HET COLLEGE VOOR DE TOELATING VAN GEWASBESCHERMINGSMIDDELEN EN BIOCIDEN

BIJLAGE II bij het besluit d.d. 2 september 2010 tot vereenvoudigde uitbreiding van de toelating van het middel Previcur Energy, toelatingnummer 13221 N

RISKMANAGEMENT

Contents Page

1. Identity of the plant protection product 3

2. Physical and chemical properties 5

3. Methods of analysis 5

4. Mammalian toxicology 7

5. Residues 24

6. Environmental fate and behaviour 32

7. Ecotoxicology 56

8. Efficacy 81

9. Conclusion 81

10. Classification and labelling 81

1. Identity of the plant protection product

1.1 Applicant

Stichting Trustee Bijzondere Toelatingen

Hogeweg 16

2585 JD 'S-GRAVENHAGE

1.2 Identity of the active substance

Fosetyl

Fosetyl was included in Annex I of Directive 91/414/EEC on May 1^st, 2007.

Fosetyl-sodium is produced in the same manufacturing site that produces fosetyl-aluminium. Batch data supports the conclusion that the material is almost identical to the fosetyl-aluminium as assessed for Annex I inclusion. The specification is supported by batch data. The active substance is considered to be equivalent to the active substance as included in Annex I of directive 91/414/EEC.

Data on the identity is taken from the List of Endpoints (identity: EFSA Review Report, December 2005). Changes and/or additions are taken up in italics (e.g. the information on fosetyl-sodium).

Active substance (ISO Common Name)	fosetyl (unless otherwise specified the following data relates to the variant fosetyl-Al)
Chemical name (IUPAC)	aluminium tris-O-ethyl phosphonate (fosetyl-Al) Ethyl hydrogen phosphonate, aluminium salt (fosetyl-Al) sodium ethyl phosphonate (fosetyl-sodium)
Chemical name (CA)	Aluminium tris-O-ethyl phosphonate Phosphonic acid ethyl ester, aluminium salt
CIPAC No	384.013 (fosetyl-Al) and 384 (fosetyl) 384.011 (fosetyl-sodium)
CAS No	39148-24-8 (fosetyl-Al) and 15845-66-6 (fosetyl) 39148-16-8 (fosetyl-sodium)
EEC No (EINECS or ELINCS)	254-320-2 (fosetyl-aluminium) 444-960-2 (fosetyl-sodium)
FAO Specification (including year of publication)	FAO (2000) : 960 g/kg impurities : - Inorganic phosphite (384/TC/M/4 ,CIPAC G, p.86) ; Maximum: 10 g/kg expressed as aluminium phosphite. - Water (CIPAC MT 30.1, CIPAC F, p.91) ; Maximum: 10 g/kg.
Minimum purity of the active substance as manufactured (g/kg)	≥ 960 g/kg (expressed as fosetyl-Al, as TC) ≥ 365 g/kg (expressed as fosetyl-sodium as TK)
Identity of relevant impurities (of toxicological, environmental and/or other significance) in the active substance as manufactured (g/kg)	None
Molecular formula	C₆ H₁₈ Al O₉P₃ C₂H₆ NaO₃P (fosetyl-sodium)
Molecular mass	354.14 132 g/mol (fosetyl-sodium)
Structural formula

Propamocarb

The active substance was included in Annex I of Directive 91/414/EEC on October 1^st, 2007.

Data on the identity is taken from the List of Endpoints (identity: EFSA Review Report, April 2007). Changes and/or additions are taken up in italics.

Active substance (ISO Common Name)	propamocarb The physical/chemical and residue evaluation related to the variant Propamocarb HCl. Parent Propamocarb was considered to be the residue definition from a residue viewpoint.
Chemical name (IUPAC)	Propyl 3-(dimethylamino) propylcarbamate hydrochloride
Chemical name (CA)	carbamic acid, [3-dimethylaminopropyl]-, propyl ester, monochloride
CIPAC No	399 (Propamocarb) 399.601 (Propamocarb HCl)
CAS No	25606-41-1 (Propamocarb HCl) 24579-73-5 (Propamocarb)
EEC No (EINECS or ELINCS)	247-125-9 (Propamocarb HCl)
FAO Specification (including year of publication)	No FAO specification
Minimum purity of the active substance as manufactured (g/kg)	920 g/kg (as propamocarb)
Identity of relevant impurities (of toxicological, environmental and/or other significance) in the active substance as manufactured (g/kg)	None identified
Molecular formula	C₉H₂₁ClN₂O₂
Molecular mass	224.7
Structural formula

1.3 Identity of the plant protection product

Name

Previcur Energy

Formulation type

Content active substance

530 g/L pure propamocarb

310 g/L pure fosetyl

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

1.4 Function

Fungicide.

1.5 Uses applied for

See GAP (Appendix 1)

1.6 Background to the application

It concerns a symplified third party extension.

1.7 Packaging details

Evaluation of (suitability) of packaging is not required for simplified extension applications.

2. Physical and chemical properties

Evaluation of the physical and chemical properties of the active substances and the plant protection product is not required for simplified extension applications.

3. Methods of analysis

3.1. Analytical methods in technical material and plant protection product

Evaluation of the analytical methods for the technical material and the plant protection product is not required for simplified extension applications.

3.2 Residue analytical methods

Information on the analytical methods is taken from the List of Endpoints (DAR, February 2006 for propamocarb, and List of Endpoints September 2005 with EFSA peer review report December 2005 for fosetyl). Changes and/or additions are taken up in italics.

For simplified extension applications only the residue analytical methods for food/feed of plant and animal origin are evaluated.

Based on the proposed use of the plant protection product pertaining to the simplified extension only, analytical methods for determination of residues in food/feed of plant origin are required for watery (endives, fresh herbs) matrices and hot pepper as special matrix. It is assumed that no residues will occur in crops grown from seeds obtained from plants treated with the plant protection product.

Fosetyl

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

GC/FPD: LOQ = 0.5 mg/kg (grapes, oranges, bananas, wine, orange juice, beer) for "fosetyl-Al" and phosphorous acid (with ILV) GC-NPD can be used for confirmation*

2.0 mg/kg (hop) "fosetyl-Al"

20.0 mg/kg phosphorous acid

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

GC/FPD: LOQ = 0.1 mg/L milk

0.5 mg/kg (meat, kidney, liver, eggs)

for "fosetyl-Al" and phosphorous acid

GC-NPD can be used for confirmation*

* A second proposed method ( “analog to DFG S522”, described in addendum of DAR of fosetyl-aluminium) uses diazomethane, which is not acceptable. It was however shown that a different detector, NPD instead of FPD, can be used as confirmatory method.

Definition of the residue and MRL’s for fosetyl
Matrix	definition of the residue for monitoring	EU-MRL
Food/feed of plant origin	sum of fosetyl, phosphorous acid and their salts expressed as fosetyl	endives: 75 mg/kg fresh herbs: 75 mg/kg Hot pepper: 130 mg/kg
Food/feed of animal origin	sum of fosetyl, phosphorous acid and their salts expressed as fosetyl	meat: 0.5 mg/kg milk 0.1 mg/kg egg: 0.1 mg/kg

The residue analytical method for plant material, included in the above List of Endpoints, uses trimethylsilyl diazomethane for derivatization, which is considered acceptable because this agent is less toxic and less explosive than diazomethane itself.

For hot peppers no validation is submitted. According to HTB 1.0 hot pepper is a commodity that has to be validated separately because it is difficult to analyse. However, based on the risk assessment, there is no unacceptable risk when residues in hot pepper are determined using the method for residues in watery matrices which is not especially validated for hot peppers.

The methods are therefore suitable for monitoring of the MRLs of fosetyl.

Propamocarb

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

Propamocarb residues were extracted with acetic acid (1% aqueous solution), eluted from C18 SPE with acetonitrile/water/acetic acid (20:80:1, v/v). Residues were determined by HPLC with MS/MS detection.

Detection was at m/z = 189 (parent ion) –>102 + 144 (daughter ion).

LOQ = 0.01 mg/kg.

The method was independently validated for tomatoes and lettuce.

The method is acceptable for analysis of residues of propamocarb and its salts in food/feed with watery matrices

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

An analytical method is not required due to fact that no MRL is proposed.

Definition of the residue and MRLs for propamocarb
Matrix	Definition of the residue for monitoring	EU-MRL
Food/feed of plant origin	Propamocarb	endives: 10 mg/kg fresh herbs: 30 mg/kg Hot pepper: 10 mg/kg
Food/feed of animal origin	No definition of the residue is proposed. No relevant residues are expected to occur in food/feed of animal origin.

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

Conclusion

The submitted analytical methods meet the requirements for a simplified extension application.

3.3 Data requirements

None.

3.4 Physical-chemical classification and labelling

Evaluation of the classification and labelling of the active substances and the formulation is not required for simplified extension applications. Existing labelling (no classification/labelling necessary) is maintained.

4. Mammalian toxicology

List of Endpoints

Fosetyl-sodium is used in Previcur Energy, whereas the toxicity part of the DAR is mainly based on studies with fosetyl-Al. Based on the physical chemical properties, it was concluded that they are equivalent. Moreover, several bridging studies were submitted, indicating that both substances are toxicologically equivalent.

Fosetyl

Fosetyl is an existing active substance substance, included in Annex I of 91/414/EEC. The final List of Endpoints presented below is taken from the EFSA Scientific report on fosetyl (2005) 54; 1-79 (d.d. 14 December 2005), also taking into account the final review report on fosetyl (SANCO/10015/06 – final, d.d. 4 April 2006). Where relevant, some additional remarks/information are given in italics.

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

Unless otherwise specified the following data relate to the variant fosetyl-Al.

Rate and extent of absorption ‡	Rapid and extensive (80 –100%) within 24 h over the dose rate range of 100 to 3000 mg/kg bw.
Distribution ‡	Wide spread distribution and concentration in tissues proportional to dose at lower dose rates. Tissue concentrations not exceeding 6% after 168h. Highest concentration found in fat, kidneys, skin, spleen and adrenals
Potential for accumulation ‡	None
Rate and extent of excretion ‡	Rapid elimination via urine, faeces and expired air. Exact proportions measured via each elimination route depend on position on radiolabel
Metabolism in animals ‡	Metabolised to ethanol, phosphites (phosphorous acid) and CO₂
Toxicologically significant compounds ‡ (animals, plants and environment)	Fosetyl-Al and phosphorous acid

Acute toxicity (Annex IIA, point 5.2)

Rat LD50 oral ‡	> 2000 mg/kg bw
Rat LD50 dermal ‡	> 2000 mg/kg bw
Rat LC50 inhalation ‡	> 5.11 mg/L (4h)
Skin irritation ‡	Not irritant
Eye irritation ‡	Severely irritating	R41
Skin sensitization ‡ (test method used and result)	Not sensitizer (Magnusson and Kligman test)

Short term toxicity (Annex IIA, point 5.3)

Target / critical effect ‡	Urinary tract, changes in urine physical/chemical composition and subsequent chronic irritation¹.
Lowest relevant oral NOAEL / NOEL ‡	1270 mg/kg bw/day, 90 day male rat
Lowest relevant dermal NOAEL / NOEL ‡	> 1050 mg/kg bw/day (highest dose tested)
Lowest relevant inhalation NOAEL / NOEL ‡	No data, not required

1 These effects are observed in the 90-d mechanistic study. EFSA conclusion report indicates that fosetyl-Al does not induce adverse effects after oral administration, except for a marginal increase in the incidence and severity of extramedullary haematopoiesis in the spleen at the top dose (1922 and 2499 mg/kg bw/day in males and females, respectively) in an old study (1977) which results were considered doubtful. The most recent oral 90-day rat study (Dange 1999) was acceptable and showed no effects up to 1270 mg/kg bw/day (highest dose tested).

Dermal application of fosetyl-Al (semi-occlusive, 6-7 h/d for 28 consecutive days, one limit dose of 1050 mg/kg bw/day) in rats caused dermal irritation, no signs of systemic toxicity were recorded. Treatment related dermal irritation was observed with slight erythema (4/10 females), moderate erythema (2/10 males and 4/10 females), slight edema (2/10 males and 4/10 females) and slight desquamation (2/10 males and 3/10 females). Macroscopic and histological examination revealed treatment skin lesions, including crusted areas and erosions, hyperkeratosis and acute inflammation. The irritation was observed only after 3-4 weeks of treatment.

Genotoxicity ‡ (Annex IIA, point 5.4)

No genotoxic potential ²

2 The genotoxic potential was investigated in in vitro studies (2 Ames tests, 1 mammalian cell gene mutation test in Chinese hamster lymphoma L5178Y cells, 1 mammalian cytogenetic test in Chinese hamster ovary cells, 1 DNA repair test in E. coli, 1 induct test in E. coli, and 1 genetic events test in yeast) and in vivo studies (3 micronucleus tests in mouse bone marrow).

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

Target/critical effect ‡	Urinary tract, changes in urine physical/chemical composition and subsequent chronic irritation.³
Lowest relevant NOAEL / NOEL ‡	300 mg/kg bw/day, 2 year dog and 2 year rat
Carcinogenicity ‡	No carcinogenic potential

3 The repeated administration of high doses severely altered the calcium/phosphorous balance and modified the urine composition, leading to the formation of calculi in the urinary tract of treated animals. These changes were closely related to the subsequent development of hyperplasia in the urinary bladder within a relatively short time.

Reproductive toxicity (Annex IIA, point 5.6)

Reproduction target / critical effect ‡	No adverse reproduction toxicity observed in the rat.
Lowest relevant reproductive NOAEL / NOEL ‡	Parental toxicity: 1782 mg/kg bw/day (highest does tested) Reproduction toxicity: 1997 mg/kg bw/day (highest does tested)
Developmental target / critical effect ‡	No developmental toxicity at non maternal toxic doses, in the rabbit.
Lowest relevant developmental NOAEL / NOEL ‡	Maternal and developmental toxicity 300 mg/kg bw/day

2-generation study: The evaluation of the study in the DAR is not very clearly reported as to the NOAELs, and the doses in mg/kg bw/d. Parental and pup effects were observed at the mid (slight effects) and high dose group. The overall NOAEL parental and developmental appears to be ca 440 mg/kg bw/d, despite the value for parental NOAEL mentioned in the LoEP.

Developmental studies:

Rat: NOAELmaternal and developmental;: 1000 mg/kg bw/d

Rabbit: NOAEL maternal and developmental: 300 mg/kg bw/d

Neurotoxicity / Delayed neurotoxicity ‡ (Annex IIA, point 5.7)

Fosetyl-Al did not show any neurotoxic potential

Other toxicological studies ‡ (Annex IIA, point 5.8)

Studies on metabolites

Mechanistic studies

Phosphorus acid

LD₅₀oral > 2000 mg/kg bw

LD₅₀ dermal 1650 mg/kg bw

LC₅₀ inhalation > 6.14 mg/L

Not skin irritating

Slight eye irritant

Non genotoxic

Short term NOAEL 400 mg/kg bw/day, 90-day rat

Long term toxicity 390 mg/kg bw/day, 117 week rat

No carcinogenic potential

ADI 3.9 mg/kg bw/day based on the 117 week rat study

500 mg/kg bw/day, 90 day rat⁴

4 Dietary administration of 50,000 ppm (3500 and 4200 mg/kg bw/d for males and females resp.) and possibly 30,000 ppm (2100 and 2500 mg/kg bw/d for males and females resp.) in rats for up to 13w induced some mortality, marked diuresis, reduction in food consumption and in bw gain, increased water consumption; increased BUN, phosphorous and calcium levels, decreased serum total protein; increased urine volume and decreased urine pH, specific gravity and electrolytes except calcium which was increased; all these changes, except bw, occurred shortly after initiation of treatment and reverse more or less completely during the recovery periods. Urolithiasis which occurred in high dose rats and in mid dose males was then considered to cause irritation of the urinary tract and subsequent papillary hyperplasia which was partly reversible after cessation of treatment. The NOAEL was 8,000 ppm i.e. 500 and 600 mg/kg bw in males and females, respectively.

Medical data ‡ (Annex IIA, point 5.9)

No reports of health effects have been recorded during medical surveillance of workers involved in the manufacturing process of fosetyl-Al technical.

Summary (Annex IIA, point 5.10)	Value	Study	Safety factor
ADI ‡	3 mg/kg bw/day	2 year dog and 2 year rat	100
AOEL ‡	5 mg/kg bw/day	90 day rat, mechanistic study	100
ARfD ‡ (acute reference dose)	Not allocated

Dermal absorption (Annex IIIA, point 7.3)

ALIETTE 800 WG

1 % for dilution and concentrate based on in vitro study human and rat skin.

Propamocarb

Propamocarb is an existing active substance, included in Annex I of 91/414/EEC. The final List of Endpoints presented below is taken from the final EFSA Scientific report on propamocarb (2006) 78; 1-80 (d.d. 12 May 2006), also taking into account the final review report on propamocarb (SANCO/10057/2006 – final, d.d. 25 April 2007).

Where relevant, some additional remarks/information are given in italics.

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

Rate and extent of absorption ‡	Rapid (78 – 96%) within 72h
Distribution ‡	Mainly in organs associated with biotransformation (liver, lung, kidney). These were the only ones which had quantifiable amounts recorded (<0.17 mg equivalents/kg tissue). The highest transitory concentrations of radiolabel were detected in liver and kidneys between 0.75 and 3 hours post-dosing. Terminal half-life for all tissues was 11 – 26h
Potential for accumulation ‡	No evidence of accumulation
Rate and extent of excretion ‡	Rapid excretion - 91 to 94% within 72h for LD and HD respectively. Majority via urine (88 – 92% in 72h). Gender independent
Metabolism in animals ‡	Extensively metabolised with only between 1.1 and 11% excreted as unchanged propamocarb-anion in the low dose animals and up to 20% in high dose. Four major metabolites identified: 2-hydroxypropyl 3-(dimethylamino)propylcarbamate, propyl [3-(methylamino)propyl]carbamate, propyl-3-(dimethylamino)propylcarbamate-N-oxide and 3-(3-dimethylaminopropyl)-4-hydroxy-4-methyloxazolidin-2-one
Toxicologically significant compounds ‡ (animals, plants and environment)	Propamocarb hydrochloride, 2-hydroxypropyl 3-(dimethylamino)propylcarbamate, propyl [3-(methylamino)propyl]carbamate, propyl-3-(dimethylamino)propylcarbamate-N-oxide and 3-(3-dimethylaminopropyl)-4-hydroxy-4-methyloxazolidin-2-one

Acute toxicity (Annex IIA, point 5.2)

LD₅₀ oral	LD₅₀ > 2000 mg/kg bw
LD₅₀ dermal	LD₅₀> 2000 mg/kg bw
LC₅₀ inhalation	LC₅₀> 5.01 mg/L
Skin irritation	Non-irritant
Eye irritation	Non-irritant
Skin sensitization (result and test method used)	Sensitiser (9/20 animals sensitised) (Magnusson and Kligman) R43

Short term toxicity (Annex IIA, point 5.3)

Target / critical effect ‡	Vacuolar alterations of secretory epithelial cells in rat and dog. In the rat vacuolation occurred in the choroid plexus and lacrimal glands; in the dog vacuolation was evident in salivary glands, tracheal glands, lungs (bronchial glands), oesophagus, stomach (pyloric glands), duodenum (brunners glands), lacrimal glands and mandibular lymph nodes.
Lowest relevant oral NOAEL / NOEL ‡¹	< 39 mg/kg /day propamocarb (lowest dose tested), in a 1-year dog feeding study. 45 mg/kg bw/day in 90 day dog study 100 mg/kg bw/day in 28 day rat study
Lowest relevant dermal NOAEL / NOEL ‡ ²	300 mg/kg propamocarb, based on vacuolation of the choroid plexus in a 28-day rat study. Dermal irritation was observed at 71.7 mg/kg a.s. in a 21-day rat study.
Lowest relevant inhalation NOAEL / NOEL ‡	No data, not required

1 In the DAR the following is stated regarding the semi-chronic NOAEL: “The overall lowest relevant NOAEL was considered to be <39 mg/kg/day propamocarb hydrochloride, based on the vacuolar alterations observed in the 52-week dog study (Frieling, 2003). A proper NOAEL could not actually be determined exactly because in this 52-week dog study, vacuolation was observed at 1000 ppm, the lowest dose tested (equivalent to 39 and 42 mg/kg/day of active substance in males and females respectively). Therefore 39 mg/kg/day corresponds to the lowest LOEL rather than the NOEL. However, the vacuolation findings were all graded minimal to moderate and were not seen in all animals at this dose level. In addition, no effects were noted in the 90-day dog study at this dose level (Schoenmakers, 2001b). It is acceptable to assume that this dose can be considered as a threshold effect level and the NOEL for the above effects is only slightly lower than the threshold level. Moreover, the physiological meaning or adverse character of these lesions, i.e. their toxicological impact on the animal’s life (quality), appeared to be rather unobtrusive. A recovery period of 4 weeks (see 90-day rat study) did not abolish these findings but diminished the severity of vacuolation, suggesting, at least, partial reversibility. Finally, these lesions do not appear to affect all species: dog seems to be the most sensitive as well as rat to a lesser extent whereas vacuolation was not observed in mouse. In the dog the vacuolar changes appeared to be quite widespread, occurring within a range of secretory tissues and organs, whereas in the rat, the principle target organ appears to be the choroid plexus (and, in some cases, also the lacrimal glands). The toxicological significance to humans of these rather uncommon lesions remains therefore uncertain.”

2 The LoEP appears incorrect: In the DAR 2 short-term dermal toxicity studies in the rat are evaluated. In study 1, rats were dermally exposed for 5d/w during 3 weeks (occlusive exposure) to Previcur N. No systemic effects were observed (NOAEL 717 mg as/kg bw/d), dermal effects (scabbing and histopathologically dermatitis) were observed at 358 mg as/kg bw/d (NOAEL 71.7 mg as/kg bw/d). In study 2 (28 d study duration, exposure occlusive, 5d/w, tested formulation: Proplant), local and systemic effects were observed at 1200 mg as/kg bw/d (NOAEL 300 mg as/kg bw/d).

Genotoxicity ‡ (Annex IIA, point 5.4)

No genotoxic potential³

3 Negative in Ames tests, chromosome aberration studies in vitro and mammalian cell gene mutation tests in vitro. Also negative in the following in vivo studies: mouse micronucleus and dominant lethal essays.

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

Target/critical effect ‡	Vacuolar change, choroid plexus
Lowest relevant NOAEL / NOEL ‡	29 mg/kg bw/day (female rat; 52-week dietary study)
Carcinogenicity ‡	No evidence of carcinogenic potential

Reproductive toxicity (Annex IIA, point 5.6)

Parental/maternal critical effect ‡	Bodyweight, food consumption and vacuolar changes (F_o females)
Lowest relevant parental/maternal NOAEL / NOEL ‡	37 mg/kg bw/day as (rat, gavage)
Reproduction target / critical effect	Sperm concentration and count (F1 males)
Lowest relevant reproductive NOAEL / NOEL	37.5 mg/kg bw/day as (rat, gavage)
Developmental target / critical effect ‡	Increased number of small foetuses and ↓ weight of live foetuses
Lowest relevant developmental NOAEL / NOEL ‡	31 mg/kg bw/day (rat, dietary)

Neurotoxicity / Delayed neurotoxicity ‡ (Annex IIA, point 5.7)

Target / critical effects

Vacuolation of choroids plexus in ventricles of cerebrum and cerebellum

Lowest relevant NOAEL / NOEL

72(♂); 86(♀) (1500 ppm) from rat 90-day study

Acute neurotoxicity – no neurotoxicity at 1321 mg/kg bw (highest dose tested), NOAEL 134 mg/kg bw (reduced bodyweight)

Other toxicological studies ‡ (Annex IIA, point 5.8)

None available.

Medical data ‡ (Annex IIA, point 5.9)

No actual cases of human intoxication with propamocarb (hydrochloride) documented. The low animal toxicity of the active substance suggests accidental or occupational poisoning to be unlikely. No known cases of general ill health in production plant workers.

Summary (Annex IIA, point 5.10)	Value	Study	Safety factor
ADI ‡	0.29 mg propamocarb hydrochloride/kg bw/day	52-week dietary study in rats	100
AOEL_Systemic ‡⁴	0.29 mg propamocarb hydrochloride/kg bw/day	52-week dietary study in rats	100
ARfD ‡ (acute reference dose)	1 mg propamocarb hydrochloride/kg bw/day	28-day rat study (gavage)	100

4 In the expert meeting, the experts noted that, based on the proposed pattern of use (e.g. greenhouses) a long term study was appropriate for the derivation of the AOEL, instead of the 90-day study in dogs, leading to an AOEL of 0.45 mg/kg bw/day. Therefore an AOEL of 0.29 mg propamocarb hydrochloride/kg bw/day was derived, based on the NOAEL of 29 mg/kg bw/day in the 52 week rat study and a safety factor of 100.

Dermal absorption (Annex IIIA, point 7.3)

In vivo dermal absorption, human

Provisional value of 10% for concentrate and dilution based on rat in vivo and rat/human in vitro (Previcur N).⁵

5 In the DAR, dermal absorption values from two in vivo rat studies were used (12% for the concentrated formulation and 10% for the spray strength dilution).

During the EPCO meeting, an addendum with the evaluation of a new in vitro rat/human skin study was produced by the rapporteur, which has not been peer reviewed. The rapporteur Member State proposes new, lower, dermal absorption values. EFSA proposes to remain with the provisional dermal absorption value of 10% and that the new study and evaluation by the rapporteur Member State is to be considered by MS at national level.

Local effects

Fosetyl: is not a skin irritant, nor a skin sensitiser, however, it is a severe eye irritant. Moreover, dermal irritation is observed in the repeated dose dermal study at the limit dose of 1050 mg/kg bw/d, without systemic effects. The NAEL for dermal irritation could be even lower than the overall NOAEL (via oral route: 500 mg/kg bw/d). It should be realised that the exposure of laboratory animals in the repeated dose dermal toxicity study is not comparable to the human exposure, mainly because the lab-animals are exposed under (semi)occlusion, whereas humans will be exposed to bare skin. This makes it very difficult to use the results from the lab-animals for human risk assessment.

Moreover, in this dermal toxicity study, the irritation effects were observed mainly at the 4-week observation, with some animals affected at the 3-week observation. Furthermore, the rats were exposed to 1050 mg/kg bw, at 10% of their body surface; assuming a body surface of area of 400 cm2, this will result in an area dose of 1050 mg/40cm² = 26 mg/cm². The estimated maximum external human exposure is 160 mg at mixing and loading; assuming an exposed area of 2000 cm², this equals an area dose of 160/2000 = 0.08 mg/cm².

Taking into account the area doses, high NOAEL, and time of occurrence of effects, and comparing this to the use as described in the GAP (low frequency of application although in the greenhouse, high PHI) and the lack of effects in medical reports, it is not expected that adverse local effects will occur in the unprotected operator and worker after dermal and respiratory exposure to fosetyl as a result of the application of Previcur Energy in lettuce, cucumber, zucchini, pattison, eggplants, tomato, peppers, chilli peppers and radish.

Propamocarb: is not a skin irritant, but is a skin sensitiser; these local effects are covered in the risk assessment/management by means of assignment of R- and S-phrases. Propamocarb does produce local effects after repeated exposure at a dose level below the level producing systemic effects in that specific study. However, it should be taken into account that the substance is a skin sensitiser, and the NOAEL for local effects after repeated exposure is higher than the overall NOAEL for systemic effects. Therefore, the risk associated with local effects are covered in the risk assessment, and risk management.

Data requirements active substance

Fosetyl: No additional data requirements are identified.

Propamocarb: No additional data requirements are identified.

4.1 Toxicity of the formulated product (IIIA 7.1)

The formulation Previcur Energy does not need to be classified on the basis of its acute oral (LD₅₀ rat >2000 mg/kg bw), dermal (LD₅₀ rat >2000 mg/kg bw), and inhalation toxicology (No study submitted, not required).

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

The formulation Previcur Energy is positive in an LLNA test for skin sensitisation and needs to be classified as R43 ‘May cause sensitisation by skin contact’.

4.1.1 Data requirements formulated product

No additional data requirements are identified.

4.2 Dermal absorption (IIIA 7.3)

Fosetyl

See List of Endpoints. It can be assumed that the dermal absorption of fosetyl-Al in the WG formulation Aliette 800 WG (evaluated in the DAR) is comparable to the dermal absorption of fosetyl-Na in an SL formulation Previcur Energy, since in the evaluated study in the DAR the WG 800 g/kg formulation (actual content: 794 g/kg Fosetyl-Al) was applied on skin membranes as a 1 g/L and 500g/L dilution. Previcur Energy contains a slightly lower amount of fosetyl-Na and similar amounts of water as the 500 g/L dilution used in the study.

Propamocarb

See List of Endpoints; the applicant refers to the dermal absorption values in the DAR, and has not submitted in vitro rat/human data. It can be assumed that the dermal absorption of propamocarb in the SC formulation Previcur N (evaluated in the DAR) is comparable to the dermal absorption of propamocarb in the SL formulation Previcur Energy.

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

None of the other formulants raises concerns that have not been addressed in the submitted studies.

4.4 Exposure/risk assessments

Previcur Energy is an SL formulation and contains 310 g/L fosetyl-Na and 530 g/L propamocarb.

The intended uses are listed under in the GAP (Appendix 1).

4.4.1 Operator exposure/risk

According to the Dutch Plant Protection Products and Biocides Regulations the risk assessment is performed according to a tiered approach. There are four possible tiers:

Tier 1: Risk assessment using the EU-AOEL without the use of PPE

Tier 2: Risk assessment using the NL-AOEL without the use of PPE

Tier 3: Refinement of the risk assessment using new dermal absorption data

Tier 4: Prescription of PPE

Fosetyl

Tier 1

Calculation of the EU-AOEL / Tolerable Limit Value (TLV)

For fosetyl no TLV has been set. The AOEL will be used for the risk assessment.

Since the formulation can be applied year-round, a chronic exposure duration is applicable for the operator (including contract workers) and workers. A chronic AOEL is therefore derived and will be based on the NOAEL of 300 mg/kg bw/d in the 2-year studies in rats and dogs. Application of a safety factor of 100 results in a chronic AOEL of 3 mg/kg bw/day (= 210 mg/day for a 70-kg operator).

Exposure to fosetyl during mixing and loading and application of Previcur Energy is estimated with models. The exposure is estimated for the unprotected operator. In general, mixing and loading and application is performed by the same person. Therefore, for the total exposure, the respiratory and dermal exposure during mixing/loading and application have to be combined.

In the Table below the estimated internal exposure is compared with the systemic EU-AOEL.

For each application method, the exposure is only estimated with the highest dose. Upward spraying was calculated as a worst-case assumption for many crops, even though the height of some crops might indicate downward spraying.

For drip irrigation operator exposure is only expected during mixing and loading.

Table T.1 Internal operator exposure to fosetyl and risk assessment for the use of Previcur Energy

	Route	Estimated internal exposure ^a(mg /day)	Systemic EU-AOEL (mg/day)	Risk-index ^b
Manual up and downward spraying on endive, herbs, ornamental brassica, anemone, euphorbia, lisanthus, lily, and culture of seeds (covered)
Mixing/ Loadingand Application^c	Respiratory	0.78	210	<0.01
Mixing/ Loadingand Application^c	Dermal	1.6	210	0.01
	Total	2.3	210	0.01
Mechanical downward spraying on ornamental brassica, anemone, culture of seed (uncovered)
Mixing/ Loading^d	Respiratory	0.02	210	<0.01
Mixing/ Loading^d	Dermal	0.93	210	<0.01
Application^d	Respiratory	0.04	210	<0.01
Application^d	Dermal	0.14	210	<0.01
	Total	1.1	210	0.01
Manual downward spraying on ornamental brassica, anemone, culture of seed (uncovered)
Mixing/ Loading^e	Respiratory	<0.01	210	<0.01
Mixing/ Loading^e	Dermal	0.60	210	<0.01
Application^e	Respiratory	0.19	210	<0.01
Application^e	Dermal	1.58	210	<0.01
	Total	2.38	210	<0.01
Mechanical upward spraying on euphorbia, lisanthus, delphinium, echinops, helichrysum, sunflowers, rose and perennials, culture of seed (uncovered)
Mixing/ Loading^d	Respiratory	0.01	210	<0.01
Mixing/ Loading^d	Dermal	0.56	210	<0.01
Application^d	Respiratory	0.08	210	<0.01
Application^d	Dermal	2.12	210	0.01
	Total	2.8	210	0.01
Manual upward spraying on euphorbia, lisanthus, delphinium, echinops, helichrysum, sunflowers, rose and perennials, culture of seed (uncovered)
Mixing/ Loading^f	Respiratory	<0.01	210	<0.01
Mixing/ Loading^f	Dermal	0.60	210	<0.01
Application^f	Respiratory	0.56	210	<0.01
Application^f	Dermal	2.59	210	0.01
	Total	3.76	210	0.02
Drip irrigation on hot peppers (covered)
Mixing/ Loading^d	Respiratory	0.09	210	<0.01
Mixing/ Loading^d	Dermal	1.21	210	0.01
	Total	1.3	210	0.01

a Internal exposure was calculated with:

· biological availability via the dermal route: 1% (concentrate) and 1% (spray dilution) (see 4.2)

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

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

c External exposure is estimated with the Dutch greenhouse model.

d External exposure is estimated with EUROPOEM I.

e External exposure is estimated with EUROPOEM I (dermal, M&L) Dutch model (inhalation, M&L), and UK-POEM (application).

f External exposure is estimated with EUROPOEM I (dermal, M&L) Dutch model (inhalation, M&L), and German model 90^th percentile (application).

The seed treatment for indoor tree nursery and floriculture just prior to planting, can be regarded as a small scale use. Even when, as a worst case scenario, the sowing of 10 ha per day is assumed, the operator will handle maximally 1.5 L formulation per day (0.15 L/ha) which is below the maximum amount handled during manual or mechanical field spraying, including mixing and loading. The field spraying applications can therefore be considered worst case scenarios for the operator exposure estimation during the small scale seed treatment for tree nursery and floriculture.

Since the EU-AOEL is not exceeded without the use of PPE, a higher tier assessment is not required.

Propamocarb

Tier 1

Calculation of the EU-AOEL / Tolerable Limit Value (TLV)

For propamocarb no TLV has been set. The AOEL will be used for the risk assessment.

Since the formulation is applied year-round in greenhouses, a chronic exposure duration is applicable for the operator (including contract workers). Propamocarb is included in Annex I of 91/414/EEC, hence the chronic EU-AOEL of 0.29 mg/kg bw/day (= 20.3 mg/day for a 70-kg operator), based on the 52-week study in rats is used for the risk assessment (see List of Endpoints).

Exposure to propamocarb during mixing and loading and application of Previcur Energy is estimated with models. The exposure is estimated for the unprotected operator. In general, mixing and loading and application is performed by the same person. Therefore, for the total exposure, the respiratory and dermal exposure during mixing/loading and application have to be combined.

In the Table below the estimated internal exposure is compared with the systemic EU-AOEL.

For drip irrigation operator exposure is only expected during mixing and loading.

Table T.2 Internal operator exposure to propamocarb and risk assessment for the use of Previcur Energy

	Route	Estimated internal exposure ^a(mg /day)	Systemic EU-AOEL (mg/day)	Risk-index ^b
Manual up and downward spraying on endive, herbs, ornamental brassica, anemone, euphorbia, lisanthus, lily, and culture of seeds (covered)
Mixing/ Loadingand Application^c	Respiratory	1.32	20.3	0.07
Mixing/ Loadingand Application^c	Dermal	26.5	20.3	1.3
	Total	27.8	20.3	1.4
Mechanical downward spraying on ornamental brassica, anemone, culture of seed (uncovered)
Mixing/ Loading^d	Respiratory	0.04	20.3	<0.01
Mixing/ Loading^d	Dermal	15.9	20.3	0.78
Application^d	Respiratory	0.06	20.3	<0.01
Application^d	Dermal	2.4	20.3	0.12
	Total	18.4	20.3	0.91
Manual downward spraying on ornamental brassica, anemone, culture of seed (uncovered)
Mixing/ Loading^e	Respiratory	<0.01	20.3	<0.01
Mixing/ Loading^e	Dermal	10.34	20.3	0.51
Application^e	Respiratory	0.32	20.3	0.02
Application^e	Dermal	27.0	20.3	1.33
	Total	37.7	20.3	1.86
Mechanical upward spraying on euphorbia, lisanthus, delphinium, echinops, helichrysum, sunflowers, rose and perennials, culture of seed (uncovered)
Mixing/ Loading^d	Respiratory	0.02	20.3	<0.01
Mixing/ Loading^d	Dermal	9.54	20.3	0.47
Application^d	Respiratory	0.14	20.3	0.01
Application^d	Dermal	36.3	20.3	1.79
	Total	46.0	20.3	2.26
Manual upward spraying on euphorbia, lisanthus, delphinium, echinops, helichrysum, sunflowers, rose and perennials, culture of seed (uncovered)
Mixing/ Loading^f	Respiratory	<0.01	20.3	<0.01
Mixing/ Loading^f	Dermal	10.34	20.3	0.51
Application^f	Respiratory	0.96	20.3	0.05
Application^f	Dermal	44.2	20.3	2.18
	Total	55.5	20.3	2.73
Drip irrigation on hot peppers (covered)
Mixing/ Loading^d	Respiratory	0.16	20.3	0.01
Mixing/ Loading^d	Dermal	20.7	20.3	1.02
	Total	20.8	20.3	1.03

a Internal exposure was calculated with:

· biological availability via the dermal route: 10% (concentrate) and 10% (spray dilution) (see 4.2)

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

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

c External exposure is estimated with the Dutch greenhouse model.

d External exposure is estimated with EUROPOEM I.

e External exposure is estimated with EUROPOEM I (dermal, M&L) Dutch model (inhalation, M&L), and UK-POEM (application).

f External exposure is estimated with EUROPOEM I (dermal, M&L) Dutch model (inhalation, M&L), and German model 90^th percentile (application).

Since for several scenarios the EU-AOEL is exceeded without the use of PPE, a tier 2 assessment has to be performed using the NL-AOEL for these scenarios.

Tier 2

Calculation of the NL-AOEL

The risk index calculated with the EU-AOEL is >1. Therefore, the Plant Protection Products and Biocides Regulations (NL: Rgb) prescribe the calculation of the risk with an AOEL based on allometric extrapolation (known as the NL-AOEL). This method takes into account the caloric demand of the species studied and results in a more specific value than the EU-AOEL for which a standard factor of 100 is applied.

The calculation of the systemic AOEL for chronic exposure is based on the NOAEL of 29 mg/kg bw/day in the 52-week study with the rat. Calculations from other studies result in higher AOELs.

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

Used factors are:

· extrapolation rat® human on basis of caloric demand 4

· other interspecies differences: 3

· intraspecies differences: (professional use) 3

· biological availability via oral route: >80%*

· weight of professional operator/worker: 70 kg

* If the absorbed dose is significantly lower (<80%) than the administered dose, this is adjusted by a correction factor equal to the percentage absorption.

AOEL_systemic: 29 x 1 x 70 / (4 x 3 x 3) = 56 mg/day

Table T.3 Internal operator exposure to propamocarb and risk assessment for the use of Previcur Energy

	Route	Estimated internal exposure ^a(mg /day)	Systemic EU-AOEL (mg/day)	Risk-index ^b
Manual up and downward spraying on endive, herbs, ornamental brassica, anemone, euphorbia, lisanthus, lily, and culture of seeds (covered)
Mixing/ Loadingand Application^c	Respiratory	1.32	56	0.02
Mixing/ Loadingand Application^c	Dermal	26.5	56	0.47
	Total	27.8	56	0.50
Manual downward spraying on ornamental brassica, anemone, culture of seed (uncovered)
Mixing/ Loading^e	Respiratory	<0.01	56	<0.01
Mixing/ Loading^e	Dermal	10.34	56	0.18
Application^e	Respiratory	0.32	56	<0.01
Application^e	Dermal	27.0	56	0.48
	Total	37.7	56	0.67
Mechanical upward spraying on euphorbia, lisanthus, delphinium, echinops, helichrysum, sunflowers, rose and perennials, culture of seed (uncovered)
Mixing/ Loading^d	Respiratory	0.02	56	<0.01
Mixing/ Loading^d	Dermal	9.54	56	0.17
Application^d	Respiratory	0.14	56	<0.01
Application^d	Dermal	36.3	56	0.65
	Total	46.0	56	0.82
Manual upward spraying on euphorbia, lisanthus, delphinium, echinops, helichrysum, sunflowers, rose and perennials, culture of seed (uncovered)
Mixing/ Loading^f	Respiratory	<0.01	56	<0.01
Mixing/ Loading^f	Dermal	10.34	56	0.18
Application^f	Respiratory	0.96	56	0.02
Application^f	Dermal	44.2	56	0.79
	Total	55.5	56	0.99
Drip irrigation on hot peppers (covered)
Mixing/ Loading^d	Respiratory	0.16	56	<0.01
Mixing/ Loading^d	Dermal	20.7	56	0.37
	Total	20.8	56	0.37

a Internal exposure was calculated with:

· biological availability via the dermal route: 10% (concentrate) and 10% (spray dilution) (see 4.2)

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

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

c External exposure is estimated with the Dutch greenhouse model.

d External exposure is estimated with EUROPOEM I.

e External exposure is estimated with EUROPOEM I (dermal, M&L) Dutch model (inhalation, M&L), and UK-POEM (application).

f External exposure is estimated with EUROPOEM I (dermal, M&L) Dutch model (inhalation, M&L), and German model 90^th percentile (application).

Since the NL-AOEL is not exceeded without the use of PPE, a higher tier assessment is not required.

4.4.2 Bystander exposure/risk

Fosetyl

During spraying operations there should be no bystanders present in the greenhouse. No exposure to bystanders is therefore expected. For field application, the bystander exposure is only a fraction of the operator exposure. Based on the low risk-index for the operator, no exposure calculations are performed for bystanders.

Propamocarb

During spraying operations there should be no bystanders present in the greenhouse. No exposure to bystanders is therefore expected. For field application, the bystander exposure is only a fraction of the operator exposure. Based on the risk-index for the operator without PPE, no exposure calculations are performed for bystanders.

4.4.3 Worker exposure/risk

Fosetyl

Tier 1

Shortly after foliar application it is possible to perform re-entry activities during which intensive contact with the treated crop will occur. Therefore, worker exposure is calculated for the foliar applications.

The exposure is estimated for the unprotected worker. In Table T.4 the estimated internal exposure is compared with the systemic EU-AOEL.

Table T.4 Internal worker exposure to fosetyl and risk assessment after application of Previcur Energy

	Route	Estimated internal exposure ^a(mg /day)	Systemic EU-AOEL (mg/day)	Risk-index ^b
Re-entry activities in endive, herbs, ornamental brassica, anemone, euphorbia, lisanthus, lily, and culture of seeds (covered)
	Respiratory	0.256	210	<0.01
	Dermal	0.349	210	<0.01
	Total	0.605	210	<0.01
Re-entry activities in ornamental brassica, anemone, culture of seed, euphorbia, lisanthus, delphinium, echinops, helichrysum, sunflowers, rose and perennials (uncovered)
	Respiratory	-	210	-
	Dermal	0.42	210	<0.01
	Total	0.42	210	<0.01

a External exposure was estimated with Dutch greenhouse model/ EUROPOEM II. Internal exposure was calculated with:

· biological availability via the dermal route: 1% (spray dilution) (see 4.2)

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

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

Since the EU-AOEL is not exceeded without the use of PPE, a higher tier assessment is not required.

Propamocarb

Tier 1

The exposure is estimated for the unprotected worker. In Table T.4 the estimated internal exposure is compared with the systemic EU-AOEL.

Table T.4 Internal worker exposure to propamocarb and risk assessment after application of Previcur Energy

	Route	Estimated internal exposure ^a(mg /day)	Systemic EU-AOEL (mg/day)	Risk-index ^b
Re-entry activities in endive, herbs, ornamental brassica, anemone, euphorbia, lisanthus, lily, and culture of seeds (covered)
	Respiratory	0.44	20.3	0.02
	Dermal	11.9	20.3	0.59
	Total	12.4	20.3	0.61
Re-entry activities in ornamental brassica, anemone, culture of seed, euphorbia, lisanthus, delphinium, echinops, helichrysum, sunflowers, rose and perennials (uncovered)
	Respiratory	-	20.3	-
	Dermal	7.16	20.3	0.35
	Total	7.16	20.3	0.35

a External exposure was estimated with Dutch greenhouse model/ EUROPOEM II. Internal exposure was calculated with:

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

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

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

Since the EU-AOEL is not exceeded without the use of PPE, a higher tier assessment is not required.

4.4.4 Re-entry

Fosetyl

See 4.4.3 Worker exposure/risk.

Propamocarb

See 4.4.3 Worker exposure/risk.

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

The product complies with the Uniform Principles.

Operator exposure

Based on the risk assessment, it can be concluded that no adverse health effects are expected for the unprotected operator after dermal and respiratory exposure to fosetyl and propamocarb as a result of the application of Previcur Energy in endive, herbs, ornamental brassica, anemone, euphorbia, lisanthus, lily, culture of seeds, delphinium, echinops, helichrysum, sunflowers, rose and perennials, hot peppers, and seed treatment for tree nursery and floriculture.

Bystander exposure

Based on the risk assessment, it can be concluded that no adverse health effects are expected for the unprotected bystander due to exposure to fosetyl and propamocarb during application of Previcur Energy in endive, herbs, ornamental brassica, anemone, euphorbia, lisanthus, lily, culture of seeds, delphinium, echinops, helichrysum, sunflowers, rose, and perennials, hot peppers, and seed treatment for tree nursery and floriculture.

Worker exposure

Based on the risk assessment, it can be concluded that no adverse health effects are expected for the unprotected worker after dermal and respiratory exposure during re-entry activities in endive, herbs, ornamental brassica, anemone, euphorbia, lisanthus, lily, culture of seeds, delphinium, echinops, helichrysum, sunflowers, rose, and perennials, hot peppers, and seed treatment for tree nursery and floriculture due to exposure to fosetyl and propamocarb after application of Previcur Energy.

These conclusions are also valid for the simultaneous exposure to fosetyl and propamocarb.

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

See List of Endpoints.

4.6 Data requirements

Based on this evaluation, no additional data requirements are identified.

4.7 Combination toxicology

The formulation Previcur Energy is a mixture of 2 active substances. The combined toxicological effect of these active substances has not been investigated with regard to repeated dose toxicity. Possibly, the combined exposure to these active substances may lead to a different toxicological profile than the profile(s) based on the individual substances.

The 2 active substances have different toxicological profiles; fosetyl has effects mainly on the urinary tract, and propamocarb induces vacuolisation in different organs.

It is therefore not expected that combined exposure to (residues of) the 2 active substances in Previcur Energy will result in an additional risk above the estimated risks based on the individual substances, when used in accordance with Good Agricultural Practice.

4.8 Mammalian toxicology classification and labelling

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

Fosetyl

Symbol:

Indication of danger: Irritant

Risk phrases

R41

Risk of serious damage to eyes

Propamocarb

Symbol:

Indication of danger: Irritant

Risk phrases

R43

May cause sensitisation by skin contact.

Proposal for the classification and labelling of the formulation concerning health

The current classification and labelling (Xi, R43, S36/37 and DPD01), which is prepared in conformity with Directive 1999/45/EG, can be maintained.

5. Residues

An application for extension of the authorisation of the plant protection product Previcur Energy, a fungicide based on the active substances propamocarb (hydrochloride) and fosetyl (sodium) in the protected cultivation of hot pepper, endive and fresh herbs, was submitted.

The other crops for which extension is requested do not concern crops used for food or feed. Therefore, an assessment of the residual behaviour in/on these crops is not necessary.

Fosetyl

Fosetyl is an existing active substance, included in Annex I of 91/414/EEC. The List of Endpoints presented below was extracted from EFSA Scientific Report (2005) 54, 1-79 on fosetyl of 14 December 2005.

List of Endpoints

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

Plant groups covered	Fruits and fruiting vegetable (citrus, apples, pineapples, tomatoes), leafy vegetables (by studies on apple and vines leaves)
Rotational crops	Radish, lettuce and barley
Plant residue definition for monitoring	sum of fosetyl, its salts and phosphorous acid expressed as fosetyl (or sum of fosetyl, phosphorous acid and their salts expressed as fosetyl – EFSA proposal)
Plant residue definition for risk assessment	sum of fosetyl, its salts and phosphorous acid expressed as fosetyl (or sum of fosetyl, phosphorous acid and their salts expressed as fosetyl – EFSA proposal)
Conversion factor (monitoring to risk assessment)	No

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

Animals covered	Goat
Animal residue definition for monitoring	sum of fosetyl, its salts and phosphorous acid expressed as fosetyl (or sum of fosetyl, phosphorous acid and their salts expressed as fosetyl – EFSA proposal)
Animal residue definition for risk assessment	sum of fosetyl, its salts and phosphorous acid expressed as fosetyl (or sum of fosetyl, phosphorous acid and their salts expressed as fosetyl – EFSA proposal)
Conversion factor (monitoring to risk assessment)	No
Metabolism in rat and ruminant similar (yes/no)	Yes
Fat soluble residue: (yes/no)	Not fat soluble

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

Residues of phosphorous acid in the range of the LOQ (0.5 mg/kg) can be present for short time intervals between application and planting or sowing of a rotational crop. A pre-planting interval of 30 days is recommended

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

The sum of phosphorous acid and fosetyl is stable during 12 months at – 18°C

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

	Ruminant:	Poultry:		Pig:
	Conditions of requirement of feeding studies
Expected intakes by livestock ³ 0.1 mg/kg diet (dry weight basis) (yes/no - If yes, specify the level)	Yes (4 and 12 mg/kg dry diet for diary and beef cattle respectively)	No		No
Potential for accumulation (yes/no):	No	No		No
Metabolism studies indicate potential level of residues ≥ 0.01 mg/kg in edible tissues (yes/no)	Metabolism studies cannot be used for indicative information as the phosphorus acid moiety of the compound is not appropriate for radioactive labeling
	Feeding study in dairy cattle with a mixture of fosetyl and phosphorous acid (1 and 9 mg/kg diet respectively) Residue levels in matrices : Mean concentration (mg/kg)
Muscle	0.048		Study not required		Study not required
Liver	Not detected		Study not required		Study not required
Kidney	0.16		Study not required		Study not required
Fat	0.13		Study not required		Study not required
Milk	0.024
Eggs			Study not required

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

Crop/processed crop	Number of studies	Transfer factor	% Transference *
Orange/pulp	2 (8 results)	0.41	Not calculated
Oranges/ juice	3	1.1
Orange/pomace	3	0.90
Grapes/ wine	15	0.91
Grapes/ juice	7	0.93

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

Propamocarb

Propamocarb is an existing active substance, included in Annex I of 91/414/EEC. The List of Endpoints presented below was extracted from EFSA Scientific Report (2006) 78, 1-80 on propamocarb of 12 May 2006.

List of Endpoints

Metabolism in plants (Annex IIA, point 6.1 and 6.7, Annex IIIA, point 8.1 and 8.6)
Plant groups covered	Leafy crops (spinach and lettuce), fruits (tomatoes and cucumbers) and root vegetables (potatoes).
Rotational crops	Lettuce, radish and wheat.
Plant residue definition for monitoring	Sum of propamocarb and its salts, expressed as propamocarb
Plant residue definition for risk assessment	Same definition as above.
Conversion factor (monitoring to risk assessment)	Not applicable

Metabolism in livestock (Annex IIA, point 6.2 and 6.7, Annex IIIA, point 8.1 and 8.6)
Animals covered	A metabolism study was not required. A metabolism study in the cow was however submitted.
Animal residue definition for monitoring	None required or proposed.
Animal residue definition for risk assessment	None required or proposed.
Conversion factor (monitoring to risk assessment)	Not applicable
Metabolism in rat and ruminant similar (yes/no)	Yes
Fat soluble residue: (yes/no)	Non fat soluble

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

Information was provided

The studies indicate that residues may be present in crops planted within 30 after the application of

propamocarb. The residue pattern in rotational crops is similar to that in primary crops. A recommendation on propamocarb products should indicate that crops should not be sowed or planted on soil within 120 days of the application of

propamocarb.

Stability of residues (Annex IIA, point 6 introduction, Annex IIIA, point 8 introduction)
Stability studies were presented.	Propamocarb was found to be stable in lettuce, cucumber, tomato and in Brussels sprouts when stored in a freezer for the duration of the test periods which ranged from 1 to 2 years.

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

Intakes by livestock ³ 0.1 mg/kg diet/day:

Ruminant:

Poultry:

Pig:

No feeding studies required

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

Crop/processed crop

Number of studies

Transfer factor

% Transference *

Not applicable

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

Comments on/additions to List of Endpoints

Fosetyl: No additions to the List of Endpoints. In the evaluation table rev. 2-1 (17088/EPCO/BVL/04 (30.09.2005)), no open points or data requirements were identified.

Propamocarb: No additions to the List of Endpoints. In the evaluation table rev. 2 (17706/EPCO/BVL/05 (09.05.2006)), no open points or data requirements were identified.

5.1 Summary of residue data

The assessment below is based on the DARs for fosetyl and propamocarb and the summaries by Ctgb 20071173-sava-res (September 2008) and 20070123-sava-res (September 2008).

5.1.1 Metabolism in plants

Fosetyl

Metabolism studies in the crops category fruit has been summarised and evaluated in the DAR. Studies in apple and vine leaves were classified as leafy vegetables, which was considered acceptable in EPCO 19. It was also considered that the information on fruits and leaves available and the fact that the metabolism pathway is simple, no more information is considered necessary as not other metabolites are expected.

Propamocarb

Metabolism studies in the crops categories fruit (tomato), leafy vegetables (spinach and lettuce) and root/tuber vegetable (root vegetable) have been summarised and evaluated in the DAR.

The crops applied for belong to these crop category leafy crops. No additional studies are required.

5.1.2 Metabolism in livestock

Fosetyl

The crops in the intended use are not generally used as livestock feed. Metabolism studies are therefore not required.

Propamocarb

The crops in the intended use are not generally used as livestock feed. Metabolism studies are therefore not required.

5.1.3 Residue definition (plant and animal)

Fosetyl

The residue definition for monitoring and risk assessment for products of plant an animal origin is: fosetyl-Al (sum of fosetyl + phosphorous acid and their salts expressed as fosetyl).

Propamocarb

The residue definition for monitoring and risk assessment for products of plant an animal origin is: Propamocarb (Sum of propamocarb and its salt expressed as propamocarb)

5.1.4 Stability of residues

Fosetyl

Storage stability was studied in grapes, cucumber, potatoes and lettuce, which all have a watery matrix, as do the crops applied for. Fosetyl residues were proven to be stable during at least 12 months of frozen storage.

Propamocarb

Storage stability was studied in lettuce, cucumber, tomatoes and Brussels sprouts, which all have a watery matrix, as do the crops applied for. Propamocarb residues were proven to be stable during at least 12 months of frozen storage.

5.1.5 Supervised residue trials

Fosetyl and propamocarb

Endive and fresh herbs

Residue levels found in trials with lettuce can be extrapolated to endive and herbs as,

the cGAPs-NL for lettuce, endive and fresh herbs are identical.

Twelve supervised residue trials in lettuce have been submitted for the application for authorisation of Previcur Energy (20071173 TG) and were summarised by Ctgb (September 2008). The dose range used in the trials (two drench applications of 15.9 kg propamocarb/ha and 9.4 kg fosetyl/ha, followed by two spray applications of ca. 1.325 kg propamocarb/ha and ca. 0.775 kg fosetyl/ha, PHI 21d) does not represent the cGAP-NL (1x 1.32 kg propamocarb/ha, 0.775 kg fosetyl/ha, PHI 21d). The applicant stated that the trials were performed to represent the cGAP-EU, which is worst-case compared to the cGAP-NL. The trials were performed with the last two applications at the dose range prescribed in the cGAP-NL. This is acceptable. Higher residue levels detected at later PHIs are considered relevant for MRL setting and are therefore selected.

Lettuce is a major crop; a minimum of 8 supervised residue trials is therefore required. A sufficient number of acceptable trials is available.

Trials with lettuce can be extrapolated to endive and fresh herbs. The residue levels selected are presented in table R1.

Sweet pepper

Twelve supervised residue trials in pepper have been submitted. The dose range used in eight trials was one drench applications of ca. 31.8 kg propamocarb/ha and ca. 18.9 kg fosetyl/ha, followed by one drench application of 15.9 kg propamocarb/ha and ca. 9.4 kg fosetyl/ha, followed by four spray applications of 1.59-3.3 kg propamocarb/ha and 0.93-1.96 kg fosetyl/ha, PHI 3d. In the four remaining trails, the application regime was two drench applications of ca. 15.9 kg propamocarb/ha and ca. 9.3 kg fosetyl/ha, followed by four spray applications of 1.59 kg propamocarb/ha and 0.93 kg fosetyl/ha, PHI 3d. These application regimes do not represent the cGAP-NL (4x 1.59 kg propamocarb/ha, 0.93 kg fosetyl/ha by drip irrigation, PHI 3d). The applicant stated that the trials were performed to represent the cGAP-EU, which is worst-case compared to the cGAP-NL. This is acceptable. Pepper is a major crop; a minimum of 8 supervised residue trials is therefore required. A sufficient number of acceptable trials is available.

Trials with (sweet) pepper can be extrapolated to hot pepper. The residue levels selected are presented in table R1.

Table R1: Selected residue levels from trials with propamocarb-fosetylate

Crop	Residue levels selected for MRL setting (mg/kg)
Crop	PropamocarbxHCL	Fosetyl-AL	Phosphorous acid
Sweet pepper and hot pepper	<0.01 (2x), 0.02, 0.03, 0.08, 0.13 (2x), 0.15, 0.16, 0.17, 0.26, 1.2	<0.01 (4x), <0.06 (4x), <0.2 (4x)	<0.2 (2x), 0.2 (2x), 0.28 (2x), 0.4, 0.62, 2.0, 2.4, 3.1, 3.5
Lettuce, endive and fresh herbs	0.01, 0.77, 0.85, 0.9, 1.3, 2.0, 3.5, 4.8, 5, 6.5, 9.0, 9.7	<0.01, 0.01, 0.12, <0.2 (7x), 0.3, 1.3	1.2, 1.4, 1.7, 2.3, 2.7, 2.9, 3.7 (2x), 3.9, 5.2, 8.6, 11

5.1.6 Residues in succeeding crops

Fosetyl

The recommendation from the List of Endpoints is adopted for the use of Previcur Energy in the cultivation of endive and fresh herbs:

As the plant back restriction for propamocarb is 120 days, this will apply to the formulation.

Propamocarb

The recommendation from the List of Endpoints is adopted for the use of Previcur Energy in the cultivation of endive and fresh herbs:

A recommendation on propamocarb products should indicate that crops should not be sowed or planted on soil within 120 days of the application of propamocarb.

5.1.7 Residues from livestock feeding studies

Fosetyl

The crops in the intended use are not generally used as livestock feed. Metabolism studies are therefore not required.

Propamocarb

The crops in the intended use are not generally used as livestock feed. Metabolism studies are therefore not required.

5.1.8 Processing factors

Fosetyl

No processing studies have been submitted. Studies are not necessary as the total theoretical daily intake (TMDI) is less than 10% of the ADI for the crops of interest..

Propamocarb

No processing studies have been submitted. Studies are not necessary since the total theoretical daily intake (TMDI) is less than 10% of the ADI for the crops of interest.

5.1.9 Calculation of the ADI and the ARfD

Fosetyl

Calculation of the ADI

The ADI is based on the NOAEL of 300 mg/kg bw/d in the 2-year rat and 2-year dog studies. Application of a safety factor for inter- and intraspecies differences of 100 results in an ADI of 3 mg/kg bw/day (see the List of Endpoints for mammalian toxicology).

Calculation of the ARfD

No ARfD is derived, since fosetyl has no acute toxic properties.

Propamocarb

Calculation of the ADI

The ADI is based on the NOAEL of 29 mg/kg bw/d in the 52-week dietary rat study. Application of a safety factor for inter- and intraspecies differences of 100 results in an ADI of 0.29 mg/kg bw/day (see the List of Endpoints for mammalian toxicology).

Calculation of the ARfD

The ARfD is based on the NOAEL of 100 mg/kg bw/d in the 28-day rat gavage study. Application of a safety factor for inter- and intraspecies differences of 100 results in an ARfD of 1 mg/kg bw/day (see the List of Endpoints for mammalian toxicology).

5.2 Maximum Residue Levels

Fosetyl and propamocarb

Crop	MRL (mg/kg
	Propamocarb (Sum of propamocarb and its salt expressed as propamocarb)	Fosetyl (sum fosetyl + phosphorous acid and their salts, express as fosetyl)
Sweet pepper Hot pepper	10	130
Lettuce	50	75
Endive	10	75
Fresh herbs	30	75

EU-MRLs have been established for propamocarb and fosetyl in Annex III to Regulation 396/2005 by means of Regulation 149/2008.

It can be concluded that the MRLs for lettuce, endive, fresh herbs and spinach cover the intended use of Previcur Energy.

No revised MRLs need to be notified.

5.3 Consumer risk assessment

Fosetyl

Risk assessment for chronic exposure through diet

Based on the proposed residue tolerances, a calculation of the National Theoretical Maximum Daily Intake (NTMDI) was carried out using the National Dutch diet and the harmonised EU-MRLs. Calculation of the NTMDI shows that 18.8% and 44.4% of the ADI is used for the general population and for children, respectively.

Risk assessment for acute exposure through diet

As no ARfD was derived for fosetyl, a risk assessment for acute exposure was not performed.

Propamocarb

Risk assessment for chronic exposure through diet

Based on the proposed residue tolerances, a calculation of the National Theoretical Maximum Daily Intake (NTMDI) was carried out using the National Dutch diet and the temporary EU-MRLs. Calculation of the NTMDI shows that 18.3% and 47.3% of the ADI is used for the general population and for children, respectively.

Risk assessment for acute exposure through diet

A calculation of the National Estimated Short Term Intake (NESTI) was carried out using the National Dutch diet (‘large portion sizes’; 97.5 percentile from dietary data), the UK ‘unit weights’ and HRs for crops applied for. The NESTI for lettuce uses the highest percentages of the ARfD: 30,5% and 62,6% for the general population and for children, respectively.

Risk assessment for combined exposure to fosetyl and propamocarb

See point 4.7.

Conclusion

The product complies with the Uniform Principles for endive, fresh herbs and hot pepper.

Based on the assessment for residues, no risk for the consumer is expected.

5.4 Data requirements

None.

6. Environmental fate and behaviour

For the current application of Previcur Energy, risk assessment is done in accordance with Chapter 2 of the RGB.

Fosetyl is an existing active substance listed on Annex I (2006/64/EC). For the Assessment the final List of Endpoints included in the final EFSA conclusion (January 2006) is used. RMS is France.

Special remarks at inclusion on Annex I:

PART A

Only uses as fungicide may be authorised.

PART B

For the implementation of the uniform principles of Annex VI, the conclusions of the review

report on fosetyl, and in particular Appendices I and II thereof, as finalised in the Standing

Committee on the Food Chain and Animal Health on 4 April 2006 shall be taken into account.

In this overall assessment Member States:

— must pay particular attention to the protection of birds, mammals, aquatic organisms and

non-target arthropods.

Conditions of authorisation should include risk mitigation measures, where appropriate, such

as buffer zones.

The concerned Member States shall request the submission of further studies to confirm the

risk assessment for non-target arthropods, in particular with regard to in-field recovery, and

for herbivorous mammals. They shall ensure that the notifier at whose request fosetyl has been

included in this Annex provide such studies to the Commission within two years from the entry into force of this Directive.

In the DAR fosetyl-Al was the actual substance tested. As this salt will dissociate in the environment there is no difference in fate and behaviour with the fosetyl-Na salt in Previcur Energy.

Propamocarb HCl is an existing active substance included in Annex I of 91/414 (2007/25/EG). For propamocarb-HCl the List of Endpoints included in the EFSA conslusion d.d. May 2006 is used for the assessment. Notifiers are Bayer and Agriphar. Agriphar has given access to Stichting Trustee Bijzondere Toelatingen to all studies submitted by Agriphar for the DAR. RMS is Ireland.

Special remarks at inclusion on Annex I:

“In assessing applications to authorise plant protection products containing propamocarb for uses other than foliar applications, Member States shall pay particular attention to the criteria in Article 4(1)(b), as regards worker exposure and shall ensure that any necessary data and information is provided before such an authorisation is granted. For the implementation of the uniform principles of Annex VI, the conclusions of the review report on propamocarb, and in particular Appendices I and II thereof, as finalised in the Standing Committee on the Food Chain and Animal Health on 24 November 2006 shall be taken into account.”

In this overall assessment Member States must pay particular attention to:

- the operators and workers safety. Conditions of authorisation should include protective measures, where appropriate;

- the transfer of soil residues for rotating or succeeding crops;

- the protection of surface and groundwater in vulnerable zones;

- the protection of birds, mammals and aquatic organisms. Conditions of authorisation should include risk mitigation measures, where appropriate.'

List of Endpoints Fate/behaviour

Fosetyl

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

Mineralization after 100 days ‡

ethyl moiety: > 70 % (4-16 d)

Non-extractable residues after 100 days ‡

ethyl moiety: max. 33.5-41.3 % (2-4 d)

phosphorous acid : 49.4-74.2 % after 87-117 d (probably insoluble forms of phosphite and of phosphate derived from oxidation of phosphite, low availability to plants)

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

Ethanol (max. 78 % after 1.5 hours) and 2 unknown metabolites (max. 12.8 % and 17.2 % after < 1 h) derived from the ethyl moiety, transient (1 d), not relevant.

Phosphorous acid (100 % assumed, turned into phosphate by biological process)

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

Anaerobic degradation ‡

Similar to aerobic degradation

ethyl moiety : ethanol 22 %, CO₂ 45 %, bound < 10 %

phosphorous acid : no study, no specific metabolite expected

Soil photolysis ‡

Not relevant for fosetyl

Light could favour degradation of phosphorous acid
(indirect photolysis, phosphate likely to be formed)

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

Method of calculation	First order (R2 > 0.83 for phosphorous acid)
Laboratory studies ‡ (range or median, with n value, with r² value)	DT_50lab (20°C, aerobic): Fosetyl : 3 h (10 soils, pH 5.3-7.6), total extract < 1 d Phosphorous acid : - clay loam : 96 d (bare soil) and 27 d (amended soil) at 28° C (157 d and 49 d at 20° C) - sandy loam : 119 d at 20° C - clay loam : similar to sandy loam - loamy sand : about 2 months (outdoor), shorter in presence of plants. typical value 119 d, max. 157 d
	DT_90lab(20°C, aerobic): Fosetyl : total extract < 4 d Phosphorous acid : typical value 395 d, max. 521 d (extrapolated)
	DT_50lab (10°C, aerobic): Fosetyl : total extract < 2 d (1 soil, 12° C)
	DT_50lab (20°C, anaerobic): Fosetyl : 14-40 hours (2 soils)
	degradation in the saturated zone: not required
Field studies ‡ (state location, range or median with n value)	DT_50f: No data. Not required
	DT_90f: No data. Not required
Soil accumulation and plateau concentration ‡	Assuming application to citrus (4x7 kg/ha), no foliage interception, DT₅₀ max. 157 d, the upper accumulation plateau for phosphorous acid is calculated to be 33 mg/kg in 5 cm soil.

Soil adsorption/desorption (Annex IIA, point 7.1.2)

K_f /K_oc ‡

K_d ‡

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

Fosetyl : not adsorbed on soil

Phosphorous acid: (indicative values)

Kd 44-48 mL/g from column leaching studies (see below). Complex phenomenon (possible formation of insoluble salts and/or complexes). Significant variability between soils not expected.

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

Column leaching ‡

¹⁴C-Fosetyl : 4 soils (OC 0.76-2.09 %), 200 mm. RA in leachates : 0.36-43.8 % (fosetyl < 3.4 %, ethanol < 36 %, unknowns < 10 %, phosphorous acid <1-12.6 % could derive from degradation of fosetyl in leachates)

³³P-Phosphorous acid: 15 kg/ha, 2 soils (clay 5.1-8.9 %, OC 2.4-3.0 %, pHw 5.4-6.9), 508 mm. RA in leachates : < 0.00 %. RA in soil : 78.7-90.9 % in 0-2.5 cm, 5.6-17.2 % in 2.5-5 cm, 0.01-0.09 % in 5-10 cm, < 0.00-0.22 % in 10-15 cm, and < 0.00 % below 15 cm.

Aged residues leaching ‡

¹⁴C-Fosetyl : 1 soil (OC 2.09 %), 30 d incubation period, 4.9 mm for 45 d

Negligible mobility but incubation period too long.

Lysimeter/ field leaching studie ‡

No data, not required.

Phosphorous acid

Uses : Citrus (4 x 7 kg fosetyl/ha , 28 d interval), cucumber (4 x 4.5 kg fosetyl/ha , 10 d interval) and grapes (6 x 2 kg fosetyl /ha , 10 d interval), no interception, total conversion of fosetyl to phosphorous acid, MW taken into account (354 for fosetyl-Al and 3 x 82 for phosphorous acid). For the applied for uses assessed on citrus or grapes it would be appropriate to consider 70% and 50% crop interception respectively (FOCUS groundwater interception values) which would give lower PECsoil than those outlined below.

Single application : 6.5 mg/kg (4.9 kg H₃PO₃/ha) for citrus, 4.2 mg/kg (3.1 kg H₃PO₃/ha) for cucumber, 1.9 mg/kg (1.4 kg H₃PO₃/ha) for grapes.

Multiple applications : 26.0 mg/kg (19.5 kg H₃PO₃/ha) for citrus, 16.7 mg/kg (12.5 kg H₃PO₃/ha) for cucumber, 11.1 mg/kg (8.3 kg H₃PO₃/ha) for grapes, assuming no degradation between treatments.

Accumulation : for single yearly application at the total annual rate and the max. DT_50lab of 157 d, upper plateau 33 mg/kg (24.4 kg H₃PO₃/ha) for citrus, 21 mg/kg (15.6 kg H₃PO₃/ha) for cucumber, 14 mg/kg (10.4 kg H₃PO₃/ha) for grapes.

Aluminium ions

Soils at pH > 5 : negligible concentrations due to rapid adsorption and/or conversion into insoluble forms.

Soils at pH < 5 : max 2.85 mg/kg for multiple application to citrus without interception (worst case). Negligible as compared to natural exchangeable fraction (>> 72 mg/kg, up to > 1350 mg/kg).

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

Hydrolysis of active substance and relevant metabolites (DT₅₀) ‡ (state pH and temperature)	pH 5: fosetyl and phosphorous acid are stable pH 7: fosetyl and phosphorous acid are stable pH 9 : fosetyl and phosphorous acid are stable
Photolytic degradation of active substance and relevant metabolites ‡	Fosetyl : no light absorption at 290 nm Phosphorous acid is stable (except in presence of titanium oxide, metabolite PO₄H₃)
Readily biodegradable (yes/no)	Yes (75 % mineralization at 28 d)
Degradation in water/sediment - DT₅₀ water ‡	3.75-4.3 d
- DT₉₀ water ‡	12.5-14.2 d
- DT₅₀ whole system ‡	3.9-4.5 d
- DT₉₀ whole system ‡	12.9-14.8 d
Mineralization	ethyl moiety : 70.3-75.9 % (100 d)
Non-extractable residues	ethyl moiety : max. 24.0-28.8 % (14-30 d)
Distribution in water / sediment systems (active substance) ‡	negligible amounts of fosetyl in sediment
Distribution in water / sediment systems (metabolites) ‡	Ethanol : max. 16 % in water, 4.2 % in sed., transient. Unknown : max. 4.1 % in sed., transient. Phosphorous acid : expected to be rapidly released in water (100 % assumed) and then adsorbed on sediment (100 % assumed) where it could be slowly oxidized to phosphate.

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

Direct photolysis in air ‡	Latitude: ................ Season: ................. DT₅₀ no data, not required
Quantum yield of direct phototransformation	no data, not required
Photochemical oxidative degradation in air ‡	46 hours (12 h photoperiod)
Volatilization ‡	from plant surfaces: no data, not required
	from soil: no data, not required

Definition of the Residue (Annex IIA, point 7.3)

Relevant to the environment

Soil and water : fosetyl, fosetyl salts and phosphorous acid

Sediment : phosphorous acid

Air : fosetyl-Al

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

Soil (indicate location and type of study)	No data
Surface water (indicate location and type of study)	No data
Ground water (indicate location and type of study)	No data
Air (indicate location and type of study)	No data

Classification and proposed labelling (Annex IIA, point 10)

with regard to fate and behaviour data

No labelling proposed (readily biodegradable)

Propamocarb

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

Mineralization after 100 days ‡

At 20 °C:

11.7-52.5% AR after 90d (n = 9)

At 25 °C

82.2-83.6% AR after 90d (n = 2)

Two different radiolabelled versions (aminopropyl-1-[¹⁴C] and aminopropyl-2-[¹⁴C]) of propamocarb hydrochloride were used in the fate studies. The position of radiolabelling was not observed to have an effect on any fate endpoint.

Non-extractable residues after 100 days ‡

NER maximum levels

17.8-49.0% AR after 90d at 20 °C (n=9)

11.8-12.6% AR after 90d at 25 °C (n=2)

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

Transient unidentified metabolites reached maximum individual levels ranging from 1.0-8.7% of applied radioactivity (time of maximum occurrence = 0-90 days) (n = 22 incubations; 15 soils tested – 9 soils incubated at 20 °C, 3 soils incubated at 10 °C, 1 soil incubated at 15 °C, 1 soil incubated at 22 °C, 5 soils incubated at 25 °C)

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

Anaerobic degradation ‡

n = 2 soils (>30 days conditioning under anaerobic conditions followed by 121-365 days anaerobic incubation)

Mineralisation: CO₂ = 1.9, 3.5, and 7.7% after 365, 121, and 90 days, respectively

Non-extractable residues: 8.1, 33.5, and 40.64% after 14, 269, and 121 days, respectively

Metabolites:

Transient unidentified metabolites reached maximum individual levels of <2.0% and 6.65% after 180 and 365 days, respectively

Soil photolysis ‡

n = 2 soils

Mineralisation: CO₂ = 1.9-2.7% after 31 days (irradiated samples), CO₂ = 0.0-8.8% after 31 days (non-irradiated samples)

Non-extractable residues: 9.5-21.0% after 31 days (irradiated samples), 6.6-15.6% after 31 days (non-irradiated samples)

Metabolites:

Transient unidentified metabolites reached maximum individual levels of 1.0% and 8.7% after 14 and 30 days, respectively

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

Method of calculation	Laboratory: Aerobic studies on propamocarb hydrochloride – non-linear simple first order, mono-exponential regression of parent (using Microsoft Excel tools Solver and RATEFIT). Where a short lag phase was observed the lag time data was fitted using zero-order degradation. Aerobic studies on metabolites – not applicable Anaerobic study – non-linear simple first order, mono-exponential and simple linear first order regression of parent, was used for the total system. A bi-exponential equation was used for the water phase. Soil photolysis study – non-linear simple first order, mono-exponential and simple linear first order regression, accounting for the effect of non-photolytic degradation Saturated zone degradation studies – not applicable Field studies: Non-linear simple first order regression of parent.
Laboratory studies ‡ (range or median, with n value, with r² value)	Aerobic studies (HCl: hydrochloride): Propamocarb HCl DT_50lab (20 °C, aerobic): 10.9, 11.7, 14.1, 17.8, 22.4, 23.4, 29.7, 87.7, 137 days (n = 9 soils, r² = 0.91-0.98), mean = 39.3 days Propamocarb HCl DT_50lab (25 °C, aerobic): 10.0, 13.0, 14.0, 28.0 days, (n = 3 soils) mean = 16.25 days Propamocarb HCl DT_50lab (22 °C, aerobic): 17.7 days (n = 1 soil) Metabolites: Not applicable For FOCUSgw modeling (two studies): Propamocarb HCl DT_50lab (aerobic, 1^st order kinetics): mean = 17.08 days and 10.20 days (normalised to 10kPa, 20 °C with Q10 of 2.2) If the datasets of both notifiers are considered as a whole, the geometric mean DT₅₀ value of laboratory aerobic topsoil values normalised to 20 °C and pF2 moisture content from both datasets is 13.91 days (n = 17 values). Metabolites: Not applicable
	Propamocarb HCl DT_90lab (20 °C, aerobic): 36.1-452.0 days (n = 8 soils, r² = 0.91-0.98), mean = 130.6 days Propamocarb HCl DT_90lab (25 °C, aerobic): 17.0-72.4 days (n = 3 soils), mean = 35.5 days Propamocarb HCl DT_90lab (22 °C, aerobic): 27.8 days (n = 1 soil) Metabolites: Not applicable
	(10 °C, aerobic): laboratory values Propamocarb HCl DT_50lab (10 °C, aerobic): 25.3, 47.2, 73.7 days (n = 3 soils, r² = 0.93), mean = 48.7 Propamocarb HCl DT_50lab (15 °C, aerobic): 22.0, 24.0 days (n = 2 soils), mean = 23.0 days Metabolites: Not applicable Propamocarb HCl DT_90lab (10 °C, aerobic): 84.1, 156.9, 245.0 days (n = 3 soils, r² = 0.93), mean = 162.0 Propamocarb HCl DT_90lab (15 °C, aerobic): 73.1, 79.7 days (n = 2 soils), mean = 76.4 days Metabolites: Not applicable
	Anaerobic soil: Propamocarb HCl DT_50lab (20 °C, anaerobic): 65.68-308.16 days (n = 1 soil type, 2 incubations, r² = 0.9815-9838) Propamocarb HCl DT_50lab (25 °C, anaerobic): 459.0 days (n = 1 soil, r² = 0.76) Metabolites: Not applicable [Rates are whole-system values (soil and flood water combined)] Anaerobic water phase: Propamocarb HCl DT_50lab (20 °C, anaerobic): 7.03-14.70 days (n = 1 water system type, 2 incubations, r² = 0.9797-0.9873) Metabolites: Not applicable
	Soil photolysis: Propamocarb HCl DT_50lab (irradiated samples): 35.4, 199.2 days (8 h light, 16 h dark, and 12 h light and dark photoperiods) (n = 2 soils, r² = 0.812-0.819) mean = 117.3 days Propamocarb DT_50lab (dark control samples): 103.1 days (n = 1 soil, r² = 0.86) Metabolites: Not applicable
	Aerobic subsoil degradation (n = 1 soil, 10 °C): Propamocarb HCl DT_50lab (aerobic): 73.7, 136.0, 239.0, 267.0 days (n = 4 subsoil horizons 20-90cm) mean = 178.9 days Metabolites: Not applicable
Field studies ‡ (state location, range or median with n value)	DT_50f: USA, Georgia, loamy sand (bare soil): Propamocarb HCl DT_50field: 17.6 days (n = 1, r² = 0.76) USA, Georgia, loamy sand (thatch): Propamocarb HCl DT_50field: 17.4 days (n = 1, r² = 0.78) Metabolites: Not applicable USA, California, sandy loam (bare soil): Propamocarb HCl DT_50field: 22.1 days (n = 1, r² = 0.99) USA, California, sandy loam (thatch): Propamocarb HCl DT_50field: 23.7 days (n = 1, r² = 0.92) Metabolites: Not applicable
	DT_90f: USA, Georgia, loamy sand (bare soil): Propamocarb HCl DT_90field: 58.6 days (n = 1, r² = 0.76) USA, Georgia, loamy sand (thatch): Propamocarb HCl DT_90field: 57.7 days (n = 1, r² = 0.78) Metabolites: Not applicable USA, California, sandy loam (bare soil): Propamocarb HCl DT_90field: 73.3 days (n = 1, r² = 0.99) USA, California, sandy loam (thatch): Propamocarb HCl DT_90field: 78.6 days (n = 1, r² = 0.92) Metabolites: Not applicable
Soil accumulation and plateau concentration ‡	Not applicable

Soil adsorption/desorption (Annex IIA, point 7.1.2)

K_f /K_oc ‡

K_d ‡

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

Propamocarb HCl (topsoil):

K_f: 0.671-77.20 mL/g (mean = 10.50 mL/g, 12 soils)

K_foc: 41.0-2451.0 mL/g (mean = 535.56 mL/g, 12 soils)

1/n: 0.822-0.926 (mean = 0.867, 12 soils)

K_d: 1.34-17.6 mL/g (mean = 7.77 mL/g, 4 soils)

K_oc: 59.14-1680.79 mL/g (mean = 718.81 mL/g, 4 soils)

Propamocarb HCl (subsoil horizons):

K_f: 0.72-1.04 mL/g (mean = 0.93 mL/g, 1 soil)

K_foc: 171.0-3600.0 mL/g (mean = 1190.0 mL/g, 1 soil)

1/n: 0.86-0.91 (mean = 0.872, 1 soil)

[K_foc = K_f normalized to organic carbon content, K_oc = K_d normalized to organic carbon content]

Metabolites: not applicable

No obvious pH dependence for Propamocarb. However, there is a possibility that adsorption to soil may depend on the clay content of the soil.

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

Column leaching ‡

Guideline: BBA Part IV, Section 4-2 (1986)

Precipitation: 200 mm

Time period: 5 days

Leachate: 0.043-0.260% total residues in leachate, 37.0-92.8% radioactivity retained in top 5 cm, 0.5-41.62% radioactivity retained in 5-10 cm column segment, 0.5-13.1% radioactivity retained in 10-15 cm column segment, <0.1-0.2% radioactivity retained in 15-20 cm column segment, <0.1% radioactivity retained in the remaining segments 20-25 cm and 25-30 cm

Aged residues leaching ‡

Guideline: SETAC (1995), Part 1, Section 6

Aged for: 12 days (Midwest 3), 23 days (Speyer 2.3)

Time period: 2 days

Precipitation: 200 mm

Leachate: 0.67-0.90% radioactivity in leachate, 27.88-44.49% radioactivity retained in top 6 cm, 6.21-14.86% radioactivity retained in 6-12 cm column segment, 1.60-10.90% radioactivity retained in 12-18 cm column segment, 0.28-3.90% radioactivity retained in 18-24 cm column segment, 0.07-1.06% radioactivity retained in 24-30 cm column segment

Lysimeter/ field leaching studie ‡

Not required

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

Hydrolysis of active substance and relevant metabolites (DT₅₀) ‡ (state pH and temperature)	pH 4 and pH 5 (HCl: hydrochloride) Propamocarb HCl DT₅₀ (pH 4 & 5, 50 °C): stable (DT₅₀ >365 days) Propamocarb HCl DT₅₀ (pH 4 & 5, 25 °C): stable (DT₅₀ >365 days) Metabolites: not applicable
	pH 7 Propamocarb HCl DT₅₀ (50 °C): stable (DT₅₀ >365 days) Propamocarb HCl DT₅₀ (25 °C): stable (DT₅₀ >365 days) Metabolites: not applicable
	pH 9 Propamocarb HCl DT₅₀ (50 °C): stable (DT₅₀ >365 days) Propamocarb HCl DT₅₀ (25 °C): stable (DT₅₀ >365 days) Metabolites: not applicable
Photolytic degradation of active substance and relevant metabolites ‡	Propamocarb HCl: (pH 4-5, 24 °C) stable [Irradiation with artificial light, stated to be equivalent to 4´ light intensity seen in summer at Les Borges, Switzerland.] UV-VIS study indicates that wavelength of maximum absorption is <250 nm. Irradiation at wavelengths ³290 nm are not expected to induce any photochemical transformation. Metabolites: not applicable
Readily biodegradable (yes/no)	[Mean cumulative CO2 production data obtained from Propamocarb HCl test mixtures are ambivalent. Results from a study indicate highly variable CO2 evolution from test replicates. However, Propamocarb HCl route and rate of degradation has been extensively investigated in soil metabolism and water/sediment studies.]
Degradation in water/sediment DT₅₀ water ‡ DT₉₀ water ‡ DT₅₀ whole system ‡ DT₉₀ whole system ‡	[Two aerobic studies provided and one anaerobic study for Propamocarb HCl] Water phase: Propamocarb HCl (aerobic) DT₅₀ = 11.6-12.0 days, DT₉₀ = 38.4-39.9 days (1^st order, n = 2, r² = 0.894-0.967) Propamocarb HCl (aerobic) DT₅₀ = 10.0-15.0 days, DT₉₀ = 34.0-49.0 days (non-linear 1^st order using KIM B1.0 model, n = 2) Metabolites: not applicable Propamocarb HCl (anaerobic) DT₅₀ = 12.1 days, DT₉₀ = 40.1 days (linear 1^st order regression, n = 1) Metabolites: not applicable Whole system: Propamocarb HCl (aerobic) DT₅₀ = 15.5-15.9 days, DT₉₀ = 51.5-52.7 days (1^st order, n = 2, r² = 0.905-0.913) Propamocarb HCl (aerobic) DT₅₀ = 16.0-21.0 days, DT₉₀ = 53.0-69.0 days (non-linear 1^st order using KIM B1.0, n = 2) Metabolites: not applicable Propamocarb HCl (anaerobic) DT₅₀ = 100.0 days, DT₉₀ = 332.3 days (linear 1^st order regression, n = 1) Metabolites: not applicable
Mineralization	CO₂ maximum (aerobic) = 67.5-94.7% (at 104-105 days, study end, n = 4) CO₂ maximum (anaerobic) = 69.0 % (at 370 days, study end, n = 1)
Non-extractable residues	Non-extractable maximum residues (aerobic) = 10.3-16.0% (at 42-63 days, n = 4) Non-extractable maximum residues (anaerobic) = 20.1% (at 110 days, n = 1)
Distribution in water / sediment systems (active substance) ‡	Water phase: Propamocarb HCl (aerobic) = 87.0-102.3% (day 0), 82.7-86.9% (day 1) and not detected by day 104/105 (n = 4 systems) Propamocarb HCl (anaerobic) = 100.9% (day 0), 53.3% (day 13), 0.3% (day 370) (n = 1 system) Sediment phase: Propamocarb HCl (aerobic) = 12.4-21.5% (day 1), 15.8-36.9% (7-28 days), 0.0-5.6% (104/105 days) (n = 4 systems) Maximum of 36.9% applied radioactivity in sediment after 14 days. DT₅₀ in sediment (aerobic) 23-26 days (1^st order, n = 2) Propamocarb HCl (anaerobic) = 2.0% (day 0), 80.1% (day 54), 14.0% (day 370) (n = 1 system) Maximum of 80.1% applied radioactivity in sediment after 54 days. DT₅₀ in sediment (anaerobic) 93 days (1^st order, n = 1) [Dosing method – application to water, no mixing]
Distribution in water / sediment systems (metabolites) ‡	Transient unidentified metabolites reached maximum individual levels in aerobic water and sediment phases combined of 1.7-5.6% of applied radioactivity (time of maximum occurrence = 7-28 days) (n = 4 systems, incubated at 20 °C) Transient unidentified metabolites reached maximum individual levels in anaerobic water and sediment phases of 3.9% and 0.9%, respectively (time of maximum occurrence = 13 days) (n = 1 system, incubated at 25 °C)

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

Direct photolysis in air ‡	Not determined – no data requested
Quantum yield of direct phototransformation	Not determined in air
Photochemical oxidative degradation in air ‡	DT₅₀ = 4.03 and 13.4 hours (Atkinson method)
Volatilization ‡	From plant surfaces: Propamocarb hydrochloride was found to volatilise from plant surfaces (French beans) <10.0%, this value is less than the BBA trigger value of 20.0% in volatilisation studies conducted over a 24 hour period.
	from soil: volatilisation loss of Propamocarb hydrochloride is estimated to be <0.0001% of the applied amount within 24 hours after treatment (Dow method) and was found to evaporate <15.0% in volatilisation studies conducted over a 24 hour period, which is less than the BBA trigger value of 20.0%.

Definition of the Residue (Annex IIA, point 7.3)

Relevant to the environment

Soil:

Propamocarb and its salts, expressed as propamocarb

Water (surface and ground water):

Propamocarb and its salts, expressed as propamocarb

Air:

Propamocarb and its salts, expressed as propamocarb

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

Soil (indicate location and type of study)	Relevant European data not available
Surface water (indicate location and type of study)	Relevant European data not available
Ground water (indicate location and type of study)	Relevant European data not available
Air (indicate location and type of study)	Relevant European data not available

Classification and proposed labelling (Annex IIA, point 10)

with regard to fate and behaviour data

Candidate for

R53 May cause long-term adverse effect in the aquatic environment

6.1 Fate and behaviour in soil

6.1.1 Persistence in soil

Article 2.8 of the Plant Protection Products and Biocides Regulations (RGB) describes the authorisation criterion persistence. If for the evaluation of the product a higher tier risk assessment is necessary, a standard is to be set according to the MPC-INS^{^[1]} method. Currently this method equals the method described in the Technical Guidance Document (TGD). Additional guidance is presented in RIVM^{^[2]}-report 601782001/2007^{^[3]}.

For the current application this means the following:

Fosetyl

Fosetyl-Sodium is a salt. The true active substance is fosetyl. The following laboratory DT₅₀ values are available for the active substance fosetyl: mean 3 hours. The mean DT₅₀-value of the a.s. can thus be established to be <90 days. Furthermore it can be excluded that after 100 days there will be more than 70% of the initial dose present as bound (non-extractable) residues together with the formation of less than 5% of the initial dose as CO₂.

In this way, the standards for persistence as laid down in the RGB are met.

For the metabolite phosphorous acid the following DT₅₀-values are available: 157, 119, and 49 days (geomean 97 days).

Due to the exceeding of the threshold value of 60 days for the geomean DT₅₀ (lab) for metabolite, it must be demonstrated by means of field dissipation studies that the field DT₅₀ is < 90 days. No field data are provided.

Based on the above, the proposed applications of the pesticide Previcur energy in principle do not meet the standards for persistence as laid down in the RGB, because of the high DT₅₀ value of phosphorous acid. However, it is considered not convenient to require fielddata nor to derive a MPC-INS value for phosphoric acid, as the background concentration in soil as well as the amount added by nutrients exceeds by far the amount of phosphorous acid added by the use of the active substance fosetyl.

propamocarb-HCl

The following laboratory DT₅₀ values are available for the active substance fosetyl: 10.9, 11.7, 14.1, 17.8, 22.4, 23.4, 29.7, 87.7, 137 days (n = 9 soils, geomean = 26.3 days). The mean DT₅₀-value of the a.s. can thus be established to be <90 days. Furthermore it can be excluded that after 100 days there will be more than 70% of the initial dose present as bound (non-extractable) residues together with the formation of less than 5% of the initial dose as CO₂.

In this way, the standards for persistence as laid down in the RGB are met.

Based on the above, the proposed applications of the pesticide Previcur energy meet the standards for persistence as laid down in the RGB.

PECsoil

The concentration of the a.s. in soil is needed to assess the risk for soil organisms (earthworms, micro-organisms). The PECsoil is calculated for the upper 5 cm of soil using a soil bulk density of 1500 kg/m³. PECsoil is calculated for all uses, except the use in hot peppers as this use is on artifical substrate only.

The following input data are used for the calculation:

PEC soil:

Active substance fosetyl:

Mean Maximum lab DT₅₀ for degradation in soil: 3 hours

Molecular weight: 132 g/mol (fosetyl-Na); 110 g/mol (fosetyl)

Metabolite H₃PO₃:

Maximum lab DT₅₀ for degradation in soil (20°C): 157days

Molecular weight: 82 g/mol

Correction factor: 0.742 (maximum fraction of occurrence) * 0.746 (relative molar ratio = M metabolite/M parent) = 0.553

Active substance propamocarb:

Mean Maximum lab DT₅₀ for degradation in soil: 137 days

Molecular weight: 224.7 g/mol (propamocarb-HCl); 188.3 g/mol (propamocarb)

See Table M.1 for other input values and results.

Use 1 : Endive, Herbs (glasshouse use)

Use 2 : withdrawn

Use 3: Ornamental brassica, anemone, Euphorbia, Lisanthus, Lilly flower production, Plant breeding and the culture of seeds (glasshouse use)

Use 4: Ornamental brassica, anemone, Euphorbia,Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials (field use)

Use 5 : Seed treatment for tree nursery (glasshouse use)

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

6.1.2 Leaching to shallow groundwater

Article 2.9 of the Plant Protection Products and Biocides Regulations (RGB) describes the authorisation criterion leaching to groundwater.

The leaching potential of the active substance (and metabolites) is calculated in the first tier using Pearl 2.2.2. and the FOCUS Kremsmünster scenario. Input variables are the actual worst-case application rate 0.775 kg/ha respectively 1.32 kg/ha , the crop, winter cereals as surrogate for radish and an interception value appropriate to the crop of [0,2 default for radish, 0.5 for lettuce]. First date of yearly application is 25/05/1901. For metabolites all available data concerning substance properties are regarded. Metabolite phosphorous acid from fosetyl is included in the calculations. No other metabolites occurred above > 10 % of AR, > 5 % of AR at two consecutive sample points or had an increasing tendency. Based on substance properties (DT₅₀<10days, K_om<10L/kg) for fosetyl, the first tier assessment with PEARL 2.2.2 is not suitable and the assessment should directly be based on GeoPEARL calculations. However, the DT₅₀ of fosetyl is 3 hours. Therefore, the expected leaching to groundwater will be negligible and calculations with GeoPEARL are not required. Calculations are not necessary for the use on hot peppers, as this is on artificial soil only.

The following input data are used for the calculation:

PEARL:

fosetyl:

Geometric mean DT₅₀ for degradation in soil (20°C): 3 hours

Arithmetic mean K_om (pH-independent): 0.06 L/kg

Arithmetic mean 1/n: 1

Saturated vapour pressure fosetyl-sodium: <1.0 x 10^-3 Pa at 20°C

Solubility in water fosetyl-sodium: 770 g/L at 20°C at pH 5

Molecular weight: 132 g/mol fosetyl-sodium; 110 g/mol (fosetyl)

Metabolite phosphoric acid (H₃PO₃):

Geometric mean DT₅₀ for degradation in soil (20°C): 106 days

Arithmetic mean Kd (pH-independent): 723 L/kg

Arithmetic mean 1/n: 1

Arithmetic mean formation fraction: 1

Saturated vapour pressure: 1x 10^-7 Pa (25°C)

Solubility in water: 4250 g/L (20°C)

Molecular weight: 82 g/mol

propamocarb-HCl:

Geometric mean DT₅₀ for degradation in soil (20°C): 13.91 days (normalised value based on all data from both notifiers, n=17)

Arithmetric mean K_om (pH-independent): 310.7 L/kg (topsoil data, conservative values)

Arithmetric mean 1/n: 0.867

Saturated vapour pressure: 8.1e^-5 – 1.66e^-3 Pa (25 °C) (lowest value used since this is worst-case for leaching)

Solubility in water: Between 89.1 and 93.8 % w/w at pH 7, which equals 892-935 g/L. Value 935 g/L used for conservative leaching assessment.

Molecular weight: 224.7 g/mol (propamocarb-HCl); 188.3 g/mol (propamocarb)

Other parameters: standard settings of PEARL 2.2.2

The following concentrations are predicted for the a.s. Propamocarb and the metabolite H₃PO₃ from fosetyl following the realistic worst case GAP, see Table M.2.

Table M.2 Leaching of a.s. Propamocarb-HCl and metabolite H₃PO₃ as predicted by PEARL 2.2.2

No./ Use	Substance	Rate substance [kg/ha]	Frequency	Interval [days]	Fraction intercepted	PEC groundwater [mg/L]	PEC groundwater [mg/L]
						spring	autumn
Use 1	propamocarb H₃PO₃	1.32 -^*	1	-	0.5	<0.001	n.a.
Use 2	propamocarb H₃PO₃	1.32 -^*	3	7	0.2	<0.001 3.179**	<0.001 3.626**
Use 3	propamocarb H₃PO₃	0.795 -^*	2	7	0.2	<0.001	n.a.
Use 4	propamocarb H₃PO₃	0.795 -^*	2	7	0.2	<0.001	<0.001
Use 5	propamocarb H₃PO₃	0.0795 -^*	1	-	0	<0.001	n.a.

Use 1 : Endive, Herbs (glasshouse use)

Use 2 : withdrawn (but data kept here for comparative purpose)

Use 3: Ornamental brassica, anemone, Euphorbia, Lisanthus, Lilly flower production, Plant breeding and the culture of seeds (glasshouse use)

Use 4: Ornamental brassica, anemone, Euphorbia,Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials (field use)

Use 5 : Seed treatment for tree nursery (glasshouse use)

* modelled via transformation scheme

** worst case leaching concentrations for H₃PO₃

Results of Pearl 2.2.2. using the Kremsmünster scenario are examined against the standard of 0.01 µg/L. This is the standard of 0.1 µg/L with an additional safety factor of 10 for vulnerable groundwater protection areas (NL-specific situation).

From Table M.2 it reads that the expected leaching based on the PEARL-model calculations for the a.s. propamocarb-HCl is smaller than 0.01 µg/L for all proposed applications. For the active substance fosetyl-Na the expected leaching can also be concluded to be smaller than 0.01 µg/L for all proposed applications.

Hence, the applications meet the standards for leaching as laid down in the RGB.

For the metabolite H₃PO₃ concentrations are equal to or larger than 0.1 µg/L. Concentrations resulting from the worst case application (use no.2, withdrawn for other reasons than leaching) are given in table M.2.

However, for this inorganic salt the drinking water directive set at a maximum value of 200 mg/L total phosphate applies. Hence, the applications meet the standards for leaching.

Monitoring data

fosetyl

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

Propamocarb-HCl

There are no relevant EU data available regarding the presence of the substance propamocarb-HCl in groundwater.

Regarding the presence of metabolite phosphorous acid there are probably a lot of monitoring data available in public literature, non of those is considered relevant for the application of fosetyl as a plant protection product.

Conclusions

The proposed applications of the product complies with the requirements laid down in the RGB concerning persistence in soil and leaching to groundwater.

6.2 Fate and behaviour in water

6.2.1 Rate and route of degradation in surface water

The exposure concentrations of the active substances fosetyl-Na and propamocarb-HCl and metabolite phosphorous acid in surface water have been estimated for the various proposed uses using calculations of surface water concentrations (in a ditch of 30 cm depth), which originate from spray drift during application of the active substance. The spray drift percentage depends on the use. Concentrations in surface water are calculated using the model TOXSWA. The following input data are used for the calculation:

TOXSWA:

Fosetyl:

Geometric mean DT₅₀ for degradation in water at 20°C: 4 days

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

Arithmetic mean K_om for suspended organic matter: 0.06 L/kg

Arithmetic mean K_om for sediment: 0.06 L/kg

Arithmetic mean 1/n: 1

Saturated vapour pressure fosetyl-sodium: <1.0 x 10^-3 Pa at 20°C

Solubility in water fosetyl-sodium: 770 g/L at 20°C at pH 5

Molecular weight fosetyl-sodium: 132 g/mol (foseyl-Na); 110 g/mol (fosetyl)

Metabolite phosphorous acid:

Geometric mean DT₅₀ for degradation in water at 20°C: 1000 days

DT₅₀ for degradation in sediment at 20°C: 1000 days (default).

Arithmetic mean K_om for suspended organic matter: 1200 L/kg

Arithmetic mean K_om for sediment: 1200 L/kg

Arithmetic mean 1/n: 1

Saturated vapour pressure: 1x 10^-7 Pa (25°C)

Solubility in water: 4250 g/L (20°C)

Molecular weight: 82 g/mol

Correction factor: 1 (arithmetic mean formation fraction) * 0.74 (relative molar ratio = M metabolite/ M parent)= 0.74

Propamocarb-HCl:

Mean DT₅₀ for degradation in water at 20°C: geomean of mean values from each notifier (15.7 and 18.5) = 17.0 days

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

Mean K_om for suspended organic matter: 310.7 L/kg

Mean K_om for sediment: 310.7 L/kg

1/n: 0.867

Saturated vapour pressure: 8.1e^-5 Pa (25 °C)

Solubility in water: 935 g/L (20 °C, pH 7)

Molecular weight: 224.7 g/mol (propamocarb-HCl); 188.3 g/mol (propamocarb)

Other parameters: standard settings TOXSWA

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

In Table M.5, the drift percentages and calculated surface water concentrations for the active substances fosetyl and propamocarb and metabolite phosphorous acid from fosetyl for the intended uses 1 to 4 are presented. The other uses are not spray drift applications, there is no exposure of surface water. Therefore these uses are not listed in table M.5

Table M.5 Overview of surface water concentrations for active substance and metabolite(s) following spring and autumn application

No/ Use	Substance	Rate a.s. [kg/ha]	Freq.	Inter-val	Drift [%]	PIEC [mg/L]^*		PEC21 [mg/L]^*		PEC28 [mg/L]^*
						spring	autumn	spring	autumn	spring	autumn
1	fosetyl propamocarb propamocarb-fosetylate phosphorous acid	0.775 1.32 0.57	1	-	0.1	0.396 0.627 1.023 0.269	0..396 0.627 1.023 0.269	0.176 0.453 0.629 0.230	0.047 0.086 0.133 0.038	0.145 0.417 0.562 0.222	0.035 0.065 0.100 0.028
3	fosetyl propamocarb propamocarb-fosetylate phosphorous acid	0.465 0.795 0.342	2	7	0.1	0.345 0.673 1.018 0.289	0.222 0.380 0.602 0.1633	0.193 0.507 0.700 0.238	0.056 0.104 0.160 0.045	0.166 0.462 0.628 0.222	0.042 0.078 0.120 0.034
4	fosetyl propamocarb propamocarb-fosetylate phosphorous acid	0.465 0.795 0.342	2	7	1.0	3.451 6.725 10.18 2.890	-	1.929 5.071 7.000 2.381	-	1.663 4.622 6.285 2.216	-

Use 1 : Endive, Herbs (glasshouse use)

Use 2 : withdrawn

Use 3: Ornamental brassica, anemone, Euphorbia, Lisanthus, Lilly flower production, Plant breeding and the culture of seeds (glasshouse use)

Use 4: Ornamental brassica, anemone, Euphorbia,Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials (field use)

^*calculated according to TOXSWA

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

Monitoring data

The Pesticide Atlas on internet (www.pesticidesatlas.nl, www.bestrijdingsmiddelenatlas.nl) is used to evaluate measured concentrations of pesticides in Dutch surface water, and to assess whether the observed concentrations exceed threshold values.

Dutch water boards have a well-established programme for monitoring pesticide contamination of surface waters. In the Pesticide Atlas, these monitoring data are processed into a graphic format accessible on-line and aiming to provide an insight into measured pesticide contamination of Dutch surface waters against environmental standards.

Recently, the new version 2.0 was released. This new version of the Pesticide Atlas does not contain the land use correlation analysis needed to draw relevant conclusions for the authorisation procedure. Instead a link to the land use analysis performed in version 1.0 is made, in which the analysis is made on the basis of data aggregation based on grid cells of either 5 x 5 km or 1 x 1 km.

Data from the Pesticide Atlas are used to evaluate potential exceeding of the authorisation threshold and the MPC (ad-hoc or according to INS) threshold.

For examination against the drinking water criterion, another database (VEWIN) is used, since the drinking water criterion is only examined at drinking water abstraction points. For the assessment of the proposed applications regarding the drinking water criterion, see next section.

Fosetyl

The active substance fosetyl was observed in the surface water (most recent data used for this assessment are from 2007). In Table M.6 the number of observations in the surface water are presented.

In the Pesticide Atlas, surface water concentrations are compared to the authorisation threshold value of 100 µg/L (1/11/1998, C-80-3-13, consisting of first or higher tier acute or chronic ecotoxicological threshold value, including relevant safety factors, which is used for risk assessment *, in this case [0.1 * NOEC algea]) and to the indicative Maximum Permissible Concentration (MPC) of 100 µg/L as presented in the Pesticide Atlas (data source for the MPC: Zoeksysteem normen voor het waterbeheer, http://www.helpdeskwater.nl/normen_zoeksysteem/normen.php).

Currently, this MPC value is not harmonised, which means that not all available ecotoxicological data for this substance are included in the threshold value. In the near future and in the framework of the Water Framework Directive, new quality criteria will be developed which will include both MPC data as well as authorisation data.

The currently available MPC value is reported here for information purposes. Pending this policy development (finalisation for all substances expected in 2009-2010), however, no consequences can be drawn for the proposed application(s).

Table M.6 Monitoring data in Dutch surface water (from www.pesticidesatlas.nl, version 2.0)

Total no of locations

(2007)

n > authorisation threshold

n > indicative/ad hoc MPC threshold

n > MPC-INS threshold *

14**

n.a.

* n.a.: no MPC-INS available. < : exceeding expected to be lower than with indicative/ad hoc MPC value; > : exceeding expected to be higher than with 4^th Document MPC value

** ** the number of observations at each location varies between 1 and 3, total number of measurements is 56 in 2007.

The correlation of exceedings with land use is derived from the 1.0 version of the Pesticide Atlas. Hence, the correlation is not based on the exact same monitoring data. However, this is the best available information and therefore it is used in this assessment.

In version 1.0 of the Pesticide Atlas fosetyl-Al nor fosetyl-Na is included in the observations, therefore, no colletation to the proposed or already authorised uses is possible.

propamocarb

The active substance propamocarb was observed in the surface water (most recent data used for this assessment are from 2007). In Table M.7 the number of observations in the surface water are presented.

In the Pesticide Atlas, surface water concentrations are compared to the authorisation threshold value of 0.63 µg/L (C-207-3-12, consisting of first or higher tier acute or chronic ecotoxicological threshold value, including relevant safety factors, which is used for risk assessment *, in this case [0.1*NOEC fish]) and to the indicative Maximum Permissible Concentration (MPC) of 710 µg/L as presented in the Pesticide Atlas (data source for the MPC: Zoeksysteem normen voor het waterbeheer, http://www.helpdeskwater.nl/normen_zoeksysteem/normen.php).

Table M.7 Monitoring data in Dutch surface water (from www.pesticidesatlas.nl,
version 2.0)

Total no of locations

(2007)

n > authorisation threshold

n > indicative/ad hoc MPC threshold

n > MPC-INS threshold *

149**

n.a.

* n.a.: no MPC-INS available. < : exceeding expected to be lower than with indicative/ad hoc MPC value; > : exceeding expected to be higher than with 4^th Document MPC value

** ** the number of observations at each location varies between 1 and 30, total number of measurements is 583 in 2007

In version 1.0 of the Pesticide Atlas propamocarb nor propamocarb-HCl is included in the observations, therefore, no colletation to the proposed or already authorised uses is possible.

Regarding the presence of metabolite phosphorous acid there are probably a lot of monitoring data available in public literature, none of those is considered relevant for the application of fosetyl as a plant protection product.

Drinking water criterion

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

Fosetyl-Na

Fosetyl has been on the Dutch market for > 3 years (authorised since 30-09-1997). This period is sufficiently large to consider the market share to be established. From the general scientific knowledge collected by the Ctgb about the product and its active substance, the Ctgb concludes that there are in this case no concrete indications for concern about the consequences of this product for surface water from which drinking water is produced, when used in compliance with the directions for use. The Ctgb does under this approach expect no exceeding of the drinking water criterion. The standards for surface water destined for the production of drinking water as laid down in the RGB are met.

Propamocarb-HCl

Propamocarb is an existing substance (on the Dutch market since 1990). From the general scientific knowledge collected by the Ctgb about the product and its active substance, the Ctgb concludes that there are in this case no concrete indications for concern about the consequences of this product for surface water from which drinking water is produced, when used in compliance with the directions for use. The Ctgb does under this approach expect no exceeding of the drinking water criterion. The active substance propamocarb-HCl meets the standards for surface water destined for the production of drinking water as laid down in the RGB.

6.3 Fate and behaviour in air

Route and rate of degradation in air

Fosetyl

The active substance fosetyl-Al is little volatile. The vapour pressure is 1 x 10^-7Pa at 20°C. The Henry constant is 3.2 x 10^-10 at 20°C. The half-life in air is 0.96 days. The Fosetyl-Na salt can be considered to have comparable values.

Propamocarb-HCl

The vapour pressure is 8.1 x 10^-5 Pa and 1.66 x 10^-3 Pa at 25 ºC (two notifiers). The Henry constant is 8.5 x 10^-9 Pa.m³.mol^-1 at 20°C. The half-life in air is 4.03 and 13.4 hours (two notifiers).

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

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

See List of Endpoints.

6.5 Data requirements

None.

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

6.6 Overall conclusions fate and behaviour

It can be concluded that:

the active substances fosetyl-Na and propamocarb-HCl meet the standards for persistence in soil as laid down in the RGB.
metabolite phosphorous acid meets the standards for persistence in soil as laid down in the RGB.
all proposed applications of the active substances fosetyl and propamocarb meet the standards for leaching to the shallow groundwater as laid down in the RGB.
all proposed applications of inorganic metabolite phosphorous acid meet the standards for leaching to shallow groundwater.
all proposed applications of the active substances fosetyl and propamocarb meet the standards for surface water destined for the production of drinking water.

7. Ecotoxicology

For the current application of Previcur Energy, risk assessment is done in accordance with Chapter 2 of the RGB.

Previcur Energy is a fungicide based on propamocarb-fosetylate, which was constructed from Propamocarb-HCl and fosetyl-Na. The applicant refers to the DARs of propamocarb-HCL and Fosetyl-Al. Several studies were submitted for bridging the List of Endpoints of Fosetyl-Al to fosetyl-Na. Summaries of these studies are found below the List of Endpoints of fosetyl-Al.

Fosetyl-Al is an existing active substance listed on Annex I. Notifier is Bayer. For the Assessment the final List of Endpoints included in the final EFSA conclusion (January 2006) is used. RMS is France.

Propamocarb-HCl is an existing active substance included in Annex I of 91/414 (2007/25/EG). Notifiers are Bayer and Agriphar. Agriphar has given access to Bayer to all studies submitted by Agriphar for the DAR.

Additional studies with the formulation were submitted. These are summarized and evaluated by the RIVM (11705a00, 07/2008). Summaries of these studies are given below the List of Endpoints of the active substances.

List of Endpoints Ecotoxicology

Fosetyl-Al

Appendix 1.6: Effects on non-target Species

Effects on terrestrial vertebrates (Annex IIA, point 8.1, Annex IIIA, points 10.1 and 10.3)

Acute toxicity to mammals	a.s.: LD₅₀ > 7 080 mg kg bw H₃PO₃: LD₅₀ = 3 624 mg kg bw EXP10369F ¹: LD₅₀ > 2 000 mg/kg bw EXP10745D ²: LD₅₀ > 2 000 mg/kg bw
Chronic toxicity to mammals	a.s.: NOEC = 6 000 mg/kg feed (3 generations) (equ. to 439 mg/kg bw/d) H₃PO₃: NOAEC = 8 000 mg/kg feed (equ. to 390 mg/kg bw/d)
Acute toxicity to birds	a.s.: LD₅₀ (Bobwhite quail) > 8 000 mg/kg bw a.s.: LD₅₀ (Japanese quail) = 4 997 mg/kg bw EXP10369F ¹: LD₅₀ (Bobwhite quail) > 6 400 mg/kg bw EXP10745D ²: LD₅₀ (Bobwhite quail) > 2 000 mg/kg bw H₃PO₃: LD₅₀ (bobwhite quail) > 675 mg/kg bw
Dietary toxicity to birds	a.s.: LC₅₀ (quail, duck) > 20 000 mg/kg feed (equ. to 3 541 mg/kg bw/d) H₃PO₃: LC₅₀ (bobwhite quail) > 1 692 mg/kg feed (equ. to 508 mg/kg bw/d)
Reproductive toxicity to birds	a.s.: NOEC (quail) = 1 500 mg/kg feed (equ. to 216 mg/kg bw/d)

¹ WG containing 800 g a.s./kg

² WG containing 667 g a.s./kg and 44.4 g fenamidone/kg

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	Endpoint	Toxicity (mg/L)
Laboratory tests
O. mykiss	a.s.	96 h	LC₅₀	> 122
L. macrochirus		96 h	LC₅₀	> 60
D. magna		48 h	LC₅₀	> 100
Sc. subspicatus		72 h	E_bC₅₀	5.9
L. gibba		14 d	LC₅₀	79.67
O. mykiss		28 d	NOEC	100
D. magna		21 d	NOEC	17
O. mykiss	EXP10369F	96 h	LC₅₀	> 120 (> 96 a.s.)
D. magna		48 h	LC₅₀	37 (29.6 a.s.)
Sc. subspicatus		72 h	E_bC₅₀ E_rC₅₀	8.0 (6.4 a.s.) 27.7 (22.2 a.s.)
O. mykiss	EXP10745D	96 h	LC₅₀	13
D. magna		48 h	LC₅₀	0.64
Sc. subspicatus		72 h	E_bC₅₀ E_rC₅₀	14 29
O. mykiss	H₃PO₃	96 h	LC₅₀	> 28.6
L. macrochirus		96 h	LC₅₀	> 35.7
D. magna		48 h	LC₅₀	> 29.7
C. riparius		21 d	NOEC	100.2
S. capricornutum		72 h	E_bC₅₀ E_rC₅₀	8.6 29.4
Microcosm or mesocosm tests:
No data required

Endpoints used in the TER calculation for fosetyl-Al: LC₅₀ fish > 60 mg/L, EC₅₀ invertebrate = 29.6 mg/L, EC₅₀ algae = 5.9 mg/L, NOEC fish = 100 mg/L, NOEC invertebrate = 17 mg/L.

Endpoints used in the TER calculation for H₃PO₃: LC₅₀ fish > 28.6 mg/L, EC₅₀ invertebrate > 29.7 mg/L, EC₅₀ algae = 8.6 mg/L, NOEC sed. organism = 100.2 mg/L.

Bioconcentration
Bioconcentration factor (BCF) ‡	Log Pow – 2.1 to – 2.7
Annex VI Trigger:for the bioconcentration factor	-
Clearance time (CT₅₀) (CT₉₀)	-
Level of residues (%) in organisms after the 14 day depuration phase	-

Effects on honeybees (Annex IIA, point 8.3.1, Annex IIIA, point 10.4)

Acute oral toxicity ‡

a.s. LD₅₀ = 462 µg/bee

EXP10369F LD₅₀ > 440 µg product/bee

H₃PO₃LD₅₀ > 212 µg/bee

EXP10745D LD₅₀ > 118 µg product/bee

Acute contact toxicity ‡

a.s. LD₅₀ > 1 000 µg/bee

EXP10369F LD₅₀ > 390 µg product/bee

H₃PO₃ LD₅₀ > 29.7 µg/bee

EXP10745D LD₅₀ > 100 µg product/bee

Field or semi-field tests:

A semi field test at 80 kg EXP10369F/ha. No effect on mortality, bee flight intensity and foraging activity, bee brood development and general behaviour

Effects on other arthropod species (Annex IIA, point 8.3.2, Annex IIIA, point 10.5)

Preparations WG containing 80% fosetyl-Al

Species

Stage

Test

Substance

Dose

(kg a.s./ha)

corrected for a.s.

Endpoint

Effect

(%)

Annex VI

Trigger

Laboratory and extended laboratory tests

A rhopalosiphi

(laboratory)

adult

EXP10369F

9.6

Mortality / parasitism

- 2.6 / 8.5

0 / 41

30%

A rhopalosiphi

(laboratory)

adult

AE F053616 WG 80

4 – 64

LR₅₀

Mortality / parasitism

LR₅₀ > 64 kg a.s./ha

0 / 30.2

5 / - 6.8

0 / 13.6

0 / 15.2

2.5 / 10.9

30%

T pyri

(laboratory)

nymph

EXP10369F

9.6

Mortality / reproduction

86.7 / 100

77.1 / 96.9

30%

T pyri

(extended laboratory)

nymph

EXP10369F

Mortality / reproduction

98.9 / -

69.3 / 77.5

T pyri

(laboratory)

nymph

ALIETTE WG = EXP10369F

Mortality / reproduction

1.1 / 58.5

1.1 / 59.3

- 4.4 / 22.2

30%

P cupreus

(laboratory)

adult

EXP10369F

9.6

Mortality / predation

0 / - 20

30%

C 7-punctata

(laboratory)

larvae

EXP10369F

9.6

Mortality / reproduction

78.6 / - 57.3

- 2.4 / 19.7

30%

A bilineata

(laboratory)

adult

EXP10369F

9.6

Reproduction

14.8

9.8

30%

Field or semi-field tests:

no data

EXP10369F = ALIETTE WG and AE F053616 WG80 are WG preparations containing 80% w/w fosetyl-Al

Preparation EXP10745D (WG containing 66.7% fosetyl-Al and 4.44% fenamidone)

Species

Stage

Test

Substance

Dose

(kg p.f./ha)

(doses fosetyl-Al / fenamidone)

Endpoint

Effect

(% ))

Annex VI

Trigger

Laboratory and extended laboratory tests

A rhopalosiphi

(laboratory)

adult

EXP10745D

4.6 (3.065 / 0.204)

1.15 (0.766 / 0.051)

Mortality / parasitism

42.5 / 86

50 / 75

30%

A rhopalosiphi

(extended laboratory)

adult

EXP10745D

5.75 (3.832 / 0.255)

2.87 (1.916 / 0.128)

0.215 (0.143 / 0.0096)

Mortality / parasitism

100 / -

90 / -

5 / - 2.7

T pyri

(laboratory)

nymph

EXP10745D

4.6 (3.065 / 0.204)

1.15 (0.766 / 0.051)

Mortality / reproduction

79.78 / 100

4.49 / 16.2

30%

T pyri

(extended laboratory)

nymph

EXP10745D

3.45 (2.300 / 0.153)

1.15 ( 0.766 / 0.051)

Mortality / reproduction

10.87 / 41

9.78 / 12

P cupreus

(laboratory)

adult

EXP10745D

6.756 (4.506 / 0.300)

1.689 (1.127 / 0.075)

mortality / predation

0 / - 24.3

0 / - 22.0

30%

C carnea

(laboratory)

larvae

EXP10745D

4.59 (3.065 / 0.204)

1.15 (0.766 / 0.051)

mortality / reproduction

13.9 / not valid

3.5 / not valid

30%

Effects on earthworms (Annex IIA, point 8.4, Annex IIIA, point 10.6)

Acute toxicity

a.s. LC₅₀ > 1 000 mg /kg soil

EXP10369F. LC₅₀ > 4 000 mg product/kg soil

H₃PO₃ LC₅₀ > 1 000 mg/kg soil

EXP10745D LC₅₀ = 130 mg product/kg soil ¹

Reproductive toxicity

EXP10369F ²NOEC = 1 667 mg product /

kg soil (equ. 499 mg H₃PO₃ /kg soil)

EXP10745D NOEC = 4.16 kg product/ha
(equ. to 5.55 mg product /kg soil ³)

¹ The endpoints in the summary B.9.6.1.3 in DAR are not for the a.s. but for the product.

² The test item is EXP10369F (WG 80% fosetyl-Al) and the NOEC is also expressed as H₃PO₃

³ WG containing 667 g a.s./kg and 44.4 g fenamidone/kg. A refined calculation taking into account the tests parameters would gives a NOEC value of 20.7 mg/kg soil

Effects on soil micro-organisms (Annex IIA, point 8.5, Annex IIIA, point 10.7)

Nitrogen mineralization ‡	No significant effect (± 25%) at 20 kg a.s./ha
Carbon mineralization ‡	No significant effect (± 25%) at 20 kg a.s./ha

Classification and proposed labelling (Annex IIA, point 10)

with regard to ecotoxicological data

None

Bridging studies fosetyl-Na

Summarized and evaluated by the RIVM (11705a00, 07/2008). AE C529354 22.1% = 22.1% Na-ethyl phosphonate = 22.1% fosetyl-Na.

Toxicity aquatic organisms

Substance	Species	Method	Duration [h]	Criterion	Value [mg as /L]
AE C529354 22.1%	Oncorhynchus mykiss	Flow-trough	96	LC₅₀	>100
	Daphnia magna	static	48	EC₅₀	>121.6
	Pseudokirchneriella subcapitata	static	72	E_rC₅₀ E_bC₅₀	>100 >100

Activated sludge

Substance

Sludge source

Criterion

Dose

[mg total a.s./L]

AE C529354 22.1%

Domestic waste-water

EC₅₀

>1000

------------------------------------------------------------------------------------------------------------------------------

List of Endpoints Propamocarb-HCl

It should be noted that all the values given in this section belong to propamocarb hydrochloride, a variant of propamocarb.

Effects on terrestrial vertebrates (Annex IIA, point 8.1, Annex IIIA, points 10.1 and 10.3)

Acute toxicity to mammals ‡	>1330 mg a.s./kg b.w./day
Long-term toxicity to mammals	104 mg a.s./kg b.w./day
Acute toxicity to birds ‡	>1842 mg a.s./kg b.w./day
Dietary toxicity to birds ‡	>962 mg a.s./kg b.w./day
Reproductive toxicity to birds ‡	105 mg a.s./kg b.w./day

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	Endpoint	Toxicity (mg/L)
Acute
Rainbow trout (Onchoryhynchus mykiss)	Propamocarb-HCl	96 hours	Mortality, LC50	>99
Bluegill Sunfish (Lepomis macrochirus)	Propamocarb-HCl	96 hours	Mortality, LC50	>92
Daphnia magna	Propamocarb-HCl	48 hours	Mortalities, EC50	>100
Pseudokirchneriella subcapitata	Propamocarb-HCl	72 hours	Growth Rate, EC50	>85
Lemna gibba	Propamocarb-HCl	14 days	Frond No., EC50	>18
Chronic
Bluegill sunfish (Lepomis macrochirus)	Propamocarb-HCl	32 days	NOEC	>6.3
Daphnia magna	Propamocarb-HCl	21 days	NOEC	12.3

Microcosm or mesocosm tests

Not required

Bioconcentration
Bioconcentration factor (BCF) ‡	Not required as Log P_ow<3
Annex VI Trigger: for the bioconcentration factor	>3
Clearance time (CT₅₀) (CT₉₀)	Not relevant
Level of residues (%) in organisms after the 14 day depuration phase	Not relevant

Effects on honeybees (Annex IIA, point 8.3.1, Annex IIIA, point 10.4)

Acute oral toxicity ‡	LD₅₀ >84 µg a.s./bee
Acute contact toxicity ‡	LD₅₀>100 µg a.s./bee

Effects on other arthropod species (Annex IIA, point 8.3.2, Annex IIIA, point 10.5)

Previcur N¹

Species	Stage	Study type	Toxicity Endpoints (g a.s./ha)
Species	Stage	Study type	LD/EC₅₀	LOEL	NOEL
Aphidius rhopalosiphi	Adults	Lab (glass)	500	500	170
Aphidius rhopalosiphi	Adults	Ext. Lab (barley)	>4315 CTB : >6500 *	>4315	4315
Diaeretiella rapae	Adults	Lab (glass)	>2190	>2190	<2190
Trichogramma caoeciae	Adults	Lab (glass)	790	790	-
Typhlodromus pyri	Adults	Lab (glass)	>360	>360	360
Typhlodromus pyri	Protonymphs/ Adults	Ext. Lab (lettuce)	>3 x 1450	>3 x 1450	3 x 1450
Aleochara bilineata	Adults	Lab (sand)	>9690	>9690	9690
Poecilus cupreus	Adults	Lab (sand)	>9690	>9690	9690
Chrysoperla carnea	2-3 day old larvae 2-3 day old larvae	Lab (glass)	>1080	>1080	<1080
Chrysoperla carnea	2-3 day old larvae	Ext. Lab (lettuce)	>3 x 1453	>3 x 1453	3 x 1453
Coccinella septempunctata	2-3 day old larvae	Lab (glass)	>1920	>1920	1920

* a mistake seems to have been made in the DAR: endpoint is > 9 L/ha, corresponding to >6500 kg a.s./ha

¹Previcur N = 720 g/L propamocarb-HCL

Field or semi-field tests

Not required

Proplant¹

Species	Stage	Test Substance	Dose (kg as/ha)	Endpoint	Adverse Effect²
Aphidius rhopalosiphi	Adults	Proplant	1.083*	Mortality / Fertility	32.6% +72.4%
Aphidius rhopalosiphi^#	Adults		3.450	Mortality / Fertility	9.1% +23.9%
Typhlodromus pyri	Protonymph/ Adult		1.083	Mortality / Fertility	-1.1% 21.1%
Coccinella septempunctata	Larvae		1.083	Mortality / Fertility	-3.5% 19.0%
Chrysoperla carnea	Larvae		1.083	Mortality / Fertility	-7.2% 10.04%
Poecilus cupreus	Adults		108.3	Mortality / Food consumption	3.6% +4.4%
Pardosa sp.^#	Adults		108.3	Mortality / Food consumption	0.0% +7.5%

¹ Test substance Proplant = 722 g propamocarb-HCl/L

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 parameter 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 effectpercentages (i.e. increase compared to control) and a – sign for mortality effectspercentages (i.e. decrease compared to control).

^#: extended lab (A. rhopalosiphi on barley seedlings, Pardosa sp. on soil), all others glass plate tests

Field or semi-field tests

Not required

Effects on earthworms (Annex IIA, point 8.4, Annex IIIA, point 10.6)

Acute toxicity ‡	LC₅₀ > 660 mg a.s./kg dry soil
Reproductive toxicity ‡	NOEC 362 mg a.s./kg dry soil

Effects on soil micro-organisms (Annex IIA, point 8.5, Annex IIIA, point 10.7)

Nitrogen mineralization ‡	No adverse effects up to 28.9 kg a.s./ha
Carbon mineralization ‡	No adverse effects up to 28.9 kg a.s./ha

Effects on non target plants (Annex IIA, point 8.6, Annex IIIA, point 10.8)

Preliminary screening data (Tier 1):

Previcur N had no phytotoxic effect on seed germination or vegetative vigour over a range of monocotyledons and dicotyledons that were exposed to a concentration of 9.18 kg Propamocarb HCl/ha.

Emergence of cucumber and wheat was adversely effected in a Tier I study at an exposure rate of 9.18 kg Propamocarb HCl/ha.

Dose Response Studies (Tier II):

Seedling emergence: Cucumber seedling emergence was significantly lower than the control at 27.54 and 82.62 kg a.s./ha (% effect ranged from –16% to +2%). There was no effect on this parameter in wheat.

Mean Length: In cucumber, mean length was significantly different in the highest treatment group. No effects were observed in wheat.

Dry weight: There was no significant different in the dry weight of either cucumber or wheat exposed to up to 82.62 kg a.s./ha.

Effects on biological methods for sewage treatment (Annex IIA 8.7)

Test type	Endpoint
Activated sludge	EC₅₀ (3h) >100 mg propamocarb HCl/L

Classification and proposed labelling (Annex IIA, point 10)

with regard to ecotoxicological data

R52 Harmful to aquatic organisms

S61 Avoid release to the environment. Refer to special instructions/Safety data sheets.

------------------------------------------------------------------------------------------------------------------------------

Formulated product Previcur Energy

Summarized and evaluated by the RIVM (11705a00, 07/2008)

Propamocarb fosetylate EXP 11047A = Previcur Energy = 75.04% propamocarb fosetylate = 47.06% propamocarb. / 528 g/L propamocarb + 314 g fosetyl/L (equivalent to 632.4 g propamocarb-HCl/L + 332.5 g fosetyl-Al/L.)

Toxicity aquatic organisms

Substance	Species	Method	Duration [h]	Criterion	Value [mg as /L]
Previcur Energy	Oncorhynchus mykiss	static	96	LC₅₀	>98
	Daphnia magna	static	48	EC₅₀	>97
	Pseudokirchneriella subcapitata	static	72	E_rC₅₀ E_bC₅₀	>97 >97

Toxicity terrestrial organisms

(Bumble)bees

Substance

Species

Method

Duration

[h]

Criterion

Value

[μg a.s./bee]

Previcur Energy

Apis mellifera

oral

contact

LD₅₀

>100

Non-target arthropods

Form.¹	Species	Method	Dose [g a.s./ha]	Parameter	Adverse effects² [%]	LR₅₀ [g a.s./ha]
Previcur Energy	Typhlodromus pyri	Lab.test				3500
			1040	Reproduction	48
Previcur Energy	Aphidius rhopalosiphi	Lab.test				4900
			2800	Reproduction	45
Previcur Energy	Poecilus cupreus	Lab.test	4200	Mortality Food consumption	0 0
Previcur Energy	Chrysoperla carnea	Lab.test	4200	Mortality Reproduction	0 3.6

¹ Previcur Energy = EXP 11047A = 528 g propamocarb/L + 314 g fosetyl/L

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 parameter compared to control

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

Earthworms

Substance

Species

Soil type

[%]

Duration

[d]

Criterion

Dose

[mg total a.s./kg]

Previcur Energy

Eisenia

fetida

artificial

LC₅₀

>1000

------------------------------------------------------------------------------------------------------------------------------

Bridgeing between the active substances

In a position paper, the applicant gives a statement why the endpoints of fosetyl-Al and propamocarb-HCl can be used:

Fosetyl-Al is a fungicide included on annex I, while fosetyl-Na is a pre-manufacturing product for the synthesis of fosetyl-Al and for propamocarb fosetylate. The formulation Previcur Energy is an ionic association of the anion fosetylate and the cation propamocarb, which dissociated during application of the product. In water, the fosetyl and propamocarb moieties are equivalent to the fosetyl moiety in fosetyl-Al and propamocab moiety in propamocarb-HCl.

Several studies were submitted to further show that fosetyl-Na and fosetyl-Al have a similar ecotoxicological profile:

Testorganism	Endpoint	fosetyl-Na [mg/L]	fosetyl-Al [mg/L]
Oncorhynchus mykiss	LC50	>100	>122
Daphnia magna	EC50	>121.6	>100
Algae*	ErC50	>100	>16
Activated sludge	EC50	>1000	>100

*Fosetyl-Na tested with Pseudokirchneriella subcapitata, fosetyl-Al tested with Scenedesmus subspicatus

Based on this information, it is concluded that the endpoints from the LoEP of fosetyl-Al and propamocarb-HCl can be used for risk assessment.

Correction active substances.

The proposed dose values and the calculated PEC concentrations are based on fosetyl and propamocarb, while the endpoints in the ecotoxicology section are based on fosetyl-Al or fosetyl-Na and propamocarb-HCL. Therefore a correction for molecular weight should be taken into account. This means:

Fosetyl-Na : fosetyl = 132: 110 = 1.2

Fosetyl-Al: fosetyl = 354: (3x110) = 1.07 (fosetyl-Al is a complex of three fosetyl with one Al)

Propamocarb-HCL : propamocarb = 224.7: 188.3 = 1.19

Combination toxicology

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

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

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

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

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

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

An acceptable risk is expected when TER_combi > trigger.

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

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

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

An acceptable risk is expected when TER_combi > trigger_combi.

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

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

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

7.1 Effects on birds

Birds can be exposed to the active substances fosetyl and propamocarb in several ways: via

- natural food (sprayed insects, seeds and leafs): field use in Ornamental brassica, anemone, Euphorbia, Lisanthus, Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials;

- drinking water: Endive, Herbs, Ornamental brassica, anemone, Euphorbia, Lisanthus, Lilly flower production, Plant breeding and the culture of seeds, Rose and perennials;

- secondary poisoning via earthworms: field uses in Ornamental brassica, anemone, Euphorbia,Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials;

- secondary poisoning via fish: Endive, Herbs, Ornamental brassica, anemone, Euphorbia, Lisanthus, Lilly flower production, Plant breeding and the culture of seeds, Rose and perennials.

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

Table E.1 presents an overview of toxicity data. These data are expressed as fosetyl-Al and propamocarb-HCl in the LoEPs. Since the dose rate is expressed in fosetyl and propamocarb, the toxicity data have been corrected for molecular weight to make comparison with the dose rate possible.

Table E.1 Overview of toxicity data for birds

	Endpoint	Value	Value corrected to fosetyl or propamocarb
Fosetyl-Al
Acute toxicity to birds:	LD₅₀	4997 mg a.s./kg bw	4657 mg a.s./kg bw
Dietary toxicity to birds:	LC₅₀	>3541 mg a.s./kg bw/d	>3300 mg a.s./kg bw/d
Reproductive toxicity to birds:	NOEL	216 mg a.s./kg bw/d	201 mg a.s./kg bw/d
H3PO3
Acute toxicity to birds:	LD₅₀	>675 mg a.s./kg bw
Dietary toxicity to birds:	LC₅₀	>508 mg a.s./kg bw/d
Reproductive toxicity to birds:	NOEL	not available
Propamocarb-HCl
Acute toxicity to birds:	LD₅₀	>1842 mg a.s./kg bw	>1548 mg a.s./kg bw
Dietary toxicity to birds:	LC₅₀	>962 mg a.s./kg bw/d	>808 mg a.s./kg bw/d
Reproductive toxicity to birds:	NOEL	105 mg a.s./kg bw/d	88 mg a.s./kg bw/d

7.1.1 Natural food and drinking water

Sprayed products

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

In this section, sprayed field uses are considered. These uses can be categorized as leafy crops. The indicator species for this crop category are the medium herbivorous bird and the insectivorous bird.

Table E.2a-c shows the estimated daily uptake values (ETE, Estimated Theoretical Exposure) for acute, short-term and long-term exposure, using the Food Intake Rate of the indicator species (FIR) divided by the body weight of the indicator species (bw), the Residue per Unit Dose (RUD), a time-weighted-average factor (f_TWA, only for long term) and the application rate. For uses with frequency of > 1, a MAF (Multiple Application Factor) may be applicable. The ETE is calculated as application rate * (FIR/bw) * RUD * MAF [* f_TWA, only for long term].

Calculations are done for the use in Ornamental brassica, anemone, Euphorbia,Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials (use no.4).

Table E.2a Acute ETE in terms of daily dose (mg/kg bw)

Crop	Indicator species	sub-stance	FIR / bw	RUD (90%)	MAF	Appl. rate (kg as/ha)	Acute ETE (mg/kg bw/d)
field use in Ornamental brassica, anemone, Euphorbia, Lisanthus, Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials	Medium herbivorous bird	fosetyl	0.76	87	1.4	0.465	43
	Medium herbivorous bird	propa-mocarb	0.76	87	1.4	0.795	74
	Insectivorous bird (small insects)	fosetyl	1.04	52	-	0.465	25
	Insectivorous bird (small insects)	propa-mocarb	1.04	52	-	0.795	43

Table E.2b Short-term ETE in terms of daily dose (mg/kg bw)

Crop	Indicator species	Sub-stance	FIR / bw	RUD (mean)	MAF	Appl. rate (kg as/ha)	Short-term ETE (mg/kg bw/d)
field use in Ornamental brassica, anemone, Euphorbia, Lisanthus, Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials	Medium herbivorous bird	fosetyl	0.76	40	1.6	0.465	23
	Medium herbivorous bird	propa-mocarb	0.76	40	1.6	0.795	39
	Insectivorous bird (small insects)	fosetyl	1.04	29	-	0.465	14
	Insectivorous bird (small insects)	propa-mocarb	1.04	29	-	0.795	24

Table E.2c Long-term ETE in terms of daily dose (mg/kg bw)

Crop	Indicator species	Sub-stance	FIR / bw	RUD (mean)	MAF	f_TWA	Appl. rate (kg as/ha)	Long-term ETE (mg/kg bw/d)
field use in Ornamental brassica, anemone, Euphorbia, Lisanthus, Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials	Medium herbivorous bird	fosetyl	0.76	40	1.6	0.53	0.465	12
	Medium herbivorous bird	propa-mocarb	0.76	40	1.6	0.53	0.795	20
	Insectivorous bird (small insects)	fosetyl	1.04	29	-	-	0.465	14
	Insectivorous bird (small insects)	propa-mocarb	1.04	29	-	-	0.795	24

Based on the ETE-values in Table E.2a-c the TER-values for the acute, short-term and long-term risk are presented in table E.3.

Table E.3 Toxicity Exposure Ratios for birds

Time scale	Substance		Toxicity (LD₅₀/ LC₅₀/ NOEL)	ETE value (mg a.s./kg bw/d)	TER value	Trigger value
leafy crops: field use in Ornamental brassica, anemone, Euphorbia, Lisanthus, Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials; medium herbivorous bird
Acute	fosetyl propamocarb combination		4657 >1548	43 74	108 >21 >18	10
Short-term	fosetyl propamocarb combination		>3300 >808	23 39	>143 >21 >18	10
Long-term	fosetyl propamocarb combination		201 88	12 20	17 4.3 3.4	5
leafy crops: field use in Ornamental brassica, anemone, Euphorbia, Lisanthus, Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials; insectivorous bird
Acute	fosetyl propamocarb combination	4657 >1548		25 43	186 >36 >30	10
Short-term	fosetyl propamocarb combination	>3300 >808		14 24	>236 >34 >30	10
Long-term	fosetyl propamocarb combination	201 88		14 24	14 3.7 2.9	5

Taking the results in Table E.3 into account, it appears that a long-term risk to birds for the proposed field uses in Ornamental brassica, anemone, Euphorbia, Lisanthus, Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials cannot be excluded.

Refined risk assessment.

Medium herbivorous bird

Focal species

The applicant proposes the wood pigeon as focal species. Although this is not substantiated with monitoring data in the specific crops, it is considered acceptable. The pigeon is one of the two medium herbivorous species indicated in the guidance document (Sanco/4145/2000) and the wood pigeon is a common species in the Netherlands.

Diet

Based on a range of articles on the woodpigeon from the public literature, the applicant states that ‘the diet of pigeons varies with season and also with abundance of available crops. Nevertheless, it can be taken from the data, that pigeons favour cereals and various seeds and grains, but also feed on leafy crops, even though to a lower extent (worst-case: 32.5% = PT).’

The proposed value of 32.5% would be a PD, not PT refinement, and is based on dry weight. It should be corrected to wet weight to use it in the ETE calculations. Besides this, the exact value cannot be accepted because it is not based on diet analysis in the crops under evaluation.

The data indicate a mixed diet of seeds, grain and foliage, so it is likely that the woodpigeon will not only feed on non-grass herbs. However, Previcur Energy is applied by spray, so other feed types in the field (seeds) will also be contaminated. This was not taken into account by the applicant. The residue level on weed seeds is taken to be equal to that on foliage, although in later stages of application (from BBCH 50), interception of the crop may occur.

Whether grains (which will not be present in the treated fields) will be available in the landscape around the proposed uses in flowers etc. is unknown, so it cannot be excluded that wood pigeons foraging in the proposed crops will not have grains in their diet. Even so, it is not likely that wood pigeons will obtain 100% of their food in the treated fields in the long term.

In conclusion, there are some indications that a diet based on 100% foliage and 100% treated food is overconservative and that the exposure will be lower in reality, although it is unclear how much lower.

FIR/bw

The woodpigeon is heavier than the other pigeons. With a bodyweight of about 480 g, the applicant calculates a FIR/bw of 0.68 instead of 0.76 for a diet based on foliage. This would lead to slightly higher TER values.

Residue degradation

propamocarb

In the addendum of January 2006 to the DAR of propamocarb, residue data on lettuce are available and used for refinement of the risk to herbivorous birds. RMS used a refined DT50 of 4.69 days, but the calculation method was questioned. Austria commented as follows (comment submitted for Evaluation Meeting of April 2006):

“In EPCO 32 it was agreed that DT50 values should be calculated for each residue trial separately and data from different trials should not be pooled to derive an "overall" DT50.

As demanded the RMS calculated DT50 values for the individual trials. However, for risk assessment the residue data from all trials were averaged for days 0, 14 and 21 and from these mean residue values an overall DT50 of 4.69 days was estimated. We think that an average DT50 has to be derived by calculating the mean of the individual DT50 values estimated for the individual residue trials. According to this procedure the correct mean DT50 would be 8.8 days.”

Ctgb considers in agreement with Austria that the correct mean DT50 is 8.8 days.

The refined DT50 is considered to be an acceptable approach for refinement in lettuce, crops similar to lettuce and small weeds. However, for the leafy crops currently under evaluation, the residue trials in lettuce are not relevant. Furthermore, the refined DT50 is hardly lower than the standard DT50 of 10 days and the ftwa calculated over the interval of 7 days would even be higher than the default DT50 of 0.53.

New EFSA guidance

In the new EFSA guidance document for birds and mammals (2009), the only generic focal species indicated for the proposed uses (falling in the category ornamentals/nursery) are the small insectivorous species and the small insectivorous/worm feeding species.

Conclusion

Considering that the exposure to the medium herbivorous bird will be lower than calculated in Table E.2, that the TER values are not much below the trigger, and that the new guidance indicates that herbivorous birds are less relevant for the proposed uses, the risk to the medium herbivorous bird is considered to be acceptable.

Small insectivorous bird

Insect residues

A general option for refinement of insect residues is available, since new RUD values for insects are available in the new guidance document for bird and mammals risk assessment. This GD currently still has a draft status in the Netherlands. Therefore, it cannot be used in general yet. A PPR-opinion of the GD by the PPR-panel was published in June 2008 (Question No EFSA-Q-2006-064. The EFSA Journal (2008) 734:1-181). Based on the state of the art the Ctgb agrees to use the revised arthropod residue data as evaluated in the new GD as a higher tier in national risk assessment now that this PPR opinion has become available. (NB: Other aspects of the new GD will not be used until official approval of the GD on national level.)

The revised RUD values for arthropods are given in the Table below (data taken from Appendix 14 to the PPR-opinion). These values can be used for risk assessment.

Crop/category of insects	Crop stage	mean	90^th percentile
Ground dwelling invertebrates without interception¹	ground directed applications	7.5	13.8
Ground dwelling invertebrates with interception²	applications directed to crop canopies	3.5	9.7
Insects (foliar dwelling invertebrates³)	whole season	21.0	54.1

¹applications on bare soil, or ground directed applications up to principle growth stage 3, ground directed applications in orchards/vines (e.g. herbicides)

²applications directed to crop canopies (orchards/vines), ground directed applications on top of crops with principle growth stage of 4 or greater

³no data are available for canopy dwelling invertebrates in winter or before the leaves appear (interception would be less)

For the proposed uses, the mean RUD of 21 can be used for refined long-term risk assessment.

Furthermore, the PPR-opinion indicates that the default DT50 of 10 days, which is applied to plant-like food items, can also be used for arthropods. Multiple applications on the same individual insect are not expected; therefore the exposure is equal for single and multiple uses. This implies that the ftwa of 0.53 (currently only used for herbaceous food types) can also be used for insects.

The refined ETEs and TERs are given in table E.4.

Table E.4 Refined long-term ETE and TER in terms of daily dose (mg/kg bw) for the insectivorous bird in Ornamental brassica, anemone, Euphorbia, Lisanthus, Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials

substance	FIR / bw	RUD (mean)	MAF	f_TWA	Application rate (kg as/ha)	Long-term ETE (mg/kg bw/d)	NOEC (mg/kg bw/d)	TER
fosetyl	1.04	21	-	0.53	0.465	5.4	201	37
propa-mocarb	1.04	21	-	0.53	0.795	9.2	88	9.6
							combination	7.6

Table E.4 shows that the risk to the insectivorous bird is acceptable based on new residue data on arthropods.

The glasshouse uses in endive, herbs, ornamental brassica, anemone, Euphorbia, Lisanthus

Lilly flower production, plant breeding and the culture of seeds, seed treatment for tree nursery, and hot peppers, do not lead to exposure via food and are therefore acceptable.

drinking water

The risk from exposure through drinking surface water is calculated for a small bird with body weight 10 g and a DWI (daily water intake) of 2.7 g/d. Surface water concentrations are calculated using TOXSWA (see paragraph 6.2.1). In first instance, acute exposure is taken into account. See Table E.5 for TER calculations.

Table E.5 Risk for birds of drinking water of Previcur Energy

Time of exposure

substance

FIR / bw

[kg a.s./kg bw/d]

PIEC

[mg a.s./L]

LD50

(mg a.s./ kg bw)

TER

Trigger value

acute

fosetyl

propamocarb

combination

0.27

0.006725

0.003451

4657

>1548

2.6*10⁶

1.7*10⁶

1.0*10⁶

Since TER >> 10, the risk is acceptable.

7.1.2 Secondary poisoning

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

The logKow of fosetyl-Al = -2.1 and of propamocarb = -1.3. Since all values are < 3, the potential for bioaccumulation is considered low and no further assessment is deemed necessary. No logPow is available for metabolite H3PO3, but considering its structure (acid) it is unlikely to bioaccumulate.

Conclusions birds

All uses comply with the RGB.

7.2 Effects on aquatic organisms

7.2.1 Aquatic organisms

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

Toxicity data for aquatic organisms are presented in Table E.6

Table E.6 Overview toxicity endpoints for the active substances and metabolite

Substance	Organism	Lowest		Toxicity value	Toxicity value corrected
		L(E)C₅₀ [mg/L]	NOEC [mg/L]	[mg/L]	[mg/L]
Fosetyl-Al	Acute
	Algae	5.9		5900	5499
	Daphnids	>100		>100000	>93200
	Fish	>60		>60000	>55920
	Macrophytes	79.67		79670	74252
	Chronic
	Daphnids		17	17000	15844
	Fish		100	100000	93200
Fosetyl-Na	Acute
	Algae	>100		>100000	>83000
	Daphnids	>121.6		>121600	>101000
	Fish	>100		>100000	>83000
H₃PO₃	Acute
	Algae	8.6		8600
	Daphnids	>29.7		>29700
	Fish	>28.6		>28600
Propamocarb-HCl	Acute
	Algae	>85		>85000	>71000
	Daphnids	>100		>100000	>84000
	Fish	>92		>92000	>77000
	Macrophytes	>18		>18000	>15000
	Chronic
	Daphnids		12.3	12300	10000
	Fish		6.3	6300	5190
Previcur Energy	Acute
	Algae	>97		>97000¹
	Daphnids	>97		>97000¹
	Fish	>98		>98000¹

¹Endpoint expressed as total a.s.

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

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

The use in hot peppers has no spray drift, so exposure of surface water does not occur from these uses.

In table E.7 TER values for aquatic organisms are shown. Only the highest spring use is calculated as worst-case assessment. When available, the toxicity value based on the test with fosetyl-Na is preferred above the value for fosetyl-Al.

Table E.7a TER values: acute

use	Substance	PIEC (µg	TER_st (trigger 10)	TER_st (trigger 100)	TER_st (trigger 100)	TER_st (trigger 10)
		a.s./L)	Algae	Daphnid	Fish	Macrophytes
Field uses (worst Case)	Fosetyl H₃PO₃	3.451 2.890	>24051 2976	>29267 >10277	>24051 >9896	7169 -
	Propamocarb	6.725	>10558	>12491	>11450	>2230
	Combination		>1000	>1000	>1000	>1000
	Previcur Energy	10.18¹	>9528	>9528	>9528	-

¹PIEC expressed as total a.s.

Table E.7b TER values: chronic

use	Substance	PIEC (µg	TER_lt (trigger 10)	TER_lt (trigger 10)
		a.s./L)	Daphnid	Fish
Field uses	Fosetyl	3.451	4591	27007
(worst	Propamocarb	6.725	1487	772
Case)	Combination		1123	751

Taking the results in Table E.7a and b into account, the acute TERs for fish and Daphnia magna are above the relevant Annex VI triggers of 100 and the acute TERs for algae and Lemna are above the relevant Annex VI triggers of 10. The chronic TERs for fish and Daphnia magna are above the relevant Annex VI triggers of 10. Thus, it appears that for formulated product Previcur Energy the proposed uses meet the standards for aquatic organisms as laid down in the RGB.

7.2.2 Risk assessment for bioconcentration

The Log Pow is < 3 for both active substances: around -2.1 for fosetyl and around –1.3 for propamocarb. Therefore the risk to bioconcentration is considered to be low.

Hence, the active substances meet the standards for bioconcentration as laid down in the RGB.

7.2.3 Risk assessment for sediment organisms

Fosetyl-Al is not relevant is sediment, nor are any of its metabolites.

Propamocarb-HCl is relevant in sediment. However, since the NOEC for daphnids is > 0.1 mg a.s./L, the risk for sediment organisms is considered to be low.

Therefore, the standards for sediment organisms as laid down in the RGB are met.

Conclusions aquatic organisms

The proposed application of the product complies with the RGB.

7.3 Effects on terrestrial vertebrates other than birds

Mammals can be exposed to the active substances fosetyl and propamocarb in several ways: via

- drinking water: Endive, Herbs, Ornamental brassica, anemone, Euphorbia, Lisanthus, Lilly flower production, Plant breeding and the culture of seeds, Rose and perennials;

- secondary poisoning via fish: Endive, Herbs, Ornamental brassica, anemone, Euphorbia, Lisanthus, Lilly flower production, Plant breeding and the culture of seeds, Rose and perennials.

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

Table E.8 presents an overview of toxicity data. These data are expressed as fosetyl-Al and propamocarb-HCl in the LoEPs. Since the dose rate is expressed in fosetyl and propamocarb, the toxicity data have been corrected for molecular weight to make comparison with the dose rate possible.

Table E.8 Overview of toxicity data for mammals

	Endpoint	Value	Value corrected to fosetyl or propamocarb
Fosetyl-Al
Acute toxicity to mammals:	LD₅₀	>7080 mg a.s./kg bw	>6599 mg a.s./kg bw
Reproductive toxicity to mammals:	NOEL	439 mg a.s./kg bw/d	409 mg a.s./kg bw/d
H3PO3
Acute toxicity to mammals:	LD₅₀	3624 mg a.s./kg bw
Reproductive toxicity to mammals:	NOEL	390 mg a.s./kg bw
Propamocarb-HCl
Acute toxicity to mammals:	LD₅₀	>1330 mg a.s./kg bw	>1118 mg a.s./kg bw
Reproductive toxicity to mammals:	NOEL	104 mg a.s./kg bw/d	87 mg a.s./kg bw/d

7.3.1 Natural food and drinking water

Sprayed products

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

In this section, sprayed field uses are considered. These uses can be categorized as leafy crops. The indicator species for this crop category is the medium herbivorous mammal.

Table E.9a-b shows 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 Residue per Unit Dose (RUD), a time-weighted-average factor (f_TWA, only for long term) and the application rate. For uses with frequency of > 1, a MAF (Multiple Application Factor) may be applicable. The ETE is calculated as application rate * (FIR/bw) * RUD * MAF [* f_TWA, only for long term].

Calculations are done for the use in Ornamental brassica, anemone, Euphorbia,Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials (use no.4).

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

Crop

Indicator species

sub-stance

FIR / bw

RUD (90%)

MAF

Appl. rate (kg as/ha)

Acute ETE

(mg/kg bw/d)

field use in Ornamental brassica, anemone, Euphorbia, Lisanthus, Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials

Medium herbivorous mammal

fosetyl

0.28

1.4

0.465

propa-mocarb

0.28

1.4

0.795

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

Crop

Indicator species

Sub-stance

FIR / bw

RUD (mean)

MAF

f_TWA

Appl. rate (kg as/ha)

Long-term ETE

(mg/kg bw/d)

field use in Ornamental brassica, anemone, Euphorbia, Lisanthus, Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials

Medium herbivorous

fosetyl

0.28

1.6

0.53

0.465

4.4

mammal

propa-mocarb

0.28

1.6

0.53

0.795

7.6

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

Table E.10 Toxicity Exposure Ratios for mammals

Time scale	Substance	Toxicity (LD₅₀/ NOEL)	ETE value (mg a.s./kg bw/d)	TER value	Trigger value
leafy crops: field use in Ornamental brassica, anemone, Euphorbia, Lisanthus, Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials; medium herbivorous mammal
Acute	fosetyl propamocarb combination	>6599 >1118	16 27	>412 >41 >37	10
Long-term	fosetyl propamocarb combination	409 87	4.4 7.6	93.0 11.5 10	5

Taking the results in Table E.10 into account, it appears that that the uses in Ornamental brassica, anemone, Euphorbia, Lisanthus, Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials will lead to a low risk for mammals.

drinking water

The risk from exposure through drinking from surface water is calculated for a small mammal with body weight 10 g and a DWI (daily water intake) of 1.57 g/d. Surface water concentrations are calculated using TOXSWA (see paragraph 6.2.1). In the first instance, acute exposure is taken into account. See Table E.14 for TER calculations.

Table E.14 Risk for mammals of drinking water of Previcur Energy

Time of exposure

substance

FIR / bw

[kg a.s./kg bw/d]

PIEC

[mg a.s./L]

LD50

(mg a.s./ kg bw)

TER

Trigger value

acute

fosetyl

propamocarb

combination

0.157

0.006725

0.003451

>6599

>1118

>6.3*10⁶

>2.1*10⁶

>1.0*10⁶

Since TER >> 10, the risk is acceptable.

7.3.2 Secondary poisoning

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

Conclusions mammals

All uses comply with the RGB.

7.4 Effects on bees

The risk assessment for bees is based on the ratio between the highest single application rate and toxicity endpoint (LD₅₀ value). An overview of the risk at the proposed uses is given in Table E.15.

Table E.15 Risk for bees

Use	Substance	Application rate	LD₅₀	Rate/LD₅₀	Trigger value
		[g a.s./ha]	[µg/bee]
Endive and herbs	Fosetyl Fosetyl-Al H₃PO₃	775 798 574²	- 462 >29.7	1.7 <19	50
	Propamocarb Propamocarb-HCl	1320 1571	- >84	<19
	Combination¹ Previcur Energy	2095	>100	<21 <21

¹Combination based on fosetyl-Al and propamocarb-HCl

²Assuming 100% formation. Relative molar ratio is 0.74.

Since the ratio rate/LD₅₀ of the use with the highest exposure 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 arthopods is assessed by calculating Hazard Quotients. For this, Lethal Rate values (LR₅₀) are needed. Based on LR₅₀-values from studies with the two standard species Aphidius rhopalosiphi and Typhlodromus pyri an in-field and an off-field Hazard Quotient (HQ) can be calculated according to the assessment method established in the SETAC/ESCORT 2 workshop and described in the HTB (v 1.0). Hazard Quotients should be below the trigger value of 2 to meet the standards. The resulting Hazard Quotients from the use in hot peppers (highest dose & frequency; no direct exposure occurs at this use but direct exposure is assumed to cover all other uses) are presented in Table E.16.

Table E.16 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	2520	2.7	-	-	4900	1.38
T. pyri	2520	2.7	-	-	3500	1.94
Off-field
A. rhopalosiphi	2520	2.7	0.01	10	4900	0.14
T. pyri	2520	2.7	0.01	10	3500	0.19

¹: Multiple Application Factor

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

As the above table shows, both in- and off-field HQ values are below the trigger value of 2 even under extreme worst case assumptions.

Therefore, no risk is expected.

Additional species: Poecilus cupreus & Chrysoperla carnea

Additional species were tested in standard laboratory tests. In both tests no lethal or sublethal effects were found at 4.2 kg a.s./ha, the highest concentration tested. This concentration is lower than the highest total dose of the worst case use calculated with a worst-case MAF (2520 x 2.7 = 6804). However, since the first tier risk assessment with A. rhopalosiphi and T. pyri is acceptable, and no effects were found on P. cupreus and C. carnea at the highest tested dose, the risk to non-target arthropods is considered to be low.

Hence, the standards for non-target arthropods as laid down in the RGB are met for Previcur Energy for all uses.

7.5.2 Earthworms

The acute risk for earthworms is calculated as TER-value(trigger value 10). Since the logPow of the active substances < 2, no correction to the reference soil containing 4.7 % organic matter is necessary. Exposure is expressed as the initial PEC soil. PEC soil is calculated in section 6.1.1. Exposure to soil organisms is not relevant for the glasshouse uses.

Table E.17 presents endpoints, PECsoil and TER values for the field uses.

Table E.17 Overview of soil concentrations and acute TERs

Use	Substance	LC50_corr [mg/kg]	PIECsoil [mg/kg]	TER	Trigger value
field use in Ornamental brassica, anemone, Euphorbia, Lisanthus, Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials	fosetyl	>932¹	0.496	>1879	10
	propamocarb	>555²	1.666	>333	10
	combination			>283	10
	Previcur Energy	>1000³	2.162³	>463	10
	Metabolite H₃PO₃	>1000	0.540	>1852	10

¹LC50 fosetyl-Al >1000 mg/kg soil, corrected to fosetyl.

²LC50 propamocarb-HCl >660 mg a.s./kg dry soil, corrected to propamocarb.

³Expressed as total a.s.

In view of the results presented in Table E.17, a low acute risk for earthworms is expected at all proposed uses.

In the subchronic risk assessment for earthworms, a long-term TER-value is calculated. Examination of the PIEC takes place against the trigger of 0.2*NOEC. See Table E.18 for TER calculation.

Table E.18 Overview of soil concentrations and chronic TERs

Use	Substance	NOEC_corr [mg/kg]	PIECsoil [mg/kg]	TER	Trigger value
field use in Ornamental brassica, anemone, Euphorbia, Lisanthus, Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials	fosetyl	1243¹	0.496	2507	5
	propamocarb	304²	1.666	183	5
	combination			171	5
	Metabolite H₃PO₃	499	0.540	924	5

¹1667 mg product/kg soil = 1334 mg fosetyl-Al/kg soil, corrected to fosetyl.

²NOEC propamocarb-HCl 362 mg a.s./kg dry soil, corrected to propamocarb.

Table E.18 shows that a low chronic risk for earthworms is expected at all proposed uses.

7.5.3 Effects on soil micro-organisms

The following results are available in the respective LoEPs:

- fosetyl-Al: no significant effect at 20 kg as/ha = 18.6 kg fosetyl/ha.

- propamocarb-Hcl: no adverse effects up to 28.9 kg a.s./ha = 24 kg propamocarb/ha.

These studies cover the effects of metabolites.

Thus, in the tested soils no effects are observed on nitrogen transformation and carbon respiration processes at relevant application rates. The standards from the RGB regarding soil micro-organisms are met.

7.5.4 Effects on activated sludge

An EC₅₀ value of >100 mg/L is available for both fosetyl-Al and Propamocarb-HCl.

The trigger is set to 0.1* EC₅₀ corresponding to 10000 µg/L for both active substances. The concentration in the influent of the sewage treatment plant (STP) has to be examined against this trigger using the model application USES. However, to date there is no module available to calculate influent concentrations for most application types (with the exception of mushroom use, public gardens and amenity uses).

Therefore, the proposed applications in the glasshouse cannot be examined against the standard for activated sludge as laid down in the RGB. For the time being this issue is not taken into consideration, but the available toxicity values indicate a low toxicity to activated sludge. For the field uses, no exposure of activated sludge is expected. Therefore, the proposed field applications comply with the standards for activated sludge as laid down in the RGB.

7.5.5 Effects on non target-plants

No exposure to non-target plants is expected from the glasshouse uses. Thus, only the field uses in Ornamental brassica, anemone, Euphorbia, Lisanthus, Delphinium, Echinops, Helichrysum, sunflowers, Plant breeding and the culture of seeds, Rose and perennials are assessed. For these uses, the risk assessment for non-target plants is based on an off-crop situation with a drift percentage of 10%. The exposure thus equals 0.1 * the application rate.

The LoEP of fosetyl gives no data on non-target plants, but in the DAR a vegetative vigour study is available in which six plant species were tested. The most sensitive species is tomato with an EC50 of >80 kg a.s./ha which equals >25 kg fosetyl/ha. Seedling emergence data are not available.

For propamocarb-HCl, from Tier II studies an ER50 >82.62 kg a.s./ha can be derived. This equals 69.4 kg propamocarb/ha.

The ratio between EC₅₀ and the exposure concentration is calculated in Table E.19:

Table E.19 Overview of exposure concentrations and TERs for non target plants

Use	Substance	Dose [kg a.s. /ha]	MAF	Drift% (off-field exposure)	Exposure (kg a.s./ha)	EC₅₀ [kg a.s./ha]	TER	Trigger value
Field uses	fosetyl	0.465	1.7	10%	0.079	>25	>316	5
	propamocarb	0.795	1.7	10%	0.135	>82.62	>611	5
	combination						>208	5

Table E.19 shows that the TER values are much above the trigger. Thus, no risk is expected. Considering the low toxicity and the fact that the active substances are fungicides, no further data are necessary.

The product complies with the RGB.

Conclusions any other organisms

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

7.6 Appropriate ecotoxicological endpoints relating tot the product and approved uses

See List of Endpoints.

7.7 Data requirements

None.

7.8 Classification and labelling

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

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

Symbol:	-	Indication of danger:	-
R phrases	-	-

S phrases	-	-

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

7.9 Overall conclusions regarding ecotoxicology

It can be concluded that:

all proposed applications of Previcur Energy meet the standards for birds as laid down in the RGB.
all proposed applications of Previcur Energy meet the standards for aquatic organisms as laid down in the RGB.
the active substances fosetyl and propamocarb meets the standards for bioconcentration as laid down in the RGB.
all proposed applications of Previcur Energy meet the standards for mammals as laid down in the RGB.
all proposed applications of Previcur Energy meet the standards for bees as laid down in the RGB.
all proposed applications of Previcur Energy meet the standards for non-target arthropods as laid down in the RGB.
all proposed applications of Previcur Energy meet the standards for earthworms as laid down in the RGB.
all proposed applications of Previcur Energy meet the standards for soil micro-organisms as laid down in the RGB.
all proposed applications of Previcur Energy meet the standards for activated sludge as laid down in the RGB or cannot be examined against the standards as laid down in the RGB; for the time being this issue is not taken into consideration.
all proposed applications of Previcur Energy meet the standards for non-target plants as laid down in the RGB.

8. Efficacy

The extension of use of Previcur Energy concerns a simplified extension of use. For a simplified extension of use efficacy is not reviewed (art. 31.1 of Wet gewasbeschermingsmiddelen en Biociden). For the use in spinach it is proven that it concerns a minor use.

9. Conclusion

The product complies with the Uniform Principles.

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

10. Classification and labelling

Proposal for the classification and labelling of the formulation

Based on the profile of the substance, the provided toxicology of the preparation, the characteristics of the co-formulants, the method of application and the risk assessments, the following labelling of the preparation is proposed:

Substances, present in the formulation, which should be mentioned on the label by their chemical name (other very toxic, toxic, corrosive or harmful substances):
-
Symbol:	Xi	Indication of danger:	Irritating
R phrases	43	May cause sensitisation by skin contact.

S phrases	36/37	Wear suitable protective clothing and gloves.

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.

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

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

[3] 601782001/2007: P.L.A. van Vlaardingen and E.M.J. Verbruggen, Guidance for the derivation of environmental risk limits within the framework of 'International and national environmental quality standards for substances in the Netherlands' (INS). Revision 2007’.

werkzame stof:	gehalte:
propamocarb	530 g/l
fosetyl	310 g/l

gevaarsymbool:	aanduiding:
Xi	Irriterend