science memo - epa
TRANSCRIPT
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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
November 2018
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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
November 2018
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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
November 2018
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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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 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
organ systemic toxicity
(dermal)
NA ND No data on any of the
components
Subclass 6.9 Target
organ systemic toxicity
(inhalation)
NA NA Physical from, granules,
10mm (±2mm) length
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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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.
Subclass 9.1 Aquatic
ecotoxicity (Fish) NA ND
The provided studies were
considered of insufficient
quality to classify the
substance
Subclass 9.1 Aquatic
ecotoxicity (Crustacean) NA 9.1B
The provided studies were
considered of insufficient
quality to classify the
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.
Subclass 9.1 Aquatic
ecotoxicity (Algal) NA ND
The provided studies were
considered of insufficient
quality to classify the
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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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
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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
November 2018
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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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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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.
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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
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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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Soil toxicity
Table 8 contains the acute and chronic soil toxicity test results for the formulated product.
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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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Table 8: Summary of soil toxicity data for PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron
Test species Test type and duration
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
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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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
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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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
Test species Test type and duration
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
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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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
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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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
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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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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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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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
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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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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.
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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).
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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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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.
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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
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Table 20: Substance Acute Dermal Toxicity
Study type Acute dermal 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 dermal 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 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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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
Test Substance Slug & Snail Killer
Endpoint Draize score
Value Erythema: 1.22, Oedema: 0.00
Reference
Gruszka K., 2009. Slug & Snail Killer, skin irritation/corrosion study on rabbits.
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 404 / Method B.4.
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
Test Substance Slug & Snail Killer
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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.
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 405 / Method B.5.
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
Test Substance Slug & Snail Killer
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
Test Guideline/s OECD Guideline No 406 / Method B.6.
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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.
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Table 24: Acute toxicity to fish
Study type Acute toxicity test
Flag Supportive study
Test Substance Slug & Snail Killer
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.
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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
Flag Supportive study
Test Substance Slug & Snail Killer
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
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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
Test Guideline/s OECD 201
Dose Levels Water Accommodated Fractions prepared at 10, 18, 32, 56, 100 and 180
mg/L
Analytical measurements None
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.
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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
Study type Acute toxicity test
Flag Supportive study
Test Substance Slug & Snail Killer
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
Amendments/Deviations None
GLP Yes
Test Guideline/s OECD 202
Dose Levels Water Accommodated Fractions prepared at 10, 18, 32, 56 and 100 mg/L
Analytical measurements None
Study Summary Generally the OECD 202 guideline was followed.
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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 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 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
Study type Acute toxicity test
Flag Key Study
Test Substance Slug & Snail Killer
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
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Klimisch Score 1
Amendments/Deviations The temperature deviation is minimal and is considered not to have influenced
the results.
GLP Yes
Test Guideline/s OECD 207
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 applicant confirmed that the test substance is the same as the substance
for which approval is sought.
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
Test Substance Slug & Snail Killer
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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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
Amendments/Deviations None
GLP Yes
Test Guideline/s OECD 217
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 applicant confirmed that the test substance is the same as the substance
for which approval is sought.
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
Test Substance Slug & Snail Killer
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
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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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Klimisch Score 1
Amendments/Deviations None
GLP Yes
Test Guideline/s OECD 216
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. 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 applicant confirmed that the test substance is the same as the substance
for which approval is sought.
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
Test Substance Slug & Snail Killer
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
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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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
Analytical measurements None required
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
The applicant confirmed that the test substance is the same as the substance
for which approval is sought.
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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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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Application for approval to import or manufacture PROTECT-US™ Mineral Snail and Slug Killer with Elemental Iron for release (APP202870)
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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.