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SCIENCE MEMO
APP203638 – Custodia®
FEBRUARY/ 2020
Page 2 of 131
Science memo for application to import or manufacture Custodia® for release (APP203638)
FEBRUARY 2020
Executive Summary
The applicant, Adama New Zealand Limited, submitted an application to the Environmental Protection
Authority (EPA) on 1 June 2018 to seek approval for Custodia®, a fungicide containing 200 g/L tebuconazole
and 120 g/L azoxystrobin in a suspension concentrate formulation, for control of foliar diseases of forage
beet crops. It was given Application Number APP203638 and was formally received on 26 June 2019 as a
Category B application.
Both tebuconazole and azoxystrobin are approved individually in New Zealand on a wide range of crops
(except sugar beet and fodder beet) at rates higher than those of Custodia® (up to 375 g/ha for
tebuconazole and up to 620 g azoxystrobin/ha), with different application methods (including aerial
application). The crops on which both active ingredients are currently used are listed below:
Azoxystrobin: barley, field tomato, grape, maize, onion, pea, potato, rye grass seed crop, sweetcorn, turf,
wheat.
Tebuconazole: wheat, barley, oats, ryegrass seed crop, pea, onion, summer fruit, pasture, grape.
However, they have never been approved as a combination in New Zealand previously.
Mammalian toxicity studies with Custodia® indicate that the substance is of low acute toxicity and should be
classified 6.1D for acute oral toxicity. The substance is not irritating to the skin or eyes, and is not a contact
sensitiser. Based on mixture rules, Custodia® should be classified 6.8B and 6.9B (oral). Based on test data
for the formulation, Custodia® should also be classified 6.1D and 9.1B but does not require classification as
being toxic to terrestrial vertebrates or invertebrates.
It is considered that there is potential for significant exposure to people and the environment during the use
phase of the lifecycle of Custodia®. As such, quantitative risk assessments have been undertaken to
understand the likely exposures to the substance under the use conditions proposed by the applicant, using
the endpoint data available and the standard risk assessment methodologies used by the EPA.
It is considered that the risks to human health from the proposed use of Custodia® are acceptable with the
use of appropriate and full Personal Protective Equipment (PPE). No REIs are required to protect crop
worker re-entry. No buffer zone is required to protect bystanders.
It is considered that the risks to the environment from the proposed use of Custodia® are acceptable with
the proposed controls.
A set of controls have been proposed for Custodia®, and are detailed under section 6.
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Science memo for application to import or manufacture Custodia® for release (APP203638)
FEBRUARY 2020
Table of Contents
APP203638 – Custodia® ....................................................................................................................... 1
Executive Summary .............................................................................................................................. 2
1. Introduction/Background ........................................................................................................... 7
2. Hazardous properties ................................................................................................................. 9
Hazard classification of Custodia® ............................................................................................... 9
3. Risk assessment context ........................................................................................................... 9
4. Human health risk assessment................................................................................................ 10
5. Environmental risk assessment .............................................................................................. 10
6. Proposed controls ..................................................................................................................... 12
Additional and varied controls ..................................................................................................... 12
Application rate ............................................................................................................................ 12
Application method ...................................................................................................................... 12
Buffer zones ................................................................................................................................ 12
Additional label statements ......................................................................................................... 12
Appendix A: Identity of the active ingredient, use pattern and mode of action ........................... 14
Identity of the active ingredient and metabolites ......................................................................... 14
Regulatory status ........................................................................................................................ 14
Impurities and or restrictions on purity or composition ................................................................ 15
Use pattern and mode of action .................................................................................................. 15
Use pattern ........................................................................................................................ 15
Mode of action ................................................................................................................... 15
Table 5: List of intended uses for Custodia® ................................................................... 16
Appendix B: Physico-chemical properties of Custodia® ................................................................ 18
Appendix C: Mammalian toxicology .................................................................................................. 19
Executive summaries and list of endpoints for Custodia® .......................................................... 19
Appendix D: Environmental fate ........................................................................................................ 21
Residues relevant to the environment ......................................................................................... 21
Azoxystrobin ...................................................................................................................... 21
Tebuconazole .................................................................................................................... 21
Degradation and fate of azoxystrobin and tebuconazole in aquatic environments..................... 21
Degradation and fate of azoxystrobin and tebuconazole in soil.................................................. 23
General conclusion about environmental fate ............................................................................. 25
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Science memo for application to import or manufacture Custodia® for release (APP203638)
FEBRUARY 2020
Azoxystrobin ...................................................................................................................... 25
Tebuconazole .................................................................................................................... 25
Appendix E: Ecotoxicity ..................................................................................................................... 26
List of endpoints .......................................................................................................................... 26
Aquatic toxicity ............................................................................................................................ 26
General conclusion about aquatic toxicity......................................................................... 31
Soil toxicity................................................................................................................................... 32
General conclusion about soil toxicity ............................................................................... 36
Terrestrial vertebrate toxicity ....................................................................................................... 36
General conclusion about ecotoxicity to terrestrial vertebrates ........................................ 38
Ecotoxicity to bees and other terrestrial invertebrates ................................................................ 38
General conclusion about ecotoxicity to bees and terrestrial invertebrate toxicity ........... 40
Appendix F: Hazard classification of Custodia® ............................................................................. 41
Appendix G: Human health risk assessment ................................................................................... 43
Quantitative risk assessment ...................................................................................................... 43
Input values for the human health risk assessment .................................................................... 43
Operator exposure assessment .................................................................................................. 45
Re-entry worker exposure assessment ....................................................................................... 46
Quantitative bystander risk assessment ..................................................................................... 46
Groundwater contamination risk assessment ............................................................................. 47
Conclusions of the human health risk assessment ..................................................................... 48
Appendix H: Environmental risk assessment .................................................................................. 49
Evaluation of toxicity of the mixture ............................................................................................. 49
Aquatic risk assessment .............................................................................................................. 52
Calculation of expected environmental concentrations .................................................... 52
Output from the GENEEC2 model .................................................................................... 54
Azoxystrobin ................................................................................................................................ 54
Tebuconazole .............................................................................................................................. 55
Calculated risk quotients ................................................................................................... 57
Refinement of the aquatic risk assessment ...................................................................... 59
Spray drift .................................................................................................................................... 59
Input variables used for the aerial AGDISP v8.15 modelling ...................................................... 61
Aerial buffer zones ...................................................................................................................... 63
Overall conclusion ....................................................................................................................... 63
Runoff .......................................................................................................................................... 66
Conclusions of the aquatic risk assessment ..................................................................... 66
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Science memo for application to import or manufacture Custodia® for release (APP203638)
FEBRUARY 2020
Use restrictions ............................................................................................................................ 66
Buffer zones ................................................................................................................................ 67
Groundwater risk assessment ..................................................................................................... 67
Conclusions of the groundwater risk assessment ............................................................ 67
Sediment risk assessment .......................................................................................................... 68
Conclusions of the sediment risk assessment .................................................................. 68
Terrestrial risk assessment ......................................................................................................... 68
Soil macro-organisms ....................................................................................................... 68
Soil micro-organisms ......................................................................................................... 70
Conclusions of the soil organism risk assessment ........................................................... 70
Non-target plant risk assessment ................................................................................................ 70
Conclusion for non-target plant risk assessment .............................................................. 71
Bird risk assessment ................................................................................................................... 72
Screening assessment ...................................................................................................... 72
Calculation of TERs ..................................................................................................................... 73
Conclusions of the bird screening risk assessment .................................................................... 74
Tier 1 assessment ............................................................................................................. 74
Conclusion for bird risk assessment (Tier 1) ............................................................................... 75
Refinement ........................................................................................................................ 75
Scenario 1 ................................................................................................................................... 75
Secondary poisoning ......................................................................................................... 76
Conclusions for bird risk assessment ............................................................................... 76
Pollinator risk assessment ........................................................................................................... 76
Conclusions of the pollinator risk assessment .................................................................. 77
Non-target arthropod risk assessment ........................................................................................ 77
Conclusion for non-target arthropod risk assessments .................................................... 79
Conclusions of the ecological risk assessment ........................................................................... 79
Aquatic environment: ..................................................................................................... 79
Groundwater: ................................................................................................................... 79
Sediment: ......................................................................................................................... 79
Soil organisms: ............................................................................................................... 80
Terrestrial plants: ............................................................................................................ 80
Birds: ................................................................................................................................ 80
Bees and non-target arthropods: .................................................................................. 80
Appendix I: Study summaries ............................................................................................................ 82
Toxicity ........................................................................................................................................ 82
Mammalian toxicology - Robust study summaries for Custodia® .................................... 82
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Science memo for application to import or manufacture Custodia® for release (APP203638)
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Ecotoxicity ................................................................................................................................... 90
Aquatic organisms ............................................................................................................. 91
Terrestrial toxicity .............................................................................................................. 99
Non-target plants ............................................................................................................. 103
Soil micro-organisms ....................................................................................................... 105
Birds ................................................................................................................................ 109
Pollinators ....................................................................................................................... 111
Non-target arthropods ..................................................................................................... 113
Appendix J: Standard terms and abbreviations ............................................................................. 127
Appendix K: References ................................................................................................................... 130
Appendix L: Confidential Composition ........................................................................................... 131
Page 7 of 131
Science memo for application to import or manufacture Custodia® for release (APP203638)
FEBRUARY 2020
1. Introduction/Background
1.1. This application is to import or manufacture for release Custodia®, a Suspension Concentrate (SC)
containing the active ingredients tebuconazole (200 g/L) and azoxystrobin (120 g/L), plus other
components.
1.2. Custodia® is intended to be used as a fungicide for the control of foliar diseases in forage beet crops.
It is intended to be applied using ground-based and aerial application methods at the maximum
application rate of 0.12 kg/ha azoxystrobin and 0.2 kg/ha tebuconazole.
1.3. Both tebuconazole and azoxystrobin are approved individually in New Zealand on a wide range of
crops (except sugar beet and fodder beet) at rates higher than those of Custodia® (up to 375 g/ha for
tebuconazole and up to 620 g azoxystrobin/ha), with different application methods (including aerial
application). The crops on which both active ingredients are currently used are listed below:
Azoxystrobin: barley, field tomato, grape, maize, onion, pea, potato, rye grass seed crop, sweetcorn,
turf, wheat.
Tebuconazole: wheat, barley, oats, ryegrass seed crop, pea, onion, summer fruit, pasture, grape.
However, they have never been approved as a combination in New Zealand previously.
1.4. The active ingredient tebuconazole has been approved internationally in Australia, Europe, Japan,
Canada and USA.
1.5. The active ingredient azoxystrobin has been approved internationally in Australia, Europe, Japan,
Canada and USA.
1.6. The substance Custodia® is also registered internationally, for instance in Australia and Europe.
1.7. More details about the use pattern of Custodia® and the regulatory status of tebuconazole and
azoxystrobin can be found in Appendix A.
1.8. It is considered that there is potential for significant exposure to people and the environment during
the use phase of the lifecycle of Custodia®. As such, quantitative risk assessments have been
undertaken to understand the likely exposures to the substance under the use conditions proposed by
the applicant, using the endpoint data available and the standard risk assessment methodologies used
by the EPA.
1.9. Physical and Chemical properties of Custodia® can be found in Appendix B.
1.10. Mammalian toxicological properties Custodia® have been reported in Appendix C.
1.11. Environmental Fate properties of tebuconazole, azoxystrobin and their respective metabolites have
been reported in Appendix D.
1.12. Ecotoxicological properties of Custodia®, azoxystrobin and tebuconazole have been reported in
Appendix E.
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1.13. Hazard properties and classification determination of Custodia® derived from their properties can be
found under section 2 and Appendix F.
1.14. Mammalian toxicological data have subsequently been used to generate human health risk
assessment and this is detailed in Appendix G.
1.15. Environmental Fate, Ecotoxicological and other relevant data have subsequently been used to
generate environmental risk assessment and this is detailed in Appendix H.
1.16. Relevant study summaries can be found in Appendix I.
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2. Hazardous properties
Hazard classification of Custodia®
2.1. The hazard classifications of Custodia® determined by the EPA are 6.1D, 6.8B, 6.9B and 9.1B (Table
1). The hazard classifications of Custodia® were determined based on the information provided by the
applicant (including toxicity and ecotoxicity studies), information on the individual components of
Custodia®, mixture rules and other available information. Table 30 in Appendix F shows the method
used for classification and indicates the main component that contributes to each hazard
classification).
Table 1: Hazard classification of Custodia®
Hazard EPA classification
Acute toxicity (oral) 6.1D
Reproductive/ developmental toxicity 6.8B
Target organ or systemic (routes) 6.9B
Aquatic ecotoxicity 9.1B
2.2. Mammalian toxicity studies with Custodia® indicate that the substance is of low acute toxicity and
should be classified 6.1D for acute oral toxicity. The substance is not irritating to the skin or eyes, and
is not a contact sensitiser. Based on mixture rules, Custodia® should be classified 6.8B and 6.9B
(oral). Based on test data for the formulation, Custodia® should also be classified 6.1D and 9.1B but
does not require classification as being toxic to terrestrial vertebrates or invertebrates.
3. Risk assessment context
3.1. It is considered that there is potential for significant exposure to people and the environment during
the use phase of the lifecycle of Custodia®. As such, quantitative risk assessments have been
undertaken to understand the likely exposures to the substance under the use conditions proposed by
the applicant, using the endpoint data available and the standard risk assessment methodologies used
by the EPA (EPA 2018).
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 EPA Notices around packaging,
identification and disposal of hazardous substances. In addition, the Land Transport Rule 45001, Civil
Aviation Act 1990, Maritime Transport Act 1994 and New Zealand’s Health and Safety at Work (HSW)
requirements all have provisions for the safe management of hazardous substances.
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4. Human health risk assessment
4.1. The risks from the use of tebuconazole are considered as a proxy for Custodia® on users and
operators of the substance, re-entry workers and bystanders. Full details can be found in Appendix G:
Human health risk assessment.
4.2. Operator Exposure:
Predicted operator exposures to tebuconazole are below the Acceptable Operator Exposure Level
(AOEL), provided full PPE (gloves, hood/visor, coveralls, and heavy boots without a respirator) is worn
during mixing, loading, and application. Therefore operator exposures to Custodia® are not expected
to result in adverse health effects, if adequate PPE is worn.
4.3. Worker Re-Entry:
Risk Quotient resulting from predicted exposures to tebuconazole for workers re-entering and working
in areas where Custodia® has been applied are below the LOC. No re-entry intervals are necessary.
4.4. Bystanders:
Estimated bystander exposure from spray drift after application of Custodia® to the soil around fodder
beet and sugar beet is below the AOEL. No buffer zone is required in protect bystanders.
4.5. Groundwater:
The estimated ground water concentration of 1,2,4-triazole from the application of Custodia® has
been estimated using SciGrow as 0.11 μg/L (see Appendix H). The EPA notes that this value is lower
than the TEL (Drinking Water) derived for 1,2,4-triazole which suggests that ground water
concentrations result in acceptable risks after use of Custodia®.
4.6. Overall human health conclusion:
It is considered that the risks to human health from the proposed use of Custodia® are acceptable
with the use of appropriate and full Personal Protective Equipment (PPE). No REIs are required to
protect crop worker re-entry. No buffer zone is required to protect bystanders..
5. Environmental risk assessment
5.1. The risks to a range of environmental receptors, from the use of azoxystrobin and tebuconazole are
considered as a proxy for the risks from Custodia®. Full details can be found in Appendix H:
Environmental risk assessment.
5.2. Aquatic environment:
Predicted chronic exposures concentrations of azoxystrobin and tebuconazole, applied as the
formulated product Custodia® resulted in calculated Risk Quotients above the Level Of Concern
(LOC) for the aquatic environment (fish, crustacean). To manage these risks, it is proposed to apply
controls to reduce spray-drift into the aquatic environment. Together with prescribed controls,
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additional controls setting a maximum application rate and use restrictions regarding the droplet size
will reduce the risks to below the level of concern. Details are provided in section 6.
5.3. Groundwater:
The EPA considers the environmental risk as below the level of concern for aquatic organisms.
5.4. Sediment:
The risk quotient of tebuconazole for sediment-dwelling organisms was below the level of concern.
Due to a lack of data on the active ingredient azoxystrobin, the risk to sediment-dwelling organisms
resulting from the application of Custodia® cannot be determined. However, azoxystrobin is already
approved in New Zealand at a higher rate (250 g ai/ha) than the proposed rate (120 g ai/ha).
5.5. Soil organisms:
Acute and chronic risk quotient to soil organisms applicable to azoxystrobin and tebuconazole
following the application of Custodia® are below the Level Of Concern (LOC).
For 1,2,4-triazole (metabolite tebuconazole) the chronic risk to threatened earthworms was above the
level of concern. Further evaluation indicated that threatened species are unlikely present in the
application areas of Custodia®, as a result, the risk is considered to be below the level of concern.
5.6. Non-target Plants:
Overall, it is considered that the risks to non-target plants following an application of Custodia® are
likely below the LOC.
5.7. Birds:
TER values for birds calculated for azoxystrobin and tebuconazole, when applied to fodder and sugar
beet as the formulated product Custodia®, are below the level of concern for acute risks, and any
risks are negligible. In the reproductive screening assessments, the TER values indicate a chronic risk
below the level of concern to birds for azoxystrobin but above the level of concern to birds from the
use of tebuconazole in fodder and sugar beet. After refinement, it is considered that it is likely that
threatened species will obtain less than 60% of their food from the treated fields as agricultural areas
are not the natural habitat of threatened bird species. Therefore, the risks from tebuconazole is
considered to be low. Furthermore, both active ingredients are already approved in New Zealand at
higher rates than the proposed rate. The risks from secondary poisoning is considered to be low as
both active ingredients are not considered to be bioaccumulative.
5.8. Pollinators:
The acute risks to pollinators are below the level of concern. Chronic risks could not be evaluated due
to a lack of data. However, both active ingredients are already approved in New Zealand at higher
rates than the proposed rate.
5.9. Non-target Arthropods:
Risks to non-target arthropods are above the level of concern for the in-field situation for parasitic
wasps following an application with Custodia®. For the other tested and assessed non-target
arthropods, the risks are below the level of concern. For the off-field situation, the risks for parasitic
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wasps are below the level of concern using the GENEEC model drift factors (aerial application). Re-
colonization from off-field is expected when the concentration has decreased.
The EPA recommends a label statement to warn end-users on the potential impact on beneficial
insects as risks cannot be fully excluded. Label statement indicating “WARNING” the substance might
not be compatible with Integrated Pest Management (IPM).
5.10. Overall Ecological risk assessment conclusion:
It is considered that the risks to the environment from the proposed use of Custodia® are acceptable
with the proposed controls.
6. Proposed controls
Additional and varied controls
Application rate
6.1. The maximum application rate is 120 g azoxystrobin and 200 g tebuconazole/ha, with a maximum of 2
applications/year and a minimum interval of 14 days.
Application method
6.2. When applied using ground-based or aerial application methods, the nozzle must be set to coarse
droplet quality spray, as defined by the American Society of Agricultural and Biological Engineers
ASABE Standard (S572) or the British Crop Production Council guideline.
Buffer zones
6.3. The following buffer zones have been determined for Custodia® for aerial application:
Table 2: Proposed buffer zones to downwind water body for aerial applications of Custodia®
Application method Aerial
BBCH-stage 12-19 31-39 >40
Bufferzone control (metres) 120 70 30
Additional label statements
6.4. Label statement indicating “WARNING” the substance might not be compatible with Integrated Pest
Management (IPM).
6.5. A label statement indicating: “DO NOT apply when wind speeds are less than 3 km/hr or more than 20
km/hr as measured at the application site”.
6.6. A label statement indicating the buffer zones for aerial applications:
BBCH stage 12-19: A downwind buffer zone of 120 m is required to mitigate the risks
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BBCH stage 31-39: A downwind buffer zone of 70 m is required to mitigate the risks
BBCH stage >49: A downwind buffer zone of 30 m is required to mitigate the risks
6.7. For aerial and ground-based application, use minimum coarse droplets, as defined by the American
Society of Agricultural and Biological Engineers ASABE Standard (S572) or the British Crop
Production Council guideline. This information should be required on the label so that users are aware
of this control.
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Appendix A: Identity of the active ingredient, use pattern and mode of action
Identity of the active ingredient and metabolites
General data on tebuconazole and azoxystrobin are provided in Table 3.
Table 3: Identification of tebuconazole and azoxystrobin
Common name Tebuconazole Azoxystrobin
IUPAC name
(RS)-1-p-chlorophenyl-4,4-dimethyl-
3-(1H-1,2,4-triazol-1-
ylmethyl)pentan-3-ol
methyl (2E)-2-{2-[6-(2-
cyanophenoxy)pyrimidin-4-
yloxy]phenyl}-3-methoxyacrylate
CAS name
α-[2-(4-chlorophenyl)ethyl]-α-(1,1-
dimethylethyl)-1H-1,2,4-triazole-1-
ethanol
methyl (αE)-2-[[6-(2-cyanophenoxy)-
4-pyrimidinyl]oxy]-α-
(methoxymethylene)benzeneacetate
Molecular formula C16H22ClN3O C22H17N3O5
CAS Number 107534-96-3 131860-33-8
Molecular weight 307.82 g/mol 403.39 g/mol
Structural formula
Purity 975 g/kg 965 g/kg
Regulatory status
The regulatory history of azoxystrobin and tebuconazole is summarised in Table 4 below.
Table 4: Active ingredients regulatory status
Active ingredient
name
Regulatory history in
New Zealand
International regulatory history
(Australia, Canada, Europe,
Japan, USA)
Tebuconazole Approved (HSR002879) Approved in Australia, Canada,
Europe, Japan and USA
Azoxystrobin Approved (HSR100142) Approved in Australia, Canada,
Europe, Japan and USA
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Both tebuconazole and azoxystrobin are approved individually in New Zealand on a wide range of crops
(except sugar beet and fodder beet) at rates higher than those of Custodia® (up to 375 g/ha for
tebuconazole and up to 620 g azoxystrobin/ha), with different application methods (including aerial
application). The crops on which both active ingredients are currently used are listed below:
Azoxystrobin: barley, field tomato, grape, maize, onion, pea, potato, rye grass seed crop, sweetcorn, turf,
wheat.
Tebuconazole: wheat, barley, oats, ryegrass seed crop, pea, onion, summer fruit, pasture, grape.
However, they have never been approved as a combination in New Zealand previously.
Impurities and or restrictions on purity or composition
No relevant impurities have been identified by the Food and Agriculture Organization (FAO) or the Australian
Pesticides and Veterinary Medicines Authority (APVMA) on either active ingredient.
Use pattern and mode of action
Use pattern
Custodia® is intended to be used on sugar beet and fodder beet at rates of 1 L formulated product/ha,
corresponding to 200 g/ha tebuconazole and 120 g/ha azoxystrobin, with two application methods
(broadcast ground-based and aerial application). Full details are given in Table 5.
Mode of action
Tebuconazole belongs to the triazole group of fungicides that inhibit the 14-alpha-demethylase enzyme
which results in a disruption of the permeability of the fungal cell membrane. The accumulation of lanosterol
and other methylated sterols and a decrease in sterols, especially ergosterols, results in decreased fungal
growth and finally death. Tebuconazole does not prevent spore germination and some species of fungi can
still produce infective structures.
Azoxystrobin belongs to the oximino-acetate group of fungicides that has a different mode of action to
tebuconazole. The site of action of this group is in the mitochondrial respiration pathway (Complex III:
cytochrome bc1 and Qo site). This impacts cell respiration. It is an inhibitor of spore germination and mycelial
growth.
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Table 5: List of intended uses for Custodia®
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
Fodder
beet
Sugar
beet
F
Cercospora
beticola;
Erisiphe
betae;
Uromyces
beticola;
SC
Azoxystrobin
120g/L
Tebuconazole
200g/L
Ground
based
broadcast
spray
BBCH
12-BBCH
49
Spring-
Autumn
1-2 14 days
Azoxystrobin
Min: 0.03
Max: 0.06
Tebuconazole
Min: 0.050
Max: 0.100
200L
min
400L
max
Azoxystrobin
Min. 0.120
Max: 0.120
Tebuconazole
Min: 0.200
Max: 0.200
Fodder
beet
Sugar
beet
F
Cercospora
beticola;
Erisiphe
betae;
Uromyces
beticola;
SC
Azoxystrobin
120g/L
Tebuconazole
200g/L
Aerial
application
BBCH
12-BBCH
49
Spring-
Autumn
1-2 14 days
Azoxystrobin
Min: 0.1240
Max: 0.240
Tebuconazole
Min: 0.200
Max: 0.400
50L min
100L
max
Azoxystrobin
Min. 0.120
Max: 0.120
Tebuconazole
Min: 0.200
Max: 0.200
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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
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Appendix B: Physico-chemical properties of Custodia®
The physico-chemical properties of Custodia® are listed in Table 6.
Table 6: Physical and chemical properties of Custodia®
Property Value Reference
Colour White Liquid Application form
Odour Characteristic Application form
Physical state Suspension Concentrate Application form
Density 1.085 g/ml Application form
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Appendix C: Mammalian toxicology
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.
Executive summaries and list of endpoints for Custodia®
The mammalian toxicology data for Custodia® are summarised in Table 7.
Table 7: Summary of mammalian toxicology data for Custodia®
Endpoint
(Test Guideline)
Klimisch
score Result
HSNO
Classification Reference
Acute oral toxicity
(EC method B.1 and
OECD 423)
1 300 < LD50 ≤ 2000
mg/kg bw 6.1D
Appendix I; Table 62 ;
Report number: 24364
Acute dermal toxicity
(EC method B.3 and
OECD 402)
1 LD50 >2000 mg/kg bw No
Appendix I;
Table 63 ; Report
number: 24365
Acute inhalation toxicity
(EC method B.2 and
OECD 403)
1 LC50 >4.79 mg/L No
Appendix I; Table 64 ;
Project Number:
2684/0002
Skin irritation/corrosion
(EC method B.4 and
OECD 404)
1
Mean irritation score
(24, 48, and 72 hrs) –
Erythema: 0.1
Oedema: 0.0
No Appendix I; Table 65 ;
Report number: 24367
Eye irritation/corrosion
(EC method B.5 and
OECD 405)
1
Mean Draize Score
(24, 48, 72 hrs) –
Conjunctiva
-Redness: 0.33
-Chemosis: 0.0
Corneal opacity: 0.0
iritis: 0.0
No Appendix I; Table 66 ;
Report number: 24368
Contact sensitisation
(EC method B.6 and
OECD 406)
1
Magnusson and
Kligman grading scale:
Grade 1 skin reaction
in induction phases
and grade 0 in
challenge phase
No Appendix I;Table 67 ;
Report number: 24369
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Dermal absorption studies with tebuconazole are summarised in Table 8.
Table 8: Summary of dermal absorption studies with tebuconazole
Study type Results
Dermal absorption
Applicant has submitted in vitro dermal absorption studies on a number of formulation
types: soluble concentrate (SC), emulsifiable concentrate (EC), WG (water dispersible
granules) and flowable concentrate (FC) in rat and human skin and an in vivo dermal
absorption in rat on an EC formulation conducted using the concentrate and dilutions of
the formulations. The absorption values derived from in vitro human/rat studies were not
markedly different and are judged similar for occupational risk assessments. Average
dose and potentially absorbed dose differences for rat and human skin were calculated.
An in vivo dermal absorption study in rats on an EC formulation was considered to be
represent all tebuconazole formulations, based on the similarity of integrated data from
the in vitro human/rat studies.
Triple pack calculations were based on averaging maximum flux ratios across studies
and then calculating the ratio and using the average absorption values from the in vitro
studies. The most conservative absorption factors from these calculations were 1% for
the concentrate and 13% for the field dilution (OCS 2015). The in vivo dermal absorption
data from a monkey study summarised in EC DAR (EC 2007) further supports the
absorption factors derived from triple pack calculations.
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Appendix D: Environmental fate
Both active ingredients, azoxystrobin and tebuconazole, are already approved in New Zealand and data
were sourced from previous applications and the EPA substance database. Some data for azoxystrobin and
its metabolites were sourced from the European Union (EU) Renewal Assessment Report (RAR) on
azoxystrobin [ European Commission ; (EC 2009)].
Residues relevant to the environment
For both active ingredients in laboratory and field degradation studies in soil and water, major metabolites
(ie, those found at ≥ 10% applied radioactivity (AR) at any sample interval) were identified.
Azoxystrobin
For azoxystrobin, the metabolite, R234886 was considered a major metabolite in soil (laboratory maximum
28.8% and field maximum 67.7%) as well as in surface water (maximum 17.7% of applied radiation). In soil
two more major metabolites were identified namely R401553 and R402173 which were both observed at a
maximum of 17.7% of the applied radiation in the field studies.
The other major metabolite observed in the water was R230310 during the photolysis study (>10% of applied
radiation).
Ecotoxicological information was sourced from the European Union (EU) Renewal Assessment Report
(RAR) on azoxystrobin (EC 2009).
Tebuconazole
For tebuconazole, the metabolite 1,2,4-triazole accounted for up to 32.1% of applied radioactivity in soil
under aerobic conditions. No other information was provided that would indicate that any other soil
metabolites were exceeding 10% of applied radioactivity.
In aqueous systems, 1,2,4-triazole was found at levels up to 14%. Two additional major water metabolites
were identified: HWG 1608-pentanoic acid (maximum 40.2% AR) and HWG 1608-lactone (maximum 21.0%
AR).
Degradation and fate of azoxystrobin and tebuconazole in aquatic
environments
Information on the degradation and fate of azoxystrobin and tebuconazole in the aquatic environment is
summarised in Table 9 and Table 10 respectively. Information on bioaccumulation potential for azoxystrobin
and tebuconazole is listed in Table 11 and Table 12 respectively.
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Table 9: Degradation and fate in aquatic environments of azoxystrobin
Test type Value or conclusion for
azoxystrobin Reference
Ready biodegradation ND, considered to be not
readily biodegradable
EU RAR (EC 2009)
Aqueous photolysis half-life (DT50) 13.9 d
Degradation in aerobic water/sediment (DT50) 180- 234 d (whole system)
Water solubility at 20°C [mg/L] 6.0
Hydrolysis half-life (DT50) Stable at pH 5-9
Table 10: Degradation and fate in aquatic environment of tebuconazole
Test type tebuconazole Reference
Ready biodegradation No EPA substance database
Aqueous photolysis half-life (DT50) 590 d (pH 7, sunlight irradiation
for 30 d)
Degradation in aerobic water/sediment (DT50) 38.7 d (whole system)
Water solubility at 20°C [mg/L] 32
Hydrolysis half-life (DT50) Stable at pH 5, 7, 9.
Table 11: Bioaccumulation potential of azoxystrobin
Test type azoxystrobin Reference
Partition coefficient octanol/water [Log Kow] 2.5 EU RAR (EC 2009)
Fish bioconcentration (whole fish) ND
Table 12: Bioaccumulation potential of tebuconazole
Test type Active ingredient Reference
Partition coefficient octanol/water (Log Kow) 3.7 (pH 7.2, 20oC) EPA substance database
Fish bioconcentration (whole fish) BCF = 78 L/kg
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Degradation and fate of azoxystrobin and tebuconazole in soil
Information on the degradation and fate of azoxystrobin and its relevant metabolites in the soil environment
is summarised in Table 13 and information on the degradation and fate of tebuconazole and its major
metabolite 1,2,4-T triazole is given in Table 14.
Table 13: Degradation and fate of azoxystrobin and its metabolites in soil
Test type azoxystrobin metabolite Reference
Aerobic half-life in soil
(DT50lab)1 56.4, 66.9, 94.1, 72.8, 87,
141.6, 118.4, 153.4 days
80th percentile = 132.32
days
R234886
29.9, 25.5, 56.5, 31.8, 23.7
days
R4015531.4, 1.6, 2.0
daysR4021738.4, 4.2, 9.8
days
EU RAR (EC 2009)
Anaerobic degradation
in soil (DT50lab) 59.8, 49 days
EU RAR (EC 2009)
Aerobic half-life in soil
(DT50field)
186.4, 120.9 and 261.9
(SFO)
80.6, 61.3, 93.7, 121.6, 68,
34.5, 105, 66, 93.7, 73.7
(DOFB slow phase)
EU RAR (EC 2009)
Sorption to soil (Kd /
Koc)2
Kd:
12 sandy clay loam, 6.0
loamy sand, 9.0 loamy sand,
2.1 sand, 12 silty clay loam,
20 clay loam
Koc:
690 sandy clay loam,
357 loamy sand,
304 loamy sand,
724 sand,
739 silty clay loam,
718 clay loam
R234886
Kd: 1.0 loamy sand, 14.2
clay loam, 0.6 loamy sand,
2.3 sand, 9.1 silty clay loam,
1.1 sandy clay loam
Koc: 34 loamy sand, 514
clay loam, 32.4 loamy sand,
772 sand, 564 silty clay
loam, 65 sandy clay loam
R401553
Kd: 3 sandy clay loam, 1.1
loamy sand, 3.6 sandy loam,
17.6 silty clay loam, 2.2 silty
clay loam, 3.6 clay loam
Koc: 172 sandy clay loam,
376 loamy sand, 121 sandy
loam, 808 silty clay loam, 90
silty clay loam, 138 clay loam
R402173
EU RAR (EC 2009)
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Test type azoxystrobin metabolite Reference
Kd: 0.7 sandy clay loam, 0.3
loamy sand, 0.8 sandy loam,
5.5 silty clay loam, 2.4 silty
clay loam, 3.2 clay loam
Koc: 40 sandy clay loam,
101 loamy sand, 27 sandy
loam, 254 silty clay loam,
100 silty clay loam, 124 clay
loam
1: Upper 80% of stated values used for risk assessment
2: Lowest value non-sandy soil used for risk assessment
Table 14: Degradation and fate in soil of tebuconazole and its major soil metabolite 1,2,4-triazole
Test type Reference
Active ingredient Tebuconazole
Aerobic half-life in soil
(DT50lab)1 > 1 year (770 days)
EPA substance database
Aerobic half-life in soil
(DT50field)
57.5 days (upper 80th percentile of 57.5, 28.9, 29.5,
65.3, 25.8 and 48.4 days)
EPA substance database
Sorption to soil (Kd / Koc)1
Kd = 16.39; Koc = 910.4
Sandy loam kd = 12.69 koc = 906
Silt kd = 16.39 koc = 910.4
Low-humus sand kd = 7.67 koc = 1023
Sandy loam kd = 15.89 koc = 1249
EPA substance database
Metabolite 1,2,4-triazole
Aerobic half-life in soil
(DT50lab) No data available
Aerobic half-life in soil
(DT50field)
92.8 days (upper 80th percentile of slow phase DT50s
of 70.7, 59.8, 25.1 and 126 days).
EPA substance database
Sorption to soil (Kd / Koc)1
Koc = 43 (clay loam); Kd = 0.722 L/kg (silty clay loam)
Silty clay, Kd = 0.833 Koc = 120;
Clay loam Kd = 0.748 Koc = 43;
Sand Kd = 0.234 Koc = 2.2;
Silty clay loam Kd = 0.722 Koc = 104;
Sandy loam Kd = 0.719 Koc = 89
EPA substance database
1: Lowest non-sand value
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General conclusion about environmental fate
Azoxystrobin
Azoxystrobin is not readily biodegradable in the aquatic environment according to HSNO criteria (DT50 =16
days – 2 months and not readily biodegradable). The photolysis half-life is 13.9 days makes it a relevant
degradation pathway, azoxystrobin does not degrade via hydrolysis.
In aerobic soils laboratory studies, the DT50 ranged from 56.4 to 153.4 days and considered to be persistent
(DT50 80th percentile = 30 days – 6 months). Azoxystrobin has a medium to low mobility in soil according to
McCall classification system (McCall P.J., Laskowski D.A. et al. 1981).
Azoxystrobin has a low potential for bioaccumulation based on the log Kow of 2.5.
Three metabolites were formed in soil environment, R234886 (67.7% after 181 days), R401553 (5% day 9.8
and 5.7% day 31.3, in field 17%) and R402173 (5.4% day 9.8 and 7.6% day 31.3, in field 17%). These
metabolites are less persistent than the parent but all three have a very high to low mobility according to
McCall classification system (McCall P.J., Laskowski D.A. et al. 1981). R234886 is also formed in the aquatic
environment (17.7%) however, no information on the environmental fate of this metabolite in this medium is
available.
Tebuconazole
Tebuconazole is not readily biodegradable in aquatic environment according to HSNO criteria (DT50 16 days
– 2 months). Photolysis (DT50 = 590 days) and hydrolysis (stable) are not considered important degradation
pathways.
In soil, tebuconazole was persistent in laboratory (DT50 = 770 days) studies but not under field conditions
(representative DT50field = 57.5 days). It is expected to exhibit low mobility in soil according to McCall
classification system (McCall P.J., Laskowski D.A. et al. 1981).
It is not considered bioaccumulative in the environment based on the BCF for fish (78 L/kg).
The only soil metabolite considered in this assessment was 1,2,4-triazole, formed up to 32.1% AR. No
information is available for persistence of this metabolite in soil in a controlled environment, however the
metabolite is considered slightly degradable in field studies (DT50 = 92.8 days). The metabolite may be
considered very highly mobile in the soil environment based on standard soil adsorption/desorption data
(Koc = 43 L/kg) according to McCall classification system (McCall P.J., Laskowski D.A. et al. 1981).
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Appendix E: Ecotoxicity
Both active ingredients, azoxystrobin and tebuconazole, are already approved in New Zealand and data
were sourced from previous applications and the EPA substance database. Some data for azoxystrobin and
its metabolites were sourced from the European Union (EU) Renewal Assessment Report (RAR) on
azoxystrobin (EC 2009).
The applicant provided studies with the formulated product, these are summarised in Appendix I. Unless
otherwise noted, all studies were conducted according to GLP and were fully compliant with all requirements
of the standard international test methods used.
List of endpoints
Aquatic toxicity
Table 15 contains the acute and chronic aquatic toxicity test results for the active ingredient azoxystrobin,
Table 16 contains the acute and chronic aquatic test results for the azoxystrobin metabolites,
Table 17 contains the acute and chronic aquatic toxicity test results for the active ingredient tebuconazole,
Table 18 contains the acute and chronic aquatic test results for the tebuconazole metabolites and Table 19
contains the acute and chronic aquatic toxicity test results for the formulated product Custodia®. Values in
bold are those used for the risk assessment. Underlined values are those used to determine the
classification.
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Table 15: Summary of aquatic toxicity data for azoxystrobin
Test species Test type and
duration
Endpoint value
(mg/L) Reference
Fish Acute
Rainbow trout. Oncorhynchus
mykiss
96 hr LC50
0.47 EU RAR (EC 2009)
Common carp, Cyprinus carpio 1.6
Bluegill sunfish, Lepomis
macrochirus 1.1
Fish Chronic
Fathead minnow, Pimephales
promelas
33-d, ELS, Flow-
through, NOEC 0.147
EPA substance
database
Invertebrates Acute
Daphnia magna 48 hr EC50 0.23 EU RAR (EC 2009)
Macrocyclops fuscus 48 hr EC50 0.13 EPA substance
database
Chironomus riparius 48 hr EC50
(spiked water) 0.21
EU RAR (EC 2009)
Chronic
Daphnia magna
21-d
reproduction
NOEC
0.044
EU RAR (EC 2009)
Algae and aquatic macrophytes
Green alga, Selenastrum
capricornutum 72 hr ErC50 0.36
EU RAR (EC 2009)
Duckweed, Lemna gibba 7-d EC50 0.64 EPA substance
database
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Table 16: Summary of aquatic toxicity data for azoxystrobin metabolites
Test species Test type and
duration
Tebuconazole metabolites
Metabolite Value Reference
Rainbow trout, Oncorhynchus mykiss
96 hr LC50 R234886 >150 mg/L EU RAR (EC
2009)
Daphnia magna 48 hr EC50 R234886 >180
Green alga, Selenastrum capricornutum
72 hr EC50 R234886 47.0
Table 17: Summary of aquatic toxicity data for tebuconazole
Test species Test type and
duration
Tebuconazole
Reference
Fish Acute
Rainbow trout, Oncorhynchus
mykiss
96 hr LC50
4.4 mg/L
EPA substance
database
Bluegill sunfish, Lepomis
macrochirus 5.7 mg/L
Golden orfe (Leuciscus idus) 8.7 mg/L
Sheepshead minnow
(Cyprinodon variegatus)
5.9 mg/L
>7.82 mg/L
Chronic
Rainbow trout. Oncorhynchus
mykiss
83 d ELS, NOEC 0.012 mg/L
EPA substance
database
21 d, semi static,
NOEC 0.010 mg/L
Fathead minnow, Pimephales
promelas
FSDT1, 122-125 d,
NOEC
NOAEC
0.00625 mg/L;
0.0125 mg/L
Sheepshead minnow
(Cyprinodon variegatus)
36 d ELS, NOEC 0.0219 mg/L
FFLC2, 203 d,
NOEC 0.0436 mg/L
EPA substance
database
Invertebrates Acute
Daphnia magna 48 hr EC50 2.79 mg/L
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Test species Test type and
duration
Tebuconazole
Reference
Mysid shrimp (Mysidisopsis
bahia) 96 hr LC50 0.46 mg/L
EPA substance
database Eastern oyster (Crassostrea
virginica) 96 hr EC50 3.0 mg/L
Chronic
Daphnia magna
21 d flow through
NOEC 0.12 mg/L
EPA substance
database
21 d semi static
NOEC 0.010 mg/L
Mysid shrimp (Mysidisopsis
bahia)
28 d
NOEC
0.035 mg/L (formulation
FOLICUR)
Chironomus riparius
28 d, spiked water
NOEC emergence 2.33 mg/L
28 d spiked
sediment, NOEC
emergence
40 mg/kg sediment dw
Algae and aquatic macrophytes
Green alga,
Pseudokirchneriella
subcapitata
72 hr ErC50 2.83 mg/L
EPA substance
database Algae, Desmodesmus
subspicatus 72 hr ErC50 5.30 mg/L
Duckweed, Lemna gibba 14 d ErC50 0.144 mg/L
1) FSDT = Fish Sexual Development Test; 2) FFLC = Fish Full Life Cycle
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Table 18: Summary of aquatic toxicity data for tebuconazole metabolites
Test species Test type and
duration
Tebuconazole metabolites
Metabolite Value Reference
Rainbow trout,
Oncorhynchus
mykiss
96 hr LC50
HWG 1608-pentanoic acid >10 mg/L EPA substance
database
HWG 1608-lactone >10 mg/L
Daphnia magna 48 hr EC50
1,2,4-Triazole >100 mg/L EPA substance
database
HWG 1608-pentanoic acid >100 mg/L
HWG 1608-lactone >100 mg/L
Green alga,
Pseudokirchneriella
subcapitata
72 hr EC50
1,2,4-Triazole >31 mg/L EPA substance
database
HWG 1608-pentanoic acid >100 mg/L
HWG 1608-lactone >100 mg/L
Chironomus riparius 28 d EC15 HWG 1608-lactone 51.2 mg/L EPA substance
database
Table 19: Summary of aquatic toxicity data for Custodia®
Test species Test type and
duration
Test substance
Value Reference
Fish Acute
Rainbow trout. Oncorhynchus mykiss
96 hr LC50
5.4 mg formulation/L Appendix I, Table 69 ;
Project 47653230
Zebrafish, Danio rerio 7.8 mg formulation/L Appendix I, Table 68 ;
Project 44748230
Invertebrates Acute
Daphnia magna 48 hr EC50 2.15 mg formulation/L Appendix I, Table 70 ;
project 47652220
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Test species Test type and
duration
Test substance
Value Reference
Algae and aquatic macrophytes
Acute
Green alga, Pseudokirchneriella
subcapitata 72 hr ErC50 8.72 mg formulation/L
Appendix I; Table 71 ;
project 47651210
General conclusion about aquatic toxicity
Both active ingredients are already approved and are classified as 9.1A HSNO classification.
The metabolites for both active ingredients show a much lower toxicity profile compared with the parent
substance and therefore the aquatic risk assessment is considered to cover the metabolites (assuming the
persistence is similar to the parent). As the metabolites formed in soil (R234886, R401553, R402173, 1,2,4-
triazole) show a higher mobility, a groundwater assessment will be performed.
Custodia® triggers a 9.1B HSNO classification (ecotoxic in the aquatic environment) based on the provided
data with the formulation on fish, invertebrates and algae.
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Soil toxicity
Table 20 contains the acute and chronic soil toxicity test results for the active ingredient azoxystrobin and its
metabolites and Table 21 for the active ingredient tebuconazole and its metabolites.
Table 22 contains the acute and chronic soil toxicity test results for the formulated product Custodia®.
Values in bold are those used for the risk assessment.
Underlined values are those used to determine the classification.
Table 20: Summary of soil toxicity data for azoxystrobin and its metabolites
Test species Test type and duration Value Reference
Azoxystrobin
Earthworm, Eisenia
fetida
Acute, 14-d LC50 283 mg/kg dw soil
(EC50= 28.3 mg/kg dry soil)
EU RAR (EC 2009)
Reproduction, ND
Metabolites
Earthworm, Eisenia
fetida
Acute, 14-d LC50 R234886, R401553 and
R402173
> 1000 mg/kg dw soil
EU RAR (EC 2009)
Terrestrial plants
Azoxystrobin
Six dicot and four
monocot crop
species
Vegetative vigour, 21 days
Foliar application to
seedling plants
ND
Seedling emergence, 21
days
Application to soil surface
ER50 > 20 mg/kg dw soil
(equivalent to 15 kg ai/ha
based on 5 cm depth and
density 1.5 g/cm3)
EU RAR (EC 2009)
Soil microbial function
Soil microflora Nitrogen mineralisation, 28
days
No significant effects were
observed on nitrogen and
carbon mineralisation up to 2.5
g ai/ha.
The metabolites, R234886 (up
to 10 mg/kg soil), R401553 (up
to 2.6 mg kg/soil) and R402173
(up to 4.1 mg/kg soil), appear to
EU RAR (EC 2009)
Carbon mineralisation, 28
days
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Test species Test type and duration Value Reference
have no effects on soil
microbial processes
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Table 21: Summary of soil toxicity data for tebuconazole and its major soil metabolite
Test species Test type and
duration Test substance Result Reference
Soil macro fauna
Earthworm,
Eisenia
foetida
Acute, 14-day LC50 Tebuconazole LC50 = 1381 mg/kg soil dw EPA substance
database 1,2,4-Triazole LC50 >1000 mg/kg soil dw
Reproduction, Tebuconazole NOEC = 10 mg/kg soil dw
1,2,4-Triazole NOEC = 1.0 mg/kg soil dw
Springtail,
Folsomia
candida
Reproduction 28-
day
Tebuconazole NOEC = 250 mg/kg soil dw
1,2,4-Triazole NOEC = 1.8 mg/kg soil dw
Soil microbial function
Soil
microflora
Nitrogen
mineralisation, 28
days
Tebuconazole <25% effects at 8.23 mg/kg
soil dw
EPA substance
database
Carbon
mineralisation, 28
days
Table 22: Summary of soil toxicity data for Custodia®.
Test species Test type and
duration Custodia® Reference
Earthworm, Eisenia
fetida
Acute, 14-d LC50 >1000 mg formulation/kg soil Appendix I, Table
72; project
47657021
Reproduction, ND
Springtail, Folsomia
candida
Reproduction 28-d
NOEC
500 mg formulation/ kg soil Appendix I, Table
73; project
47742016
Terrestrial plants
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Test species Test type and
duration Custodia® Reference
Six dicot and four
monocot crop species
Vegetative vigour,
21-d NOER
Foliar application
to seedling plants
EC50 >3.375 L formulation/ha (limit test, tested
concentration)
(> 4.88 mg formulation/kg soil, based on 5 cm
depth and 1.5 g/cm3 density)
NOER ND
Appendix I, Table
74 ; project
47650087
Seedling
emergence, 21
days
Application to soil
surface
ND
Soil microbial function
Soil microflora Nitrogen
mineralisation, 56
days
No long term adverse effects, maximum
tested concentration 18 mg formulation/
kg dw soil (12.5 L formulation/ha)
Appendix I, Table
75 ; project
51941080
Carbon
mineralisation, 28
days
No adverse effects, maximum tested
concentration 18 mg formulation/ kg dw
soil (12.5 L formulation/ha)
Nitrogen
mineralisation, 41
days
No long term adverse effects, maximum
tested concentration 14.4 mg formulation/ kg
dw soil (5 L formulation/ha)
Appendix I, Table
76 ; project
47659080
Carbon
mineralisation, 28
days
No adverse effects, maximum tested
concentration 14.4 mg formulation/ kg dw soil
(5 L formulation/ha)
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General conclusion about soil toxicity
Both active ingredients are already approved. Azoxystrobin triggers 9.2C HSNO classification and
tebuconazole does not trigger the HSNO threshold for toxicity to the soil environment.
The toxicity of Custodia® could not be determined based on the formulation data available. Custodia®
shows some toxicity in the vegetative vigour test (13.1% at >3.375 L formulation/ha), however the
mechanism is unknown and could potentially also effect seedling emergence (exposure via soil). No
information on seedling emergence has been provided, and as effects cannot be excluded the
substance can potentially be toxic to seedlings via exposure through the soil.
The EPA attempted to classify the substance using mixture rules but insuffient information was
available. Given that the classification of multiple components is not known, the EPA could not
determine the classification, therefore it is ND for soil toxicity.
The major soil metabolites of azoxystrobin (R234886, R401553 and R402173) do not indicate toxicity,
these metabolites also degrade faster than the parent. Therefore, the risk assessment for the parent
is considered to cover the risks from the metabolites.
The major soil metabolite of tebuconazole (1,2,4-triazole) has a higher chronic soil toxicity and a
higher DT50 value in soil. Therefore, this metabolite has been included in the risk assessment.
Terrestrial vertebrate toxicity
For effects on terrestrial vertebrates other than birds, refer to the mammalian toxicity section.
Table 23 contains the acute and chronic avian toxicity test results for the active azoxystrobin and
Table 24 for the active ingredient tebuconazole.
Table 25 contains the acute and chronic avian toxicity test Custodia®.
Table 23: Summary of terrestrial vertebrate toxicity data for azoxystrobin
Test species
Test type
and
duration
azoxystrobin Reference
xBobwhite quail,
Colinus
virginianus
Acute oral
LD50 >2000 mg/kg bw
EU RAR (EC 2009)
8-d dietary
LC50
>5200 mg/feed
(>1179 mg/kg bw/day)
Reproductive
1 generation,
22 weeks
NOEL
1200 mg/kg feed
(117 mg/kg bw/day)
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Test species
Test type
and
duration
azoxystrobin Reference
Mallard duck,
Anas
platyrhynchos
Acute oral
LD50 >2000 mg/kg bw1
EU RAR (EC 2009)
8-d dietary
LC50
>5200 mg/kg feed
(>1754 mg/kg bw/day)
Reproductive
1 generation,
21 weeks
NOEC
1200 mg/feed
(187 mg/kg bw/day)
1: regurgitation observed and the recommended reduction of the LD50 is 1000 mg/kg bw. However, as no mortality was
observed and the study with the bobwhite quail also has an LD50 of 2000 mg/kg bw the endpoint for risk assessment will be
2000 mg/kg bw.
Table 24: Summary of terrestrial vertebrate toxicity data for tebuconazole
Test species
Test type
and
duration
Test item Reference
Bobwhite quail,
Colinus
virginianus
Acute oral
LD50
1555 mg/kg bw
EPA substance database
1988 mg/kg bw
8-day dietary
LC50
>703 mg/kg bw bw/d (>5000 mg/kg
diet)
Reproductive
NOEL = 5.8 mg/kg bw/d (73.5
mg/kg diet)
LOEL = 12.4 mg/kg bw/d (156
mg/kg diet)
Mallard duck
(Anas
platyrhynchos)
8-day dietary
LC50 >4816 mg/kg diet
Reproductive
NOEC reproduction 75.8 mg/kg diet
NOEC reproduction 170 mg/kg
diet (17.7 mg/kg bw/d)
Table 25: Summary of terrestrial vertebrate toxicity data for Custodia®
Test species Test type and
duration Custodia® Reference
Japanese quail,
Coturnix japonica Acute oral LD50 >2000 mg ai/kg bw
Appendix I, Table 77 ; project
24366
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Test species Test type and
duration Custodia® Reference
8-d dietary LC50 ND
Reproductive 1
generation, 22 weeks
NOEC
ND
General conclusion about ecotoxicity to terrestrial vertebrates
Both active ingredients are already approved. Tebuconazole triggers 9.3C HSNO classification and
azoxystrobin does not trigger the HSNO threshold for toxicity to terrestrial vertebrates based on the
data available.
Custodia® does not trigger the HSNO thresholds for toxicity to the terrestrial vertebrates based on the
data available.
Ecotoxicity to bees and other terrestrial invertebrates
Table 26 contains the toxicity test results for the active ingredient azoxystrobin on non-target
organisms and Table 27 for the active ingredient tebuconazole.
Table 28 contains the toxicity test results for Custodia® on non-target organisms.
Table 26: Summary of terrestrial invertebrate toxicity data for azoxystrobin
Test species Test type and
duration azoxystrobin Reference
Honeybee, Apis
mellifera
48 hr, Acute
oral, LD50 >25 µg ai/ bee EU RAR (EC 2009)
24 hr Acute
contact LD50 >200 µg ai/ bee
EU RAR (EC 2009)
Parasitic wasp,
Aphidius
rhopalosiphi
48 hr LR50
laboratory glass
plate
>1000 g ai/ha
Predatory mite,
Typhlodromus pyri
48 hr LR50
laboratory glass
plate
>1500 g ai/ha
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Table 27: Summary of bees toxicity data for tebuconazole
Test species Test type and
duration tebuconazole Reference
Tebuconazole
Honeybee, Apis
mellifera
Acute oral LD50 >83.05 µg/bee
EPA substance database
Acute contact LD50 >100 µg/bee
Table 28: Summary of bees toxicity data for Custodia®
Test species Test type and
duration Custodia® Reference
Honeybee, Apis
mellifera
Acute oral, 48 hr
LD50
>208.4 μg
formulation/bee Appendix I, Table 78 ;
project 47741035
Acute contact LD50 >200 μg
formulation/bee
Table 29: Summary of terrestrial invertebrate toxicity data for Custodia®
Test species Test type and
duration Custodia® Reference
Parasitic wasp,
Aphidius rhopalosiphi
48 hr LR50 Extended
laboratory residues
on barley
605 mL formulation/ha
Appendix I, Table
79 ; project
47744002
48 hr LR50 Extended
laboratory dry
residues on beans
The effects of MCW 710
SC (3.38 L/ha) were
below the trigger value of
50% on mortality and
fecundity.
Appendix I, Table
80 ; project
47654003
Predatory mite,
Typhlodromus pyri
7 d LR50
Extended laboratory
dry residues on
beans
> 3375 mL
formulation/ha
Effects on reproduction
are above 50% for the
dose rates 171, 463 and
3375 mL formulation/ha.
Appendix I, Table
84 ; project
47745062
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Test species Test type and
duration Custodia® Reference
7 d LR50
Extended laboratory
fresh and dry
residues on beans
> 3.38 L/ha.
Appendix I, Table
83 ; project
47655060
Field study, grape
vines effect on
population
No unacceptable effects
were observed after 2
applications with MCW
710 SC at a rate of 0.263
and 0.438 L/ha.
Appendix I, Table
85 ; project FCS02
Green lacewing,
Chrysoperla carnea
48 hr LR50
Extended laboratory
dry residues on
beans
>3.375 L formulation/ha
Appendix I, Table
82 ; project
47747047
Ladybird beetle,
Coccinella
septempunctata
20 d LR50
extended laboratory
dry residues on
beans
>3.375 L formulation/ha
Appendix I, Table
81 ; project
47746012
General conclusion about ecotoxicity to bees and terrestrial invertebrate toxicity
Both active ingredients are already approved. Azoxystrobin and tebuconazole do not trigger the
HSNO threshold for toxicity to terrestrial invertebrates.
Custodia® does not trigger the HSNO thresholds for toxicity to the terrestrial invertebrates based on
the data available.
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Appendix F: Hazard classification of Custodia®
The hazard classifications of Custodia® are listed in Table 30.
Table 30: Applicant and EPA classifications of Custodia®1
Hazard Class/Subclass
Mixture
classification
by:
Method of classification
Remarks
Applicant EPA
Mix
ture
data
Read
acro
ss
Mix
ture
ru
les
Class 1 Explosiveness No ND
Class 2, 3 & 4 Flammability No ND
Class 5 Oxidisers/Organic
Peroxides No ND
Subclass 8.1 Metallic
corrosiveness No ND
Subclass 6.1 Acute toxicity
(oral) 6.1E 6.1D
300 < LD50 ≤ 2000
mg/kg bw
Subclass 6.1Acute toxicity
(dermal) No No LD50 >2000 mg/kg bw
Subclass 6.1 Acute toxicity
(inhalation) No No LC50 >4.79 mg/L
Subclass 6.1 Aspiration
hazard No No
Subclass 6.3/8.2 Skin
irritancy/corrosion No No
Subclass 6.4/8.3 Eye
irritancy/corrosion No No
Subclass 6.5A Respiratory
sensitisation No ND
Subclass 6.5B Contact
sensitisation No No
Subclass 6.6 Mutagenicity No ND
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.
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Hazard Class/Subclass
Mixture
classification
by:
Method of classification
Remarks
Applicant EPA
Mix
ture
data
Read
acro
ss
Mix
ture
ru
les
Subclass 6.7
Carcinogenicity No ND
Subclass 6.8 Reproductive/
developmental toxicity 6.8B 6.8B Tebuconazole
Subclass 6.8 Reproductive/
developmental toxicity (via
lactation)
Subclass 6.9 Target organ
systemic toxicity (oral) 6.9B 6.9B
Tebuconazole ;
azoxystrobin
Subclass 6.9 Target organ
systemic toxicity (dermal)
Subclass 6.9 Target organ
systemic toxicity (inhalation)
Subclass 9.1 Aquatic
ecotoxicity 9.1A 9.1B
EC50 Daphnia magna =
2.15 mg formulation/L
Subclass 9.2 Soil ecotoxicity No ND
Subclass 9.3 Terrestrial
vertebrate ecotoxicity No No
Subclass 9.4 Terrestrial
invertebrate ecotoxicity No No
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: No Data or poor quality data [according to Klimisch criteria (Klimisch, Andreae et al. 1997)]. There is a lack
of data for one or more components.
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.
Mammalian toxicity studies with Custodia® indicate that the substance is of low acute toxicity and
should be classified 6.1D for acute oral toxicity. The substance is not irritating to the skin or eyes, and
is not a contact sensitiser. Based on mixture rules, Custodia® should be classified 6.8B and 6.9B
(oral). Based on test data for the formulation, Custodia® should also be classified 6.1D and 9.1B but
does not require classification as being toxic to terrestrial vertebrates or invertebrates
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Appendix G: Human health risk assessment
Quantitative risk assessment
The operator exposure assessment is based on a modification of the approach used by European
regulators, taking into account New Zealand specific factors. The model is based on the results of
actual measurements carried out in the field and has an established history of providing reliable and
reproducible results.
The re-entry worker exposure assessment is based on a modification of the approach used by
European regulators and the US EPA. The parameters for the modelling are based on empirical data
relating to measurements of dermal exposure of workers from contact with residues on foliage for
various activities and the amount of foliar residues that are dislodgeable.
The bystander exposure assessment is based on a modification of the approaches used by European
regulators and the US-EPA. Spray drift deposition from ground based application is estimated using
the AgDrift model using the curves produced by the Australian Pesticides and Veterinary Medicines
Authority [APVMA, (APVMA 2010)]. The parameters are based on empirical data. Spray drift
deposition from aerial application is estimated using the AGDISP model along with appropriate New
Zealand input parameters.
Full details of the methodology can be found in the EPA risk assessment methodology document
(EPA 2018).
To assess risks the predicted systemic exposures to the active ingredient(s) are compared with an
acceptable operator exposure limit (AOEL) for the active ingredient and a risk quotient (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
Custodia® is a fungicide containing 200 g/L tebuconazole and 120 g/L azoxystrobin in a suspension
concentrate formulation for control of foliar diseases of forage beet crops. Neither tebuconazole nor
azoxystrobin are approved on sugar beet and fodder beet. In addition, there is no existing approved
substance that contain both active ingredients in combination to date. The EPA decided to
quantitatively assess the risk only for tebuconazole because it has higher application rates (200 g
ai/ha versus 120 g ai/ha), a more conservative AOEL (0.03 mg/kg bw/day versus 0.20 mg/kg bw/day),
and is present at a higher concentration in the substance (200 g/L versus 120 g/L) than azoxystrobin.
Thus, all controls used to support the safe use of tebuconazole will automatically support and protect
against any risk associated with azoxystrobin.
Reference doses for tebuconazole established by internationally reputable regulatory authorities are
summarised in Table 31.
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Table 31: Reference doses established by regulators
Available
international
Reference
doses
Key systemic
effect
NOAEL
mg/kg
bw/d
Uncertaint
y factors
Reference
value (nature
of the value)
mg/kg bw/d
Staff’s
modifications Remarks
ADI-
Tebuconazole –
(EFSA 2014)
Subtle hypertrophy of
adrenal zona
fasciculate cells in all
animals of the 150 ppm
group was observed.
3 100 0.3 None None
ARfD-
Tebuconazole –
(EFSA 2014)
Increased enzyme
activity in livers and
increased post
implantation loss,
increased external
skeletal and visceral
anomalies
10 100 0.1 None None
The relevant toxicity studies that were considered to derive an acceptable operator exposure level
(AOEL) for tebuconazole are summarised in Table 32.
Table 32: Summary of studies relevant for establishing an AOEL
Key systemic effect
NOAEL
(mg/kg
bw/d)
Uncertainty
factors
Absorption
factor
AOEL
mg/kg
bw/d
Justification
Subtle hypertrophy of
adrenal zona fasciculate
cells in all animals of the
150 ppm group was
observed.
3 100 - 0.03
Conservative NOAEL; dogs were
found to be the most sensitive
species in short-term studies
Other input values for the exposure assessment are summarised in Table 33.
The applicant has submitted in vitro dermal absorption studies on a number of formulation types:
soluble concentrate (SC), emulsifiable concentrate (EC), WG (water dispersible granules) and
flowable concentrate (FC) in rat and human skin and an in vivo dermal absorption in rats on an EC
formulation conducted using the concentrate and dilutions of the formulations. The absorption values
derived from in vitro human/rat studies were not markedly different and are judged similar for
occupational risk assessments. Average dose and potentially absorbed dose differences for rat and
human skin were calculated. An in vivo dermal absorption study in rats on an EC formulation was
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considered to be represent all tebuconazole formulations, based on the similarity of integrated data
from the in vitro human/rat studies.
Triple pack calculations were based on averaging maximum flux ratios across studies and then
calculating the ratio and using the average absorption values from the in vitro studies. The most
conservative absorption factors from these calculations were 1% for the concentrate and 13% for the
field dilution (OCS 2015). The in vivo dermal absorption data (13.02%) from a rhesus monkey study
summarised in EC DAR (EC 2007) and EFSA (EFSA 2014) further supports the absorption factors
derived from triple pack calculations.
Table 33: Input values for human exposure modelling
Active
ingredient
Physical
form
Concentration
of each active
(%)
Maximum
application rate
(for each active,
for each
method of
application)
g ai/ha
Dermal absorption
(%)
AOEL
mg/kg
bw/d
Concentrate Spray
Tebuconazole Liquid
(suspension
concentrate)
18.433 200 (for aerial and
ground based
application)
1 13 0.03
Operator exposure assessment
The results of the operator exposure assessment are shown in Table 34.
Table 34: Output of operator mixing, loading and application exposure assessment for
tebuconazole
Exposure Scenario Estimated operator
exposure (mg/kg bw/d)
Risk
Quotient
Boom
No personal protective equipment (PPE)2 during mixing, loading and
application
0.0623 2.08
Gloves only during mixing and loading 0.0577 1.92
Gloves only during application 0.0528 1.76
Full PPE during mixing, loading and application (excluding respirator) 0.0042 0.14
2 ‘Full PPE’ includes: gloves, hood/visor, coveralls, and heavy boots during application and gloves during mixing and loading.
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Full PPE during mixing, loading and application (including FP1, P1 and
similar respirator achieving 75 % inhalation exposure reduction)
0.0040 0.13
Full PPE during mixing, loading and application (including FP2, P2 and
similar respirator achieving 90 % inhalation exposure reduction)
0.0039 0.13
Predicted operator exposures to tebuconazole are below the Acceptable Operator Exposure Level
(AOEL), provided full PPE (gloves, hood/visor, coveralls, and heavy boots without a respirator) is
worn during mixing, loading, and application. Therefore operator exposures to Custodia® are not
expected to result in adverse health effects, if adequate PPE is worn. Risks associated with the
operator during aerial application are believed to be lower than those determined for boom as
exposure to the applicator is qualitatively deemed to be negligible during application. Accordingly, no
PPE is required for the operator during aerial application.
Re-entry worker exposure assessment
The results of the re-entry worker exposure assessment are summarised in Table 35.
Table 35: Output of the re-entry worker exposure assessment for tebuconazole
Active
ingredient Crop/activity
Internal (absorbed)
dose available for
systemic
distribution
(mg/kg bw/8 hours)
AOEL
(mg/kg
bw/d)
Risk Quotient
immediately
after
application
Re-entry
interval
without
gloves
Tebuconazole
Fodder beet and
sugar beet /
scouting,
irrigation
0.02 0.03 0.61 0.0
Risk Quotient resulting from predicted exposures to tebuconazole for workers re-entering and working
in areas where Custodia® has been applied are below the LOC. No re-entry intervals are necessary.
Quantitative bystander risk assessment
It is considered that the main potential source of exposure to the general public for substances of this
type (other than via food residues which will be considered as part of the registration of this substance
under the Agricultural Compounds and Veterinary Medicines (ACVM) Act 1997) is via spray drift. In
terms of bystander exposure, toddlers are regarded as the most sensitive sub-population and are
regarded as having the greatest exposures. For these reasons, the risk of bystander exposure is
assessed in this sub-population. The AOEL calculated for the operator and re-entry worker exposure
assessments has been used for the bystander assessment, as the use of an oral chronic reference
dose (CRfD) is usually likely to be over precautionary.
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The results of the bystander exposure assessment are summarised in Table 36.
Table 36: Output of the bystander exposure assessment for tebuconazole
Exposure Scenario
Estimated exposure of
15 kg toddler exposed
through contact to
surfaces 8 m from an
application area
(µg/kg bw/d)
Risk Quotient
Buffer zone needed
to reduce toddler
exposure to the
AOEL
Boom
High boom, fine droplets 1.30 0.0433 0
High boom, coarse droplets 0.21 0.0069 0
Low boom, fine droplets 0.44 0.0146 0
Low boom, coarse droplets 0.10 0.0035 0
Aerial - agriculture
Swath width 20 m, Med-coarse
droplet size
7.73 0.2576 0
Swath width 20 m, coarse- v.
coarse droplets
6.77 0.2257 0
Swath width 20 m, extremely
coarse droplets
6.05 0.2018 0
Swath width 24 m, v. fine-fine
droplets
10.53 0.3511 0
Swath width 24 m, fine-med.
droplets
12.17 0.4058 0
Swath width 24 m, med.-coarse
droplets
13.01 0.4337 0
Estimated bystander exposure from spray drift after application of Custodia® to the soil around fodder
beet and sugar beet is below the AOEL. No buffer zone is required in protect bystanders.
Groundwater contamination risk assessment
The ecotoxicity assessment (see appendix H; Table 48) has identified that the metabolite 1,2,4-triazole
may occur in ground water after application of the substance. Therefore TEL (Drinking Water) have
been derived which can be used if necessary to assess the significance of ground water concentrations
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if the residues are found in sources used for human consumption. For this, ADI for 1,2,4-triazole
established by the European Food Safety Authority (EFSA 2014) is summarised in Table 37 below.
Table 37: Using an existing ADE, ADI or CRfD for 1,2,4-triazole
Available
international
toxicological
thresholds
NOAEL
(mg/kg
bw/day)
Uncertainty
factors
ADE
(mg/kg
bw/day)
EPA
Modifications Remarks
[ADI]
(EFSA 2014) 20.0 1000 0.02 None
Based on the rat
multigeneration study.
Exposure Thresholds
The EPA has reviewed health based exposure guidance values established by overseas regulators
(Table I-3) to inform the selection of ADE and PDE values for 1,2,4-triazole (Table 38).
Table 38: Metabolite exposure thresholds
Metabolite
Acceptable Daily
Exposure (ADE) – mg/kg
bw/d
Potential Daily
Exposure (PDE) –
mg/kg bw/d
Tolerable Exposure
Limit (TEL)
mg/L (water)
1,2,4-triazole 0.02 PDE (Drinking water) =
0.004
TEL (Drinking Water) =
0.004
TEL (Drinking Water) = [PDE (Drinking Water) x adult body weight]/ 2 L
TEL (Drinking Water) = 0.004 (mg/kg bw/day) x 70 kg/2L/day = 0.14 mg/L
The assumptions involved are that the value applies to an adult human with a body weight of 70 kg and
that an adult who consumes 2 litres of drinking water/day (the standard value used by the Ministry of
Health and the World Health Organization to derive drinking water standards).
The estimated ground water concentration of 1,2,4-triazole from the application of Custodia® has been
estimated using SciGrow as 0.11 μg/L (see Appendix H). The EPA notes that this value is lower than
the TEL (Drinking Water) derived for 1,2,4-triazole which suggests that ground water concentrations
result in acceptable risks after use of Custodia®.
Conclusions of the human health risk assessment
It is considered that the risks to human health from the proposed use of Custodia® are acceptable
with the use of appropriate and full Personal Protective Equipment (PPE). No REIs are required to
protect crop worker re-entry. No buffer zone is required to protect bystanders.
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Appendix H: Environmental risk assessment
Evaluation of toxicity of the mixture
The formulations and tank mixes consist of multiple components which potentially can have effects
deviating from additivity by showing toxicity which is more than additive (synergism) or less than
additive (antagonism). The nature of these mixtures will be evaluated if the formulation consists of
multiple active ingredients or when tank mixes are considered “mandatory” on the label (ie the
formulation should be mixed with a specific other product). To evaluate the toxicity of the components
in the formulation the toxicity is evaluated using the methodology described by EFSA (EFSA 2013).
Evaluation of mixtures is complicated for long-term scenarios, since environmental fate information on
the whole formulation is generally not available.
To enable an assessment regarding the relative toxicity of the formulation the calculated toxicity of the
formulation is determined using the Concentration Addition (CA) model (see equation 1).
𝐸𝐶𝑥𝑓𝑜𝑟𝑚𝑢𝑙𝑎𝑡𝑖𝑜𝑛−𝐶𝐴 = (∑𝑃𝑖
𝐸𝐶𝑥𝑖
𝑛
𝑖=1
)
−1
Equation 1: Determination of calculated toxicity following the concentration addition model
Where:
n: number of components included in evaluation
i: index from 1 – n mixture components
Pi: The ith component as relative fraction of the mixture (sum of Pi should be 1, therefore a final component with very low toxicity, 10,000 mg/L, 10,000 mg/kg, 10,000 mg/ha, 10,000 mg/kg bw is added to the equation)
ECxi: Concentration of component i provoking X% effect.
This calculated toxicity is compared with the toxicity of the formulation measured in the toxicity test to
calculate the Model Deviation Ratio (MDR) which can be found in equation 2.
𝑀𝐷𝑅 = 𝐸𝐶𝑥𝑓𝑜𝑟𝑚𝑢𝑙𝑎𝑡𝑖𝑜𝑛−𝐶𝐴
𝐸𝐶𝑥𝑓𝑜𝑟𝑚𝑢𝑙𝑎𝑡𝑖𝑜𝑛
Equation 2: Calculation of the Model Deviation Ratio (MDR)
ECxi: Concentration of component i provoking X% effect, formulation-CA (see equation X), formulation measured toxicity.
Based on the values of the MDR it can be determined if the formulation shows additive, more than
additive or less than additive toxicity.
MDR 0.2 – 5: Non-additive / Additive: independent toxic effects / one substance contributes to
the effect of one or more of the other substances (concentration addition / partial addition)
MDR >5: More than additive (synergism): enhancement of effects, the combined effect is
greater than the sum of the individual effects
MDR <0.2: Less than additive (antagonism): attenuation of toxic effects
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Table 39: Additivity evaluation
Test Azoxystro
bin
Tebuco-
nazole
Formulation
calculated
Formulation
measured MDR Conclusion
Fish acute
LC50 (mg/L) 0.47 4.4 3.6 5.4 0.7 In agreement
Daphnid
acute
EC50 (mg/L)
0.23 2.79 1.8 2.15 0.85 In agreement
Algae
ErC50 (mg/L) 0.36 2.83 2.7 8.72 0.31 In agreement
Earthworm
acute
LC50 (mg/kg)
283 1381 1681 >1000 <1.68
Inconclusive likely
in agreement. Else
less than additive
Bird acute
LD50 (mg/kg
bw) >2000 1555 4092.5 >2000 >/<2.0
Inconclusive likely
in agreement.
Toxicity low
therefore no
concern
Bee oral
LD50 (µg/bee) >25 >83.05 148.9 >208.4 >/<0.7
Inconclusive likely
in agreement.
Toxicity low
therefore no
concern
Bee dermal
LD50 (µg/bee) >200 >100 405.4 >200 >/<2.0
Inconclusive likely
in agreement.
Toxicity low
therefore no
concern
For active ingredients in formulations that behave in an additive manner it is considered that a risk
assessment based on the test results with “pure” active ingredients will adequately reflect the toxic
effects in the field.
For active ingredients in formulation that behave in a less than additive manner considered that a risk
assessment based on the test results with “pure” active ingredients results in the most conservative
approach potentially overestimating the effects in the environment. However, the antagonistic
interaction only occurs when an organism is exposed to the antagonistic components at the same
time. It is highly likely that these antagonistic components have a different degradation pattern and
thus it is still possible that the components will not behave antagonistically in the environment.
Therefore, the approach to evaluate toxicity using the test results with “pure” active ingredients is
considered justified.
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For active ingredients in formulations that behave in a more than additive manner the risk
assessments based on the test results of “pure” active ingredients are likely to be underestimating the
risks. Co-occurrence of the synergistic components is likely directly after the application and therefore
the potential risk from the formulation should be considered and not just the acute risk from the active
ingredient. Based on the results expert judgement is required to determine which assessment is the
most appropriate one (eg more sensitive species were tested with the active ingredient).
Based on the additivity assessment, it was determined that for the endpoints that are assessed, the
components in the formulation interacted in agreement. Consequently, the acute assessment for the
endpoints will be based on the “pure” active ingredients. For all endpoints, controls managing the
risks from the “pure” active ingredients will manage the risks from the formulation.
For practical application, if a single active ingredient can be shown to contribute ≥90% towards toxicity
and the formulation does not deviate from additivity, the (acute) risk assessment will be performed for
that active constituent only. The relative contribution of each active constituent may be determined
according using the toxic unit concept (Equation 3). This approach can only be taken for the acute
toxicity assessment since during prolonged exposure environmental fate processes are likely
changing the ratio of the components in the formulation.
%𝑟𝑒𝑙𝑎𝑡𝑖𝑣𝑒_𝑒𝑐𝑜𝑡𝑜𝑥𝑖𝑐𝑖𝑡𝑦_𝑐𝑜𝑛𝑡𝑟𝑖𝑏𝑢𝑡𝑖𝑜𝑛 =
𝑝𝑖𝐸𝐶𝑥𝑖
∑𝑝𝑖
𝐸𝐶𝑥𝑖
𝑛𝑖=1
× 100
Equation 3: Determination of contribution of toxicity of the active ingredients
n: number of components included in evaluation
i: index from 1 – n mixture components
Pi: The ith component as relative fraction of the mixture (sum of Pi should be 1, therefore a final component with very low toxicity, 10,000 mg/L, 10,000 mg/kg, 10,000 mg/ha, 10,000 mg/kg bw is added to the equation)
ECxi: Concentration of component i provoking X% effect.
Table 40: Contribution of active ingredients to toxicity of formulation
Test azoxystrobin tebuconazole
Fish acute 85 15
Daphnid acute 88 12
Algae 82 17
Earthworm
acute
66 22
Bird acute 32 68
Bee oral 66 33
Bee dermal 22 75
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Based on the relative contribution of the active ingredients to the toxicity of the formulation, it was
concluded that the risk assessment has to be performed for both active ingredients.
When data on metabolites of the active ingredients indicate that these are less toxic than the parent
for a specific environment , the risk assessment focusses on the active ingredient. When data on
metabolites of the active ingredients indicate that these are more toxic than the parent, an
assessment of this metabolite will be performed as well.
Aquatic risk assessment
The basis for the aquatic risk assessment is a comparison of the Expected Environmental
Concentrations (EEC) with toxicity endpoints to which safety factors have been applied. The EEC is
divided by the toxicity endpoint to calculate a risk quotient (RQ) value. The methodology for the aquatic
risk assessment, including the level of concern (LOC) ascribed to specific RQ values, is described in
detail in the EPA standard risk assessment methodology (EPA 2018).
The major metabolites of tebuconazole (HWG 1608-pentanoic, HWG 1608-lactone, 1,2,4-triazole)
have a lower acute toxicity for aquatic species than the parent tebuconazole. Therefore, the
assessment of the parent covers these metabolites as well.
The major metabolites of azoxystrobin (R401553 and R402173) have a lower acute toxicity for
aquatic species than the parent azoxystrobin. Therefore, the assessment of the parent covers these
metabolites as well.
Calculation of expected environmental concentrations
The parameters used in GENEEC2 modelling are listed in Table 41.
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Table 41: Input parameters for GENEEC2 analysis for the active ingredients
Parameter Azoxystrobin Tebuconazole
Crop(s) Fodder and sugar beet Fodder and sugar beet
Application rate
(kg/ha)
0.12 0.2
Application
frequency
2 2
Application interval
(days)
14 14
Kd 12 16.39
Aerobic soil DT50
(days)
132.32 57.5
Pesticide wetted in? no no
Methods of
application
Ground boom, high boom
Aerial
Ground boom, high boom
Aerial
‘No spray’ zone 0 0
Water solubility
(ppm)
6.0 32
Hydrolysis (DT50 in
days)
stable stable
Aerobic aquatic
DT50 whole system(days)
234 38.7
Aqueous photolysis
DT50 (days)
13.9 590
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Output from the GENEEC2 model
Azoxystrobin
Ground based
RUN No. 2 FOR azoxystrobin ON beet * INPUT VALUES *
--------------------------------------------------------------------------------------------------------------
RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP
ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)
-------------------------------------------------------------------------------------------------------------
0.107( 0.206) 2 14 12.0 6.0 GRHIFI( 6.6) 0.0 0.0
FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)
--------------------------------------------------------------------
METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED
(FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)
--------------------------------------------------------------------------------------------------------------------------
132.32 2 N/A 13.90- 1723.60 234.00 206.03
GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001
---------------------------------------------------------------------------------------------------------------
PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY
GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC
--------------------------------------------------------------------------------------------------------------
4.84 4.81 4.62 4.23 3.97
Aerial
RUN No. 2 FOR azoxystrobin ON beet * INPUT VALUES *
------------------------------------------------------------------------------------------------------------
RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP
ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)
-------------------------------------------------------------------------------------------------------------------
0.107( 0.206) 2 14 12.0 6.0 AERL_B( 13.0) 0.0 0.0
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FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)
------------------------------------------------------------------------------------------------------------------------
METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED
(FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)
------------------------------------------------------------------------------------------------------------------------
132.32 2 N/A 13.90- 1723.60 234.00 206.03
GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001
---------------------------------------------------------------------------------------------------------------
PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY
GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC
------------------------------------------------------------------------------------------------------------------
5.36 5.33 5.12 4.70 4.40
Tebuconazole
Ground based
RUN No. 3 FOR tebuconazole ON beet * INPUT VALUES *
------------------------------------------------------------------------------------------------------------------
RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP
ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)
--------------------------------------------------------------------------------------------------------------
0.178( 0.328) 2 14 16.4 32.0 GRHIFI( 6.6) 0.0 0.0
FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)
--------------------------------------------------------------------------------------------------------------------
METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED
(FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)
--------------------------------------------------------------------------------------------------------------------
57.50 2 N/A 590.00-73160.00 38.70 38.68
GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001
------------------------------------------------------------------------------------------------------------
PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY
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GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC
----------------------------------------------------------------------------------------------------------------
5.96 5.85 5.23 4.11 3.48
Aerial
RUN No. 4 FOR tebuconazole ON beet * INPUT VALUES *
-----------------------------------------------------------------------------------------------------------------
RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP
ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)
---------------------------------------------------------------------------------------------------------------
0.178( 0.328) 2 14 16.4 32.0 AERL_B( 13.0) 0.0 0.0
FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)
---------------------------------------------------------------------------------------------------------------------
METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED
(FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)
---------------------------------------------------------------------------------------------------------------------
57.50 2 N/A 590.00-73160.00 38.70 38.68
GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001
---------------------------------------------------------------------------------------------------------------------
PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY
GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC
----------------------------------------------------------------------------------------------------------------------
6.70 6.59 5.90 4.65 3.93
The maximum Estimated Environmental Concentrations (EEC) for azoxystrobin when used in
Custodia® as estimated by GENEEC2 is 5.36 μg/L for the aerial application.
The maximum Estimated Environmental Concentrations (EEC) for tebuconazole when used in
Custodia® as estimated by GENEEC2 is 6.70 μg/L for the aerial application.
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Calculated risk quotients
The calculated acute risk quotients for each trophic level considering the above EEC and lowest
relevant toxicity figures are presented in Table 42. The calculated chronic risk quotients are presented
in Table 43.
The aerial application is worst case. Therefore, the assessment focusses on this application first.
When the model indicates that the risks of this application is below LOC, the ground-based
application will not be assessed.
Table 42: Acute risk quotients derived from the GENEEC2 model and toxicity data
Species
Peak EEC
from
GENEEC2
(mg/L)
LC50 or
EC50
(mg/L)
Acute
RQ Conclusion
AERIAL
Azoxystrobin
Fish, Oncorhynchus
mykiss 0.00536 0.47 0.011
Below LOC for threatened/non-
threatened species
Crustacea, Macrocyclops
fuscus 0.00536 0.13 0.041
Below LOC for threatened/non-
threatened species
Algae, Selenastrum
capricornutum 0.00536 0.36 0.015 Below LOC
Aquatic plants, Lemna
gibba 0.00536 0.64 0.008
Below LOC for threatened/non-
threatened species
Tebuconazole
Rainbow trout.
Oncorhynchus mykiss 0.0067 4.4 0.002
Below LOC for threatened/non-
threatened species
Crustacea, Daphnia
magna 0.0067 2.79 0.002
Below LOC for threatened/non-
threatened species
Green alga,
Pseudokirchneriella
subcapitata
0.0067 2.83 0.002 Below LOC
Duckweed, Lemna gibba 0.0067 0.144 0.047 Below LOC for threatened/non-
threatened species
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Table 43: Chronic risk quotients derived from the GENEEC2 model and toxicity data
Species
Relevant EEC
from GENEEC2
(mg /L)*
NOEC
(mg/L)
Chronic
RQ Conclusion
AERIAL
Azoxystrobin
Fish, Pimephales
promelas
(33 d ELS)
0.00512 0.147 0.035
Below LOC for threatened/non-
threatened species
Crustacea, Daphnia
magna (21 d) 0.00512 0.044 0.116
Below LOC for non-threatened
species
Above LOC for threatened
species
Tebuconazole
Rainbow trout.
Oncorhynchus mykiss
(83 d ELS)
0.00465 0.012 0.3875
Below LOC for non-threatened
species
Above LOC for threatened
species
Crustacea, Daphnia
magna (21 d) 0.00590 0.010 0.59
Below LOC for non-threatened
species
Above LOC for threatened
species
GROUND BASED
Azoxystrobin
Fish, Pimephales
promelas
(33 d ELS)
0.00462 0.147 0.03
Below LOC for threatened/non-
threatened species
Crustacea, Daphnia
magna (21 d) 0.00462 0.044 0.11
Below LOC for non-threatened
species
Above LOC for threatened
species
Tebuconazole
Rainbow trout.
Oncorhynchus mykiss
(83 d ELS)
0.00348 0.012 0.29
Below LOC for non-threatened
species
Above LOC for threatened
species
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Species
Relevant EEC
from GENEEC2
(mg /L)*
NOEC
(mg/L)
Chronic
RQ Conclusion
Crustacea, Daphnia
magna (21 d) 0.00523 0.010 0.52
Above LOC for non-threatened
and threatened species
* EEC selected must be as close as possible to the exposure duration of the study selected for risk assessment purposes.
Refinement of the aquatic risk assessment
RQs resulting from predicted acute exposures are below the LOC for threatened/ non-threatened
species for both active ingredients for aerial application. As exposure for ground based application is
lower than for aerial application, the exposure is below the LOC as well.
The predicted chronic exposures are above LOC for threatened species for both active ingredients
after aerial application. Using ground based application, the chronic exposures are above LOC for
threatened species and for tebuconazole also for non-threatened species. The scenario modelled is a
worst-case, using the maximum application rate at the shortest interval and maximum frequency of
application. Because risks were identified further modelling was performed to consider whether buffer
zones may be able to mitigate risks from spray drift and runoff.
Spray drift
The Agdrift model was used to calculate the required downwind buffer zone to protect the aquatic
environment from adverse effects of the substance due to spray drift using high boom [see Table 44
and relevant spray drift scenarios (APVMA 2010)].
For aerial application the AGDisp® model was used to calculate the deposition curves. The input
parameters are in Table 45.
For the formulation Custodia®, the same spray-drift curve as for the active ingredient was used.
Exact buffer zones are impractical and too precise to be applied in the real world. Therefore, the
buffer zone distance is rounded so it can be visualized and remembered by end-users.
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Table 44: Input parameters and calculation of spray drift buffer zone for the refined risk
assessment of azoxystrobin and tebuconazole (groundbased application)
Azoxystrobin Tebuconazole
Input parameters Ground based Ground based
Application rate (kg
ai/ha)
0.12 0.2
Number of applications 2 2
Application interval 14 d 14 d
Koc 690 mL/g 910.4 mL/g
DT50 soil 132.32 d 57.5 d
DT50 water 234 d 38.7 d
Toxicity endpoint
(chronic)
0.044 mg/L 0.010 mg/L
Assessment factor 10 10
Buffer zone (m) - model
Using the average time of
21 days to reflect the
used study data:
0
Using the average time of 21 days to reflect the used
study data:
High boom
fine 18 m (BBCH < 09: no interception)
fine 12 m (BBCH 10-19: 20% interception)
fine 2 m (BBCH 31-39: 70% interception)
fine 0 m (BBCH >49: 90% interception)
coarse 2 m (all BBCH stages)
Buffer zone (m) – control
(coarse droplets)
0 Highboom coarse (all BBCH stages):
0 m3
With coarse droplets the model indicates that there is a need for a 2 m buffer zone to protect the
aquatic environment if the product is applied using ground based equipment with coarse droplets.
However, 20 - 90% of the substance is likely to be intercepted (depending on growth stage) and
therefore no downwind buffer zone is required if the substance is applied using a coarse droplet with
a high boom.
3 To simplify the controls and to have consistent controls with aerial spray the staff suggest to limit the dropletsize to coarse.
The applicant has confirmed that this does not impact the use of the product.
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Input variables used for the aerial AGDISP v8.15 modelling
The input variables for the aerial modelling are presented in Table 45. Aircraft information was
provided by the New Zealand Agricultural Aviation Association (NZAAA). The EPA assumes a flat
surface given the proposed use pattern in fodder and sugar beet. The applicant confirmed that the
proposed crop will not be grown on slopes.
Table 45: Aerial modelling input variables
Aerial Agricultural Fungicide/ Insecticide
Aircraft FW Air Tractor AT-402B
Wing semispan 7.79 m
Rotor radius NA
Weight 4000 kg
Typical speed 60 m/s
Propeller / Rotor
RPM 2000
Propeller radius 1.33 m
Biplane separation 0
Planform area 26.02 m2
Engines 1
Engine vertical 0 m
Engine forward 4.35 m
Engine horizontal 0 m
Wing vertical 0.3622 m
Boom vertical 0.38 m
Boom forward 0.3 m
Release height 3 m
Swath width 24 m
Swath displacement 2 m
Droplet size American Society of Agricultural and Biological Engineers (ASABE) medium and fine
American Society of Agricultural and Biological Engineers (ASABE) coarse
Water rate 50 – 100 L/ha, 50 L is worst case
Spray lines 10 (typical width of a NZ spray block assumed to be 240 m; sensitivity analysis
showed this was not very important for predicting spray drift)
Side slope angle 0 degrees (assume flat terrain)
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Aerial Agricultural Fungicide/ Insecticide
Canopy height 0 m (assume no canopy)
Active Fraction 0.0024 (azoxystrobin)
0.004 (tebuconazole)
Non volatile fraction 0.0064
Boom length relative
to wingspan 73 %
Number of nozzles 60 (67 used on typical NZ boom but 60 is maximum that can be used in AGDISP)
Wind Speed 3 m/s
Temperature 21°C
Relative Humidity 46 % (obtained from NIWA data)
Surface roughness 0.005 m (lowest value recommended equivalent to grass)
Canopy roughness NA
Canopy displacement NA
Atmospheric stability Overcast
The input parameters for the spreadsheet to calculate the buffer zones are the same as in Table 44
with the exception of the refined endpoint for tebuconazole.
The tebuconazole endpoint applied in the assessment is from the 21 day Daphnia magna study.
There is evidence that under more realistic exposure conditions, toxicity to this organism is reduced
(Kern and Lam, 2005). The change to the chronic tebuconazole endpoint, however, will not change
significantly as results for fish will need to be adopted. There are several longer term fish endpoints
based on early life cycle testing and full fish life cycle testing (see Table 17). An evaluation of these
different studies, with the intention of confirming an appropriate chronic fish endpoint, was provided
(Grau and Breur, 2007), and it was concluded that the overall population relevant No Observed
Adverse Effect Concentration (NOAEC) for chronic risk assessments of fish of 12 µg ai/L is
considered to be justified. The EPA agrees with this conclusion.
That endpoint is from an 83 day early life stage test with rainbow trout. Applying this endpoint and an
83 day exposure period in the EPA’s spreadsheet allows a reduction in chronic buffer zones.
Crop interception has been applied for BBCH 10-19 (20% crop interception) and BBCH 31-30 (70%
crop interception).
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Aerial buffer zones
BBCH 0 – 09 (No crop interception)
For azoxystrobin, a 134 metre downwind buffer zone is required to mitigate the risks when a fine –
medium droplet size is used. This buffer zone is reduced to 82 metres when a coarse droplet size is
used.
For tebuconazole a 436 metre downwind buffer zone is required to mitigate the risks when a fine –
medium droplet size is used. This buffer zone is reduced to 130 metres when a coarse droplet size is
used.
BBCH 10-19 (20% crop interception)
For azoxystrobin, a 132 metre downwind buffer zone is required to mitigate the risks when a fine –
medium droplet size is used. This buffer zone is reduced to 72 metres when a coarse droplet size is
used.
For tebuconazole a 292 metre downwind buffer zone is required to mitigate the risks when a fine –
medium droplet size is used. This buffer zone is reduced to 116 metres when a coarse droplet size is
used.
BBCH 31-39 (70% crop interception)
For azoxystrobin, a 66 metre downwind buffer zone is required to mitigate the risks when a fine –
medium droplet size is used. This buffer zone is reduced to 34 metres when a coarse droplet size is
used.
For tebuconazole a 112 metre downwind buffer zone is required to mitigate the risks when a fine –
medium droplet size is used. This buffer zone is reduced to 70 metres when a coarse droplet size is
used.
BBCH >40 (90% crop interception)
No buffer zone is required for azoxystrobin.
For tebuconazole a 44 metre downwind buffer zone is required to mitigate the risks when a fine –
medium droplet size is used. This buffer zone is reduced to 26 metres when a coarse droplet size is
used.
Overall conclusion
Table 46 summarizes the calculated downwind buffer zones and proposed controls for all scenarios.
To mitigate the risks to the aquatic environment from ground-based high boom applications, no
buffer zones are required when applied using with coarse droplet size.
To mitigate the risks to the aquatic environment from aerial applications the following downwind
buffer zone controls based on BBCH stage are required:
1. BBCH stage 12-19: A downwind buffer zone of 120 m is required to mitigate the risks
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2. BBCH stage 31-39: A downwind buffer zone of 70 m is required to mitigate the risks
3. BBCH stage >49: A downwind buffer zone of 30 m is required to mitigate the risks
The substance should only be applied using a coarse droplet.
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Table 46: Overview of modelled downwind buffer zones and corresponding control (in bold and underlined EPA recommendation for
the controls)
Application
method
Groundbased Aerial
Droplet size Fine-medium Coarse Fine-medium Coarse
BBCH-stage 0-09 10-19 31-39 >40 0-09 10-19 31-39 >40 0-09 10-19 31-39 >40 0-10 09-19 31-39 >40
Bufferzone model 18 12 2 0 2 436 292 112 44 130 116 70 26
Bufferzone
control
20 20 0 0 0 0 0 0 450 300 120 50 130 120 70 30
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Runoff
The REXTOX model was also used to calculate the required buffer zone to protect the aquatic
environment from adverse effects of the substance due to runoff (see Table 47). A crop interception
value of 20% has been used and no slope.
Table 47: Input parameters and calculation of runoff buffer zone for the refined risk
assessment
Input parameters Azoxystrobin Tebuconazole
Application rate (kg ai/ha) 0.12 0.2
Kd 12 16.39
DT50 soil 132.32 d 57.5 d
Crop interception 20% (BBCH 10-19)
Slope 0.1
Toxicity endpoint 0.044 0.010
Assessment factor 10 10
Buffer zone (m) – model 0 0
Buffer zone (m) – control 0 0
The model indicates that there is no need for a buffer zone to protect the aquatic environment from
adverse effects of runoff if applied after BBCH 10.
Conclusions of the aquatic risk assessment
Predicted chronic exposures concentrations of azoxystrobin and tebuconazole, applied as the
formulated product Custodia® resulted in calculated Risk Quotients above the Level Of Concern
(LOC) for the aquatic environment (fish, crustacean). To manage these risks, it is proposed to apply
controls to reduce spray-drift into the aquatic environment. Together with prescribed controls,
additional controls setting a maximum application rate and use restrictions regarding the droplet size
will reduce the risks to below the level of concern.
The following controls are proposed to reduce exposures below the level of concern:
Use restrictions
The maximum application rate is 120 g azoxystrobin and 200 g tebuconazole/ha, with a maximum
of 2 applications/year and a minimum interval of 14 days.
Apply with a minimum coarse droplets, as defined by the American Society of Agricultural and
Biological Engineers ASABE Standard (S572) or the British Crop Production Council guideline.
This information (all of the above restrictions) should be required on the label so that users are
aware of this control.
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Buffer zones
To mitigate risks from spraydrift, when applied using aerial equipment, the substance should not
be applied within (this information should be required on the label so that users are aware of this
control):
o 120 m downwind of any waterbody when applied to crops at BBCH 12-19
o 70 m downwind of any waterbody when applied to crops at BBCH 19-39
o 30 m downwind of any waterbody when applied to crops at BBCH >40
A label statement indicating: “DO NOT apply when wind speeds are less than 3 km/hr or more
than 20 km/hr as measured at the application site”.
Groundwater risk assessment
The predicted concentration of azoxystrobin and tebuconazole and its relevant metabolite 1,2,4-
triazole in groundwater, calculated using the Sci-Grow model, is shown in Table 48. The
concentration is initially compared to the EU limit for the maximum permissible concentration of
pesticide active ingredients and their relevant metabolites of 0.1 µg/L.
Table 48: Input parameters for Sci-Grow analysis and resulting PEC values
Input
parameters Azoxystrobin Tebuconazole
1,2,4-triazole
Application rate
(kg ai/ha) 0.12 0.20
0.0642 (fraction
formation = 0.321)
70% crop
interception: 0.019
Application rate (lb
ai/acre)1 0.107 0.178 0.0573 0.017
Number of
applications 2 2
2
Koc2 690 910.4 43
Aerobic soil DT50
(days) 132.32 57.5 92.8
PECgw (µg/L) 0.0377 0.0251 0.369 0.11
1 The application rate is conversion from kg ai/ha to lb/acre (the units required to be entered into the model) by multiplying it by 0.892
2 Lowest Koc from a non-sandy soil (normalised values for the OC, temp and pH)
Conclusions of the groundwater risk assessment
For azoxystrobin and tebuconazole, the concentration is below the 0.1 µg/L trigger level set by the
European regulators. The concentration of the metabolites will be lower than that of the parent
substance. Therefore, the risks are considered below the level of concern.
However, for the metabolite of tebuconazole, 1,2,4,-triazole, the model indicated that the
concentration in the groundwater might reach concentrations above the trigger level and therefore
risks are potentially above the level of concern. If a crop interception value of 70% is applied the
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groundwater concentration is just above 0.1 µg/L. However, the predicted concentration is
significantly lower than the aquatic EC50 values for this metabolite (lowest algae > 31 mg/L). The EPA
considers the environmental risk as below the level of concern for aquatic organisms. The risks to
human health are addressed in Appendix G.
Sediment risk assessment
The sediment risk assessment for tebuconazole is performed following the method outlined in the
EPA standard risk assessment methodology (EPA 2018). For the active ingredient azoxystrobin no
data of sediment dwelling organisms are available.
The input parameters used in the risk assessment are summarised in Table 49.
Table 49: Input values and calculations for sediment risk assessment
Input parameters Tebuconazole
Ground based Aerial
PEC local water 0.00596 mg/L 0.0067 mg/L
Koc 910.4 910.4
Toxicity value 40 mg/kg sediment (NOEC) 40 mg/kg sediment (NOEC)
Assessment factor 100 100
PEC local sediment 0.1839 mg/kg sediment 0.1378 mg/kg sediment
RQ 0.31 0.34
Conclusions of the sediment risk assessment
The risk quotient of tebuconazole for sediment-dwelling organisms was below the level of concern.
Due to a lack of data on the active ingredient azoxystrobin, the risk to sediment-dwelling organisms
resulting from the application of Custodia® cannot be determined. However, azoxystrobin is already
approved in New Zealand at a higher rate (250 g ai/ha) than the proposed rate (120 g ai/ha).
Terrestrial risk assessment
The terrestrial risk assessment considers the risks to soil organisms, terrestrial plants, birds, bees and
non-target arthropods.
The methodology for the terrestrial risk assessment is described in the EPA standard risk assessment
methodology (EPA 2018).
Soil macro-organisms
The soil organism risk assessment is based on a comparison of the Predicted Environmental
Concentration (PEC) with acute toxicity values for the azoxystrobin. The toxicity value is divided by
the PEC to give a Toxicity Exposure Ratio (TER). The different levels of concern assigned to specific
TER values are listed in the EPA standard risk assessment methodology (EPA 2018).
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The results of the acute risk assessment for soil organisms are summarised in Table 50.
For the active ingredient azoxystrobin, no chronic data are available, the formulation data have been
used as an alternative. Chronic data of tebuconazole are available. The results of this chronic risk
assessment are summarised in Table 51and this will provide an indication of the risks after an
application with Custodia®.
Table 50: Acute TER values for soil organisms
Species
LC50
(mg/kg
soil)
Drift (%)
PEC
(mg/kg
soil)
TER
acute Conclusion
Azoxystrobin – 120 g/ha – “in-field”
Earthworm 283 NA 0.31 917 Below LOC for threatened/non-
threatened species
Tebuconazole – 200 g/ha – “in-field”
Earthworm 1381 NA 0.49 2807 Below LOC for threatened/non-
threatened species
Table 51: Chronic TER values of tebuconazole for soil organisms
Species
NOEC
(mg/kg
soil)
Drift
factor
PEC
(mg/kg
soil)1
TER chronic Conclusion
Azoxystrobin – 120 g/ha – “in-field”
Springtail 55.31 NA 0.31 179 Below LOC for threatened/non-threatened
species
Tebuconazole – 200 g/ha – “in-field”
Earthworm 10 NA 0.49 20 Below LOC for threatened/non-threatened
species
1,2,4-triazole (tebuconazole metabolite – 64.2 (fraction formation = 0.321) – “in-field”
Earthworm 1.0 NA 0.16 6.15 Below LOC for non-threatened species
Above LOC for threatened species
1,2,4-triazole (tebuconazole metabolite – 64.2 (fraction formation = 0.321) – “off-field”
Earthworm 1.0 NA 0.004 260 Below LOC for threatened/non-threatened
species
1: 11.06% (maximum concentration azoxystrobin) of 500 mg formulation/kg soil (NOEC for Custodia®)
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The acute toxicity of the metabolites of azoxystrobin and tebuconazole is less than that of the parent.
Therefore, the risks to soil organisms from these metabolites are considered below the LOC as well.
The chronic toxicity of the metabolites of azoxystrobin is less than that of the parent. Therefore, the
risks to soil organisms from these metabolites are considered below the LOC as well. The risks for
tebuconazole are below the LOC. The toxicity of the metabolite 1,2,4-triazole is higher than that of
tebuconazole and in combination with the higher DT50 in soil, the risks are above the LOC for
threatened earthworm species.
There are 179 taxa or earthworms in New Zealand with only one species reported as “at risk –
declining” (Deinodrilus gorgon) and 31 reported as “at risk – naturally uncommon” (Department Of
Conservation (DOC) 2014). Despite a potentially large distribution area for this earthworm species on
the West Coast, the best documented natural habitat is not threatened by agriculture but rather by on-
going and future mining activities on the Stockton and Denniston Plateaus. Furthermore, Deinodrilus
gorgon is reported have a total area of occupancy ≤1000 ha (10 km2) in New Zealand. The other 31
species ranked as “naturally uncommon” are predominantly endemic to New Zealand. These 32
earthworm species are confined to a specific forestry areas or occur within naturally small and widely
scattered populations, where this distribution is not the result of human disturbance.
A recent survey (Kim Y. 2017) sampled earthworms on the South Island including several locations in
the Canterbury region. Samples collected from agricultural land found only native earthworm species
classified as “not threatened” and/or earthworm species exotic to New Zealand. The additional lines of
scientific evidence provided by the Department of Conservation (2014) and Kim Y. et al (2017)
indicate threatened species of earthworms in New Zealand are unlikely to be exposed to Custodia®.
Therefore this risk is considered to be below the level of concern.
Soil micro-organisms
For Custodia®, the provided data indicate that there are no effects on the nitrogen and carbon
transformation at application rates up to 12.5 L formulation/ha (highest concentration tested). The
proposed application rate is lower (1 L formulation/ha) and therefore this risk is considered below the
level of concern.
Conclusions of the soil organism risk assessment
Acute and chronic risk quotient to soil organisms applicable to azoxystrobin and tebuconazole
following the application of Custodia® are below the Level Of Concern (LOC).
For 1,2,4-triazole (metabolite tebuconazole) the chronic risk to threatened earthworms was above the
level of concern. Further evaluation indicated that threatened species are unlikely present in the
application areas of Custodia®, as a result, the risk is considered to be below the level of concern.
Non-target plant risk assessment
The non-target plant risk assessment is based on a comparison of the PEC with toxicity values for the
active ingredient azoxystrobin and the formulated product. Depending on the type of data provided,
for non-threatened plants a TER or an RQ is calculated (a TER is used when an EC50 is available, an
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RQ is used when an EC25 is available). For threatened non-target plants a RQ is calculated by
comparing the PEC with a NOEC. The different levels of concern assigned to specific TER/RQ values
are listed in the EPA standard risk assessment methodology (EPA 2018)
TER values for non-threatened non-target plants are shown in Table 52. TER values for threatened
non-target plants are shown in Table 53.
Table 52: TER value for non-target plant
Scenarios
Exposure
(g ai/ha) *
drift factor
EC50
(g ai/ha) TER Conclusion
Azoxystrobin- seedling emergence
Fodder and
sugar beet –
ground based
4.86 15000 3089
Below LOC for non-threatened
species
Fodder and
sugar beet –
aerial
26.5 15000 566
Below LOC for non-threatened
species
Custodia® – Vegetative vigour
Fodder and
sugar beet –
ground based
0.040 >3.375 >83
Below LOC for non-threatened
species
Fodder and
sugar beet –
aerial
0.22 >3.375 >15
Below LOC for non-threatened
species
Table 53: TER value for threatened non-target plant
Scenarios
Exposure (L
formulation/ha)
* drift factor
NOEC
(L
formulation/ha)
RQ Conclusion
Custodia® - 1 L product/ha- vegetative vigour
Fodder and
sugar beet 0.040 <3.375 >0.012
Most likely below LOC for
threatened species as the RQ is
far below the threshold and the
proposed rate is considerably
lower (1 L/ha).
Conclusion for non-target plant risk assessment
The risks to non-target plants, for seedling emergence, calculated for azoxystrobin, are below the
level of concern. No information is available of the effects of tebuconazole on seedling emergence.
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No data on vegetative vigour of the individual active ingredients are available, however, the
information of Custodia® has been used. Risks were considered below the level of concern for non-
threatened plant species.
Insufficient information is available to determine the effects on threatened non-target plants. For
vegetative vigour, data on vegetative vigour with the formulation Custodia® is available. The NOEC
could not be determined as a 13.1% effect on fresh weight was observed on one of the tested
species. Although the NOEC could not be determined, it is considered that the risks are most likely
below LOC as the RQ calculated with the highest value tested, which only showed 13% effect on
fresh weight, is far below the threshold (RQ >0.012 and >0.06) and the proposed rate is considerably
lower (1 L/ha) than the tested rate (3.375 L/ha). Furthermore, crop interception (20-70% for this
product has not been included in the RQ calculation).
Off-target seeds are likely sheltered and interception by other plants is not taken into account and this
will reduce possible drift. However, risks cannot be fully excluded.
Overall, it is considered that the risks to non-target plants following an application of Custodia® are
likely below the LOC.
Bird risk assessment
The bird risk assessment is based on a comparison of the PEC with toxicity values for the active
ingredients azoxystrobin and tebuconazole. The toxicity value is divided by the PEC to give a Toxicity
Exposure Ratio (TER). The different levels of concern assigned to specific TER values are listed in
the EPA standard risk assessment methodology (EPA 2018).
Screening assessment
Predicted exposure to both active ingredients under the bird acute dietary and reproduction screening
assessments is shown in Table 54.
Table 54: Exposure of birds for acute and reproduction screening assessments
Screening
type1
Indicator
species2
Application
rate
(kg/ha)
Short-
cut
value
(90th%)3
TWA4
MAF
(90th
%)5
No of
applications DDD
Azoxystrobin
Acute Small
omnivorous
bird
0.12 158.8 NA 1.2 2 22.87
Reproduction 0.12 64.8 0.53 1.4 2 5.77
Tebuconazole
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Acute Small
omnivorous
bird
0.2 158.8 NA 1.2 2 38.11
Reproduction 0.2 64.8 0.53 1.4 2 9.62
1 EFSA (EFSA 2009), Table 5 p27 2 EFSA, (EFSA 2009), Table 6 p28 3 90th %ile short-cut value used for the acute assessment, mean value used for the reproduction assessment. EFSA
(EFSA 2009), Table 6 p28 4 The exposure assessment of the reproduction assessment uses time-weighted average (TWA) exposure estimates
over 1, 2, 3 or 21 days for different phases of the assessment. 1 d = 1.0; 2 days = 0.93; 3 days = 0.9; 21 days = 0.53. EFSA, (EFSA 2009), Table 11 p34.
5 90th %ile MAF value used for the acute assessment, mean value used for the reproduction assessment. EFSA, (EFSA 2009), Table 7 p29
Calculation of TERs
TER calculations for the acute dietary risk assessment are detailed in Table 55 and calculations for
the reproductive risk assessment are shown in Table 56.
Table 55: TER values for acute dietary risk assessment (TWA = 0.53; MAF=1.2)
Crops & BBCH
class
Generic focal
species1
Daily
dietary
dose (DDD)
Toxicity
endpoint value
(mg/kg bw/d)*
TER ratio Conclusion
Azoxystrobin-0.12 kg/ha twice
Fodder and sugar
beet
Small
omnivorous bird
22.87 >2000 >87.5 Below LOC for
threatened/non-
threatened
species
Tebuconazole- 0.2 kg/ha twice
Fodder and sugar
beet
Small
omnivorous bird
38.11 1555 40.8 Below LOC for
threatened/non-
threatened
species
Table 56: TER values for reproductive risk assessment (TWA = 0.53; MAF=1.4).
Crops &
BBCH class
Generic
focal
species1
DDD
Toxicity
endpoint
value
(mg/kg
bw/d)*
TER ratio
Conclusion
Azoxystrobin-0.12 kg/ha twice
Fodder and
sugar beet
Small
omnivorous
bird
5.77 117 20.3 Below LOC for
threatened/non-
threatened species
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Crops &
BBCH class
Generic
focal
species1
DDD
Toxicity
endpoint
value
(mg/kg
bw/d)*
TER ratio
Conclusion
Tebuconazole-0.2 kg/ha twice
Fodder and
sugar beet
Small
omnivorous
bird
9.62 5.8 0.6 Above LOC for
threatened/non-
threatened species
* Normally the NOAEL has to be converted from units of ppm (mg/kg diet) to mg/kg bw/d. In the first instance a factor of 0.1 is used for such conversion. If specific information is available from the test reports, this is preferable. When reported as ppm in the studies, daily dose (mg/kg/d) = [Concentration in food (mg/kg) * Daily food consumption (g/bird/d)] / body weight (g) (over the entire exposure period).
Conclusions of the bird screening risk assessment
The acute screening risk assessment indicates an acute risk below the level of concern to birds from
azoxystrobin and tebuconazole from the use of Custodia®. In the reproductive screening assessment,
the TER values indicate a chronic risk above the level of concern to birds for tebuconazole. As risks
were above the level of concern, a Tier 1 risk assessment was performed.
Tier 1 assessment
Tier 1 uses the same general approach as the screening assessment but requires more specific
exposure scenarios. More details are provided in the EPA standard risk assessment methodology
(EPA 2018).
For each generic focal species, the Daily Dietary Dose (DDD) is presented in Table 57.
The toxicity figures are the same than those considered in the screening assessment.
The indicator species mentioned in Table 57 (chronic) are not real species but have to be considered
as representative of groups of birds of the same size and same feeding behaviour.
Table 57: TER values for chronic risk assessment – Tier 1 assessment
Crops &
BBCH
class
Focal species
Short-
cut
value2
(90th %)
DDD Toxicity
endpoint
(mg/kg
bw)
TER
ratio Conclusion
Tebuconazole-0.2 kg/ha twice
Fodder and
sugar beet
Small
insectivorous
bird, ground
invertebrates
without
interception
5.9 0.876 5.8 6.6 Above LOC for
threatened species
Below LOC for non-
threatened species
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Small
insectivorous
bird, ground
invertebrates
with interception
2.8 0.416 5.8 14.0 Below LOC for threatened/
non-threatened species
Small
insectivorous
bird with
interception 50%
ground
arthropods 50%
foliar arthropods
9.7 1.44 5.8 4.0 Above LOC for
threatened/ non-
threatened species
Small
omnivorous bird
10.9 1.62 5.8 3.6 Above LOC for
threatened/ non-
threatened species
Small
granivorous bird
11.4 1.69 5.8 3.4 Above LOC for
threatened/ non-
threatened species
Conclusion for bird risk assessment (Tier 1)
The chronic Tier 1 risk assessment indicates risks above the level of concern to both threatened and
non-threatened birds from the use of Custodia®.
Refinement
Scenario 1
The chronic risk has been triggered by the active ingredient tebuconazole.
The initial assessment was based on the most sensitive species, however, chronic NOEC values of
another species are available. The long term NOEC to mallard duck is 170 mg tebuconazole/kg diet
to mallard duck. Applying the group mean body weights and daily food consumption, a daily dietary
dose of 17.7 mg/kg bw/d is derived. A geometric mean NOEC of 10.1 mg/kg bw/d is derived. Using
this endpoint, the TER ranges from 6.0 to 24.3 (maintaining the TWA = 0.53), which indicate that the
risk to non-threatened birds is below the level of concern. Generally, this type of refinement is only
applied to acute data, however, the NOECs were in the same order of magnitude and therefore it was
considered acceptable to apply this approach in this particular case to chronic data.
Using the geometric mean a risk for threatened birds is identified. Using the DDD of the worst case
situation (1.69) for small granivorous birds and the geometric mean NOEC of 10.1, these birds must
forage circa 40% outside the treated area. It is considered that it is likely that threatened species will
obtain less than 60% of their food from the treated fields as agricultural areas are not the natural
habitat of threatened bird species. Therefore, the risks from tebuconazole is considered low.
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Secondary poisoning
Given the criteria under the HSNO Act azoxystrobin and tebuconazole are not considered to be
bioaccumulative (BCF < 500). Therefore, no risk assessment via secondary poisoning is performed.
Conclusions for bird risk assessment
TER values for birds calculated for azoxystrobin and tebuconazole, when applied to fodder and sugar
beet as the formulated product Custodia®, are below the level of concern for acute risks, and any
risks are negligible. In the reproductive screening assessments, the TER values indicate a chronic
risk below the level of concern to birds for azoxystrobin but above the level of concern to birds from
the use of tebuconazole in fodder and sugar beet. After refinement, it is considered that it is likely that
threatened species will obtain less than 60% of their food from the treated fields as agricultural areas
are not the natural habitat of threatened bird species. Therefore, the risks from tebuconazole is
considered to be low. Furthermore, both active ingredients are already approved in New Zealand at
higher rates than the proposed rate. The risks from secondary poisoning is considered to be low as
both active ingredients are not considered to be bioaccumulative.
Pollinator risk assessment
The basis for the pollinator risk assessment is a comparison of the environmental exposure
concentration (EEC) with toxicity endpoints to which safety factors have been applied. The EEC is
divided by the toxicity endpoint to calculate a risk quotient (RQ) value. The methodology for the
pollinator risk assessment, including the level of concern (LOC) ascribed to specific RQ values, is
described in detail in the EPA standard risk assessment methodology (EPA 2018). The results of the
bee risk assessment are shown in Table 58.
Table 58: Bee exposure estimates and RQ values
Use scenario
Application rate
(kg ai/product
/ha)
EEC (µg
ai/product
/bee)
Toxicity
endpoint
value (µg
ai/product
/bee)
RQ Conclusion
Acute / Adult bees – contact
Azoxystrobin
Fodder and
sugar beet 0.12
0.288 >200 <0.00144 Below LOC
Tebuconazole
Fodder and
sugar beet
0.2 0.48 >100 <0.0048
Below LOC
Custodia®
Fodder and
sugar beet
11 2.4 >2001 <0.012
Below LOC
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Acute / Adult bees – oral
Azoxystrobin
Fodder and
sugar beet 0.12
3.43 >25 <0.14 Below LOC
Tebuconazole
Fodder and
sugar beet
0.2 5.72 >83.05 <0.07
Below LOC
Custodia®
Fodder and
sugar beet
11 28.62 >208.41
<0.14 Below LOC
1: units are L/ha
Conclusions of the pollinator risk assessment
The acute risks to pollinators are below the level of concern. Chronic risks could not be evaluated due
to a lack of data. However, both active ingredients are already approved in New Zealand at higher
rates than the proposed rate.
Non-target arthropod risk assessment
The non-target arthropod risk assessment is a comparison of the predicted environmental
concentration (PEC) with toxicity endpoints to which safety factors have been applied. The PEC is
divided by the toxicity endpoint to calculate a hazard quotient (HQ) value. The methodology for the
non-target arthropods risk assessment, including the level of concern (LOC) ascribed to specific HQ
values, is described in detail in the EPA standard risk assessment methodology (EPA 2018).
No data on non-target arthropods of tebuconazole are available. Results of the in-field and off-field
non-target arthropods risk assessment of azoxystrobin are shown in Table 59 and Table 60,
respectively.
Table 59: In-field HQ values for non-target arthropods (TIER I)
Species LR50
(mL/ha)
Application rate
(mL/ha) MAF
Hazard
Quotient Conclusion
Custodia®
Parasitic wasp, Aphidius
rhopalosiphi1 605 1000 1.7 2.8 Above LOC
Predatory mite,
Typhlodromys pyri1 >3375 1000 1.7 <0.504 Below the LOC
1: note this is an extended study which normally is evaluated in Tier II
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Table 60: Off-field HQ values for non-target arthropods (TIER I)
Species
LR50
(g /ha or mL
/ha)
Application rate
(g /ha or mL /ha) MAF
Hazard
Quotient Conclusion
Custodia®, (drift factor =2.38%, BBA driftcurves for ground based)
Parasitic wasp, Aphidius
rhopalosiphi1 605 1000 1.7 0.07 Below the LOC
Custodia®, (drift factor =13%, aerial GENEEC)
Parasitic wasp, Aphidius
rhopalosiphi1 605 1000 1.7 0.37 Below the LOC
1: note this is an extended study was normally is evaluated in Tier II
Tier I could not be performed according to the ESCORT II guidance (Workshop, Candolfi et al.), the
reason is that only extended laboratory tests were available which normally are evaluated in Tier II.
However, the EPA considers it acceptable as also the impact of fresh residue was evaluated in these
studies.
As effects were observed one additional species were evaluated in Tier II as per ESCORT II
guidance. In the table the study with the Green Lacewing has been added, however, another study
with ladybirds was provided. The endpoint for this study was identical to the endpoint of the Green
Lacewing and outcomes would therefore be identical.
Table 61: In-field HQ values for non-target arthropods (TIER II)
Species LR50
(mL/ha)
Application rate
(mL/ha) MAF
Hazard
Quotient Conclusion
Parasitic wasp, Aphidius
rhopalosiphi1 605 1000 1.7 2.8
Above LOC
(1.4x)
Green Lacewing,
Chrysoperla carnea >3375 1000 1.7 <0.504 Below the LOC
1: already included in TIER I but as this is a TIER II test also included here.
The EPA informed the applicant about the identified risk for parasitic wasps using the most
conservative value available. The EPA requested more information as the results of two studies both
performed with the parasitic wasps are conflicting. One study resulted in an LR50 of 605 mL
formulation/ha (see Appendix I, Table 79 ; project 47744002) while the other indicated that less than
50% of mortality was observed at 3.38 L formulation/ha (see Appendix I, Table 80; project 47654003).
Both studies are performed according to the guideline. No additional information was provided by the
applicant to clarify the difference. Therefore, the EPA has taken the precautionary approach and used
the most conservative data for the assessment which indicated that in-field, the risks for parasitic
wasps are above the level of concern (1.4x).
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Conclusion for non-target arthropod risk assessments
Risks to non-target arthropods are above the level of concern for the in-field situation for parasitic
wasps following an application with Custodia®. For the other tested and assessed non-target
arthropods, the risks are below the level of concern. For the off-field situation, the risks for parasitic
wasps are below the level of concern using the GENEEC model drift factors (aerial application). Re-
colonization from off-field is expected when the concentration has decreased.
The EPA recommends a label statement to warn end-users on the potential impact on beneficial
insects as risks cannot be fully excluded. Label statement indicating “WARNING” the substance might
not be compatible with Integrated Pest Management (IPM).
Conclusions of the ecological risk assessment
The EPA assessed the potential risk to be triggered by the use of Custodia® following the instructions
captured in the proposed label and GAP table.
It is considered that the risks to the environment from the proposed use of Custodia® are acceptable
with the proposed controls.
Aquatic environment:
For azoxystrobin and tebuconazole chronic risks were identified. These risks can be managed with
controls.
Predicted chronic exposures concentrations of azoxystrobin and tebuconazole, applied as the
formulated product Custodia® resulted in calculated Risk Quotients above the Level Of Concern
(LOC) for the aquatic environment (fish, crustacean). To manage these risks, it is proposed to apply
controls to reduce spray-drift into the aquatic environment. Together with prescribed controls,
additional controls setting a maximum application rate and use restrictions regarding the droplet size
will reduce the risks to below the level of concern.
Groundwater:
For azoxystrobin and tebuconazole, the concentration is below the 0.1 µg/L trigger level set by the
European regulators. Therefore, the risks are considered below the level of concern. However, there
is a risk for groundwater contamination with 1,2,4-triazole. The predicted concentration is significantly
lower than the aquatic EC50 values for this metabolite (lowest algae > 31 mg/L). Therefore, the EPA
considers the risk as below the LOC for aquatic organisms.
Sediment:
The risk quotient of tebuconazole for sediment-dwelling organisms was below the level of concern.
Due to a lack of data on the active ingredient azoxystrobin, the risk to sediment-dwelling organisms
resulting from the application of Custodia® cannot be determined. However, azoxystrobin is already
approved in New Zealand at a higher rate (250 g ai/ha) than the proposed rate (120 g ai/ha).
Terrestrial environment
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Soil organisms:
Acute risk quotient to soil organisms applicable to azoxystrobin following the application of Custodia®
are below the LOC.
Due to a lack of chronic data of azoxystrobin, the chronic risk assessment is performed with the other
active ingredient tebuconazole. The model indicates a chronic risk below the LOC for tebuconazole, a
chronic risk to threatened earthworms was determined for 1,2,4-triazole, however, it is considered
unlikely that threatened earthworms are present at the application site.
Chronic data for springtail of the formulated product Custodia® is available indicating a low toxicity to
soil organisms. Overall, it is considered that the risks to soil organisms (macro and micro-organisms)
following an application of Custodia® are below LOC.
Terrestrial plants:
The risks to non-target plants, for seedling emergence, calculated for azoxystrobin, are below the
LOC. No information is available of the effects of tebuconazole on seedling emergence. No data on
vegetative vigour of the individual active ingredients are available however the information of
Custodia® has been used. Risks were considered below the LOC for non-threatened plant species.
Insufficient information is available to determine the effects on threatened non-target plants. For
vegetative vigour, data on vegetative vigour with the formulation Custodia® is available. The NOEC
could not be determined as a 13.1% effect on fresh weight was observed on one of the tested
species. Although the NOEC could not be determined, it is considered that the risks are most likely
below LOC as the RQ calculated with the highest value tested, which only showed 13% effect on
fresh weight, is far below the threshold (RQ >0.012 and >0.06) and the proposed rate is considerably
lower (1 L/ha) than the tested rate (3.375 L/ha).
Off target seeds are likely sheltered and interception by other plants is not taken into account and this
will reduce possible drift. However, risks cannot be fully excluded.
Overall, it is considered that the risks to non-target plants following an application of Custodia® are
likely below LOC.
Birds:
No acute risks from the use of Custodia® are identified. Chronic risks are identified and the risk
assessment was refined. Based on these results, it was identified that there is a low risk to threatened
birds. No other risks were identified. Given the criteria under the HSNO Act azoxystrobin and
tebuconazole are not considered to be bioaccumulative (BCF < 500). Therefore, no risk assessment
via secondary poisoning is performed.
Bees and non-target arthropods:
There are no concerns for adult honeybees from acute exposure. Possible chronic effects could not
be assessed due to a lack of data. However, both active ingredients are already approved in New
Zealand at higher rates than the proposed rate.
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Risks to non-target arthropods are above the level of concern for the in-field situation for parasitic
wasps following an application with Custodia®. For the other tested and assessed non-target
arthropods, the risks are below the level of concern. For the off-field situation, the risks for parasitic
wasps are below the level of concern for both use patterns. Re-colonization from off-field is expected
when the concentration has decreased.
The risks for predatory mites are below the 50% threshold for both fresh and aged residues after an
application with the product at 3.38 L/ha. Further in a field study, focussing on the population of
predatory mites, no unacceptable effects were observed after 2 applications with Custodia® at a rate
of 0.263 and 0.438 L/ha [note: proposed rate is 1 L/ha].
The EPA recommends a label statement to warn end-users on the potential impact on beneficial
insects as risks cannot be fully excluded (parasitic wasps). Label statement indicating “WARNING”
the substance might not be compatible with Integrated Pest Management (IPM).
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Appendix I: Study summaries
The manufacturer code name for Custodia® is MCW 710 SC
Toxicity
Mammalian toxicity studies on Custodia® 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 have been used for classifying the active ingredient and the
formulated substance and for derivation of appropriate health-based criteria which are used in risk
assessment. The summary of the studies is provided in Table 62 to Table 67.
Mammalian toxicology - Robust study summaries for Custodia®
Acute toxicity [6.1]
Table 62: Acute Oral Toxicity [6.1 (oral)]
Type of study Acute oral toxicity in rats
Flag Key study
Test Substance MCW 710 SC (Azoxystrobin: 120 g/L and Tebuconazole: 193 g/L)
Endpoint Acute lethality (LD50), signs of toxicity
Value 300 < LD50 ≤ 2000 mg/kg bw
Reference
2009. Acute oral toxicity study of MCW 710 SC in rats.
Klimisch Score 1
Amendments/Deviations None of significance
GLP Yes
Test Guideline/s EC method B.1
OECD 423
Species Rat
Strain CD:Crl
No/Sex/Group 9/F
Dose Levels 300 and 2000 mg/kg bw
Exposure Type Oral by gavage
Study Summary
An acute oral toxicity test was conducted in rats to determine the
potential for MCW 710 SC to produce toxicity from single dose.
Set I animals (n=6) received test substance at the dose of 300 mg/kg
bw. No mortality and signs of toxicity were observed.
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Set II animals (n=3) received test substance at the dose of 2000 mg/kg
bw. Slight to severely reduced motility, slight to severe ataxia, slight to
moderate dyspnoea and slightly to moderately reduced muscle tone was
observed in all animals. Two of three animals revealed lateral position
and died prematurely.
Additional Comments No additional comments
Conclusion The LD50 of MCW 710 SC in CD rats was estimated to be in the range of
300 < LD50 ≤ 2000 mg/kg bw.
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Table 63: Acute Dermal Toxicity [6.1 (dermal)]
Type of study Acute dermal toxicity in rats
Flag Key study
Test Substance MCW 710 SC (Azoxystrobin: 120 g/L and Tebuconazole: 193 g/L)
Endpoint Acute lethality (LD50), signs of toxicity
Value LD50 >2000 mg/kg bw
Reference
2007. Acute dermal toxicity study of MCW 710 SC in rats.
Klimisch Score 1
Amendments/Deviations None of significance
GLP Yes
Test Guideline/s EC method B.3. (92/69/EEC)
OECD 402
Species Rat
Strain CD / Crl: CD(SD)
No/Sex/Group 5/sex/group
Dose Levels 2000 mg/kg bw
Exposure Type Dermal, on the shaved intact dorsal skin
Study Summary
An acute dermal toxicity study was conducted in rats (5/sex/group).
Animals received MCW 710 SC (undiluted) at dose level of 2000 mg/kg
bw. The test substance was administered for 24 hours on shaved intact
dorsal skin area. The patched were removed without washing skin and
animals were observed for 14 days. At the end of study all animals were
sacrificed and gross necropsy was performed.
All animals survived during the study. There were no signs of toxicity. No
skin reactions at the application site were observed. All animals gained
the expected body weight throughout the whole study period. No
macroscopic findings were observed at necropsy.
Additional Comments No additional comments
Conclusion The acute dermal LD50 of MCW 710 SC in rats was estimated to be
greater than 2000 mg/kg bw for each sex.
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Table 64: Acute Inhalation Toxicity [6.1 (inhalation)]
Type of study Acute inhalation toxicity in rats
Flag Key study
Test Substance MCW 710 SC (Azoxystrobin: 120 g/L and Tebuconazole: 193 g/L)
Endpoint Acute lethality (LC50), signs of toxicity
Value LC50 >4.79 mg/L
Reference
2010. MCW 710 SC: Acute inhalation toxicity (nose only)
study in the rat.
Klimisch Score 1
Amendments/Deviations None of significance
GLP Yes
Test Guideline/s EC method B.2
OECD 403
Species Rat
Strain HsdRccHan : WIST
No/Sex/Group 5/sex/group
Dose Levels 4.79 mg/L; Mass Mean Aerodynamic Diameter (MMAD): 2.46 µm;
Geometric Standard Deviation (GSD): 2.94
Exposure Type Nose only
Study summary
An acute inhalation toxicity study was conducted on rats (5/sex/group)
which were exposed for 4 hours using nose only exposure system
followed by 14 day observation period. Due to the nature of the test
substance it was considered that a suitable atmosphere would not be
able to be generated from material as supplied. Hence, a formulation
was prepared with sterile water to improve aerosolisation properties of
the material.
No mortality was observed in rats when exposed to a mean achieved
atmosphere concentration of 4.79 mg/L. Increased respiration rate,
hunched posture, pilo-erection and wet fur were noted. However,
animals appeared normal on Day 4 to 8 post-exposure. Reduced body
weight gain or slight body weight. No macroscopic abnormalities were
detected in animals at necropsy.
Additional Comments No additional comments
Conclusion The LC50 was greater than 4.79 mg/L in combined male and female
groups.
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Table 65: Skin Irritation [6.3/8.2]
Type of study Acute skin irritation in rabbits
Flag Key study
Test Substance MCW 710 SC (Azoxystrobin: 120 g/L and Tebuconazole: 193 g/L)
Endpoint Mean Draize Score
Value 0.1 for erythema and 0.0 for oedema at 24, 48 and 72 hours
Reference
2009. Acute dermal irritation/corrosion test (patch test)
of MCW 710 SC in rabbits.
:
Klimisch Score 1
Amendments/Deviations None of significance
GLP Yes
Test Guideline/s EC method B.4. (2004/73/EC)
OECD 404
Species Rabbit
Strain Himalayan
No/Sex/Group 3 Male
Dose Levels 0.5 mL of undiluted MCW 710 SC
Exposure Type Dermal application onto the shaved, intact dorsal skin (semi-occlusive)
Study Summary
In a skin irritation study, 0.5 mL of undiluted test substance was applied
to dorsal area (about 6 cm2) of the trunk of rabbits (n=3) for 4 hours and
was then covered with a gauze patch. The patch was held in place with
non-irritating tape. After 4 hours, the patch was removed and skin sites
were examined and scored for erythema and oedema formation at 60
minutes, and at 24, 48 and 72 hours.
At 60 minutes, very slight erythema was observed in two animals and
remained only in one animal at 24 hour after patch removal. All animals
exhibited an oedema score of 0 during the observation.
Additional Comments No additional comments
Conclusion The substance was non-irritant.
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Table 66: Eye Irritation [6.4/8.3]
Type of study Acute eye irritation
Flag Key study
Test Substance MCW 710 SC (Azoxystrobin: 120 g/L and Tebuconazole: 193 g/L)
Endpoint Mean Draize Score
Value 0.33 for conjunctival redness and 0.0 for cornea opacity, iris lesion and
chemosis
Reference
2009. Acute eye irritation/corrosion test of MCW 710
SC in rabbits.
Klimisch Score 1
Amendments/Deviations None of significance
GLP Yes
Test Guideline/s EC method B.5. (2004/73/EC)
OECD guideline 405
Species Rabbit
Strain Himalayan
No/Sex/Group 3/male/group
Dose Levels 0.1 mL of MCW 710 SC (undiluted)
Exposure Type Single instillation into the conjunctival sac
Study Summary
An eye irritation study was performed in himalayan rabbits (n=3). 0.1 mL
of undiluted MCW 710 SC of was instilled into right conjunctival sac of
all rabbits. After 24 hours, the eyes were rinsed with 20 mL of sodium
chloride solution. After instillation (day 0), eyes were observed for
irritation reactions and abnormalities in cornea, iris, and conjunctiva. The
left eye of all animals was untreated and served as control.
Cornea opacity, iris lesion and chemosis were not observed in any
animal.
The Mean Draize Score (24, 48, 72 hours) for conjunctival redness was
0.33 and 0.0 for cornea opacity, iris lesion and chemosis.
Additional Comments No additional comments
Conclusion The test substance is not an eye irritant.
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Table 67: Contact Sensitisation [6.5]
Type of study Sensitisation in the Guinea Pigs
Flag Key study
Test Substance MCW 710 SC (Azoxystrobin: 120 g/L and Tebuconazole: 193 g/L)
Endpoint Magnusson and Kligman grading scale (maximisation test)
Value Grade 1 skin reaction in induction phases and grade 0 in challenge
phase
Reference
2009. Examination of MCW 710 SC in the skin
sensitisation test in guinea pigs according to Magnusson And Kligman
(maximisation test)
Klimisch Score 1
Amendments/Deviations None
GLP Yes
Test Guideline/s EC method B.6. (96/54/EC)
OECD 406
Species Guinea Pigs
Strain Hartley strain
No/Sex/Group 15 male
Dose Levels
Stage 1 (induction): 0.5% suspension of MCW 710 SC in aqua ad
iniectabilia
Stage 2 (induction): undiluted MCW 710 SC
Stage 3 (Challenge): 50% suspension of MCW 710 SC in aqua ad
iniectabilia
Exposure Type
Intracutaneous (shoulder region) in stage 1
topical (shoulder region) in stage 2
topical (flank region) in stage 3
Study Summary
Sensitization study with the guinea pig maximization test was performed
with MCW 710 SC which consisted of two group: vehicle control and
main test. Animals in main test received the test substance in three
stages:
Stage 1 (intradermal induction): animals received three pairs of
intradermal injections in the shoulder region a) 0.1 mL of 0.5%
suspension of MCW 710 SC. b) Freund's complete adjuvant and c) test
substance in a 1:1 mixture (v/v) FCA/physiological saline.
Stage 2 (topical induction): After seven days, the shoulder region of the
same animals was shaved again and coated with sodium lauryl sulfate
to induce local irritation before administration of test substance. Topical
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patch containing 2 mL of undiluted test substance was then
administered for 48 hours exposure time.
Stage 3 (challenge): On day 21, after the topical application the flanks of
same animals were shaved and filter paper containing 2 mL of 50% test
substance in water was applied to the left flank and the right flank was
untreated.
Animals were observed for mortality, body weight, clinical signs and skin
reactions.
In both induction phases after intracutaneous injection and topical
administration of the test substance, skin reaction grade 1 was observed
in all animals at 24, 48 and 72 hours post application. Mortalities were
not observed during the study and the body weight gain of treated
animals was within the range of vehicle control group animals.
Behaviour of the animals remain unchanged.
Additional Comments No additional comments
Conclusion The test substance is not a contact sensitiser.
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Ecotoxicity
Both active ingredients azoxystrobin and tebuconazole are already approved in New Zealand.
Therefore, no ecotoxicity data for the active ingredients are provided. Endpoints are summarised in
Appendix E and sourced from previous applications and the EPA internal database.
Several studies on the toxicity of Custodia® (code name MCW 710 SC) on environmental receptors
have been provided by the applicant and summarised and reviewed by the EPA. The data from the
studies have been used for classifying Custodia®. Summary of these studies is provided in Table 68
to Table 85.
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Aquatic organisms
Table 68: Aquatic toxicity: Acute toxicity to zebrafish, formulation, key study
Study type
Acute toxicity to fish
Flag
Key study
Test Substance
MCW-710 SC
Endpoint
96h-LC50
Value
7.8 mg formulation/L
Reference
(2010). Acute toxicity of MCW-710 SC to
zebrafish (Danio rerio) in a 96-hour flow through test.
Klimisch Score
1
Amendments/Deviations
None that impacted the study
GLP
Yes
Test Guideline/s
OECD 203, 1992
Nominal Dose Level
0.0, 0.3, 0.8, 1.7, 3.6 and 8.0 mg formulation/L
Mean measured Dose
Level
0.0, 0.3, 0.8, 1.7, 3.6 and 8.0 mg formulation/L (based on tebuconazole and
azoxystrobin, analytical confirmed nominal)
Analytical measurements
HPLC
Validity criteria met Yes
Study Summary
5 concentrations of the formulation plus a control containing 7 fish each were
tested for a period of 96 hours in a flow-through setting.
Fish were observed after approximately 2, 24, 48, 72 and 96 hours after the
start of exposure to observe lethal and sub lethal effects. Dead fish were
removed at least once daily.
Environmental conditions were within the limits set by the guideline. The
exposure at the start of the test was determined to be nominal and remained
stable during the test (based on tebuconazole and azoxystrobin).
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In the control and up to 3.6 mg/L all fish survived till the end of the test with
no sub lethal signs. In the highest concentration 4 fish died after 72 hours of
exposure.
The 96h-LC50 was determined to be 7.8 mg/L.
Comments
The fish are slightly outside the range of the new guideline
recommendations (OECD 203, 2019) (1-2 cm). This deviation might have
decrease the sensitivity of the fish to the formulation.
Conclusion
The 96h-LC50 was determined to be 7.8 mg formulation/L
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Table 69: Aquatic toxicity: Acute toxicity to rainbow trout, formulation, key study
Study type
Acute toxicity to fish
Flag
Key study
Test Substance
MCW-710 SC
Endpoint
96h-LC50
Value
5.4 mg formulation/L
Reference
(2010). Acute toxicity of MCW-710 SC to
rainbow trout (Oncorhynchus mykiss) in a 96-hour flow through test.
Klimisch Score
1
Amendments/Deviations
None that impacted the study
GLP
Yes
Test Guideline/s
OECD 203,1992
Nominal Dose Level
0.0, 0.3, 0.8, 1.7, 3.6 and 8.0 mg formulation/L
Mean measured Dose
Level
Yes, endpoint is based on nominal of the formulation
Analytical measurements
HPLC
Validity criteria met Yes
Study Summary
5 concentrations of the formulation plus a control containing 7 fish each were
tested for a period of 96 hours in a flow-through setting.
Fish were observed after approximately 2, 24, 48, 72 and 96 hours after the
start of exposure to observe lethal and sub lethal effects. Dead fish were
removed at least once daily.
Environmental conditions were within the limits set by the guideline. The
exposure at the start of the test was determined to be nominal. For
azoxystrobin the mean value ranged from 80 to 97% of nominal, the
exception was 3.6 mg/L which had a geometric mean of 58%. The mean
value for tebuconazole ranged from 65 to 125% of nominal. The endpoint is
based on the nominal concentration of the formulation.
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In the control and up to 3.6 mg/L all fish survived till the end of the test with
no sub lethal signs. In the highest concentration all fish died within 2 hours of
exposure.
The 96h-LC50 was determined to be 5.4 mg/L
Conclusion
The 96h-LC50 was determined to be 5.4 mg formulation/L
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Table 70: Aquatic toxicity: Acute toxicity to Daphnia magna, formulation, key study
Study type
Acute toxicity to daphnia
Flag
Key study
Test Substance
MCW-710 SC
Endpoint
48h-EC50
Value
2.15 mg formulation/L
Reference
Hoffmann, K. and Wydra V. (2010). Acute toxicity of MCW-710 SC to
Daphnia magna in a static 48-hour immobilisation test. IBACON Project
47652220
Klimisch Score
1
Amendments/Deviations
None that impacted the study
GLP
Yes
Test Guideline/s
OECD 202, 2004
Nominal Dose Level
0.0, 0.08, 0.2, 0.4, 0.8, 1.8 and 4 mg formulation/L
Measured Dose Level
Within nominal, 0.0, 0.08, 0.2, 0.4, 0.8, 1.8 and 4 mg formulation/L
(based on tebuconazole and azoxystrobin, analytical confirmed nominal)
Analytical measurements
HPLC
Validity criteria met Yes
Study Summary
6 concentrations of the formulation plus a control containing 20 daphnids
each were tested for a period of 48 hours in a static test.
Immobility was determined after 24 and 48 hours.
Environmental conditions were within the limits set by the guideline. The
exposure at the start of the test was determined to be nominal and
remained stable during the test (based on tebuconazole and
azoxystrobin).
After 48 hours of exposure no immobilisation was observed at 0.08 and
0.4 mg/L. One animal was immobilized in the control and at 0.2 mg/L. At
0.8 mg/L two animals were immobilized. At the two highest
concentrations, 1.8 and 4.0, 5 and 18 daphnids were immobilized
respectively.
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The 48h-EC50 was determined to be 2.15 mg/L
Conclusion
The 48h-EC50 was determined to be 2.15 mg formulation/L
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Table 71: Aquatic toxicity: Algal growth inhibition, formulation, key study
Study type
Acute toxicity to algae
Flag
Key study
Test Substance
MCW-710 SC
Endpoint
72h-ErC50
Value
8.72 mg/L
Reference
Hoffmann, K. and Wydra V. (2010). Acute toxicity of MCW-710 SC to
Pseudokirchneriella subcapitata in an algal growth test. IBACON Project
47651210
Klimisch Score
1
Amendments/Deviations
None that impacted the study
GLP
Yes
Test Guideline/s
OECD 201,2006
Nominal Dose Level
0.0, 0.1, 0.34, 1.1, 3.4 and 10.5 mg formulation/L
Measured Dose Level
Within nominal, 0.0, 0.1, 0.34, 1.1, 3.4 and 10.5 mg formulation/L (based
on tebuconazole and azoxystrobin, analytical confirmed nominal)
Analytical measurements
HPLC
Validity criteria met Yes
Study Summary
5 concentrations of the formulation plus a control containing 3 replicates
per treatment level and 6 for the control. Test was run for a period of 72
hours under static conditions.
Cell density was determined after 24, 48 and 72 hours. Growth rate and
yield were determined after 72 hours. Inoculation density was 5000
cells/mL obtained from an exponentially growing culture.
Environmental conditions were within the limits set by the guideline. The
exposure at the start of the test was determined to be nominal and
remained stable during the test (based on tebuconazole and azoxystrobin).
The shape of the algal cells was not obviously affected by the test
substance. The 72h-ErC50 was determined to be 8.72 mg/L and EbC50 was
1.34 mg/L. NOEC was 0.34 mg/L.
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At 0.1 mg/L the pH deviated more than 1.5 units during the test namely
1.7. This is a minor deviation that unlikely impacts the results
Conclusion
The 72h-ErC50 was determined to be 8.72 mg formulation/L
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Terrestrial toxicity
Table 72: Soil toxicity: Acute toxicity to earthworm, formulation, key study
Study type
Acute toxicity earthworm
Flag
Key study
Test Substance
MCW-710 SC
Endpoint
LC50
Value
>1000 mg formulation/ kg soil
Reference
Witte B (2009) Acute toxicity (14 days) of MCW-710 SC to the earthworm
Eisenia fetida in artificial soil with 5% peat. Report 47657021
Klimisch Score
1
Amendments/Deviations
None that affected the study results
GLP
yes
Test Guideline/s
OECD 207,1984
Nominal Dose Level
62.5, 125, 250, 500 and 1000 mg formulation/ kg soil
Analytical measurements
NA
Validity criteria met yes
Study Summary
The objective of this study was to investigate the acute toxicity of MCW-
710 SC to the earthworm Eisenia fetida after 7 and 14 days exposure.
Effects on behaviour weight and mortality were evaluated.
The formulation was applied at the rates 62.5, 125, 250, 500 and 1000
mg formulation/ kg soil to artificial soil. Peat content was decreased to
5% to consider the Kow of the active ingredients (>2).
The test was performed in 4 replicates with 10 individuals per replicate.
The pH ranged from 5.6 to 6.2, and maximum WHC was 39%.
After 14 days of exposure no mortality was observed in the control or any
test item concentration. The body weight changes were statistically
significantly different compared to the control at all test concentrations
except at the concentration of 125 mg/kg soil. The significant effect
observed at 62.5 mg/kg soil was considered not biologically relevant as
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the higher concentration was not significant different. No behavioural
effects were observed in any treatment group.
The LC50 was determined to be higher than 1000 mg formulation/kg soil.
Conclusion LC50>1000 mg formulation/ kg soil
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Table 73: Soil toxicity: Chronic toxicity to Collembola, formulation, key study
Study type
Reproduction Folsomia candida
Flag
Key study
Test Substance
MCW 170 SC
Endpoint
NOEC
Value
500 mg MCW 170 SC/ kg soil
Reference
Witte B (2009) Effects of MCW 170 SC of the Collembola Folsomia
candida in artificial soil with 5% peat. Project 47742016
Klimisch Score
1
Amendments/Deviations
None
GLP
Yes
Test Guideline/s
ISO 11267
Nominal Dose Level
62.5, 125, 250, 500 and 1000 mg formulation/kg soil
Analytical measurements
NA
Validity criteria met Yes
Study Summary
Ten juvenile Folsomia candida (5 replicates, 10-12 days old) were
exposed in an artificial soil system with 5% peat content over a period
of 28 days to MCW 170 SC. The test concentrations were 62.5, 125,
250, 500 and 1000 mg formulation/kg soil. A toxic reference
(phenmedipham) was tested in a separate study.
Temperature was 18-21°C and the photoperiod was 16 h light (420-800
lux) and 8 hours dark. pH ranged from 5.5 to 5.7. WHC was 52.8 to
54.4% at the start of the test and 48.8 to 51.2% at the end of the test.
Mortality and reproduction were determined and were used to
determine the endpoints.
The validity criteria were met. Mortality in control ≤ 20% (observed
16%) and number of juvenils per replicate ≥100 (observed 379). and
coefficient of variance of reproduction in the control ≤30% (observed
20.6%).
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The LC50 mortality value of the toxic reference was 143 mg/ kg soil and
EC50 was 70.9 mg /kg soil.
Mean mortality of the test susbtance was ranged from 16% up to 52%
for the highest test concentration. The LC50 was estimated to be more
than 1000 mg /kg soil.
Mean number of offspring after 28 days ranged from 345 at the lowest
concentration to 196 at the highest concentration. The EC50 for
reproduction was 1010.63 mg / kg soil.
Only at the highest concentration were the differences signficant
compared to the control.
The NOEC was determined to be 500 mg test substance / kg dry
weight soil.
Conclusion
NOEC = 500 mg MCW 170 SC/ kg soil
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Non-target plants
Table 74: Non-target plant toxicity: Vegetative vigour, formulation, key study
Study type
Limit test: Vegetative vigour
Flag
Key study
Test Substance
MCW 170 SC
Endpoint
NOER
Value
Not determined (< 3.375 L formulation/ha)
Reference
Butzler R., Mollandin G. (2010) Effects of MCW 170 SC on terrestrial (non-
target) plants: vegetative vigour test Project 47650087
Klimisch Score
1
Amendments/Deviatio
ns
None that affected the study results
GLP
Yes
Test Guideline/s
OECD 227
Nominal Dose Level
3.375 L/ha
Analytical
measurements
HPLC/ UV detection
Validity criteria met Yes
Study Summary
This study aimed to determine the effects of the test item with respect to
vegetative vigour. The study was performed on ryegrass, onion, cabbage,
soybean, sugar beet and sunflower. The test treatment at a rate of 3.375 L/ha
were sprayed on the 2 to 4 true leaf stage. A minimum of 20 plants per
treatment and species were used.
Endpoints measured were mortality, phytotoxicity, growth stages and
determination of NOER based on fresh weight.
The analytical recovery of both active ingredeints was 118% for azoxystrobin
and 110% of tebuconazole of the nominal value.
No mortality was observed for any species tested. No phytotoxicity was
observed 21 days after application.
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The plant development was not delayed.
Sugar beet was the only sensitive species regarding fresh weight with a
statistical significant reduction of 13.1%. The other species did not show
significant effects.
The NOER for all species was 3.375 L formulation/ha with the exception of
sugar beet for which the NOER could not be determined (NOER < 3.375 L
formulation/ha).
Conclusion
NOER not determined (<3.375 L formulation/ha)
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Soil micro-organisms
Table 75: Soil toxicity: Nitrogen and carbon transformation, formulation, key study
Study type
Toxicity soil microflora, nitrogen and carbon transformation
Flag
Key study
Test Substance MCW-710 SC
Exposure
28 d, carbon transformation
56 d, nitrogen transformation
Test species Soil microflora
Endpoint Effects on nitrogen and carbon transformation
Value
Carbon transformation: No adverse effects observed
Nitrogen transformation: no long term adverse effects observed.
Reference
Feil N (2010), Effects of MCW-710 SC on the activity of soil microflora
in the laboratory. Report no 51941080
Klimisch Score 1
Amendments/Deviations None
GLP yes
Test Guideline/s OECD 216 and 217
Dose Levels
3.6 and 18 mg MCW-710 SC / kg dry soil
(equivalent to 2.5 and 12.5 L formulation/ha)
Validity criteria met Yes
Study Summary
The aim of the study was to determine the effects of MCW-710 SC to
soil microflora activity (nitrogen and carbon transformation).
Application rates were equivalent to 2.5 and 12.5 L test substance/ha.
The used soil was a mid-loamy sand soil with pH of 6.9, % C 1.17, and
WHC 42.4% enriched with Lucerne meal enriched with Lucerne meal
for nitrogen transformation test and added glucose for the respiration
test. Three replicates were used.
Nitrogen transformation
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NH4-nitrogen, NO3- and NO2- nitrogen were determined by an ion
chromatograph at different sampling intervals (0, 7, 14 and 28, 41 and
56 days after treatment).
The variation of the control was below 15%, except for day 98 for soil
respiration and day 14 for nitrogen content. In a separate study the
reference substance sodium chloride (16 g/kg soil) had a retarding or
stimulating effect of more than 25% compared to the control at days 28
and 98 after application.
MCW-710 SC caused a temporary inhibition of the nitrate
transformation at both concentrations at day 28 (-29.1% low rate and -
26.6% high rate). At day 56 the inhibition was decreased to -16.5%
(low rate) and -14.1% (high rate).
At day 28 after application, the differences between the soil nitrate
content of MCW-710SC treated soil at both concentrations and the
control were below the 25% trigger value (-17.87% low rate and -
18.23% high rate). After 56 days the differences compared to the
control were -12.65% and -11.81% for the lower and higher
concentrations, respectively.
Mineral nitrogen content: at day 56 the deviation from the control was
-12.37% and 11.89% at the lower and higher concentration,
respectively.
Carbon transformation
At day 7, 14 and 28 after application Co2 production was determined
using the BSB-Sensomat system for 24 hours.
The variation of the control was below 15%
At day 28 the respiration rates of MCW-710SC treated soils differed
from the control by 0.05% and 3.93% at the lower and higher
concentration, respectively.
Conclusion
MCW-710 SC did not cause long term adverse effects on nitrogen and
carbon transformation up to a rate of 18 mg/ kg soil (equivalent to 12.5
L formulation/ha).
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Table 76: Soil toxicity: Nitrogen and carbon transformation, formulation, key study
Study type
Toxicity soil microflora, nitrogen and carbon transformation
Flag
Key study
Test Substance MCW-710 SC
Exposure
28 d, carbon transformation
41 d, nitrogen transformation
Test species Soil microflora
Endpoint Effects on nitrogen and carbon transformation
Value
Carbon transformation: No adverse effects observed
Nitrogen transformation: no long term adverse effects observed.
Reference
Feil N (2010), Effects of MCW-710 SC on the activity of soil microflora in
the laboratory. Report no 47659080
Klimisch Score 1
Amendments/Deviations None
GLP yes
Test Guideline/s OECD 216 and 217
Dose Levels
5.76 and 14.4 mg MCW-710 SC / kg dry soil
(equivalent to 2 and 5 L formulation/ha)
Validity criteria met Yes
Study Summary
The aim of the study was to determine the effects of MCW-710 SC to soil
microflora activity (nitrogen and carbon transformation).
Application rates were equivalent to 2 and 5 L test substance/ha. The used
soil was a mid-loamy sand soil with pH of 6.9, % C 1.17, and WHC 42.4%
enriched with Lucerne meal for nitrogen transformation test and added
glucose for the respiration test. Three replicates were used.
Nitrogen transformation
NH4-nitrogen, NO3- and NO2- nitrogen were determined by an ion
chromatograph at different sampling intervals (0, 7, 14 and 28, 41 days
after treatment).
The variation of the control was below 15%. In a separate study the
reference substance sodium chloride (16 g/kg soil) had a retarding or
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stimulating effect of more than 25% compared to the control at days 28
and 98 after application.
Nitrate content: at day 28 the differences compared to control were -
21.31% and -16.41% for the lower and higher concentrations, respectively.
At day 41 the deviation was -21.39% (low rate) and -19.42% (high rate).
Nitrate formation: for the lower test concentration the deviation compared
to control was less than 25% at the 14-28 day interval. At the higher test
concentration the deviation was more than 25% at the 14-28 day interval (-
29.45%) and remained within the trigger level at 28-41 day interval (-
23.33%).
Mineral nitrogen content: for both concentrations the differences were
below the 25% trigger value at 28-41 day interval. At day 41 the deviation
from the control was -20.88 % and -18.73% at the lower and higher
concentration, respectively.
Carbon transformation
Co2 production was determined by the BSB-Sensomat system for 24
hours at different sampling intervals (0, 7, 14 and 28 days after treatment).
The variation of the control was below 15%. In a separate study the
reference substance sodium chloride (16 g/kg soil) showed the required
response.At day 28 after application, the respiration rates of MCW-710SC
treated soils differed from the control by -0.5% and -0.7% at the lower and
higher concentration, respectively.
Conclusion
MCW-710 SC did not cause long term adverse effects on nitrogen and
carbon transformation up to a rate of 14.4 mg/ kg soil (equivalent to 5 L
formulation/ha).
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Birds
Table 77: Terrestrial toxicity: Acute toxicity to quail, formulation, key study
Study type
Limit acute toxicity test to birds
Flag
Key study
Test Substance MCW 170 SC
Exposure oral
Test species Japanese quail
Endpoint LD50
Value >2000 mg ai/ kg bw
Reference
(2009), Avian acute toxicity study of MCW 170 SC-
Japanese quail – limit test.
Klimisch Score 1
Amendments/Deviations None that impacted the results of the study
GLP yes
Test Guideline/s SETAC and OPPTS 850.2100
Dose Levels 2000 mg ai/ kg bw
Analytical measurements NA
Study Summary
The aim of the study was to determine the acute effects of MCW 170 SC to
Japanese quail (Coturnix coturnix japonica).
Forty day old adult Japanese quails (5 males and 5 females) were orally
dosed by gavage into the birds crop at a limit dose level of 2000 mg
formulation/kg body weight. The control group (5 males and 5 females)
were treated with the vehicle tap water. Observations included
regurgitation, mortality, signs of intoxication and remission and abnormal
behaviour. Body weight was determined within 24 hours of dosing and
weekly after administration. Food consumption was recorded for periods 1-
3 days, 4-7 days, 8-14 days.
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Under the present test conditions, a single oral administration of 2000 mg
MCW 710 SC/kg b.w. did not reveal any signs of toxicity. No mortality
occurred. Normal body weight development was observed for all animals
during the course of the study.
No signs or abnormalities were noted at necropsy.
LD50 > 2000 mg/kg
Conclusion LD50 > 2000 mg ai/ kg bw
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Pollinators
Table 78: Terrestrial toxicity: Acute toxicity to honey bees, formulation, key study
Study type
Acute contact and oral toxicity. Limit test
Flag
Key study
Test Substance
MCW 710 SC
Endpoint
LD50
Value
Contact: > 200 μg formulation/bee
Oral: >208.4 µg formulation/ bee
Reference
Sekine T. (2010) Effects of MVW 710 SC (acute contact and oral) on honey
bee Apis mellifera in the laboratory. Project 47741035
Klimisch Score
1
Amendments/Deviations
None that impacted the study
GLP
Yes
Test Guideline/s
OECD 213 and 214
Nominal Dose Level
Contact and oral: 200 µg formulation/ bee
Measured dose level
Oral: 208.4 μg formulation/bee
Analytical measurements
NA
Validity criteria met Yes
Study Summary
The aim of this study was to assess the acute contact and oral toxicity of
MCW 710 SC to the honey bee, Apis mellifera, in a laboratory study. The
nominal dose levels for the contact toxicity test was 200 μg formulation/bee
and for the oral test 208.4 μg formulation/bee.
For the contat test MCW 710 SC was applied with tap water with 0.5%
wetting agent. Bees in the control group received tap water with wetting
agent.
MCW 710 SC was diluted with 50 % sugar syrup solution for the oral test.
Bees in the control group received tap water with sugar syrup. A toxic
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reference (dimethoate) was used. The test solutions were offered to the bees
for 4.5 hours.
In both tests, 5 replicates with 10 bees each were tested. Assessments of
mortality and abnormal behavioural effects were carried out at 4, 24 and 48
hours after start of feeding the test solutions.
Contact test
No mortality was observed in the control and treatment group. No abnormal
behaviour was observed in the control and treatment group. Therefore, the
LD50 is considered to be higher than 200 µg formulation/ bee.
Oral test
No mortality occurred in the control group fed with pure 50% sugar solution
and 2.0% mortality was observed in the treatment group.
No abnormal behaviour was observed in the control and treatment group.
Therefore, the LD50 is considered to be higher than 208.4 µg formulation/
bee.
Conclusion
Contact LD50 > 200 μg formulation/bee
Oral LD50 > 208.4 μg formulation/bee oral
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Non-target arthropods
Table 79: Terrestrial toxicity: Toxicity to parasitoids, formulation, key study
Study type Beneficial insect toxicity
Flag Key study
Test Substance MCW-710 SC
Endpoint LR50
Value 605 mL product/ha
Reference
Moll M. (2009) Effects of MCW-710 SC on the parasitoid Aphidius rhopalosiphi
extended laboratory study-Dose response test. Project 47744002
Klimisch Score 1
Amendments/Deviatio
ns
None that affected the study results
GLP Yes
Test Guideline/s Mead Briggs et al
Nominal Dose Level 144, 317, 697, 1534 and 3375 mL formulation/ha
Validity criteria met Yes
Study Summary
In a laboratory test parasitoid wasp, Aphidius rhopalosiphi, were exposed to
dried residues of MCW 710 SC for 48 hours. Test product was applied at rates
of 144, 317, 697, 1534 and 3375 mL formulation/ha on barley plants. A water
control and a reference product (dimethoate) were included in the test. Six
replicates of 5 wasps (females) were used for each treatment. Survival and
behaviour were assessed at 2, 24 and 48 hours. Fecundity was assessed after
48 hours from concentrations with >50% corrected survival. Females were
transplanted onto aphid invested plants and were removed after 24 hours. After
11 days mummies were assessed.
In the control no mortality was observed and in the toxic reference 100%.
The mortality in the treatments was 0, 20, 50, 96.7 and 100% at 144, 317, 697,
1534 and 3375 mL formulation/ha respectively. The LR50 was determined to be
605 mL product/ha.
The number of mummies per female was 71.1 in the control. The number of
mummies per female was 61.1, 55.5 and 36.2 at 144, 317 and 697 mL
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product/ha respectively. Only at 697 mL product/ha the difference compared to
control was significant but the effect on reproduction was just below the trigger
value of 50% (49.2%).
Conclusion LR50 is 605 mL product/ha
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Table 80: Terrestrial toxicity: Toxicity to parasitoids, formulation, key study
Study type Beneficial insect toxicity
Flag Key study
Test Substance MCW-710 SC
Endpoint Effects on survival and reproduction
Value
The effects of MCW 710 SC were below the trigger value of 50% on
mortality and fecundity after application with the product at 3.38 L/ha.
Reference
Moll M. (2010) Effects of MCW-710 SC on the parasitoid Aphidius
rhopalosiphi extended laboratory study- aged residue test. Project
47654003
Klimisch Score 1
Amendments/Deviations None that affected the study results
GLP Yes
Test Guideline/s Mead Briggs et al
Nominal Dose Level 3.38 L formulation/ha
Validity criteria met Yes
Study Summary
In a laboratory test parasitoid wasp, Aphidius rhopalosiphi, were exposed
to freshly dried residues of MCW 710 SC for 48 hours. Test product was
applied at the rate of 3.38 L product/ha on leaves of bean plants. A water
control and a reference product (dimethoate) were included in the test.
Four replicates of 10 wasps (7 females and 3 males) were used for each
treatment. Survival and behaviour were assessed at 2, 24 and 48 hours
and fecundity was assessed after 48 hours. Females were transplanted
onto aphid invested plants and were removed after 24 hours. After 11
days mummies were assessed.
In the control no mortality was observed and in the toxic reference 100%.
The mortality in the treatment was 15% (significant different compared to
control).
The number of mummies per female was 36.8 in the control group and
38.7 in the treatment group.
The effects of MCW 710 SC were below the trigger value of 50%.
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Conclusion
The effects of MCW 710 SC were below the trigger value of 50% on
mortality and fecundity.
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Table 81: Terrestrial toxicity: Toxicity to ladybird beetles, formulation, key study
Study type Beneficial insect toxicity
Flag Key study
Test Substance MCW-710 SC
Endpoint LR50
Value >3375 mL product/ha
Reference
Moll M. (2009) Effects of MCW-710 SC on the ladybird beetle Coccinella
septempunctata extended laboratory study-Dose response test. Project
47746012
Klimisch Score 1
Amendments/Deviations None that affected the study results
GLP Yes
Test Guideline/s Schmuck et al
Nominal Dose Level 63.5, 171, 463, 1250, 3375 mL formulation/ha
Validity criteria met Yes
Study Summary
In a laboratory test the ladybird beetle Coccinella septempunctata (4-5
day old larvae), were exposed to dried residues of MCW 710 SC. Test
product was applied at rates of 63.5, 171, 463, 1250, 3375 mL
formulation/ha on bean leaves. A water control and a reference product
(dimethoate) were included in the test. Forty replicates containing one
beetle larva were used for each treatment. Survival and behaviour were
assessed during 20 days. Fecundicy of the survival was assessed for 2
weeks from concentrations with >50% corrected survival.
In the control 10% mortality was observed and in the toxic reference
100%.
The corrected mortality in the treatments was -5.6, -5.6, 0, 2.8 and
16.7% at 63.5, 171, 463, 1250, 3375 mL formulation/ha respectively. The
LR50 was determined to be >3375 mL product/ha.
The number of fertile eggs per female per day was 6.4 in the control. The
number of fertile eggs/female/day was 10.2, 5.3, 7.5, 11.4, 7.4 at 63.5,
171, 463, 1250, 3375 mL product/ha respectively.
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Conclusion LR50 >3375 mL product/ha
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Table 82: Terrestrial toxicity: Toxicity to lacewings, formulation, key study
Study type Beneficial insect toxicity
Flag Key study
Test Substance MCW-710 SC
Endpoint LR50
Value >3375 mL product/ha
Reference
Moll M. (2009) Effects of MCW-710 SC on the lacewing Chrysoperla
carnea extended laboratory study-Dose response test. Project
47747047
Klimisch Score 1
Amendments/Deviations None that affected the study results
GLP Yes
Test Guideline/s Vogt et al
Nominal Dose Level 63.5, 171, 463, 1250, 3375 mL formulation/ha
Validity criteria met Yes
Study Summary
In a laboratory test the lacewing Chrysoperla carnea larvae (2 days
old), were exposed to dried residues of MCW 710 SC. Test product
was applied at rates of 63.5, 171, 463, 1250, 3375 mL formulation/ha
on bean leaves. A water control and a reference product (dimethoate)
were included in the test. Forty replicates containing one larva were
used for each treatment. Exposure lasted as long as pupae were
transferred to the reproduction units for development of adults
(concentrations with corrected mortality <50%). Mortality (until hatching
of adults) and reproduction were assessed.
In the control 7.5% mortality was observed and in the toxic reference
100%.
The corrected mortality in the treatments was 24.3, 13.5, 8.1, 13.5 and
8.1 at 63.5, 171, 463, 1250, 3375 mL formulation/ha respectively.
Mortality at 63.5 mL/ha was significantly impacted but considered not
biologically relevant as higher concentrations were not significantly
impacted. The LR50 was determined to be >3375 mL product/ha.
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The number of eggs per female per day was 19.0 in the control. The
number of eggs/female/day was 26.8, 24.7, 19.0, 22.5 and 28.9 at
63.5, 171, 463, 1250, 3375 mL product/ha respectively.
Fertility was 79.7% in the control. Fertility was 60.7, 68.5, 40.9, 58.7
and 48.6% at 63.5, 171, 463, 1250, 3375 mL product/ha respectively.
Mortality was not affected but there was an effect on fertility.
Conclusion LR50 >3375 mL product/ha
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Table 83: Terrestrial toxicity: Toxicity to predatory mites, formulation, key study
Study type Beneficial insect toxicity
Flag Key study
Test Substance MCW-710 SC
Endpoint Effects on survival and reproduction
Value
Effects on mortality and reproduction were below the 50% threshold for
both fresh and aged residues after application with the product at 3.38
L/ha.
Reference
Schwarz A. (2010) Effects of MCW-710 SC on the predatory mite
Typhlodromus pyri, extended laboratory study- Aged residue test. Project
47655060
Klimisch Score 1
Amendments/Deviations None that affected the study results
GLP Yes
Test Guideline/s Blumel et al, Oomen
Nominal Dose Level 3.38 L product/ha
Validity criteria met
In the study with fresh residues the reproduction of the control was below 4
eggs per female. Therefore, the study with aged residues was performed.
The reproduction in the control in this study was conform the guideline.
Study Summary
In a laboratory test the predatory mite Typhlodromus pyri, were exposed to
dried residues (fresh and 7 days aged) of MCW 710 SC. Test product was
applied at a rate of 3.38 L formulation/ha on bean leaves. A water control
and a reference product (dimethoate, not in ages residue test) were
included in the test. Ten replicates containing ten mites were used for each
treatment. Mortality was assessed 7 days after exposure and reproduction
were assessed (as corrected mortality was <50%).
Fresh residue
In the control 13% mortality was observed and in the toxic reference 78.2%
(corrected). The corrected mortality in the treatment was 24.1%.
The number of eggs per female was 2.7 in the control and 5.6 in the
treatment of test item. The validity criteria in the control were not fulfilled.
Aged residue
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In the control 18% mortality was observed and the corrected mortality in
the treatment was 27%.
The number of eggs per female was 4.2 in the control and 7.2 in the
treatment of test item.
Conclusion
Effects on mortality and reproduction were below the 50% threshold for
aged residues.
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Table 84: Terrestrial toxicity: Toxicity to predatory mites, formulation, key study
Study type Beneficial insect toxicity
Flag Key study
Test Substance MCW-710 SC
Endpoint Effects on mortality and reproduction
Value
Effects on mortality are below 50% threshold.
Effects on reproduction are above 50% for the dose rates 171, 463 and 3375
mL formulation/ha.
Reference
Schwarz A. (2009) Effects of MCW-710 SC on the predatory mite
Typhlodromus pyri, extended laboratory study- Dose response test. Project
47745062
Klimisch Score 1
Amendments/Deviations None that affected the study results
GLP Yes
Test Guideline/s Blumel et al, Oomen
Nominal Dose Level 63.5, 171, 463, 1250, 3375 mL formulation/ha
Validity criteria met Yes
Study Summary
In a laboratory test the predatory mite Typhlodromus pyri, were exposed to
dried residues of MCW 710 SC. Test product was applied once at rates of
63.5, 171, 463, 1250, 3375 mL formulation/ha on bean leaves. A water
control and a reference product (dimethoate) were included in the test. Six
replicates containing ten mites were used for each treatment. Mortality was
assessed 3 and 7 days after exposure and reproduction were assessed for
test group with <50% corrected mortality.
In the control 6.7% mortality was observed and in the toxic reference 100%.
The mortality in the treatments was 28.3, 40.0, 11.7, 31.7, 36.7% ( corrected
mortality 23.3, 35.7, 5.4, 26.8, 32.1%) at the rates 63.5, 171, 463, 1250, 3375
mL formulation/ha respectively. With the exception of the mortality of 463 mL
formulation/ha, the difference compared to the control was statistically
significant.
The number of eggs per female was 4.9 in the control. In the treatments the
number of eggs per female were 3.5, 2.4, 2.2, 3.5 and 1.4 at the rates 63.5,
171, 463, 1250, 3375 mL formulation/ha respectively (no significant
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differences). The effect on reproduction was 28.8, 51.2, 54.9, 29.2 and 71.9%
at the rates 63.5, 171, 463, 1250, 3375 mL formulation/ha respectively.
The reproduction for all treatments was below the trigger value of 4
eggs/female and the effects on reproduction are above 50% for the dose rates
171, 463 and 3375 mL formulation/ha.
Conclusion
Effects on mortality are below 50% threshold.
Effects on reproduction are above 50% for the dose rates 171, 463 and 3375
mL formulation/ha.
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Table 85: Terrestrial toxicity: Toxicity to predatory mites, formulation, key study
Study type Beneficial insect toxicity
Flag Key study
Test Substance MCW-710 SC
Endpoint Effects on population predatory mites
Value
No unacceptable effects were observed after 2 applications with MCW
710 SC at a rate of 0.263 and 0.438 L/ha.
Reference
Ipach R. (2012) Effects of MCW-710 SC on predatory mites
(Typhlodromus pyri), under typical vine culture conditions after 2
applications (beginning BBCH 55-57); grapevines, Germany 2011
Study number FCS02
Klimisch Score 1
Amendments/Deviations None that affected the study results
GLP Yes
Test Guideline/s Blumel et al, BBA-Guideline VI, 23-2.3.4
Nominal Dose Level 0.263 and 0.438 L formulation/ha
Validity criteria met NA
Study Summary
The purpose of the field trial was to assess the effect of MCW 710 SC
on the populations of the predatory mite Typhlodromus pyri in
grapevines. The formulation was applied twice at a rate of 0.263 and
0.438 L/ha at growth stage BBCH 55-57 and 69. A water control and a
reference product (deltamethrin) were also applied twice. The
application interval was 14 days. All treatments were conducted in five
replicates with 15 vines each.
The population development of mites was assessed by determining the
number of mites on leaf samples, using a washing method. 25
leaves/plot were taken before the 1st application, 6 days and 28 days
after the 2nd application.
The pre-assessment one day before the 1st application showed that the
mite population was homogenous.
Mean number of predatory mites per 25 leaves are presented in the
table below.
Mean number of mites/25 leaves
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Assessment
timing
control MCW 710 SC reference
Pre assessment 125 135 130
6DAA2 85 73 7
28DAA2 95 88 1
Effects of MCW 710 SC compared to the control according to Abbott is
14% 6DAA2 and 7% 28DAA2. Effects of the reference according to
Abbott is 92 and 99% at 6DAA2 and 28DAA2 respectively. The results
of the reference indicate that the test system is suitable to determine
the effects of the treatments.
Conclusion
No unacceptable effects were observed after 2 applications with MCW
710 SC at a rate of 0.263 and 0.438 L/ha.
[Note that the proposed application rate is 1 L formulation /ha.]
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Appendix J: Standard terms and abbreviations
Abbreviation Definition
ai active ingredient
ADE Acceptable Daily Exposure
ADI Acceptable Daily Intake
AOEL Acceptable Operator Exposure Level
BBA Biologishe Bundersantalt für Land- und Forstwirtschaft
BBCH Biologische Bundesanstalt, Bundessortenamt und CHemische Industrie
BCF BioConcentration Factor
Bw body weight
CAS # Chemical Abstract Service Registry Number
cm centimetres
CoA Certificate of Analysis
CRfD Chronic Reference Dose
DDD Daily Dietary Dose
DT50 Dissipation Time (days) for 50% of the initial residue to be lost
dw dry weight
EbC50 EC50 with respect to a reduction of biomass
EyC50 EC50 with respect to a reduction of yield (y)
EC European Commission
EC25 Effective Concentration at which an observable adverse effect is caused in 25 %
of the test organisms
EC50 Effective Concentration at which an observable adverse effect is caused in 50 %
of the test organisms
EEC Estimated Environmental Concentration
EEL Environmental Exposure Limit
EFSA European Food Safety Authority
ErC50 EC50 with respect to a reduction of growth rate (r)
ER50 Effective Residue concentration to 50% of test organisms
FAO Food and Agriculture Organization
g grams
GAP Good Agricultural Practice
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GENEEC Generic Estimated Environmental Concentration
ha hectare
HQ Hazard Quotient
Kd partition (distribution) coefficient
Koc organic carbon adsorption coefficient
Kow octanol water partition coefficient
Kg Kilogram
L litres
Lb pounds
LC50 Lethal Concentration that causes 50% mortality
LD50 Lethal Dose that causes 50% mortality
LOAEC Lowest Observable Adverse Effect Concentration
LOAEL Lowest Observable Adverse Effect Level
LOC Level Of Concern
LOD Limit Of Detection
LOEC Lowest Observable Effect Concentration
LOEL Lowest Observable Effect Level
LR50 Lethal Rate that causes 50% mortality
M Molar
m3 cubic metre
MAF Multiple Application Factor
μm micrometre (micron)
mg milligram
μg microgram
mol mole(s)
MSDS Material Safety Data Sheet
NAEL No Adverse Effect Level
ng nanogram
NOAEC No Observed Adverse Effect Concentration
NOAEL No Observed Adverse Effect Level
NOEC No Observed Effect Concentration
NOED No Observed Effect Dose
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NOEL No Observed Effect Level
NOER No Observed Effect Rate
OCS Office of Chemical Safety
OECD Organisation for Economic Cooperation and Development
OPPTS Office of Prevention, Pesticides, and Toxic Substances (US Environmental
Protection Agency)
PDE Potential Daily Exposure
PEC Predicted Environmental Concentration
PHI Pre-Harvest Interval
pKa Acid dissociation constant (base 10 logarithmic scale)
PNEC Predicted No Effect Concentration
POW Partition coefficient between n-octanol and water
ppb parts per billion (10-9)
PPE Personal Protective Equipment
ppm parts per million (10-6)
REI Restricted Entry Interval
RPE Respiratory Protective Equipment
RQ Risk Quotient
TER Toxicity Exposure Ratio
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Appendix K: References
APVMA (2010). "Standard spray drift risk assessment scenarios."
Department Of Conservation (DOC) (2014). Conservation status of New Zealand earthworms, 2014.
EC (2007). Draft Assessment Report - Initial risk assessment provided by the rapporteur Member
State Denmark for the existing active substance tebuconazole.
EC (2009). Azoxystrobin - Report and Proposed Decision of The United Kingdom made to the
European Commission under Commission Regulation 737/2007.
EFSA (2009). "Risk Assessment for Birds and Mammals." EFSA Journal 7(12): 1438.
EFSA (2013). "Guidance on tiered risk assessment for plant protection products for aquatic organisms
in edge-of-field surface waters." EFSA Journal 11(7): 3290.
EFSA (2014). "Conclusion on the peer review of the pesticide risk assessment of the active substance
tebuconazole." EFSA Journal 12(1): 3485.
EPA (2018). Risk Assessment Methodology for Hazardous Substances ; Draft for Consultation.
HSNO
Kim Y., D. N., Nowie M., Robinson B., Boyer S. (2017). "Molecular identification and distribution of
native and exotic earthworms in New Zealand human-modified soils." New Zealand Ecological
Society(41(2)).
Klimisch, H. J., M. Andreae and U. Tillmann (1997). "A systematic approach for evaluating the quality
of experimental toxicological and ecotoxicological data." Regul Toxicol Pharmacol 25(1): 1-5.
McCall P.J., Laskowski D.A., Swann R.L. and D. H.J. (1981). Measurement of sorption coefficients of
organic chemicals and their use, in environmental fate analysis. Test Protocols for Environmental
Fate and Movement of Toxicants, Proceedings of AOAC Symposium, AOAC. Washington DC.
OCS (2015). Health Risk Assessment - Technical Report - Custodia Fungicide.
Workshop, E., M. P. Candolfi, S. Europe and C. Commission of the European Guidance document on
regulatory testing and risk assessment procedures for plant protection products with non-target
arthropods : from the ESCORT 2 Workshop (European Standard Characteristics of Non-Target
Arthropod Regulatory Testing) : a joint BART, EPPO/CoE, OECD, and IOBC workshop organised in
conjunction with SETAC Europe and EC : held at Wageningen International Conference Center,
Wageningen, the Netherlands, 21-23 March 2000, Pensacola, FL, Society of Environment Toxicology
and Chemistry.
Science memo for application to import or manufacture Custodia® for release (APP203638)
FEBRUARY 2020
Appendix L: Confidential Composition
Recommended