﷡﷡﷡﷡﷡

HET COLLEGE VOOR DE TOELATING VAN BESTRIJDINGSMIDDELEN

BIJLAGE II bij het besluit d.d. 16 oktober 2007 tot toelating van het middel TOKI, toelatingnummer 12968 N

RISKMANAGEMENT

Contents Page

1. Identity of the plant protection product 2

2. Physical and chemical properties 3

3. Methods of analysis 8

4. Mammalian toxicology 10

5. Residues 16

6. Environmental fate and behaviour 16

7. Ecotoxicology 24

8. Efficacy 35

9. Conclusion 38

10. Classification and labelling 38

1. Identity of the plant protection product

1.1 Applicant

Sumitomo Chemical Agro Europe

2 rue Claude Chappe

69370 St Didier au Mont d’Or

France

1.2 Identity of the active substance

ISO common name	Flumioxazin
Name in Dutch	Flumioxazin
Chemical name	N-(7-fluoro-3,4-dihydro-3-oxo-4-prop-2-ynyl-2H-1,4-benzoxazin-6-yl)cyclohex-1-ene-1,2-dicarboximide (IUPAC)
CAS nr	103361-09-7
EEG nr	Not allocated

The active substance was included on October 10th 2002 in Annex 1 of directive 91/414/EEC.

1.3 Identity of the plant protection product

Name	Toki
Formulation type	Wettable powder (WP)
Content active substance	500 g/kg pure active substance

The formulation is identical to that assessed for the inclusion of the active substance in Annex 1 of directive 91/414/EEC.

1.4 Function

The formulation is used as a herbicide.

1.5 Uses applied for

Uses

Dose a.s.

(g a.s./ha)

Number of applications

Interval between applications

Application time (growth stage and season)

Permanent non cultivated land, excluding hard surfaces

600

March-July

Roadsides, under roadsigns, along roads and paths (max 25 cm).

600

March-July

1.6 Background to the application

It concerns an application for registration of a an herbicide.

1.7 Packaging details

1.7.1 Packaging description

Material:	Primary internal packaging: PVAL-film (water soluble bag) Secondary internal packaging: PE
Capacity:	200 g
Type of closure and size of opening:	The water soluble bag is sealed at the bottom and at the top
Other information	UN registration No. of the packaging: 4G/Z16/F/<manufacturing year>/D/BAM9249

1.7.2 Detailed instructions for safe disposal

See application form and MSDS

2. Physical and chemical properties

2.1 Active substance: Flumioxazin

Data about the identity and the physical and chemical properties are taken from the List of Endpoints (ECCO 73). Changes and/or additions are taken up in italics.

Identity

Active substance (ISO Common Name)	Flumioxazin
Chemical name (IUPAC)	N-(7-fluoro-3,4-dihydro-3-oxo-4-prop-2-ynyl-2H-1,4-benzoxazin-6-yl)cyclohex-1-ene-1,2-dicarboximide
Chemical name (CA)	2-[7-fluoro-3,4 -dihydro-3-oxo-4-(2-propynyl)-2H-1,4-benzoxazine-6-yl]-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione
CIPAC No	578
CAS No	103361-09-7
EEC No (EINECS or ELINCS)	Not allocated
FAO Specification (including year of publication)	Not available
Minimum purity of the active substance as manufactured (g/kg)	960 g/kg (specifications for full scale active substance)
Identity of relevant impurities (of toxicological, environmental and/or other significance) in the active substance as manufactured (g/kg)	No impurity of toxicological or environmental significance
Molecular formula	C₁₉H₁₅FN₂O₄
Molecular mass	354.33
Structural formula

Physical-chemical properties

Melting point (state purity)	202.8 °C (97.6 % purity)
Boiling point (state purity)	Not required
Temperature of decomposition	Not required as decomposition or sublimation does not occur up to the temperature at which measurement of melting point was taken
Appearance (state purity)	Odourless, brown yellow powder (97.6 % purity)
Relative density (state purity)	1.5 at 20 °C (97.6 % purity)
Surface tension	70.9 mN/m at 20 °C
Vapour pressure (in Pa, state temperature)	3.2 x 10^-3 Pa at 22 °C
Henry’s law constant (in Pa·m³·mol^-1)	6.36 ·10^-2 Pa·m³·mol^-1
Solubility in water (in g/l or mg/l, state temperature)	1.79 mg/l at 25 °C The effect of pH on solubility in water has not been studied as the compound has no dissociation constant
Solubility in organic solvents (in g/l or mg/l, state temperature)	At 25 °C: acetone: 17 g/l Acetonitrile: 32.3 g/l ethyl acetate: 17.8 g/l Dichloromethane: 191 g/l hexane: 2.5 ·10^-2 g/l methanol: 1.6 g/l n-octanol: 0.16 g/l
Partition co-efficient (log P_ow) (state pH and temperature)	2.55 at 20 °C (neutral pH) no effect of pH as the compound has no dissociation constant
Hydrolytic stability (DT₅₀) (state pH and temperature)	at 25°C DT ₅₀ : 3.4 - 5.2 days at pH 5 DT ₅₀ : 19-26 hours at pH 7 DT ₅₀ : 14-23 min at pH 9
Dissociation constant	Compound has no dissociation constant
UV/VIS absorption (max.) (if absorption >290 nm state ε at wavelength)	lmax 215 nm (e =57861 l·mol^-1·cm^-1) acid pH lmax 215 nm (e = 58211 l·mol^-1·cm^-1) neutral pH l max 219.8 nm (e = 27512 l·mol^-1·cm^-1) alkaline pH
Photostability (DT₅₀) (aqueous, sunlight, state pH)	21 h at 25 °C
Quantum yield of direct photo- transformation in water at λ > 290 nm	As both hydrolysis and photolysis in water are very rapid, quantum yield has not been requested. In addition, no maximum absorption at l >290 nm
Photochemical oxidative degradation in air	Atmospheric Oxidation (25 deg C) [AopWin v1.91]: Hydroxyl Radicals Reaction: OVERALL OH Rate Constant = 56.7867 E-12 cm3/molecule-sec Half-Life = 0.188 Days (12-hr day; 1.5 E6 OH/cm3) Half-Life = 2.260 Hrs Stability in air was carried out following Atkinson equation (doc. SBP-0039). The calculated decomposition rate was 5.49x10^-11 cm³mol^-1sec^-1 Half-life was calculated to be 5.8 hours
Flammability	Not flammable
Auto-flammability	No autoflammability up to 420 °C
Oxidative properties	Not oxidising (statement)
Explosive properties	Not explosive

2.2 Plant protection product: Toki

Data about the plant protection product are taken from the monograph.

Section (Annex point)	Study	Guidelines and GLP	Findings	Evaluation and conclusion
B.2.2.1 (IIIA 2.1)	Appearance: physical state	GLP: yes Method EPA 63-2	solid	acceptable
B.2.2.2 (IIIA 2.1)	Appearance: colour	GLP: yes Method EPA 63-3	Typically tan	acceptable
B.2.2.3 (IIIA 2.1)	Appearance: odour	GLP: yes Method EPA 63-4	odourless	acceptable
B.2.2.4 (IIIA 2.2)	Explosive properties	GLP: yes Method EEC A14	No explosive properties	acceptable
B.2.2.5 (IIIA 2.2)	Oxidising properties	GLP: yes Method EEC A17	No oxidising properties	acceptable
B.2.2.6 (IIIA 2.3)	Flammability	GLP: yes Method EEC A10	No flammable properties	acceptable
B.2.2.7 (IIIA 2.3)	Auto-flammability	GLP: yes Method EEC A16	No self-ignition up to 420 °C	acceptable
B.2.2.8 (IIIA 2.3)	Flash point		Not applicable
B.2.2.9 (IIIA 2.4)	Acidity/alkalinity	GLP: yes Method CIPAC MT 31.2	0.007356 % H₂SO₄	acceptable
B.2.2.10 (IIIA 2.4)	pH	GLP: yes Method CIPAC MT 31.2	pH: 6.00-6.06 at 22 °C (5 % w/w aqueous dispersion)	acceptable
B.2.2.11 (IIIA 2.5)	Surface tension		Not applicable
B.2.2.12 (IIIA 2.5)	Viscosity		Not applicable
B.2.2.13 (IIIA 2.6)	Relative density		Not applicable
B.2.2.14 (IIIA 2.6)	Bulk (tap) density	GLP: yes Method EPA 63-7	Pour density: 0.366 g/ml Tap density: 0.492 g/ml at room temperature	acceptable
B.2.2.14 (IIIA 2.7)	Storage stability	GLP: yes Method CIPAC MT 46	2 weeks at 54 °C: Characteristics and content of the formulation are stable after a storage at 54°C for 14 days in water soluble PVA bags.	acceptable
B.2.2.15 (IIIA 2.7)	Shelf life	GLP: yes GIFAP 17	2 weeks at 54 °C: Physically and chemically stable after a storage at ambient temperature for 2 years in water soluble PVA bags.	acceptable
B.2.2.16 (IIIA 2.8)	Wettability	GLP: yes Method CIPAC MT 53.3	In water soluble PVA bags: Without swirling: 2minutes 55 seconds With swirling: 1minute 40 seconds	acceptable
B.2.2.17 (IIIA 2.8)	Persistent foaming	GLP: yes Method CIPAC MT 47.1	In water soluble PVA bags: After 1 min: 6.3 ml	acceptable
B.2.2.18 (IIIA 2.8)	Active suspensibility	GLP: yes Method CIPAC MT 15.1	With bagging material present: 86.7% Without bagging material present: 86.5%	acceptable
B.2.2.19 (IIIA 2.8)	Active suspension stability		Not applicable
B.2.2.20 (IIIA 2.8)	Dilution stability		Not applicable
B.2.2.21 (IIIA 2.8)	Dry sieve test	GLP: yes Method CIPAC MT 170	Distribution by weight: More than 90 % are below 300 µm Less than 10 % are above 2 mm	Acceptable (data is non-essential; the study is not required for wettable powders)
B.2.2.22 (IIIA 2.8)	Wet sieve test	GLP: yes Method CIPAC MT 59.3	In water soluble PVA bags: All formulation passed through a 38 µm sieve	acceptable
B.2.2.23 (IIIA 2.8)	Particle size distribution	GLP: yes Method OECD 110	Volume medium diameter is 5.8 µm 100 % (w/w) of particles are < 100 µm 82 % (w/w) of particles are < 10 µm 100 % (number) of particles are < 10 µm	acceptable
B.2.2.24 (IIIA 2.8)	Content of dust/fines		Not applicable
B.2.2.25 (IIIA 2.8)	Attrition and friability		Not applicable
B.2.2.26 (IIIA 2.8)	Emulsifiability, re-emulsifiability and emulsion stability		Not applicable
B.2.2.27 (IIIA 2.8)	Stability of dilute emulsion		Not applicable
B.2.2.28 (IIIA 2.8)	Flowability		Not applicable
B.2.2.29 (IIIA 2.8)	Pourability (rinsibility)		Not applicable
B.2.2.30 (IIIA 2.8)	Dustability		Not applicable
B.2.2.31 (IIIA 2.8)	Adherence and distribution to seeds		Not applicable
2.9.1	Physical compatibility with other products		Not applicable; no mixing is proposed.
2.9.2	Chemical compatibility with other products		Not applicable; no mixing is proposed.
	Dissolution rate of water soluble bags	GLP: yes CIPAC MT176	10 g/L in CIPAC D water at 20 ^oC: complete dissolution after 11 seconds.	Acceptable

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

Conclusion

The physical and chemical properties of the 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.

2.3 Data requirements

None.

3. Methods of analysis

Description and data about the analytical methods are taken from the List of Endpoints (ECCO 73). Changes and/or additions are taken up in italics.

3.1. Analytical methods in technical material and plant protection product

Technical as (principle of method)	Dilution in acetonitrile. Quantification by reversed phase chromatography, UV detection
Impurities in technical as (principle of method)	Dilution in acetonitrile. Reversed phase chromatography, UV detection
Preparation (principle of method)	Extraction in acetonitrile/water. Reversed phase chromatography, UV detection

Conclusion

These analytical methods have been assessed in the monograph and are considered to be acceptable.

3.2 Residue analytical methods

Food/feed of plant origin (principle of method and LOQ for methods for monitoring purposes)	Extraction with acetonitrile/water. Determination with GC equipped with NPD detection. LOQ = 0.02 mg/kg in corn grains and 0.05 mg/kg in grapes and vines
Food/feed of animal origin (principle of method and LOQ for methods for monitoring purposes)	Extraction with acetone. Determination with GC equipped with NPD. LOQ = 0.02 ppm in meat, fat, liver, egg, kidney LOQ = 0.02 mg/kg
Soil (principle of method and LOQ)	Extraction with acetonitrile-water. Determination with GC equipped with FTD. LOQ = 0.5 ppm LOQ = 0.05 ppm = 0.05 mg/kg according to the evaluation table 7/2/2003
Water (principle of method and LOQ)	Determination with reversed phase liquid chromatography, UV detection. LOQ = 0.05 ng/ml water LOQ = 0.05 µg/l
Air (principle of method and LOQ)	Determination with reversed phase liquid chromatography, UV detection. LOQ = 5 µg/l air = 5 mg/m³air
Body fluids and tissues (principle of method and LOQ)	Not required, non toxic compound

Based on the proposed use of the plant protection product, the analytical methods for determination of residues in food/feed of plant origin are not required to be validated for food/feed of animal or plant origin.

Definition of the residue and proposed MRL’s for Flumioxazin
Matrix	Proposed definition of the residue for monitoring	Proposed MRL
Food/feed of plant origin	Flumioxazin. However the product is not used on or near edible crops	Not applicable
Food/feed of animal origin	Not required (no uses on animal feed)	Not applicable
		Required LOQ
Soil	Flumioxazin.	0.05 mg/kg (default)
Drinking water	Flumioxazin.	0.1 µg/L (Dutch drinking water guideline)
Surface water	Flumioxazin.	0.35 µg/L (EC50 for L. Gibba)
Air	Flumioxazin.	0.0054 mg/m³ (derived from the AOEL [0.018 mg/kg bw/d] 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 for water, soil and air, evaluated in the monograph, are acceptable and suitable for monitoring residues in the environment.

The LOQ of the residue analytical method for air is 5 µg/l air, which is too high according to the present guidelines. Based on the AOEL the LOQ should be no higher than 5.4µg/m³. The active substance flumioxazin is only slightly volatile and the AOEL is based on oral intake, not on an inhalation study (rat LC₅₀ > 3.93 g/l). Therefore, in this case, the residue analytical method for air can be accepted.

Conclusion

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

3.3 Data requirements

None.

3.4 Physical-chemical classification and Labelling

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

Symbol(s):

Indication(s) of danger: -

Risk phrase(s)

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

Based on the profile of the substance, the provided toxicology of the preparation, the characteristics of the co-formulants, the method of application, 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:	-	Indication of danger:	-
R phrases	-	-

S phrases	21	When using do not smoke.

Special provisions: DPD-phrases	-	-

Child-resistant fastening obligatory?			not applicable
Tactile warning of danger obligatory?			not applicable

Explanation:
Hazard symbol:	-
Risk phrases:	-
Safety phrases:	ppp contains halogenated a.s.
Other:	-

4. Mammalian toxicology

List of End-points

Flumioxazin is included in Annex I of Directive 91/414/EEC. The List of Endpoints is copied from the review report (7471/V/98-Final, 27 June 2002). Remarks are added in italics.

Absorption, distribution, excretion and metabolism in mammals
Rate and extent of absorption:	83 % based on urinary and biliary excretions in the rat
Distribution:	Widely distributed
Potential for accumulation:	No potential for accumulation
Rate and extent of excretion:	Rapidly excreted, 30-40 % via urine and 60 % via faeces within 7 days
Toxicologically significant compounds:	Parent compound
Metabolism in animals:	Extensively metabolised; hydroxylation of cyclohexene ring and cleavage of the imide linkage

Acute toxicity
Rat LD₅₀ oral:	> 5000 mg/kg bw
Rat LD₅₀ dermal:	> 2000 mg/kg bw
Rat LC₅₀ inhalation:	> 3.93 mg/l
Skin irritation:	Non-irritant
Eye irritation:	Non-irritant
Skin sensitization (test method used and result):	Non-sensitising (M & K)

Short term toxicity
Target / critical effect:	Reversible hematotoxicity (heme synthesis), liver¹
Lowest relevant oral NOAEL / NOEL:	30 ppm (2.2 mg/kg bw/d; 90-d rat)
Lowest relevant dermal NOAEL / NOEL:	300 mg/kg bw/d (21-d rat)
Lowest relevant inhalation NOAEL / NOEL:	No data, no study required

Genotoxicity	No genotoxic potential

Long term toxicity and carcinogenicity
Target / critical effect:	Reversible hematotoxicity (heme synthesis), liver¹
Lowest relevant NOAEL:	50 ppm (1.8 mg/kg bw/d; 2 y rat)
Carcinogenicity:	No carcinogenic potential

Reproductive toxicity
Target / critical effect - Reproduction:	Impairment of reproductive capacity at systemic toxic dose levels.
Lowest relevant reproductive NOAEL / NOEL:	100 ppm (7.5 mg/kg bw/d)²
Target / critical effect - Developmental toxicity:	Teratogenic and foetotoxic in absence of maternal toxicity in rat, but not in rabbit.
Lowest relevant developmental NOAEL / NOEL:	Rat, oral: 10 mg/kg bw/d; ³ Rat, dermal:100 mg/kg bw/d

Delayed neurotoxicity	Not relevant

Other toxicological studies	Mechanistic studies suggest an association between impairment of heme synthesis and toxicity in rats.¹

Medical data	No data, new compound.
Summary
	Value	Study	Safety factor
ADI:	0.009 mg/kg bw/d	Rat, 2-y study	200⁴
AOEL systemic:	0.018 mg/kg bw/d	Rat, 90-d study, corrected for 83 % oral absorption	100⁴
ARfD (acute reference dose)	0.05mg/kgbw/d	Rat, developmental toxicity study (10 mg/kg bw/d)	200

Dermal absorption	5.5 % in 24 h (in vivo, rat)

¹ The critical effect of flumioxazin is inhibition of protoporphyrinogenoxidase (PPO) in bone marrow and liver, resulting in reversible effects on red blood cell formation (heme synthesis) and liver (cytochromes).

²Parental NOAEL < 7.5 mg/kg bw/d

³ Maternal NOAEL > 30mg/kg bw/day. The Scientific Committee on plants was asked to advise on the relevance for humans of the developmental effects seen in animal studies (SCP/FLUMIO/002-Final, 23 May 2001).

The opinion of the committee was:

The developmental effects observed in animals consist of increases in the incidence of ventricular septal defects, wavy ribs, curvature of the scapula and decreased ossification of sacrococcygeal vertebral bodies. All of these occur in rats, but not in rabbits. Only the ventricular septal defects are important and considered to be relevant for humans. However, the data are sufficient to support the establishment of a NOEL for the developmental effects. The proposed mechanism by which flumioxazin causes developmental toxicity in rats but not in rabbits is the inhibition of the enzyme protoporphyrinogen oxidase, thereby interfering with normal heme synthesis and resulting in anaemia. The rat enzyme is about 2.5 fold more sensitive than human which is about 8 fold more sensitive than the rabbit enzyme.

⁴ The reason why an extra safety factor is applied for the ADI and ARfD but not for the AOEL is not clear from the EU-dossier. This point has been put forward by NL during the evaluation process. Based on the knowledge of the underlying mechanism and the availability of a clear no effect level for developmental effects and the lower sensitivity in humans for this effect a SF 100 should be sufficient for derivation of ADI, AOEL and ARfD. Since the intended use is not on edible corps, this problem is not relevant for the applications claimed.

Data requirements active substance

None

4.1 Toxicity of the formulated product (IIIA 7.1)

The formulation Toki does not need to be classified on the basis of its acute oral (LD₅₀ rat > 5000 mg/kg bw), dermal (LD₅₀ rat > 2000 mg/kg bw), and inhalation toxicology (LC₅₀ rat > 0.97 g/m³,highest attainable concentration).

The formulation Toki does not need to be classified for dermal irritation, eye irritation or skin sensitisation.

4.1.1 Data requirements formulated product

None

4.2 Dermal absorption (IIIA 7.3)

See List of Endpoints. The value for dermal absorption is based on an in vivo study with the active ingredient. The value can be used for the WP formulation.

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

Other formulants: no reason for toxicological concern.

4.4 Exposure/risk assessments

Overview of the proposed uses

Toki is a wettable powder formulation containing 500 g/kg flumioxazin. It is sold in water soluble bags of 200 g. Toki is a herbicide for application on permanent non cultivated land, including applications under crash barriers, around road markings and signposts and border strips of max. 25 cm between roads and paths and roadsides, excluding hard surfaces,. It can be applied by mechanical downward spraying (vehicle ground boom) or by handheld downward spraying. Application is on young weeds, preferably in spring. Therefore risk assessment for semi chronic exposure will cover the operators, including contract workers.

Calculation of the AOEL

The EU-AOEL for semi chronic exposure is set at 0.018 mg/kg bw/day (1.3 mg/day for a 70 kg operator), based on a 90 d oral study in rats.

4.4.1 Operator exposure/risk

Exposure to flumioxazin during mixing and loading and application of Toki is estimated with models. The exposure is estimated for the unprotected operator. In the table below the estimated internal exposure is compared with the systemic AOEL. In general, mixing and loading and application is performed by the same person. Therefore, for the total exposure, the respiratory and dermal exposure during mixing/loading and application of the formulation have to be combined.

The prescribed dose is 1.2 L Toki/ha. For risk assessment a maximum treatment of 10 ha/day is assumed for mechanical spraying on permanently non cultivated land, and 0,5 ha/day for hand held spraying. Applications under crash barriers, around road markings and signposts and border strips of 25 cm between roads and paths and roadsides may also be done with special mechanical methods. At present there are no models for estimation of operator exposure in small scale mechanical treatments. The exposure estimation for hand held applications is used as a worst case for small scale mechanical applications.

Tabel T.1 Internal Operator exposure to flumioxazin and risk assessment for the use of Toki

	Route	Estimated internal exposure ^a(mg /day)	Systemic AOEL (mg/day)	Risk-index ^b
Mechanical downward spraying
Mixing/ Loading	Respiratory	0.075	1.3	0.06
Mixing/ Loading	Dermal	0.550	1.3	0.42
Application	Respiratory	0.048	1.3	0.04
Application	Dermal	1.000	1.3	0.77
	Total	1.7	1.3	1.3
Hand held downward spraying
Mixing/ Loading	Respiratory	0.019	1.3	0.02
Mixing/ Loading	Dermal	0.140	1.3	0.11
Application	Respiratory	0.525	1.3	0.40
Application	Dermal	11.500	1.3	8.85
	Total	12.2	1.3	9.4

a exposure was estimated by NL model for mixing loading and hand held spraying, EUROPOEM for mechanical application. For the use of water soluble bags a reduction factor 100 in comparison to powder formulations was applied for exposure during mixing/loading.

biological availability via the dermal route: 5.5%

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

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

4.4.2 Bystander exposure/risk

Mechanical application

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

Hand held application (including small scale mechanical application)

There are no models available for estimating the exposure to bystanders as a result of hand held applications. Hand held spraying is to be expected for applications around road markings and signposts and border strips of 25 cm between roads and paths and roadsides. Close presence of bystanders during these applications can not be excluded. At this moment a quantitative risk assessment for this application is not possible. However, exposure of bystanders will be of very short duration. Since flumioxazin has no acute toxic effects, no risk for bystanders is expected.

4.4.3 Worker exposure/risk

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

4.4.4 Re-entry

See 4.4.3 Worker exposure/risk.

Overall conclusion of the exposure/risk assessments of operator, bystander, and worker

The product complies with the Uniform Principles.

Operator

Mechanical spraying

Based on the risk assessment it can be concluded that no adverse health effects are expected for the unprotected operator after respiratory exposure to flumioxazin as a result of the application of Toki in permanent non cultivated land.

For the unprotected operator the estimated dermal exposure exceeds the AOEL only marginally. Since the estimation of the dermal exposure does not include reduction of exposure by clothes and since a reduction factor of 100 at mixing/loading for a water soluble formulation is a very conservative assumption, actual exposure will be lower. Therefore, no risk is expected for the operator as result of dermal exposure to flumioxazin due to the use of Toki on permanent non cultivated land.

Hand held spraying

For the unprotected operator, adverse health effects after dermal exposure to flumioxazin as a result of the application of Toki on permanent non cultivated land, including also applications under crash barriers, around road markings and signposts and border strips of 25 cm between roads and paths and roadsides cannot be excluded. Correct use of personal protective equipment can reduce the dermal exposure with a factor of 10. This results in sufficient reduction of the dermal exposure to flumioxazin for the application of Toki on permanent non cultivated land, including also applications under crash barriers, around road markings and signposts and border strips of 25 cm between roads and paths and roadsides.

Bystanders

Based on the risk assessment it can be concluded that no adverse health effects are expected

for the unprotected bystander due to exposure to flumioxazin during mechanical or hand held application of Toki on permanent non cultivated land, including also applications under crash barriers, around road markings and signposts and border strips of 25 cm between roads and paths and roadsides.

Worker

Based on the risk assessment it can be concluded that no adverse health effects are expected

for the unprotected worker due to exposure to flumioxazin during application of Toki on permanent non cultivated land, including also applications under crash barriers, around road markings and signposts and border strips of 25 cm between roads and paths and roadsides for mechanical applications.

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

See List of end-points.

4.6 Data requirements

None.

4.7 Combination toxicology

Toki contains only 1 active substance and it is not mentioned that it should be used in combination with other formulations.

4.8 Mammalian toxicology classification and labelling

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

Symbol:

Indication of danger: Toxic

Risk phrases

R61

May cause harm to the unborn child

Proposal for the classification and labelling of the formulation concerning health

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

Substances, present in the formulation, which should be mentioned on the label by their chemical name (other very toxic, toxic, corrosive or harmful substances):
-
Symbol:	T		Indication of danger:	toxic
R phrases	R61		May cause harm to the unborn child.

S phrases	36/37		Wear suitable protective clothing and gloves.
	45		In case of accident or if you feel unwell, seek medical advice immediately (show the label where possible).
	53		Avoid exposure - obtain special instructions before use.
	SPo2		Wash all protective clothing after use.

Special provisions: DPD-phrases	-		-

Plant protection products phrase: DPD-phrase	DPD01		To avoid risk for man and the environment, comply with the instructions for use
Child-resistant fastening obligatory?				n.a.
Tactile warning of danger obligatory?				n.a.
Explanation:
Hazard symbol:		-
Risk phrases:		-
Safety phrases:		36/37 is assigned based on the operator risk assessment SPo2 is assigned as the a.i. is included on annex I of 91/414 and is obligatory when formulation is labeled with T.
Other:		-

5. Residues

Since Toki is intended only for use as a herbicide in the uses listed in §1.5, no intake of residues will take place to consumers. Therefore, no risk is expected for consumers.

6. Environmental fate and behaviour

Background

It concerns an application for authorisation of the plant protection product Toki (500 g flumioxazin/L) as a herbicide in the uses listed in Table M.1.

Table M.1 Overview of intended use

Use	Application rate a.s. [kg/ha]	Frequency	Interval [days]	Time of application
Permanent non-cultivated area’s (i.e. verges, underneath crash-barriers, traffic signs etc.) excluding hard surfaces	0.6	1	-	spring

Use

Application rate a.s.

[kg/ha]

Frequency

Interval

[days]

Time of application

Permanent non-cultivated area’s (i.e. verges, underneath crash-barriers, traffic signs etc.) excluding hard surfaces

0.6

spring

List of Endpoints Fate and behaviour

Flumioxazin is a new substance, placed on Annex I (10/10/2002). For the risk assessment the LoEP is used. Comments are given in italic.

The 50 WP formulation mentioned in the LoEP is the formulation Pledge. This is comparable with the WP50% formulation Toki. The endpoints of Pledge will be used for the risk assessment of Toki.

Fate and behaviour in the environment

Fate and behaviour in soil

Route of degradation
Aerobic:
Mineralization after 100 days:	Phenyl moiety: 5.6 % (59 d), 11.5 % (181 d) at 25°C 13.5 % (100 d) at 20° C THP moiety: 54.9 % (91 d) at 25°C
Non-extractable residues after 100 days:	Phenyl moiety: 71.3 % (59 d), 73.6 % (181 d) at 25°C 62.4 % (100 d) at 20° C THP moiety: 29 % (91 d) at 25°C
Relevant metabolites above 10 % of applied active substance: name and/or code % of applied rate (range and maximum)	None

Supplemental studies
Anaerobic:	Phenyl moiety: same as under aerobic condition THP moiety: no data provided, not required (spring application, high mineralization) CO₂ about 3 %, bound 47 % (85 d)

Soil photolysis:	Light has no effect on degradation route but degradation rate is slightly enhanced.

Remarks:	None

Rate of degradation
Laboratory studies
DT₅₀lab (20 °C, aerobic):	Soil type pH OC % Temp. DT50 (in days) Sandy loam 7.8 0.7 25°C 11.9 Sandy loam 7.9 0.8 17.5 Loamy sand 5.8 1.2 20°C 27.5 Sand 4.4 0.7 120.0* Clay loam 5.4 2.0 23.5 Loamy sand 7.4 1.7 15.2 Sandy loam 5.6 2.5 19.0 * soil type not relevant for the intended uses
DT₉₀lab (20 °C, aerobic):	Soil type pH OC % Temp. DT90 (days) Loamy sand 5.8 1.2 20°C 91.4 Sand 4.4 0.7 399.0* Clay loam 5.4 2.0 78.2 Loamy sand 7.4 1.7 50.5 Sandy loam 5.6 2.5 63.3 * soil type not relevant for the intended uses
DT₅₀lab (10 °C, aerobic):	89 d (sandy loam, pH 5.4, OC 1.7 %)
DT₅₀lab (20 °C, anaerobic):	43 d (sandy loam, pH 5.6, OC 2.5 %)

Field studies (country or region)
DT_50f from soil dissipation studies:	DT_50f: Not precisely determined (few data points available) but short persistence confirmed by 2 field dissipation studies carried out in France (soil residue < 0.01 mg/kg (about 4 %) after 56 - 112 d).
DT_90f from soil dissipation studies:	DT_90f: _{Not precisely determined (few data points available) but short persistence confirmed by 2 field dissipation studies carried out in France (soil residue < 0.01 mg/kg (about 4 %) after 56 - 112 d).}
Soil accumulation studies:	Not relevant, not required
Soil residue studies:	Not relevant, not required

Remarks:	None

Adsorption/desorption
K_f / K_OC: K_d pH dependence:	_{Koc estimated to be 1412 ml/g (95% CI = 758-2884) by HPLC method because of rapid degradation in water. Kd 12.3-24.6 (3 soils, OC 1.3-2.5 %, pH 5.5-7.1 Koc 739-983, mean 889 (3 soils) no pH dependence}

Mobility
Laboratory studies:
Column leaching:	525 mm over 2 days (data in %, except pH) Soil type sand clay OC pH RA in leachates (flumioxazin) Sand 97 2 0.2 5.4 63.9 - 67.4 Sandy loam 67 4 0.7 7.8 51.2 - 54.6 Silt loam 29 13 0.6 7.0 7.4 - 15.3 Clay loam 21 32 2.9 7.0 3.0 - 5.0
Aged residue leaching:	Loamy sand (71% sand, 11% clay, 1.2 % OC, pH 5.8); incubation 20°C, 31 d; 200 mm water over 2 d: 49 % flumioxazin remaining after incubation 0.55 % of applied RA in leachates

Field studies:
Lysimeter/Field leaching studies:	No data, not required

Remarks:	None

Fate and behaviour in water

Abiotic degradation
Hydrolytic degradation:	pH 5 (25° C): DT₅₀ = 3-5 d metabolites : THPA (95.5 %) and APF (86.8 %) - stable pH 7 (25° C): DT₅₀ = 19-26 hours metabolites : - 482HA (max. 62.9 % after 1 d, DT50 = 10.7 d) - THPA (83.6 %) and APF (80.0 %) - stable pH 9 (25° C): DT₅₀ = 14-23 minutes metabolites : 482HA (98.5 %, DT50 = 72 d)
Relevant metabolites:	THPA, APF, 482-HA (depends on pH)
Photolytic degradation:	pH 5 (25°C): DT₅₀ = 21-26 hours metabolites: - polar compound shown to probably result from opening of the phenyl ring max. 70 % (7 d) - THPA max. 20.2 % (7 d)
Relevant metabolites:	THPA

Biological degradation
Readily biodegradable:	Not readily biodegradable
Water/sediment study: DT₅₀ water: DT₉₀ water: DT₅₀ whole system: DT₉₀ whole system: Mineralization Non extractable residues Distribution in water / sediment systems (active substance) Distribution in water / sediment systems (metabolites)	DT₅₀ water < 1.85 d DT₅₀ whole system < 1.85 d DT₉₀ whole system 25-69 d 27-31%(THP), <9% (phenyl) after 98d 29-47%(THP), 60-61% (phenyl) after 98d Flumioxazin max. 27 % in sediment (7 d) APF max. 58 % in water (7 d), DT₅₀ 29 d THPA max. 63 % in water and 18 % in sediment (7 d), DT₅₀ 28 d in water
Accumulation in water and/or sediment:	Not relevant

Degradation in the saturated zone	No data available, not required.

Remarks:	None

Fate and behaviour in air

Volatility
Vapour pressure:	3.2 ·10^-3Pa at 22 °C
Henry's law constant:	6.36 ·10^-2Pa·m³·mol^-1

Photolytic degradation
Direct photolysis in air:	No data provided, not required (no absorbance above 290 nm)
Photochemical oxidative degradation in air DT₅₀:	5.8 h
Volatilisation:	From plant surfaces: no data provided From soil: 7.7 % (DOW model)

Remarks:	None

In the Dutch Pesticide Law the Uniform Principles are implemented in the Regulation of Uniform Principles for Plant protection products (BUBG).

6.1 Fate and behaviour in soil

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

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

Article 2 of the Regulation elaborating the uniform principles for plant protection products contains the authorisation criterion persistence. The Board for the authorization of pesticides in the Netherlands (CTB) has to evaluate persistence in compliance with INS[1]. Reference is made to a new ‘decision tree’, which has been laid down in the RIVM[2] report 601506008/2005: ‘Persistence of plant protection products in soil; a proposal for risk assessment. Persistence has to be evaluated by the CTB on the basis of this decision tree.

However, this decision tree is currently still under development, which means that immediate application is not possible. So, application of the new method for the assessment of persistence of plant protection products for authorization will start in the near future.

As long as the mentioned RIVM report has not yet been laid down by the competent authorities, the CTB will fall back on the tested and applied method as it has been in use until now for the evaluation of applications for authorisation of plant protection products.

In this case this means the following for the evaluation of persistence of plant protection product.

6.1.1 Persistence in soil

The following laboratory DT50 values are available for the active substance flumioxazin: 11.9, 17.5, 27.5, 120.0, 23.5, 15.2, 19.0 days (median 19.0 days, range 11.9 - 120 days). The mean DT₅₀-value of the a.i. can thus be established to be <90 days. Furthermore it can be excluded that after 100 days there will be more than 70% bound (non-extractable) residues of the initial dose together with the formation of less than 5% CO₂ of the initial dose.

Herewith, the standards for persistence as laid down in the Regulation of Uniform Principles for Plant protection products (BUBG) are met.

The concentration of flumioxazin in soil is needed to assess the risk for soil organisms (earthworms, micro-organisms). The PIECsoil is calculated for the upper 5 cm of soil using a soil bulk density of 1500 kg/m³. See Table M.2 for input values and results.

Table M.2 PEC soil calculations (5 cm and 20 cm)

Use

Rate

[kg a.s./ha]

Frequency

Fraction on soil

PECsoil 5 cm

(mg/kg)

Permanent non-cultivated area’s (i.e. verges, underneath crash-barriers, traffic signs etc.) excluding hard surfaces

0.6

0.80

Herewith, the proposed applications of the pesticide meet the standards for persistence as laid down in the Regulation of Uniform Principles for Plant protection products (BUBG).

6.1.2 Leaching to shallow groundwater

The leaching potential of the a.i. flumioxazin) is calculated in the first tier using Pearl 2.2.2. and the FOCUS Kremsmünster scenario. The new decision tree for leaching including the new model GeoPEARL has been released for use in risk assessment at the end of 2004. In a letter of minister Veerman of the department of Agriculture, Nature and Food quality he asked the CTB to anticipate on the revision of the Rumb (2000) concerning the assessment of leaching to groundwater. This request is based on article 6 of the Pesticide act (state of science) in combination with article 6 of the Regulation (new models). The methodology as described in the report "The new decision tree for the evaluation of pesticide leaching from soils", A.M.A van der Linden, J.J.T.I. Boesten, A.A. Cornelese, R. Kruijne, M. Leistra, J.B.H.J Linders, J.W. Pol, A. Tiktak and A.J Verschoor, RIVM report 601450019/2004, RIVM, Bilthoven (2004) has to be used.

Input variables are the actual application rate [0.6 kg/ha], the crop [bare soil] and an interception value appropriate to the crop of [0][3].

The following input data are used for the calculation:

PEARL:

Active substance:

Median DT₅₀ for degradation in soil (20°C): 19.0 days

Median K_om (pH-independent): 523 L/kg .

Saturated vapour pressure: 3.2 x 10^-3 Pa (22°C)

Solubility in water: 1.79 mg/L (25°C)

Molecular weight: 354.3 g/mol

Other parameters: standard settings of PEARL 2.2.2

The following concentrations are predicted for the a.i. flumioxazin following spring applications, see table M.3.

Table M.3 Leaching of a.i. and metabolites as predicted by PEARL 2.2.2

Use	Substance	Rate substance	Frequency	Interval	Fraction on soil	PEC groundwater
		[kg/ha]		[days]		spring [mg/L]
Permanent non-cultivated area’s (i.e. verges, underneath crash-barriers, traffic signs etc.) excluding hard surfaces	flumioxazin	0.6	1	-	1	<0.001

Use

Substance

Rate substance

Frequency

Interval

Fraction

on soil

PEC

groundwater

[kg/ha]

[days]

spring

[mg/L]

Permanent non-cultivated area’s (i.e. verges, underneath crash-barriers, traffic signs etc.) excluding hard surfaces

flumioxazin

0.6

<0.001

Results of Pearl 2.2.2. using the Kremsmünster scenario are examined against the standard of 0.01 µg/l. This is the BUBG 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 it reads that the expected leaching based on the PEARL-model calculations for the a.i. flumioxazin is <0.001.

Hence, the formulation meets the standards laid down in the Regulation of Uniform Principles for Plant protection products (BUBG) for the proposed applications.

Lysimeterstudies

Monitoring data

There are no data available regarding the presence of the substance flumioxazin in groundwater.

Conclusions

The product complies with the requirements laid down in BUBG 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 flumioxazin and metabolites in the surface water are 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. For the active substance and the metabolite(s) the following input is required (all on the basis of mean values):

TOXSWA:

Active substance:

DT₅₀ for degradation in water at 20°C: 1.85 days

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

K_om for suspended organic matter: 523 L/kg

K_om for sediment: 523 L/kg

Saturated vapour pressure: 3.2 x 10^-3 Pa (22°C)

Solubility in water: 1.79 mg/L (20°C)

Molecular weight: 354.3 g/mol

Metabolite 482 HA:

DT₅₀ for degradation in water at 20°C: 10.7 days

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

K_om for suspended organic matter:? L/kg

K_om for sediment: ? L/kg

Formation fraction: 62.9%

Molecular weight: 372.3 g/mol

Metabolite APF:

DT₅₀ for degradation in water at 20°C: 29 days

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

K_om for suspended organic matter:? L/kg

K_om for sediment: ? L/kg

Formation fraction: 58%

Molecular weight: 220.2 g/mol

Metabolite THPA:

DT₅₀ for degradation in water at 20°C: 28 days

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

K_om for suspended organic matter:? L/kg

K_om for sediment: ? L/kg

Formation fraction: 63% in water

17% in sediment

Molecular weight: 170.08 g/mol

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 substance flumioxazin and its metabolites APF and THPA for each intended use are presented.

Because insufficient data are available for the metabolites, exposure concentrations can be calculated from the active substance, correcting for formation percentage and relative molecular weight.

Table M.4 Overview of surface water concentrations for flumioxazin and metabolites following spring application

Use	Substance	Rate a.s. [kg/ha]	Drift [%]	PIEC [mg/L]^*	PEC21 [mg/L]^*	PEC28 [mg/L]^*	PECsed [mg/kg]**
				spring	spring	spring
Permanent non-cultivated areas (i.e. verges, underneath crash-barriers, traffic signs etc.) excluding hard surfaces	Flumioxazin	0.60	1	2.85	0.56	0.43	0.0727
	482 HA	0.397	1	1.88	-	-
	APF	0.216	1	1.03	-	-
	THPA	0.182	1	0.866	-	-	0.0059

^*calculated according to TOXSWA

**calculated by taking the highest concentration in sediment in TOXSWA and a bulk density of 80 kg/m³ (dw).

These exposure concentrations are examined against ecotoxicological threshold values in section 7.2.

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 Act Administrative Law)) that the Ctb should for an authorisation, on the basis of the scientific and technical knowledge, considering the data submitted with the application, also test against the drinking water criterion as regards surface water intended for drinking water production to establish whether the product has no effect that is unacceptable for the environment. A mathematical model for this aspect is not available. This means that possibly available data cannot be taken into account adequately. It is therefore not possible to arrive at a scientifically well-based assessment of an expectation for this criterion. The Ctb has not been given the instruments for testing surface water from which drinking water is produced against the drinking water criterion. In order to meet the Court decision, however - from which it can be concluded that the Ctb should make an effort to arrive at a judgement on this point – and as transitional period, to prevent that not a single authorisation can be granted in the period during which a model is being developed and data need to be generated for the application for authorisation, the Ctb has investigated whether the product under consideration and the active substance could give cause for concern about the drinking water criterion.

Flumioxazin

As flumioxazin is a new active substance, no knowledge exists on its potential presence in surface water. At the moment, a preliminary decision tree (C-163.5) is used to address this matter, while waiting for the final decision tree that is currently under construction by the Drinking Water Criterion Project Team (expected in 2007-2008).

For the time being a refinement considering the remaining time in water (14 days) and a dilution factor (10) can be used.

Permanent non-cultivated area’s excluding hard surfaces

The maximum predicted concentration in water, calculated with TOXWA amounts 2.85 µg a.s./L. Assuming a remaining time before intake of 14 days and a dilution factor of 10, the maximum predicted concentration in drinking water abstraction points is 0.0015 µg/L. For metabolites 482 HA, APF and THPA this is respectively 0.076, 0.074 and 0.061 µg/L. These concentrations are <0.1 µg/L and no exceeding of the drinking water criterion is to be expected.

Therefore, the proposed application meets the drinking water criterion.

Monitoring data

There are no data available regarding the presence of the flumioxazin in surface water.

6.3 Fate and behaviour in air

Route and rate of degradation in air

The active substance is moderately volatile. The vapour pressure is 3.2 x10^-3Pa at 22 °C. The Henry constant is 6.36 x·10^-2Pa·m³·mol^-1 at 20°C. The half-life in air is 5.8 h.

At present there is no framework to assess fate and behaviour in air of plant protection products.

6.4 Appropriate fate and behaviour end-points relating to the product and approved uses

See List of End-points.

6.5 Data requirements

7. Ecotoxicology

List of Endpoints Ecotoxicology

Flumioxazin is a new substance, placed on Annex I (10/10/2002). For the risk assessment the LoEP is used. Commands are given in Italic.

The 50 WP formulation mentioned in the LoEP is the formulation Pledge. This is comparable with the WP50% formulation Toki. The endpoints of Pledge will be used for the risk assessment of Toki.

An additional study for non-target arthropods was submitted. This study has been evaluated and summarised by the CTB (toki_20050109_a-rhopalospihi_extlabtest_samenv).

Ecotoxicology

Terrestrial Vertebrates

Acute toxicity to mammals:	LD50 (rat) > 5000 mg/kg
Acute toxicity to birds:	LD50 (bobwhite quail) > 2250 mg/kg bw LD50 (mallard duck) > 2250 mg/kg bw
Dietary toxicity to birds:	LC50 (bobwhite quail) > 1870 mg/kg bw LC50 (mallard duck) > 2130 mg/kg bw
Reproductive toxicity to birds:	NOEC (bobwhite quail) = 500 ppm NOEC (mallard duck) = 250 ppm
Short term oral toxicity to mammals:	NOEL = 300 ppm(1^st oral 90-d study, rat) NOEL = 10 mg/kg/d(teratogenicity study, rat)

Aquatic Organisms

Acute toxicity fish:	LC50 = 2.3 mg/l (96 h, Oncorhynchus mykiss) LC50 > 21 mg/l (96 h, Lepomis macrochirus) LC50 > 26 mg a.s./l (96 h, O. mykiss, 50% WP)
Long term toxicity fish:	NOEC = 0.37 mg/l (21 d, O. mykiss)
Bioaccumulation fish:	Not relevant (log Pow = 2.55)
Acute toxicity invertebrate:	EC50 = 5.9 mg/l (48 h, D. magna)
Chronic toxicity invertebrate:	NOEC = 0.057 mg/l (21 d, D. magna)
Acute toxicity algae:	EC50 = 0.000852 mg/l (72 h; Selenastrum capricornutum) EC50 = 0.0015 mg/l (120 h; Navicula pelliculosa) EC50 = 0.00078 mg a.s./l (72 h; Pseudokirchneriella subcapitata, 50% WP)* EC50 = 0.0015 mg a.s./l (120 h; Navicula pelliculosa, 50% WP)*
Chronic toxicity sediment dwelling organism:	NOEC = 0.73 mg/kg (23 d; Chironomus riparius)
Acute toxicity aquatic plants:	EC50 = 0.00035 mg/l (14 d; Lemna gibba)
Acute toxicity aquatic plants with sediment:	14 d, Lemna gibba, 50% WP: EC50 = 0.0023 mg a.s./l (biomass)**

*Taken from monograph (addendum ecotox):

In addition, the exposure was prolonged to 7 d in the new studies with 50WG in order to observe potential recovery. The green alga and diatom began the exponential growing within 2-3 days delay even in the highest test concentrations of 2.2 and 14 microg as/l, respectively. A few days delay for algal growth should be regarded as not significant and considered as acceptable to the aquatic ecosystems.

**Taken from monograph (addendum ecotox):

In addition, continuous frond production was observed up to 10 microg as/l with 5 days delay to achieve or exceed frond density similar to the control. Considering the fluctuation of aquatic plant populations in the field due to the daily weather conditions especially for the sunlight intensity, 5 days delay of the growth should be regarded as not significant and considered acceptable to the aquatic ecosystems. In addition, it is likely that aquatic plants immigrate from other areas by water flow or attaching to materials or organisms in the actual field, and immigrations accelerate the re-colonisation of aquatic plants due to rapid dissipation of the compound.

Honeybees

Acute oral toxicity:

LD50 > 100 µg a.s./bee

LD50 > 200 µg 50% WP/bee

Acute contact toxicity:

LD50 > 105 µg a.s./bee

LD50 > 200 µg 50% WP/bee

Other arthropod species

	% Adverse effect
Typhlodromus pyri	Mortality, fertility: 2 % (protonymphs; 50% WP, 0.6 kg a.s./ha)
Aphidius rhopalosiphi	Mortality, parasitism: 75 % (adults; 50% WP, 0.6 kg a.s./ha)
Poecilus cupreus	Mortality, food consumption: 0 % (adults; 50% WP, 0.6 kg a.s./ha)
Chrysoperla carnea	Mortality: 0 % (larvae; 50% WP, 0.6 kg a.s./ha)
Aleochara bilineata	Reproduction: < 0 % (adults; 50% WP, 0.6 kg a.s./ha)
Pardosa amentata.	Mortality, food consumption: 0 % (adults; 50% WP, 0.6 kg a.s./ha)

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 of e.g. reproduction) and a – sign for mortality effect percentages (i.e. decrease of mortality).

Additional study with Aphidius rhopalosiphi:

Extended laboratory study with Toki 50% WP on barley. LR50 > 1.2 kg a.s./ha, EC50 > 1.2 kg a.s./ha.

Earthworms

Acute toxicity:

LC50 > 982 mg/kg soil

NOEC = 61 mg/kg soil

Reproductive toxicity:

Not required.

Soil micro-organisms

Nitrogen mineralization:	1.75 mg a.s./kg d.w. soil (equivalent to 1.2 kg a.s./ha): no effect
Carbon mineralization:	1.75 mg a.s./kg d.w. soil (equivalent to 1.2 kg a.s./ha: no effect

In the Dutch Pesticide Law the Uniform Principles are implemented in the Regulation of Uniform Principles for Plant protection products (BUBG).

7.1 Effects on birds

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

7.1.1 Natural food and drinking water

The threshold value for birds is based on the trigger from the BUBG. The threshold value for acute and short term exposure is set to 0.1 times the LD₅₀ en LC₅₀ value, and the threshold value for chronic exposure is set to 0.2 times the NOEC. In table E.1 an overview of toxicity data and resulting threshold values are presented.

In the risk assessment a small bird with a body weight (BW) of 10 gram, a daily food intake (DFI) of 2.9 g/day and a daily water intake (DWI) van 3 g is chosen as representative target species.

Table E.1 Overview of threshold values for birds

Substance	Exposure		Endpoint	Safety factor	Threshold value
			[mg/kg bw]		[mg/bird]
flumioxazin	Acute	LD50	>2250	10	>225
			[mg/kg food]		[mg/kg food]
	Short term	LC50	>1870	10	>187
	Long term	NOEC	250	5	50

The initial concentration in food is calculated using the relationship of Luttik et al. for [leafs, leafy crops, fodder crop and small seeds and insects] as 25 * application rate* number of applications. In first instance, acute, short term and long term exposure is examined against the PIEC_food, without taking decline of the residue between applications into account.

Surface water concentrations are calculated using TOXSWA (see paragraph 6.2.1). In first instance, acute exposure is compared to the maximum PIEC_water(1.77mg/L).

In table E.2 an overview is presented of the calculated concentrations in food.

Tabel E.2 Overview of concentrations in food

use	Rate	RUD *	Max. freq.	PIEC_food
	[kg a.s./ha]			[mg/kg]
Permanent non-cultivated area’s excluding hard surfaces (i.e. verges, underneath crash-barriers, traffic signs etc.)	0.60	25	1	15

* residue per unit dose according to Luttik

In table E.3, threshold exceeding factors at exposure to food and drinking water are presented.

Table E.3 Threshold exceeding factors for natural food and drinking water

Use	Threshold exceeding factors
	water, acute	food, acute	food, short term	food, long term
	*PIECDWI/ 0.1LD50_{target species}*	*PIECDFI/ 0.1LD50_{target species}*	*PIEC/ 0.1LC50**	*PIEC/ 0.2NOEC**
Permanent non-cultivated area’s (i.e. verges, underneath crash-barriers, traffic signs etc.) excluding hard surfaces	<0.024	<0.019	<0.08	0.3

Taking the results in Table E.3 into account, a low risk for birds can be expected due to foraging and drinking of surface water for all proposed uses.

The proposed uses meet the standards laid down in the Regulation of Uniform Principles for Plant protection products (BUBG).

7.1.2 Secondary poisoning

Since the log K_ow of flumioxazin is 2.55 and thus < 3, the risk on secondary poisoning is acceptable.

Hence, the proposed application meets the standards for secondary poisoning as laid down in the Regulation of Uniform Principles for Plant protection products (BUBG).

Conclusions birds

The product complies with the Regulation of Uniform Principles for Plant protection products (BUBG).

7.2 Effects on aquatic organisms

7.2.1 Aquatic organisms

The threshold values based on toxicity data for aquatic organisms are presented in table M.9 for the active substance flumioxazin. Threshold values for acute exposure are 0.01 times the L(E)C₅₀-value (daphnids and fish) and 0.1 times the lowest EC₅₀-value for algae.

Because the application for authorisation concerns an herbicide, also the effects on macrophytes/aquatic plants are evaluated against the acute threshold value (0.1 times the lowest EC₅₀).

Threshold values for chronic exposure are 0.1 times the lowest NOEC-value for daphnids and fish. See Table E.4 for the derivation of acute and chronic threshold values.

Table E.4 Overview toxicity endpoints and threshold values for flumioxazin

Substance	Organism	Lowest		Safety factor	Threshold value
		L(E)C₅₀ [mg/L]	NOEC [mg/L]		[mg/L]	[mg/L]
Flumioxazin	Acute
	Algae	0.00085		10	0.000085	0.085
	Daphnids	5.9		100	0.059	59
	Fish	2.3		100	0.023	23
	Macrophytes	0.00035		10	0.000035	0.035
	Chronic
	Daphnids		0.057	10	0.0057	5.7
	Fish		0.37	10	0.037	37
50% WP	Acute
	Algae	0.00078		10	0.000078	0.078
	Daphnids	-		100		-
	Fish	>26		100	>0.26	>260
	Macrophytes*	0.0023*		10	0.00023	0.23

*test with sediment

For the risk assessment the lowest endpoints are used.

The risk for aquatic organisms for the various uses of the active substance is assessed by comparing surface water exposure concentrations (from section 6.2) with the above trigger values. In table E.5 it is indicated if and to what extent exceeding of the threshold values for aquatic organisms occurs.

Table E.5 Threshold exceeding factors for flumioxazin

Use	Substance	*PIEC/ (0.1* EC₅₀)**	*PIEC/ (0.01EC₅₀)*	*PIEC/ (0.01LC₅₀)*	*PIEC/ (0.1* EC₅₀)**	*PEC21/ (0.1NOEC)*	*PEC28/ (0.1NOEC)*
		Algae	Daphnids	Fish	Lemna¹	Daphnid	Fish
		Spring	Spring	Spring	Spring	Spring	Spring
Permanent non-cultivated area’s (i.e. verges, underneath crash-barriers, traffic signs etc.) excluding hard surfaces	Flumioxazin	36.5	0.048	0.12	81.4/12.4	0.098	0.012

^*calculated according TOXSWA

¹x /x = normal study / study with sediment

On the basis of the above risk assessment, a risk for flumioxazin cannot be excluded for algae and macrophytes. Therefore, it has to be demonstrated by means of an adequate risk assessment that the risk is acceptable. The following data are provided and used in the refined risk assessment described below.

Second tier (refinement of the risk assessment)

From the addendum (ecotox) of the monograph it appears that the studies with algae and Lemna gibba (50% WP formulation) were prolonged with 7 days. From these studies it appears that the effects on algae and water plants disappeared within 7 days for algae and 5 days for Lemna gibba at concentrations up to 14 µg a.s./L (algae) and 10 µg a.s./L (Lemna). It is stated that these short lasting effects are of no ecological significance.

The maximal predicted concentration in the use on permanently non-cultivated areas excluding hard surfaces (i.e. verges, underneath crash-barriers, traffic signs etc.) is 2.85 µg a.s./L. For this use, the expected risk is acceptable and the standards for aquatic organisms as laid down in the Regulation of Uniform Principles for Plant protection products (BUBG) are met.

Metabolites

Metabolites 482-HA, APF and THPA are considered relevant for the aquatic system. However, no ecotoxicological data is available. In the Addendum on Ecotoxicology (B8.2.9.2) a reasoning is provided concerning these metabolites, stating that any effects of the metabolites will be sufficiently covered by the tests with the active substance (the standard toxicity tests will have addressed the hydrolysis product 482-HA, and the higher tier studies will have covered APF and THPA). This reasoning is acceptable. Therefore, the expected risk is acceptable and the standards for aquatic organisms as laid down in the Regulation of Uniform Principles for Plant protection products (BUBG) are met.

7.2.2 Risk assessment for bioconcentration

Since the logPow is 2.55 and below 3, the risk for bioconcentration is small. Therefore the active substance meets the standards for bioconcentration as laid down in the BUBG.

7.2.3 Risk assessment for sediment organisms

Since the NOEC for daphnids is below 0.1 mg/L and the water–sediment study indicates that over 10% of flumioxazin is found in the sediment after 14 days, there is a potential risk for sediment organisms.

The threshold value for Chironomus is 0.1 x NOEC = 0.1 x 0.3 =0.073 mg/kg. When this value is examined against the PIEC in sediment for the use in permanent non-cultivated areas excluding hard surfaces of 0.0727 mg/kg, the threshold exceeding value is 0.996.

The maximum percentage of metabolite THPA in sediment is 17%. No ecotoxicological data is available. However, since the maximum concentration was found after 7 days and the study for C. riparius was 23 days, effects of this metabolite should be included in the test with the active substance.

For the use in permanently non-cultivated areas excluding hard surfaces, the standards for sediment organisms as laid down in the Regulation of Uniform Principles for Plant protection products (BUBG) are met.

Conclusions aquatic organisms

The product complies with the Regulation of Uniform Principles for Plant protection products (BUBG).

An adequate risk evaluation for the use on hard surfaces (i.e. concentrations in STP or in run-off water) and ecotoxicological data for the metabolites APF and THPA for aquatic organisms are required

7.3 Effects on terrestrial vertebrates other than birds

Mammals can be exposed to the active substance by natural food (sprayed insects, seeds, leafs), granules as food, drinking water and as a result of secondary poisoning.

7.3.1 Natural food and drinking water

The threshold value for mammals is based on the trigger from the BUBG. The threshold value for acute and short term exposure is set to 0.1 times the LD₅₀ en LC₅₀ value, and the threshold value for chronic exposure is set to 0.2 times the NOEC. In table E.6 an overview of toxicity data and resulting threshold values are presented.

In the risk assessment a small mammal with a body weight (BW) of 6 gram (i.e., a mouse), a daily food intake (DFI) of 1.025 g/day and a daily water intake (DWI) van 1.8 g is chosen.

Table E.6 Overview of threshold values for mammals

Substance	Exposure		Endpoint	Safety factor	Threshold value
			[mg/kg bw]		[mg/mammal]
Flumioxazin	Acute	LD50	>5000	10	>500
			[mg/kg food]		[mg/kg food]
	Long term	NOEC	300	5	60

The initial concentration in food is calculated using the relationship of Luttik et al. for leafs, leafy crops, fodder crop and small seeds and insects as [25] * application rate* number of applications. In first instance, acute, short term and long term exposure is examined against the PIEC_food, without taking decline of the residue between applications into account.

Surface water concentrations are calculated using TOXSWA (see paragraph 6.2.1). In first instance, acute exposure is compared to the PIEC_water.

In table E.7 an overview is presented of the calculated concentrations in food.

Table E.7 Overview concentrations in food

Use	Rate	RUD *	Max. freq.	PIEC_food
	[kg/ha]			[mg/kg]
Permanent non-cultivated area’s (i.e. verges, underneath crash-barriers, traffic signs etc.) excluding hard surfaces	0.6	25	1	15

* residue per unit dose according to Luttik

In table E.8, threshold exceeding factors at exposure to food and drinking water are presented.

Table E.8 Threshold exceeding factors for natural food and drinking water

Use	Threshold exceeding factors
	water, acute	food, acute	food, long term
	*PIECDWI/ 0.1LD50_{target species}*	*PIECDFI/ 0.1LD50_{target species}*	*PIEC/ 0.2NOEC**
Permanent non-cultivated area’s (i.e. verges, underneath crash-barriers, traffic signs etc.) excluding hard surfaces	<0.0011	<0.0051	0.25

Taking the results in Table E.8 into account, it appears that a low risk for mammals can be expected due to foraging and drinking of surface water for all proposed uses.

The proposed uses meet the standards laid down in the BUBG.

7.3.2 Secondary poisoning

Since the log K_ow of flumioxazin is 2.55 and thus < 3, the risk on secondary poisoning is acceptable.

Hence, the proposed application meets the standards for secondary poisoning as laid down in the Regulation of Uniform Principles for Plant protection products (BUBG).

Conclusions mammals

The product complies with the Regulation of Uniform Principles for Plant protection products (BUBG)

7.4 Effects on bees

The risk assessment for bees and bumblebees is based on the ratio between the single application rate and toxicity endpoint (LD₅₀ value). An overview of the risk at the proposed applications/uses is given in table E.9.

Tabel E.9 Risk for bees and bumblebees

Use

Application rate a.s.

[g/ha]

LD₅₀

[µg/bee]

Rate/LD₅₀

Permanent non-cultivated area’s (i.e. verges, underneath crash-barriers, traffic signs etc.) excluding hard surfaces

600

>100

Since the ratio rate/LD₅₀ is below 50, the risk for bees is considered to be low. Hence, all proposed applications meet the standards for bees and bumblebees as laid down in the Regulation of Uniform Principles for Plant protection products (BUBG).

Conclusions bees

The product complies with the Regulation of Uniform Principles for Plant protection products (BUBG).

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 arthopods is assessed by calculating Hazard Quotients. To enable this, Lethal Rate values (LR₅₀) are needed.

Based on LR₅₀-values from laboratory studies with Typhlodromus pyri (LR₅₀ > 0.60 kg a.s./ha) an in-field and an off-field Hazard Quotient (HQ) can be calculated according to the (new) assessment method established in the SETAC/ESCORT 2 workshop and described in the HTB (v 0.2). Hazard Quotients should be below the trigger value of 2 to meet the standards. Resulting Hazard Quotients are presented in Table E.10.

Table E.10 HQ-values for T. pyri

	Application rate (kg a.s./ha)	MAF¹	Drift factor/ Vegetation factor²	Safety factor²	LR₅₀ (kg a.s./ha)	HQ
In-field
T. pyri	0.600	1	-	-	>0.600	<1
Off-field
T. pyri	0.600	1	1	10	>0.600	<0.1

¹: Multiple Application Factor

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

From the above Table, it reads that both in- and off-field HQ values are below/above the trigger value of 2.

For the standard species Aphidius rhopalosiphi an extended laboratory study is available. Based on LR₅₀-values from extended laboratory studies with Aphidius rhopalosiphi (LR₅₀ > 1.2 kg a.s./ha and ER₅₀ > 1.2 kg a.s./ha) an in-field and an off-field Hazard Quotient (HQ) can be calculated according to the (new) assessment method established in the SETAC/ESCORT 2 workshop and described in the HTB (v 0.2). Hazard Quotients should be below the trigger value of 1 to meet the standards. Resulting Hazard Quotients are presented in Table E.11.

Table E.11 HQ-values for A. rhopalosiphi

	Application rate (kg a.s./ha)	MAF¹	Drift factor/ Vegetation factor²	Safety factor²	L(E)R₅₀ (kg a.s./ha)	HQ
In-field
A. rhopalosiphi	0.6	1	-	-	>1.200	<0.5
Off-field
A. rhopalosiphi	0.600	1	1	10	>1.200	<0.05

¹: Multiple Application Factor

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

Several other non target arthropods were tested. In laboratory test with an application rate of 0.6 kg a.s./ha (maximum proposed concentration) no lethal and sublethal effects were found for Crysoperla carnea, Poecilus cupreus, Aleochara bilineata and Pardosa amentata.

Therefore, the formulation meets the standards as laid down in the Regulation of Uniform Principles for Plant protection products (BUBG).

7.5.2 Earthworms

The trigger value for acute toxicity to earthworms is based on the standards from the BUBG and amounts 0.1 * LC₅₀. The initial PEC soil is examined against that value. Since the logPow of the active substance > 2, correction to the reference soil containing 4.7 % organic matter is necessary. The trigger value for earthworms based on this normalised 14-day LC₅₀(>462 mg/kg) of the active substance amounts >46.2 mg/kg. 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. Table E.12 presents the PECsoil and the threshold exceeding for flumioxazin.

Table E.12 Overview of soil concentrations and exceeding of threshold values at acute exposure

Application/

use

Substance

Application rate

[kg/ha]

Fre

quency

Interval

[day]

Fraction on soil

PIECsoil

[mg/kg]

Exceeding of threshold

Permanent non-cultivated area’s (i.e. verges, underneath crash-barriers, traffic signs etc.) excluding hard surfaces

Flumioxazin

0.600

0.800

<0.017

Since the threshold exceeding factor is 0.001 – 0.1, the frequency of application is £ 3 per season and the DT₉₀-value of the active substance is < 100 days, sublethal studies are not required.

However, since a sublethal study is available, the chronic risk will be assessed.

Examination of the PIEC is against the trigger of 0.2*NOEC. The NOEC is 61 mg a.s./kg soil. Corrected for the organic matter this amounts 28.68 mg a.s./kg. Thus, the trigger value is 5.73 mg a.s./kg.

Table E.13 Overview of soil concentrations and threshold exceeding factors at chronic exposure

Use

Substance

Application rate

[kg/ha]

Fre

quency

Interval

[day]

Fraction on soil

PIECsoil

[mg/kg]

Threshold exceeding factor

Permanent non-cultivated area’s (i.e. verges, underneath crash-barriers, traffic signs etc.) excluding hard surfaces

Flumioxazin

0.600

0.80

0.14

The threshold value for earthworms at chronic exposure to flumioxazin is not exceeded. Therefore, all proposed applications/uses meet the standards as laid down in the Regulation of Uniform Principles for Plant protection products (BUBG).

7.5.3 Effects on soil micro-organisms

In the tested soils no effects are observed on nitrogen and carbon metabolisation processes at application rates of 1.75 mg a.s./kg soil (equivalent to 1.2 kg a.s./ha) with flumioxazin. Since the reduction percentage is below 25% after 28 days, the standards from the Regulation of Uniform Principles for Plant protection products (BUBG) regarding soil micro-organisms are met.

7.5.4 Effects on activated sludge

For the proposed use (permanently non-cultivated areas excluding hard surfaces), no exposure of activated sludge is expected. Therefore, the proposed applications comply with the standards for activated sludge as laid down in the BUBG.

N.B. In the monograph is stated that:

‘Due to:

- the rapid and extensive degradation of flumioxazin and limited usage

- the absence of significant effect on soil micro-organisms

- the negative results of microbial mutagenicity assays

no significant contamination of sewage treatment plants is anticipated to arise from the proposed agricultural use.’

Furthermore, the notifier has provided a study (not evaluated; Noack, M. Ecological study – respiration inhibition test with activated sludge, 2002) in which no EC50 could be determined within the range tested due to no clear dose-response relation. All effect % were below 20%. The EC50 is > 10000 mg/L.

The use on permanent non-cultivated area’s excluding hard surfaces meets the standard for activated sludge as laid down in the Regulation of Uniform Principles for Plant protection products (BUBG).

7.5.5 Effects on non target-plants

No data to evaluate the risk on non-target plants are available. This data is not needed for this risk assessment, but is required for future risk assessments (coming under HTB 1.0). For future assessments an adequate risk assessment according to the guidance document on terrestrial organisms is needed.

Conclusions any other organisms

The product complies with the Regulation of Uniform Principles for Plant protection products (BUBG).

7.6 Appropriate ecotoxicological end-points relating tot the product and approved uses

See List of End-points.

7.7 Data requirements

· none

For future assessments (coming under HTB 1.0):

· an adequate risk assessment for effects on non-target plants, according to the guidance document on terrestrial organisms.

7.8 Classification and Labelling

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

Symbol:

Indication of danger: dangerous for the environment

Risk phrases

R50

Very toxic to aquatic organisms.

Proposal for the classification and labelling of the formulation concerning the environment

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.
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.
Special provisions: DPD-phrases³	-	-

Plant protection products phrase: DPD-phrase	DPD01	To avoid risk for man and the environment, comply with the instructions for use
Child-resistant fastening obligatory?			n.a.
Tactile warning of danger obligatory?			n.a.

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

7.9 Overall conclusions regarding the environment

It can be concluded that:

the active substance flumioxazin meets the standards for persistence in soil as laid down in the Regulation of Uniform Principles for Plant protection products (BUBG).
all proposed applications of the active substance flumioxazin meet the standards for leaching to the shallow groundwater as laid down in the BUBG.
all proposed applications of the active substance flumioxazin meet the standards for aquatic organisms as laid down in the BUBG.
all proposed applications of the active substance flumioxazin meet the standards for birds as laid down in the BUBG.
the active substance flumioxazin meets the standards for bioconcentration as laid down in the BUBG.
all proposed applications of the active substance flumioxazin meet the standards for mammals as laid down in the BUBG.
all proposed applications of the active substance flumioxazin meet the standards for bees as laid down in the BUBG.
all proposed applications of the active substance flumioxazin meet the standards for non-target arthropods as laid down in the BUBG.
all proposed applications of the active substance flumioxazin meet the standards for earthworms as laid down in the BUBG.
all proposed applications of the active substance flumioxazin meet the standards for soil micro-organisms as laid down in the BUBG.
all proposed applications of the active substance flumioxazin meets the standards for activated sludge as laid down in the BUBG.
all proposed applications of the active substance flumioxazin meet the standards for non-target plants as laid down in the BUBG.

8. Efficacy

8.1 Efficacy evaluation

Dose justification

In 12 proeven is naast de geclaimde dosering van Toki (1,2 kg/ha) ook een lagere dosering (0,8 kg/ha) beproefd, terwijl in de 3 in België uitgevoerde proeven ook een hogere dosering (1,6 kg/ha) werd beproefd. Tussen de 3 doseringen waren geen grote verschillen in werking aanwezig. Wel was in een aantal proeven de tendens aanwezig dat de dosering van 0,8 kg/ha een kortere werkingsduur had dan de hogere doseringen en dat de werking van 0,8 kg/ha een wat mindere werking had tegen een aantal monocotylen.

Efficacy against weeds

In totaal zijn 12 werkingsproeven uitgevoerd waarvan 3 in België en 9 in Nederland, verdeeld over de jaren 2001 en 2002.

Tien proeven werden uitgevoerd op terreinen waarop op het moment van toepassing nog geen onkruiden aanwezig waren; in een proef werden de middelen op een aanwezige onkruidvegetatie toegediend. In enkele proeven was een zware onkruidvegetatie aanwezig die 1 week voor toediening van de middelen werd doodgespoten met paraquat, Roundup of MCPA. Dit zou een negatief effect kunnen hebben gehad op de proefresultaten.

Naast de geclaimde dosering van 1,2 kg/ha werd in alle proeven een dosering van 0,8 kg/ha toegediend en in 3 proeven een dosering van 1,6 k/ha.

Een dosering van 0,8 kg/ha lijkt marginaal gezien het feit dat in een aantal proeven de werkingsduur t.o.v. de hogere doseringen wat te kort schoot en gezien het feit dat de werking tegen een aantal monocotylen wat minder was dan van de hogere doseringen.

Tussen 1,2 kg/ha en 1,6 kg/ha waren weinig verschillen aanwezig.

In de proeven is een grote verscheidenheid aan dicotyle onkruiden voorgekomen. Hoewel een aantal onkruiden slechts in beperkte mate voorkwam en de bezetting niet overal de gewenste omvang had kan toch worden geconcludeerd dat Toki in de geclaimde dosering van 1,2 kg/ha een goede en langdurige werking heeft gegeven. Dit omdat de resultaten over de proeven heen consistent zijn.

Alleen tegen enkele wilgenroosjessoorten was de werking wat minder.

De werking was gelijk of beter dan die van de standaardmiddelen op basis van dichlobenil en diuron.

In een andere proef werden de middelen op een bestaande vegetatie toegepast en in 1 proef waarin een zware onkruidvegetatie aanwezig was werden de middelen 1 week nadat deze vegetatie met paraquat was doodgespoten toegediend. In beide proeven gaf Toki op enkele onkruidsoorten een wat mindere werking. Waarschijnlijk waren in laatstgenoemde proef de onkruiden op het moment van toediening van Toki nog niet geheel dood.

Uit de resultaten van deze beide proeven kan worden afgeleid dat Toki bij voorkeur op een onkruidvrije bodem dient te worden toegediend.

Het aantal gegevens dat van de bestrijding van monocotylen werd verkregen is vrij beperkt. De resultaten zijn wat wisselend. Geconcludeerd kan worden dat tegen monocotylen de werkingsduur van Toki korter is dan tegen dicotylen.

Conclusion

The product complies with the Uniform Principles because, in accordance with article 2.1, it controls the claimed weeds on permanent non cultivated land (excluding hard surfaces),

8.2 Harmful effects

Harmfull effects on plants or plant products are not relevant for phytotoxicity, yield, succeeding or substitution crops and plants or plant parts used for propagation, because the use of the product is restricted to non-cultivated areas were no crops are grown.

8.2.1 Phytotoxicity

Not relevant

8.2.2 Yield

Not relevant

8.2.3 Effects on succeeding crops or substitution crops

Not relevant

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

Not relevant

8.2.5 Effects on adjacent crops

Due to the field of use claimed (non cultivated land where plant growth is unwanted), and the fact that crops are seldom grown within the near vicinity (1-5 metres) of these areas, no unacceptable adverse effects on adjacent crops are expected.

Conclusion

Based on the characteristics of the product and the field of use claimed, no unacceptable side effects 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 in this case plant products, when used and applied in accordance with the proposed label.

8.3 Resistance

No data are provided. Hardly any resistance has been found against flumioxazin or PPO-inhibitors. One case of resistance in Amaranthus rudis has been reported in the United States. Considering the single application per year and the mode of action, resistance build up risk is considered small.

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

Not applicable. This aspect is not relevant as no vertebrates are controlled.

8.5 Any other relevant data / information

The following relevant data was used.

Appendix A of chapter 8 (efficacy) of the Manual for the authorisation of pesticides contains a list of crop and uses hierarchy to be used on the labels of authorisations.

The relevant part for the uses claimed is described in 9.2 permanent non cultivated areas (table 8.1).

This group contains both hardened and non-hardened surfaces. The numbers 9.2.1, 9.2.3, 9.2.5, 9.2.7, 9.2.8, 9.2.9 and 9.2.14 are hardened surfaces and use on these areas is excluded, with a remark for 9.2.7, 9.2.8 and 9.2.9 that the use is allowed provided the soil is not paved or covered with concrete. 9.2.15 (grafzerken) is excluded as it nowadays is a biocidal use.

Table W.1 Overview permanent non cultivated areas

9.2.	Permanent onbeteeld terrein
9.2.1.	Verharde wegen en paden
9.2.2.	Onverharde wegen en paden
9.2.3.	Trottoirs, straatgoten
9.2.4.	Spoor- en trambanen
9.2.5.	Parkeerterreinen, (bij) benzinestations
9.2.6.	Grensstrook van wegen en paden met de bermen
9.2.7.	Fabrieksterreinen
9.2.8.	Opslagterreinen
9.2.9.	Laad- en losplaatsen
9.2.10.	Onder hekwerken en afrasteringen
9.2.11.	Onder vangrails
9.2.12.	Rondom wegmeubilair (verkeersborden, bermpalen)
9.2.13.	Op (rieten) daken en muren
9.2.14.	Op terrassen
9.2.15.	Op flagstones, grafzerken
9.2.16.	Op tennisbanen (niet gras) en atletiekbanen
9.2.17.	Kunststof buitenbanen, kunststof sportvelden
9.2.18.	Overig permanent onbeteeld terrein

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

Based on the profile of the substance, the provided toxicology of the formulation, the characteristics of the co-formulants, the method of application and the risk assessments, 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:	N	Indication of danger:	Dangerous for the environment.
	T	Indication of danger:	Toxic
R phrases	R50/53	Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment.
	R61	May cause harm to the unborn child.

S phrases	21	When using do not smoke
	36/37	Wear suitable protective clothing and gloves.
	45	In case of accident or if you feel unwell, seek medical advice immediately (show the label where possible).
	53	Avoid exposure - obtain special instructions before use.
	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.
	SPo2	Wash all protective clothing after use.

Special provisions: DPD-phrases	-	-

Plant protection products phrase: DPD-phrase	DPD01	To avoid risk for man and the environment, comply with the instructions for use
Child-resistant fastening obligatory?			n.a.
Tactile warning of danger obligatory?			n.a.

Explanation:
Hazard symbol:	-
Risk phrases:	-
Safety phrases:	ppp contains halogenated a.s.
	S36/37 is assigned based on the operator risk assessment
	SPo2 is assigned as the a.i. is included on annex I of 91/414 and is obligatory when formulation is labelled with T.
Other:	-

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

[2] National institute of public health and the environment.

[3] Methodology according to "The new decision tree for the evaluation of pesticide leaching from soils", A.M.A van der Linden, J.J.T.I. Boesten, A.A. Cornelese, R. Kruijne, M. Leistra, J.B.H.J. Linders, J.W. Pol, A. Tiktak and A.J. Verschoor, RIVM report 601450019/2004, RIVM, Bilthoven (2004).

- Gevaarsymbool:		- Aanduiding:
	T		Vergiftig
	N		Milieugevaarlijk

- Werkzame stof:		- Gehalte:
	flumioxazin		500 g/kg

The effect of pH on solubility in water has not been studied as the compound has no dissociation constant

Auto-flammability

No autoflammability up to 420 °C

LOQ = 0.02 mg/kg

Permanent onbeteeld terrein