SCIENCE MEMO - EPA

SCIENCE MEMO

November 2018

APP202870 – PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron

Substance database ID - 48470

November 2018

2

Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)

November 2018

Executive Summary PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron is a pellet containing the active ingredient

elemental iron, a chelating agent, and other components. It is intended to be used as a snail and slug bait

around seedlings, potted plants, vegetables, crop plants, perennials and any other plants affected by snails

or slugs. The active ingredient is new to New Zealand, it has not been previously used as a pesticide in New

Zealand; however, products containing elemental iron are used as animal supplements.

The active ingredient elemental iron is not approved as a pesticide in the European Union (EU). Iron

sulphate is approved in the EU, and its use is restricted to amenity turf and sports turf for the control of moss.

The substance, PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron, has been reviewed by the

Australian Pesticides and Veterinary Medicines Authority (APVMA) and was approved.

The risks to people and the environment in New Zealand from the use of PROTECT-US™ Mineral Snail and

Slug Killer with Elemental Iron have been assessed using the data available and a risk assessment

methodology suitable for the use pattern and physical form of the substance.

The human health assessment indicated that the risk for operators and bystanders was negligible. The

health risk from accidental consumption of granules by an infant or toddler in the field after application is low.

The risk from consumption of soil was also low. The risk from exposure to the packaged material is higher,

but precautionary advice to address this is provided on the label.

The risks to pets are unknown, but exposure to the granules is expected since the bait contains Components

B and D.

Some risks to the environment were identified of which some were considered to be mitigated by controls

while others could not be mitigated.

Due to the limited information on the actual exposure during the aquatic studies, not all provided data could

be used for the risk assessment. In the studies provided, toxicity to aquatic crustaceans has been

demonstrated at concentrations that are expected to be below the solubility in the test medium. The

Environmental Protection Authority (EPA) staff consider that this risk could be managed with a control.

Acute risks to earthworms were identified. No data were available regarding chronic toxicity but when

evaluating the acute data, chronic effects are considered likely. No controls could be formulated to mitigate

these risks, since these controls would result in the substance not being able to be used in a meaningful

manner.

One component can accumulate in fatty tissues. However, it has not been conclusively established if an

excess of this substance is harmful.

Insufficient information was available to evaluate all environmental risks. No information was available for

several environmental receptors which was considered problematic for chronic data for the aquatic

environment and birds.

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November 2018

Table of Contents APP202870 – PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron .......................... 1

1. Background .................................................................................................................................. 5

2. Hazardous properties ................................................................................................................. 5

3. Risk assessment ......................................................................................................................... 6

4. Human health risk assessment .................................................................................................. 7

Operator ........................................................................................................................................ 7

Bystanders ..................................................................................................................................... 7

5. Environmental risk assessment ................................................................................................ 8

Risks to aquatic organisms ........................................................................................................... 8

Risks to soil organisms .................................................................................................................. 8

Risks to terrestrial vertebrates ....................................................................................................... 8

Risks to pollinators and non-target arthropods ....................................................................... 8

Bioaccumulation ............................................................................................................................ 8

6. Proposed controls ....................................................................................................................... 9

Appendix A: Identity of the active ingredient, use pattern and mode of action ........................... 10

Identity of the active ingredient and metabolites ......................................................................... 10

Use pattern and mode of action .................................................................................................. 10

Appendix B: Hazard classification of the substance ....................................................................... 12

Appendix C: Physico-chemical properties of PROTECT-US™ Mineral Snail and Slug Killer with

Elemental Iron………………………………………………………………………………………………….16

Appendix D: Environmental fate ........................................................................................................ 17

Summary ..................................................................................................................................... 17

Appendix E: Mammalian toxicology .................................................................................................. 18

Executive summaries and list of endpoints for PROTECT-US™ Mineral Snail and Slug Killer with

Elemental Iron ............................................................................................................................. 18

General conclusion about mammalian toxicology of PROTECT-US™ Mineral Snail and Slug Killer with

Elemental Iron ............................................................................................................................. 18

Appendix F: Ecotoxicity ...................................................................................................................... 19

Executive summaries and list of endpoints ................................................................................. 19

Aquatic toxicity and exposure assessment ................................................................................. 21

Soil toxicity ................................................................................................................................... 22

Soil toxicity and exposure assessment ....................................................................................... 24

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November 2018

Terrestrial vertebrate toxicity ....................................................................................................... 25

Vertebrate toxicity and exposure assessment ............................................................................ 26

Ecotoxicity to bees and other terrestrial invertebrates ................................................................ 27

Bioaccumulation potential of the substance ................................................................................ 27

Summary of the environmental risk assessment ........................................................................ 27

Appendix G: Human health risk assessment ................................................................................... 29

Quantitative risk assessment ...................................................................................................... 29

Input values for the human health risk assessment .................................................................... 29

Operator exposure assessment .................................................................................................. 31

Quantitative bystander risk assessment ..................................................................................... 32

Accidental oral exposure children ............................................................................................... 32

Conclusions of the human health risk assessment ..................................................................... 34

Appendix H: Proposed controls ......................................................................................................... 35

EPA Notice controls..................................................................................................................... 35

Exposure thresholds .................................................................................................................... 35

Other toxicity controls .................................................................................................................. 36

Ecotoxicity controls ...................................................................................................................... 37

Maximum application rate ........................................................................................................... 37

Other ecotoxicity controls ............................................................................................................ 37

Appendix I: Study summaries ............................................................................................................ 38

Toxicity study summaries ............................................................................................................ 38

Environmental fate studies .......................................................................................................... 42

Ecotoxicity study summaries ....................................................................................................... 42

Appendix J: Standard terms and abbreviations ............................................................................... 52

Appendix K: References ..................................................................................................................... 54

Appendix L: Confidential Composition ................................................... Error! Bookmark not defined.

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November 2018

1. Background

1.1. PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron is a pellet containing the active

ingredient elemental iron, a chelating agent, and other components. It is intended to be used as a snail

and slug bait around seedlings, potted plants, vegetables, crop plants, perennials and any other plants

affected by snails or slugs. The active ingredient is new to New Zealand, it has not been previously

used as a pesticide in New Zealand, however, products containing elemental iron are used as animal

supplements.

1.2. The active ingredient, elemental iron, is not approved as a pesticide in the EU. Iron sulphate is

approved in the EU, and its use is restricted to amenity turf and sports turf for the control of moss.

1.3. The substance, PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron, has been reviewed

by the APVMA and was approved in January 2017.

1.4. The applicant has provided several studies to the EPA, however, these could not be considered a full

data package.

1.5. The risks to people and the environment in New Zealand from the use of PROTECT-US™ Mineral Snail

and Slug Killer with Elemental Iron have been assessed using the data available and a risk assessment

methodology suitable for the use pattern and physical form of the substance.

2. Hazardous properties

2.1. The hazard classifications proposed by the applicant and the EPA staff for PROTECT-US™ Mineral

Snail and Slug Killer with Elemental Iron are outlined in Table 1.

Table 1: Proposed classification for PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron

Hazard Classification

proposed by the

applicnat

Classification

proposed by the

EPA

Eye irritancy 6.4A No

Contact sensitisation Not applicable 6.5B

Aquatic ecotoxicity Not applicable 9.1B

2.2. Mammalian toxicity studies with the formulated substance indicate that PROTECT-US™ Mineral Snail

and Slug Killer with Elemental Iron is of low acute toxicity and should not be classified for acute toxicity.

The substance is not irritating to the skin or eyes, but is a contact sensitiser and should be classified

6.5B. It should be noted that insufficient information was available to determine all hazard classes.

2.3. PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron is considered ecotoxic to aquatic

crustaceans (9.1B), but does not require classification for soil toxicity (9.2) and terrestrial vertebrates

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November 2018

toxicity (9.3). No data were provided to determine the terrestrial invertebrate ecotoxicity (9.4) of the

substance, however, effects are considered unlikely.

2.4. The applicant proposed only a 6.4A classification and indicated that other classifications were not

applicable. The EPA staff’s assessment of the provided studies suggested that the substance should

have a 6.5B and 9.1B classifications.

2.5. The 6.5B classification was not assigned by the applicant, as a 55% positive response was observed in

the provided skin sensitisation study. Because the sensitisation response was above the 30% threshold,

the EPA staff concluded that the 6.5B classification is warranted.

2.6. The 9.1 classification was not assigned by the applicant. Studies were presented by the applicant

indicating an EC50 for crustaceans below 100 mg/L, which is the regulatory threshold for classification.

The EPA staff concluded that the 9.1B classification is warranted.

2.7. The studies provided were considered insufficient information to determine the exact aquatic toxicity of

PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron but allowed for an estimation of the

toxicity. The 48h-EC50 for crustaceans was determined to be 26.9 mg/l based on the nominal

concentration of water accommodated fractions (WAF) indicating that it is harmful to crustaceans.

2.8. With the preparation technique used for the aquatic studies, the actual exposure is lower than nominal

concentration. As a result, it was determined that the presented EC50, based on nominal concentrations,

underestimates the actual toxicity of the mixture. No analytical confirmation of the test medium was

presented to provide the actual exposure of the organisms to the formulation. Since exposure is

expected to be much lower than presented the staff considered it appropriate to take the precautionary

approach and assigned a 9.1B classification.

2.9. Iron is derived from natural sources. Therefore the impurity profile can vary significantly for materials of

different origin. The members of the European Iron Sulphate Task Force agreed to use material with

specific limits for all the present impurities (the heavy metals and arsenic are considered relevant).

Arsenic, cadmium, chromium, lead and mercury were considered as relevant impurities, with maximum

limits of 18 mg/kg, 1.8 mg/kg, 90 mg/kg, 36 mg/kg and 1.8 mg/kg of the anhydrous iron(II) sulphate

content, respectively [see European Food Safety Authority (EFSA) report, (EFSA 2012)].

3. Risk assessment

3.1. It is considered that there is potential for significant exposure to people and/or the environment during

the use phase of the lifecycle. Quantitative risk assessments have been undertaken to understand the

likely exposures to the substance under the use conditions proposed by the applicant.

3.2. During the importation, manufacture, transportation, storage and disposal of this substance, it is

estimated that the proposed controls and other legislative requirements will sufficiently mitigate risks to

a negligible level. This assessment takes into account the existing Hazardous Substances and New

Organisms (HSNO) requirements around packaging, identification and disposal of hazardous

substances. In addition, the Land Transport Rule 45001, Civil Aviation Act 1990, Maritime Transport Act

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November 2018

1994 and New Zealand’s health and safety at work requirements all have provisions for the safe

management of hazardous substances.

4. Human health risk assessment

4.1. The active ingredient is new to New Zealand, it has not been previously used as a pesticide in New

Zealand, and therefore a quantitative human health risk assessment has been performed and can be

found in Appendix G.

Operator

4.2. Predicted operator exposures to elemental iron are below the Acceptable Operator Exposure Level

(AOEL) for each use pattern, even without the use of Personal Protective Equipment (PPE). Although

the quantitative risk assessment indicates that PPE is not required to ensure that exposures are below

the AOEL, this risk assessment does not take account of site of contact effects such as irritation and

sensitisation. PPE requirements triggered by the hazard classifications of PROTECT-US™ Mineral

Snail and Slug Killer should be retained to protect operators against the potential skin sensitisation

effects of PROTECT-US™ Mineral Snail and Slug Killer.

Bystanders

4.3. Exposure to PROTECT-US™ Mineral Snail and Slug Killer is calculated from the ingestion of soil by

children, using the product label application rate recommendations. Estimated bystander exposure to

elemental iron is below the AOEL.

Accidental oral exposure children

4.4. Iron poisoning is a common toxicological emergency in young children. Contributing factors include the

availability of iron tablets and their candy-like appearance. The potential severity of iron poisoning is

based on the amount of elemental iron ingested. The amount of elemental iron ingested must be

calculated based on the number of tablets ingested and the percentage of elemental iron in the salt.

4.5. Children may show signs of toxicity with ingestions of 10-20 mg/kg of elemental iron. Serious toxicity is

likely with ingestions of more than 60 mg/kg. Iron exerts both local and systemic effects and is corrosive

to the gastrointestinal mucosa and can affect the heart, lungs, and liver. Excess free iron is a

mitochondrial toxin that leads to derangements in energy metabolism (Abhilash, Arul et al. 2013).

4.6. Case reports of accidental poisoning with medicinal iron, especially in young children, indicate acute

damage of gastrointestinal, hepatic, pancreatic and cardiovascular structures after ingestion of very high

doses. An acute oral dose of 60 mg iron/kg body weight can be lethal but oral doses below about 10-20

mg iron/kg body weight do not cause acute systemic toxicity (EFSA 2014).

4.7. The staff consider the health risk from accidental consumption of granules by an infant or toddler in the

field after application to be low. An infant (9kg) would need to find and consume 22 granules, within a

short period of time, to reach the reference dose of iron.

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November 2018

4.8. The more significant risk to the toddler is presented by the product in the package from which they may

more easily get a higher dose. The draft label submitted has warning and precautionary statements

relating to access by young children.

5. Environmental risk assessment

Risks to aquatic organisms

5.1. Due to the limited information on the actual exposure during the aquatic studies, not all provided data

could be used for the risk assessment. In the studies provided, toxicity to aquatic crustaceans has been

demonstrated at concentrations that are expected to be below the solubility level in the test medium.

Therefore, the staff consider there are potentially acute risks for the aquatic environment, however, this

risk can be managed with the prescribed control in the Hazardous Property Controls (HPC) Notice

prohibiting the application of class 9.1 substances in water.

5.2. No information on chronic toxicity has been provided and therefore the risks could not be estimated.

Risks to soil organisms

5.3. Acute risks to earthworms were identified. No information on chronic toxicity has been provided and

therefore risks could not be estimated. Additional section 77A controls were considered inappropriate to

manage these risks since they will prevent the intended use of the formulation. The staff consider it

inappropriate to advertise the substance to be safe for earthworms since long-term effects are

considered possible.

5.4. No risks to soil micro-organisms were identified.

5.5. No studies on the toxicity to plants were presented. Based on the intended use of the product (to protect

plants from damage by snails and slugs), an effect is considered unlikely.

Risks to terrestrial vertebrates

5.6. The acute risks to birds are considered below the Level Of Concern.

5.7. The risks to pets are unknown, but exposure to the granules is expected since the bait contains

Components B and D.

5.8. No information on chronic toxicity has been provided and therefore risks could not be estimated.

Risks to pollinators and non-target arthropods

5.9. No information regarding the toxicity to bees has been provided by the applicant. However, based on

the use pattern, exposure to the substance is considered unlikely.

Bioaccumulation

5.10. One component can accumulate in fatty tissues, however, it has not been conclusively established if

an excess of this substance is harmful.

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November 2018

6. Proposed controls

6.1. It is considered that the proposed controls will manage the risks to the environment. It is not considered

that setting Environmental Exposure Limits (EELs) for any component in this substance is required to

manage risks, or would be an effective control. Hence it is not proposed to set any values.

6.2. No ADE (Acceptable Daily Exposure) or PDE (Potential Daily Exposure) values had previously been

provided to set a TEL (Tolerable Exposure Limit) for the active ingredient in PROTECT-US™ Mineral

Snail and Slug Killer. ADE and PDE values are provided below but no TEL has been set 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.

6.3. The ADE and PDE shown below are proposed by the EPA as health-based exposure guidance values

that can be used to inform risk assessments as well as the setting of controls, such as Maximum

Residue Levels under the Agricultural Compounds and Veterinary Medicines Act 1997.

6.4. The following exposure guideline values are proposed for elemental iron:

ADE = 0.8 mg/kg bw/day

PDE(food) = 0.56 mg/kg bw/day

PDE(drinking water) = 0.16 mg/kg bw/day

PDE(other) = 0.08 mg/kg bw/day

6.5. The following additional controls are proposed for PROTECT-US™ Mineral Snail and Slug Killer with

Elemental Iron:

PROTECT-US™ Mineral Snail and Slug Killer must be labelled “keep out of reach of children” as

prescribed in the Hazardous Substances (Labelling) Notice 2017.

The following limits are proposed for toxicologically relevant impurities in the technical grade

active ingredient elemental iron (expressed on the basis of the anhydrous variant):

o Arsenic: maximum 18 mg/kg

o Cadmium: maximum 1.8 mg/kg

o Chromium: maximum 90 mg/kg

o Lead: maximum 36 mg/kg

o Mercury: maximum 1.8 mg/kg

Although the exposure for operators to PROTECT-US™ Mineral Snail and Slug Killer is below

the LOC it is considered appropriate to maintain the PPE control. This must appear on the

product label.

PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron can only be applied using

ground-based methods that ensure that pellets are not released into the aquatic environment.

This must appear on the product label.

The maximum application rate is 5 g formulation/m2.

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Appendix A: Identity of the active ingredient, use pattern and mode of action

Identity of the active ingredient and metabolites

This application under Part 5 of the HSNO Act 1996 considers the active ingredient elemental iron in

combination with ethylenediaminetetraacetic acid (EDTA), general data are provided in Table 2.

Table 2: Identification of the active ingredient

Name Elemental iron

Molecular formula Fe

CAS Number 7439-89-6

Molecular weight 55.85 g/mol

Purity 99.1%

Significant

impurities/additives: impurity

limit

(concentration calculated

from formulation)

Arsenic: 18 mg/kg (actual concentration: 0.7 mg/kg)

Cadmium: 1.8 mg/kg (actual concentration: not determined)

Lead: 36 mg/kg (actual concentration: 1.2 mg/kg)

Mercury: 1.8 mg/kg (actual concentration: 0.3 mg/kg)

Chromium: 90 mg/kg (actual concentration: not determined)

Use pattern and mode of action

Use pattern

The applicant seeks approval for the use of elemental iron with a chelate as a snail bait for the control of

snails in the home garden.

The substance is a granule which will be spread onto the soil where snail activity is problematic. The

applicant seeks to have the substance approved for ground-based application.

Application will be at the rate of 50 kg of product per hectare which is equivalent to 0.5 kg of active ingredient

per hectare. More details on the intended uses for PROTECT US™ Mineral Snail and Slug Killer with

Elemental Iron are given in Table 3.

Mode of action

The chelator is capable of binding all kinds of metals forming metal chelates. This chelate increases the

solubility of the metal. The chelator cannot bind the elemental iron since it can only bind metal ions.

The elemental iron is converted to Fe(III) which in turn is converted into the more reactive Fe(II) inside the

snail after which it forms the iron-chelator complex. The Fe(III) is able to compete with oxygen in binding to

the haemocyanin active site. This will cause the snail to stop feeding and die.

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Table 3: List of intended uses for PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron

Crop and/or

situation (a)

Use

pattern

(b)

Pests or

group of

pests

controlled

(c)

Mixture Application Application rate per treatment

Remarks

(l) Type

(d-f)

Conc of ai

(g)

Method

and

kind

(h-i)

Growth

stage &

season

(j)

Number

Min max

(k)

Interval

between

applications –

days (minimum)

kg ai/hL

min max

water

L/ha

min

max

kg ai/ha

max

Any plant

affected by

snails or slugs

F Snails and

slugs GR 10 g/kg Scattering All stages

Until no

longer

required

When

consumed, after

heavy rain or at

least biweekly

Not

applicable

(NA)

NA

5 g

formulation

/m2 (50 kg

formulation

/ha)1

None

a Where relevant, the use situation should be described (eg fumigation of soil) b Outdoor or field use (F), glasshouse application (G) or indoor application (I). c eg biting and sucking insects, soil borne insects, foliar fungi, weeds d eg wettable powder (WP), emulsifiable concentrate (EC), granule (GR) e CropLife international, 2008. Technical Monograph no 2, 6th edition. Catalogue of pesticide formulation types and international coding system f All abbreviations used must be explained g g/kg or g/l or others h Method, eg high volume spraying, low volume spraying, spreading, dusting, drench, aerial, etc , i Kind, eg overall, broadcast, aerial spraying, row, individual plant, between the plant - type of equipment used must be indicated. If spraying include droplet size spectrum j growth stage at last treatment (BBCH Monograph, Growth Stages of Plants, 1997, Blackwell (ISBN 3-8263-3152-4) , including where relevant, information on season at time of application k Indicate the minimum and maximum number of application possible under practical conditions of use l Remarks may include: Extent of use/economic importance/restrictions

1 Please note that the application form indicates a different application rate. However, this does not correspond with the label which indicates an application rate of 5 g product/m2 corresponding to 50 kg formulation/ha this results in 0.5 kg iron/ha (1% of formulation). The staff decided to evaluate the risks of the substance using the application rate mentioned on the label since this corresponds with the PEC calculated in the soil microbial toxicity study.

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Appendix B: Hazard classification of the substance

The hazard classifications of PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron are listed in

Table 4.

Table 4: Applicant and EPA Staff classifications for PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron

Hazard

Class/Subclass

Mixture

classification by:

Method of

classification

Remarks

Applicant EPA

Staff

Mix

ture

data

Read

acro

ss

Mix

ture

rule

s1

Class 1 Explosiveness NA NA

No data on several

components (6% of

mixture).

No UN packaging number

was provided by the

applicant, indicating that a

risk is unlikely.

Class 2, 3 & 4

Flammability NA

No / NA

/ND

No: Based on SDS

NA: Not applicable due to

physical form of the

substance.

ND: insufficient information

available for all sub

classifications

Class 5

Oxidisers/Organic

Peroxides

NA ND & NA

NA: some classifications

do not apply due to the

physical state of the

substance

No data on several

components (14.6% of

mixture).

Subclass 8.1 Metallic

corrosiveness NA ND

No data on several

components

Subclass 6.1 Acute

toxicity (oral) NA No LD50 > 2000 mg/kg bw

Subclass 6.1Acute

toxicity (dermal) NA No LD50 > 2000 mg/kg bw

Subclass 6.1 Acute

toxicity (inhalation) NA NA

Physical from, granules,

10mm (±2mm) length

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Hazard

Class/Subclass

Mixture

classification by:

Method of

classification

Remarks

Applicant EPA

Staff

Mix

ture

data

Read

acro

ss

Mix

ture

rule

s1

Subclass 6.1 Aspiration

hazard NA NA

Physical from, granules,

10mm (±2mm) length

Subclass 6.3/8.2 Skin

irritancy/corrosion NA No

Subclass 6.4/8.3 Eye

irritancy/corrosion 6.4A No

Unclear why classified by

the applicant, likely

different interpretation of

the study results.

Subclass 6.5A

Respiratory sensitisation NA ND

No data on any of the

components

No suitable studies are

available to assess this

endpoint

Subclass 6.5B Contact

sensitisation NA 6.5B

55% allergic response in

the animal study

Subclass 6.6

Mutagenicity NA ND

No data on component A-

C, E, G, I

Subclass 6.7

Carcinogenicity NA ND

No data on component A-

C, E, G, I

Subclass 6.8

Reproductive/

developmental toxicity

NA ND No data on component B,

C, E, I

Subclass 6.8

Reproductive/

developmental toxicity

(via lactation)

NA ND No data on any of the

components

Subclass 6.9 Target

organ systemic toxicity

(oral)

NA ND

No data on any of the

components except

component H

Subclass 6.9 Target


(dermal)

NA ND No data on any of the

components

Subclass 6.9 Target


(inhalation)

NA NA Physical from, granules,

10mm (±2mm) length

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November 2018

Hazard

Class/Subclass

Mixture

classification by:

Method of

classification

Remarks

Applicant EPA

Staff

Mix

ture

data

Read

acro

ss

Mix

ture

rule

s1

Subclass 9.1 Aquatic

ecotoxicity (Overall) NA 9.1B

Based on the toxicity to

Daphnia.


ecotoxicity (Fish) NA ND

The provided studies were

considered of insufficient

quality to classify the

substance


ecotoxicity (Crustacean) NA 9.1B




substance.

The EC50 for daphnids is

26.9 mg/l, please note that

this is based on a nominal

concentration and no

analytical confirmation has

been presented. The actual

exposure is lower than the

nominal concentration. As

a result, the presented

EC50 underestimates the

actual toxicity. Therefore,

by following the

precautionary approach,

the 9.1B classification is

assigned.


ecotoxicity (Algal) NA ND




substance

Subclass 9.2 Soil

ecotoxicity NA No

EC50 earthworm > 100

mg/kg soil

Subclass 9.3 Terrestrial

vertebrate ecotoxicity NA No

LC50 birds > 2000 mg/kg

bw

Subclass 9.4 Terrestrial

invertebrate ecotoxicity NA ND

No studies were provided

by the applicant.

No data on components A,

C-I.

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November 2018

Hazard

Class/Subclass

Mixture

classification by:

Method of

classification

Remarks

Applicant EPA

Staff

Mix

ture

data

Read

acro

ss

Mix

ture

rule

s1

The physical form of the

substance limits the

exposure of pollinators to

the substance

1 Use of mixture rules may not adequately take into account interactions between different components in some

circumstances and must be considered of lower reliability than substance (formulation) data.

NA: Not Applicable. For instance testing for a specific endpoint may be omitted if it is technically not possible to conduct

the study as a consequence of the properties of the substance: eg very volatile, highly reactive or unstable substances

cannot be used, mixing of the substance with water may cause danger of fire or explosion or the radio-labelling of the

substance required in certain studies may not be possible.

ND: Not determined. See comments for full explanation.

No: Not classified based on actual relevant data available for the substance or all of its components. The data are

conclusive and indicate the threshold for classification is not triggered.

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Appendix C: Physico-chemical properties of PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron

The physico-chemical properties of PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron are

listed in Table 5.

Table 5: Physical and chemical properties of PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron

Property Reference

Colour Dark brown to black SDS

Odour Weak, food SDS

Physical state Free-flowing extruded granules Application form

Size 10 mm (±2 mm) SDS

Flash point Not flammable SDS

Vapour pressure Negligible at room temperature SDS

Water Solubility (20°C) Mostly insoluble SDS

Storage stability (14 days 54°C) Stable

Simms (2012). Molluscicide granular

bait – Stability Report Test Method

and Validation. LabTec Scientific

and Technical Services, New

Zealand. Report 5793

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Appendix D: Environmental fate

Summary

No studies on the environmental fate of the substance have been provided by the applicant. However, most

of the components are likely to be biodegradable. Components with more complex molecular structures like

the chelating agent and components G and I are likely to take longer to degrade.

Elemental iron is likely to be transferred into Fe (II) after weathering. The Fe (II) will be transferred into Fe

(III) which is likely to be taken up by plants as a nutrient.

Based on the composition of the substance, no long-term contamination of the environment is expected,

however, if the substance is used several times a year, this will increase the period of time that the

substances are present in the soil.

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November 2018

Appendix E: Mammalian toxicology

Executive summaries and list of endpoints for PROTECT-US™ Mineral Snail

and Slug Killer with Elemental Iron

Unless otherwise noted, all studies were conducted according to Good Laboratory Practice (GLP) and were

fully compliant with the requirements of the international test guidelines followed. The mammalian toxicology

data for PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron are summarised in Table 6.

Table 6: Summary of mammalian toxicology data for PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron

Endpoint

(Test Guideline) Result HSNO Classification

Acute oral toxicity

[Organisation for Economic

Cooperation and Development

(OECD) Technical Guidance (TG)

420]

>2000 mg/kg bw

[no effects observed] No

Acute dermal toxicity

(OECD TG 402)

>2000 mg/kg bw

[no effects observed] No

Skin irritation/corrosion

(OECD TG 404)

Mildly irritating

[Erythema: 1.22 < 1.5,

Oedema: 0.00 < 1.5]

No

Eye irritation/corrosion

(OECD TG 405)

Mildly irritating

[Cornea: 0.00 < 1; Iris: 0.00

< 1; conjunctival redness:

1.22 < 2; chemosis: 0.33 < 2]

No

Contact sensitisation

(OECD TG 406)

Positive reaction: 55% of the

animals >30% positive

reactions

6.5B

General conclusion about mammalian toxicology of PROTECT-US™ Mineral

Snail and Slug Killer with Elemental Iron

Acute toxicity, irritation and sensitisation

PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron is of relatively low acute toxicity by the oral

and dermal routes and should not be classified. PROTECT-US™ Mineral Snail and Slug Killer with

Elemental Iron is not a skin or eye irritant and should not be classified. PROTECT-US™ Mineral Snail and

Slug Killer was shown to be a contact sensitiser and should be classified 6.5B.

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November 2018

Appendix F: Ecotoxicity

Executive summaries and list of endpoints

Unless otherwise noted, all studies were conducted according to GLP and were fully compliant with all

requirements of the standard international test methods used. Studies were provided by the applicant. It

should be noted that the test substance name in the tests is different from the formulation. The staff have

requested the applicant to confirm that the test substance is the same substance as the substance for which

approval is sought. The applicant confirmed it is the same substance.

Table 7 contains the acute aquatic toxicity test results for the formulated product.

20


November 2018

Table 7: Summary of aquatic toxicity data for PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron

Test species Test type and duration

Fish Acute

Rainbow trout. Oncorhynchus mykiss 96 hr LC50 Endpoint not determined study deemed unreliable.

Effects were observed indicating toxicity

Chronic

Early Life Stage test Not provided

Invertebrates Acute

Daphnia magna 48 hr EC50 Endpoint not determined study deemed unreliable, toxicity was observed

Chronic

Reproduction Not provided

Algae and aquatic macrophytes

Green alga, Pseudokirschneriella subcapitata 72 hr ErC50 Endpoint not determined study deemed unreliable

21


November 2018

Aquatic toxicity and exposure assessment

The staff determined that the information provided by the studies was considered insufficient to allow precise

classification. The main issue was related to the test substance preparation in combination with the lack of

analytical confirmation of the exposure concentrations.

The test substance preparation did not allow for the maximum soluble concentration in test medium to be

reached. This means that a lack of response does not necessarily mean that no effects will be observed at a

higher concentration. It is expected that a higher concentration could be reached if the appropriate OECD

guidelines were followed. As a result the presented LC50 and EC50 are not based on the actual exposure

concentrations and therefore underestimate actual toxicity.

If the actual exposure concentration could be estimated using analytical confirmation of the concentration of

one of the components, then more accurate estimation could have been allowed. However, in the fish and

algae study, the results would still not allow a thorough assessment of the toxicity because the maximum

soluble concentration was not reached. The EC/LC50 could still be below the maximum soluble

concentration. Therefore, the staff consider that insufficient information regarding the acute aquatic toxicity of

the substance is available for a comprehensive assessment.

It should be noted that adverse effects to daphnids were observed and that an EC50 below 100 mg/l was

calculated. This indicates that the substance has an ecotoxic potential. Due to the test substance preparation

and the absence of analytical confirmation of the actual concentration, the staff were unable to determine the

exact toxicity. The actual toxicity is below the presented EC50 value of 26.9 mg/l. It has not been established

which component drives the toxicity of the mixture. Due to limited information concerning the actual toxicity

and information on environmental fate of the components of the formulation, Risk Quotients (RQs) could not

be calculated. However, a potential for effects in the aquatic environment has been identified.

No data on the chronic toxicity of the substance have been provided by the applicant. Since acute risks for

crustaceans have been identified, it is likely that chronic effects could be observed if sufficiently high

concentrations are reached for a long period of time.

Based on the physical form of the formulation, the staff consider that the main risk to the aquatic

environment will be the result of the granules being released into the aquatic environment. It is expected that

when applied to the soil the runoff into the aquatic environment will be limited due to the granular form and it

is expected that most components will slowly degrade in the soil prior to runoff.

However, to protect the aquatic environment the following section 77A control is proposed:

PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron can only be applied using ground-

based methods which ensure that pellets are not released into the aquatic environment.

This control is formulated to prevent accidental release into the aquatic environment during application.

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November 2018

Soil toxicity

Table 8 contains the acute and chronic soil toxicity test results for the formulated product.

23


November 2018

Table 8: Summary of soil toxicity data for PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron


Earthworm Acute

Earthworm, Eisenia fetida Acute, 14-day LC50 1000 mg/kg soil

Chronic

Reproduction Not provided

Terrestrial plants

Six dicotyledon and four

monocotyledon crop species

Vegetative vigour, 21 days

Foliar application to seedling plants

Not provided

Seedling emergence, 21 days

Application to soil surface

Not provided

Soil microbial function

Soil microflora Nitrogen mineralisation, 28 days No effects up to 333.5 mg/kg soil

Carbon mineralisation, 28 days No effects up to 333.5 mg/kg soil

24


November 2018

Soil toxicity and exposure assessment

The formulated product does not trigger a 9.2 classification based on the EC50 value for earthworms.

The Predicted Environmental Concentration (PEC) in the soil after one application is calculated using the

FOCUS (1997) document “soil persistence models and EU registration” (FOCUS 1997). Soil concentrations

of the formulation are calculated by assuming the deposition would mix into the top 5 cm of soil, and this soil

would have a bulk density of 1,500 kg/m3, ie the deposition expressed in mg/m2 would mix into 75 kg of soil.

The following equation is used:

𝑃𝐸𝐶 𝑠𝑖𝑛𝑔𝑙𝑒 𝑎𝑝𝑝𝑙𝑖𝑐𝑎𝑡𝑖𝑜𝑛 (𝑚𝑔/𝑘𝑔 𝑠𝑜𝑖𝑙) =𝑎𝑝𝑝𝑙𝑖𝑐𝑎𝑡𝑖𝑜𝑛 𝑟𝑎𝑡𝑒 (𝑘𝑔/ℎ𝑎) × 100

75 𝑘𝑔 𝑜𝑓 𝑠𝑜𝑖𝑙

The PEC calculated for the soil after a single application for the formulation is 66.67 mg/kg soil. It should be

noted that multiple applications are requested and that the actual exposure concentration in the soil might be

higher.

Earthworms

The estimate LC50 is ~1000 mg/kg dw (dry weight) soil, which when divided by the PEC of a single

application result in a Toxicity Exposure Ratio (TER) of ~15 which indicates that the acute risks are below

the LOC (TER < 10). Therefore, acute risks for earthworms are below the LOC.

No chronic data have been provided by the applicant. However, an estimate could be made using the acute

No Observed Effect Concentration (NOEC). There is no LOC established for acute NOEC values. However,

it can be evaluated in which range this value should be.

Since the acute NOEC is considered more protective than an EC50, the LOC established for te acute NOEC

value will be lower than 10 (which is the LOC for the less conservative, acute, EC50 values), .

Furthermore, the LOC established for the acute NOEC value should be higher than 5 since this corresponds

to the LOC for a chronic, more conservative NOEC.

As such, the LOC for an acute NOEC should be between 5 and 10.

A TER below the chosen value within this range indicates that the risk is above the LOC, a TER above these

values indicates the risk is below the LOC.

The acute NOEC was determined to be 320 mg/kg since no effects on mobility were observed at this

concentration (5% mortality) while significant effects on mobility as well as mortality were observed at higher

concentrations. At the higher concentrations, earthworms were observed dead or less mobile, no healthy

earthworms were observed at a concentration of 560 mg/kg and higher. Both observation endpoints

(mortality and mobility) are likely to influence the reproductive output of the populations and therefore the

NOEC of the reproduction test is expected to be lower than these concentrations. Therefore, the acute

NOEC of 320 mg/l is considered a non-conservative estimate of a chronic NOEC. The TER calculated using

25


November 2018

the acute NOEC of 320 mg/kg is 4.8. Therefore, chronic risks for earthworms are expected to be above the

LOC after one application.

Additional section 77A controls were considered inappropriate to manage these risks since this would

prevent the intended use of the formulation. The staff consider it inappropriate to advertise the substance as

safe for soil organisms.

Microorganisms

Two studies with soil microorganisms have been provided, one performed at the calculated PEC and another

at five times the calculated PEC. The last concentration can be considered a worst-case scenario after five

applications assuming no biodegradation has taken place between the first and last applications.

The studies evaluating carbon and nitrogen transformation both indicate that there will be no long-term

impact at the highest concentration (being five times the PEC calculated after a single application).

Therefore, the risks to soil microorganisms are considered below the LOC.

Plants

No studies assessing the toxicity of the formulation to plants have been provided. Considering the use

pattern, the staff consider an effect on plants highly unlikely. If effects were observed during the efficacy

testing, the product would not have been marketed as a snail bait around plants.

Terrestrial vertebrate toxicity

For effects on terrestrial vertebrates other than birds, refer to the mammalian toxicity section (Appendix E).

Table 9 contains the acute avian toxicity test results for PROTECT-US™ Mineral Snail and Slug Killer with

Elemental Iron.

Table 9: Summary of terrestrial vertebrate toxicity data for PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron


Bobwhite quail,

Colinus virginianus

Acute

Acute oral LD50 >2000 mg/kg bw

8-day dietary LC50 Not provided

Chronic

Reproductive 1 generation, 22 weeks

NOEC Not provided

26


November 2018

Vertebrate toxicity and exposure assessment

The acute toxicity to birds does not trigger a 9.3 classification.

Birds can be exposed to the formulation when mistaking the bait for food, grit and accidental ingestion when

feeding in the soil and contaminated water. The main pathways for exposure are considered the ingestion of

the bait as grit and food.

Birds might be interested in the granules as a food source since one of the carriers (Component B) has

some calorific value. Birds consume grit particles to meet their mineral requirements as well as using grit

particles for mastication. Granivorous birds actively select grit particles while non-granivorous birds usually

consume grit particles “accidentally” with soil.

The following assessment is based on the EFSA Risk Assessment for birds and mammals (EFSA 2009) and

uses formulation data and input parameters rather than information from the active ingredient. Risk

estimations will be the same. It should be noted that the size of the bait granules (10 mm ±2 mm) is slightly

above the limits described for the model (6 mm).

Ingestion as grit

The acute daily granule dose due to ingestion of granules by birds seeking grit is calculated using the

following equation:

𝐴𝑐𝑢𝑡𝑒 𝐷𝑎𝑖𝑙𝑦 𝐺𝑟𝑎𝑛𝑢𝑙𝑒 𝐷𝑜𝑠𝑒 = 2453 × 𝐺𝑟𝑎𝑛𝑢𝑙𝑒𝑑𝑒𝑛𝑠𝑖𝑡𝑦

71 + 𝐺𝑟𝑎𝑛𝑢𝑙𝑒𝑑𝑒𝑛𝑠𝑖𝑡𝑦

× 𝐺𝑟𝑎𝑛𝑢𝑙𝑒 𝑤𝑒𝑖𝑔ℎ𝑡

Granuledensity should if possible be based on actual field incorporation efficiencies. However, such data are

not available. The applicant has indicated that the granule loading is 318 per m2. With a loading of 5 gram

per m2 the weight per granule is calculated to be 15.7 mg. This results in a dose of 31,530 mg formulation in

case birds’ only source of grit particles are the granules. The value of 71 reflects the number of soil particles

at the soil surface in the size range of 6 to 8 mm at the soil surface, the actual number of soil particles in the

size range of the bait granules is assumed to be lower.

The calculated acute daily grit dose is above the maximum dose which was tested and no effects were

observed. As a result, the effects could not be fully excluded at the higher daily dose. It should be noted that

this assessment is highly conservative and assumes that the granules are the only source of grit particles

which is considered unlikely. Based on the size of the bait granules, it is concluded that the risks to small

birds are negligible since preferred grit size is expected to be much smaller [<0.6 mm for free-range house

sparrows and robins; (Gionfriddo and Best 1995), (Best and Fischer 1992)]. Black and brown granules and

granules consisting of “non-grit” carriers (eg Component B) are generally not preferred over more common

components (eg silica). The baits containing “non-grit” carriers are generally consumed to a lesser extent

than coloured silica based granules, further reducing the risks. Based on this rationale, it is considered that

27


November 2018

the baits will not be preferred over naturally occurring grit particles. Although the risks cannot be fully

quantified, it is estimated that the risks to birds due to ingestion of the bait granules as grit is low.

Ingestion as food

The daily granule dose due to ingestion of granules by birds as food is calculated using the following

equation:

𝐴𝑐𝑢𝑡𝑒 𝐷𝑎𝑖𝑙𝑦 𝐺𝑟𝑎𝑛𝑢𝑙𝑒 𝐷𝑜𝑠𝑒 = 620 × 𝐺𝑟𝑎𝑛𝑢𝑙𝑒𝑑𝑒𝑛𝑠𝑖𝑡𝑦

100 + 𝐺𝑟𝑎𝑛𝑢𝑙𝑒𝑑𝑒𝑛𝑠𝑖𝑡𝑦

× 𝐺𝑟𝑎𝑛𝑢𝑙𝑒 𝑤𝑒𝑖𝑔ℎ𝑡

Based on this equation, which assumes a small granivorous bird, the acute daily granule dose is 7416 mg

formulation per kg bw. This is above the maximum dose which was tested and thus effects could not be fully

excluded at higher concentrations. It is generally assumed that the seeds consumed by small birds are 1 mm

in diameter. The size of the bait granules are 10 mm ± 2 mm and therefore it is unlikely that the diet of small

birds will consist of a great portion of bait granules. Therefore, the risks to small birds are considered

negligible. It should be noted that the assessment is highly conservative and assumes that the granules are

the only source of food which is considered unlikely. It is likely that in the area where the bait granules are

applied, a significant amount of other naturally occurring familiar food (eg seedlings, fruit, insects) is

available for the birds therefore limiting the intake of granules as food. Although the risks cannot be fully

quantified, it is estimated that the risks to birds due to ingestion of the bait granules as food is low.

Long-term effects

No information regarding the chronic toxicity of the substance to birds has been provided.

Ecotoxicity to bees and other terrestrial invertebrates

No information regarding the toxicity to bees has been provided by the applicant. However, based on the use

pattern, exposure to the substance is considered unlikely. Therefore, the risks to bees are considered to be

below the LOC.

Bioaccumulation potential of the substance

It has been determined, based on information in the internal EPA database and external sources, that

components B, C, D, F and H have a bioaccumulative potential. No information was received or available on

components E and I, however, bioaccumulation of these components is unlikely.

Component G, a common vitamin, is known to accumulate in fat tissue. It is likely that these reserves will be

used in time of shortage.

Summary of the environmental risk assessment

Aquatic toxicity

Due to the limited information on the actual exposure during the aquatic studies, not all provided data could

be used for the risk assessment. During the studies, toxicity of the substance to aquatic crustaceans has

28


November 2018

been demonstrated at concentrations below the solubility level in the test medium. Therefore, the staff

consider there are potentially acute risks for the aquatic environment, however, these risks can be managed

with prescribed and section 77A controls.

No information on chronic toxicity has been provided and therefore risks could not be estimated.

Soil toxicity

Acute risks to earthworms were identified. No information on chronic toxicity has been provided and

therefore risks could not be estimated. Additional section 77A controls were considered inappropriate to

manage these risks since it would prevent the intended use of the formulation.

No risks to soil micro-organisms were identified. Although no studies on the toxicity to plants were presented,

based on the intended use of the product (around plants), an effect is considered unlikely.

Toxicity to birds

The acute risks to birds are considered low.

No information on chronic toxicity has been provided and therefore risks could not be estimated.

Risks to pollinators and non-target arthropods

No information regarding the toxicity to pollinators has been provided by the applicant. However, based on

the use pattern, exposure to the substance is considered unlikely.

Bioaccumulation

One component can accumulate in fat however, risks are considered below the LOC.

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November 2018

Appendix G: Human health risk assessment

Quantitative risk assessment

The operator and bystander exposure assessment is based on UK POEM for Amateur (Home garden)

model.

The UK POEM assumes no PPE is used during application. Levels of operator exposure for non-

professionals when using dust formulations packaged in puffer packs and granule formulations packaged in

shaker packs are based on an approach taken in the EU for biocides.

At present, there is no available exposure model for predicting exposure for amateur users applying granules

(ie via a shaker pack). In the absence of specific exposure data for granule products, the puffer pack model

for users applying dustable powder formulations via puffer packs could be used as surrogate data for this

exposure scenario.

For products applied as granules, there is a potential for these to be ingested by children who may enter

treated areas soon after the granules have been applied. The UK Chemicals Regulation Directorate (CRD)

Exposure Guidance for Amateur (Home Garden) Pesticides (CRD 2016) includes an approach for

calculating children’s exposure to granule applications.

To assess risks, the predicted systemic exposures to the active ingredient are compared with an AOEL for

the active ingredient and a RQ is calculated. RQ values greater than one indicate that predicted exposures

are greater than the AOEL and potentially of concern. RQ values below one indicate that predicted

exposures are less than the AOEL and are not expected to result in adverse effects.

Input values for the human health risk assessment

Reference doses for iron sulfate established by EFSA (EFSA 2012) are summarised in Table 10.

Medical data indicate that health effects can occur with intakes from >20 mg Fe/kg bw onwards, resulting in

symptoms such as vomiting, gastrointestinal bleeding, diarrhoea and liver alterations; chronic intoxications

(leading to liver and spleen haemosiderosis, liver cirrhosis and renal failure) can occur with repeated

exposures well above the therapeutic dose for pregnant women (50 mg Fe/day), which corresponds to an

Acceptable Daily Intake (ADI) of 0.8 mg Fe/kg bw/day. Taking into account a 50 % oral bioavailability, an

AOEL of 0.4 mg Fe/kg bw/day can be established. An Acute Reference Dose (ARfD) was not deemed

necessary.

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November 2018

Table 10: Reference doses established by overseas regulators

Available

international

Reference doses

Key systemic

effect

No

Observed

Adverse

Effect

Level

(NOAEL)

Uncertainty

factors AOEL

Staff

modifications Remarks

AOEL

(EFSA 2012)

Derived from

human

intakes,

supported by

teratogenicity

study in mice

and rats

380 mg/kg

bw/day

FeSO4

100 0.4 Fe/kg

bw/day None

50% oral

Bioavailabilit

y

Other input values for the exposure assessment are summarised in Table 11.

The applicant has indicated that the granule loading is 318 per m2. With a loading of 5 gram per m2 the

weight per granule is calculated to be 15.7 mg.

No dermal absorption data were provided for PROTECT-US™ Mineral Snail and Slug Killer so default values

have been used in the risk assessment. For pesticides, default dermal absorption values proposed by

Aggarwal et al. (Aggarwal, Fisher et al. 2015), which are based on a review of a robust data set of 295 in

vitro human dermal absorption studies with over 150 agrochemical active ingredients have been adopted.

These default values are 2% for solid concentrates, 6% for liquid concentrates and 30% for spray dilutions.

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November 2018

Table 11: Input values for human exposure modelling

Active

ingredient

Physical

form

Concentration

of each active

ingredient

(%)

Maximum

application rate

(for each active

ingredient, for

each method of

application)

g ai/ha

Dermal absorption (%) AOEL

mg/kg bw/day Concentrate Spray

Elemental iron Granule 1 50 2 NA 0.4

Operator exposure assessment

The results of the operator exposure assessment are shown in Table 12.

Table 12: Output of operator mixing, loading and application exposure assessment for elemental iron

Exposure Scenario elemental iron Estimated operator

exposure (mg/day)

Exposure

Duration

(mins)

Dermal 0.0305 30

Inhalation 0.0091 30

Total 0.0395 30

OPERATOR EXPOSURE (mg/kg bw/day) 0.0007

AOEL 0.4

RQ 0.002

Predicted operator exposures to elemental iron are below the AOEL for each use pattern, even without the

use of PPE.

Although the quantitative risk assessment indicates that PPE is not required to ensure that exposures are

below the AOEL, this risk assessment does not take account of site of contact effects such as irritation and

sensitisation. An additional label control is proposed to alert user to use gloves when handling the substance

to mitigate the risks from the irritation and sensitisation properties of PROTECT-US™ Mineral Snail and Slug

Killer.

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November 2018

Quantitative bystander risk assessment

The AOEL calculated for the operator exposure assessments for the bystander assessment has been used,

as the use of an oral Chronic Reference Dose (CRfD) is usually likely to be over-precautionary.

Exposure to this product is calculated from the ingestion of soil by children, using the product label

application rate recommendations.

Separate calculations have been performed for infants and toddlers. Infants are considered to be 6 to 12

months old, both male and female, with a mean body weight of 9 kg. Toddlers are considered to be 18

months to 4 years old, both male and female, with a mean body weight of 15 kg.

Active ingredient concentration in soil = 5 g/m2 (rate of application for product) × 1% elemental iron

(concentration of ai in product) × 100%/cm (100% of ai in top 1cm of soil) ×106 μg/g × m2/10000 cm2

(conversion factor) × 0.67 cm3/g (soil density) = 3.35 μg Fe /g soil.

The ingestion of granules may be higher for children with pica behaviour. Pica is an eating disorder typically

defined as the persistent eating of non-nutritive substances. Pica is observed most frequently in children and

individuals with pica have been reported to mouth and/or ingest a wide variety of non-food substances which

include clay, sand, stones and pebbles. Exposures of children with pica behaviour is not considered for this

exposure scenario.

Exposure to the active ingredient via ingestion of soil is calculated for a child (non pica) ingesting 200 mg soil

ingested per day (mean value). This value is taken from the United States Environmental Protection

Agency’s (US-EPA) Exposure Factors Handbook (US-EPA 2011).

3.35 μg Fe /g soil × 0.2 g/day (average daily soil ingestion rate) = 0.00067 mg/child/day. For an infant of 9kg

bw intake = 7.44444E-05 mg/kg bw/day. For a toddler of 15kg bw intake = 4.46667E-05 mg/kg bw/day

The results of the bystander exposure assessment are summarised in Table 13.

Table 13: Output of the bystander exposure assessment for elemental iron

Estimated exposure

(mg/kg bw/day)

AOEL

(mg/kg bw/day) RQ

Estimated exposure of 9 kg infant exposed

through contact to surfaces 0 m from an

application area

7.44444E-05 0.4 0.0002

Estimated exposure of 15 kg toddler

exposed through contact to surfaces 0 m

from an application area

4.46667E-05 0.4 0.0001

The estimated bystander exposure to elemental iron is below the AOEL.

Accidental oral exposure of children

Iron poisoning is a common toxicological emergency in young children. Contributing factors include the

availability of iron tablets and their candy-like appearance. The potential severity of iron poisoning is based

33


November 2018

on the amount of elemental iron ingested. The amount of elemental iron ingested must be calculated based

on the number of tablets ingested and the percentage of elemental iron in the salt.

The lethal dose of iron for a 2 year old child is 3 g, and 1 g leads to severe poisoning. Accidental iron

poisoning occurs in children consuming 10-50 iron tablets in the form of ferrous sulfate, over a period of a

few hours [See British National Foundation reference, (BNF 1995)].

Children may show signs of toxicity with ingestions of 10-20 mg/kg of elemental iron. Serious toxicity is likely

with ingestions of more than 60 mg/kg. Iron exerts both local and systemic effects and is corrosive to the

gastrointestinal mucosa and can affect the heart, lungs, and liver. Excess free iron is a mitochondrial toxin

that leads to derangements in energy metabolism (Abhilash, Arul et al. 2013).

Iron overdose is the most common cause of poisoning death in children. Accidental ingestion is common

because iron-containing compounds are readily available and brightly coloured (Anderson 1994).

Another study conducted from 1983-1990, reported in “Pediatrics”, reported that 53 children younger than 6

died as a direct result of unintentional ingestion. Iron supplements caused the death of 16 of these children.

Iron supplements, causing 30.2% of fatalities, are the single most frequent cause of paediatric

pharmaceutical unintentional fatalities (Litovitz and Manoguerra 1992).

The average granule weight is 15.7 mg and the size is 10mm (±2mm) length. An average granule contains

0.157 mg of elemental iron. The certificate of analysis listed the dust content at <0.01, and the particle size

distribution as follows; >2000µm (93.06%), 1000-2000µm (6.72%), 500-1000µm (0.01%), 250-500µm

(0.02%). These values were used for the risk assessment.

Separate calculations have been performed for infants and toddlers.

No ARfD or AAOEL (Acute Acceptable Operator Exposure Level) is set by EFSA (EFSA 2012), or any other

overseas regulator. Furthermore, the applicant has not provided data to the EPA staff to establish the ARfD

or the AAOEL. Due to the lack of an ARfD, the AOEL is used to assess the reverse reference scenario for

children.

𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑔𝑟𝑎𝑛𝑢𝑙𝑒𝑠 =𝐴𝑂𝐸𝐿 (𝑚𝑔 𝑘𝑔⁄ 𝑏𝑤 𝑑𝑎𝑦⁄ ) × 𝐵𝑜𝑑𝑦 𝑊𝑒𝑖𝑔ℎ𝑡 (𝑘𝑔 𝑏𝑤)

𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑜𝑓 𝑎. 𝑖. (𝑚𝑔 𝑔𝑟𝑎𝑛𝑢𝑙𝑒⁄ )

Table 14: Output accidental exposure children

Active ingredient

(mg/granule)

AOEL

(mg/kg bw/day)

Estimated number

of granules for the

reverse reference

scenario for an

infant

Estimated number of

granules for the

reverse reference

scenario for a toddler

Elemental iron 0.157 0.4 23 38

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November 2018

Outcomes of the accidental exposure assessment

The staff consider the health risk from consumption of granules by an infant or toddler in the field after

application to be low. An infant (9kg) would need to find and consume 23 granules, within a short period of

time, to reach the reference dose of iron. The reference dose is a value which they should not exceed on a

daily basis. Therefore the likelihood of a risk for the dispersed granules in a garden is considered low.

The more significant risk to the toddler is presented by the product in the package from which they may more

easily get a higher dose. The prescribed controls for class 6.5B substance require the label to state “Keep

out of reach of children”, therefore the risk of ingestion from the package is considered mitigated with this

prescribed control. The EPA staff note that although the product does not trigger 6.1 (oral) toxicity, the draft

label submitted has warning and precautionary statements relating to access by young children.

Conclusions of the human health risk assessment

Predicted operator exposures to elemental iron are below the AOEL for the use pattern, even without the use

of PPE.

Although the quantitative risk assessment indicates that PPE is not required to ensure that exposures are

below the AOEL, this risk assessment does not take account of site of contact effects such as irritation and

sensitisation. An additional label control is proposed to alert the user to use gloves when handling the

substance to mitigate the risks from the irritation and sensitisation properties of PROTECT-US™ Mineral

Snail and Slug Killer.

Exposure to PROTECT-US™ Mineral Snail and Slug Killer is calculated from the ingestion of soil by children,

using the product label application rate recommendations. Estimated bystander exposure to elemental iron is

below the AOEL.

The staff consider the health risk from accidental consumption of granules by an infant or toddler in the field

after application to be low. An infant (9 kg) would need to find and consume 23 granules within a short period

of time to reach the reference dose of iron.

The more significant risk to the toddler is presented by the product in the package from which they may more

easily get a higher dose. The prescribed controls for class 6.5B substance require the label to state “Keep

out of reach of children”, therefore the risk of ingestion from the package is considered mitigated with this

control.

35


November 2018

Appendix H: Proposed controls

EPA Notice controls

The Labelling, Safety Data Sheet (SDS), Packaging, Disposal and HPC Part 1, Part 3, Part 4A and Part 4B

Notices apply to PROTECT-US™ Mineral Snail and Slug Killer.

The name and concentration of the following components need to be specified on the label and SDS (Table

15).

Table 15: List of components requiring identification

Label SDS

Component G, H (6.5B) Component G, H (6.5B)

The following label statements are required by clause 18 of the Labelling Notice because the substance is a

consumer product. The label must include the following statements:

“Read label before use”

“Keep out of reach of children”

“If medical advice is needed, have the product container or label at hand”.

The following label statements are required by clauses 19 and 20 of the Labelling Notice because the

substance has a class 9 classification. The label must include the following statements:

“Take all reasonable steps to ensure that the substance does not cause any significant adverse

effects to the environment beyond the application area.”

“Do not apply directly into or onto water.”

Exposure thresholds

Exposure thresholds proposed for elemental iron are shown in Table 16. ADE and PDE values are not

controls as such, but are health-based exposure guidance values which can be used to inform risk

assessments as well as the setting of controls, such as Maximum Residue Levels (MRLs) under the

Agricultural Compounds and Veterinary Medicines (ACVM) Act.

EPA staff have reviewed health based exposure guidance values established by overseas regulators (shown

in Table 16) to inform the selection of ADE and PDE values for elemental iron (Table 16).

36


November 2018

Table 16: Using an existing ADI for elemental iron

Available international

toxicological

thresholds

Key

Systemic

effect

NOAEL

(mg/kg

bw/day)

Uncertainty

factors

Value

(mg/kg

bw/day)

Modifications Remarks

ADI

(EFSA 2012)

Derived

from human

intakes

NA Not required 0.8 None

Table 17: Active ingredient exposure thresholds

Active Ingredient ADE (mg/kg bw/d) PDE (mg/kg bw/d) TEL

mg/L (water)

mg/kg (soil)

mg/m3 (air)

Elemental iron 0.8 PDE (food) = 0.56

PDE (drinking water) = 0.16

PDE (other) = 0.08

Not set at this time

Other toxicity controls

The following limits are proposed for toxicologically relevant impurities in the technical grade active

ingredient elemental iron (expressed on the basis of the anhydrous variant):

Arsenic: maximum 18 mg/kg

Cadmium: maximum 1.8 mg/kg

Chromium: maximum 90 mg/kg

Lead: maximum 36 mg/kg

Mercury: maximum 1.8 mg/kg

The following additional label control (or words to the same effect) is proposed:

“A person who handles this substance must wear gloves”

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November 2018

Ecotoxicity controls

Maximum application rate

A maximum application rate is proposed to be set for PROTECT-US™ Mineral Snail and Slug Killer with

Elemental Iron, as shown in

Table 18.

Table 18: Maximum application rates

Maximum application rate2

50 kg formulation/ha, which corresponds with 5 g formulation/m2

Other ecotoxicity controls

PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron can only be applied using ground-

based methods which ensure that pellets are not released into the aquatic environment.

2 The Hazardous Substances (Hazards Property Control) Notice 2017 relates to the requirement to set an application

rate for a class 9 substance that is to be sprayed or applied to an area of land (or air or water) and for which an EEL has

been set.

38


November 2018

Appendix I: Study summaries

Toxicity study summaries

Several studies on the toxicity of the substance on mammals have been reviewed. These studies are used to

describe potential risks to human health. The effects on mammals in these studies are used as proxies for

the impact on humans. Data from the studies for classifying the active ingredient and the formulated

substance have been used. A summary of the studies is provided in Table 19 to Table 23.

Table 19: Substance Acute Oral Toxicity

Study type Acute oral toxicity study

Flag Key study

Test Substance Slug & Snail Killer

Endpoint >2000 mg/kg bw

Value LD50

Reference

Gruszka K., 2009. Slug & Snail Killer, acute oral toxicity study on rats. Institute

of industrial organic chemistry, Department of Toxicological Studies

Doświadczalna 27, 43-200 Pszczyna, POLAND. Study code: OS-25/08

Klimisch Score 1

Amendments/Deviations None

GLP Yes

Test Guideline/s OECD Guideline No 420 / Method B.1.BIS.

Species Rat

Strain Wistar

No/Sex/Group 5F

Dose Levels 2000 mg/kg bw in 0.5% aqueous solution of carboxymethylcellulose, fasted

Exposure Type Oral, gavage

Study Summary

No clinical signs were stated in all animals and they survived a 14-day period

of the experiment. During the entire experiment, normal body weight gain was

stated in all animals, and no pathological changes in animals were stated at

necropsy.

Conclusion LD50: >2000 mg/kg bw

39


November 2018

Table 20: Substance Acute Dermal Toxicity

Study type Acute dermal toxicity study

Flag Key study


Endpoint >2000 mg/kg bw

Value LD50

Reference

Gruszka K., 2009. Slug & Snail Killer, acute dermal toxicity study on rats.

Institute of industrial organic chemistry, Department of Toxicological Studies


Klimisch Score 1


GLP Yes

Test Guideline/s OECD Guideline No 402 / Method B.3.

Species Rat

Strain Wistar

No/Sex/Group 5M/5F

Dose Levels 2000 mg/kg bw moistened

Exposure Type Topical, occlusive for 24 hours on clipped skin

Study Summary

After application of the test, item erythema was stated on the skin of two

males in the site of test item application from 1st to the 2nd day of observation.

Furthermore, in one male dryness of epidermis was stated from 3rd to 4th day

of observation. The following changes were stated on treated skin of all

females: erythema from 1st to 2nd day of observation as well as dryness of

epidermis from 2nd –

3rd to 4th – 6th day of observation. Desquamation of epidermis was observed in

one female on the 3rd day of observation. Oedema was observed in two

females on the 1st day of observation. Furthermore, scabs were observed in

two females on 3rd – 4th day of observation. No other clinical changes

connected with administered test item were observed in examined animals.

All animals survived a 14-day period of observation.

During 14-day period of experiment body weight loss was stated only in one

male (in which abscesses in lungs were stated at necropsy). Body weight

gains were recorded in the remaining animals during the 14-day period of the

experiment.

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November 2018

At necropsy abscesses in lungs were stated in one male. These changes

were not connected with administered test item. The respiratory system

infections occur quite often in laboratory rats. At necropsy, no pathological

changes were stated in the remaining animals.

Conclusion LD50: >2000 mg/kg bw

Table 21: Substance skin irritation/corrosion study

Study type Skin irritation/corrosion study

Flag Key study


Endpoint Draize score

Value Erythema: 1.22, Oedema: 0.00

Reference

Gruszka K., 2009. Slug & Snail Killer, skin irritation/corrosion study on rabbits.



Klimisch Score 1


GLP Yes


Species Rabbits

Strain New Zealand

No/Sex/Group 1M/2F

Dose Levels 0.5 g moistened

Exposure Type Topical, semi-occlusive for 4 hours on clipped skin, washed

Study Summary

During reading after 1 and 24 hours since the end of the exposure, well-

defined erythema was stated on treated area of skin of rabbits. Furthermore,

very slight (barely perceptible) oedema was stated in one rabbit. No

pathological changes were observed on treated area of skin of all rabbits.

Conclusion Mildly irritating

Table 22: Substance eye irritation/corrosion study

Study type Eye irritation/corrosion study

Flag Key study


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November 2018

Endpoint Draize score

Value Cornea: 0.00; Iris: 0.00; conjunctival redness: 1.22; chemosis: 0.33

Reference

Gruszka K., 2009. Slug & Snail Killer, eye irritation/corrosion study on rabbits.



Klimisch Score 1


GLP Yes


Species Rabbits

Strain New Zealand

No/Sex/Group 2M/1F

Dose Levels 0.08 g (0.1mL) moistened

Exposure Type single dose to conjunctival sack of one eye of each rabbit

Study Summary

After administration of test item, pathological changes were stated only in the

conjunctiva of the eye of examined rabbits. No changes were stated in cornea

and iris of the eye. Congestion of nictating membrane as well as

circumcorneal injection were stated in three rabbits.

Conclusion Mildly irritating

Table 23: Substance skin sensitisation study

Study type Skin sensitisation study - Magnusson and Kligman

Flag Key study


Endpoint 55% of treated animals

Value Positive reaction

Reference

Mrzyk I., 2009. Slug & Snail Killer, skin sensitization study. Institute of

industrial organic chemistry, Department of Toxicological Studies

Doświadczalna 27, 43-200 Pszczyna, POLAND. Study code: Al-53/08

Klimisch Score 1

Amendments/Deviations None that influenced study course and results

GLP Yes


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November 2018

Species Guinea pig

Strain Dankin Hartley

No/Sex/Group Treated group: 6M/5F

Control group: 3M/2F

Dose Levels

Induction: intradermal injections, 0.5% aqueous suspension

Induction: topical, 30% aqueous suspension

Challenge: 10% aqueous suspension

Exposure Type

Induction: intradermal injections

Induction: topical, occlusive for 48 hours on clipped skin

Challenge: topical, occlusive for 24 hours on clipped skin

Study Summary

During the experiment, distinct body weight loss was observed in one female

of the treated group. Body weight gain was stated in the remaining animals.

The average body weight gain in males of the control group was level with

males of the treated group. The average body weight gain in females of the

control group was greater than the average body weight gain in females of the

treated group.

During the experiment, no changes in behaviour were observed in animals of

the control group. No clinical signs were stated in animals of the control

group. During experiment, accelerated respiration was stated in one female of

the treated group from 12th day till the end of the experiment. No changes in

behaviour, as well as no clinical signs, were stated in the remaining animals of

the treated group.

No pathological changes were stated on the skin of control animals on the site

of test item application. No pathological changes were stated also on the skin

in the site of medium application. During readings, allergic skin reactions were

stated in five males and one female of the treated group, that is 55% of

treated animals.

Conclusion Sensitising

Environmental fate studies

No studies on the environmental fate of the formulation or the components have been provided.

Ecotoxicity study summaries

Several studies on the toxicity of the substance on several environmental compartments have been

reviewed. No studies on the toxicity to terrestrial invertebrates (eg bees) was provided. The summaries of

these studies are provided in Table 24 to Table 30.

43


November 2018

Table 24: Acute toxicity to fish

Study type Acute toxicity test

Flag Supportive study


Species Oncorhynchus mykiss (Rainbow trout)

Exposure type Static, 96 hours

Endpoint LC50

Value Not determined

Reference

Olek, J (2008). SLUG & SNAIL KILLER Acute toxicity for rainbow trout

according to OECD Guideline No 203/ method C.1. Institute of industrial

organic chemistry, Poland. Study code: W/89/08

Klimisch Score 3

Amendments/Deviations The loading of the tank was higher than recommended (2.15 g of fish /L)

GLP Yes

Test Guideline/s OECD 203

Dose Levels Water Accommodated Fractions prepared at 10, 18, 32, 56 and 100 mg/L

Analytical measurements None

Study Summary

In general, the OECD 203 was followed.

Water Accommodated Fractions (WAFs) were prepared by stirring the

solutions for two hours in 2 L vessels after which the insoluble fraction was

removed by filtration. These solutions were diluted to reach the nominal

concentrations. No analytical confirmation of the exposure concentration was

provided.

The maximum loading was higher than recommended by the guideline.

In the preliminary test a Water Accommodated Fraction prepared at 100 mg/L

was tested which resulted in complete mortality after 48 hours. Therefore, a

final experiment was performed with WAFs prepared at 10, 18, 32, 56 and

100 mg/L.

No mortalities or other clinic effects were observed during the final experiment

at any of the tested concentration. This lead the authors to conclude that the

test item has no toxic effect up to 100 mg/L of nominal concentration. The

authors claim that during the preliminary test, the circumstances causing fish

mortality (eg contaminated tank) were not related to the test substance. As a

result the NOEC is considered 100 mg/L.

Comments The applicant confirmed that the test substance is the same as the substance

for which approval is sought.

44


November 2018

The loading of the tank was 2.15 g of fish/L which is too high, this adds an

additional stress on the fish and should be avoided.

The solution was stirred for 2 hours in 2 L to establish the water soluble

fractions, however, it is recommended to stir solutions for 48 hours to

establish the maximum water soluble concentration. These solutions were

filtered and further diluted. The staff are not convinced that the maximum

water soluble concentration was reached and therefore the reported nominal

concentrations are considered not to be appropriate and the presented

endpoints unreliable.

Since the test substance was insoluble and was consisting of several

components, it was considered inappropriate to dilute the mixed concentration

because different components will have different solubilities. The solutions

should not have been diluted. The exposure concentration is lower than the

nominal concentration due to the test preparation method.

No analytical confirmation of the test concentrations was performed and it has

not been demonstrated that the test substances was dissolved.

The staff do not agree with the conclusion that mortality in the limit test is

certainly not due to the substance. The preparation method of the poorly-

soluble substance potentially caused a difference in exposure concentration

between the two tests. If such a major difference in response was observed

another test should have been performed to confirm the toxicity of the

substance. Since no analytical confirmation of the substance has been

included, the exposure concentrations remain unknown.

Conclusion The results are considered unreliable for the determination of the hazard class

Table 25: Algal growth inhibition test, supportive study

Study type Algal growth inhibition test



Species Pseudokirchneriella subcapitata SAG 61.81

Exposure Static-72 hours

Endpoint ErC50

Value 180 mg/L (nominal)

Reference

Olek, J (2008). SLUG & SNAIL KILLER growth inhibition test with

Pseudokirchneriella subcapitata SAG 61.81 according to OECD Guideline No

201/ method C.3. Institute of industrial organic chemistry, Poland. Study code:

W/19/08

45


November 2018

Klimisch Score 3

Amendments/Deviations

The mean coefficient of variation for section-by-section specific growth rates

in the control cultures was 43.7% which is above the validation criteria set by

the guideline

GLP Yes


Dose Levels Water Accommodated Fractions prepared at 10, 18, 32, 56, 100 and 180

mg/L


Study Summary

The test has generally been performed according to OECD 201.

Water Accommodated Fractions were prepared by stirring the solutions for

two hours after which the insoluble fraction was removed by filtration. The

three lowest concentrations were prepared by dilution. No analytical

confirmation of the exposure concentrations was provided.

The algal densities were determined using a photo spectrometer. The slight

elevation in temperature variation observed during the test is considered not

to have influenced the final results.

All validity criteria were met except the mean coefficient of variation for

section-by-section specific growth rates (43.7%, criterion – not more than

35%). The authors estimate that the values ErC50 and EyC50 based on nominal

concentrations of the test preparation are: EyC50/72 h = 66.97 mg/L, EyC20/72

h = 40.27 mg/L, EyC10/72 h = 30.82 mg/L, ErC50/72 h > 180 mg/L, ErC20/72 h =

84.66 mg/L and ErC10/72 h = 46.16 mg/L. The authors estimate the LOEC and

NOEC values based on nominal concentrations of the test item calculated

from yield and average specific growth rate to be: LOEC = 56 mg/L for yield

and for average specific growth rate, NOEC = 32 mg/L for yield for average

specific growth rate.

Comments

The applicant confirmed that the test substance is the same as the substance

for which approval is sought

The solution was stirred for 2 hours to establish the water soluble fractions,

however, it is recommended to stir solutions for 48 hours to establish the

maximum water soluble concentration. Therefore, the staff is not convinced

that the maximum water soluble concentration was reached.

Since the test substance was insoluble consisting of several components it

was considered inappropriate to dilute the lowest concentration since different

components will have different solubilities. The exposure concentration is

lower than the nominal concentration due to the test preparation method.

46


November 2018

No analytical confirmation of the test concentrations was performed and it has

not been demonstrated that the test substances was dissolved. Based on the

results observed at 100 and 180 mg/L, a toxic substance had been added,

however, it is not confirmed this is the test substance.

The section-by-section specific growth rate exceeds the validity criteria of the

test. It is observed that at the start of the test the specific growth rate is lower

which indicate a lag phase in the growth of the algal cultures. This could be

related to the treatment of the algal culture. Less than optimal growth in the

control might mask certain toxicological effects, the specific growth rate of the

control seems to stabilize at the two later sampling points and therefore the

staff considers the endpoints calculated at 72 hours acceptable.

Conclusion

Nominal concentrations are not suitable to determine hazard classifications

on, especially when it is likely that the maximum soluble concentration in the

test medium has not been reached.

Table 26: Daphnia acute toxicity study




Species Daphnia magna

Exposure Static, 48 hours

Endpoint EC50

Value 26.9 mg/L

Reference

Olek, J (2008). SLUG & SNAIL KILLER Daphnia acute immobilisation test

according to OECD Guideline No 202/ method C.2. Institute of industrial

organic chemistry, Poland. Study code: W/90/08

Klimisch Score 2


GLP Yes


Dose Levels Water Accommodated Fractions prepared at 10, 18, 32, 56 and 100 mg/L


Study Summary Generally the OECD 202 guideline was followed.

47


November 2018

Water Accommodated Fractions were prepared by stirring the solutions for

two hours after which the insoluble fraction was removed by filtration. No

analytical confirmation of the exposure concentration was provided.

A definitive test was performed based on the results of the preceding range-

finding test. The EC50 48 h was determined to be 26.9 mg/L based on the

nominal test concentrations.

Comments



The solution was stirred for 2 hours to establish the water soluble fractions,

however, it is recommended to stir solutions for 48 hours to establish the

maximum water soluble concentration. Therefore, the staff are not convinced

that the maximum water soluble concentration was reached. No analytical

confirmation regarding the exposure concentrations has been provided.

Exposure is lower compared to the nominal concentrations and therefore the

presented EC50 does not reflect actual toxicity.

Nominal concentrations are not suitable to determine hazard classifications,

especially when it is likely that the maximum soluble concentration in the test

medium has not been reached.

The substance is clearly toxic to aquatic crustaceans and the nominal

classification would be 9.1C/9.1D. However, since this is based on a nominal

concentration the actual classification is higher.

Conclusion

Nominal concentrations are not suitable to determine hazard classifications

on, especially when it is likely that the maximum soluble concentration in the

test medium has not been reached.

Table 27: Earthworm acute toxicity test


Flag Key Study


Species Eisenia fetida Sav.

Exposure Artificial soil

Endpoint EC50

Value ~100 mg/kg dw soil

Reference

Olek, J (2008). SLUG & SNAIL KILLER Acute toxicity to earthworms (Eisenia

fetida Sav.) according to OECD Guideline No 207/ method C.8. Institute of

industrial organic chemistry, Poland. Study code: W/54/08

48


November 2018

Klimisch Score 1

Amendments/Deviations The temperature deviation is minimal and is considered not to have influenced

the results.

GLP Yes


Dose Levels 100, 180, 320, 560 and 1000 mg/kg dw soil

Analytical measurements Not required

Study Summary

The study was performed according to OECD 207.

After 7 and 14 days, earthworms exposed to the dry artificial soil containing

the test substance at a concentration of 560 and 1000 mg/kg were less mobile

in comparison to control animals. After 14 days of exposure the test

substance had no negative effects of earthworms’ weight.

After 14 days no mortality was observed at concentrations up to 180 mg/kg

dw soil. 5, 20 and 50% mortality was observed at a concentration of 320, 560

and 1000 mg/kg dw soil respectively. The LC0 was 180 mg/kg dw soil. The

LC50 could not be determined.

Comments



The temperature deviation is minimal and is considered not to have influenced

the results. The staff consider the LC50 ~1000 mg/kg dw soil, based on the

clear dose response curve observed during the test. This results in an EC50 of

~100 mg/kg dw soil which is a borderline case for the 9.2C/9.2D classification.

When considering mobility, it is observed that more than 50% of the

earthworms are less mobile at a concentration of 560 and 1000 mg/kg dw soil.

At 320 mg/kg dw soil, besides a mortality of 5%, no effects were observed. In

conclusion, the EC50 for mobility is between 320 and 560 mg/kg dw. No

negative effects were observed on the weight of the earthworms resulting in

an EC50 > 1000 mg/kg dw soil. Combining the estimated EC50 based on

mortality and the EC50 for mobility and weight the staff consider that the

substance does not classify for the toxicity to earthworms.

Conclusion The substance does not classify for the 9.2 classification

Table 28: Carbon transformation in soil

Study type Carbon transformation test

Flag Key study


49


November 2018

Endpoint Carbon transformation

Value No effect at 5x PEC (single application)

Reference

Olek, J (2008). SLUG & SNAIL KILLER Soil Microorganisms: Carbon

Transformation test according to OECD Guideline No 217/ method C.22.

Institute of industrial organic chemistry, Poland. Study code: W/56/08

Klimisch Score 1


GLP Yes


Dose Levels 66.7 and 333.5 mg/kg soil

Analytical measurements None required

Study Summary

The control soil and soil treated with test material were incubated in three replicates.

Substrate-induced respiration was measured using the trapping of CO2. The

pressure drop was registered as O2 consumption.

The concentrations of 66.7 and 333.5 mg/ kg soil are considered to have no

long-term influence on carbon transformation in soil.

Comments



The concentrations of 66.7 and 333.5 mg/kg soil correspond to an application

of 50 kg/ha which is similar the requested application rate of the substance. It

should be noted that the applicant requested multiple applications, however,

no effects were observed at 5x the predicted field concentrations so it can be

considered that 5 applications will not influence the carbon transformation

rates.

Conclusion No effect on carbon transformation

Table 29: Nitrogen transformation in soil

Study type Nitrogen transformation test

Flag Key study


Endpoint Nitrogen transformation

Value No effect at 5x maximum PEC (single application)

Reference

Olek, J (2008). SLUG & SNAIL KILLER Soil Microorganisms: Nitrogen

Transformation test according to OECD Guideline No 216/ method C.21.

Institute of industrial organic chemistry, Poland. Study code: W/55/08

50


November 2018

Klimisch Score 1


GLP Yes


Dose Levels 66.7 and 333.5 mg/kg soil


Study Summary

The control soil and soil treated with test material were incubated in three

replicates. The principle of the method was based on the spectrophotometric

measurement of the nitrate ions concentration in soil extract of the 1 %

potassium sulfate (VI) solution.

The concentrations of 66.7 and 333.5 mg/ kg soil are considered to have no

long-term influence on nitrogen transformation in soil.

Comments



The concentrations of 66.7 and 333.5 mg/kg soil correspond to an application

of 50 kg/ha which is similar to the requested application rate of the substance.

It should be noted that the applicant requested multiple applications, however,

no effects were observed at 5x the predicted field concentrations so it can be

considered that 5 applications will not influence the nitrogen transformation

rates.

Conclusion No effect on nitrogen transformation

Table 30: Acute toxicity to birds

Study type Acute Toxicity test

Flag Key study


Species Coturnix coturnix japonica

Exposure gavage

Endpoint LC50

Value > 2000 mg/kg bw

Reference

Olek, J (2008). SLUG & SNAIL KILLER acute oral toxicity test with Japanese

Quail (Coturnix coturnix japonica) according to EPA guideline OPPTS

850.2100. Institute of industrial organic chemistry, Poland. Study code:

W/53/08

Klimisch Score 1

51


November 2018

Amendments/Deviations Relatively young birds were used for the test

Cage surface was 360 cm2 per bird which is too small

GLP Yes

Test Guideline/s OPPTS 850.2100

Dose Levels 2000 mg/kg bw

No 10 per treatment


Study Summary

Taking into account the obtained results, it was assessed that SLUG & SNAIL

KILLER caused no mortality of tested birds at the dose of 2000 mg/kg of body

weight. In the control group of birds, no mortality was also recorded. During

the experiment, no differences in behaviour of treated birds in comparison to

the control were observed. In gross pathology examination of survivors, no

pathological changes were recorded. During the experiment, no differences in

body weight as well as in food consumption of exposed birds as compared to

control was observed. The dose causing 50% of mortality (LD50) of Japanese

quail (Coturnix coturnix japonica) population is higher than 2000 mg/kg of

body weight.

Comments



Relatively young birds were used for the test, the staff consider this deviation

from the recommendations of the guideline acceptable.

Recommended cage size is 500 cm2 per bird, provided space is 360 cm2

which is too small and might cause unnecessary stress resulting in a higher

variation. However, results clearly show that the LC50 is above 2000 mg/kg

bw.

Conclusion LC50 > 2000 mg/kg bw, the substance does not classify as a Class 9.3

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November 2018

Appendix J: Standard terms and abbreviations

Abbreviation Definition

AAOEL Acute Acceptable Operator Exposure Level

ai active ingredient

ACVM Agricultural Compounds and Veterinary Medicines

ADE Acceptable Daily Exposure

ADI Acceptable Daily Intake

AOEL Acceptable Operator Exposure Level

APVMA Australian Pesticides and Veterinary Medicines Authority

ARfD Acute Reference Dose

BNF British National Foundation

Bw body weight

CAS # Chemical Abstract Service Registry Number

cm centimetres

CoA Certificate of Analysis

CRfD Chronic Reference Dose

EC50 Effective Concentration at which an observable adverse effect is caused in 50 %

of the test organisms

EDTA ethylenediaminetetraacetic acid

EEL Environmental Exposure Limit

EFSA European Food Safety Authority

EPA New Zealand Environmental Protection Authority

ErC50 EC50 with respect to a reduction of growth rate (r)

EU European Union

Fe Iron

g grams

GLP Good Laboratory Practice

ha hectare

HPC Hazardous Property Controls

HSNO Hazardous Substances and New Organisms

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November 2018

kg Kilogram

L litres

LC50 Lethal Concentration that causes 50% mortality

LD50 Lethal Dose that causes 50% mortality

LOC Level Of Concern

LOEC Lowest observed effects concentration

m3 cubic metre

mg milligram

μg microgram

MRL Maximum Residue Level

NOAEL No Observed Adverse Effect Level

NOEC No Observed Effect Concentration

OECD Organisation for Economic Cooperation and Development

PDE Potential Daily Exposure

PEC Predicted Environmental Concentration

PPE Personal Protective Equipment

RQ Risk Quotient

TG Technical Guidance

TEL Tolerable Exposure Limit

US-EPA United States Environmental Protection Agency

WAF Water Accommodated Fraction

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November 2018

Appendix K: References

Abhilash, K. P., Arul, J. J., Bala, D. (2013). "Fatal overdose of iron tablets in adults." Indian J Crit Care Med 17(5): 311-313. Aggarwal, M., Fischer, P., Hüser, A., Kluxen, F. M., Parr-Dobrzanski, R., Soufi, M., Strupp, C., Wiemann, C., Billington, R. (2015). "Assessment of an extended dataset of in vitro human dermal absorption studies on pesticides to determine default values, opportunities for read-across and influence of dilution on absorption." Regul Toxicol Pharmacol 72(1): 58-70. Anderson, A. C. (1994). "Iron poisoning in children." Curr Opin Pediatr 6(3): 289-294. Best, L. and D. Fischer (1992). "Granular insecticides and birds: Factors to be considered in understanding exposure and reducing risk." Environmental Toxicology and Chemistry 11: 1495-1508. BNF (1995). Iron: Nutritional and physiological significance The Report of the British Nutrition Foundation’s Task Force, Springer Netherlands. CRD (2016). OPERATOR EXPOSURE GUIDANCE FOR AMATEUR (HOME GARDEN) PESTICIDES. EFSA (2009). "Risk Assessment for Birds and Mammals." EFSA Journal 7(12): 1438. EFSA (2012). "Conclusion on the peer review of the pesticide risk assessment of the active substance iron sulfate." EFSA Journal 10(1): 2521. EFSA (2014). "Scientific Opinion on the safety and efficacy of iron compounds (E1) as feed additives for all species: Ferrous sulphate monohydrate based on a dossier submitted by Kronos International, Inc." EFSA Journal 12(3): 3607. FOCUS (1997). Soil persistence models and EU registration. Gionfriddo, J. P. and L. B. Best (1995). "Grit Use by House Sparrows: Effects of Diet and Grit Size." The Condor 97(1): 57-67. Litovitz, T. and A. Manoguerra (1992). "Comparison of Pediatric Poisoning Hazards: An Analysis of 3.8 Million Exposure Incidents A Report from the American Association of Poison Control Centers." Pediatrics 89(6): 999-1006. US-EPA (2011). Exposure Factors Handbook 2011 Edition (Final Report). Washington, U.S. Environmental Protection Agency.

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