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HET COLLEGE VOOR DE TOELATING VAN GEWASBESCHERMINGSMIDDELEN EN BIOCIDEN

BIJLAGE II bij het besluit d.d. 7 november 2008 tot uitbreiding van de toelating van het middel Proplant, toelatingnummer 12918 N

RISKMANAGEMENT

Contents Page

1. Identity of the plant protection product 2

2. Physical and chemical properties 3

3. Methods of analysis 8

4. Mammalian toxicology 12

5. Residues 18

6. Environmental fate and behaviour 22

7. Ecotoxicology 33

8. Efficacy 40

9. Conclusion 41

10. Classification and labelling 42

1. Identity of the plant protection product

1.1 Applicant

AGRIPHAR S.A.

Rue de Renory 26 -1

4102 OUGREE

België

1.2 Identity of the active substance

Common name	propamocarb
Name in Dutch	propamocarb
Chemical name	Propyl 3-(dimethylamino) propylcarbamate
CAS no	24579-73-5
EC no	247-125-9

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

1.3 Identity of the plant protection product

Name	Proplant
Formulation type	SL (soluble concentrate)
Content active substance	722 g/L pure propamocarb hydrochloride, which is equal to 605 g/L pure propamocarb

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

1.4 Function

Fungicide.

1.5 Uses applied for

Uses

Dose a.s.

(g a.s./ha)

Number of applications

Interval between applications (days)

Application time (growth stage and season)

Protected culture of tomato, eggplant and

sweet pepper grown on artificial substrate

0.7-1.4

1-4

1^st: 10,

2^nd-3^rd: 28

After transplanting

Repeat after 10 days if necessary

BBCH 20-89

Jan-Dec

Protected culture of cucumber, zucchini and melon grown on artificial substrate

1.4

1-4

1^st: 10,

2^nd-3^rd: 28

After transplanting

Repeat after 10 days if necessary

BBCH 20-89

Jan-Dec

1.6 Background to the application

It concerns an extension.

1.7 Packaging details

1.7.1 Packaging description

Material:	HDPE with PA of EVOH inner barrier
Capacity:	1 and 5 litre
Type of closure and size of opening:	screw cap
Other information	packaging in compliance with STORL and ADR

1.7.2 Detailed instructions for safe disposal

See application form and MSDS (no particular recommendations).

2. Physical and chemical properties

2.1 Active substance: propamocarb

Data on the identity and the physical and chemical properties is taken from the Review report (April 2007) and the EFSA conclusion (May 2006). Changes and/or additions are taken up in italics.

Identity

Active substance (ISO Common Name)	propamocarb (unless otherwise stated, the following data relate to the variant propamocarb hydrochloride)
Chemical name (IUPAC)	Propyl 3-(dimethylamino)propylcarbamate (propamocarb) Propyl 3-(dimethylamino) propylcarbamate hydrochloride
Chemical name (CA)	Propyl [3-(dimethylamino)propyl]carbamate (propamocarb) 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)	TC: 92% w/w, 920 g/kg (Bayer CropScience)*** 97% w/w, 970 g/kg (Chimac Agriphar) TK: 69% w/w, 749 g/L (Bayer CropScience)
Identity of relevant impurities (of toxicological, environmental and/or other significance) in the active substance as manufactured (g/kg)	None identified
Molecular formula	C₉H₂₁ClN₂O₂(Propamocarb-HCl) C₉H₂₀N₂O₂(Propamocarb)
Molecular mass	224.7 (Propamocarb-HCl) 188.3 (Propamocarb)
Structural formula

***) According to the inclusion directive the minimal purity is 920 g/kg expressed as propamocarb (expressed as dry material). However according to all the other documentations this should be expressed as propamocarb hydrochloride. Correcting for the content of the hydrochloride would result in a minimum purity for propamocarb hydrochloride of 110%, which is clearly wrong.

Physical-chemical properties

Melting point (state purity)	64.2 ºC (100.3%)
Boiling point (state purity)	Product decomposed at 150 ºC (99.1 %)
Temperature of decomposition	150 ºC (99.1 %)
Appearance (state purity)	White/cream soft solid (99.1 %)
Relative density (state purity)	1.16 at 20.5 ºC (97.2 %)
Surface tension	71.98 mN/m at 20 ºC (97.2 %) Concentration of test substance = 1g/L
Vapour pressure (in Pa, state temperature)	Two values have been submitted 8.1 x 10^-5Pa at 25 ºC [97.7% purity] 1.66 x 10^-3Pa at 25 ºC [99.1% purity] Test substance is slightly volatile
Henry’s law constant (in Pa·m³·mol^-1)	K = 8.5 x 10^-9 Pa.m³/mol
Solubility in water (in g/l or mg/l, state temperature)	between 89.2 and 93.5 %w/w at pH 4 between 89.1 and 93.8 %w/w at pH 7 between 89.6 and 94.6 %w/w at pH 10 (20°C) purity of test substance 99.1%
Solubility in organic solvents (in g/l or mg/l, state temperature)	Solvent	g/l
	Hexane Toluene Methanol Dichloromethane Ethyl acetate Acetone Xylene Heptane	<0.01 0.04 >656 >626 4.3 560 1.6 x 10^-2 <1 x 10^-4
	Purity test substance 100.0%
Partition co-efficient (log P_ow) (state pH and temperature)	Two values have been submitted (at 22 °C) Log P_OW= -2.9, -1.2 & 0.67 at pH 2, 7 & 9, respectively Log P_OW= -0.98, -1.4 & 0.32 at pH 2, 7 & 9, respectively
Hydrolytic stability (DT₅₀) (state pH and temperature)	<10% hydrolysis at pH 4, 7 & 9 at 50 ºC over a five day period
Dissociation constant	pK_{a =}9.6 at 20 ºC
UV/VIS absorption (max.) (if absorption >290 nm state ε at wavelength)	Absorption observed at λ 203 and 217 nm at pH 7, in 0.1M HCl and in 0.1M NaOH. No absorbance >290 nm.
Photostability (DT₅₀) (aqueous, sunlight, state pH)	No degradation of a.s. in aqueous solution when irradiated for 92hr. at 20 ºC with a wavelength of λ >290nm.
Quantum yield of direct photo- transformation in water at λ > 290 nm	N.A. No photodegradation.
Photochemical oxidative degradation in air	T_1/2= 4 hr in air (OH radical constant was estimated to be > 9.54 x 10^-11 cm³ molecule^-1 sec^-1)
Flammability	Not flammable (TK)
Auto-flammability	312 °C (99.1%)
Oxidative properties	Not oxidising
Explosive properties	Not explosive

The water solubility study was submitted after the PRAPeR meeting but is accepted by the Netherlands.

2.2 Plant protection product: Proplant

Data on the plant protection product is taken from the Draft Asessment Report (DAR) (September 2004).

The range of the application concentration of the plant protection product is 0.08-0.36 %.

Section (Annex point)	Study	Guidelines and GLP	Findings	Evaluation and conclusion
B.2.2.1 (IIIA 2.1)	Appearance: physical state	GLP: y	vicous liquid	acceptable
B.2.2.2 (IIIA 2.1)	Appearance: colour	GLP: y	clear	acceptable
B.2.2.3 (IIIA 2.1)	Appearance: odour		no data	acceptable, not required
B.2.2.4 (IIIA 2.2)	Explosive properties	EEC A.14	statement: not explosive. based on active substance on composition of formulation	acceptable
B.2.2.5 (IIIA 2.2)	Oxidising properties	EEC A.21	statement: not oxidising. based on active substance on composition of formulation	acceptable
B.2.2.6 (IIIA 2.3)	Flammability		not required
B.2.2.7 (IIIA 2.3)	Auto-flammability	GLP:Y EEC A.15	> 400°C	acceptable
B.2.2.8 (IIIA 2.3)	Flash point	GLP:Y EEC A.9	> 100 °C	acceptable
B.2.2.9 (IIIA 2.4)	Acidity / alkalinity		no data
B.2.2.10 (IIIA 2.4)	pH	GLP:Y CIPAC 75	1% dilution in water: 5.3 at 25°C undiluted: 2.99 at 20 – 25°C	acceptable
B.2.2.11 (IIIA 2.5)	Surface tension	GLP:Y “surface ring tensiometer”	70.2 mN/m at 20°C for a 0.85 g/L dilution.	Test not of undiluted product so not acceptable. However not required in this case because of the composition.
B.2.2.12 (IIIA 2.5)	Viscosity		no data	not required because of the composition.
B.2.2.13 (IIIA 2.6)	Relative density	GLP:Y EEC A.3	1.079 at 20°C	acceptable
B.2.2.14 (IIIA 2.6)	Bulk (tap) density		not required
B.2.2.15 (IIIA 2.7)	Storage stability	GLP:Y CIPAC MT 46.3 GLP:Y CIPAC MT39.2	tested in HDPE container for 14 days at 54°C: pH (neat) changed from 2.99 to 3.64 pH (1%dilution) changed from 5.31 tot 5.34 dilution remains stable a.s. content changed from 733 to 722 g/L (98.6%) visual stable after 48 hours at 0.5°C	acceptable stability should be determined for 7 days. However in this case acceptable because of the composition
B.2.2.16 (IIIA 2.7)	Shelf life	GLP:Y GIFAP 10	after two years at ambient temperature in commercial packaging, not change in a.s. content, pH (neat and 1% dilution), appearance or dilution stability was observed. packaging was stable	acceptable
B.2.2.17 (IIIA 2.8)	Wettability		not required
B.2.2.18 (IIIA 2.8)	Persistent foaming	GLP:Y CIPAC MT47	the undiluted, 1% diluted or 10% diluted products does not foam.	acceptable, the lower proposed concentrations are not expected to show more foaming
B.2.2.19 (IIIA 2.8)	Suspensibility		not required
B.2.2.20 (IIIA 2.8)	Spontaneity of dispersion		not required
B.2.2.21 (IIIA 2.8)	Dilution stability	GLP:Y CIPAC MT41	stable	acceptable
B.2.2.22 (IIIA 2.8)	Dry sieve test		not required
B.2.2.23 (IIIA 2.8)	Wet sieve test		not required
B.2.2.24 (IIIA 2.8)	Particle size distribution		not required
B.2.2.25 (IIIA 2.8)	Content of dust/fines		not required
B.2.2.26 (IIIA 2.8)	Attrition and friability		not required
B.2.2.27 (IIIA 2.8)	Emulsifiability, re-emulsifiability and emulsion stability		not required
B.2.2.28 (IIIA 2.8)	Stability of dilute emulsion		not required
B.2.2.29 (IIIA 2.8)	Flowability		not required
B.2.2.30 (IIIA 2.8)	Pourability (rinsibility)		not required
B.2.2.31 (IIIA 2.8)	Dustability		not required
B.2.2.32 (IIIA 2.8)	Adherence and distribution to seeds		not required
2.9.1	Physical compatibility with other products		not required
2.9.2	Chemical compatibility with other products		not required

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

Conclusion

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

2.3 Data requirements

None.

3. Methods of analysis

Data on the identity and the physical and chemical properties is taken from the EFSA conclusion (May 2006), the DAR and addenda. Changes and/or additions are taken up in italics.

3.1. Analytical methods in technical material and plant protection product

Technical as (principle of method)

Test substance dissolved in methanol/water (80:20, v/v) and analysed using HPLC with UV detection.

Impurities in technical as (principle of method)

The following methods were used for analysis of the various impurities.

1. Test substance dissolved in dichloromethane, analysed using GC with FID detection.

2. Test substance dissolved in DMSO, equilibrated at 75 °C prior to head space injection and analysis using GC/FID.

3. Test material was dissolved in water, to which aqueous sodium hydroxide was added. Following extraction with dichloromethane, the aqueous solution was derivatized using benzoyl chloride and the resultant derivative extracted into dichloromethane and analysed using GC/FID.

4. Test material diluted in methanol/water was analysed using HPLC, with UV detection.

5. Test material was dissolved in water, diluted to 50ml with 1,4-dioxane and filtered. The sample was then analysed using GC/FID.

Preparation (principle of method)

Test substance dissolved in methanol/water (80:20, v/v) and analysed using HPLC with UV detection at 210 nm. (CIPAC method 399, 1993).

Conclusion

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

3.2 Residue analytical methods

Food/feed of plant origin (principle of method and LOQ for methods for monitoring purposes)	1. 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. 2. Propamocarb residues were soxhlet extracted with methanol containing 1M HCl. The extract was cleaned up by partitioning with diethyl ether prior to basification with 10M NaOH and partitioning of free propamocarb into di-isopropyl ether. Determination was by GC with MSD. Detection was at m/z = 58 and m/z 188 for propamocarb LOQ = 0.05 mg/kg for leeks, onions, brassiceae, melons, tomatoes and potatoes. 3. The revised version of Method MEREPROPAM, based on a method published by Dutch authorities (Ministry of Public Health, Welfare and Sport, The Netherlands. General Inspectorate for Health Protection. Analytical method for pesticide residues in foodstuffs, sixth edition, June 1996. Part II, special methods, Propamocarb). The revision included centrifugation in stainless steel vessels instead of polypropylene, and use of a capillary column. LOQ = 0.1 mg/kg for propamocarb residues in lettuce and potatoes.
Food/feed of animal origin (principle of method and LOQ for methods for monitoring purposes)	Residues of Propamocarb can be analysed in animal tissue using a method which was submitted. Following extraction with acidified methanol, residues were analysed using LC/MS/MS. LOQ = 0.01mg/kg The method was independently validated using meat, milk and eggs.
Soil (principle of method and LOQ)	1. 1N Hydrochloric acid was added to soil and the samples were shaken on a horizontal flatbed shaker for approx. 60min., then centrifuged and the supernatant removed. The extracts were collected and brought to pH 6-7 with an ammonia solution (~25%). The extract was cleaned up on a C18 column and analysed using HPLC/MS/MS. Atmospheric pressure chemical ionisation (APCI) mode was used. The parent ion m/z 189 and two fragment ions m/z 102.1 and 144 were used for Quantitation. LOQ = 0.02 mg/kg 2. Soil samples were shaken in methanol/saturated NaCl (5:1, v/v) and the methanol fraction was evaporated. The aqueous fraction was adjusted to pH 3-4 using a 0.1N HCl solution. This was then washed with dichloromethane and the pH of the aqueous phase was adjusted to >11.5. Combined dichloromethane fractions were evaporated to dryness, reconstituted in methanol/water (80:20, v/v) and analysed using HPLC/MS/MS in the positive ion mode. The ions monitored were m/z 189.3 (parent ion) and m/z 102.3 (fragment ion). LOQ = 0.02 mg/kg
Water (principle of method and LOQ)	Alkaline treated water was extracted with dichloromethane. Dichloromethane was evaporated off and the extract reconstituted in a suitable solvent prior to analysis using HPLC/MS/MS in the positive ion mode. The ions monitored were m/z 189 (parent ion) and m/z 102 (fragment ion). LOQ = 0.05 µg/L (drinking and surface water)
Air (principle of method and LOQ)	Two methods were considered suitable for analysis of residues of propamocarb in air. 1. Samples of air were drawn through silica gel adsorption tubes at a flow rate of ~0.3L/min. for a period of 6 hr. (total air sampling volume = 0.1m³). The silica gel was extracted three times with a mixture of acetonitrile/water/acetic acid/ammonia (200:800:10:2, v/v/v/v). The total combined extract was analysed using LC/MS/MS with atmospheric pressure chemical ionisation (APCI) source. Quantification was based on MS of the daughter ion peak 144m/z, resulting from the protonated molecular propamocarb ion observed at 189m/z. For further confirmation a second transition resulting in a daughter ion at 102m/z was included in the method. LOQ = 9 µg/m³. 2. Tenax TA was spiked with a methanol solution of propamocarb. The efficiency of the extraction procedure with methanol/water (80:20) was assessed by recovery after 7.5hr. with an air flow of 3L/min. The degree of trapping was assessed by 2hr. and 7.5hr. recovery tests of samples, with an air flow of 3L/min at 35ºC and >80% relative humidity. The stability of propamocarb adsorbed on Tenax TA was demonstrated for a period of 14 days at ambient temperature and at -20ºC. Residues were determined by GC-MS-MS. LOQ = 0.4 µg/m³.
Body fluids and tissues (principle of method and LOQ)	Not required, non toxic compound

Based on the proposed use of the plant protection product analytical methods for determination of residues in food/feed of plant origin are required for watery matrices (cucumber, lettuce, tomatoes and others).

Definition of the residue and MRL’s for propamocarb
Matrix	definition of the residue for monitoring	EU-MRL
Food/feed of plant origin	Propamocarb (sum of propamocarb and its salt expressed as propamocarb)	lettuce: 50 mg/kg solanaceae: 10 mg/kg cucurbits: 10 mg/kg melons: 5 mg/kg
Food/feed of animal origin	no residue definition proposed as the proposed uses do not contain products for animal feed
		Required LOQ
Soil	Propamocarb (sum of propamocarb and its salt expressed as propamocarb)	0.05 mg/kg (default)
Drinking water	Propamocarb (sum of propamocarb and its salt expressed as propamocarb)	0.1 µg/L (drinking water guideline)
Surface water	Propamocarb (sum of propamocarb and its salt expressed as propamocarb)	0.1 µg/L (HTB 1.0)
Air	propamocarb	7.3 µg/m³ (derived from the AOEL according to SANCO/825/00)
Body fluids and tissues	The active substance is not classified as (very) toxic thus no definition of the residue is proposed.

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

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

Conclusion

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

3.3 Data requirements

None.

3.4 Physical-chemical classification and labelling

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

Symbol(s):	-	Indication(s) of danger: -
Risk phrase(s)	-	-

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

Regarding the physical and chemical properties of the formulation, the method of application and the further information on the plant protection product, the following labelling of the preparation is proposed:

Substances, present in the formulation, which should be mentioned on the label by their chemical name (other very toxic, toxic, corrosive or harmful substances):
-
Symbol:	-	Indication of danger:	-
R phrases	-	-
S phrases	21	when using do not smoke
Special provisions: DPD-phrases	-	-
Child-resistant fastening obligatory?			not applicable
Tactile warning of danger obligatory?			not applicable

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

Supported shelf life of the formulation: 2 years

The proposed labelling above is equal to the previous decision regarding the labelling of the plant protection product (dated 20 April 2007).

4. Mammalian toxicology

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.

List of Endpoints

Absorption, distribution, excretion and metabolism in mammals (Annex IIA, 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, 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, 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 / NOEL¹	< 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 / NOEL²	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 List of Endpoints 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, 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, 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, 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, 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, 5.8)
	None available

Medical data (Annex IIA, 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, 5.10)	Value	Study	Safety factor
ADI	0.29 mg propamocarb hydrochloride/ kg bw/day	52-week dietary study in rats	100
AOEL_Systemic⁴	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, 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

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

No data requirements were identified.

4.1 Toxicity of the formulated product (IIIA 7.1)

No new studies were provided. The results are derived from the acute toxicology studies submitted for the application of authorisation of the formulation Proplant.

The formulation Proplant 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 (LC₅₀ rat >5.01 mg/L).

The formulation Proplant is not classifiable as a skin or eye irritant.

The formulation Proplant gave a negative response in a modified Buehler test for skin sensitisation. However, Proplant will be classified as R43 ‘May cause sensitisation by skin contact’, as the active substance was positive in a maximisation study and is present in a concentration greater than the concentration limit for classification.

4.1.1 Data requirements formulated product

No data requirements were identified.

4.2 Dermal absorption (IIIA 7.3)

The dermal absorption studies in the DAR were performed with a formulation similar to Proplant. The dermal absorption value of 10% can also be applied to both the spray dilution as to concentrated Proplant.

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

The other formulant does not raise concerns that have not been addressed in the submitted studies.

4.4 Exposure/risk assessments

Overview of the intended uses

An application has been submitted for the authorisation of the plant protection product Proplant, a fungicide based on the active substance propamocarb.

Proplant is an SC formulation and contains 722 g/L propamocarb.

The intended uses are listed under 1.5.

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

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 can be applied year-round as it concerns the protected cultivation of fruiting vegetables, chronic exposure duration is applicable for the operator (including contract workers). A chronic AOEL is therefore derived.

As propamocarb is included in Annex I of 91/414/EEC, 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 dietary study in rat is used for the risk assessment (see List of Endpoints).

Exposure to propamocarb during mixing and loading and application of Proplant is estimated with models. The exposure is estimated for the unprotected operator. As application of Proplant is performed as a mechanical irrigation drip, only exposure during mixing/loading is estimated. In the Table below the estimated internal exposure is compared with the systemic EU-AOEL.

Table T.1 Internal operator exposure to propamocarb and risk assessment for the use of Proplant

	Route	Estimated internal exposure ^a(mg /day)	Systemic EU-AOEL (mg/day)	Risk-index ^b
Drip irrigation in fruiting vegetables
Mixing/ Loading^c	Respiratory	<0.01	20.3	<0.01
Mixing/ Loading^c	Dermal	2.89	20.3	0.14
	Total	2.9	20.3	0.14

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 EUROPOEM.

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

4.4.2 Bystander exposure/risk

During application there should be no bystanders present in the greenhouse. No exposure to bystanders is therefore expected.

4.4.3 Worker exposure/risk

For the drip irrigation the worker exposure is expected to be lower than for foliar application; propamocarb is transported to the upper plant parts, however, considerable amounts of dislodgable residues are not expected.

4.4.4 Re-entry

See 4.4.3 Worker exposure/risk.

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

The product complies with the Uniform Principles.

Operator 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 propamocarb as a result of the application of Proplant in the protected cultivation on artificial substrate of eggplants, zucchini, cucumbers, melons, sweet peppers and tomatoes.

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 propamocarb during application of Proplant in the protected cultivation on artificial substrate of eggplants, zucchini, cucumbers, melons, sweet peppers and tomatoes.

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 the protected cultivation on artificial substrate of eggplants, zucchini, cucumbers, melons, sweet peppers and tomatoes due to exposure to propamocarb after application of Proplant.

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 data requirements are identified.

4.7 Combination toxicology

Proplant contains only one active substance and it is not described that it should be used in combination with other formulations.

4.8 Mammalian toxicology classification and labelling

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

Symbol:

Indication of danger: Irritant

Risk phrases

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), which is prepared in conformity with Directive 1999/45/EEG, can be maintained.

5. Residues

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

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 following assessment is based on a summary by DE of March 2007 for establishing of EU-tMRLs in Annex III to Regulation 396/2005. This summary is available on the Circa website, section SANCO: Plant protection products and their residues.

Only points that are not covered by the List of Endpoints or that need clarification are discussed below.

5.1.1 Metabolism in plants

Eggplants, zucchini, cucumbers, melons, sweet peppers and tomatoes all belong to the crop group “fruiting vegetables”, when metabolism is concerned. Metabolism was studied in tomatoes; no additional metabolism studies are required.

5.1.2 Metabolism in livestock

No study is required, as eggplants, zucchini, cucumbers, melons, sweet peppers and tomatoes are generally not used as livestock feed.

5.1.3 Residue definition (plant and animal)

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)

5.1.5 Residue data

Cucumbers and zucchini

Sixteen supervised residue trials in cucumber are available to which the applicant was granted access by the owner of the data. The trials were summarised by Germany.

The trials were performed indoor Northern Europe (N-EU) and Southern-Europe (S-EU).

In three trials, two application were made of either 0.09, 0.18 or 0.72 g a.s./ha. Considering a maximum plant density of 3000 per 100 m², this results in 27 to 216 kg a.s./ha per treatment.

In four trials, four applications of 0.722 (2x) or 2.166 (2x) kg a.s./ha were made. In the remaining nine trials, one application at sowing of ca. 28.9 kg a.s./ha was made, followed by 6 applications of ca. 2.8 kg a.s./ha (4 trials), ca. 2.0 kg a.s./ha (3 trials) or ca. 3.2 kg a.s./ha.

These trials can be considered to be worst-case compared to the cGAP-NL.

Residue levels of the sixteen trials were:

0.38, 0.66, 0.8, 1.0, 1.2 (2x), 1.5, 1.7 (2x), 2.0, 2.2, 2.44, 3.3, 3.5, 4.0 mg/kg.

Results with cucumber can be extrapolated to zucchini.

The EU-tMRL of 10 mg/kg for Cucurbits-edible peel is based on the cGAP-EU of N-EU outdoor, 4 x 1.8 kg as/ha, PHI 4 d. The intended use of Proplant in the cultivation of cucumbers and zucchinis will results in residue levels below the EU-tMRL.

Tomato and eggplant

Fifteen supervised residue trials in tomatoes are available to which the applicant was granted access by the owner of the data. Nine trials were summarised by Germany, six trials were summarised by Ctgb.

In the nine trials performed indoor in N- and S-EU, summarised by DE, one application at sowing of ca. 29 kg a.s./ha was made, followed by 4 applications of ca. 2.8 kg a.s./ha (2 trials), 2.2 kg a.s./ha (1 trial), 3.3 kg a.s./ha (2 trials), ca. 3.6 kg a.s./ha (2 trials) or 4.6 kg a.s./ha.

Residue levels in all but one trial were <0.01 mg/kg at PHI 0, 3, 5 and 7d. In one trial residues in the range of 0.06-0.1 mg/kg were present at PHI 0 to 7d. This trial is not considered acceptable.

Even though the residue trials were performed with an overdose, the trials are considered acceptable as they result in a “zero-residue situation”.

The six additional supervised residue trials, summarised by Ctgb, were all performed in the Netherlands in glasshouses.

In five trials two application of 1.44 kg a.s./ha were made, followed by two applications of 3.61 kg a.s./ha. In one trial one application of 1.44 kg a.s./ha was made, followed by two applications of 3.61 kg a.s./ha.

Two of the trials are not acceptable as recovery rates for the method of analysis was insufficient in the recovery tests. Samples were taken at PHI 0d or PHI 7d, but not at PHI 3d.

The residue levels in the four acceptable trials were <0.05 (3x) and 0.05 at PHI 0d.

Results with tomato can be extrapolated to eggplant.

The intended use of Proplant in the cultivation of tomatoes and eggplants will results in residue levels below the EU-tMRL of 10 mg/kg.

Sweet pepper

Eleven supervised residue trials in tomatoes are available to which the applicant was granted access by the owner of the data. Three trials were summarised by Germany, eight trials were summarised by Ctgb.

In the three trials performed indoor in N- and S-EU, summarised by DE, two applications were performed of 0.018, 0.036 or 0.114 kg a.s./hL with 15 L water per 25 plants at a 7d interval.

Residue levels were <0.1(2x) and 0.503 mg/kg at PHI 3d. Residue levels increased in time and therefore the highest residue level detected is considered relevant. In all three trials last sampling was performed at PHI 21d and in these samples highest residue levels were detected of all samples (sampling at PHI 0, 1, 3, 7, 14 and 21d). Residue levels at PHI 21d were 0.208, 0.851, 1.71 mg/kg.

The eight additional supervised residue trials, summarised by Ctgb, were all performed in the Netherlands in one glasshouse, but trials are not replicates of each other.

In all trials one application of 28.88 kg a.s./ha was made at sowing, followed by two applications of 0.722 kg a.s./ha and finally two applications of 2.166 kg as/ha..

All trials are considered acceptable.

The residue levels were <0.01 (8x) PHI 3d.

The intended use of Proplant in the cultivation of sweet peppers will results in residue levels below the EU-tMRL of 10 mg/kg.

Melons

No supervised residue trials in melon are available. According to guideline SANCO 7525/VI/95 rev. 8, results of residue trails in tomato and cucumber can be extrapolated to the whole group of Fruiting Vegetables, except sweet corn for “active substances used early in the growing season” As applications are made up to 3d before harvest, this is not applicable and the extrapolation with applications for “active substances used up to or close to harvest” should be used. Extrapolation is then only possible from melon to other cucurbits with inedible peel, but not from other fruiting vegetables.

However, in view of the residue levels found in tomato and cucumber with the same cGAP and regarding the application regime (first application at transplanting), it is considered that residue levels in melons will be of the same magnitude as the residue levels found in supervised residue trials in cucumber and tomato. The intended use of Proplant in the cultivation of sweet peppers will results in residue levels below the EU-tMRL of 5 mg/kg.

For re-registration of the product Proplant, eight supervised residue trials for melons performed in accordance with the cGAP-NL or the cGAP-EU are required (propamocarb included in Annex I since October 1^st 2007).

5.1.6 Residues in succeeding crops

As the intended use is on artificial substrate only, no plant back restriction is required,

5.1.8 Processing factors

No data was provided. Studies are not necessary as TMDI is less than 10% of the ADI (maximum 2.2% for tomatoes).

5.1.9 Calculation of the ADI and the ARfD

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

EU-tMRLs have been established in Annex II of Regulation 396/2005 (by means of Regulation 149/2008).

The product complies with the MRL Directives/Regulation.

5.3 Consumer risk assessment

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 temporary EU-MRLs and accompanying HRs for crops applied for, except melon. The NESTI for cucumber uses the highest percentages of the ARfD: 7.9% and 23.5% for the general population and for children, respectively.

Conclusion

Based on the assessment for residues, no risk for the consumer due to the exposure to propamocarb is currently expected.

The product complies with the Uniform Principles.

5.4 Data requirements

None.

6. Environmental fate and behaviour

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

Risk assessment is done in accordance with Chapter 2 of the RGB for products based on
- active substances which have already been placed on Annex I of directive 91/414/EEC

- “new” active substances;

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

This means that for the current application of Proplant, risk assessment is done in accordance with Chapter 2 of the RGB.

List of Endpoints Fate/behaviour

For the risk assessment the final List of Endpoints from the EFSA scientific report (07/2006) is used.

Appendix 1.5: Fate and Behaviour in the Environment

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 study ‡

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

The application concerns a drip treatment on artificial substrate. Therefore no exposure to soil is expected.

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

The proposed application concerns a drip treatment on artificial substrate. Exposure to surface water is expected to be low. As a worst-case, an emission of 0.1% is used. This is equal to the general emission that is expected from green houses.

This percentage is based on the following possible ways of exposure from greenhouses:

-leaching through to soil to surface water

-transport of water from condensation

-cleaning of used equipment

-hose ends of sprinkles

-emission to air

-discharge of used water (rinse water, sluiceway of drip water, or water from artificial substrate)

Although the emission to surface water in the proposed use is probably lower than in general greenhouse uses, exposure cannot be excluded and an emission percentage of 0.1 is used as a worst-case.

6.2.1 Rate and route of degradation in surface water

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

TOXSWA:

Active substance:

Geometric mean DT₅₀ for degradation in water at 20°C: 18.3 days

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

Arithmetic mean K_om for suspended organic matter: 304 L/kg

Arithmetic mean K_om for sediment: 304 L/kg

Arithmetic mean 1/n: 0.871

Saturated vapour pressure: 8.1 x 10^-5 Pa (25 °C)

Solubility in water: 850 g/L (20 °C)

Molecular weight: 224.7 g/mol

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

In Table M.1, the drift percentages and calculated surface water concentrations for the active substance propamocarb-HCl for each intended use are presented. As a worst-case, only the concentration in spring is calculated.

Table M.1 Overview of surface water concentrations for active substance following spring application

Use

Substance

Rate a.s.

[kg/ha]

Freq.

Inter-val (days)

Drift

[%]

PIEC

[mg/L]^*

PEC21

[mg/L]^*

PEC28

[mg/L]^*

Tomato, Eggplant, Sweet peppers, Cucumber, zucchini, melon

Propamocarb-HCl

1.4

0.1

1.76

1.36

1.26

^*calculated according to TOXSWA

Monitoring data

There are no relevant data available regarding the presence of the substance Propamocarb-HCl in surface water.

Drinking water criterion

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

Propamocarb-HCl has been on the Dutch market for > 3 years (authorised since <01/101994). 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.

6.3 Fate and behaviour in air

Route and rate of degradation in air

Propamocarb-HCl

The vapour pressure is 1.66 x 10^-3 – 8.1 x 10^-5Pa at 25°C. The Henry constant is 8.5 x 10^-9 Pa m³ mol ^-1 at 20°C.

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 substance propamocarb-HCl meets the standards for persistence in soil as laid down in the RGB.
all proposed applications of the active substance propamocarb-HCl meet the standards for leaching to the shallow groundwater as laid down in the RGB.
all proposed applications of the active substance propamocarb-HCl meet the standards for surface water destined for the production of drinking water.

7. Ecotoxicology

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

Risk assessment is done in accordance with Chapter 2 of the RGB for products based on
- active substances which have already been placed on Annex I of directive 91/414/EEC

- “new” active substances;

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

This means that for the current application of Proplant, risk assessment is done in accordance with Chapter 2 of the RGB.

List of Endpoints Ecotoxicology

Propamocarb-HCl is placed on annex I. For the risk assessment the final List of Endpoints from the EFSA scientific report (07/2006) is used.

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 Ctgb : >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 difference 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.

7.1 Effects on birds

The application concerns greenhouse uses. No direct exposure via food is expected. Considering the low expected worst-case concentrations in surface water and a Log Pow of –1.3, the risk for birds via drinking water and secondary poisoning is low.

Therefore, the active substance propamocarb-HCl meets the standards for birds as laid down in the RGB.

Conclusions birds

The product complies 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 substance Propamocarb-HCl 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.1 for the active substance Propamocarb-HCl.

Table E.1 Overview toxicity endpoints for the active substance

Substance	Organism	Lowest		Toxicity value
		L(E)C₅₀ [mg/L]	NOEC [mg/L]	[mg/L]
Propamocarb-HCl	Acute
	Algae	>85		>85000
	Daphnids	>100		>100000
	Fish	>92		>92000
	Macrophytes	>18		>18000
	Chronic
	Daphnids		12.3	12300
	Fish		6.3	6300

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.

In table E.2. TER values for aquatic organisms are shown.

Table E 2a TER values: acute

use

Substance

TER_st

(trigger 10)

TER_st

(trigger 100)

TER_st

(trigger 100)

TER_st

(trigger 10)

Algae

Daphnid

Fish

Macrophytes

Tomato, Eggplant, Sweet peppers, Cucumber, zucchini, melon

Propamocarb-HCl

>4.8 x10⁴

>5.7 x10⁴

>5.2 x10⁴

>1.0 x10⁴

Table E. 2b TER values: chronic

use	Substance		TER_lt (trigger 10)	TER_lt (trigger 10)
			Daphnid	Fish
Tomato, Eggplant, Sweet peppers, Cucumber, zucchini, melon		Propamocarb-HCl	7.0 x10⁴	3580

Taking the results in Table E.2a and b into account, the acute TERs for fish and Daphnia magna are above the relevant Annex VI triggers of 100 and the acute TERs for algae and Lemna are above the relevant Annex VI triggers of 10. The chronic TERs for fish and Daphnia magna are above the relevant Annex VI triggers of 10. Thus, it appears that for the active substance Propamocarb-HCl 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 (around –1.3). Therefore the risk to bioconcentration is considered to be low.

Hence, the active substance propamocarb-HCl meets the standards for bioconcentration as laid down in the RGB.

7.2.3 Risk assessment for sediment organisms

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 active substance propamocarb-HCl meets the standards for sediment organisms as laid down in the RGB.

Conclusions aquatic organisms

The proposed application of the product complies with the RGB.

7.3 Effects on terrestrial vertebrates other than birds

Therefore, the active substance propamocarb-HCl meets the standards for mammals as laid down in the RGB.

Conclusions mammals

The product complies with the RGB.

7.4 Effects on bees

The application concerns a drip treatment on artificial substrate. However, Propamocarb-HCL is systemic and pollinators can be exposed to the active substance through the pollen. No information on pollen is available. However as a worst-case the risk assessment is performed equivalent to spray application.

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.3.

Table E.3 Risk for bees

Use	Substance	Application rate	LD₅₀	Rate/LD₅₀	Trigger value
		[g a.s./ha]	[µg/bee]
Tomato, Eggplant, Sweet peppers, Cucumber, zucchini, melon	Propamocarb-HCl	1400	>84	<16.67	50

Since the ratio rate/LD₅₀ is below 50, the risk for bees is considered to be low.

Hence, all proposed uses meet the standards for bees as laid down in the RGB.

Conclusions bees

The product complies with the RGB.

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

7.5.1 Effects on non-target arthropods

The application concerns a drip treatment on artificial substrate. No direct exposure to non-target arthropods will occur. Indirect exposure is possible, since Propamocarb-HCl is systemic. However, considering the low toxicity of Proplant to Aphidius rhopalosiphi and Typhlodromus pyri (LR50 > 1.083 kg a.s./ha), the risk to non-target arthropods is considered to be negligible.

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

7.5.2 Earthworms

The application concerns a drip treatment on artificial substrate. No exposure to soil is expected.

The proposed applications of the product therefore meets the standards as laid down in the RGB.

7.5.3 Effects on soil micro-organisms

The application concerns a drip treatment on artificial substrate. No exposure to soil is expected.

The proposed applications of the product therefore meets the standards as laid down in the RGB.

7.5.4 Effects on activated sludge

An EC₅₀ value of >100 mg/L is available.

The trigger is set to 0.1* EC₅₀ corresponding to >10000 µg/L. 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 application 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.

7.5.5 Effects on non target-plants

The application concerns a drip treatment on artificial substrate. No exposure to soil is expected.

The proposed applications of the product therefore meets the standards as laid down in 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 propamocarb-hydrochloride concerning the environment

Symbol:	-	Indication of danger:	-
R phrases	52/53	Harmful to aquatic organisms, may cause long-term adverse effects in the aquatic environment.

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

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

Symbol:	-	Indication of danger:	-
R phrases	52/53	Harmful to aquatic organisms, may cause long-term adverse effects in the aquatic environment.

S phrases	61	Avoid release to the environment. Refer to special instructions/safety data sheets.

Explanation:
Hazard symbol:	-
Risk phrases:	Based on toxicity values for aquatic organisms lower than 100 a.s.mg/L, R52/53 is applicable to the active substance and the formulation. This is in accordance with the classification proposal in the EU (discussed in EPCO 31 and 32).
Safety phrases:	S61 is applied to formulations with R52/53.
Other:	-

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

8. Efficacy

The applicant refers to already existing comparable registrations.

Extrapolation from existing registrations is possible on the basis of the open dossier and experiences in practice.

Conclusion

The product complies with the Uniform Principles because it does in accordance with article 2.1, control Pythium in the protected culture of tomato, eggplant, sweet pepper, cucumber, zucchini and melon grown on artificial substrate.

8.2 Harmful effects

The applicant refers to already existing comparable registrations.

Extrapolation from existing registrations is possible on the basis of the open dossier and experiences in practice.

Conclusion

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

8.3 Resistance

Resistance in Phythium against propamocarb-HCl is reported in the United States in protected crops. The Fungicide Resistance Action Committee (FRAC) does not have a specific advice on the use of propamocarb-HCl, but states that the resistance risk is low to medium and that resistance management is required. Single use of the product must be prevented and rotation of treatments should take place with suitable rotation partners from another mode of action group.

Conclusion

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

8.4 For vertebrate control agents: impact on target vertebrates

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

8.5 Any other relevant data / information

None.

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:	irritant
R phrases	43	May cause sensitisation by skin contact.
	52/53	Harmful to aquatic organisms, may cause long-term adverse effects in the aquatic environment.
S phrases	21	When using do not smoke.
	36/37	Wear suitable protective clothing and gloves.
	61	Avoid release to the environment. Refer to special instructions/safety data sheets.
Special provisions: DPD-phrases

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

werkzame stof:	gehalte:
propamocarb hydrochloride	722 g/l

gevaarsymbool:	aanduiding:
Xi	Irriterend

Toepassingen

Cucumbers and zucchini

Calculation of the ADI

Calculation of the ARfD

Chronic