conversion factor (monitoring to risk assessment)	-

Metabolism in livestock
Animals covered	Lactating goats and laying hens.
Animal residue definition for monitoring	Parent compound
Animal residue definition for risk assessment	Parent compound
Conversion factor (monitoring to risk assessment)	-
Metabolism in rat and ruminant similar (yes/no)	Yes (although 2 metabolites are not present in rat metabolism, but at a very low concentration
Fat soluble residue: (yes/no)	No

Residues in succeeding crops

The uptake of florasulam in edible plant parts of leafy vegetables, root vegetables, oil seed crop and cereals installed as succeeding crops is not sufficient to reach measurable levels in monitoring

Stability of residues
	No loss of florasulam residues during frozen storage over 683 days

Residues from livestock feeding studies

Intakes by livestock < 0.1 mg/kg diet/day:	Ruminant: yes	Poultry: yes	Pig: yes
Muscle	-	-	-
Liver	-	-	-
Kidney	-	-	-
Fat	-	-	-
Milk	-	-	-
Eggs	-	-	-

List of Endpoints (Fluroxypyr)

Primstar contains fluroxypyr-mepthyl. The trials in this evaluation are performed with fluroxypyr. Fluroxypyr-mepthyl is directly metabolised to fluroxypyr in plants and animals. The concentration of 144 g/L fluroxypyr-mepthyl is comparable to 100 g/L fluroxypyr.

The List of Endpoints on residues is taken form the ‘Full report on Fluroxypyr d.d. April 9^th 1997.

Metabolism in plants:

plant groups covered:

Cereals (spring wheat), Broad-leaved weeds (chickweed, bedstraw)

rotational crops:

Wheat, broad beans (30 days crop rotation)

soybeans (120 days crop rotation)

plant residue definition for monitoring:

fluroxypyr including ester expressed as fluroxypyr

plant residue definition for risk assessment:

same as above

conversion factor (monitoring to risk assessment):

not applicable

Metabolism in livestock:

animals covered:

laying hens and lactating goats

metabolism rat versus ruminants the same:

similar

animal residue definition for monitoring:

fluroxypyr (acid) only

animal residue definition for risk assessment:

fluroxypyr (acid) only

conversion factor (monitoring to risk assessment):

not applicable

log Po/w (at PH):

4,5 +/- 0,3 at pH 7 (1-methylheptyl ester)

1,74 (acid)

fat soluble residue:

ester: yes, acid: no

Methods of analysis:

plant products:

GC-ECD or GC-MS

general LOD for monitoring:

0.05 mg/kg for all commodities of plant origin, except hops and tea

0.1 mg/kg for hops, tea

animal products:

GC-ECD

general LOD for monitoring:

0.05 mg/kg for poultry (whole product basis)

Stability of residues

Stable in wheat grain, forage and straw under freezer conditions over the period of 24 months

Residues from livestock

feeding studies:

intakes by livestock 0.1 mg/kg diet:

ruminant: yes

poultry: no

pig: yes

Muscle:

0.05* mg/kg poultry

Liver:

0.05* mg/kg poultry

Kidney:

0.05* mg/kg poultry

Fat:

Milk:

Eggs:

0.05* mg/kg poultry

Residues in succeeding crops:

1 x 0.6 kg a.s./ha (ca. double rate)

lettuce, turnips, broad beans, soya beans, wheat

30, 120, 365 DAT: <LOD

sugar beet (dry matter basis)

547 DAT: 0.018 (roots), 0.012 (leaves) mg/kg

no residues above LOD expected

Processing factors

No study was conducted based on the low residue situation in crops

Comments on/additions to List of Endpoints

Florasulam: The intended uses of Annex I inclusion involved the application on winter and spring cereals only. The application on grass seed culture and pastures is separately evaluated for this national authorisation.

Fluroxypyr: The intended uses of Annex I inclusion involved the application on cereals and pastures. The application on grass seed culture is separately evaluated for this national authorisation.

5.1 Summary of residue data

5.1.1 Residue data

Florasulam

Wheat

Eleven residue trials performed with one time 7.5 g a.i./ha before or at growth stage BBCH 49 were performed in northern Europe. In all trials, which were evaluated in the Draft Assessment Report, residues in grains as well as in straws were < 0.01 mg/kg. Results form residue trials performed with wheat can be extrapolated to rye and triticale.

Barley

Six residue trials performed with one time 7.5 g a.i./ha before or at growth stage BBCH 49 were performed in northern Europe. In all trials, which were evaluated in the Draft Assessment Report, residues in grains were < 0.002 mg/kg and in straws < 0.01 mg/kg. Six trials is sufficient in case of a zero residue situation. Results from residue trials performed with barley can be extrapolated to oats.

Spelt

No residue trials are performed with spelt. However, because the intended uses on wheat and barley result in a zero residue situation, it is very likely that the use on spelt also results in a zero residue situation.

Grass seed straw

Results from residue trials performed with cereals (straw) can be extrapolated to grass seed straw. For grass seed straw therefore a residue level < 0.01 mg/kg is expected.

Grass/pasture

Four residue trials were performed with florasulam in pastures performed with 7.5 to
10 g a.i./ha and a PHI of 0-7 days. The trials were evaluated for the national authorisation of a similar product. Residues declined from 0.17-0.31 mg/kg to < 0.01 mg/kg at day 7. It is concluded that residues have already been dissipated at the time of grazing/re-entry of cattle.

Fluroxypyr

Wheat

Thirty five residue trials (winter and spring wheat) performed with one time 0.28-0.60 kg a.i./ha before or at growth stage BBCH 49 were performed in northern Europe. In seventeen trials which were performed with 0.14-0.18 kg a.i./ha, residues in grains were < 0.05 mg/kg. Residues in straws were up to 0.30 mg/kg. Results from residue trials performed with wheat can be extrapolated to rye and triticale.

Barley

Twenty residue trials (winter and spring barley) performed with one time 0.15-0.60 g a.i./ha before or at growth stage BBCH 49 and were performed in northern Europe. In all twenty trials, residues in grains were < 0.05 mg/kg. In straws residues were detected up to 2.48 mg/kg. In barley exposed to 0.14-0.18 mg/kg (15 trials) residue levels in straw were up to 0.28 mg/kg. Results from residue trials with barley can be extrapolated to oat.

Spelt

No residue trials are performed with spelt. However, because the intended uses of wheat and barley result in a zero residue situation for grain, it is very likely that the use on spelt also results in a zero residue situation for grain. For straw, residue trials from barley should be extrapolated because they are worst case.

Grass seed straw

Results form residue trials performed with cereals can be extrapolated to grass seed. For grass seed straw therefore a residue level < 0.01 mg/kg is expected.

Grass/pasture

Twenty three residue trials were performed with fluroxypyr in pastures performed with
0.29-0.58 kg a.i./ha and a PHI of 0-41 days. Residues declined from 6.2-25.5 mg/kg directly after application to < 0.95-15.8 mg/kg at day 7.

5.1.2 Residues from livestock feeding studies

Florasulam

The intended use on winter and spring cereals was evaluated for Annex I inclusion. The claimed use for this extension of Primstar included the use on grass seed culture and pastures (with re-entry of livestock after 14 days after application).

Now, a re-entry of livestock after 7 days is evaluated. It was seen from the residue trials that no residues are expected in straws from grass seed cultures nor grass/hay after a waiting period of 7 days. Therefore, no additional intake of residues is expected to occur to livestock. Since intake of residues to livestock is still < 0.1 mg/kg dry feed, no residues are expected in animal products and no MRLs will be set.

Fluroxypyr

Livestock feeding studies were performed with lactating cows. Dietary intake of fluroxypyr residues was calculated from residue data of grass directly after application multiplied by a factor of 5 (converting to dry weight). The calculated intake (120 mg/kg dry feed) was compared tot the middle dose group (1.6N). Residues in animal products were < 0.05* mg/kg, except for kidney which yielded 0.63 mg/kg.

Dietary intake of poultry was negligible since residues in cereal grains were < 0.05 mg/kg.

5.1.3 Calculation of the ADI and the ARfD

Florasulam

The ADI and ARfD were derived from the toxicological dossier as summarised in the corresponding List of Endpoints (see above).

ADI: 0.05 mg/kg/bw/d

ARfd: not allocated since florasulam has no acute toxic properties.

Fluroxypyr

The ADI and ARfD were derived from the toxicological dossier as summarised in the corresponding List of Endpoints (see above).

ADI: 0.8 mg/kg/bw/d

ARfd: not allocated.

5.2 Maximum Residue Levels

Florasulam

MRLs for cereals have been set by means of directive 2003/60/EC. The MRL is 0.01* mg/kg (all cereals). The intended uses of Primstar on cereals comply with these MRLs. Therefore, MRLs need not to be notified to member states and the European Commission.

MRLs have not been set for grass/hay, since it is not a human food but animal feed.

Fluroxypyr

MRLs for cereals have been set by means of directive 2001/57/EC. The MRL is 0.1 mg/kg for barley, rye, triticale, wheat and oat. The MRL for animal products is 0.05 mg/kg, except for kidney which is 0.5 mg/kg. The intended uses from Primstar on cereals, grass seeds and pastures comply with these MRLs. Therefore, MRLs do not need to be notified to member states and the European Commission.

MRLs have not been set for grass, since it is not a human food but animal feed.

5.3 Consumer risk assessment

Florasulam

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. Calculation of the NTMDI using EU-MRLs shows that 2.2% of the ADI is used for the general population and 7.7% of the ADI is used for children.

Risk assessment for acute exposure through diet

A calculation of the National Estimated Short Term Intake (NESTI) was not carried out since allocation of the ARfD was not considered necessary.

Fluroxypyr

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. Calculation of the NTMDI using EU-MRLs, shows that 0.2% of the ADI is used for the general population and 0.5% for children.

Risk assessment for acute exposure through diet

A calculation of the National Estimated Short Term Intake (NESTI) was not carried out since allocation of the ARfD was not considered necessary.

Conclusion

Authorisation of Primstar will not result in any unacceptable risk from intake of florasulam and fluroxypyr to consumers. Primstar can be authorised for the requested claim on cereals and pastures as well as grass leys, sport fields and lawns.

5.4 Data requirements

None.

6. Environmental fate and behaviour

The Plant Protection Products and Biocides Regulations (RGB) published in the Government Gazette (Staatscourant) 188 of 28 September 2007 came into effect on 17 October 2007, while repealing the Uniform Principles Decree on Plant Protection Products (BUBG) and the Regulation elaborating the uniform principles for plant protection products (RUUBG).

For applications for formulations received and taken into the assessment procedure before 17-10-2007 containing active substances of the following category

- active substances which have already been included in Annex I of directive 91/414/EEC

- “new” active substances;

risk assessment is done in accordance with HTB 1.0.

Risk assessment is done in accordance with Chapter 10 of the RGB for products based on
- active substances which have not been included in Annex I of directive 91/414/EEC

This means that for the current application of Primstar, risk assessment is done in accordance with HTB 1.0.

Florasulam and Fluroxypyr are both placed on Annex I.

List of Endpoints Fate/behaviour

Florasulam

Florasulam is a new substance included in Annex I of 91/414/EEC since 18/07/2002, inclusion directive 2002/64/EC. The current assessment is based on the List of Endpoints from the final draft review report, of 18 September 2002 and C-153.3.13. For the rate of degradation in soil geomean DT₅₀ values were added in italics as they are used in the risk assessment. For the aspect Fate and Behaviour in the environment no additional studies were used for the assessment.

Fate and behaviour in the environment

Fate and behaviour in soil

Route of degradation
Aerobic:
Mineralization after 100 days:	4.8-13.5% after 100 d
Non-extractable residues after 100 days:	29.6-57.1% after 100 d
Major metabolites above 10 % of applied active substance: name and/or code % of applied rate (range and maximum)	5-OH (max 71.6 %), DFP-ASTCA (max 17.8%), ASTCA (max 40.0%), TSA (max 15.9%)

Supplemental studies
Anaerobic:	Degradation to metabolite 5-OH (max 87%) Low mineralization (1.3% max) Bound residue (max 11.2% after 365 d)

Soil photolysis:	DT50 of 44 and 158 d , respectively under light and in the dark 5-OH and unknown 1 at maximum level of 2.1 and 2.8%; 27.7% bound residue

Remarks:	-

Rate of degradation
Laboratory studies
DT₅₀lab (20 °C, aerobic):	DT_50lab (20°C, aerobic, a.s.): 0.7-4.5 days (median : 1.6 d; 4 soils)_{geomean 1.7 days} DT_50lab (20°C, aerobic, field cap, a.s.): 7.4-10 days (2 soils) DT_50lab (20°C, aerobic, 5-OH): 10-31 days (median: 27 d; 4 soils) geomean 22.4 days DT_50lab (20°C, aerobic, DFP-ASTCA): 8-25 days (2 soils) geomean 14 days DT_50lab (20°C, aerobic, ASTCA): 158-502 days (2 soils) geomean 282 days DT_50lab (5°C, aerobic, a.s.): 19-45 days (2 soils) DT_50lab (20°C, anaerobic, a.s.): 11-14 days (2 labellings)




DT₉₀lab (20 °C, aerobic):	DT_90lab(20°C, aerobic, a.s.): 2.2-15 days (median : 5.3 d; 4 soils) DT_90lab(20°C, aerobic, 5-OH): 34-102 days (median: 89 d; 4 soils)
DT₅₀lab (10 °C, aerobic):	DT_50lab (5°C, aerobic, a.s.): 19-45 days (2 soils)
DT₅₀lab (20 °C, anaerobic):	DT_50lab (20°C, anaerobic, a.s.): 11-14 days (2 labellings)

Field studies (country or region)
DT_50f from soil dissipation studies:	DT_50f: a.s. = 2-18 days, (median : 8.5d ; 6 locations in France, UK, Germany, Greece)
	DT_50f: 5-OH = 9-95 days, (median : 15.5 d; 6 locations in France, UK, Germany, Greece)
DT_90f from soil dissipation studies:	DT_90f: a.s. = 23-61 days, (median : 40.5 d; 6 locations in France, UK, Germany, Greece)
	DT_90f: 5-OH = 41-209 days, (median : 60 d; 6 locations in France, UK, Germany, Greece)
Soil accumulation studies:	Not required
Soil residue studies:	*Not required*

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

Adsorption/desorption
K_f / K_oc: K_d: pH dependence:	Koc (a.s.) = 4-54 (mean = 22; 1/n = 0.86-1.00; n = 6 ); Kd (a.s.) = 0.14-0.94 (mean = 0.46; n = 6 ) Koc (5-OH) = 7-32 (mean = 18; 1/n = 0.88-1.10; n= 6); Kd (5-OH) = 0.07-1.73 (mean = 0.375; n = 6 ) Koc (DFP-ASTCA) = 24-110 (mean = 53.1; n = 10); Kd (DFP-ASTCA) = 0.26-1.10 (mean = 0.71; n = 10) Koc (ASTCA) = 27-159 (mean = 83; n = 10); Kd (ASTCA) = 0.30-1.87 (mean = 1.17; n = 10) no

Mobility
Laboratory studies:
Column leaching:	15 g a.s./ha, 2 days, 200 mm rainfall : 67.7-92.1% applied radioactivity in the leachate
Aged residue leaching:	*Not required*

Field studies:
Lysimeter/Field leaching studies:	1 appl at 5 g a.s./ha on sand : total residue of 1 year = 0.03-0.05 µg /l 1 appl at 5 g a.s./ha on loam : total residue of 1 year < 0.01 to 0.01 µg /l 1 appl at 25 g a.s./ha on sand (exaggerated rate) : total residue of 1 year = 0.27µg /l = metabolites 5-OH, ASTCA, DFP-TSA, polar compounds, a.s. is absent

Remarks:	-

Fate and behaviour in water

Abiotic degradation
Hydrolytic degradation:	pH 5, 25 °C: no hydrolysis after 30 d
	pH 7, 25°C: no hydrolysis after 30 d
	pH 9, 25°C: t1/2 = 98-100 d
Major metabolites:	major metabolite : 5-OH
Photolytic degradation:	_{pH 5, 25 °C, natural sunlight 40°N, June and May; t1/2 = 88-223 d}
Major metabolites:	*Triazolosulfonic acid (TPSA)* 17%.

Biological degradation
Readily biodegradable:	No
Water/sediment study: DT₅₀ water: DT₉₀ water: DT₅₀ whole system: DT₉₀ whole system: Distribution in water / sediment systems (active substance) Distribution in water / sediment systems (metabolites)	DT50 (a.s., water) » DT50 whole system DT90 (a.s., water) » DT90 whole system DT50 (a.s., whole system) = 8.7-18.0 d DT90 (a.s., whole system) = 28.7-59.7 d DT50 (5-OH, whole system) = 68.59-243.96 d Mainly present in water phase 5-0H distributed in water and sediment phases (max. 64%) mineralisation : max 3.7% after 100 days bound residue : maximum 11% after 100 days
Accumulation in water and/or sediment:	no

Degradation in the saturated zone	-

Remarks:	-

Fate and behaviour in air

Volatility
Vapour pressure:	_{1 x 10-5 Pa at 25°C}
Henry's law constant:	_{3.29 x 10-5 Pa.m3/mol (pH 5) at 20°C} _{4.35 x 10-7 Pa.m3/mol (pH 7) at 20°C} 2.94 x 10^-8 Pa.m³/mol (pH 9) at 20°C

Photolytic degradation
Direct photolysis in air:	-
Photochemical oxidative degradation in air DT₅₀:	DT₅₀ = 1.82 h, Atkinson method
Volatilisation:	from plant surfaces: -0.8% volatilisation within 24 h
	from soil: 1.3% volatilisation within 24 h

Remarks:	-

Fluroxypyr

Fluroxypyr-meptyhepthyl ester (= mhe) is an old substance, placed on Annex I. For the risk assessment the List of Endpoints of September 1999 from the DAR is used. Additions are placed in italic. Fluroxypyr-mhe is quickly transformed into fluroxypyr acid. Some endpoints are therefore expressed as only fluroxypyr acid or fluroxypyr mhe + acid.

Fate and behaviour in the environment

Fate and behaviour in soil

Route of degradation
Aerobic:
Mineralization after 100 days:	Up to 65 % at 20 °C
Non-extractable residues after 100 days:	Up to 29.7 % at 20 °C
Relevant metabolites above 10 % of applied active substance: name and/or code % of applied rate (range and maximum)	4-Amino-3,5-dichloro-6-fluoro-2-pyridinol (metabolite II) up to 11.5 % after 7 d 4-Amino-3,5-dichloro-6-fluoro-methoxypyridine (metabolite III) up to 17.8 % after 28 d

Supplemental studies
Anaerobic:	Mineralization < 0.1%, non-extractables up to 33.5 % (after 56 d, 25 °C) Relevant metabolites: metabolite III, up to 12 % after 112 d

Soil photolysis:	DT₅₀ = 153 d [MHE]

Rate of degradation
Laboratory studies
DT₅₀lab (20 °C, aerobic):	3 - 55 d at 20 - 22 °C [acid] Metabolite II, DT₅₀= 21 - 53 d; average 38d Metabolite III, DT₅₀= 20 - 429 d; average 152d
DT₉₀lab (20 °C, aerobic):	15 – 40 d [acid]; 53 - 220 d [MHE plus acid]
DT₅₀lab (10 °C, aerobic):	No data available, if use required in Nordic region then data will be required.
DT₅₀lab (20 °C, anaerobic):	91 - 210 d at 25 °C [acid]

Field studies (country or region)	Canada, UK

DT_50f from soil dissipation studies:	< 3 d [MHE] 34 - 68 d [acid] 11 - 38 d [acid, MHE]
DT_90f from soil dissipation studies:	Metabolite II: 3 - 16 %, but not detectable after 16 months Metabolite III: 9 - 43 % after 16 months
Soil accumulation studies:	No data available
Soil residue studies:	UK, Italy, Germany: [MHE plus acid] - spring wheat: 0.12 mg/kg (74 d) - winter wheat, bean, turnip: 0.025 mg/kg (404 d) - soft wheat, winter barley, durum wheat each: < 0.01 mg/kg (88, 72, 101 d) - summer wheat 0.018 mg/kg (95 d) - winter rye, winter barley each: < 0.01 mg/kg (92, 75 d)/0-5, 10, 20 cm
Remarks
e.g. effect of soil pH on degradation rate	In general, as soil pH decreases then DT₅₀ increases

Adsorption/desorption
K_OC / K_OM: Soil type, pH, OC/OM content:	K_OC of adsorption: MHE: 6200 – 43000 (av 19550) acid: 51 - 81 (av 68) Metabolite II: 580 Metabolite III: 1337 (DAR) Silt loam (pH 5.9, OC 2.2 %) Sandy loam (pH 7.5, OC 0.2 %) Loam (pH 6.8, OC 3.1 %) Clay (pH 7.0, OC 1.3 %)

Mobility
Laboratory studies:
Column leaching:	MHE: < 2 % in leachate Acid: 18 - 74 % (as equivalents) in leachate
Aged residue leaching:	60 d ageing (approximately equivalent to the worst case DT₅₀) at 22 °C: Acid: 10% in leachate Metabolite II: not detected at 5 µg/l Metabolite III : not looked for

Field studies:
Lysimeter/Field leaching studies:	Lysimeter studies: Single spring application (200 and 400 g/ha): MHE: not detected Acid: 0.008 and 0.0034 µg/l (2 y averages), 0.034 and 0.008 µg/l (maximum). Metabolite II: 0.0009 and < 0.0001 µg/l (2 y averages) 0.0038 and 0.001 µg/l (maximum) Metabolite III: 0.0003 and 0.0002 µg/l (2 y averages) 0.0009 and 0.0006 µg/l (maximum)

Remarks:	Lysimeter studies would be more useful if results were presented separately for each year rather than as 2 year averages. Field leaching data submitted was not acceptable as the limit of detection was too high.

Fate and behaviour in water

Abiotic degradation
Hydrolytic degradation: Relevant metabolites:	MHE: acid: DT₅₀ at pH 4/5: stable* stable* 7: stable* stable* 9: 3.2 d stable* *no significant degradation during study period of 30 d None
Photolytic degradation:	Molar absorption coefficient < 10 l·mol^-1·cm^-1 for wavelengths ³ 290 nm [MHE]

Biological degradation
Ready biological degradability:	No
Water/sediment study: Relevant metabolites - residues in the water phase (% of applied) maximum at day .... at the end of the study at day.... - residues in the sediment (% of applied) maximum at day.... at the end of the study at day....	DT₅₀ (water): The MHE was found immediately after application in the sediment. Hydrolysis occurred to release the more soluble acid in the water. DT₅₀ (whole system): MHE: 2 d, acid: 24 d Metabolite II IV^{^[1]} (25 °C, aerobic, dark) 44 17.9 14 28 13.2 6.5 7 28
Accumulation in water and/or sediment:	---

Degradation in the saturated zone	No data available

Remarks:	---

Fate and behaviour in air

Volatility
Vapour pressure:	MHE: 1.3 · 10^-6 Pa at 20 °C Acid: 3.8 · 10^-9 Pa at 20 °C
Henry's law constant:	MHE: 5.5 · 10^-3 Pa·m³·mol^-1 Acid: 1.06 10^-8 Pa·m³·mol^-1

Photolytic degradation
Direct photolysis in air:	Molar absorption coefficient < 10 l·mol^-1·cm^-1 for wavelengths ³ 290 nm [MHE]
Photochemical oxidative degradation in air DT₅₀:	MHE: 3.3 - 9.8 h Acid: 4.5 - 13.4 h

Remarks:	---

6.1 Fate and behaviour in soil

6.1.1 Persistence in soil

The Board for the authorization of plant protection products and biocides in the Netherlands (Ctgb) has to evaluate persistence in compliance with the INS^{^[2]} method. This is done with a new ‘decision tree’, which has been laid down in the RIVM^{^[3]} report 601506008/2005: ‘Persistence of plant protection products in soil; a proposal for risk assessment. Persistence has to be evaluated by the Ctgb on the basis of this decision tree.

However, this decision tree is currently still under development, which means that it cannot be put into practice immediately. The new procedure for the assessment of persistence of plant protection products for authorization will be implemented in the near future.

As long as the mentioned RIVM report has not been laid down by the competent authorities, the Ctgb will fall back on the tried and tested method which has hitherto been in use for evaluating applications for the authorisation of plant protection products.

If for the evaluation of the product a higher tier risk assessment is necessary, a standard is to be set according to the MPC-INS method.

For the current application this means the following:

Florasulam

The following non-normalised laboratory DT₅₀ values are available for the active substances florasulam: range 0.7 – 4.5 days (n=4, geomean 1.7 days). The mean DT₅₀-value of the a.s. can thus be established to be <90 days. Furthermore, it can be excluded that after 100 days there will be more than 70% of the initial dose present as bound (non-extractable) residues together with the formation of less than 5% of the initial dose as CO₂.

Based on the above, the standards of persistence as laid down in the RGB are met.

For the metabolite 7-OH-florasulam the following non normalised laboratory DT₅₀-values are available: range 10-31 days (geomean 22.4 days).

Based on the above, the standards of persistence as laid down in the RGB are met.

For the metabolite DFP-ASTCA the following non normalised laboratory DT₅₀-values are available: 8 and 25 days (geomean 14 days).

Based on the above, the standards of persistence as laid down in the RGB are met.

For the metabolite ASTCA the following normalised DT₅₀-values are available: 158 and 502 days (geomean 282 days).

Due to the exceeding of the threshold value of 60 days for the mean DT₅₀ (lab) for metabolite ASTCA, it must be demonstrated by means of field dissipation studies that the field DT₅₀ is < 90 days or, it has to be demonstrated that application of the pesticide does not lead to accumulation of the metabolites ASTCA to the extent that it will have an unacceptable effect on non-target-organisms. In order to prevent this, the sum of the concentrations in which ASTCA is present 2 years after the last application after 10 years of annual application in the upper 20 cm of the soil where the pesticide has been applied (Gp,10) (see Table M.4), should not exceed the MPC-INS value for soil organisms.

For the metabolite TSA no laboratory DT₅₀-values are available. According to the information in the DAR this metabolite was found as a metabolite >10% as a result of the extraction method used in the study. Therefore, this metabolite is not considered for risk assessment.

Fluroxypyr-mhe

In soil, fluroxypyr-mhe is transformed completely into fluroxypyr acid (DT50 = 0.32 days).

The average laboratory DT₅₀ value of fluroxypyr acid is 20 days (range 3-55 days). The mean DT₅₀-value can thus be established to be <90 days. Furthermore it can be excluded that after 100 days there will be more than 70% of the initial dose present as bound (non-extractable) residues together with the formation of less than 5% of the initial dose as CO₂.

Herewith, the standards for persistence are met.

For the metabolite MII the average DT₅₀-values is 38 days (range 21-53 days).

Herewith, the standards of persistence are met.

For metabolite MIII the average DT₅₀-values is 152 days (range 20-429 days). Due to the exceeding of the threshold value of 60 days for the mean DT₅₀ (lab) for metabolite MIII, it has to be demonstrated by means of field dissipation studies that the field DT₅₀ is < 90 days.

In field studies, performed in Canada and the UK, concentrations of metabolite III increased over time and the residues found after 16 months varied substantially, between 9 and 43% of applied, which may be related to the absence of a cover crop throughout the study period. No DT90 _field was derived for this metabolite.

Because the lab DT50 is > 90 days and field DT₉₀ is could be > 1 year, it has to be demonstrated that application of the pesticide does not lead to accumulation of metabolite III to the extent that it will have an unacceptable effect on non-target-organisms. In order to prevent this, the time-weighted mean plateau concentration after several years of application of metabolite III in the upper 20 cm of the soil where the pesticide has been applied (see Table M.1) is not to exceed the MPC-INS value for soil organisms.

MPC soil

MPC ASTCA (metabolite of florasulam)

Metabolite ASTCA is persistent in soil. The following DT₅₀-values are available: 158 and 502 days, based on laboratory data. The metabolite was not detected in the field, but it is not known if ASTCA was included in the analyses of the field studies.

Considering the G_P,10 of 0.0001 mg/kg soil (see table M.1), after 10 years of worst-case application of the product, it is questionable whether the metabolite could be detected in the field under normal agricultural practices.

The parent compound florasulam, shows a very low toxicity to earthworms and soil micro-organisms; the worst-case acute TER for earthworms is >3x10E5 (LC50 > 1320 mg a.s./kg soil). Only a risk to non-target plants is expected (not surprising, since this is a herbicide), for all other organisms, the risk is low.

Very little toxicity data is available for metabolite ASTCA. The LC₅₀ for earthworms is > 0.1 mg/kg soil. From herbicidal screening data, it appears that this metabolite does not show any herbicidal activity.

No further data requirements were made for this metabolite during the EU registration process, the metabolite was not considered relevant for further investigation.

Considering the low expected long-term concentration in soil, the low toxicity of the parent compound for all tested organisms except plants, and the absence of herbicidal toxicity for ASTCA, it is concluded that this metabolite will not be of greater long-term risk for soil organisms than the parent compound. Therefore the risk is considered to be acceptable.

Metabolite III (fluroxypyr)

In RIVM report 11548a00 the Maximum Permissible Concentration (MPC; MTR in Dutch) for soil is derived for metabolite III of fluroxypyr.

Data sources

The derivation of the MPC for metabolite III van fluroxypyr is based on the data available in the EU-dossier, and the EU review report and three additional studies summarised in SEC report 12379a00. In addition, an on-line literature search was performed via SCOPUS, available via http://www.scopus.com/. For information on coverage, see http://info.scopus.com/detail/what/

This search did not result in any references from which an endpoint could be derived.

Ecotoxicological effect data

Laboratory data

The available chronic ecotoxicity data for soil organisms and/or processes are summarised in Table M1.

Table M.1. Ecotoxicity data for soil organisms

Endpoints	NOEC/LC50 test soil [mg/kg dw soil]	NOEC standard soil 10% OM [mg/kg dw soil]	Remark
Microbial processes
Nitrification	NOEC ≥ 0.66	≥ 1.83-3.88	OM 1.7-3.6
Carbon mineralisation	NOEC ≥ 0.66	≥ 1.83-3.88	OM 1.7-3.6
Annelida
Eisenia fetida	LC₅₀ 313 (10% OM)	313	LC50
Eisenia fetida	NOEC ≥ 1.170	≥ 2.340	OM 5 %
Plants
Vicia faba	NOEC ≥ 2.984	≥ 21.47	OM 1.39 %
Daucus carota	NOEC 0.187	1.35	OM 1.39 %

Field data

No field data available.

MPC_{eco, soil} according to applicant

The applicant calculated the MPC_{eco, soil}by applying an assessment factor of 10 to the NOEC value for Daucus carota, resulting in a MPC_soil of 0.0187 mg/kg. It is argued that chronic toxicity data are available for soil micro-organisms, earthworms and plants, so that an assessment factor of 10 can be applied.

MPC_eco,
soil – ecotoxicity data

According to the guidance, when chronic toxicity data for three species representing three trophic levels are availabe, an assessment factor of 10 may be applied. This results in a MPC_{eco, soil} of 0.135 mg/kg soil d.w. for standard soil with 10% OM, based on the NOEC for Daucus carota.

From Table M1 it is clear that for the other species in the tests no effects are found in the highest concentrations tested, resulting in NOEC values expressed as ≥ the highest value tested. Since the NOEC for Daucus carota is lower than these values, it can be assumed that a MPC based on Daucus carota will be protective for the other species tested as well.

It should be noted, that for this compound there is the possibility that the aromatic amines form irriversable bounds with humic acids, and for these kinds of substances correlation of sorption with organic content may differ from linearity. Since at the moment no data are available to refine the correlation, the standard lineair correlation is followed.

MPC_{sp, soil} – secondary poisoning

Since the calculated log K_ow is 2.61, which is ≤ 3, the trigger for bioconcentration and biomagnification is not exceeded and a risk due to secondary poisoning is not expected.

MPC_{human, soil} – human exposure

No Risk Phrases have been be assigned to metabolite III, and an ADI is not derived Therefore the MPC_{human, soil} cannot be derived. Since the compound is not expected to be of concern with respect to human toxicology, a risk to human health via contaminated soil is not to be expected.

Conclusion

The MPC_{eco, soil} is 0.135 mg/kg soil d.w. for standard soil with 10% OM.

PECsoil

The concentration of the a.s. and metabolites in soil is needed to assess the risk for soil organisms (earthworms, micro-organisms). The PECsoil for spray applications is calculated for the upper 5 cm of soil using a soil bulk density of 1500 kg/m³. The following input data are used for the calculation:

PEC soil:

Florasulam:

Worst case field DT₅₀ for degradation in soil: 18 days

Molecular weight: 359.3 g/mol

Metabolite 5-OH:

Worst case field DT₅₀ for degradation in soil (20°C): 95 days

Molecular weight: 345.3 g/mol

Correction factor: 0.72 (formation fraction metabolite) *0.96 (relative molar ratio = M metabolite/M parent) = 0.69

Metabolite DFP-ASTCA:

Worst case DT₅₀ for degradation in soil (20°C): 25 days

Molecular weight: 302 g/mol

Correction factor: 0.178 (formation fraction metabolite) *0.84 (relative molar ratio = M metabolite/M parent) = 0.15

Metabolite ASTCA:

Worst case DT₅₀ for degradation in soil (20°C): 502 days

Molecular weight: 192 g/mol

Correction factor: 0.401 (formation fraction metabolite) *0.53 (relative molar ratio = M metabolite/M parent) = 0.21

Fluroxypyr-MHE:

Worst case field DT₅₀ for degradation in soil: 3 days

Molecular weight: 367.3 g/mol

Fluroxypyr-acid:

Worst case field DT₅₀ for degradation in soil (20°C): 68 days

Molecular weight: 255 g/mol

Correction factor: 1 (formation fraction metabolite) *0.69 (relative molar ratio = M metabolite/M parent) = 0.69

Metabolite MII:

Worst case DT₅₀ for degradation in soil (20°C): 53 days

Molecular weight: 197 g/mol

Correction factor: 0.115 (formation fraction metabolite) *0.54 (relative molar ratio = M metabolite/M parent) = 0.062

Metabolite MIII:

Worst case DT₅₀ for degradation in soil (20°C): 429 days

Molecular weight: 211 g/mol

Correction factor: 0.178 (formation fraction metabolite) *0.57 (relative molar ratio = M metabolite/M parent) = 0.10

See Table M.2 for other input values and results. Only the application resulting in the highest PECsoil values is reflected. The plateau concentration is calculated for those metabolites that can be considered potentially persistent. The PECplateau value is calculated as the GP10, the concentration in the top 20 cm of the soil after 2 years following 10 years of application. Only the worst-case concentrations are calculated.

Table M.2 PECsoil calculations (5 cm (and 20 cm))

No./Use

Substance

Corr. factor

Rate

[kg a.s./ha]

Freq.

Fraction on soil

PIECsoil

5 cm

[mg a.s./kg]

PECsoil_{21 d}

5 cm

[mg a.s./kg]

PECsoil (plateau)

20 cm

[mg a.s./kg]

springcereals

Florasulam

5-OH

DFP-ASTCA

ASTCA

Fluroxypyr-MHE

Fluroxypyr-acid

MII

MIII

0.69

0.15

0.21

0.69

0.062

0.10

0.0038

0.0026

0.0006

0.0008

0.22

0.15

0.014

0.022

0.75

0.0045

0.0031

0.00068

0.00095

0.26

0.17

0.016

0.034

0.0031

0.0029

0.0005

0.0009

0.053

0.16

0.014

0.033

<0.0001

0.0001

0.0096

These exposure concentrations are examined against ecotoxicological threshold values in section 7.5.2.

The accumulation PEC is examined against the overall MPC soil. See next section.

Risk assessment of accumulation PEC_soil/MPC_soil

Metabolite ASTCA from florasulam

Metabolite MIII from fluroxypyr

The overall MPC is 0.135 mg/kg for a standard soil with 10% OM. This value has to be corrected to 4.7 % OM (representative for agricultural soil). Hence, the corrected MPC is 0.063 mg/kg.Since the Gp,10 is higher than the MPCsoil for metabolite MIII, it is concluded that the standards for persistence as laid down in the RGB are met.

6.1.2 Leaching to shallow groundwater

The leaching potential of the active substance (and metabolites) is calculated in the first tier using Pearl 2.2.2. and the FOCUS Kremsmünster scenario. Input variables are the actual worst-case application rate for cereals 0.0045 kg/ha, and grassland 0.0048 kg/ha, the crop and an interception value appropriate to the crop of 0,75 and 0.9 respectively; date of yearly application is 15/04 for cereals (designed application period March-May) and 01/11 for all grassland application (worst case period for autumn application. For metabolites all available data concerning substance properties are regarded. The transformation scheme is incorporated in the model and, if available, the kinetic formation fraction is used. If this is not available the maximum observed formation is implemented. The following input data are used for the calculation:

PEARL:

Active substance florasulam:

Geometric mean lab DT₅₀ for degradation in soil (20°C): 2.9 days (n=6)

Arithmetric mean K_om (pH-independent): 12.8 L/kg (n=6)

1/n: 0.925

Saturated vapour pressure: 1 x 10^-5 Pa (20ºC)

Solubility in water: 0.121 g/L (20ºC, pH 7)

Molecular weight: 359.3 g/mol

Metabolite 5-OH florasulam:

Geometric mean lab DT₅₀ for degradation in soil (20°C): 22.4 days (n=4)

Arithmetric mean K_om (pH-independent): 10.4 L/kg (n=6)

1/n: 0.935

Maximum fraction of occurence: 0.716

Molecular weight: 345.3 g/mol

Metabolite DFP-ASTCA:

Geometric mean lab DT₅₀ for degradation in soil (20°C): 14 days (n=2)

Arithmetric mean K_om (pH-independent): 30.8 L/kg (n=10)

1/n: 1 (default)

Maximum fraction of occurence: 0.178

Molecular weight: 316.3 g/mol

Metabolite ASTCA:

Geometric mean lab DT₅₀ for degradation in soil (20°C): 282 days (n=2)

Arithmetric mean K_om (pH-independent): 48.1 L/kg

1/n: 1 (default)

Maximum fraction of occurence: 0.40

Molecular weight: 204.3 g/mol

Saturated vapour pressure florasulam: 1 x 10^-5 Pa (20ºC)

Solubility in water florasulam: 0.121 g/L (20ºC, pH 7)

Fluroxypyr-MHE:

Geomean DT₅₀ for degradation in soil (20°C; 10 kPa): 0.32 days (n=4)

Arithmetic mean K_om (pH-independent): 19550 L/kg,

1/n: 0.9 (default)

Saturated vapour pressure: 3.78·10^-09 Pa (25ºC)

Solubility in water: 91 mg/L (20ºC)

Molecular weight: 369 g/mol

Metabolite fluroxypyr-acid:

Worst case lab DT₅₀ (n=3) for degradation in soil (20°C): 20 days

Arithmetic mean K_om (pH-independent): 40 L/kg, 1/n: 0.921

Saturated vapour pressure: 3.78·10^-09 Pa (25ºC), parent value

Solubility in water: 91 mg/L (20ºC), parent value

Molecular weight: 255 g/mol

Correction factor: 100% (maximum observed formation) * 0.69 (relative molar ratio = M metabolite/M parent) = 0.69

Metabolite MII:

Worst case lab DT₅₀ (n=3) for degradation in soil (20°C): 38 days

K_om (pH-independent): 337 L/kg, 1/n: default 0.9

Saturated vapour pressure: 1.88·10^-05 Pa (25ºC), parent value

Solubility in water: 128 mg/L (20ºC), parent value

Molecular weight: 197 g/mol

Correction factor:11.5% (maximum observed formation) * 0.54 (relative molar ratio = M metabolite/M parent)= 0.062

Metabolite MIII:

Worst case lab DT₅₀ (n=3) for degradation in soil (20°C): 152 days

Arithmetic mean K_om (pH-independent): 1337 L/kg, 1/n: default 0.9

Saturated vapour pressure: 0.0805 Pa (25ºC), parent value

Solubility in water: 71.4 mg/L (20ºC), parent value

Molecular weight: 211 g/mol

Correction factor: 17.8% (maximum observed formation) * 0.57 (relative molar ratio = M metabolite/M parent)= 0.10

Other parameters: standard settings of PEARL 3.3.3

The following concentrations are predicted for the a.s. florasulam and fluroxypyr and their metabolites following spring or autumn applications, see Table M.3.

Table M.3(a) Leaching of a.s. florasulam and fluroxypyr and metabolites as predicted by PEARL 2.2.2

No./ Use	Substance	Rate substance	Frequency	Interval	Fraction intercepted	PEC groundwater	PEC groundwater
		[kg/ha]		[days]		spring [mg/L]	autumn [mg/L]
Winter cereals and newly sown grass	Florasulam 5-OH DFP-ASTCA ASTCA Fluroxypyr-MHE Fluroxypyr-acid MII MIII	0.0045 0.26 0.18 0.011 0.018	1	-	0.25	<0.001 0.016 0.008 0.012 <0.001 <0.001 <0.001 <0.001	<0.001 0.030 0.017 0.012 <0.001 <0.001 <0.001 <0.001
Grassland full cover	Florasulam 5-OH DFP-ASTCA ASTCA Fluroxypyr-MHE Fluroxypyr-acid MII MIII	0.0048 0.27 0.19 0.012 0.019	1	-	0.90	<0.001 0.0019 0.0001 0.0016 <0.001 <0.001 <0.001 <0.001	<0.001 0.0035 0.0002 0.0017 <0.001 <0.001 <0.001 <0.001

Results of Pearl 3.3.3 using the Kremsmünster scenario are examined against the standard of 0.01 µg/L. This is the standard of 0.1 µg/L with an additional safety factor of 10 for vulnerable groundwater protection areas (NL-specific situation).

From Table M.3(a) it reads that the expected leaching based on the PEARL-model calculations for the a.s. fluroxypyr and its metabolites fluroxypyr acid, MII and MIII is smaller than 0.01 µg/L for all proposed applications. Hence, the applications meet the standards for leaching. Furthermore, it is clear that for the a.s. florasulam the expected leaching based on the PEARL-model calculations is smaller than 0.01 µg/L for all proposed applications.

For metabolites 5-OH and DFP-ASTCA and ASTCA from florasulam the expected leaching based on the PEARL-model calculations is larger than 0.01 µg/L but smaller than 0.1 µg/L. For the application in established grassland the expected leaching of metabolite ASTCA based on the PEARL-model calculations is also larger than 0.01 µg/L but smaller than 0.1 µg/L.. The applications meet the standards for leaching. However, as the predicted concentrations are larger than 0.01 µg/L, a restriction on the use in groundwater protection areas should be placed on the label for professional uses. For non-professional use it is taken into account that only a limited area is treated. Therefore PEC groundwater calculation should have been performed with 10% of the dose rate. For non-professional uses the expected concentration in groundwater is <0.01 g/L for all substances.

Further study into the leaching behaviour is necessary for the professional use only.

In the second tier, leaching in potential area of use is evaluated using the spatial distribution model GeoPEARL 3.3.3.

GeoPEARL

The leaching potential of substances to the shallow groundwater in the potential area of use within The Netherlands is calculated using the GeoPEARL model. The same input data as used in the first tier with Pearl 3.3.3 is employed. Additional input is the crop and the number of plots (minimum 250). For results see Table M.3b.

Table M.3b Leaching of metabolite ASTCA as predicted by GeoPEARL 1.1.1.

No./ Use	Substance	Rate a.s.	Frequency	Interval	Fraction intercepted	PEC groundwater	PEC groundwater
		[kg/ha]		[days]		spring [mg/L]	autumn [mg/L]
Winter cereals	Florasulam 5-OH DFP-ASTCA ASTCA	0.0045	1	-	0.25	<0.001 0.0037 0.00012 0.0036
Grassland full cover	Florasulam 5-OH DFP-ASTCA ASTCA	0.0048	1	-	0.90		<0.001 0.013 0.0005 0.004

GeoPEARL calculations show that the predicted leachate concentrations for 5-OH florasulam,DFP-ASTCA and ASTCA are smaller than 0.1 µg/L. Hence, the metabolites meet the standards for the proposed applications.

However, as the predicted overall 90^th percentile concentration for metabolite 5-OH florasulam for the late uses is 0.013 mg/L and therefore larger than 0.01 µg/L, a restriction on the use in groundwater protection areas in principle should be placed on the label.

The toxicological relevance of the 5-hydroxy and ASTCA metabolites of florasulam has been assessed according to the Guidance Document on the Assessment of the Relevance of Metabolites in Groundwater of Substances Regulated under Council Directive 91/414/EEC (Sanco/221/2000 –rev.10- final 25 February 2003). The structures of florasulam and the metabolites are shown below:

Biological (herbicidal) activity

The activity of florasulam and its major soil metabolites was evaluated on the herbicide target enzyme, acetolactate synthase (ALS) and in hydroponic phytotoxicity assays on Lemna minor and bentgrass (Agrostis palustris). The 5-hydroxy metabolite was at least 4000 times less active than florasulam at the ALS target site and ASTCA was 250 times less active. On Lemna, the 5-hydroxy metabolite was about 75,000 times less active then florasulam and the ASTCA metabolite had even less activity than the 5-hydroxy metabolite. The metabolites had little or no activity on bentgrass at 100 ppm.

Genotoxicity

The 5-hydroxy and ASTCA metabolites of florasulam have been screened for their genotoxic activity in the following in vitro studies: Ames test, gene mutation test with mammalian cells, chromosome aberration test.

For both metabolites, there was no mutagenic response in either the Ames test or the Forward Mutation Assay and the Chromosomal Aberration Study was negative. Therefore these studies demonstrate that the metabolites are not mutagenic.

Other Toxicity

Florasulam is not classified as acutely or chronically toxic or very toxic, for reproductive toxicity, or as a carcinogen, and according to the applicant there is no reason to expect the 5-hydroxy or ASTCA metabolites to have toxic or highly toxic properties. However, both metabolites were not found in the rat metabolism and there is actually no information on the toxicity of these metabolites, except the genotoxicity studies. At least a (Q)SAR analysis would have been helpful in determining possible toxic properties of these metabolites to substantiate the applicant’s statement. However, considering the clear negative result in the genotoxicity tests and the very low exposure to both metabolites – at least a factor of 40 below the toxicological threshold of concern (see below) – more toxicological data are not required for these two metabolites.

Exposure assessment – threshold of concern approach

Following the “threshold of concern” approach, a toxicological threshold of concern of 1.5 μg/person/day has been proposed by the Scientific Committee on Plants, which is in line with the threshold developed by the US-FDA. The highest calculated concentration in the groundwater is 0.0128 μg/L for 5-OH florasulam (GeoPEARL) and 0.012 μg/L for ASTCA (PEARL). Assuming a consumption of 2 L of water per day this results in a maximum exposure of 0.036 μg/person/day to 5-OH florasulam and 0.028 μg/person/day to ASTCA. This is well below the toxicological threshold of concern of 1.5 μg/person/day.

It can be concluded that the groundwater metabolites 5-hydroxy florasulam and ASTCA are not relevant.

Lysimeter/field leaching studies

No standardised lysimeter studies are available.

Monitoring data

There are no data available regarding the presence of the substances florasulam and fluroxypyr in groundwater.

Regarding the presence of metabolites 5-OH-florasulam, DFP-ASTCA, ASTCA, MII and MIII no monitoring data are available.

Conclusions

All proposed applications of the product comply with the requirements concerning persistence and leaching in soil.

6.2 Fate and behaviour in water

6.2.1 Rate and route of degradation in surface water

The exposure concentrations of the active substance florasulam and fluroxypyr and their metabolites in surface water have been estimated for the various proposed uses using calculations of surface water concentrations (in a ditch of 30 cm depth), which originate from spray drift during application of the active substance. The spray drift percentage depends on the use. Concentrations in surface water are calculated using the model TOXSWA. The following input data are used for the calculation:

TOXSWA:

Active substance florasulam:

Mean DT₅₀ for degradation in water at 20°C: 13.4 days

DT₅₀ for degradation in sediment at 20°C: 10000 days (default).

Mean K_om for suspended organic matter: 13 L/kg

Mean K_om for sediment: 13 L/kg

Saturated vapour pressure: 1 x 10^-5 Pa (25°C)

Solubility in water: 0.121 g/L (20°C)

Molecular weight: 359.3 g/mol

Metabolite 5-OH:

Mean DT₅₀ for degradation in water at 20°C: 156 days

DT₅₀ for degradation in sediment at 20°C: 10000 days (default).

Mean K_om for suspended organic matter: 11 L/kg

Mean K_om for sediment: 11 L/kg

Saturated vapour pressure: see parent

Solubility in water: see parent

Molecular weight: 345 g/mol

Correction factor: 0.64 (formation fraction metabolite) * 0.69 (relative molar ratio = M metabolite/ M parent) = 0.44

Fluroxypyr-mhe:

DT₅₀ for degradation in water at 20°C: 2 days

DT₅₀ for degradation in sediment at 20°C: 10000 days (default).

K_om for suspended organic matter: 19500 L/kg

K_om for sediment: 19500 L/kg

Saturated vapour pressure: 1.3 x 10^-6 Pa (20°C)

Solubility in water: 0.000109 g/L (temperature dependent)

Molecular weight: 367.3 g/mol

Fluroxypyr acid:

DT₅₀ for degradation in water at 20°C: 24 days

DT₅₀ for degradation in sediment at 20°C: 10000 days (default).

K_om for suspended organic matter: 40 L/kg

K_om for sediment: 40 L/kg

Saturated vapour pressure: 3.78 x 10^-9 Pa (20°C)

Solubility in water: 6.5 g/L

Molecular weight: 255 g/mol

Correction factor: 1 (formation fraction metabolite) *0.69 (relative molar ratio = M metabolite/M parent) = 0.69

Other parameters: standard settings TOXSWA

Because there is no standard method to determine separate degradation rates in water and sediment from the water/sediment study, the DT₅₀ system is used for the water phase and degradation in the sediment is assumed to be zero, which is simulated using a DT₅₀ value of 10000 days.

In Table M.4, the drift percentages and calculated surface water concentrations for the active substances florasulam and fluroxypyr and their metabolite for the worst-case uses (cereals, aircraft application and pastures, lawns and sport fields (professional use) and pastures and lawn (non-professional use)) are presented.

Table M.4 Overview of surface water concentrations for active substance and metabolites following spring and autumn application

No/ Use

Substance

Rate a.s.

[kg/ha]

Freq.

Drift

[%]

PIEC

[mg/L]^*

PEC21

[mg/L]^*

PEC28

[mg/L]^*

spring

autumn

spring

autumn

spring

autumn

Winter cereals (aircraft application)

Florasulam

5-OH

fluroxypyr-MHE

Fluroxypyr acid

0.0045

0.0020

0.26

0.18

0.109

0.048

5.47

4.26

0.109

0.048

5.47

4.26

0.080

0.044

1.17

3.5

0.015

0.0067

0.58

0.59

0.075

0.042

0.92

3.25

0.011

0.0051

0.43

0.45

Pastures, lawns and sport fields

Florasulam

5-OH

fluroxypyr-MHE

Fluroxypyr acid

0.0048

0.0021

0.27

0.19

0.024

0.010

1.12

0.89

0.024

0.010

1.12

0.89

0.018

0.009

0.23

0.72

0.003

0.001

0.112

0.124

0.016

0.009

0.19

0.68

0.002

0.001

0.085

0.094

Pastures, lawns(Non-professional use)

Florasulam

5-OH

fluroxypyr-MHE

Fluroxypyr acid

0.0048

0.0021

0.27

0.19

0.5

0.0095

0.0048

0.557

0.452

0.0095

0.0048

0.557

0.452

0.007

0.0044

0.116

0.368

0.001

0.0007

0.058

0.063

0.0065

0.0042

0.092

0.345

0.001

0.0005

0.044

0.047

^*calculated according to TOXSWA

Fluroxypyr metabolites MII and MIV were found at a maximum of 44 and 18%. Since the proposed applications all have a frequency of 1, it can be expected that the PIEC concentrations of these metabolites are lower than the concentration of the parent.

The exposure concentrations in surface water (and sediment) are compared to the ecotoxicological threshold values in section 7.2.

Monitoring data

There are no data available regarding the presence of the substance florasulam or fluroxypyr in surface water.

Drinking water criterion

It follows from the decision of the Court of Appeal on Trade and Industry of 19 August 2005 (Awb 04/37 (General Administrative Law Act)) that when considering an application, the Ctgb should, on the basis of the scientific and technical knowledge and taking into account the data submitted with the application, also judge the application according to the drinking water criterion ‘surface water intended for drinking water production’. No mathematical model for this aspect is available. This means that any data that is available cannot be adequately taken into account. It is therefore not possible to arrive at a scientifically well-founded assessment according to this criterion. The Ctgb has not been given the instruments for testing surface water from which drinking water is produced according to the drinking water criterion. In order to comply with the Court’s decision, however - from which it can be concluded that the Ctgb should make an effort to give an opinion on this point – and as provisional measure, to avoid a situation where no authorisation at all can be granted during the development of a model generation of the data necessary, the Ctgb has investigated whether the product under consideration and the active substance could give cause for concern about the drinking water criterion.

Considering the first authorization for florasulam was in 2001, for fluroxypyr was in 1996, both substances should have been detected on monitoring.

From the general scientific knowledge collected by the Ctgb about the product and its active substance, the Ctgb concludes that there are in this case no concrete indications for concern about the consequences of this product for surface water from which drinking water is produced, when used in compliance with the directions for use. The Ctgb does under this approach expect no exceeding of the drinking water criterion. The standards for surface water destined for the production of drinking water are met.

6.3 Fate and behaviour in air

Route and rate of degradation in air

Florasulam

The vapour pressure is 1 x 10^-5 Pa at 25°C. The Henry constant is 2.29 x 10^-5Pa.m³/mol at 20°C.

Fluroxypyr-MHE

The vapour pressure is 1.3 x 10^-6 Pa at 20 °C. The Henry constant is 5.5 x 10^-3 Pa·m³·mol^-1. The half-life in air is 3.3 - 9.8 h.

Fluroxypyr-acid

The vapour pressure is 3.78 x 10^-9 Pa at 20 °C. The Henry constant is 1.06 x 10^-8 Pa·m³·mol^-1. The half-life in air is 4.5 - 13.4 h.

Since at present there is no framework to assess fate and behaviour in air of plant protection products, for the time being this issue is not taken into consideration.

6.4 Appropriate fate and behaviour endpoints relating to the product and approved uses

See List of Endpoints.

6.5 Data requirements

None.

The following restriction sentences were proposed by the applicant:

Based on the current assessment, the following has to be stated in the GAP/legal instructions for use:

6.6 Overall conclusions fate and behaviour

It can be concluded that:

the active substance florasulam and its metabolites meet the standards for persistence in soil.
the active substance fluroxypyr and metabolites meet the standards for persistence in soil.
all proposed applications of the active substance florasulam and metabolites DFP-ASTCA and ASTCA meet the standards for leaching to the shallow groundwater.
metabolite 5-OH florasulam of florasulam can be considered a non relevant metabolite that need not comply with the standards for leaching to shallow groundwater.
all proposed applications of the active substance fluroxypyr and its metabolites meet the standards for leaching to shallow groundwater.
all proposed applications of the active substance florasulam meet the standards for surface water destined for the production of drinking water.
all proposed applications of the active substance fluroxypyr meet the standards for surface water destined for the production of drinking water.

7. Ecotoxicology

Risk assessment is done in accordance with HTB 1.0 for products based on
- active substances which have already been placed on Annex I of directive 91/414/EEC

- “new” active substances;

for other plant protection products, HTB 0.2 applies.

This means that for the current application of Primstar, risk assessment is done in accordance with HTB 1.0.

List of Endpoints Ecotoxicology

Florasulam

Florasulam is a new substance, placed on Annex I. For the risk assessment the final List of Endpoints of February 2002 is used. Additions are added in italic.

Ecotoxicology

Terrestrial Vertebrates

Acute toxicity to mammals:	LD50 = 5000 mg a.s./kg bw (mice)
Acute toxicity to birds:	LD50 = 1046 mg a.s./kg bw
Dietary toxicity to birds:	LC50 > 5000 mg a.s./kg food ~ >1750 mg/kg bw*
Reproductive toxicity to birds:	NOEC = 1500 mg a.s./kg food ~ 225 mg/kg bw*
Reproductive toxicity to mammals:	NOAEL = 100 mg a.s./kg bw or 2000 mg a.s./kg food

* Recalculated to daily dose based on default factors for dietary and reproduction studies of 0.35 and 0.15 resp. (based on EFSA-opinion on azinphos-methyl)

Aquatic Organisms

Active substance

	Time-scale	Endpoint	Toxicity
Acute toxicity fish:	96 h	LC50	> 100 mg a.s./l
Long term toxicity fish:	28 d	NOEC	119 mg a.s./l
Bioaccumulation fish:			BCF = 0.8-2.2
Acute toxicity invertebrate:	Daphnia: 48 h	LC50	> 292 _{mg a.s./l}
Chronic toxicity invertebrate:	Daphnia: 21 d	NOEC	38.9 _{mg a.s./l}
Acute toxicity algae:	72 h	ErC50	0.00894 mg a.s./l
Chronic toxicity sediment dwelling organism:	Chironomus: 28 d	NOEC	10 mg a.s./l
Acute toxicity aquatic plants:	Lemna: 14 d	EC50	0.00118 mg a.s./l

Metabolite 5-OH

	Time-scale	Endpoint	Toxicity
Acute toxicity fish:	96 h	LC50	> 91 mg/l
Acute toxicity invertebrate:	Daphnia: 48 h	LC50	> 96.7 _mg/l
Acute toxicity algae:	72 h	EbC50	21.32 _{mg /l}

Honeybees

Acute oral toxicity:	LD50 > 100 µg a.s./bee
Acute contact toxicity:	LD50 > 100 µg a.s./bee

Other arthropod species

Species	Stage		Test Substance		Dose (kg as/ha)		Endpoint		Effect¹⁾			Annex VI Trigger
Laboratory tests
Typhlodromus pyri		protonymphs		formulation		0.0075		beneficial capacity		12.3%	30%
						0.015				43.6 %
Aphidius rhopalosiphi		adults		formulation		0.0075		beneficial capacity		25.2%	30%
						0.015				49.7%
Poecilus cupreus		adults		formulation		0.0075		mortality		0%	30%
						0.015				0%
Chrysoperla carnea		first instar larvae		formulation		0.0075		beneficial capacity		77.55%	30%
						0.015				100%
Extended laboratory test
Chrysoperla carnea		first instar larvae		formulation		0.0075		beneficial capacity		0%	30%

1) The effects concern mortality and reduction of the beneficial capacity compared to the control

Earthworms

Acute toxicity:

LC50 > 1320 mg a.s./kg soil

5-OH: > 1120 mg/kg (DAR)

LC50 of DFP-ASTCA, ASTCA, TSA, STA (triazolosulfonic acid), STCA (triazolosulfonic carboxylic acid) > 0.1 mg/kg (addendum)

Reproductive toxicity:

Soil micro-organisms

Nitrogen mineralization:	Negligible effects at application rate equivalent to 0.01 and 0.05 mg a.s./kg soil
Carbon mineralization:	Negligible effects at application rate equivalent to 0.01 and 0.05 mg a.s./kg soil

Fluroxypyr

Fluroxypyr-meptylhepthyl ester (= mhe) is an old substance, placed on Annex I. For the risk assessment the List of Endpoints from the DAR is used. Additions are placed in italic.

Ecotoxicology

Terrestrial Vertebrates

	Acid	MHE
Acute toxicity to mammals:	---	LD₅₀ > 2000 mg/kg bw
Acute toxicity to birds:	LD₅₀ > 2000 mg/kg bw	LD₅₀ > 2000 mg/kg bw
Dietary toxicity to birds:	LC₅₀ > 5000 ppm ~ 1750 mg/kg bw*	LC₅₀ > 5000 ppm ~ 1750 mg/kg bw*
Reproductive toxicity to birds:	---	NOEL 500 ppm ~ 75 mg/kg bw*
Short term oral toxicity to mammals:	---	NOEL 200 mg/kg bw/d

* Recalculated to daily dose based on default factors for dietary and reproduction studies of 0.35 and 0.15 resp. (based on EFSA-opinion on azinphos-methyl)

Aquatic Organisms

	Acid (mg/l)	MHE (mg/l)	Metabolite II Fluroxypyr Pyridinol (mg/l)	Metabolite IV*	formulated product (Starane 180)	formulated product (Starane 200)**
Acute toxicity fish:	LC₅₀ 14.3	LC₅₀ > 0.2	LC₅₀ 39	LC₅₀ 95.1	LC₅₀ 3.5	LC₅₀ 2.52
Chronic toxicity fish	NOEC 100	NOEC 0.2	---	---	NOEC 0.25	---
Bioaccumulation fish:	Not relevant	Not relevant	Not relevant	Not relevant	Not relevant	Not relevant
Acute toxicity invertebrate:	NOEC > 100	LC₅₀ > 0.2	LC₅₀> 49	EC₅₀ 7.56	LC₅₀0.8	LC₅₀ 1.84
Chronic toxicity invertebrate	NOEC 56	NOEC 0.1	---	---	NOEC 0.007	---
Acute toxicity algae:	LC₅₀ 49.8	LC₅₀> 0.5	LC₅₀ >45	LC₅₀ 42.6	LC₅₀ 1.8	LC₅₀ >11.9
Toxicity higher aquatic plants	LC₅₀ 12.3	---	---			EC₅₀> 11.9
Chronic toxicity sediment dwelling organism:	Not relevant	Not relevant	Not relevant	Not relevant	Not relevant	Not relevant

*Addendum 1, February 2001

**Annex III dossier Starane 200, August 2004

Honeybees

	MHE
	LD50	Hazard quotient
Acute oral toxicity:	> 100 mg/bee	< 3.6
Acute contact toxicity:	> 100 mg/bee	< 3.6

Other arthropod species

Laboratory test	Representative formulation tested	% Adverse effects ¹
Aphidius rhopalosiphi	578 g ai/ha	100 (mortality)
Typhlodromus pyri	578 g ai/ha	33.3 (mortality)
Aleochara bilineata	360 g ai/ha	7 (mortality)
Pardosa spp.	360 g ai/ha	0 (mortality)
Poecilus cupreus	360 g ai/ha	0 (mortality)

Extended laboratory test	Representative formulation tested	% Adverse effects ¹
Aphidius rhopalosiphi	439 g ai/ha	0 (mortality)

¹ Adverse effect means:

x % effect on mortality = x % increase of mortality compared to control

y % effect on a sublethal parameter = y % decrease of sublethal paramether compared to control

(sublethal parameters are e.g. reproduction, parasitism, food consumption)

When effects are favourable for the test organisms, a + sign is used for the sublethal effect percentages (i.e. increase compared to control) and a – sign for mortality effects percentages (i.e. decrease compared to control).

Earthworms

Acid

MHE

(mg ai/kg)

Metabolite II*

Fluroxypyr dichloro-pyridinol

(mg ai/kg)

Metabolite III

Fluroxypyr methoxypyridin

(mg ai/kg)

formulated Product

(180 EC)

mg ai/kg

Acute toxicity:

---

LC₅₀ > 1000

LC₅₀ 79

LC₅₀ 313

LC₅₀ 49.7

Reproductive toxicity:

---

*Addendum 1, February 2001

Soil micro-organisms

Nitrogen mineralization:	No negative effects up to 2 kg as/ha¹.
Carbon mineralization:	No negative effects up to 2 kg as/ha¹.
Testing with the metabolite III (Fluroxypyr-Methoxypyridin):
Soil respiration	No negative effects up to 495g as/ha
Nitrogen mineralisation	No negative effects up to 495g as/ha
Testing with the metabolite II (Fluroxypyr-Pyridinol): (addendum 1, february 2001)
Soil respiration	No negative effects up to 0.33kg as/ha
Nitrogen mineralisation	No negative effects up to 0.33kg as/ha

Additional information (studies submitted for Starane and Primstar; summarized and evaluated by EPP consultancy (03/2005)).

Degradation:

DT₅₀ lab Fluroxypyr-MHE 0.30; 0.27; 0.38 d mean: 0.32 days

Fluroxypyr-acid 7; 20; 51 d mean: 26 days

Metaboliet II 37; 30; 71 d mean:46 days

The derived Kd values cannot be used for risk assessment.

Lysimeterstudy:

For the EU dossier an extra lysimeter study was performed. The study concerned a autumn application (415 g fluroxypyr MHE/ha). Fluroxypyr-acid and metabolite MII were formed in the first year (<0.02µg/L). Fluroxypyr-MCE and metabolite mIII were not found.

Aquatic organisms:

BCF fish: 167 L/kg (total); 26 L/kg (MHE)

Toxicity higher aquatic plants: (Lemna gibba tested with Starane 180): EC₅₀ 1,66 mg w.s./L (6,41 mg starane/L)

Terrestrial organisms

Non-target plants:

species	NOEC (21 d) g w.s./ha	EC50 g w.s./ha
Avena sativa	576	>576
Allium cepa	259	632
Cuperus esculentus	576	>576
Brassica napus	4.03	280
Vicia faba	8.06	102

Applied as Starane 180, calculated to g fluroxypyr-MHE/ha

Formulation Primstar

For the formulation Primstar, several studies were submitted in the original application. The endpoints are taken from the last assessment in C166.3.2 , but translated into English. Recalculation to total a.s. is based on fluroxypyr-MHE.

Toxicity to birds and mammals

Toxicity to birds

Substance

Species

Method

Duration

[d]

Criterion

Value

[mg/kg bw]

Value

[mg total a.s./kg bw]

Primstar

Colinus virginianus

Acute toxicity

LD50

> 2000

> 293

Toxicity aquatic organisms

Fish

Substance	Species	Method	Duration [h]	Criterion	Value formulation [mg /L]	Value [mg as /L]
Primstar	Oncorhynchus mykiss	static	96	LC₅₀	13.5	1.978
Primstar	Daphnia magna	static	48	EC₅₀	31.7	4.64
Primstar	Selenastrum capricornutum	static	72	E_rC₅₀ E_bC₅₀	1.58 9.03	0.23 1.32
Primstar	Lemna gibba	static	14d	EC₅₀	0.796	0.117

Toxicity terrestrial organisms

(Bumble)bees

Substance

Species

Method

Duration

[h]

Criterion

Value

product

[μL/bee]

Value

[μg a.s./bee]

Primstar

Apis mellifera

oral

contact

LD₅₀

0.362

0.967

53.0

142

Non-target arthropods

Form.¹	Species	Method	Dose [L/ha]	Dose [g a.s./ha]	Parameter	Adverse effects² [%]	L(E)R₅₀ [g a.s./ha]
Primstar	Crysoperla carnea	Lab.test	0.1 2	14.65 293		<30
Primstar	Typhlodromus pyri	Ext.Lab.test	0.1 2	14.65 293		<30
Primstar	Aphidius rhopalosiphi	Ext.Lab.test	0.1 2	14.65 293		<30

¹ Primstar : 2.5 g/L florasulam +100 g/L fluroxypyr-MHE

² Adverse effect means:

x % effect on mortality = x % increase of mortality compared to control

y % effect on a sublethal parameter = y % decrease of sublethal paramether compared to control

(sublethal parameters are e.g. reproduction, parasitism, food consumption)

Earthworms

Substance

Species

Soil type

[%]

Duration

[d]

Criterion

Dose

product

[mg/kg]

Dose

[mg total a.s./kg]

Primstar

Eisenia

fetida

artificial

LC₅₀

806

118

Micro-organisms

Substance

Dose

product

[L/ha]

Dose

[kg as/ha]

Duration

[d]

Process

Effect at test end

[%]

Effect

at test end

> 25%

(after 100 days)

[Y/N]

Primstar

3.0

15.0

0.440

2.198

Respiration

Nitrification

<25

Non target plants

Vegetative vigour

Substance	Species	Criterion	Value product [L/ha]	Value [kg a.s./ha]
Primstar	Avena sativa	ER₅₀	>1.8	>0.26
Primstar	Allium cepa	ER₅₀	0.79	0.116
Primstar	Cyperus esculentum	ER₅₀	3.16	0.463
Primstar	Daucus carota	ER₅₀	0.16	0.023
Primstar	Brassica napus	ER₅₀	0.35	0.051
Primstar	Glycine max	ER₅₀	0.68	0.100

Additional information (RIVM report 12380A01; 07-12-2009).

Toxicity earthworms

Substance

Species

[%]

Duration

[d]

Criterion

Value

[mg as/kg]

Fluroxypyr methoxypyridine

Eisenia fetida andrei

NOEC _reproduction

≥ 1.170

Effects on higher plants: vegetative vigour

Substance	Species	Duration [d]	Parameter	ER₅₀ product [mL/ha]	ER₅₀ [g as¹/ha	ER₅₀ [g as²/ha]
GF-184	Vicia faba	22	Fresh weight	190.08	27.37	0.42
	Cucumus sativa	22	Fresh weight	632.16	91.03	1.39
	Beta vulgaris	22	Fresh weight	849.58	122.34	1.87
	Solanum tuberosum	22	Fresh weight	832.95	119.95	1.83
	Allium ameloprasam	22	Fresh weight	> 3600	> 518.4	> 7.92

1: fluroxypyr-1-MHE

2: florasulam

Effects on higher plants: seedling emergence and growth

Substance

Species

Duration

[d]

Parameter

ER₅₀

[µg/kg dwt soil]

fluroxypyr methoxypyridine

Vicia faba

Emergence¹

Biomass

> 2984

fluroxypyr methoxypyridine

Daucus carota

Emergence¹

Biomass

> 2984

1127.29

1: emergence and plant survival

Combination toxicology

Combination toxicology is assessed for formulations containing more than one active substance, and for combinations of products, which are made according to the Instructions for Use as a tank mixture. Based on the precautionary principle, concentration-addition is assumed.

For pesticides the TER (Toxicity-Exposure Ratio) is used as a standard in the risk assessment (except for bees and other non-target arthropods, where HQ-values are calculated). The TER must be higher than a trigger value to comply with the standards.

For the combination risk assessment of formulations containing more than one active substance and for tank mixtures the following formula is used:

trigger_{substance 1} /TER_substance
1 + trigger_{substance 2}/TER_{substance 2}+ trigger_substance
i/TER_{substance i} .

When for each substance the trigger values are equal, the combined TER value can be calculated according to:

TER_combi= trigger/((trigger/TER_{substance 1})+(trigger/TER_{substance 2})+( trigger/TER_{substance 3}))

An acceptable risk is expected when TER_combi > trigger.

In case of unequal triggers, the combined TER value can be calculated using the following formula:

Trigger_combi = trigger_{substance 1}/trigger_{substance 2}/trigger_{substance
i}

TER_combi= trigger_combi/((trigger_{substance 1} /TER_{substance
1})+(trigger_{substance 2} /TER_{substance 2})+( trigger_{substance i} /TER_{substance i}))

An acceptable risk is expected when TER_combi > trigger_combi.

In this formula, ‘triggers’ are the trigger values as mentioned in the corresponding chapter of the HTB (v1.0).

In case toxicity of the formulation has been measured, the TER-value of the formulation is calculated with the PEC of the formulation and the toxicity value of the formulation. The PEC of the formulation is the sum of the PECs of the individual active substances. The toxicity value of the formulation is expressed in total amount active substance. Trigger/TER must be smaller than 1.

In the risk assessment, the risk of combination toxicology is assessed using the highest trigger/TER-value from the one based on the sum of the individual substances and the one based on formulation studies. When the standard of 1 is breached, the product is not permissable, unless an adequate risk assessment shows that there are no unacceptable effects under field conditions after application of the product according to the proposed GAP.

7.1 Effects on birds

Birds can be exposed to the active substance florasulam and fluroxypyr via natural food (sprayed insects, seeds, leafs), drinking water and as a result of secondary poisoning.

The threshold value for acute and short-term exposure for birds is set at 0.1 times the LD₅₀ and LC₅₀ value, and the threshold value for chronic exposure is set at 0.2 times the NOEC value. This means that TERs (Toxicity-Exposure Ratio’s) for acute and short-term exposure should be ³ 10 and TER for chronic exposure should be ³ 5.

Table E.1 presents an overview of toxicity data.

Table E.1 Overview of toxicity data for birds for substances florasulam and fluroxypyr and formulation Primstar

	Endpoint	Value
Florasulam
Acute toxicity to birds:	LD₅₀	1046 mg a.s./kg bw
Dietary toxicity to birds:	LC₅₀	> 1750 mg a.s./kg bw/d*
Reproductive toxicity to birds:	NOEL	225 mg a.s./kg bw/d*
Fluroxypyr-MHE
Acute toxicity to birds:	LD₅₀	>2000 mg a.s./kg bw
Dietary toxicity to birds:	LC₅₀	>1750 mg a.s./kg bw/d*
Reproductive toxicity to birds:	NOEL	75 mg a.s./kg bw/d*
Fluroxypyr acid
Acute toxicity to birds:	LD₅₀	>2000 mg a.s./kg bw
Dietary toxicity to birds:	LC₅₀	>1750 mg a.s./kg bw/d*
Reproductive toxicity to birds:	NOEL	- mg a.s./kg bw/d**
Primstar
Acute toxicity to birds:	LD₅₀	>205 mg a.s./kg bw

* Recalculated to daily dose based on default factors for dietary and reproduction studies of 0.35 and 0.15 resp. (based on EFSA-opinion on azinphos-methyl)

**Considering the fast conversion of flyroxypyr-MHE to fluroxypyr acid, long-term risk will be covered in the risk assessment of the parent compound.

7.1.1 Natural food and drinking water

Sprayed products

Procedures for risk assessment for birds comply with the recommendations in the Guidance Document on Risk Assessment for Birds and Mammals under Council Directive 91/414/EEC (Sanco/4145/2000).

For the current applications, uses can be categorized as grassland and cereals. Depending on the crop category, different indicator species are chosen. Table E.2 shows which indicator species are relevant for which uses.

Table E.2. Indicator species per use

No.	Use	Crop	Indicator species
1	Cereals	Cereals, early and late	large herbivorous and insectivorous
2	Grasslands (pastures, meadows, lawns)	grassland	large herbivorous and insectivorous

Table E.3.a-c shows the estimated daily uptake values (ETE, Estimated Theoretical Exposure) of florasulam and fluroxypyr for acute, short-term and long-term exposure, using the Food Intake Rate of the indicator species (FIR) divided by the body weight of the indicator species (bw), the Residue per Unit Dose (RUD), a time-weighted-average factor (f_TWA, only for long term) and the application rate. For uses with frequency of > 1, a MAF (Multiple Application Factor) may be applicable. The ETE is calculated as application rate * (FIR/bw) * RUD * MAF [* f_TWA, only for long term].

For the first assessment only the worst-case scenarios for pastures, lawns and sport fields is calculated. An acceptable risk for these scenarios implies an acceptable risk for all proposed applications.

Table E.3a Acute ETE in terms of daily dose (mg/kg bw) for florasulam and fluroxypyr

Crop (uses no.)

Substance

Indicator species

FIR / bw

RUD (90%)

MAF

Application rate (kg as/ha)

Acute ETE

(mg/kg bw/d)

Pastures, lawns (worst-case)

Florasulam

Fluroxypyr-MHE

Fluroxypyr acid

Large herbivorous bird

0.44

142

0.0048

0.27

0.19

0.30

16.9

11.9

Florasulam

Fluroxypyr-MHE

Fluroxypyr acid

Insectivorous bird (small insects)

1.04

0.0048

0.27

0.19

0.26

14.6

10.3

Table E.3b Short-term ETE in terms of daily dose (mg/kg bw) for florasulam and fluroxypyr

Crop (uses no.)

Substance

Indicator species

FIR / bw

RUD (mean)

MAF

Application rate (kg as/ha)

Short-term ETE

(mg/kg bw/d)

Pastures, lawns (worst-case)

Florasulam

Fluroxypyr-MHE

Fluroxypyr acid

Large herbivorous bird

0.44

0.0048

0.27

0.19

0.16

9.03

6.35

Florasulam

Fluroxypyr-MHE

Fluroxypyr acid

Insectivorous bird (small insects)

1.04

0.0048

0.27

0.19

0.14

8.14

5.73

Table E.3c Long-term ETE in terms of daily dose (mg/kg bw) for florasulam and fluroxypyr

Crop (uses no.)

Crop stage

Indicator species

FIR / bw

RUD (mean)

MAF

f_TWA

Application rate (kg as/ha)

Long-term ETE

(mg/kg bw/d)

Pastures, lawns (worst-case)

Florasulam

Fluroxypyr-MHE

Fluroxypyr acid

Large herbivorous bird

0.44

0.53

0.0048

0.27

0.19

0.085

4.79

3.37

Florasulam

Fluroxypyr-MHE

Fluroxypyr acid

Insectivorous bird (small insects)

1.04

0.0048

0.27

0.19

0.14

8.14

5.73

Based on the ETE-values in Table E.3.a-c the TER-values for the acute, short-term and long-term risk are presented in table E.4.

Table E.4 Toxicity Exposure Ratios for exposure of birds to florasulam and fluroxypyr in food

Time scale	Substance	Toxicity (LD₅₀/ LC₅₀/ NOEL)		ETE value (mg a.s./kg bw/d)	TER value	Trigger value
Crop Pastures and lawns (worst-case), large herbivorous bird
Acute	Florasulam Fluroxypyr-MHE Fluroxypyr acid Combination Primstar	1046 >2000 >2000 … … >293		0.30 16.9 11.9 17.2	>3487 >118 >168 >114 >17.0	10
Short-term	Florasulam Fluroxypyr-MHE Fluroxypyr acid Combination	>1750 >1750 >1750		0.16 9.03 6.35	>10948 >194 >276 >191	10
Long-term	Florasulam Fluroxypyr-MHE Fluroxypyr acid Combination	225 75		0.085 4.79 3.37	2647 15.7 15.5	5
Crop Pastures and lawns (worst-case), insectivorous bird
Acute	Florasulam Fluroxypyr-MHE Fluroxypyr acid Combination Primstar		1046 >2000 >2000 … … >293	0.26 14.6 10.3 14.9	4023 >137 >194 >132 >19.7	10
Short-term	Florasulam Fluroxypyr-MHE Fluroxypyr acid Combination		>1750 >1750 >1750	0.14 9.03 6.35	>12500 >194 >276 >191	10
Long-term	Florasulam Fluroxypyr-MHE Fluroxypyr acid Combination		225 75	0.14 8.14 5.73	1607 9.21 9.16	5

Taking the results in Table E.4 into account, it appears that all proposed uses meet the standards.

Drinking water

Florasulam

The risk from exposure through drinking surface water is calculated for a small bird with body weight 10 g and a DWI (daily water intake) of 2.7 g/d. Surface water concentrations are calculated using TOXSWA (see paragraph 6.2.1). In the first instance, acute exposure is taken into account. The highest PIEC_wateris 0.107 mg/L. It follows that the risk of drinking water is (LD50 * bw) / (PIEC*DWI) = (1046 * 0.010) / (0.000107 * 0.0027) = 3.6 x 10⁷.

Since TER ³ 10, the risk is acceptable.

Fluroxypyr-MHE

The risk from exposure through drinking surface water is calculated for a small bird with body weight 10 g and a DWI (daily water intake) of 2.7 g/d. Surface water concentrations are calculated using TOXSWA (see paragraph 6.2.1). In the first instance, acute exposure is taken into account. The highest PIEC_wateris 5.47 mg/L. It follows that the risk of drinking water is (LD50 * bw) / (PIEC*DWI) = (>2000 * 0.010) / (0.00547* 0.0027) = >1.4 x 10⁶.

Since TER ³ 10, the risk is acceptable.

Metabolites, formulation and combination toxicity

Considering the low expected concentration in water, the low toxicity for birds and the high TER values, no risk for any of the metabolites or the formulation is expected.

7.1.2 Secondary poisoning

The risk as a result of secondary poisoning is assessed based on bioconcentration in fish and worms.

Florasulam and metabolites

Since the log Kow of florasulam < 3 (-1.22) the potential for bioaccumulation is considered low and no further assessment is deemed necessary. For metabolites 5-OH, DFP-ASTCA and ASTCA no information on their Low Pow or their toxicity to birds is available. However, considering the low expected concentrations in the environment and the low toxicity of the parent to birds, no risk on secondary poisoning of any of the metabolites is expected.

Fluroxypyr-MHE and metabolites

For fluroxypyr-MHE the Log Kow is 4.5 and secondary poisoning should be considered. For Fluroxypyr acid the Log Pow is < 3 (1.7) and the risk on secondary poisoning is considered to be low. Metabolites MII, MIII, and MIV are degradation products of fluroxypyr-acid. These metabolites are more polar than the parent. Therefore the risk on secondary poisoning of these metabolites is considered to be low.

Examination takes place against the threshold value for chronic exposure of 0.2 times the NOEC value. This means that the TER should be ³ 5.

Fish

For fluroxypyr-MHE a BCF of 167 L/kg is available.

The highest PEC_water(21)(taken from paragraph 6.2.1.) amounts 1.17 mg/L = 0.00117 mg/L.

Indicator species is a 1000-g bird eating 206 g fresh fish per day.

The TER is then calculated as NOEL / (PEC_water(21)* BCF_fish * (FIR/bw) = 75 / (0.00117 * 167 * 0.21) = 1828. Since this is ³ 5, the risk for birds as a result of consumption of contaminated fish is considered to be small.

Earthworms

Since there are no experimental data the bioconcentration factor for earthworms (BCF_worm) is calculated according to the following formula: BCF = (0.84 + 0.01 * Kow) / f_oc* K_oc.

The logK_ow of fluroxypyr-MHE is 4.5, which leads to a BCF_worm= 0.478 kg soil/kg worm.

The highest PEC_soil(21)taken from paragraph 6.1.1) amounts 0.053 mg/kg soil.

Indicator species is a 100-g bird eating 113 g fresh worms per day.

The risk is then calculated as NOEL / PEC_soil(21)* BCF_worm * (FIR/bw) = 75 / (0.053 * 0.478 * 1.1) = 2691. Since this is ³ 5 , the risk for birds as a result of consumption of contaminated worms is considered to be small.

Taking the results for secondary poisoning through fish and earthworms into account, the proposed uses meet the standards for secondary poisoning.

Conclusions birds

The product meets the standards.

7.2 Effects on aquatic organisms

7.2.1 Aquatic organisms

The risk for aquatic organisms for the various uses of the active substances florasulam and fluroxypyr is assessed by comparing toxicity values with surface water exposure concentrations from section 6.2. Risk assessment is based on toxicity-exposure ratio’s (TERs).

Toxicity data for aquatic organisms are presented in Table E.5 for the active substances, their metabolites and the formulated product. Because the application for authorisation concerns a herbicide, also the effects on macrophytes (aquatic plants) are evaluated.

See Table E.5 for the acute and chronic toxicity values to be used in the risk assessment.

Table E.5 Overview toxicity endpoints for the active substances and metabolite(s)

Substance	Organism	Lowest		Toxicity value
		L(E)C₅₀ [mg/L]	NOEC [mg/L]	[mg/L]
Florasulam	Acute
	Algae	0.00894		8.94
	Daphnids	>292		>292000
	Fish	>100		>100000
	Macrophytes	0.0018		1.8
	Chronic
	Daphnids		38.9	38900
	Fish		119	119000
5-OH	Acute
	Algae	21.32		21320
	Daphnids	>96.7		>96700
	Fish	>91		>91000
Fluroxypyr-MHE	Acute
	Algae	>0.5		>500
	Daphnids	>0.2		>200
	Fish	>0.2		>200
	Macrophytes	>1.66*		>1660
	Chronic
	Daphnids		0.1	100
	Fish		0.2	200
Fluroxypyr acid	Acute
	Algae	49.8		49800
	Daphnids	>100		>100000
	Fish	14.3		14300
	Macrophytes	12.3		12300
	Chronic
	Daphnids		56	56000
	Fish		100	100000
MII	Acute
	Algae	>45		>45000
	Daphnids	>43		>43000
	Fish	39		39000
MIV	Acute
	Algae	42.6		42600
	Daphnids	7.56		7560
	Fish	95.1		95100
Primstar	Acute
	Algae	0.23		230
	Daphnids	4.64		4640
	Fish	1.98		1980
	Macrophytes	0.117		117

* Value for the Formulation Starane 180, recalculated to fluroxypyr-MHE

These toxicity values are compared to the surface water concentrations calculated in section 6.2. Trigger values for acute exposure are 100 for daphnids and fish (0.01 times the lowest L(E)C₅₀-value) and 10 for algae and macrophytes (0.1 times the lowest EC₅₀-value). Trigger values for chronic exposure are 10 for daphnids and fish (0.1 times the lowest NOEC-values).

For acute and chronic risk, the initial concentration is used (PIEC).

In Table E.6. TER values for aquatic organisms are shown. Since the frequency is only 1, expected concentrations in spring and autumn are the same.

Table E.6a TER values for active substances florasulam and fluroxypyr: acute

No./use	Substance	TER_st (trigger 10)	TER_st (trigger 100)	TER_st (trigger 100)	TER_st (trigger 10)
		Algae	Daphnid	Fish	Macrophytes
Cereals (aircraft application)	Florasulam	83.6	>2.7 x 10⁶	>9.3 x 10⁵	16.8
	5-OH	4.4x 10⁵	>2.0 x 10⁶	>2.0 x 10⁶	-
	Fluroxypyr-MHE	>91	>36.6	>36.6	>303
	Fluroxypyr acid	>10000	>10000	3357	2887
	Combination	>43.4	>36.6	>36.6	15.9
	Primstar	412	832	355	21.0

Table E. 6 b TER values for active substances florasulam and fluroxypyr: chronic

No.	Use		TER_lt (trigger 10)	TER_lt (trigger 10)
			Daphnid	Fish
cereals		Florasulam	3.6 x 10⁵	1.1 x 10⁶
		Fluroxypyr-MHE	18.3	36.6
		Fluroxypyr acid	>10000	>10000
		Combination	18.3	36.6

Since fluroxypyr metabolites II and IV have lower expected PIEC concentrations, and show a low toxicity to aquatic organisms, it is expected that the risk for the parent fluroxypyr will cover the risk for these metabolites.

Taking the results in Table E.6a and b into account, the acute TERs for fish and Daphnia magna are above the relevant Annex VI triggers of 100 and the acute TERs for algae and Lemna are above the relevant Annex VI triggers of 10. The chronic TERs for fish and Daphnia magna are above the relevant Annex VI triggers of 10. Thus, it appears that for the active substances florasulam and fluroxypyr the proposed uses meet the standards for aquatic organisms.

7.2.2 Risk assessment for bioconcentration

Florasulam

Considering the low Log Pow of –1.22, the risk for bioconcentration of florasulam is considered to be low.

Fluroxypyr

For the active substance fluroxypyr -MHE a BCF-value of 26 L/kg is available.

Since this value is below 100 L/kg, the risk for bioconcentration is small. Therefore the active substance fluroxypyr-MHE meets the standards for bioconcentration.

For fluroxypyr-acid the log Pow is 1.7. Therefore a low risk on bioconcentration is expected.

For the active substance fluroxypyr (-MHE + acid) a BCF-value of 176 L/kg is available.

Since the BCF is above 100 L/kg and the substance is not ready biodegradable, there is a risk for bioconcentration.

According to the guidance document on aquatic ecotoxicology the following points should be checked:

1) Direct long-term effects in fish due to bioconcentration;

2) Secondary poisoning for birds and mammals;

3) Biomagnification in aquatic food chains

Ad 1) An ELS study should be available if 100 < BCF < 1000 and EC₅₀ a.s. < 0.1 mg/L. A FLS should be available if BCF > 1000. These triggers are not exceeded for fluroxypyr (MHE + acid).

Ad 2) From the assessment of birds and mammals appears that there is no risk on secondary poisoning.

Ad 3) Necessary if the BCF > 1000 and the elimination in the BCF study within 14 days < 95% and the DT₉₀ water > 100 days). Since the BCF is < 1000, this trigger is not exceeded.

Hence, the active substance fluroxypyr-MHE + fluroxypyr-acid meets the standards for bioconcentration.

7.2.3 Risk assessment for sediment organisms

Florasulam

Metabolite 5-OH was found in sediment with a maximum of 64%.

No toxicity data for sediment organisms is available for this metabolite. However, from the other aquatoxicity data it appears that the metabolite is not more toxic than the parent florasulam. For Florasulam a NOEC for daphnids of 38.9 mg/L, and a NOEC for sediment organisms of 10 mg /L is available. When this value is examined against the highest PIEC in water of 0.023 µg/L, the TER value is 4.3 x 10⁵ and the trigger value of 10 is exceeded. Therefore, both the active substance florasulam and metabolite 5-OH meet the standards for sediment organisms.

Fluroxypyr

Fluroxypyr –MHE and Metabolite MII are found in sediment in concentrations of > 10%. Since the NOEC for Daphnia for fluroxypyr-MHE is 0.1 mg/L, no risk for sediment organisms is expected. Since metabolite MII is less toxic than fluroxypyr-MHE, and the LC₅₀ for Daphnia is 43 mg/L, it is expected than the NOEC for Daphnia will be > 0.1 mg/L. Therefore a low risk for sediment organisms is expected for this metabolite. The active substance fluroxypyr-MHE and metabolite MII meet the standards for sediment organisms.

Conclusions aquatic organisms

The proposed application of the product meets the standards.

7.3 Effects on terrestrial vertebrates other than birds

Mammals can be exposed to the active substances florasulam and fluroxypyr via natural food (sprayed insects, seeds, leafs), drinking water and as a result of secondary poisoning.

The threshold value for acute exposure for mammals is set at 0.1 times the LD₅₀ value, and the threshold value for chronic exposure is set at 0.2 times the NOEC value. This means that TER (Toxicity-Exposure Ratio) for acute exposure should be ³ 10 and TER for chronic exposure should be ³ 5. Dietary toxicity is not taken into account for mammals.

Table E.7 presents an overview of toxicity data.

Table E.7 Overview of toxicity data for mammals for substance florasulam and fluroxypyr

	Endpoint	Value
Florasulam
Acute toxicity to mammals:	LD₅₀	5000 mg a.s./kg bw
Reproductive toxicity to mammals:	NOEL	100 mg a.s./kg bw/d
Fluroxypyr-MHE*
Acute toxicity to mammals:	LD₅₀	>2000 mg a.s./kg bw
Reproductive toxicity to mammals:	NOEL	200 mg a.s./kg bw/d

*Considering the fast conversion of fluroxypyr-MHE to fluroxypyr acid, the endpoint for the parent would also include the toxicity of the acid metabolite.

7.3.1 Natural food and drinking water

Sprayed products

Procedures for risk assessment for mammals comply with the recommendations in the Guidance Document on Risk Assessment for Birds and Mammals under Council Directive 91/414/EEC (Sanco/4145/2000).

For the current application, uses can be categorized as grasslands and cereals. Depending on the crop category different indicator species are chosen. Table E.8 shows which indicator species are relevant for which uses.

Table E.8 Indicator species per use

No.	Use	Crop	Indicator species
1	cereals	cereals (early)	small herbivorous
2	cereals	cereals (late)	insectivorous
3	Grasslands, pastures and lawns	grasslands	small herbivorous

Table E.9a-b show the estimated daily uptake values (ETE, Estimated Theoretical Exposure) of florasulam and fluroxypyr for acute and long-term exposure, using the Food Intake Rate of the indicator species (FIR) divided by the body weight of the indicator species (bw), the Residue per Unit Dose (RUD), a time-weighted-average factor (f_TWA, only for long term) and the application rate. For uses with frequency of > 1, a MAF (Multiple Application Factor) may be applicable.

For the first assessment only the worst-case scenarios are calculated. These are winter cereals (late) for insectivorous mammals, and pastures and lawns for small herbivorous mammals.

Table E.9a Acute ETE in terms of daily dose (mg/kg bw) for florasulam and fluroxypyr

Crop (uses no.)

Substance

Indicator species

FIR / bw

RUD (90%)

MAF

Application rate (kg as/ha)

Acute ETE

(mg/kg bw/d)

Cereals

Florasulam

Fluroxypyr_-MHE

insectivorous mammal

0.63

0.045

0.26

0.40

2.29

Pastures and lawns

Florasulam

Fluroxypyr-MHE

Small herbivorous mammal

1.39

142

0.048

0.27

9.47

53.3

Table E..9b Long-term ETE in terms of daily dose (mg/kg bw) for florasulam and fluroxypyr

Crop (uses no.)

Substance

Indicator species

FIR / bw

RUD (mean)

MAF

f_TWA

Application rate (kg as/ha)

Long-term ETE

(mg/kg bw/d)

Cereals

Florasulam

Fluroxypyr-MHE

insectivorous mammal

0.63

5.1

0.045

0.26

0.14

0.84

Pastures and lawns

Florasulam

Fluroxypyr-MHE

Small herbivorous mammal

1.39

0.53

0.048

0.27

2.69

15.1

Based on the ETE-values in Table E.9.a-b the TER-values for the acute and long-term risk are presented in table E.10.

Table E.10 Toxicity Exposure Ratios for exposure of mammals to florasulam and fluroxypyr in food

Time scale	Substance		Toxicity (LD₅₀/NOEL)	ETE value (mg a.s./kg diet/bw/d)	TER value	Trigger value
Crop Wintercereals, insectivorous mammal
Acute	Florasulam Fluroxypyr Combination		5000 >2000	0.40 2.29	12500 >873 >816	10
Long-term	Florasulam Fluroxypyr Combination		100 200	0.14 0.84	714 238 179	5
Crop : Pastures and lawns, small herbivorous mammal
Acute	Florasulam Fluroxypyr Combination	5000 >2000		9.47 53.3	528 >37.5 >35.0	10
Long-term	Florasulam Fluroxypyr Combination	100 200		2.69 15.1	37.2 13.2 9.77	5

Taking the results in Table E.10. into account, it appears that all proposed uses meet the standards.

Drinking water

Florasulam

The risk from exposure through drinking surface water is calculated for a small mammal with body weight 10 g and a DWI (daily water intake) of 1.57 g/d. Surface water concentrations are calculated using TOXSWA (see paragraph 6.2.1). In the first instance, acute exposure is taken into account. The highest PIEC_wateris 0.107 mg/L. It follows that the risk of drinking water is (LD50 * bw) / (PIEC*DWI) = (5000 * 0.010) / (0.000107 * 0.00157) = 3.0 x 10⁸.

Since TER ³ 10, the risk is acceptable.

Fluroxypyr-MHE

The risk from exposure through drinking surface water is calculated for a small mammal with body weight 10 g and a DWI (daily water intake) of 1.57 g/d. Surface water concentrations are calculated using TOXSWA (see paragraph 6.2.1). In the first instance, acute exposure is taken into account. The highest PIEC_wateris 5.47 mg/L. It follows that the risk of drinking water is (LD50 * bw) / (PIEC*DWI) = (>2000 * 0.010) / (0.00547* 0.00157) = >2.3 x 10⁶.

Since TER ³ 10, the risk is acceptable.

Metabolites, formulation and combination toxicity

Considering the low expected concentration in water, the low toxicity for mammals and the high TER values, no risk for any of the metabolites or the formulation is expected.

7.3.2 Secondary poisoning

The risk as a result of secondary poisoning is assessed based on bioconcentration in fish and worms.

Florasulam and metabolites

Fluroxypyr-MHE and metabolites

For fluroxypyr-MHE the Log Kow is 4.5 and secondary poisoning should be considered. For Fluroxypyr acid the Log Pow is < 3 (1.7) and the risk on secondary poisoning is considered to be low. Metabolites MII, MIII, and MIV are degradation products of fluroxypyr-acid. These metabolites are more polair than the parent. Therefore the risk on secondary poisoning of these metabolites is considered to be low.

Examination takes place against the threshold value for chronic exposure of 0.2 times the NOEC value. This means that the TER should be ³ 5.

Fish

For fluroxypyr-MHE a BCF of 167 L/kg is available.

The highest PEC_water(21)(taken from paragraph 6.2.1.) amounts 1.17 mg/L = 0.00117 mg/L.

Indicator species is a 3000-g mammal eating 390 g fresh fish per day.

The TER is then calculated as NOEL / (PEC_water(21)* BCF_fish * (FIR/bw) = 200 / (0.00117 * 167 * 0.13) = 7874. Since this is ³ 5, the risk for mammals as a result of consumption of contaminated fish is considered to be small.

Earthworms

Since there are no experimental data the bioconcentration factor for earthworms (BCF_worm) is calculated according to the following formula: BCF = (0.84 + 0.01 * Kow) / f_oc* K_oc.

The logK_ow of fluroxypyr-MHE is 4.5, which leads to a BCF_worm= 0.478 kg soil/kg worm.

The highest PEC_soil(21)taken from paragraph 6.1.1) amounts 0.053 mg/kg soil.

Indicator species is a 10-g mammal eating 14 g fresh worms per day.

The risk is then calculated as NOEL / PEC_soil(21)* BCF_worm * (FIR/bw) = 200 / (0.053 * 0.478 * 1.4) = 5639. Since this is ³ 5 , the risk for mammals as a result of consumption of contaminated worms is considered to be small.

Taking the results for secondary poisoning through fish and earthworms into account, the proposed uses meet the standards for secondary poisoning.

Conclusions mammals

The product meets the standards.

7.4 Effects on bees

The risk assessment for bees is based on the ratio between the highest single application rate and toxicity endpoint (LD₅₀ value). An overview of the risk at the proposed uses is given in Table E.11.

Table E.11 Risk for bees

Use	Substance	Application rate	LD₅₀	Rate/LD₅₀	Trigger value
		[g a.s./ha]	[µg/bee]
Pastures, lawns	Florasulam	4.8	>100	<0.048	50
	Fluroxypyr	270	>100	<2.7	50
	Combination			<2.7
	Formulation	275	53	5.19	50

Since the ratio rate/LD₅₀ is below 50, the risk for bees is considered to be low. Hence, all proposed uses meet the standards for bees and bumblebees.

Conclusions bees

The product meets the standards.

7.5 Effects on any other organisms (see annex IIIA 10.5-10.8)

7.5.1 Effects on non-target arthropods

The risk for non-target arthropods is assessed by calculating Hazard Quotients. For this, Lethal Rate values (LR₅₀) are needed. Based on LR₅₀-values from studies with the two standard species Aphidius rhopalosiphi and Typhlodromus pyri an in-field and an off-field Hazard Quotient (HQ) can be calculated according to the assessment method established in the SETAC/ESCORT 2 workshop and described in the HTB (v 1.0). In the first tier, Hazard Quotients should be below the trigger value of 2 to meet the standards. No standard laboratory tests with Primstar are available for the standard species. Therefore, the risk assessment is based on extended laboratory tests. Both lethal and sublethal effects should be considered. For both T. pyri and A. rhopalisiphi, no effects (lethal or sublethal) > 30% were found at 2 L/ha. This results in an LR₅₀ and EC₅₀ of >205 g a.s./ha. In this second tier Hazard Quotients should be below the trigger value of 1 to meet the standards. Since the HQ in the first tier is unknown, two additional species should be tested.

The resulting Hazard Quotients are presented in Table E.12.

Table E.12 HQ-values for A. rhopalosiphi and T. pyri

	Application rate (L form.ha)	MAF¹	Drift factor/ Vegetation factor²	Safety factor²	LR₅₀ (L form./ha)	HQ
In-field
A. rhopalosiphi	1.9	1	-	-	>2	<0.95
T. pyri	1.9	1	-	-	>2	<0.95
Off-field
A. rhopalosiphi	1.9	1	0.01	10	>2	<0.095
T. pyri	1.9	1	0.01	10	>2	<0.095

¹: Multiple Application Factor

²: off-field: drift factor = 10%, vegetation dilution factor = 10, safety factor = 10 (default values)

As the above table shows, both in- and off-field HQ values are below the trigger value of 1.

The proposed application of the product therefore meets with the standards for the standard species.

Additional species

In a standard laboratory test with Crysoperla carnea, Primstar showed no effects > 30% at relevant application rates. No other species were tested with the formulated product.

When considering the separate active substances, no effects of florasulam were found on Poecilus cupreus at 15 g a.s./ha. For fluroxypyr, no effects on Aleochara bilineata, Pardosa spec. and Poecilus cupreus were found at 360 g a.s./ha.

Considering that the separate active substances showed no effect at 2-3 times the proposed application rates and that the species tested with the formulated product showed a low sensitivity to the formulated product, the risk to non-target arthropods is considered acceptable.

Hence, the standards for non-target arthropods are met.

7.5.2 Earthworms

The acute risk for earthworms is calculated as TER-value(trigger value 10). Since the logPow of the active substance florasulam and fluroxypyr acid < 2, no correction to the reference soil containing 4.7 % organic matter is necessary for this substances. For the other substances a correction is carried out, since the Log Pow is unknown or > 2. The (corrected) toxicity value for earthworms based on the 14-day LC₅₀ of the active substances, metabolites and formulated product is given in Table E.13. Exposure is expressed as the initial PEC soil. PEC soil is calculated for a soil layer of 5 cm taking into account the application rate, application frequency, fraction on soil, soil bulk density, and degradation of the substance (see also section 6.1.1). for the first assessment, only the worst-case is calculated. Table E.13 presents the PECsoil and the TERs for the active substances.

Table E.13 Overview of soil concentrations and acute TERs for florasulam, fluroxypyr, their metabolites and the formulated product Primstar

No/use.	Substance	PIECsoil [mg/kg]	LC50_corr [mg a.s. /kg]	TER	Trigger value
cereals	Florasulam	0.0045	>1320	>2.9x10⁵	10
cereals	5-OH	0.0031	>526	>1.7x10⁵	10
	DPF-ASTCA	0.00068	>0.047	>69.1	10
	ASTCA	0.00095	>0.047	>49.5	10
	Fluroxypyr-MHE	0.26	>470	>1809	10
	Fluroxypyr-acid	0.17	-*	-	10
	MII	0.016	37.13	2321	10
	MIII	0.034	147	4324	10
	Combination			>1796	10
	Primstar	0.2645	55.5	210	10

*Since fluroxypyr-MHE is rapidly degraded to fluroxypyr acid by a simple hydrolysis step, the toxicity of fluroxypyr-acid is included in the test with fluroxypyr-MHE.

In view of the results presented in Table E.13 a low risk for earthworms is expected at all proposed uses.

Subletal studies are (not) required because a low acute risk is expected for all substances, the frequency is < 3 and the DT50 of most substances are < 90 days. For metabolite ASTCA, the DT50 is > 90 days, but considering the low expected concentration in soil and the low acute toxicity for both florasulam and ASTCA, no long-term risk is expected (see also section 6.1.1.).

For metabolite MIII the DT₅₀ is also > 90 days. A NOEC of ≥ 1.17mg a.s./kg is available. With a PIEC of 0.034 mg/kg, the TER is ≥ 34, which is above the trigger of 5. Therefore the chronic risk to earthworms is acceptable.

The proposed application of the product therefore meets the standards.

7.5.3 Effects on soil micro-organisms

In the tested soils no effects are observed on nitrogen transformation and carbon respiration processes at relevant application rates of 2.20 kg a.s./ha with the formulation Primstar. Since the reduction percentage is below 25% after 28 days, the standards regarding soil micro-organisms are met.

Metabolites

For florasulam metabolites 5-OH, DPF-ASTCA and ASTCA, no separate information is available. For metabolites 5-OH and DPF-ASTCA, the maximum formation is reached in 7 and 14 days. It is expected that the risk for these metabolites is included in the risk assessment for the formulated product. For ASTCA an MPC_soil is derived. The risk for this metabolite is therefore covered in section 6.1.1.

Considering the fast conversion of fluroxypyr-MHE to its acid form, the risk to fluroxypyr acid is covered in the risk assessment for the formulated product. For fluroxypyr metabolites MII and MIII, no effects were found at relevant application rates.

7.5.4 Effects on activated sludge

No information is available. However, for the proposed uses no exposure of activated sludge is expected. Therefore, the proposed applications comply with the standards for activated sludge.

7.5.5 Effects on non target-plants

The risk assessment for non-target plants is based on an off-crop situation with a drift percentage of 10%. The exposure thus equals 0.1 * the application rate.

A TER is calculated with the lowest EC₅₀ value from a laboratory test with higher plants and the exposure concentration. The lowest EC₅₀ is 0.023 kg a.s./ha for Daucus carota. See table E.14:

Table E.14: Overview of exposure concentrations and TERs for non target plants

Use

Substance

Dose

[kg a.s. /ha]

MAF.

Drift% (off-field exposure)

Exposure

(kg a.s./ha)

EC₅₀

[kg a.s./ha]

TER

Trigger value

Pastures, lawns and sport field (worst-case)

Primstar

0.2748

0.02748

0.023

0.84

The ratio between EC₅₀ and the exposure concentration is 0.84 < 5 for the worst-case application. A risk for non-target plants cannot be excluded.

A further refinement is required.

Refined risk assessment

The applicant provided 21-day shoot weight EC50 values for 11 plant species. For 2 species the EC50 values were reported as ‘greater than’. These values were not used in the assessment. The remaining data met the criterion for normal distribution and were used for calculating HC5. HC5 was calculated to be 155.8 mL Primstar/ha.

Furthermore, in current risk assessment, drift for proposed uses is 4.7 %.

Table E.5: Overview of exposure concentrations and TERs for non-target plants. Refined risk assessment using a probabilistic approach

Use

Substance

Dose

[L Primstar/ha]

MAF

Drift% (off-field exposure)

Exposure

(L Primstar/ha)

HC₅

[L Primstar/ha]

TER

Trigger value

Pastures, lawns and sport field (worst-case)

Primstar

1.9

4.7

0.0893

0.1558

1.74

The ratio between HC5 and the exposure concentration is >1 for the worst-case application in pastures, lawns and sport fields. Therefore, the product complies with the RGB.

Conclusions any other organisms

The proposed application of the product complies with the RGB, for the aspects non-target arthropods, earthworms, soil micro-organisms, activated sludge and non-target plants.

7.6 Appropriate ecotoxicological endpoints relating tot the product and approved uses

See List of Endpoints.

7.7 Data requirements

None.

7.8 Classification and labelling

Proposal for the classification and labelling of the active substance florasulam (symbols and R phrases)

Symbol:

Indication of danger: Dangerous for the environment.

R phrases

R50/53

Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment.

Proposal for the classification and labelling of the active substance fluroxypyr-meptyl (symbols and R phrases)

Symbol:

Indication of danger: Dangerous for the environment.

R phrases

R50/53

Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment.

Proposal for the classification and labelling of the formulation concerning the environment – Professional use

Based on the profile of the substance, the provided toxicology of the preparation and the characteristics of the co-formulants, the following labeling of the preparation is proposed:

Symbol:	N	Indication of danger:	Dangerous for the environment.
R phrases	R50/53	Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment.

S phrases	S60	This material and its container must be disposed of as hazardous waste. (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.)
	S61	Avoid release to the environment. Refer to special instructions/safety data sheets.
DPD phrase	-	-

Explanation:
Hazard symbol:	N, R50/53 is based on the toxicity of the formulated product to aquatic plants.
Risk phrases:	See above.
Safety phrases:	S60 and S61 are assigned to products for professional use carrying N, R50/53.
Other:	-

Proposal for the classification and labelling of the formulation concerning the environment – Non-professional use

Based on the profile of the substance, the provided toxicology of the preparation and the characteristics of the co-formulants, the following labeling of the preparation is proposed:

Symbol:	N	Indication of danger:	Dangerous for the environment.
R phrases	R50/53	Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment.

S phrases	S29	Afval niet in de gootsteen werpen.
DPD phrase	-	-

Explanation:
Hazard symbol:	N, R50/53 is based on the toxicity of the formulated product to aquatic plants.
Risk phrases:	See above.
Safety phrases:	S29 is assigned to products for non-professional use carrying N, R50/53.
Other:	-

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

7.9 Overall conclusions regarding the environment

It can be concluded that:

all proposed applications of the formulated product Primstar meet the standards for birds.
all proposed applications of the formulated product Primstar meet the standards for aquatic organisms.
the active substance florasulam meets the standards for bioconcentration.
the active substance fluroxypyr meets the standards for bioconcentration.
all proposed applications of the formulated product Primstar meet the standards for mammals.
all proposed applications of the formulated product Primstar meet the standards for bees.
all proposed applications of the formulated product Primstar meet the standards for non-target arthropods.
all proposed applications of the formulated product Primstar meet the standards for earthworms.
all proposed applications of the formulated product Primstar meet the standards for soil micro-organisms.
all proposed applications of the formulated product Primstar meet the standards for activated sludge.
all proposed applications of the formulated product Primstar meet the standards for non-target plants.

8. Efficacy

The evaluation is partially based on the summary and evaluation prepared by Linge Agroconsultancy on behalf of the applicant (report: Lds07dow01).

8.1 Efficacy evaluation

Dose justification

The dose justification has already been evaluated for the control of annual dicotyledonous weeds (e.g. Galium aparine, Matricaria recutita and Stellaria media) in cereals (1 l/ha), grass seed production (1 l/ha), newly sown pastures (1 l/ha), pastures (1.9 l/ha) and lawns and sport fields (1.9 l/ha).

The proposed dose rate of Primstar in grass manure plants is 1 l/ha. The claimed weeds are similar. The timing of application is similar with that in grass seed production, (newly sown) pastures and lawns and sport fields. As a consequence, no additional data are required for grass manure plants.

The proposed dose rate of Primstar is 1.8 l/ha for the control of weeds of the Brassicaceae family in winter cereals and 1.5 l/ha for the control of weeds of the Brassicaceae and Polygonaceae family in spring cereals. The effectiveness of the proposed dose rates has been discussed below.

Efficacy

A total of 36 efficacy trials was carried out in the period 1999-2005. In 17 trials, Brassicaceae weeds were present and in 19 trials Polygonaceae weeds. The trials were carried out in cereals in Belgium (1 trial), Denmark (1 trial), France (4 trials), Germany (25 trials) and the UK (5 trials).

In the 1999-trials, Primstar was applied using the EF-1466 formulation at 0.15, 0.25, 0.35, 0.5 and 0.6 l/ha which are equivalent to 0.45, 0.75, 1.05, 1.5 and 1.8 l/ha of the currently registered GF-184 formulation of Primstar. In a previous evaluation, there was found from bridging trials that the effectiveness of Primstar is comparable or better than that of EF-1466.

Brassicaceae

In 7 trials Brassica napus (BRSNW) was present, in 4 trials Capsella bursa-pastoris (CAPBP), in 2 trials Raphanus raphanistrum (RAPRA) and in 5 trials Sinapis arvensis (SINAR). The applications with Primstar were made at different stages of the cereal crop, ranging from BBCH27-39. The weed stage at application varied from BBCH12-67.

The number of trials is sufficient. The disease pressure was generally high enough to make an evaluation possible.

Primstar controlled Brassicaceae weeds well in cereals. On small weeds good results were achieved with a dose rate of 1 l/ha Primstar. In some trials, on more developed weeds, as present in more developed crops, a dose rate of 1.5 to 1.8 l/ha Primstar controlled the Brassicaceae weeds better than a dose rate of 1 l/ha. Primstar showed a similar to somewhat better control compared to that of the standard product based on florasulam, the standard product based on fluroxypyr and the standard product based on metsulfuron-methyl.

Polygonaceae

In 6 trials Polygonum aviculare (POLAV) was present, in 12 trials Polygonum convolvulus (POLCO), in 2 trials Polygonum lapathifolia (POLLA) and in 2 trials Polygonum persicaria (POLPE). The applications with Primstar were made at different stages of the cereal crop, ranging from BBCH13-31. The weed stage at application varied from BBCH10-33.

The number of trials is sufficient. The disease pressure was generally high enough to make an evaluation possible.

Primstar in 1.5 l/ha controlled Polygonaceae weeds well in spring cereals. In some trials, a dose rate was tested. In a few of those trials, on more developed weeds, as present in more developed crops, a dose rate of 1.5 l/ha Primstar controlled the Polygonaceae weeds better than lower dose rates. Primstar in 1.5 l/ha showed a similar to somewhat better control compared to that of the standard product based on florasulam, the standard product based on fluroxypyr, the standard product based on metsulfuron-methyl and the standard product based on clopyralid+ fluroxypyr+MCPA.

Combination product

Primstar has already an authorisation in cereals and grasses in the Netherlands. The added value of the combination product has already been evaluated positively when those uses were submitted.

Extrapolation possibilities

Primstar has an authorisation in the Netherlands in cereals (winter wheat, winter barley, winter rye, oat, triticale and spelt, spring wheat, spring barley, spring rye, grass seed production, newly sown pastures, pastures, lawns and sport fields.

Primstar is claimed in grass manure plants. The proposed dose rate of Primstar in grass manure plants is 1 l/ha. The claimed weeds are similar with the ones present on the registered label. The timing of application is similar with that in grass seed production, (newly sown) pastures and lawns and sport fields. It is possible to extrapolate from the registered uses to the use in grass manure plants.

Conclusion

The product complies with the Uniform Principles because, in accordance with article 2.1, it controls the claimed weeds to a good level of control.

8.2 Harmful effects

8.2.1 Phytotoxicity

Primstar has already an authorisation in cereals and grasses in the Netherlands.

On the current label a warning sentence has been written: “Overlap dient voorkomen te worden in verband met kans op gewasreacties.” This was done in the past (2004), when Primstar was first registered, since not enough selectivity data was available at that time and some phytotoxicity was observed on winter barley in 1 trial. Later on (2006), at the time of the first extension of the label, enough selectivity data was present in various cereals. Phytotoxicity was assessed in winter and spring wheat and winter and spring barley. In none of the treated objects with either the claimed dosage or with the double dosage any phytotoxicity was observed (CTB, uitbreiding toelating, aanvraag d.d. 22 december 2004 (20040506 UG)).

In some of the present trials, application of Primstar in high dose rates (> 1,8 l/ha) showed some phytotoxic spots. Those spots, however, disappeared within a few weeks in the course of the growing season, and this was considered acceptable.

In practice, no selectivity problems have occurred. As a consequence, there is no need anymore to have a warning sentence on the label. Moreover in France, Germany and the UK, the label rate is 1.5 and 1.8 l/ha in spring cereals and winter cereals, respectively. No problems are encountered there.

8.2.2 Yield

In previous trials, the effect of Primstar on yield was assessed in cereals, pastures and amenity grasses. No negative effect was observed.

8.2.3 Effects on succeeding crops or substitution crops

Primstar has already an authorisation in cereals and grasses in the Netherlands. In addition, the effect of Primstar on succeeding and substitution crops has been evaluated separately for the two active ingredients florasulam and fluroxypyr, which also have an authorisation in the Netherlands. For florasulam it was concluded that monocotyles were safe substitution crops.

The half-life time of florasulam varied from 2 to 18 days. The half-life time of fluroxypyr varied from 5 to 9 days. These half-life times of florasulam and fluroxypyr do not assume any risk for succeeding crops.

8.2.4 Effects on plants or plant products to be used for propagation

Primstar has already an authorisation in cereals, grass seed production, pastures, lawns and sport fields in the Netherlands. In conducted trials, no negative effects of Primstar on the generative plant organs was found. Due to the timing of the treatment and experiences in practice, it is not expected that problems will arise.

8.2.5 Effects on adjacent crops

Primstar has already an authorisation in cereals, grass seed production, pastures, lawns and sport fields in the Netherlands. The effect of Primstar on adjacent crops has already been evaluated separately for the two active ingredients florasulam and fluroxypyr.

For florasulam it was concluded that it can cause chlorosis or necrosis in adjacent crops when drift appears during the application. For fluroxypyr the same conclusion was drawn. With good agriculture practice during the application, no effects on adjacent crops are expected.

Conclusion

Primstar has already an authorisation in cereals and grasses in the Netherlands. Selectivity trials with assessments on phytotoxicity, yield and quality parameters for double dose rates up to 3.6 l/ha in winter cereals and up to 3.0 l/ha in spring cereals have already been evaluated. Primstar can give some phytotoxic spots. Those spots, however, disappear within a few weeks in the course of the growing season. The effect of Primstar on yield was assessed in cereals, pastures and amenity grasses. No negative effect was observed. No negative effects on succeeding crops, substitution crops, plants or products used for propagation and adjacent crops are expected.

The product complies with the Uniform Principles because it does not, in accordance with article 2.2., induce any unacceptable side effects on plants or plant products, when used and applied in accordance with the proposed label.

8.3 Resistance

Primstar is a combination product based on florasulam and fluroxypyr.

Florasulam belongs to the group of the acetohydroxyacid synthase (ALS) inhibitors. The active ingredient belongs to group B of the HRAC classification system. Resistance against this group of herbicides is already found in Europe in many weeds in cereals, for example Alopecurus myosuroides and Stellaria media.

Fluroxypyr belongs to the group of pyridine carboxylic acids. The active ingredient belongs to group O of the HRAC classification system.

Taking into account the combination of active ingredients from two different groups with different working mechanisms, the diversity of herbicides and the used crop rotation in practice, the risk on resistance of Primstar is low.

Conclusion

The product complies with the Uniform Principles, article 2.1.3 as the level of control on the long term is not influenced by the use of this product because of the possible build up of resistance.

8.4 For vertebrate control agents: impact on target vertebrates

Because no vertebrates are controlled, this point is not relevant.

8.5 Any other relevant data / information

Primstar does not affect beneficial insects and mites. Therefore, the product fits in integrated crop protection. Integrated crop protection is, however, not common practise in the claimed crops.

9. Conclusion

The product complies with the Uniform Principles.

The evaluation is in accordance with the Uniform Principles laid down in appendix VI of Directive 91/414/EEC. The evaluation has been carried out on basis of a dossier that meets the criteria of appendix III of the Directive.

10. Classification and labelling

Proposal for the classification and labelling of the formulation

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 assessments, the following labelling of the preparation is proposed:

Professional use

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:	N	Indication of danger:	Dangerous for the environment
	Xi	Indication of danger:	Irritant
R phrases	R36/38	Irritating to eyes and skin.
	R43	May cause sensitisation by skin contact.
	R50/53	Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment.
	R67	Vapours may cause drowsiness and dizziness.
S phrases	S21	When using do not smoke.
	S36/37	Wear suitable protective clothing and gloves.
	S46	If swallowed, seek medical advice immediately and show this container or label.
	S60	This material and its container must be disposed of as hazardous waste. (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.)
	S61	Avoid release to the environment. Refer to special instructions/safety data sheets.
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?			Not applicable
Tactile warning of danger obligatory?			Not applicable

Explanation:
Hazard symbol:	-
Risk phrases:	Primstar is positive in an LLNA test for skin sensitisation and needs to be classified as R43 ‘May cause sensitisation by skin contact’.
Safety phrases:	-
Other:	-

Non-professional use (Packaging ≤ 125 ml)

R & S phrases are optional for packaging ≤ 125 ml

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:	N	Indication of danger:	Dangerous for the environment
	Xi	Indication of danger:	Irritant
R phrases*	R36/38	Irritating to eyes and skin.
	R43	May cause sensitisation by skin contact.
	R50/53	Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment.
	R67	Vapours may cause drowsiness and dizziness.
S phrases*	S2	Keep out of the reach of children.
	S21	When using do not smoke.
	S29	Afval niet in de gootsteen werpen.
	S36/37	Wear suitable protective clothing and gloves.
	S46	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?			Not applicable
Tactile warning of danger obligatory?			Not applicable

[1] 4-Amino-3-chloro-6-fluoro-2-pyridinol

20 °C: 4-Amino-3,5-dichloro-6-fluoro-2-pyridone

(tentatively identified), maximum 13 % (4 - 13 weeks) and 45 % (8 weeks)(whole systems),

DT₅₀: 28 and 34 d (whole systems)

[2] INS: international and national quality standards for substances in the Netherlands.

[3] RIVM: National institute of public health and the environment.

1 Testing carried out using a herbicide containing fluroxypyr and another active substance.

werkzame stof:	gehalte:
fluroxypyr	100 g/l
florasulam	2,5 g/l

gevaarsymbool:	aanduiding:
Xi	Irriterend
N	Milieugevaarlijk