rapid science memo · rapid science memo for approval to import or manufacture ag-m4-700 of1 for...

RAPID SCIENCE MEMO

www.epa.govt.nz

13 JUNE 2019

Summary

Substance AG-M4-700 OF1

Application code APP203824

Application sub-type Rapid reduced

Applicant Adama New Zealand Limited

Purpose of the application To obtain approval for AG-M4-700 OF1, a herbicide containing 700g/L

metamitron as a suspension concentrate

Date application formally received 28 May 2019

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Rapid Science Memo for approval to import or manufacture AG-M4-700 OF1 for release (APP203824)

1. Key Points

1.1. AG-M4-700 OF1 is a herbicide in the form of a suspension concentrate (SC) containing 700 g/L of the

active ingredient metamitron. It is intended for the control of weeds in beets (red, fodder, sugar) and

applied using both ground-based and aerial application methods at rates of up to 2.8 kg metamitron/ha

in a single application and up to 4.2 kg metamitron/ha per crop per season.

1.2. AG-M4-700 OF1 is intended to be imported in New Zealand.

1.3. At the time of this evaluation, Adama New Zealand Limited, was already putting a similar substance on

the market (“Goltix Herbicide”) using the approval number HSR000535, which contains 700 g/kg

metamitron in the form of a water dispersible granule, for the control of weeds in beets (red, fodder,

sugar) and mangolds.

2. Status Of Substance (SOS) or statutory determination history

2.1. No SOS or statutory determinations were issued for AG-M4-700 OF1.

3. Identification of substance and reference

3.1. The reference proposed by the applicant and identified by the EPA are the same (see Table 1).

Table 1: Identified references for the rapid assessment of AG-M4-700 OF1

Substance to be approved Reference

Name AG-M4-700 OF1 AGPRO Metamitron

Substance database ID 49711 44396

HSNO Approval number - HSR100753

Substance physical form Suspension concentrate (SC) Suspension concentrate (SC)

Active ingredient(s) and

concentration (g/L) 700 g/L metamitron 700 g/L metamitron

4. RAPID assessment criteria

Active ingredient

4.1. This substance meets the active ingredients criteria. The concentration of the active ingredient in AG-

M4-700 OF1 is the same as that of the reference substance.

Physical form

4.2. AG-M4-700 OF1 is in the same physical form as the reference substance, namely as a suspension

concentrate.

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Use pattern

4.3. This substance meets the use pattern criteria. Both AG-M4-700 OF1 and the reference substance are

herbicides used in a similar manner (see Table 2).

Table 2: Use pattern of AG-M4-700 OF1 in comparison to its reference substance

Substance to be approved Reference

Target pest / condition

Susceptible weeds: Amaranthus spp.,

Buttercups (seedlings), Chickweed,

Docks (seedling) Fathen, Galinsoga,

Groundsel, Hawksbeard, Henbit,

Matricaria spp. (Stinking mayweed and

Chamomiles), Nettles, Pennycress,

Annual poa, Wild portulaca, Scotch

thistle (seedling), Shepherd’s purse,

Sow thistle, Speedwells, Spurrey, Twin

cress, White clover, Yarrow (seedling).

Moderately susceptible weeds: Black

nightshade, Field pansy, Fumitory,

Hedge mustard, Scarlet pimpernel,

Thorn apple, Wireweed.

Susceptible weeds: Amaranthus spp.,

Buttercups (seedlings), Chickweed,

Docks (seedling) Fathen, Galinsoga,

Groundsel, Hawksbeard, Henbit,

Matricaria spp. (Stinking mayweed and

Chamomiles), Nettles, Pennycress,

Annual poa, Wild portulaca, Scotch

thistle (seedling), Shepherd’s purse,

Sow thistle, Speedwells, Spurrey, Twin

cress, White clover, Yarrow (seedling).

Moderately susceptible weeds: Black

nightshade, Field pansy, Fumitory,

Hedge mustard, Scarlet pimpernel,

Thorn apple, Wireweed.

Target animal / crop Red beet, fodder beet, sugar beet,

mangolds

Red beet, fodder beet, sugar beet,

mangolds

Application rate (kg ai/ha)

Up to 2.8 kg metamitron/ha in a single

application and up to 4.2 kg

metamitron/ha per crop per season

4.2 kg metamitron/ha, three times per

year

Comment on any differences There is no difference between the use pattern of AG-M4-700 OF1 and the

reference substance

Are the differences

insignificant in terms of risk of

adverse effects?

As there is no difference between the use pattern of AG-M4-700 OF1 and the

reference substance, there is no difference in terms of adverse effects associated

with the use of the substances.

Major Hazardous Components

4.4. AG-M4-700 OF1 meets the major hazardous components criteria. The major hazardous components in

AG-M4-700 OF1 constitute a similar proportion as in the reference substance.

Adverse Effects

4.5. AG-M4-700 OF1 meets the adverse effects criteria, as the hazards of this substance are reduced

compared to the reference substance (see Table 3).

4.6. AG-M4-700 OF1 has a reduced hazard classification for acute toxicity via the inhalation route [6.1D

(inhalation) instead of 6.1B (inhalation)] and dermal route [6.1E (dermal) instead of 6.1D (dermal)].

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However, the 6.1D (inhalation) classification is primarily derived from a recent change in our

classification database for the active ingredient metamitron. Were the reference substance to be

assessed by mixture rules with the new classification, it would likely receive a 6.1D classification.

4.7. AG-M4-700 OF1 also has a reduced hazard classification for aquatic toxicity (9.1B instead of 9.1A) and

for soil toxicity (9.2B instead of 9.2A).

Table 3: Comparison of the respective classifications of AG-M4-700 OF1 and its reference substance

Classification comparison

Substance 6.1D (oral, inhalation), 6.1E (dermal), 9.1B, 9.2B, 9.3C

Reference 6.1B* (inhalation), 6.1D (oral, dermal), 9.1A, 9.2A, 9.3C

* The 6.1D (inhalation) classification is triggered by the active ingredient, metamitron. The classification for metamitron on the EPA

register is incorrect and will be reviewed to include the 6.1D (inhalation) classification.

5. Controls

EPA Notice controls

5.1. The Labelling, Safety Data Sheet (SDS), Packaging, Disposal and Hazardous Property Controls (HPC)

Part 1, Part 3, Part 4A and Part4B Notices apply to AG-M4-700 OF1.

5.2. The name and concentration of the following components need to be specified on the label and SDS

(see Table 4).

Table 4: Components required on the label and SDS of AG-M4-700 OF1

Labelling requirement SDS requirement

Metamitron 6.1D (oral, inhalation)

Metamitron 6.1D (oral, inhalation), 9.1A

1,2-Propanediol (WES)

Benzene, dimethyl-, mixed isomers (WES)

Benzene, ethyl- (WES)

Sodium hydroxide (WES)

5.3. No Tolerable Exposure Limit (TEL) value has been set previously for the active ingredient in AG-M4-700

OF1 because it is considered that exposure to this substance is not likely to result in an appreciable

toxic effect to people, provided controls on use are followed.

5.4. No Environmental Exposure Limit (EEL) value is set at this time, or has been set previously for the

active ingredient in AG-M4-700 OF1, as the level of risk of adverse effects to the environment has been

qualitatively assessed as being negligible, with controls in place.

5.5. AG-M4-700 OF1 has been assessed based on the use pattern described by the applicant. Additional

adverse environmental effects (which are not addressed by the prescribed controls) could occur if this

product was used outside of its intended use pattern, for example, if it was applied at higher application

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rates. Therefore, it is considered necessary to set a maximum application rate of 4 L/ha AG-M4-700

OF1 (equivalent to 2.8 kg/ha metamitron) per application, with a maximum of 6 L/ha AG-M4-700 OF1

(equivalent to 4.2 kg/ha metamitron) per season.

5.6. A maximum application rate was also set for the reference substance, which is 4.2 kg/ha metamitron,

three times per year.

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Appendix: study summaries

Summary of mammalian toxicology data for AG-M4-700 OF1

Endpoint

(Test Guideline)

Klimisch

score Result

HSNO

Classification Reference

Acute oral toxicity

(OECD TG 423; EC

method B.1)

1 300 < LD50 <

2000 mg/kg 6.1D

(2007) - Acute Oral

Toxicity Study of Goltix OF in Rats.

Acute dermal toxicity

(OECD TG 402; EC

method B.3.)

1 LD50 >2000

mg/kg bw 6.1E

(2007) - Acute Dermal

Toxicity Study of Goltix OF in CD Rats.

Acute inhalation

toxicity

(OECD TG 403;

OPPTS 870.1300;

EC method B.2;

JMAFF 12 NohSan

No. 8147 (2-1-3))

1 LC50 >3.15 mg/L 6.1D 2008) - Acute Inhalation

Toxicity (Nose Only) Study in the Rat.

Skin

irritation/corrosion

(OECD TG 404; EC

method B.4)

1 Non-irritating

Mean score (24,

48, and 72 hrs)

– - Erythema:

0.0 Oedema: 0.0

No (2007) - Acute Dermal

Irritation/ Corrosion test (Patch test) of

Goltix OF in Rabbits.

Acute Eye

Irritation/Corrosion

(OECD TG 405; EC

method B.5)

1 Non-irritating

Mean Draize

Score (24, 48,

and 72 hrs) –

Cornea

-Opacity: 0.0

Conjunctiva

-Redness: 0.0

-Chemosis: 0.0

No (2007) - Acute Eye

Irritation/Corrosion Test of Goltix OF In

Rabbits.

Skin Sensitisation

(OECD TG 406; EC

method B.6.)

1 Non-sensitising No (2007) - Examination Of

Goltix OF in the Skin Sensitisation Test in

Guinea Pigs According to Magnusson

and Kligman (Maximisation Test).

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Ecotoxicity study summaries for AG-M4-700 OF1

Aquatic toxicity

Table 1: Acute toxicity to Fish

Study type Acute Fish study

Flag Key Study

Test Substance Goltix OF

Exposure Static 96 hour

Test species Rainbow trout Oncorhynchus mykiss

Endpoint LC50

Value 283 mg/L

Reference 2007 Goltix OF Fish (Rainbow trout), Acute Toxicity Test, Static, 96

h

Klimisch Score 1

Amendments/Deviations None

GLP Yes

Test Guideline/s OECD 203

Dose Levels 25, 50, 100, 200 and 400 mg/L (nominal)

Analytical measurements Yes via HPLC

Study Summary

This study was carried out to examine the toxicity of Goltix OF to Rainbow trout.

The trout were nominally exposed to 25, 50, 100, 200 and 400 mg Goltix OF/L.

The study was carried out as per OECD 203 with no deviations from the protocol.

All of the test validity criteria were met. Measured concentrations of the active

ingredient metamitron were in the range of 89 -102% of the expected nominal

concentration throughout the test, hence it is appropriate to express the endpoints

in terms of the nominal concentrations. Metamitron is known to hydrolyse forming

the metabolite Desamino-Metamitron. Therefore recovery rates of desamino-

metamitron were analytically verified, however, it was only detected at values

below LOQ under test conditions. The LC50 was determined to be 283 mg/L

(equivalent to 169 mg ai/l). There were no mortalities up to 200 mg/L and the

NOEC was determined to be 50 mg/L based on the behaviour of the fish.

Conclusion LC50 = 283 mg/L

Table 2: Acute toxicity to aquatic invertebrates

Study type Acute aquatic invertebrate study

Flag Key Study


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Test species Daphnia magna

Endpoint EC50

Value 99.1 mg/L

Reference 2007 Goltix OF Acute Immobilization Test (Static, 48 h) to Daphnia

magna

Klimisch Score 1


GLP Yes


Dose Levels 50, 75, 113, 169 and 253 mg/L (nominal)


Study Summary

This study was carried out to examine the toxicity of Goltix OF to Daphnia magna. The daphnia were nominally exposed to 50, 75, 113, 169 and 253 mg Goltix OF/L. The study was carried out as per OECD 202 with no deviations from the protocol. All of the test validity criteria were met. Measured concentrations of the active ingredient metamitron were in the range of 90 -106% of the expected nominal concentration throughout the test, hence it is appropriate to express the endpoints in terms of the nominal concentrations. Metamitron is known to hydrolyse forming the metabolite Desamino-Metamitron. Therefore recovery rates of desamino-metamitron were analytically verified, however, it was only detected at values below LOQ under test conditions.

The EC50 was determined to be 99.1 mg/L (equivalent to 57.2 mg ai/L). The NOEC

was determined to be 50 mg/L (corresponding to 29.9 mg ai/L based on the

behaviour of the fish.

Conclusion EC50 = 99.1 mg/L

Table 2: Acute toxicity to algae

Study type Acute algae study

Flag Key Study



Test species Pseudokirchneriella subcapitata

Endpoint ErC50

Value 5.32 mg/L

Reference 2007 Goltix OF Alga, Growth Inhibition Test with

Pseudokirchneriella subcapitata, 72 h

Klimisch Score 2 (see comments for more details)

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GLP Yes


Dose Levels 0.10, 0.32, 1.0, 3.2, 10, 32, 100 mg/ L (nominal)


Study Summary

This study was carried out to examine the toxicity of Goltix OF to

Pseudokirchneriella subcapitata. The algae were nominally exposed to 0.10, 0.32,

1.0, 3.2, 10, 32 mg Goltix OF/L. The study was carried out as per OECD 201 with

no deviations from the protocol. All of the test validity criteria were met (see

comments section for details on the recovery rates). The EC50 for growth rate was

determined to be 5.32 mg/L (equivalent to 3.18 mg ai/L). The EC10 (for growth rate)

was determined to be 1.39 mg/L (corresponding to 0.83 mg ai/L.

Comments

Measured concentrations of the active ingredient metamitron decreased

significantly during the test period duration. While the initial concentrations were in

the range of 92-115% of the expected nominal concentration at the end of the test

period the recovery rate varied from 41% to 85%. This corresponds to an increase

in the concentration of the metabolite desamino-metamitron (present at the end of

test duration at between 7-43% of the nominal concentration of the active

ingredient). Based on the low recovery of the active ingredient at the test

completion it may have been more appropriate to express the results in terms of

the measured concentrations. Despite this, however, the EPA staff feel that the

study is sufficient for classification since the conclusion is the same irrespective of

which value is used, but the value may not be appropriate to use for risk

assessment.

Conclusion EC50 = 5.32 mg/L (equivalent to 3.18 mg a.i/L)

Table 4: Acute toxicity to aquatic plants

Study type Acute aquatic plant study

Flag Key Study

Test Substance AG-M4-700 OF1

Exposure Semi-static 7-day

Test species Lemna gibba L.

Endpoint ErC50

Value 1.49 mg/L – EPA calculated value for the formulation based on the measured

active ingredient EC50 value of 1.04 mg ai/L

Reference

2017 Effects of AG-M4-700 OF1 on Lemna gibba in a growth inhibition

test under semi-static test conditions

Klimisch Score 2

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Amendments/Deviations None that would affect the results

GLP Yes


Dose Levels 0.72, 1.22, 2.08, 3.53, 6.00 mg/L test item (nominal)


Study Summary

This study was carried out to examine the toxicity of AG-M4-700 OF1 to Lemna

gibba. The algae were nominally exposed to 0.72, 1.22, 2.08, 3.53, 6.00 mg/L of

the test substance which corresponds to 0.42, 0.71, 1.21, 2.06, 3.50 mg/L ai.

The study was carried out as per OECD 221 with no significant deviations from the

protocol. All of the test validity criteria were met.

The most sensitive ErC50 was 3.27 mg/L test item nominal (1.91 mg/L ai nominal;

1.04 mg/L ai mean measured) based on the assessment of dry weight.

Comments

Measured concentrations of the active ingredient metamitron decreased

significantly during the test period duration. At test start and test solution renewal

processes nominal concentrations were analytically confirmed in fresh test

solutions. Recoveries between 86 and 93% were found. In spent test solutions

taken at test solution renewals and test end, recoveries ranging from 22 to 54%

were determined.

Results are expressed in terms of the nominal concentrations and the measured

concentration of active ingredient. Based on the low recovery of the active

ingredient. The EPA have estimated the ErC50 based on the measured active

ingredient ErC50 value of 1.04 mg ai/L (1.04 x 1000/700 = 1.49 mg AG-M4-700

OF1).

Conclusion ErC50 = 1.49 mg/L – EPA calculated value for the formulation based on the

measured active ingredient ErC50 value of 1.04 mg ai/L

Conclusion about aquatic toxicity

The formulated product triggers a 9.1B HSNO classification based on its toxicity to algae and aquatic plants

and the fact that the active ingredient is not rapidly biodegradable. It is also harmful to crustaceans.

Soil toxicity

Table 5: Earthworm chronic toxicity test

Study type Earthworm chronic toxicity test

Flag Key Study


Endpoint NOEL

Value 180 mg/kg soil dry weight

Reference 2016 AG-M4-700 OF1 – Determination of chronic toxicity to the

earthworm Eisenia andrei in an artificial soil substrate

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Klimisch Score 1


GLP Yes


Dose Levels 31, 56, 100, 180, 324, 583, 1050 and 1890 mg product/kg soil dry weight

Analytical measurements None

Study Summary

The aim of the study was to determine under laboratory test conditions whether AG-

M4-700 OF1 had harmful effects on the survival, growth or reproductive capacity of

adults of the earthworm Eisenia andrei.

AG-M4-700 OF1 was evaluated at eight concentrations, equivalent to 31, 56, 100,

180, 324, 583, 1050 and 1890 mg test item/kg soil dry weight. These were

compared to a control treatment of purified water. Treatments were incorporated

into an artificial soil substrate containing 5% w/w peat, which was placed within

polystyrene boxes (17.1 cm x 11.3 cm in area, by 6 cm deep) with ventilated lids.

There were 8 replicate boxes for the control and 4 for each test-item treatment

concentration. For all treatments, the soil moisture content was maintained at 50%

(± 10%) of the maximum water-holding capacity throughout the bioassay. Ten adult

E. andrei (approx. 5.5 months old, each 300-600 mg fresh weight and with a visible

clitellum) were weighed and then placed on the surface of the soil in each arena

immediately after treatment application. One day after treatment (DAT), hydrated

oat flakes were placed on the soil surface and this food source was replenished

weekly for the first four weeks of the bioassay. At 28 DAT, the numbers of the

original worms still surviving and their fresh weights were recorded. Any apparent

change in the behaviour or physical condition of the confined worms was noted.

These adult worms were then removed and the test soil and any egg cocoons or

juvenile worms were returned to the test chambers. A final supply of oat flakes was

provided on the soil surface. After a further 28 days (ie. 56 DAT), the number of

juvenile worms that had developed in each replicate arena was recorded.

After 28 days, there was no significant mortality in any of the AG-M4-700 OF1

treatments (Fisher’s Exact Test, α = 0.05). All of the worms appeared healthy and

no abnormal behaviour was recorded. In terms of changes in mean body weight,

the only treatment to differ significantly from the control was 1890 mg test item/kg

soil dry weight (one-way ANOVA and Dunnett’s t-test, α = 0.05; or Mann-Whitney U-

test, α = 0.05). Thus, the lowest-observed-effect concentration (LOEC) for direct

effects on adult worms was 1890 mg/kg soil dry weight and the no-observed-effect

concentration (NOEC) was 1050 mg/kg soil dry weight.

In terms of the mean numbers of juveniles, statistically significant effects were

observed at treatment concentrations of 1890, 1050, 583 and 324 mg test item/kg

soil dry weight (t-test for independent samples, α = 0.05). Thus, with respect to

reproduction, the LOEC was 324 mg test item/kg soil dry weight and the NOEC was

180 mg test item/kg soil dry weight.

Conclusion NOEL = 180 mg/kg soil dry weight

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Table 6: Predatory mite Hypoaspis aculeifer chronic toxicity test

Study type Predatory mite chronic toxicity test

Flag Key Study


Endpoint NOEC

Value 1000 mg/kg soil dry weight

Reference

2016 AG-M4-700 0F1 (Metamitron 700 SC) - A laboratory test to

determine the effects of fresh residues on the predatory mite Hypoaspis aculeifer

(Acari, Laelapidae)

Klimisch Score 1

Amendments/Deviations None that affect the conclusions

GLP Yes


Dose Levels 1000 mg/kg soil dry weight


Study Summary

The aim was to determine under laboratory test conditions whether AG-M4-700

OF1 has harmful effects on the predatory soil mite Hypoaspis aculeifer (Canestrini)

(Acari, Laelapidae).

Following a preliminary range finding test, AG-M4-700 OF1 was evaluated in a

definitive bioassay at a single concentration, equivalent to 1000 mg test item/kg soil

dry weight. This was compared to an untreated control and a toxic reference

treatment of Perfekthion (nominally 400 g/L dimethoate), which was applied at a

concentration of 14 mg ai/kg soil dry weight. Treatments were incorporated into an

artificial soil substrate (containing 5% w/w peat), aliquots of which were then

transferred into small, ventilated, glass jars (n = 8 for control; n = 8 per test-item

treatment concentration; n = 5 for toxic reference). Ten female soil mites

(approximately 7-14 days after becoming adult) were then introduced into each

arena. Cheese mites (Tyrophagus putrescentiae (Schrank)) and springtails

(Folsomia Candida (Willem)) were provided as food for the predatory soil mites and

were replenished ad libitum. At 14 days after treatment (DAT), both the numbers of

surviving adult predatory soil mites and of their offspring were recorded.

The results were used to determine the no-observed-effect concentration (NOEC)

for the test item, with respect to the assessments of both mortality and reproduction.

In addition, values for key effect concentrations (EC50, EC20 and EC10) for

reproduction were estimated, as was the median lethal concentration (LC50) for the

mites originally introduced.

Based on the numbers of offspring produced, the 14-day EC50 and the EC20 and

EC10 values for AG-M4-700 OF1 were all estimated as > 1000 mg test item/kg soil

dry weight. The LC50 was also estimated to be > 1000 mg test item/kg soil dry

weight. The overall NOEC with respect to both mite survival and reproduction was

1000 mg test item/kg soil dry weight.

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Conclusion NOEC = 1000 mg/kg soil dry weight

Table 7: Predatory mite toxicity test

Study type Predatory mite toxicity test

Flag Key Study

Test Substance AG-M4-700 0F1

Test species Predatory mite Typhlodromus pyri

Endpoint NOER

Values NOER = 9200 mL product/ha

Reference

2016 AG-M4-700 0F1 (Metamitron 700 SC) - A rate-response

laboratory bioassay ofthe effects of fresh residues on the predatory mite

Typhlodromus pyri (Acari: Phytoseiidae)

Klimisch Score 1

Amendments/Deviations None noted

GLP Yes

Test Guideline/s Blumel et al. (2000)

Dose Levels 1200, 2300, 4600, 9200 and 13800 mL/ha.


Study Summary

The aim of this study was to determine the effects of fresh-dried residues of AG-

M4-700 OF1 on the predatory mite Typhlodromus pyri Scheuten (Acari:

Phytoseiidae), under worst-case laboratory test conditions. The test substance

was applied to glass plates at the doses outlined above. Twenty protonymphal T.

pyri were placed in each replicate unit, with three replicates (ie. 60 mites) prepared

per treatment. The mites were fed regularly with untreated pollen for food. Their

survival was assessed after a 7-day period, by which time the mites in the control

treatment were adult. A check was then made for sub-lethal treatment effects on

reproduction. For this, the mites were left in-situ and the numbers of eggs

produced per female were recorded over a further 7-day period. The mean number

of eggs produced per female from 7-14 days after treatment (DAT) was calculated

for each treatment. These reproduction assessments were made for mites from the

control and from the highest three treatment rates that had resulted in < 50%

corrected mortality.

Based on statistical comparison with the control, the NOER with respect to mite

survival was 13800 mL product/ha and the NOER for reproduction was 9200 mL

product/ha. A 10.2% effect on reproduction was noted at the highest dose 13800

mL/ha. The 7-day LR50 was > 13800 mL product/ha.

Conclusion NOER = 9200 mL product/ha (based on reproduction)

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Table 8: Collembola toxicity test

Study type Collembola toxicity test

Flag Key Study


Test species Collembola

Endpoint LC50

Values 0.442 mg test item/kg soil

Reference

2017 AG-M4-700 OF1 (Metamitron 700 SC) – A laboratory test to

determine the effects of fresh residues on the springtail Folsomia candida

(Collembola, Isotomidae)

Klimisch Score 1


GLP Yes


Dose Levels 0.8, 0.4, 0.2, 0.1, 0.05, 0.025, 0.0125 and 0.00625 mg/kg soil dry weight


Study Summary

The aim of this study was to determine under laboratory test conditions whether

AG-M4-700 OF1 has harmful effects on the springtail Folsomia candida

(Collembola, Isotomidae).

Following a preliminary range finding test, AG-M4-700 OF1 was evaluated in a

definitive bioassay at eight concentrations, equivalent to 0.8, 0.4, 0.2, 0.1, 0.05,

0.025, 0.0125 and 0.00625 mg test item/kg soil dry weight. This was compared to

an untreated control and a toxic reference treatment of Betosip 114 (nominally 114

g/L phenmedipham), applied at a concentration of 200 mg product/kg soil dry

weight. Treatments were incorporated into an artificial soil substrate (containing

5% w/w peat), aliquots of which were then transferred into small glass jars (n = 8

for control; n = 4 per test-item treatment concentration; n = 5 for toxic reference).

Ten juvenile F. candida (10 days old) were introduced into each jar and dry

granulated yeast was provided as food. This food was replenished at 14 days. The

jars were ventilated every 1-4 days. At 28 days, the numbers of the springtails

originally introduced that still survived and the numbers of their offspring were

recorded.

There was a statistically significant effect on adult springtail survival in the 0.8 and

0.4 mg test item/kg soil dry weight treatments, and also in the 0.025 and 0.0125

mg test item/kg soil dry weight treatments. Since there were no significant effects

observed on mortality at concentrations between these, the effects at the lower

concentrations were taken to be an anomaly and the NOEC for mortality was

assumed to be 0.2 mg/kg soil dry weight. The 28-day LC50 was estimated to be

0.442 mg test item/kg soil dry weight.

There was a statistically significant effect on reproduction at 0.025, 0.2, 0.4 and 0.8

mg/kg soil. While the effects at 0.025 mg/kg soil are statistically significant effects

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were not seen at higher doses and the % change in numbers of progeny relative to

the control (14%) is within the allowable variation for the control according the

OECD guidance (20%). The NOEC for reproduction can therefore be considered

to be 0.1 mg test item/kg soil dry weight.

Conclusion LC50 = 0.442 mg test item/kg soil

Table 9: Collembola field test

Study type Collembola field test

Flag Key Study


Test species Collembola

Endpoint NOER

Values NOER = 2 product/ha

Reference

2017 A field trial to determine the effects AG-M4-700 OF1 (Metamitron

700 SC) on natural populations of Collembola

Klimisch Score 1

Amendments/Deviations None noted

GLP Yes

Test Guideline/s

Candolfi et al. (2001). Guidance document on regulatory testing and risk

assessment procedures for plant protection products with non-target arthropods.

Barrett et al. (1994). Guidance document on regulatory testing procedures for

pesticides with non-target arthropods.

Dose Levels 2 L/ha


Study Summary

The aim of this field study was to determine the effects of three applications of AG-

M4-700 OF1 at 2 L/ha, with a nominal 7-day spray interval, on the numbers of

Collembola (springtails) present in the soil.

AG-M4-700 OF1 was evaluated at a single application rate, equivalent to 2 L

product/ha. This was applied on three consecutive occasions (times T1, T2 and

T3), with 7- and 8-day intervals in-between the respective applications. This

treatment regime was compared to a water control (applied at time T3 only) and a

toxic reference treatment of chlorpyrifos (an EC formulation nominally containing

480 g ai/L, applied as a spray at a rate equivalent to 1.5 L product/ha at time T3

only).

Twenty-four plots, each approximately 5 m x 5 m in area and separated from each

other by a 2-m-wide buffer strip were marked out in a line alongside a fallow arable

field in southern England. The soil type was characterised as being a sandy clay

loam. Each treatment was applied to eight replicate plots (arranged in a

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randomised block design), with applications being made using a boom sprayer at a

volume rate equivalent to 200 L spray solution/ha.

The Collembola present in each plot were sampled using both a soil-corer and a

motorised soil-surface suction-sampler (both being density-dependent sampling

techniques). The samples were taken within the central sampling area of each

treatment plot. They were collected in the week prior to the initial (T1) application

of the test-item treatment, in order to determine the level of any homogeneity

between the plots, and then again at 1, 4 and 8 weeks after the final (T3) treatment

application.

In the laboratory, the Collembola in the samples were extracted over a four- to six-

day period using banks of Tullgren funnels (one funnel per replicate plot and

sampling technique). The extracted springtails were stored in methyl alcohol prior

to sorting and counting of the main taxonomic groups.

The two most abundant taxa that were identified were the super-family

Entomobryoidea and the order Symphypleona. Statistical comparisons for the pre-

treatment samples did not indicate that numbers for either of these groups differed

significantly between treatments (α = 0.05). After application, there were no

statistically significant effects detected in the AG-M4-700 OF1 (3 x 2 L product/ha.)

Comment

It is noteworthy that the application rate is less than that proposed in New Zealand

(up to 4 litres of product per hectare). Also the applicant has proposed up to 6

applications per season.

Conclusion NOER = 2 product/ha

Table 10: Terrestrial plant toxicity, seedling emergence

Study type Terrestrial plants toxicity, seedling emergence

Flag Key study


Test species Oats, onion, sugar beet, rape, carrot and soybean

Endpoint Effective Dose (ED)50

Values > 5 L/ha

Reference 2007 Goltix OF Terrestrial Plants Toxicity, Seedling Emergence

Klimisch Score 1


GLP Yes


Dose Levels 5.0, 2.5, 1.25, 0.625 and 0.313 L/ha

Analytical measurements Yes- HPLC

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Study Summary

The phytotoxicity of the test item Goltix OF to six terrestrial plant species was

determined each over a period of at least 21 days. According to the results of a

range-finder, the test was conducted with the application rates listed above. Test

plants were two monocotyledons (oats, Gramineae; onion, Liliaceae) and four

dicotyledons (sugar beet, Chenopodiaceae; rape, Brassicaceae; carrot,

Umbelliferae; soybean, Leguminosae). The test item was applied once on the soil

surface after the seeds were sown.

The test containers were bottom watered with nutrient solution as needed. The

toxic effects of the test item were determined on day 7, 14 and 21 (onion and

carrot additionally on day 24) by visual observations and on day 21 and 24,

respectively by shoot height and shoot fresh weight determination.

The ED50 values for all plants were > 5 L/ha. NOEL values were 5 L/ha for all

plants with the exception of carrots which had a NOEL of 2.5 L/ha.

Conclusion ED50 > 5 L/ha

Table 11: Terrestrial plants toxicity, vegetative vigour

Study type Terrestrial plants toxicity, vegetative vigour

Flag Key study


Test species Oats, onion, sugar beet, rape, carrot and soybean

Endpoint Effective Dose (ED)50

Values 2.27 L/ha

Reference 2007 Goltix OF Terrestrial Plants Toxicity, Vegetative Vigour

Klimisch Score 1


GLP Yes


Dose Levels 0.313, 0.625, 1.25, 2.5 and 5.0 L/ha

Analytical measurements Yes- HPLC

Study Summary

The phytotoxicity of the test item Goltix OF to six terrestrial plant species was

determined each over a period of at least 21 days.

The test was conducted with the application rates 5.0, 2.5, 1.25, 0.625 and 0.313

L/ha. For the plant species carrot 0.156 L/ha was tested additionally. Test plants

were two monocotyledons (oats, Gramineae; onion, Liliaceae) and four

dicotyledons (sugar beet, Chenopodiaceae; rape, Brassicaceae; carrot,

Umbelliferae; soybean, Leguminosae). The test item was applied at test start onto

the foliage of the plants that reached the 2-4 leaf stage. The plants were watered

from the bottom and fertilised during the test with nutrient solution as needed. The

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toxic effects of the test item were assessed on day 7, 14 and 21 by visual

observations (phytotoxic effects and number of dead plants) and on day 21 by

shoot height and shoot fresh weight determination.

The lowest ED50 value was 2.27 L/ha for carrots. The lowest NOEL was 0.625 L/ha

for carrots.

Conclusion ED50 = 2.27 L/ha

Table 12: Nitrogen transformation test

Study type Nitrogen transformation

Flag Key study

Test Substance GOLTIX OF

Endpoint NOER

Value > 20 L/ha

Reference 2007 Effects of GOLTIX OF on the activity of soil microflora (Nitrogen

transformation test)

Klimisch Score 1


GLP Yes


Dose Levels 2 L/ha and 20 L/ha


Study Summary

This test examined the effects of the test substance on the soil microflora involved

in nitrogen transformation. The study was carried out in full accordance with the

OECD study guideline and fulfilled all the validity criteria. The test substance

caused no adverse effects (deviation from control <25%, OECD 216) on the soil

nitrogen transformation (measured as NO3-N production) at the end of the 28-day

incubation period up to an application rate of 20 L test item/ha.

Conclusion NOER = 20 L/ha

Table 13: Carbon transformation test

Study type Carbon transformation

Flag Key study


Endpoint NOER

Value > 20 L/ha

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Reference 2007 Effects of GOLTIX OF on the activity of soil microflora (Carbon

transformation test)

Klimisch Score 1


GLP Yes


Dose Levels 2 L/h and 20 L/ha


Study Summary

This test examined the effects of the test substance on the soil microflora involved

in carbon transformation. The study was carried out in full accordance with the

OECD study guideline and fulfilled all the validity criteria. The test substance

caused no adverse effects (deviation from control <25%, OECD 216) on the soil

carbon transformation at the end of the 28-day incubation period up to an

application rate of 20 L test item/ha.

Conclusion about soil toxicity

The formulated product triggers a 9.2B classification (ecotoxic in the soil environment). This is based on the

ED50 (equivalent to an ER50) for vegetative vigour of 2.27 L/ha. If the density of the product is 1.197 this

would be equivalent to 2.72 kg/ha. By using the EPA default values for converting field application rates to

units of milligrams of active ingredient per kilogram of dry soil this equates to an EC50 of 3.63 mg/kg soil.

Terrestrial invertebrate toxicity

Table 6: Honey bee acute toxicity test

Study type Honey bee acute oral and contact test 48 hour

Flag Key Study


Test species Honeybee Apis mellifera L.

Endpoint LD50

Values Oral LD50 > 181.55 ug/bee equivalent to >108 ug ai/bee

Contact LD50 >168.04 ug/bee equivalent to >100 ug ai/bee

Reference 2007 Acute toxicity of GOLTIX OF to the honeybee Apis mellifera L. under

laboratory conditions

Klimisch Score 1


GLP Yes

Test Guideline/s OECD 213 and OECD 214

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Dose Levels Contact test: 168.04 ug product/bee

Oral test (nominal): 201.64 ug product/bee


Study Summary

This test examined the oral and contact of the test substance on honey bees (see

dose levels above). The study was carried out in full accordance with the OECD

study guideline and fulfilled all the validity criteria. The test substance caused no

adverse effects at any of the doses tested.

The Oral LD50 was therefore determined to be > 181.55 ug/bee (equivalent to >108

ug ai/bee) while the contact LD50 was determined to be >168.04 ug/bee equivalent

to >100 ug ai/bee.

Conclusion Oral LD50 > 181.55 ug/bee equivalent to >108 ug ai/bee

Contact LD50 >168.04 ug/bee equivalent to >100 ug ai/bee

Table 8: Extended laboratory bioassay: Rove Beetles

Study type Extended laboratory bioassay

Flag Key Study


Exposure 66 day exposure to fresh residues

Test species Rove Beetle Aleochara bilinerata

Endpoint NOER

Value 6000 mL/ha

Reference

2016 AG-M4-700 OF1- An extended laboratory bioassay of the effects of

fresh residues on the rove beetle Aleochara bilinerata (Coleoptera; Staphylinidae)

Klimisch Score 1

Amendments/Deviations None reported

GLP Yes

Test Guideline/s Grimm et al. (2000)

Dose Levels 500, 1000, 2000, 4000 and 6000 ml/ha


Study Summary

This test examined the effects of fresh residues of the test item on adults of the

rove beetle Aleochara bilinerata and their larval offspring. The test item was

applied at rates of 500, 1000, 2000, 4000 and 6000 mL/ha onto replicate arenas

containing a natural sandy soil. Immediately after application 20 adult beetles of

equal sex ratio were introduced into each arena. The beetles were assessed at 1,

7 and 28 days after treatment. The success of the larval offspring of the original

beetles was assessed by the provision of ca. 500 onion fly pupae in each replicate

box on three weekly occasions i.e. at 7, 14 and 21 DAT. The original adult beetles

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were removed from the arenas at 28 days and the soil was left to dry for a week.

The fly pupae were sieved from the soil and the number of new adult beetles (in

the F1 progeny) that developed from the fly pupae was recorded over a further 31

days up until 66 DAT.

The results indicated that the NOER was 6000 mL/ha and that the ER50 >6000

mL/ha.

Conclusion NOER = 6000 mL/ha

Conclusion about terrestrial invertebrate toxicity

The formulated product does not trigger 9.4 classification

rapid science memo · rapid science memo for approval to import or manufacture ag-m4-700 of1 for...

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