For the current risk assessment, the final list of endpoints from the EFSA-conclusion for flutolanil is used (d.d. 3 march 2008). In addition, studies on toxicity to non-target arthropods and earthworms evaluated by Ctgb have been used in the assessment .
List of Endpoints Ecotoxicology
NB The formulation EXP10066A (= 460 g/L flutolanil) is mentioned in the List of Endpoints.
This formulation is not Symphonie (which contains 60 g a.s./kg), but another formulation (Monarch).
Symphony = Flutolanil 6% DP = EXP10057.
Effects on terrestrial vertebrates (Annex IIA, point 8.1, Annex IIIA, points 10.1 and 10.3)
Species Test substance Time scale End point
(mg/kg bw/day)
End point (mg/kg feed)
Birds ‡
Bobwhite quail a.s. Acute LD50 > 2000
Mallard duck a.s. Acute LD50 > 2000
Preparation Acute - -
Metabolite 1 Acute - -
Bobwhite quail a.s. Short-term LD50 > 961 LC50 > 5243 Mallard duck a.s. Short-term LD50 = 1249 LC50 > 5243
Bobwhite quail a.s. Long-term NOEL = 247 NOEC = 1920
Mallard duck a.s. Long-term NOEL = 267 NOEC = 1920
Mammals ‡
Rat a.s. Acute LD50 > 10000
Preparation Acute -
Metabolite 1 Acute -
Rat a.s. Long-term NOEL = 157 NOEC = 2000
Additional higher tier studies ‡: Not required
Toxicity data for aquatic species (most sensitive species of each group) (Annex IIA, point 8.2, Annex IIIA, point 10.2)
Group Test substance Time-scale
(Test type)
End point Toxicity1 (mg/L) Laboratory tests ‡
Fish
Salmo gairdneri Technical flutolanil
96 h (static)
Mortality, LC50 5.4 (mm)
Lepomis macrochirus 96 h
(static)
Mortality LC50 > 5.4 (mm)
Group Test substance Time-scale (Test type)
End point Toxicity1 (mg/L)
Pimephales promelas 96 h
(static)
Mortality LC50 4.8 (mm)
Pimephales promelas 30 d
(flow-through)
Growth NOEC 0.233 (mm) Aquatic invertebrate
Daphnia magna Technical flutolanil
Sediment dwelling organisms Not conducted, not required
Algae
Not conducted, not required Microcosm or mesocosm tests Not required
1 indicate whether based on nominal (nom) or mean measured concentrations (mm). In the case of preparations indicate whether end points are presented as units of preparation or a.s.
No studies on the toxicity of the product EX10066 or metabolites to aquatic organisms
Bioconcentration
Active substance Metabolites2
logPO/W 3.17 _
Bioconcentration factor (BCF)1 ‡ 100* -
Annex VI Trigger for the bioconcentration factor
100 (for not readily biodegradable
2 no studies on metabolites, not required
* based on 14C-flutolanil
Effects on honeybees (Annex IIA, point 8.3.1, Annex IIIA, point 10.4)
Test substance Acute oral toxicity
(LD50 µg/bee)
Acute contact toxicity (LD50 µg/bee)
a.s. ‡ > 208.7 > 200
Preparation1 - -
Metabolite1 - -
Field or semi-field tests
No data is submitted nor required, because the laboratory toxicity of flutolanil to honey bees is low and no risk is anticipated.
1 No studies on the effects of the product EX10066 or metabolites on honey bees, not required
Effects on other arthropod species (Annex IIA, point 8.3.2, Annex IIIA, point 10.5) Laboratory tests with standard sensitive species
The tests were performed using two dose rates (according to ESCORT 1). Thus the results could not be used to derive the LR50 or HQ values. Besides, HQ approach is validated for spray application, not seed treatment.
Species Test
Substance
End point Effect (LR50 g/ha1)
Typhlodromus pyri ‡ Mortality -
Aphidius rhopalosiphi ‡ Mortality -
1 for preparations indicate whether end point is expressed in units of a.s. or preparation
Further laboratory and extended laboratory studies ‡ Species Life stage Test
Pardosa sp. EXP10066A
(464 g/L),
Species Life stage Test
Reproduction 2.2 42.7
Reproduction 20.3 15.2 21.9
50 %
Field or semi-field tests
No data submitted nor required
1 Test substance EXP10066A = Monarch
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)
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).
Studies submitted with present application of Symphonie (20110407 THG):
Species Life stage Test
Aphidius Rhopalosiphi Adult females,
< 48 h Typhlodromus pyri Protonymph Flutolanil 70DF
(72.3% a.s.), Aleochara bilineata Adult
(2-6 days old)
Poecilus cupreus Adult (at least 2 weeks old)
Effects on earthworms, other soil macro-organisms and soil micro-organisms (Annex IIA points 8.4 and 8.5. Annex IIIA, points, 10.6 and 10.7)
Test organism Test substance Time scale End point Earthworms
Test organism Test substance Time scale End point EXP10066A
EXP10066A (mixed in soil with reduced organic matter (5%))
Chronic 8 weeks Chronic 8 weeks
NOEC1 = 12.9 mg a.s./kg soil NOEC1 = 38.0 mg a.s./kg soil
Metabolite 12 Acute -
Metabolite 12 Chronic -
Other soil macro-organisms
Soil mite a.s. ‡ -
Preparation -
Metabolite 12 -
Collembola
a.s. ‡ - -
EXP10066A Chronic 28
days
NOECcorr = 18.8 mg a.s./kg d.w.soil
Metabolite 12 Soil micro-organisms
Nitrogen mineralisation
a.s. ‡ -
EXP10066A -0.71 % effect at 1.35 kg as/ha
after 42 days Metabolite 12
Carbon mineralisation a.s. ‡ -
EXP10066A -6.5 % effect at 1.35 kg as/ha
after 28 days Metabolite 12
1 Because logKow of flutolanil is 3.17 the NOEC should be divided by 2. However, the sublethal toxicity of flutolanil is lower in soil with reduced organic matter, therefore the correction to the NOEC has not been performed and the higher NOEC from the study with soil with reduced organic matter was used for risk assessment.
2 no studies on the effects of metabolites on soil organisms (not required).
Field studies
Significant reduction (22.6-30%) of organic material docomposition was observed by EXP 10066 treatment after the application on soil at 15-kg as/ha followed by on Litter-bag at 11.3 kg/ha.
Comparing the application rates by seed tuber treatment at 276 g as/ha, however, the rates are more than 50 times higher.
In the litter bag test conducted with an application rate of 670 g a.s./ha (plateau concentration plus maximum
application rate) the decomposition in the test group was 88.4-102.3 % of the control. However, decomposition relative to the control was approximately 94 % at 162 days after exposure and at subsequent assessments (test period 616 days).
Study submitted with present application of Symphonie (20110407 THG):
Test organism Test substance Time scale End point Earthworms
EXP 80715A
(60 g/kg flutolanil and 600 g/kg mancozeb)
Acute LC50, corr >500 mg product/kg d.w.soil (>330 mg total a.s./kg soil d.w. )
Effects on non- target plants (Annex IIA, point 8.6, Annex IIIA, point 10.8) Preliminary screening data
Application of EXP10066A at a rate of 11.2 kg a.i./ha (40 times the intended use) did not cause any effects on the plant growth (tested on six terrestrial non-target plant species representing six plant families). NOEC was determined to be greater than 11.2 kg a.i./ha.
Effects on biological methods for sewage treatment (Annex IIA 8.7)
Test type/organism end point
Activated sludge EC50 > 1000 mg a.s./L
Pseudomonas sp Not conducted (not required)
Ecotoxicologically relevant compounds (consider parent and all relevant metabolites requiring further assessment from the fate section)
Compartment
soil -
water -
sediment -
groundwater -
Classification and proposed labelling with regard to ecotoxicological data (Annex IIA, point 10 and Annex IIIA, point 12.3)
RMS/peer review proposal
Active substance N, R50/53
RMS/peer review proposal
Preparation N, R50/53
7.1 Effects on birds
Birds can be exposed to the active substance flutolanil via natural food (treated potatoes), and as a result of secondary poisoning via earthworms.
The threshold value for birds is based on the trigger from the RGB. This means that Toxicity-Exposure Ratios (TERs) for acute and short-term exposure should be ≥ 10 and TER for chronic exposure should be ≥ 5.
Table E.1 Overview of toxicity data for birds Endpoint Value
Acute toxicity to birds: LD50 >2000 mg a.s./kg bw Dietary toxicity to birds: LC50 >961 mg a.s./kg bw/d Reproductive toxicity to birds: NOEL 247 mg a.s./kg bw/d 7.1.1 Natural food and drinking water
Natural food
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).
In the risk assessment of most products, a small bird is chosen as the target species.
However, a small bird is not considered relevant for the use of flutolanil as seed treatment for potatoes. In the EU assessment procedure, the common crane (Grus grus) and the badger (Meles meles) were assessed as alternative relevant focal species to represent potato eating birds and mammals respectively.
The common crane (kraanvogel) is not a common species in the Netherlands, but it does visit and forage in (parts of) the country when passing on its migratory route in spring (Mar-Apr) and winter (Oct-Dec). In some cases, other large birds like geese can eat potatoes.
However, they may feed on potatoes just before they are harvested in late autumn / winter, but they are unlikely to feed on treated potatoes which are sown in spring. In conclusion, the common crane is considered to be a reasonable focal species for the Netherlands to indicate possible risks to birds.
For the common crane, a body weight of 5371 g and a daily food intake of 380 g/day are given in addendum 1 to the DAR of flutolanil (October 2006).
The concentration of flutolanil on treated potatoes (PIEC) can be calculated using the application rate (150 g product / 100 kg potatoes) and the concentration of a.s. in the formulation (60 g a.s./kg), as follows: 0.150*60 = 9 g /100 kg potatoes = 90 mg a.s./kg potatoes.
Table E.3a-c show the TER values for birds (assuming a worst case diet of 100% treated potatoes). The estimated daily uptake values (ETE, Estimated Theoretical Exposure) for acute, short-term and long-term exposure are calculated using the Food Intake Rate of the indicator species (FIR) divided by the body weight of the indicator species (bw) and the PIEC on potatoes. For uses with frequency > 1, a MAF (Multiple Application Factor) may be
applicable. The ETE is calculated as PIEC * (FIR/bw) * MAF [* fTWA, only for long term]. The use of the standard fTWA=0.53 is not accepted in this case (planting of treated potatoes), since flutolanil is persistent in soil. The ETE is compared to the relevant toxicity figure. TER should be above the trigger for an acceptable risk.
Table E.3a Acute risk for birds Substance FIR / bw PIEC
(mg/kg)
MAF Acute ETE
LD50 (mg/kg
bw/d)
TER
(mg/kg bw/d)
(trigger 10) Common crane
flutolanil 0.071 90 1 6.39 >2000 >313
Table E.3b Short-term risk for birds Substance FIR / bw PIEC
(mg/kg)
MAF Short-term ETE
LC50 (mg/kg
bw/d)
TER
(mg/kg bw/d)
(trigger 10) Common crane
flutolanil 0.071 90 1 6.39 >961 >150
Table E.3c Long-term risk for birds Substance FIR / bw PIEC
(mg/kg)
MAF ftwa Long-term ETE
NOEL (mg/kg
bw/d)
TER
(mg/kg bw/d)
(trigger 5) Common crane
flutolanil 0.071 90 1 - 6.39 247 39
Taking the results in Table E.3a-c into account, it appears that all proposed uses meet the standards laid down in the RGB.
Two metabolites were found in potatoes at levels representing >10% of the TRR: M2 and M4. M4 was also a major metabolite in laying hens orally dosed with flutolanil (DAR, B.7), which means that the available toxicity studies with the parent cover the risk of this metabolite. M2 was a major rat metabolite but the available information from the hen
metabolism study in the DAR does not indicate that M2 was also a major metabolite in laying hens. However, M2 is formed by hydroxylation from flutolanil, and considering the structural similarity between flutolanil and M2, the toxicity of M2 is assumed to be not higher than that of flutolanil. Since its occurrence in potato tubers, and hence the exposure to M2, will be much less than that of flutolanil, the risk of M2 to birds is acceptable.
drinking water
No exposure of surface water is expected, therefore the risk from drinking water is low.
7.1.2 Secondary poisoning
The risk as a result of secondary poisoning is assessed based on bioconcentration in
earthworms. Bioconcentration in fish is not considered relevant since no exposure of surface water is expected. Examination takes place against the threshold value for chronic exposure of 0.2 times the NOEC value. This means that the TER should be ≥ 5.
Earthworms
Since there are no experimental data the bioconcentration factor for earthworms (BCFworm) is calculated according to the following formula: BCF = (0.84 + 0.01 * Kow) / foc * Koc.
The logKow of a.s. flutolanil is 3.17, the mean Koc is 683 L/Kg which leads to a BCFworm = 1.14 kg soil/kg worm.
The highest PECsoil(21) (taken from paragraph 6.1.1) is 3.77 mg/kg soil (this represents the PECplateau + PECsoil,21d).
Indicator species is a 100-g bird eating 113 g fresh worms per day.
The risk is then calculated as NOEL / PECsoil(21) * BCFworm * (FIR/bw) = 247 / (3.77 * 1.14 * 1.1)
Taking the results for secondary poisoning through fish and earthworms into account, the proposed uses meet the standards for secondary poisoning as laid down in the RGB.
Conclusions birds
The product complies with the RGB.
7.2 Effects on aquatic organisms
Based on the type of application, exposure of surface water, and hence aquatic organisms is not expected.
7.3 Effects on terrestrial vertebrates other than birds
Mammals can be exposed to the active substance via natural food (treated potatoes) and as a result of secondary poisoning via earthworms.
The threshold value for mammals is based on the trigger from the RGB. This means that the Toxicity-Exposure Ratio (TER) for acute exposure should be ≥ 10 and TER for chronic exposure should be ≥ 5. Dietary toxicity is not taken into account for mammals.
Table E.8 presents an overview of toxicity data.
Table E.8 Overview of toxicity data for mammals
Endpoint Value
Acute toxicity to mammals: LD50 >10000 mg a.s./kg bw Reproductive toxicity to mammals: NOEL 157 mg a.s./kg bw/d
7.3.1 Natural food and drinking water Natural food
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).
In the risk assessment of most products, a small mammal is chosen as the target species.
However, a small mammal is not considered relevant for the use of flutolanil as seed
treatment for potatoes. In the EU assessment procedure, the common crane (Grus grus) and the badger (Meles meles) were assessed as alternative relevant focal species to represent potato eating birds and mammals respectively.
Large mammal species that might feed on potatoes in the Netherlands are the badger (das) (as used in the EU assessment of flutolanil) and the wild boar (wild zwijn) (used in the EU risk assessment of pencycuron).
For the badger, a body weight of 10.850 kg and a daily food intake rate of 2.887 kg/day are given in addendum 1 to the DAR of flutolanil (October 2006), hence FIR/bw is 0.27. For the wild boar, the daily food intake rate is estimated at 4 kg fresh material and the body weight of adult males and females amounts to 104 and 84 kg, respectively (DAR pencycuron, October 2005), hence FIR/bw is 0.04 and 0.05, respectively. Since FIR/bw for the badger is higher than for the wild boar, and hence worst case, risk assessment is performed for the badger.
The concentration of flutolanil on treated potatoes (PIEC) can be calculated using the application rate (150 g / 100 kg potatoes) and the concentration of a.s. in formulation (60 g a.s./kg), as follows: 0.150*60 = 9 g /100 kg potatoes = 90 mg/kg potatoes.
Table E.10a-b show the estimated daily uptake values (ETE, Estimated Theoretical Exposure) 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 PIEC, a time-weighted-average factor (fTWA, only for long term). Calculations assume a worst case diet of 100% treated potatoes and are performed only for the species with the worst case FIR/bw (badger). For uses with frequency of > 1, a MAF (Multiple Application Factor) may be
applicable. The ETE is calculated as application rate * (FIR/bw) * PIEC * MAF [* fTWA, only for long term]. The use of the standard fTWA=0.53 is not accepted in this case (planting of treated potatoes), since flutolanil is persistent in soil. The ETE is compared to the relevant toxicity figure. TER should be above the trigger for an acceptable risk.
Table E.10a Acute risk for mammals Substance FIR / bw PIEC
(mg/kg)
MAF Acute ETE
LD50 (mg/kg
bw/d)
TER
(mg/kg bw/d)
(trigger 10) badger
flutolanil 0.27 90 1 24.3 >10000 >412 Table E.10b Long-term risk for mammals
Substance FIR / bw PIEC (mg/kg
)
MAF ftwa Long-term ETE
NOEL (mg/kg
bw/d)
TER
(mg/kg bw/d)
(trigger 5) Badger
Flutolanil 0.27 90 - - 24.3 157 6.5
Taking the results in Table E.10a-b into account, it appears that all proposed uses meet the standards laid down in the RGB.
Two metabolites were found in in potatoes at levels representing >10% of the TRR: M2 and M4. These two metabolites are also major rat metabolites, which means that the available toxicity studies with the parent cover the risk of the metabolites for mammals.
drinking water
No exposure of surface water is expected, therefore the risk from drinking water is low.
7.3.2 Secondary poisoning
The risk as a result of secondary poisoning is assessed based on bioconcentration in
earthworms. Bioconcentration in fish is not considered relevant since no exposure of surface water is expected. Examination takes place against the threshold value for chronic exposure of 0.2 times the NOEC value. This means that the TER should be ≥ 5.
Earthworms
Since there are no experimental data the bioconcentration factor for earthworms (BCFworm) is calculated according to the following formula: BCF = (0.84 + 0.01 * Kow) / foc * Koc.
The logKow of a.s. flutolanil is 3.17, the mean Koc is 683 L/Kg which leads to a BCFworm =
PECplateau + PECsoil,21d).
Indicator species is a 10-g mammal eating 14 g fresh worms per day.
The risk is then calculated as NOEL / PECsoil(21) * BCFworm * (FIR/bw) = 157 / (3.77 * 1.14 * 1.4)
= 26.1. Since this is > 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 as laid down in the RGB.
Conclusions mammals
The product complies with the RGB.
7.4 Effects on bees
Symphonie is proposed for use as pre-planting treatment of seed potatoes with a single application per season and crop. Taking into account the absence of plants at the time of treatment and the method of application, the possibility of exposure of bees immediately after application is minimal. As flutolanil is systemic, bees might be exposed to residues in
aboveground parts of crop as plants grow. This is however considered not to be a cause of concern for the proposed use of Symphonie in potatoes as this crop is rarely attractive to bees. Even if occasional exposure would occur, no adverse effects on bees would be expected, as flutolanil is practically non-toxic to bees by the oral route.
Although hazard quotient (HQ) calculations are not fully applicable to the application method of Symphonie, as the application is not proposed as a foliar spray to flowering crops, HQ ratios have been calculated to further demonstrate that the proposed use of Symphonie would not cause unacceptable effects on bees. The maximum application rate for Symphonie is
315 g a.s./ha and it is used to calculate the hazard quotients for bees. An overview of the risk at the proposed use with the highest application rate is given in Table E.5.
Table E.5 Risk for bees
Use Substance Application rate
LD50 Rate/LD50 Trigger value [g a.s./ha] [µg/bee]
potatoes flutolanil 315 Oral : >208.7 <1.5 50 contact: >200 <1.6 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 as laid down in the RGB.
Conclusions bees
The product complies with the RGB.
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, although this approach is actually only valid for spray applications (however, data on soil-dwelling
arthropods were submitted and are also included in the assessment below). For this, Lethal Rate values (LR50) are needed. Based on the lowest LR50-values from studies with the two standard species Aphidius rhopalosiphi and Typhlodromus pyri, performed with products other than Symphonie, 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). Hazard Quotients should be below the trigger value of 2 to meet the standards. The tests on the two standard species were performed using two dose
rates (according to ESCORT 1), thus the results could not be used to derive the LR50. However, taking into account the observed effects, an LR50-value > the highest test
concentration can be safely assumed. The resulting Hazard Quotients are presented in Table E.12.
Table E.12 HQ-values for A. rhopalosiphi and T. pyri Application rate
(kg a.s./ha)
MAF1 Drift factor/
Vegetation factor2
Safety factor2
LR50 (kg a.s./ha)
HQ In-field
A. rhopalosiphi 0.315 1 - - 0.831 0.4
T. pyri 0.315 1 - - >1.0 <0.3
Off-field
A. rhopalosiphi 0.315 1 0.1/10 10 0.831 0.04
T. pyri 0.315 1 0.1/10 10 >1.0 <0.03
1: Multiple Application Factor
2: off-field: drift factor = 10%, vegetation distribution 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 2,
As the above table shows, both in- and off-field HQ values are below the trigger value of 2,