APP203301 – Paraquat and paraquat-containing formulations · 2019. 4. 6. · paraquat...

SCIENCE MEMO

APP203301 – Paraquat and paraquat-containing

formulations Substance database ID 2761 Paraquat (HSR003041) ID 11203 Paraquat dichloride ID 8394 Soluble concentrate containing 200 – 250 g/litre paraquat as the dichloride salt (HSR000828) ID 5126 Soluble concentrate containing 115 g/litre diquat as the dibromide salt and 135 g/litre paraquat as the dichloride salt (HSR000447) ID 41233 Uniquat 250 (HSR100443) ID 43319 Parable 250 (HSR100572) ID 19527 Preeglone Inteon (HSR007854) ID 19371 Gramoxone Inteon (HSR007847) Notes:

This list includes all approved substances that contain paraquat or its salts, including paraquat as a single substance.

There is no separate approval for paraquat dichloride, or its manufacturing concentrate.

January 2019

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Science memo for application to reassess paraquat and paraquat-containing formulations (APP203301)

January 2019

Executive Summary

This application is to reassess the active ingredient paraquat. Paraquat-containing formulations are intended to be used as herbicides. The active ingredient in paraquat-containing formulations is paraquat “cation” in the

form of a dichloride salt at ~250 g/L, plus other components. Throughout this document the EPA refers to

“paraquat”, which means the paraquat ion not the dichloride salt. All application rates and toxicity endpoints relate to the paraquat ion unless otherwise noted.

The proposed classification for paraquat is 6.1C (acute oral), 6.1E (acute dermal, 6.1A (acute inhalation),

6.3B (skin irritation), 6.4A (eye irritation), 6.9A (target organ toxicity), 9.1A (aquatic ecotoxicity), 9.3B (terrestrial vertebrates) and 9.4B (terrestrial invertebrates).

It is considered that there is potential for significant exposure to people and the environment during the use

phase of the lifecycle of paraquat-containing formulations. As such, quantitative risk assessments have been undertaken to understand the likely exposures to the substance under the use conditions as summarized in

Appendix A, using the endpoint data available and the standard risk assessment methodologies used by the

EPA (EPA 2018).The EPA is aware that there is a wide variety of uses of paraquat dichloride. For the purposes of this science assessment, only a small number of representative use scenarios has been

considered. For the human health risk assessment this has focussed on the use patterns which are known to

reduce the operator risks to less than the LOC. The environmental risk assessments generally consider best and worst-case scenarios as well as a number of important use patterns.

It is considered that the risks to human health from the proposed use of paraquat-containing formulations on

50 ha fields via boom or aerial application methods with coarse droplets are acceptable as long as the appropriate level of PPE is used. Following the modelling of different application rates scenarios it was

determined that full PPE with maximum respiratory protection is needed to safely apply paraquat

formulations at rates of 325(448) – 600(828) g ion(dichloride) ai/ha. The use of full PPE excluding respiratory protection is needed for application rates between 50(69) – 325(448) g ion(dichloride) ai/ha, and no PPE is

required at applications rates below 50 g ai/ha (69 g dichloride ai/ha). Application rates above 600(828) g

ion(dichloride) ai/ha had RQ values that exceeded the AOEL even with use of PPE that included maximum respiratory protection.

When using a backpack, the maximum application rate that could be applied on 1 ha with minimal risk,

provided full PPE plus maximum respiratory protection is worn during mixing, loading, and application, was 390 g ai/ha (538 g dichloride ai/ha). The maximum application rate that could be applied using a knapsack

with minimal risk, provided full PPE with no respiratory protection is worn during mixing, loading, and

application, was 110 g ai/ha (152 g dichloride ai/ha), and the maximum amount that could be applied with minimal risk, provided no PPE be required during mixing, loading, and application, was 35 g ai/ha (48 g

dichloride ai/ha).

There is no need for the application of re-entry intervals as the functional uses of paraquat are not associated with worker re-entry and anticipated exposure was qualitatively deemed to be of low risk.

Estimated bystander exposure from spray drift 8 m away after application of paraquat-containing

formulations to the soil for agricultural uses from boom or aerial application methods at an application rate of

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600(828) g ion (dichloride) ai/ha is below the AOEL and no buffer zone is required to protect bystanders.

However, exposure from aerial forestry applications is above the AOEL using coarse droplets and will require a buffer zone of 14 m in order to ensure bystander exposures are below the AOEL.

It is considered that the risks to the environment from the proposed use of paraquat-containing formulations

are above the LOC as the identified risks to birds cannot be mitigated even with the prescribed, modified and additional controls. Further information from submitters could help refine this risk assessment. While risks to

the aquatic environment, non-target plants, bees and beneficial insects were identified there are potential

controls which could mitigate these risks

A set of proposed controls has been identified following the human health and environmental risk

assessments conducted. These have been summarized in Appendix E of the application form for the

application APP203301.

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Table of Contents APP203301 – Paraquat and paraquat-containing formulations ............................ 1

Executive Summary .................................................................................................. 2

Table of Contents ..................................................................................................... 4

1. Introduction/Background................................................................................. 7

2. Hazardous properties ...................................................................................... 9

Hazard classification of paraquat ....................................................................... 9

Hazard classification of paraquat-containing formulations ................................. 9

Identification of components of concern ........................................................... 10

3. Risk assessment context .............................................................................. 10

4. Human health risk assessment ..................................................................... 10

5. Environmental risk assessment .................................................................... 12

6. Proposed controls .......................................................................................... 14

Appendix A: Identity of the active ingredient, use pattern and mode of action 15

Identity of the active ingredient and metabolites .............................................. 15

Regulatory status ............................................................................................. 16

Impurities and or restrictions on purity or composition ............................. 16

Use pattern and mode of action ....................................................................... 17

Use pattern .............................................................................................. 17

Mode of action ......................................................................................... 18

Appendix B: Mammalian toxicology ..................................................................... 19

Executive summaries and list of endpoints for paraquat-containing formulations19

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

General conclusion about mammalian toxicology of paraquat ......................... 23

Acute toxicity, irritation and sensitisation ................................................. 24

Mutagenicity ............................................................................................. 24

Carcinogenicity ........................................................................................ 24

Reproductive and developmental toxicity ................................................. 24

Neurotoxicity ............................................................................................ 24

Target organ toxicity ................................................................................ 24

Toxicokinetics and dermal absorption ...................................................... 24

Appendix C: Environmental fate ........................................................................... 26

Environmental fate values used for risk assessment ........................................ 26

General conclusion about environmental fate .................................................. 28

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Appendix D: Ecotoxicity......................................................................................... 29

Appendix E: Hazard classification of paraquat .................................................... 32

Appendix F: Human health risk assessment ........................................................ 35

Quantitative risk assessment............................................................................ 35

Input values for the human health risk assessment ................................. 35

Operator exposure assessment ............................................................... 36

Re-entry worker exposure assessment .................................................... 38

Quantitative bystander risk assessment .................................................. 38

Conclusions of the human health risk assessment .................................. 39

Appendix G: Environmental risk assessment ...................................................... 41

Aquatic risk assessment ................................................................................... 41

Calculation of estimated environmental concentrations ........................... 41

Output from the GENEEC2 model ........................................................... 42

Best-case scenario (potatoes) ................................................................. 42

Worst-case scenario (non-selective weed control) .................................. 43

Calculated RQs ........................................................................................ 43

Refinement of the aquatic risk assessment ............................................. 45

Spray drift ................................................................................................ 45

Runoff ...................................................................................................... 47

Conclusions of the aquatic risk assessment ............................................ 47

Use restrictions ........................................................................................ 48

Label statements: ..................................................................................... 48

Buffer zones ............................................................................................. 48

Groundwater risk assessment .......................................................................... 48

Conclusions of the groundwater risk assessment .................................... 48

Sediment risk assessment ............................................................................... 49

Conclusions of the sediment risk assessment ......................................... 49

Terrestrial risk assessment............................................................................... 49

Soil macro-organisms .............................................................................. 49

Conclusions of the soil organism risk assessment ................................... 50

Soil micro-organisms ............................................................................... 50

Non-target plant risk assessment ..................................................................... 51

Conclusion for non-target plant risk assessment ..................................... 53

Bird risk assessment ........................................................................................ 55

Screening assessment ............................................................................. 55

Tier 1 assessment .................................................................................... 55

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Conclusion for bird risk assessment (Tier 1) ............................................ 65

Secondary poisoning ............................................................................... 66

Conclusions for bird risk assessment ....................................................... 66

Pollinator risk assessment ................................................................................ 66

Conclusions of the pollinator risk assessment ......................................... 67

Non-target arthropod risk assessment ............................................................. 68

Conclusion for non-target arthropod risk assessments ............................ 69

Conclusions of the ecological risk assessment ................................................ 69

Appendix H: Standard terms and abbreviations .................................................. 70

Appendix I: References .......................................................................................... 73

Appendix J: Study summaries .............................................................................. 75

Appendix K: Levels of concern used by the EPA ................................................ 78

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1. Introduction/Background 1.1. Paraquat is a general purpose herbicide which has been used in New Zealand since the 1960s. It is

used in forestry, ground, vine and tree crops, pasture renewal and to remove weeds in drains,

waterways and along fence lines.

1.2. In February 2016, the EPA completed a risk assessment for a new pesticide containing paraquat, Para-Ken 250 (application APP202697), which showed that the risks to human health and the

environment were higher than previously anticipated and that the human health risks could not be

sufficiently reduced by applying controls to the substance. The risk assessment also showed that paraquat poses high risks to aquatic organisms. The application was subsequently declined, and

information obtained from this risk assessment was used to determine grounds for reassessment of

paraquat and paraquat-containing substances.

1.3. An application (APP202788) to establish whether grounds for reassessment of paraquat and

paraquat-containing substances exist was lodged in February 2016. In July 2017, it was determined

that grounds exist for the reassessment of paraquat and paraquat-containing substances.

1.4. A call for information was subsequently opened in July 2017 until August 2017.

1.5. This application is to reassess the active ingredient paraquat. Paraquat-containing formulations are

intended to be used as herbicides. The active ingredient in paraquat-containing formulations is paraquat “cation” in the form of a dichloride salt at ~250 g/L, plus other components. Throughout

this document the EPA refers to “paraquat”, which means the paraquat ion not the dichloride salt.

All application rates and toxicity endpoints relate to the paraquat ion unless otherwise noted.

1.6. This assessment focuses on the active ingredient paraquat and its associated salt paraquat

dichloride. This does not look into the specific details of the various substances that contain the

active ingredient.

1.7. Paraquat-containing formulations are currently approved for similar use patterns in the US,

Canada, Japan and Australia. Paraquat-containing formulations are not currently registered for use

in the EU.

1.8. More details about paraquat’s mode of action and the regulatory status of paraquat can be found in

Appendix A.

1.9. It is considered that there is potential for significant exposure to people and the environment during the use phase of the lifecycle of paraquat-containing formulations. As such, quantitative risk

assessments have been undertaken to understand the likely exposures to the substance under the

use conditions as summarized in Appendix A, using the endpoint data available and the standard risk assessment methodologies used by the EPA (EPA 2018). The risk assessment of paraquat-

containing formulations is described in Appendices F and G.

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1.10. For this assessment the EPA selected data from its substance database as well as reviewing

information contained in reviews carried out by other regulators. The other regulators whose reviews were considered were:

Australian Pesticides and Veterinary Medicines (APVMA) toxicology review in 2016 (APVMA

2016)

Pest Management Regulatory Agency (PMRA) review in 2015 (PMRA 2015)

European Commission (EC) review documents in 2002 (EC 2002) and 2003 (EC 2003)

United States Environmental Protection Agency (US EPA) review in 1997 (US EPA 1997)

Food and Agriculture Organization (FAO) [Joint FAO/World Health Organization (WHO)

Meeting on Pesticide Residues (JMPR 2003) and (JMPR 2004)]

1.11. In addition, information supplied by submitters in reponse to the call for information was used to assist with the hazard classification and risk assessment. The EPA has not reviewed all the

information supplied by submitters in detail. The exception being when submitters have raised

issues relating to the values used by other regulators.

1.12. This document has a number of technical appendices which describe the EPA assessment:

Details related to paraquat properties can be found in Appendix A.

The mammalian toxicological properties of paraquat have been reported in Appendix B.

The environmental fate properties of paraquat have been reported in Appendix C.

The ecotoxicological properties of paraquat have been reported in Appendix D.

The hazard properties and classification of paraquat can be found in Appendix E.

The human health risk assessment is detailed in Appendix F.

The environmental risk assessment is detailed in Appendix G.

Summaries of studies used in the risk assessment are included in Appendix J.

The LOC used by the EPA are outlined in Appendix K.

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2.Hazardous properties

Hazard classification of paraquat 2.1. The hazard classifications proposed for paraquat are outlined in Table 1. More details can be found

in Appendix E.

Table 1: Current and proposed classification for paraquat

Hazard endpoint Classification (current) Classification (proposed)

Acute toxicity (oral) 6.1B 6.1C

Acute toxicity (dermal) 6.1B 6.1E

Acute toxicity (inhalation) 6.1A 6.1A

Skin irritation/corrosion 6.3A 6.3B

Eye irritation/corrosion 6.4A 6.4A

Target organ toxicity (oral) 6.9A 6.9A

Aquatic ecotoxicity 9.1A 9.1A

Terrestrial vertebrates 9.3A 9.3B

Terrestrial invertebrates 9.4B 9.4B

2.2. Paraquat is of relatively low acute toxicity in mammals following oral (6.1C) and dermal 6.1E)

exposure as it is poorly absorbed via those routes. However, it is very acutely toxic following inhalation exposure (6.1A). It is also classified for skin and eye irritant effects (6.3B and 6.4A,

respectively). It is not a contact sensitiser or mutagen, and is not classified for reproductive or

developmental toxicity or carcinogenicity. It is also classified for specific target organ toxicity (6.9A). Paraquat was found not to be neurotoxic in a 90-day repeated dose oral toxicity study in laboratory

animals.

2.3. Paraquat is also very ecotoxic to the aquatic organisms (9.1A), and ecotoxic to terrestrial vertebrates and terrestrial invertebrates (9.3B and 9.4B).

2.4. Proposed classification changes that have actually led to a lowering of some classifications are not

only the result of new data, but is the result of using a more weight-of-evidence approach taking into account the results of all studies, and putting emphasis on studies that are the most robust and

reliable as opposed to simply choosing the lowest possible value.

Hazard classification of paraquat-containing formulations 2.5. The hazard classifications of paraquat-containing formulations will be determined by the EPA after

the review of the active ingredient is finalised following applicant input on the risk assessments. This

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is important as currently the classification of some formulations contain non-active components that

have classifications not associated with paraquat, including 6.7 (carcinogenicity) and 6.8 (reproductive and developmental toxicity).

Identification of components of concern 2.6. There are no Carcinogenic, Mutagenic, Reprotoxic (CMR) compounds associated with the active

ingredient but currently some formulations contain some CMRs (pyridine and methanol) at very low

yet classifiable levels.

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 paraquat-containing formulations. As such, quantitative risk

assessments have been undertaken to understand the likely exposures to the substance under the use conditions as summarized in Appendix A, using the endpoint data available and the standard

risk assessment methodologies used by the EPA (EPA 2018).

3.2. Not all possible use scenarios have been modelled, and depending on the sections, particular crop/application method scenarios have been selected. Application rates in excess of acceptable

RQ have not been modelled and are not summarized in this document.

3.3. For operator exposure values, the EPA modelled multiple potential application rates (g ai/ha). The results (not reported) of the modelled application rates often showed exposure values that

exceeded the AOEL even when wearing full PPE including maximum respiratory protection.

Accordingly, the EPA determined the maximum acceptable application rates which could be applied and deemed safe under various use rates and PPE requirement scenarios. These included:

Maximum use rate acceptable with full PPE including maximum respiratory protection

Maximum use rate acceptable with full PPE excluding respiratory protection

Maximum use rate acceptable with no PPE required

4.Human health risk assessment 4.1. The risks from the use of paraquat are considered as a proxy for paraquat-containing formulations

on users and operators of the substance, re-entry workers and bystanders. Full details can be

found in Appendix F: Human health risk assessment

4.2. Operator Exposure: Overall results for operator exposure are summarized in Table 2.

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Table 2: Acceptable use rate (g paraquat ion/ha) for operator exposure under various scenarios

Level of protection Full PPE with

maximum respiratory

protection

Full PPE with no

respiratory

protection

No PPE

Surface treated

Boom/aerial sprayer 50 ha

600 325 50

Backpack 1 ha 390 110 35

4.3. Worker Re-Entry: Predicted exposures to paraquat for workers re-entering and working in areas where paraquat-containing formulations have been applied were not modelled, as the end-use

patterns for paraquat would not require workers to be entering areas where it has been applied to

conduct work activities that would result in dermal contact with sprayed foliage. Any re-entry to assess efficacy would be of a short duration and would not be deemed to represent a significant

amount of exposure. Paraquat is also noted to be rapidly absorbed into the plant minimizing the

amount available for foliar transfer. Therefore, no REI controls were deemed necessary.

4.4. Bystanders: Estimated bystander exposure from spray drift 8 m away after application of paraquat-

containing formulations to the soil for agricultural uses from boom or aerial application methods

using coarse droplets (fine droplets are not used for application of herbicides) at an application rate of 600 g ai/ha (828 g dichloride ai/ha) is below the AOEL and no buffer zone is required to protect

bystanders.

Estimated bystander exposure from spray drift for aerial forestry applications is above the AOEL using coarse droplets and will require a buffer zone of 14 m in order to ensure bystander exposures

are below the AOEL.

4.5. Overall human health conclusion: It is considered that the risks to human health from the proposed use of paraquat-containing formulations on 50 ha fields via boom or aerial application

methods with coarse droplets are acceptable as long as the appropriate level of PPE is used.

Following the modelling of different application rates scenarios it was determined that full PPE with maximum respiratory protection is needed to safely apply paraquat formulations at rates of

325(448) – 600(828) g ion(dichloride) ai/ha. The use of full PPE excluding respiratory protection is

needed for application rates between 50(69) – 325(448) g ion(dichloride) ai/ha, and no PPE is required at applications rates below 50 g ai/ha (69 g dichloride ai/ha). Application rates above

600(828) g ion(dichloride) ai/ha had RQ values that exceeded the AOEL even with use of PPE that

included maximum respiratory protection. When using a backpack, the maximum application rate that could be applied on 1 ha with minimal

risk, provided full PPE plus maximum respiratory protection is worn during mixing, loading, and

application, was 390 g ai/ha (538 g dichloride ai/ha). The maximum application rate that could be applied using a knapsack with minimal risk, provided full PPE with no respiratory protection is worn

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during mixing, loading, and application, was 110 g ai/ha (152 g dichloride ai/ha), and the maximum

amount that could be applied with minimal risk, provided no PPE be required during mixing, loading, and application, was 35 g ai/ha (48 g dichloride ai/ha).

There is no need for the application of re-entry intervals as the functional uses of paraquat are not

associated with worker re-entry and anticipated exposure was qualitatively deemed to be of low risk.


formulations to the soil for agricultural uses from boom or aerial application methods at an application rate of 600(828) g ion (dichloride) ai/ha is below the AOEL and no buffer zone is

required to protect bystanders. However, exposure from aerial forestry applications is above the

AOEL using coarse droplets and will require a buffer zone of 14 m in order to ensure bystander exposures are below the AOEL.

5. Environmental risk assessment 5.1. The risks to a range of environmental receptors, including aquatic organisms, soil organisms,

plants, birds, bees and beneficial insects from the use of paraquat were determined by carrying out

a quantitative risk assessment. Full details can be found in Appendix G. The standard risk

assessment methodologies used by the EPA are explained in the EPA risk assessment document (EPA 2018).

5.2. Aquatic environment: Predicted concentrations of paraquat, resulted in calculated RQs above the

LOC for the aquatic environment (aquatic plants). 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 are expected to reduce the risks to below the LOC.

5.3. Groundwater: Risks to groundwater from paraquat are considered below the LOC.

5.4. Sediment: The RQ for sediment-dwelling organisms was below the LOC. The risk to sediment-

dwelling organisms resulting from the application of paraquat-containing formulations is therefore considered less than the LOC.

5.5. Soil organisms: Acute and chronic risks to soil organisms applicable to paraquat following the

application of paraquat-containing formulations are below the LOC.

5.6. Non-target plants: RQs to non-target plants calculated for paraquat are above the LOC for the

majority of uses. The relationship between distance from the edge of the application area and

spraydrift can be expressed in terms of spraydrift curves. For non-target plants, the EPA has used the BBA spray drift data and the AGDISP model (with the inputs as per Table C5 of the EPA risk

assessment methodology (EPA 2018); aerial agricultural herbicide coarse to very coarse droplets)

to predict spray drift at different distances downwind. Based on the risk assessment, the EPA

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proposes that the downwind non-target buffer zones to be added to the product label so that users

are aware of how to protect non-target non-threatened and threatened plants.

5.7. Birds: Toxicity Exposure Ratio (TER) values for birds calculated for paraquat are above the LOC,

and any risks are non-negligible. Paraquat is not bioaccumulative therefore there are no concerns

about secondary poisoning.

5.8. Pollinators: RQs to bees are above the LOC for all use scenarios with the exception of the lowest

application rate 100 g ai/ha. Although a risk is identified, application of paraquat-containing

formulations for use in some situations such as a pre-emergence herbicide where exposure to bees is expected to be minimal.

As paraquat has a 9.4B hazard classification then the HPC Notice 58 will apply. This means that

the person who applies the substance must ensure the application plot does not contain any bees that are foraging or plants (including trees and weeds) that are likely to be visited by non-target

invertebrate pollinators. As such, risks to pollinators are considered to be mitigated.

5.9. Non-target arthropods: Risks to non-target arthropods are below the LOC for both off-field and in-field provided application rates are less than 1.2 kg ai/ha. If application rates higher than 1.2 kg

ai/ha are permitted there should be a label statement to advise users of the unknown risks to

arthropods.

5.10. Overall ecological risk assessment conclusion: It is considered that the risks to the

environment from the proposed use of paraquat-containing formulations are above the LOC as the

identified risks to birds cannot be mitigated even with the prescribed, modified and additional controls. Further information from submitters could help refine this risk assessment. While risks to

the aquatic environment, non-target plants, bees and beneficial insects were identified there are

potential controls which could mitigate these risks

5.11. Table 3 provides an overview of the ecological risk assessment:

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Table 3: Identified environmental risks

Risk Conclusion

Aquatic environment Below the LOC with controls

Groundwater Contamination unlikely

Sediment Below the LOC with controls

Soil organisms In-field

Below the LOC with controls

Soil organisms off-field


Non-target plants Below the LOC with controls

Birds Above the LOC for both threatened and non-threatened bird species.

Pollinators Below the LOC with controls

Non-target arthropods In-field


Non-target arthropods off-field


6. Proposed controls 6.1. A set of proposed controls has been identified following the human health and environmental risk

assessments conducted. These have been summarized in Appendix E of the application form for

the application APP203301.

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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 related to paraquat are provided in Table 4.

Table 4: Identification of paraquat

IUPAC name 1,1’-dimethyl-4,4’-bipyridinium (paraquat ion)

CAS name 1,1’-dimethyl-4,4’-bipyridinium (paraquat ion)

Molecular formula C12H14N2

CAS Number 4685-14-7 (paraquat ion)

1910-42-5 (paraquat dichloride)

Molecular weight (g/mol) 186.3 (paraquat ion)

257.2 (paraquat dichloride)

Structural formula (paraquat

dichloride)

Purity The minimum purity on a dry weight basis is 920 g/kg.

Significant

impurities/additives

(% concentration)

Total terpyridines: 0.001 g/kg (1.0 ppm) maximum Free 4,4'-bipyridyl: 1.0 g/kg (1000 ppm) maximum

Other international

classification & labelling

Paraquat dichloride

European Union

Acute Tox. 2 * ; H330



STOT SE 3 ; H335

STOT RE 1 ; H372**

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Skin Irrit. 2 ; H315

Eye Irrit. 2 ; H319

Aquatic Acute 1 ; H400

Aquatic Chronic 1 ; H410

Regulatory status The regulatory history of paraquat is summarised in Table 5 below.

Table 5: Active ingredient regulatory status

Active ingredient name Regulatory history in New

Zealand

International regulatory

history (Australia, Canada,

Europe, Japan, US)

Paraquat Approved Approved in Australia, Canada,

Japan and US

Not approved in the European

Union1

Paraquat-containing formulations are currently approved for similar use patterns in the US, Canada,

Japan and Australia. Paraquat-containing formulations are not currently registered for use in the EU.

The Chemical Review Committee of the Rotterdam Convention recommended in 2011 to the Conference of the Parties that liquid formulations (emulsifiable concentrate and soluble concentrate)

containing paraquat dichloride at or above 276 g/L, corresponding to paraquat ion at or above 200 g/L

be listed in Annex III of the Rotterdam Convention, after having determined that it met the criteria for a Severely Hazardous Pesticide Formulation in Annex IV of the Convention. To date the Conference of

the Parties has not agreed on whether it should be listed or not although a draft decision guidance

document is available (UNEP/FAO 2012).

Impurities and or restrictions on purity or composition

6.2. Impurity limits for paraquat dichloride have been identified by the APVMA (APVMA 2016).

These are:

total terpyridines: 0.001 g/kg (1.0 ppm) maximum

4,4'-bipyridyl: 1.0 g/kg (1000 ppm) maximum.

If paraquat dichloride-containing formulations are to be reapproved these restrictions should also apply.

1 Although an initial inclusion directive (Inclusion directive 03/112/EC) and review report are available, this was

annulled by Judgment of the Court of First Instance on 11/07/2007, which rendered the inclusion directive null

and void.

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Use pattern and mode of action

Use pattern

The EPA is aware that there is a wide variety of uses of paraquat dichloride. For the purposes of this

science assessment, only a small number of representative use scenarios has been considered. For

the human health risk assessment this has focussed on the use patterns which are known to reduce the operator risks to less than the LOC. The environmental risk assessments generally consider best

and worst-case scenarios as well as a number of important use patterns.

The table below has been used as the basis for the risk assessment.

Table 6: Main use categories of paraquat in New Zealand2

Application

method

Application

rate (low) /

g ai / ha

Application

rate (high) /

g ai / ha

Number of

applications

/ year

Use scenarios

Boom

135 2000 1

Weed control in crop production; Pasture renovation (400 g ai/ha); Forestry (1000 g ai/ha); Banks of drains and waterways (1500 g ai/ha); Non-agricultural weed control (1000 - 2000 g ai/ha)

125 810 2 Weed control in crop production

100 540 >2 Weed control in crop production

Directed spray

350 600 1 Weed control in crop production Banks of drains and waterways (500 g ai/ha);

Aerial 300 2200 1 Weed control in crop production (300 - 600 g ai/ha); Forestry (1000 g ai/ha); Weed control - Australian sedge (2200 g ai/ha).

Handgun 125 1500 1

Weed control in crop production (125 - 350 g ai/ha); Weed control - Australian sedge (250 g ai/ha); Banks of drains and waterways (500 - 1500 g ai/ha); Forestry - spot treatment (1000 g ai/ha); Non-agricultural weed control (1000 g ai/ha).


Knapsack 125 1000 1 Weed control in crop production (125 - 600 g ai/ha); Banks of drains and waterways (500 g ai/ha); Non-agricultural weed control (1000 g ai/ha).

2 Highlighted in green is the best-case scenario used for first-tier aquatic toxicology modelling (refer to Appendix G) Highlighted in blue is the worst-case scenario used for first-tier aquatic toxicology modelling (refer to Appendix G)

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125 513 >2 Weed control in crop production

Mode of action

Paraquat is a non-selective contact herbicide belonging to the bipyridinium class of compounds. The

mode of herbicidal action involves the inhibition of photosynthesis (specifically photosystem I) thereby

generating superoxide, leading to lipid peroxidation and membrane damage. Plants die rapidly after treatment and exposure to light.

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Appendix B: Mammalian toxicology Executive summaries and list of endpoints for paraquat-containing formulations This reassessment is for a specific active ingredient and not for a formulation. Therefore, there are no

formulation specific hazard endpoints.

Executive summaries and list of endpoints for paraquat Unless otherwise stated, data used for the hazard assessment for paraquat, its metabolites and

impurities were sourced from reviews conducted by other regulatory bodies [US EPA (US EPA 1997), JMPR (JMPR 2003), and APVMA (APVMA 2016)]. In addition, the EPA received some data directly

from paraquat manufacturers.

Acute toxicity (oral, dermal, inhalation), skin and eye irritation, contact sensitisation, and genotoxicity data for paraquat are summarised in Table 7. Results (dose administered or air concentrations) are

reported as either the amount of ion or as dichloride. In some studies the information to differentiate

what form the value is based on was not stated.

Table 7: Summary of acute toxicity, irritation, sensitisation and genotoxicity data for paraquat and paraquat dichloride

Endpoint

(Test Guideline) Result Classification Reference

Acute oral toxicity

(Guideline not stated);

(data are reported as

ion,dichloride,or the

results were not

specified)

283(F) – 344(M) mg

dichloride /kg bw (rat)

100 – 249 mg ion/kg bw (rat)

112 – 150 mg ion/kg bw (rat)

290 - 360 mg dichloride/kg

bw (mouse)

50 mg/kg bw (rabbit)

22 - 41 mg ion /kg bw

(guinea pig)

262 mg ion/kg bw (hen)

290 mg/kg bw (turkeys)

35 mg ion/kg bw (cat)

50-70 mg/kg bw (monkey)

6.1C (Based on the

majority of studies

being between 50 –

300 mg/kg)

US EPA (US EPA 1997),

APVMA (APVMA 2016),

JMPR (JMPR 2003)

Acute dermal toxicity

(Guideline not stated)

>2000 mg dichloride/kg bw

(rat) 6.1E

US EPA (US EPA 1997)

APVMA (APVMA 2016)

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January 2019

Endpoint

(Test Guideline) Result Classification Reference

>1448 mg/kg bw (rat)

>2000 mg dichloride/kg bw

(rat)

375 mg/kg bw (turkey)

JMPR (JMPR 2003)

JMPR (JMPR 2003)

Acute inhalation toxicity


1 µg/L dichloride/m3 (rat)

0.5 µg/L (rat)

0.6 – 1.4 µg ion/L (rat)

6.1A


(whole body)

APVMA (APVMA 2016)

(whole body)

JMPR (JMPR 2003) (nose

only)

Skin irritation/corrosion

(Guideline not stated) Minimal – moderate irritation 6.3B


JMPR (JMPR 2003)

(Duerden, 1994)

APVMA (APVMA 2016)

Eye irritation/corrosion

(Guideline not stated) Moderate to severe irritation 6.4A


JMPR (JMPR 2003)

(Duerden, 1994)

APVMA (APVMA 2016)

Contact sensitisation

(Buehler, Maximisation) Negative Not classified


APVMA (APVMA 2016),

JMPR (JMPR 2003)

Mutagenicity (in vitro and in vivo)


There are multiple (>80) studies with results indicating it to be positive, equivocal, and negative with most assays being negative

Not classified


APVMA (APVMA 2016),

JMPR (JMPR 2003)

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January 2019

Results of the repeated dose toxicity studies with paraquat dichloride are summarised in Table 8.

The No Observed Adverse Effect Level (NOAEL)/ Lowest Observable Adverse Effect Level (LOAEL) levels are reported on a mg (milligram)of cation per kg of body weight (bw) basis.

Table 8: Summary of repeated dose studies with paraquat dichloride

Study type

NOAEL (mg

ion/kg

bw/day)

LOAEL (mg

ion/kg

bw/day

Key effect Reference

90-day oral toxicity: rats 4.74 14.2 Lung pathology


APVMA (APVMA 2016),

JMPR (JMPR 2003)

90-day oral neurotoxicity study: rats

Organisation for Economic Cooperation and Development [(OECD) 424; Office of Prevention, Pesticides & Toxic Substances (OPPTS) 870.6200; 2004/73/EC B.43]

150 ppm (10.2 (M) and 11.9 (F) mg/kg bw/day)

150 ppm was highest dose tested

No evidence of neurotoxicity was observed

Chivers S (2006)

Paraquat: Subchronic

Neurotoxicity Study In

The Rat. Report No.

PR1322-REG.

Syngenta File No.

PP148/2883

90-day oral toxicity: mice 8.33 25.9 Lung pathology


APVMA (APVMA 2016),

JMPR (JMPR 2003)

90-day oral toxicity: dogs 0.56 1.5 Lung pathology


APVMA (APVMA 2016),

JMPR (JMPR 2003)

1-year oral toxicity: dogs 0.45 0.93 Lung pathology


APVMA (APVMA 2016),

JMPR (JMPR 2003)

2-year chronic toxicity/carcinogenicity:

Multiple studies have been conducted using rats and mice which have all concluded paraquat is not carcinogenic

Non-carcinogenic


APVMA (APVMA 2016),

JMPR (JMPR 2003)

Developmental toxicity: rats/mice

Multiple studies have been conducted using rats and mice which have all concluded

Minor effects at maternally toxic levels


APVMA (APVMA 2016),

JMPR (JMPR 2003)

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January 2019

Study type

NOAEL (mg

ion/kg

bw/day)

LOAEL (mg

ion/kg

bw/day

Key effect Reference

paraquat is not a developmental toxicant

2-generation reproductive toxicity: rats/mice

Multiple studies have been conducted using rats and mice which have all concluded paraquat is not a reproductive toxicant

Lung pathology in adults and pups; no effect of reproduction


APVMA (APVMA 2016),

JMPR (JMPR 2003)

As the primary purpose of this reassessment is to evaluate risk associated with exposure, the EPA

has not reviewed or summarized all conducted studies in detail. More thorough reviews and summaries of the studies have been completed by other regulatory agencies [US EPA (US EPA

1997), APVMA (APVMA 2016), JMPR (JMPR 2003)]. The above data set demonstrates there are

sufficient data to understand and quantify the potential hazards of paraquat in a risk assessment.

The 1997 conclusion from the US EPA Re-registration Eligibility Decision (RED) on paraquat (US

EPA 1997) was that there was no evidence to suggest the need for more in-depth studies on

neurotoxicity (acute delayed neurotoxicity study in the hen; acute and sub chronic neurotoxicity screening battery studies in the rat; and developmental neurotoxicity study in the rat).

Nonetheless, paraquat is structurally similar to the known dopaminergic neurotoxicant 1-methyl-4-

phenyl-1,2,3,6-tetrahdyropyridine (MPTP) and post the US EPA 1997 review reports (US EPA 1997) studies found in the literature have raised concerns regarding the potential for paraquat to induce

neurotoxicity, including the induction of Parkinsonian-like symptoms.

Neurotoxic effects, specifically death of dopaminergic neurons in the substantia nigra in the mouse brain, were noted when paraquat was administered by intra-peritoneal injection and this type of

degeneration is also a pathological hallmark of Parkinson's disease in humans. For this reason

research studies have been conducted to investigate paraquat as a possible aetiological factor in Parkinson’s disease.

These health concerns were addressed though a research programme conducted by Syngenta with

data being sent to the US EPA in support of its new (ongoing) re-registration review. Data were also reviewed by the APVMA who concluded in their 2016 rereview (APVMA 2016).

“In this regard, some of the original studies reporting a positive association [death of dopaminergic

neurons in the substantia nigra] have since been withdrawn due to fraudulent reporting of results.

Notwithstanding this, neurotoxicity findings are not supported by oral studies carried out according to

Organisation for Economic Co-operation and Development (OECD) guidelines (Chivers, 2006).

Importantly, exposure via injection is not considered relevant to human exposure.”

“Expert opinion on two contemporary epidemiology studies concluded that the strength of association

between paraquat exposure and Parkinson's disease cannot be considered robust. In addition, in a

recent retrospective worker cohort study, there was no evidence of an increased risk of Parkinson’s

23


January 2019

disease in workers involved in the manufacture of paraquat, and paraquat poisoning case studies

have failed to demonstrate neurotoxic effects.”

As a conclusion, the EPA believes that no classification for neurotoxicological effects is warranted for

paraquat.

Toxicokinetics and dermal absorption studies with paraquat are summarised in Table 9.

Table 9: Summary of toxicokinetics and dermal absorption studies with paraquat

Study type Results

Toxicokinetics

The pharmacokinetics and metabolism of paraquat have been the subject of

many studies. Paraquat is not well-absorbed when administered orally. After oral

administration of radiolabelled paraquat to rats, more than half the administered

dose (60–70%) appeared in the faeces and a small proportion (10–20%) in the

urine. In studies involving single or repeated doses, excretion of the radiolabel

was rapid; about 90% was excreted within 72h. Paraquat is largely eliminated

unchanged; in rats, approximately 90–95% of radiolabelled paraquat in urine was

excreted as the parent compound. Some studies have failed to show the

presence of any metabolites after oral administration of paraquat, while others

have shown a small degree of metabolism, which probably occurs in the gut as a

result of microbial metabolism. Paraquat was not found in the bile.

Dermal absorption –

In vitro

Numerous studies have shown that percutaneous paraquat absorption is low. In

vitro studies conducted on the manufacturing concentrate revealed that

absorption across rabbit skin was approximately 1% over 10 h, and 2.5% over 55

h for human skin. In addition, human skin was found to be at least 40 times less

permeable than animal skin tested in vitro (including rat, mouse, rabbit and

guinea-pig). Absorption across rat skin ranged from 0.003-16.54% of the applied

dose and was approximately proportional to the amount applied. Human skin or

isolated epidermis showed lower levels of absorption (0.0001-1.43%) and was

also proportional to the amount of paraquat applied. In most studies, absorption

rates were higher after 10-12 hours of administration, possibly due to tissue

degradation.

Dermal absorption –

In vivo

(Wester, et al., 1984)

The percentage of the applied dose that was absorbed was 0.29 ± 0.2 for the leg, 0.23 ± 0.1 for the hand, and 0.29 ± 0.1 the forearm.

General conclusion about mammalian toxicology of paraquat This reassessment is not meant to be an in-depth review of the potential hazards associated with

paraquat since it was last approved, although some concerns had risen in regard to neurotoxicity

24


January 2019

which have been reviewed by other regulatory bodies.

Hazard data of paraquat were sourced from reviews conducted by other regulatory bodies [US EPA (US EPA 1997), JMPR (JMPR 2003), and APVMA (APVMA 2016)]. In addition, the EPA received

some data directly from paraquat manufacturers.

Acute toxicity, irritation and sensitisation

Paraquat is very acutely toxic by inhalation (6.1A), moderately toxic by oral (6.1C), and of very low

toxicity by dermal exposure (6.1E) routes. The latter two routes are due to low intestinal and very low

dermal absorption potentials. It is a moderate dermal irritant (6.3B) and relatively severe ocular irritant (6.4A). It is not considered to be a contact sensitiser.

Mutagenicity

The weight-of-evidence of the numerous studies conducted on paraquat have indicated it is not genotoxic and is not classified as such.

Carcinogenicity

Paraquat is not considered to be carcinogenic or classified as such.

Reproductive and developmental toxicity

Paraquat is not considered to be a developmental or reproductive toxicant or classified as such.

Neurotoxicity

Concerns over its potential to induce neurotoxicity and Parkinson-like symptoms were addressed

though a research programme conducted by Syngenta with data being sent to the US EPA in support

of its new (currently ongoing) re-registration review. These data were also reviewed by the APVMA who recently concluded the risks of neurotoxicity are minimal (APVMA 2016).

Paraquat is not considered to be neurotoxic or classified as such.

Target organ toxicity

Several repeat dose toxicity studies have been conducted on paraquat. The major effect of paraquat

was a dose-related increase in the severity and extent of chronic pneumonitis (lung pathology). The

most sensitive species was the dog, and the NOAEL from 90-day exposure study was used in setting the AOEL.

Toxicokinetics and dermal absorption

The pharmacokinetics and metabolism of paraquat have been the subject of many studies. Paraquat is not well-absorbed when administered orally and is largely eliminated unchanged as the parent

compound. Some studies have failed to show the presence of any metabolites after oral

25


January 2019

administration of paraquat, while others have shown a small degree of metabolism, which probably

occurs in the gut as a result of microbial metabolism.

Numerous studies have shown that percutaneous absorption of paraquat is very low. The study by

Wester, et al., 1984 using human volunteers has been used by regulatory agencies in their dermal

exposure risk assessments.

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January 2019

Appendix C: Environmental fate Environmental fate values used for risk assessment The EPA selected environmental fate values from its substance database as well as reviewing

information contained in reviews carried out by other regulators. The other regulators whose reviews

were considered were


EC review documents in 2002 (EC 2002) and 2003 (EC 2003)

US EPA review in 1997 (US EPA 1997)

FAO (JMPR 2004)

Table 10 contains the environmental fate data used in the risk assessment.

Table 10: Summary of environmental fate data on paraquat ion

Test Paraquat ion Reference

Hydrolysis Hydrolytically stable (ie does not

hydrolyse)

EPA substance database and PMRA

(PMRA 2015)

Biodegradation in water

Not rapidly biodegradable (however in

the environment paraquat will be

removed from the aqueous phase due to

high Koc)

EPA substance database

Aqueous photolysis Photolytically stable. Photodegradation

in aqueous solutions is very slow.

EPA substance database and PMRA

(PMRA 2015)

Aerobic degradation in

water

(water/sediment)

The EPA had no data on degradation in

water so assumed a water sediment

(whole system) half-life of 1000 days. It

should be noted that the very high

sorption values will significantly reduce

the concentrations of paraquat in water

EPA assumption

Anaerobic degradation - No data

Bioaccumulation

The log Kow for paraquat dichloride is -

4.22 indicating that paraquat does not

bioaccumulate readily in aquatic

organisms.

The BioConcentration Factors (BCFs) in

fish range from 0.05-1.21 indicating that


27


January 2019

paraquat does not bioaccumulate readily

in aquatic organisms.

Aerobic degradation in soil

(laboratory)

Paraquat is persistent in soil. Field

studies indicated half lives of 7 - 8 years

(UK) and 10 - 20 years (US). For the

purposes of the EPA risk assessment a

half life of 1000 days was assumed

which practically means no degradation.

The estimated average field half-life of

paraquat in soil is 1000 days.

EPA substance database and EC (EC

2003)

Soil photolysis - No data

Adsorption/desorption

(Koc values)

15,473 mL/goc

This is the lowest value on the EPA

substance database for paraquat.

Although lower values are reported in

some other regulators’ reviews, it is not

clear how these values have been

determined. It is noted that there is a

wide variation in the reported values and

15,473 mL/goc is conservative (the

reported values in the EPA substance

database are 15,473-1,000,000 mL/goc).


Adsorption/desorption

(Kd values)

980 mL/g

This value was selected as it was the

lowest reported value from a non-sandy

soil. It is noted that there is a wide

variation in the reported Kd values and

that this value is conservative.

JMPR (JMPR 2004)

Volatilisation Not relevant, due to low vapour pressure

(< 10-8 kPa at 25°C) EC (EC 2003)

- No data provided

28


January 2019

General conclusion about environmental fate Paraquat is persistent in aquatic environments. Despite this, the fact that it is strongly adsorbed to sediment will mean that it is removed from the water phase relatively quickly but it will be persistent in

the sediment.

Paraquat is persistent in soil. The strong adsorption of paraquat to soil precludes paraquat degradation in soil being studied effectively by standard guideline methods. Field studies, have

however, shown that half-lives of paraquat are 7 to 8 years in the UK and 10 to 20 years in the US.

The strong adsorption also greatly reduces the rate of formation of degradation products to amounts that would not be detectable using standard methods (EC 2003). The EPA had no information in

regard to metabolites of paraquat, hence it was not possible to include these in the risk assessment. It

is noted that the issue of metabolites was not raised in any other international regulators’ review although the role paraquat in redox cycling is well known. The EPA welcomes any feedback about

this issue from submitters.

Paraquat is immobile in soil according to McCall classification system (McCall P.J., Laskowski D.A. et al. 1981). The potential for leaching is therefore low.

Paraquat has a low potential for bioaccumulation and a risk assessment for secondary poisoning is

not required.

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January 2019

Appendix D: Ecotoxicity The EPA selected ecotoxicology values from its substance database as well as reviewing information contained in reviews carried out by other regulators. The other regulators whose reviews were

considered were:


EC review documents in 2002 (EC 2002) and 2003 (EC 2003)

US EPA review in 1997 (US EPA 1997)

The general approach taken to select endpoints was to use the lowest available value for each type of species. The exceptions are the endpoints for algae and the acute bird endpoint where extra

information was provided by submitters in response to the call for information.

In the case of the algae endpoint, the EPA has accepted the rationale provided by a submitter that ecotoxicity of paraquat to algae in the aquatic environment is significantly reduced when the test is

carried out in the presence of sediment as the sediment reduces the bioavailability of paraquat. The

submitter has provided a study carried out with the presence of sediment, which provides a more realistic ecotoxicity endpoint for use in risk assessment. This study is summarised in Appendix J. It

has to be noted that a similar argument was accepted by the European Food Safety Authority (EFSA)

for the review of diquat (EFSA 2015) which has similar properties to paraquat.

In the case of the bird acute risk assessment, the EPA has used a value based on a study supplied by

a submitter. This study by Johnson (1998) is summarised in Appendix J and has been used in the risk

assessment as the EPA considers that it is more scientifically valid than the alternative study by Hudson et al. (1979) which was listed on the EPA substance database. The EPA notes the concern of

the submitter that the study by Hudson et al. (1979) was not carried out according to any recognised

test guideline and that it is not clear whether the results are expressed in terms of paraquat dichloride or the paraquat ion.

Table 9 contains the ecotoxicology data used in the risk assessment. It should be noted that in the EC

review of paraquat (EC 2003), it is not always clear whether the ecotoxicity value relates to paraquat dichloride or the paraquat ion. The EPA has assumed that the values presented in the European

assessment represent the paraquat ion. The EPA welcomes any feedback or clarification about this

assumption from submitters.

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January 2019

Table 11: Summary of ecotoxicity data for paraquat ion (bold values used in the risk assessment)

Test Paraquat ion Reference

Acute / fish LC50 = 10.85 mg/L (Barbus sharpeyi) EPA internal database

Acute / aquatic invertebrates EC50 = 1.2 mg/L (Daphnia magna) US EPA (US EPA 1997)

Algae - diatom

Two values were available using the

standard OECD methodology

EC50 = 0.00055 mg/L (Navicula pelliculosa)

EC50 = 0.00023 mg/L (Navicula pelliculosa)

For the risk assessment the following value

was used from a test with sediment

EC50 >0.29 mg/L

EPA internal database

EC (EC 2003)

Smyth D and Shikkabeer N,

2000 (see study summary in

Appendix J)

Aquatic plant

(Lemna gibba)

Two values were available:

EC50 = 0.032 mg/L

EC50 = 0.037 mg/L

Geomean value EC50 = 0.0344 mg/L


EC (EC 2003)

Chronic / fish - -

Chronic / Aquatic

invertebrates

No Observed Effect Concentration

(NOEC) = 0.12 mg/L

(Daphnia magna)

EC (EC 2003)

Chronic toxicity sediment-

dwelling organism

NOEC = 100 mg/kg (sediment)

(Chironomus riparius)

NOEC = 0.367 mg/L (water phase only)

EC (EC 2003)

Acute / Earthworm LC50 > 1000 mg/kg soil EC (EC 2003)

Chronic / Earthworm No effects at rates of 30 kg ai/ha EC (EC 2002, EC 2003)

Soil microorganisms No adverse effects on carbon or

nitrogen mineralisation were observed

EC (EC 2003)

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January 2019

after application up to 720 kg ai/ha in

one year.

Non-target plants

EC25 = 0.0146 kg/ha (vegetative vigour,

dicot species cocklebur)

NOEL = 0.00448 kg/ha (vegetative vigour,

dicot species cocklebur)


Acute / bird

LD50 = 54 mg/kg bw for mallard duck

Note that the EPA has a value of 35 mg/kg

bw from Hudson et al. (1979) in the EPA

substance database. This value has not

been used as the value from Johnson 1998

is deemed more reliable (see discussion

above for more detail)

Johnson, 1998 (see study

summary in Appendix J)

Reproduction bird NOEL = 1.7 mg/kg bw/d PMRA (PMRA 2015)

Acute / bees LD50 (contact) = 9.26 µg/bee

LD50 (oral) = 9.06 µg/bee (120-hr study) EC (EC 2003)

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January 2019

Appendix E: Hazard classification of paraquat The existing and proposed revised hazard classifications of paraquat are listed in Table 12. More details on toxicological and ecotoxicological properties can be found in Appendix B and Appendix D

respectively.

Table 12: Existing and proposed new classifications of paraquat

Hazard Class/Subclass

Active ingredient

classification

Method of

classification

Remarks

Exis

tin

g

Pro

po

sed

Test

resu

lts

Read

acro

ss

Class 1 Explosiveness

Class 2, 3 & 4 Flammability

Class 5 Oxidisers/Organic

Peroxides

Subclass 8.1 Metallic corrosiveness

Subclass 6.1 Acute toxicity (oral) 6.1B 6.1C See Table 7

Subclass 6.1Acute toxicity (dermal) 6.1B 6.1E See Table 7

Subclass 6.1 Acute toxicity

(inhalation) 6.1A 6.1A See Table 7

Subclass 6.1 Aspiration hazard NA NA

Subclass 6.3/8.2 Skin

irritancy/corrosion 6.3A 6.3B See Table 7

Subclass 6.4/8.3 Eye

irritancy/corrosion 6.4A 6.4A See Table 7

Subclass 6.5A Respiratory

sensitisation ND ND

Subclass 6.5B Contact sensitisation No No See Table 7

Subclass 6.6 Mutagenicity No No See Table 7

Subclass 6.7 Carcinogenicity No No See Table 8

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January 2019

Subclass 6.8 Reproductive/

developmental toxicity No No See Table 8

Subclass 6.8 Reproductive/

developmental toxicity (via

lactation)

ND ND

Subclass 6.9 Target organ systemic

toxicity (oral) 6.9A 6.9A

See Table 8. (dose-

related increase in

the severity and

extent of chronic

pneumonitis (lung

pathology)


toxicity (dermal) ND ND


toxicity (inhalation) ND ND

Subclass 9.1 Aquatic ecotoxicity 9.1A 9.1A

Based on the

ecotoxicity to

Navicula pelliculosa

(see Table 11)

Subclass 9.2 Soil ecotoxicity ND ND

The EPA assumes

that a 9.2

classification

should apply on the

basis of ecotoxicity

to plants, however,

no EC50 data were

available for

classification.

Subclass 9.3 Terrestrial vertebrate

ecotoxicity 9.3A 9.3B

Currently classified

based on the

ecotoxicity to

guinea pigs,

however, the LD50

for mallard duck

(54 mg ion/kg bw)

means that a 9.3B

classification

34


January 2019

should apply. (see

Table 11)

Subclass 9.4 Terrestrial

invertebrate ecotoxicity 9.4B 9.4B

Based on both oral

and contact

exposure. (see

Table 11)

NA: Not Applicable.

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. The data are conclusive and

indicate the threshold for classification is not triggered.

The proposed classification for paraquat is 6.1C (acute oral), 6.1E (acute dermal, 6.1A (acute inhalation), 6.3B (skin irritation), 6.4A (eye irritation), 6.9A (target organ toxicity), 9.1A (aquatic

ecotoxicity), 9.3B (terrestrial vertebrates) and 9.4B (terrestrial invertebrates).

35


January 2019

Appendix F: 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 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 risk assessment methodology document (EPA

2018).

To assess risks the predicted systemic exposures to the active ingredient(s) are compared with an

AOEL for the active ingredient and a RQ is calculated. RQ values greater than one indicate that

predicted exposures are greater than the AOEL and potentially of concern. RQ values below one indicate that predicted exposures are less than the AOEL and are not expected to result in adverse

effects.

Input values for the human health risk assessment

Reference doses for paraquat established by internationally reputable regulatory authorities are

summarised in Table 13

Table 13: Summary of studies relevant for establishing an AOEL

Key

systemic

effect

NOAEL

mg/kg

bw/day

Uncertainty

factors

Absorption

factor

AOEL

mg/kg

bw/day

Justification

Pulmonary lesions following 90 days of exposure in dogs

0.56 (ion) 100 13% 0.0007 This was a robust study whose results are supported by those of a one year exposure study which essentially showed an identical NOAEL. A 90-day study is commonly used for the calculation of an AOEL. The dog was more sensitive than rat. The oral adsorption adjustment of 13% was

36


January 2019

Key

systemic

effect

NOAEL

mg/kg

bw/day

Uncertainty

factors

Absorption

factor

AOEL

mg/kg

bw/day

Justification

from a robust study in dogs conducted in 2007 which was after the EU review that utilized a 10% value from another species.

Although an AOEL was previously established in 2003 by the European Regulators (EC 2003), the

EPA chooses to refine that value as new oral absorption data in dogs (the most sensitive species)

were available indicating it was absorbed from the Gastro Intestinal (GI) tract at a rate of ~13%.

For dermal adsorption, the EPA utilized the results of the study by Wester et al. (1984) which

assessed dermal absorption in human volunteers using an aqueous-based paraquat formulation. This

study was cited by the US EPA (US EPA 1997), APVMA (APVMA 2016), and the JMPR (JMPR 2003) for estimating paraquat dermal absorption. The results of this study indicated that the percentage of

the applied dose that was absorbed was ~0.3% [0.29 ± 0.2 [mean ± Standard Deviation (SD)] for the

leg, 0.23 ± 0.1 for the hand, and 0.29 ± 0.1 for the forearm]. The EPA added 1 SD to the average due to the experimental variation [per EFSA recommendation (EFSA 2017)] and utilised a value of 0.4%

for the subsequent risk assessment. The 12.6 g/L (paraquat was applied at a rate of 9 ug/cm2 spread

over 70 cm2 using 50 ul) concentration used in the Wester et al. study represents an ~20 fold dilution of a “standard” paraquat formulation that typically contains 250 g ion/L. Such formulations are then

diluted for end use to yield concentrations ranging from ~1-4 g/L. The percentage of active ingredient

absorbed usually increases with dilution. Thus, the EPA deemed the use of the 0.4% dermal absorption rate from a 12.6 g/L experimental formulation to be suitable to cover both the concentrated

and diluted paraquat formulations.

Table 14: Input values for human exposure modelling

Active

ingredient

Physical

form

Concentration

of each active

ingredient

(%)

Application rates3

for each method of

application

g ion ai/ha

Dermal absorption (%) AOEL

mg ion/kg

bw/day

Concen

trate

Spray

paraquat liquid 250 g/L 600/325/50 (boom)

390/110/35 (backpack)

0.4 0.4 0.0007

Operator exposure assessment

For operator exposure values, the EPA modelled multiple potential application rates (g ion/ha). The

results often resulted in operator exposure values that exceeded the AOEL even when wearing full

3 see Appendix A for more details about application rates

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January 2019

PPE including respiratory protection (eg application rates of 2000 and 810 g ai/ha resulted in RQ

values of 3.27 and 1.32, respectively) .

Accordingly, the EPA simply determined what might be the maximum acceptable application rates

which could be applied and deemed safe under the various application methods and PPE

requirement scenarios. These included:

Maximum use rate acceptable with full PPE including maximum respiratory protection

Maximum use rate acceptable with full PPE excluding respiratory protection

Maximum use rate acceptable with no PPE required

The results of these maximum rate operator exposure assessments are shown in Table 15.

Table 15: Output of operator mixing, loading and application exposure assessment for paraquat ion

Exposure Scenario

Estimated operator

exposure (mg ion/kg

bw/day)

RQ

Boom (600 g/ha, 50 ha coverage)

Full PPE during mixing, loading and application (including FP2, P2 and similar respirator achieving 90% inhalation exposure reduction)

0.0007 0.98


Full PPE during mixing, loading and application (excluding respirator) 0.0007 1.01


No PPE during mixing, loading and application 0.0007 0.99

Backpack - High Level Target (390 g/ha, 1 ha coverage)

Full PPE during mixing, loading and application (including FP2, P2 and similar respirator achieving 90% inhalation exposure reduction)

0.0007 1.01


Full PPE during mixing, loading and application (excluding respirator) 0.0007 0.99


No PPE during mixing, loading and application 0.0007 0.95

The above results are based on an application rate of the paraquat cation. If it is necessary to transform the application rate of paraquat cation to paraquat dichloride, these rates can be multiplied

38


January 2019

by 1.38 to adjust for the difference in molecular weight (paraquat dichloride mw = 257.16 g/mol and

the cation mw = 186.26 g/mol)

The results of the modelling determined that the maximum application rate that could be applied using

a boom on a 50 ha field with minimal risk provided full PPE with maximum respiratory protection

is worn during mixing, loading, and application was 600 g ai/ha (828 g dichloride ai/ha). This value would also be acceptable for aerial application methods.

The results of the modelling determined that the maximum application rate that could be applied using

a boom on a 50 ha field with minimal risk provided full PPE with no respiratory protection during mixing, loading, and application was 325 g ai/ha (448 g dichloride ai/ha). This value would also be

acceptable for aerial application methods.

The results of the modelling determined that the maximum application rate that could be applied using a boom on a 50 ha field with minimal risk provided no PPE be required during mixing, loading, and

application was 50 g ai/ha (69 g dichloride ai/ha). This value would also be acceptable for aerial

application methods. The results of the modelling determined that the maximum application rate that could be applied using

a knapsack on a 1 ha field with minimal risk provided full PPE plus maximum respiratory

protection is worn during mixing, loading, and application was 390 g ai/ha (538 g dichloride ai/ha). The results of the modelling determined that the maximum application rate that could be applied using

a knapsack on a 1 ha field with minimal risk provided full PPE with no respiratory protection

during mixing, loading, and application was 110 g ai/ha (152 g dichloride ai/ha). The results of the modelling determined that the maximum application rate that could be applied using

a knapsack on a 1 ha field with minimal risk provided no PPE be required during mixing, loading, and

application was 35 g ai/ha (48 g dichloride ai/ha).

An overview is provided in Table 2.

Re-entry worker exposure assessment

Predicted exposures to paraquat for workers re-entering and working in areas where paraquat-containing formulations have been applied were not modelled, as the end-use patterns for paraquat

would not require workers to be entering areas where it has been applied to conduct work activities

that would result in dermal contact with sprayed foliage. Any re-entry to assess efficacy would be of a short duration and would not be deemed to represent a significant amount of exposure. Paraquat is

also noted to be rapidly absorbed into the plant minimizing the amount available for foliar transfer.

Therefore, no REI controls were deemed necessary.

Quantitative bystander risk assessment

It is considered that the main potential source of exposure to the general public for substances of this

type 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-

39


January 2019

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.

The bystander exposure assessments are all acceptable for the lower application rates for all

exposure assessments and are not shown. The assessments for the highest rate (600 g/ha) are given

in Table 16.

Table 16: Output of the bystander exposure assessment for paraquat

Exposure Scenario (600 g ai

/ha)

Estimated exposure of

15 kg toddler exposed

through contact to

surfaces 8 m from an

application area

(µg ion/kg bw/day)

RQ

Buffer zone needed

to reduce toddler

exposure to the

AOEL

Boom

Low boom, coarse droplets 0.02 0.0293 2

Aerial – forestry

Swathe width 7.5 m, coarse- v. coarse droplets

1.33 1.90 14

Swathe width 7.5 m, extremely coarse droplets

1.19 1.70 14

Aerial – agriculture

Swathe width 20 m, coarse- v.

coarse droplets 0.26 0.372 2


formulations to the soil for agricultural uses from boom or aerial application methods using coarse droplets (fine droplets are not used for application of herbicides) at an application rate of 600 g ai/ha

(828 g dichloride ai/ha) is below the AOEL and no buffer zone is required to protect bystanders.

Estimated bystander exposure from spray drift for aerial forestry applications is above the AOEL using coarse droplets and will require a buffer zone of 14 m in order to ensure bystander exposures are

below the AOEL.

Conclusions of the human health risk assessment

It is considered that the risks to human health from the proposed use of paraquat-containing

formulations on 50 ha fields via boom or aerial application methods with coarse droplets are

acceptable as long as the appropriate level of PPE is used. Following the modelling of different application rates scenarios it was determined that full PPE with maximum respiratory protection is

needed to safely apply paraquat formulations at rates of 325(448) – 600(828) g ion(dichloride) ai/ha.

40


January 2019

The use of full PPE excluding respiratory protection is needed for application rates between 50(69) –

325(448) g ion(dichloride) ai/ha, and no PPE is required at applications rates below 50 g ai/ha (69 g dichloride ai/ha). Application rates above 600(828) g ion(dichloride) ai/ha had RQ values that

exceeded the AOEL even with use of PPE that included maximum respiratory protection.

When using a backpack, the maximum application rate that could be applied on 1 ha with minimal risk, provided full PPE plus maximum respiratory protection is worn during mixing, loading, and

application, was 390 g ai/ha (538 g dichloride ai/ha). The maximum application rate that could be

applied using a knapsack with minimal risk, provided full PPE with no respiratory protection is worn during mixing, loading, and application, was 110 g ai/ha (152 g dichloride ai/ha), and the maximum

amount that could be applied with minimal risk, provided no PPE be required during mixing, loading,

and application, was 35 g ai/ha (48 g dichloride ai/ha). There is no need for the application of re-entry intervals as the functional uses of paraquat are not

associated with worker re-entry and anticipated exposure was qualitatively deemed to be of low risk.

Estimated bystander exposure from spray drift 8 m away after application of paraquat-containing formulations to the soil for agricultural uses from boom or aerial application methods at an application

rate of 600(828) g ion (dichloride) ai/ha is below the AOEL and no buffer zone is required to protect

bystanders. However, exposure from aerial forestry applications is above the AOEL using coarse droplets and will require a buffer zone of 14 m in order to ensure bystander exposures are below the

AOEL.

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January 2019

Appendix G: Environmental risk assessment Aquatic risk assessment The basis for the aquatic risk assessment is a comparison of the Estimated Environmental

Concentrations (EEC) with toxicity endpoints to which safety factors have been applied. The EEC is

divided by the toxicity endpoint to calculate a RQ value. The methodology for the aquatic risk is described in detail in the EPA risk assessment methodology for hazardous substances (EPA 2018).

The LOC used by the EPA are outlined in Appendix K. For the initial aquatic risk assessment the EPA

has used the Generic Estimated Environmental Concentration (GENEEC2) model. This is designed as a screening tool to determine if there is a need to carry out a further more detailed assessment. As

there are many possible use scenarios of paraquat (see Appendix A), the EPA has performed two

modelling runs using GENEEC2 (best and worst-case scenarios which are considered to adequately assess any risk to the aquatic environment from exposure to paraquat) to determine if any risk is

identified and if there is a requirement to conduct further analysis.

Calculation of estimated environmental concentrations

The parameters used in GENEEC2 modelling are listed in Table 17.

Table 17: Input parameters for GENEEC2 analysis for paraquat ion

Best-case scenario Worst-case scenario

Crop(s) Potatoes (pre-emergence) Non-selective weed control

Application rate

(g/ha) 135 2200

Application rate

(lbs/acre) 0.12 1.959

Application

frequency 1 1

Application interval

(days) n/a n/a

Koc* 15,473 15,473

Aerobic soil DT50

(days) 1000 1000

Pesticide wetted

in? No No

Methods of

application Ground-spray, low boom Aerial spray

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January 2019

Best-case scenario Worst-case scenario

Droplet size Medium-Coarse Coarse to very coarse

‘No spray’ zone 0 0

Incorporation depth

(in) 0 (broadcast) n/a

Water solubility

(ppm) 620 000 620 000

Hydrolysis (DT50 in

days) Stable Stable

Aerobic aquatic

DT50 whole

system(days)**

2000 2000

Aqueous photolysis

DT50 (days) Stable Stable

*Lowest value of a non-sand soil

** Twice the value of the DT50 soil according to the GENEEC2 recommendations

Output from the GENEEC2 model

Best-case scenario (potatoes)

RUN No. 1 FOR Paraquat ON potatoes * INPUT VALUES *

--------------------------------------------------------------------

RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP

ONE(MULT) INTERVAL Koc (PPM ) (%DRIFT) (FT) (IN)

--------------------------------------------------------------------

0.120( 0.120) 1 1 15473.0******* GRLOME( 0.8) 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)

--------------------------------------------------------------------

1000.00 2 0.00 0.00- 0.00 ****** 1968.25

GENERIC EECs (IN NANOGRAMS/LITER (PPTr)) Version 2.0 Aug 1, 2001

--------------------------------------------------------------------

PEAK MAX 4 DAY MAX 21 DAY MAX 60 DAY MAX 90 DAY

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January 2019

GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

--------------------------------------------------------------------

585.61 556.91 424.61 254.78 188.48

Worst-case scenario (non-selective weed control)

RUN No. 2 FOR Paraquat ON weed control * INPUT VALUES *

--------------------------------------------------------------------

RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP

ONE(MULT) INTERVAL Koc (PPM ) (%DRIFT) (FT) (IN)

--------------------------------------------------------------------

1.959( 1.959) 1 1 15473.0******* AERL_D( 7.1) 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)

--------------------------------------------------------------------

1000.00 2 0.00 0.00- 0.00 ****** 2000

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

--------------------------------------------------------------------

11.97 11.45 8.75 5.27 3.92

The maximum EEC for paraquat ion when used in paraquat-containing formulations as estimated by

GENEEC2 is 11.97 μg/L.

Calculated RQs

The calculated acute RQs for each trophic level considering the above EEC and lowest relevant

toxicity figures are presented in Table 17. For all cases the appropriate EEC from the Generic Estimated Environmental Concentration (GENEEC) was chosen to considering the duration of the test

(where the duration from the modelling did not match the test duration, the shorter duration (more

conservative) modelling result was used).

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January 2019

Table 18: Acute RQs derived from the GENEEC2 model and toxicity data

Species

EEC from

GENEEC2

(mg/L)

LC50 or

EC50

(mg/L)

Acute

RQ Conclusion

Potatoes (pre-emergence), 135 g ai/ha (one application)

Fish, (Barbus sharpeyi) 0.00055691 10.85 0.000051 Below LOC for threatened/non-threatened species

Crustacea, Daphnia

magna

0.000558561 1.2 0.00047 Below LOC for threatened/non-threatened species

Algae, Navicula

pelliculosa) 0.00055691 >0.29 <0.0019 Below LOC for threatened/non-

threatened species

Aquatic plants, Lemna

gibba) 0.00055691 0.0344 0.016 Below LOC for threatened/non-

threatened species

Non-selective weed control, 2200 g ai/ha (one application)

Fish, (Barbus sharpeyi) 0.01145 10.85 0.0011 Below LOC for threatened/non-threatened species

Crustacea, Daphnia

magna 0.01197 1.2 0.01 Below LOC for threatened/non-

threatened species

Algae, Navicula

pelliculosa) 0.01145 >0.29 <0.04 Below LOC for threatened/non-

threatened species

Aquatic plants, Lemna

gibba) 0.01145 0.0344 0.33 Above LOC for threatened/non-

threatened species

The EPA did not carry out a chronic risk assessment since chronic exposure is not anticipated due to paraquat’s environmental fate properties, ie its rapid sorption to sediment which means that it is not

bioavailable for a long period of time. In addition, the EPA note that the chronic toxicity values

supplied by a submitter, and available to the EPA in its substance database, are higher than the acute toxicity values.Therefore further consideration of chronic effects is not required and any acute risk to

aquatic organisms are considered protective of any chronic risk.

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January 2019

Refinement of the aquatic risk assessment

For the worst-case use scenario (non-selective weed control), RQ resulting from predicted exposures are above the LOC for aquatic plant species. Since risks were identified, further modelling was

performed to consider whether buffer zones can mitigate risks to aquatic organisms from spray drift.

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 considering a low boom height

and coarse sized droplets [see Table 19 and relevant spray drift scenarios (APVMA 2010)]. In this case the EPA has modelled a number of use scenarios ranging from best to worst-case scenarios

and including some key use patterns.

For aerial application the AGDisp® model was used to calculate the deposition curves. The input parameters used in the modelling are outlined in Table C5 (aerial agricultural herbicide coarse to very

coarse droplets) of the EPA risk assessment methodology (EPA 2018). With further information (for

example, regarding the amount of water that is added to the tank mix), it is possible that the buffer zones could be refined, however, these estimates provide a reasonable worst-case scenario based

on the available information. The other input parameters used in the modelling are outlined in Table

18.

Exact buffer zones are impractical and too precise to be applied in the real world. Therefore, the

buffer zone distances are rounded using the criteria on the APVMA website (APVMA 2010) to make

them more practical to comply with.

Table 19: Input parameters and calculation of spray drift buffer zone for the refined risk assessment of paraquat

Input parameters Value

Koc (mL/g) 15 473

DT50 soil (days) 1000

DT50 water (days) 2000

Toxicity endpoint (mg/L) 0.0344 (Aquatic plants,

Lemna gibba))

Assessment factor 20

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January 2019

Table 20: Output of the spray drift risk assessment modelling paraquat

Crop Applicati

on rate (g

ai/ha)

Frequency Interval

(days)

Method Calculated

buffer zone (m)

Rounded

buffer zone

(m)

Kumara 100 6 7 Ground-

based,

coarse

droplets

2 5

Potatoes 135 1 n/a Ground-

based,

coarse

droplets

0 0

Lucerne 400 1 n/a Ground-

based,

coarse

droplets

0

0

Lucerne 400 1 n/a Aerial,

coarse to

very

coarse

droplets

4 5

Lucerne 600 1 n/a Ground-

based,

coarse

droplets

2 5

Lucerne 600 1 n/a Aerial,

coarse to

very

coarse

droplets

12 15

Forestry 1000 1 n/a Aerial,

coarse to

very

coarse

droplets

24 40

Banks of

drains

1500 1 n/a Ground-

based,

2 5

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January 2019

and

waterway

coarse

droplets

Non-

selective

weed

control

2200 1 n/a Aerial,

coarse to

very

coarse

droplets

62

60

Based on the above information, the EPA considers that downwind buffer zones are required for

some use scenarios. Based on the results of the risk assessment, it is considered that the following controls would mitigate environmental risks from spray drift:

There should be a maximum application rate of 2200 g ai/ha (for the aquatic risk assessment

only note that different maximum application rates may be required as a results of other risk assessments)

For ground-based application the spray droplet size should be coarse spray droplets as per

the American Society of Agricultural and Biological Engineers (ASABE) S572 standard

For aerial based application the spray droplet size should be coarse to very coarse spray

droplets as per the ASABE S572 standard

There should be downwind buffer zones from aquatic areas from 5 to 60 m depending on the use scenario

Runoff

Based on the fact that paraquat is immobile in soil, the EPA does not consider that paraquat is likely to pose a risk from runoff. The EPA considers that there may be merit in adding the following

statements (consistent with those required by the PMRA in Canada) to the product label however:

“To reduce runoff from treated areas into aquatic habitats avoid application to areas with a

moderate to steep slope, compacted soil, or clay.”

“Avoid application when heavy rain is forecast”

Conclusions of the aquatic risk assessment

Predicted concentrations of paraquat, resulted in calculated RQs above the LOC for the aquatic

environment (aquatic plants). 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

48


January 2019

maximum application rate and use restrictions regarding the droplet size are expected to reduce the

risks to below the LOC.

The following controls are proposed to reduce exposures below the LOC:

Use restrictions

The maximum application rate is 2200 g paraquat/ha (appropriate based on the aquatic risk assessment; note that other risk assesssments may require a different application rate).

For ground-based application the spray droplet size should be coarse spray droplets as per

the ASABE S572 standard. This information should be required on the label so that users are aware of this control.

For aerial application the spray droplet size should be coarse to very coarse spray droplets as

per the ASABE S572 standard. This information should be required on the label so that users are aware of this control.

Label statements:

“DO NOT apply when wind speeds are less than 3 km/hr or more than 20 km/hr as measured

at the application site”

To reduce runoff from treated areas into aquatic habitats avoid application to areas with a

moderate to steep slope, compacted soil, or clay” “Avoid application when heavy rain is forecast”

Buffer zones

To mitigate risks from spray drift, the substance should not be applied within 5 to 60 m (depending on the application rate) of any downwind waterbody. This information should be required on the product

label so that users are aware of this control.

Groundwater risk assessment Estimated concentrations of chemicals with organic carbon adsorption coefficient (Koc) values greater

than 9995 L/kg are beyond the scope of the regression data used in SCI-GROW model. The EPA

considers that since paraquat is almost immobile in soil, groundwater contamination is not expected.

Conclusions of the groundwater risk assessment

Risks to groundwater from paraquat are considered below the LOC.

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January 2019

Sediment risk assessment The sediment risk assessment for paraquat is performed following the method outlined in the EPA risk assessment methodology for hazardous substances (EPA 2018).The input parameters used in the

risk assessment are summarised in Table 21. In this instance, the EPA has only considered the

worst-case use scenario. As risks are less than the LOC there is no requirement to consider other use patterns.

Table 21: Input values and calculations for sediment risk assessment

Input parameters Paraquat

Predicted Environmental Concentration (PEC) local water

0.00954 mg/L

Toxicity value 100 mg/kg (Chironomus

riparius)

Assessment factor 100

Predicted No Effect Concentration (PNEC) 1 mg/kg

PEC local sediment 0.1056 mg/kg

RQ 0.1

Conclusions of the sediment risk assessment

The RQ for sediment-dwelling organisms was below the LOC. The risk to sediment-dwelling

organisms resulting from the application of paraquat-containing formulations is therefore considered less than the LOC.

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 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 toxicity values for the substance. The toxicity value is divided by the PEC to give a TER. The different LOC assigned to specific TER values are listed in Appendix L [see also

(EPA 2018)]. In this case due to the fact that paraquat is not very ecotoxic to soil macro-organisms,

50


January 2019

risks have only been assessed for the highest application rate and for the in-field scenario. This

shows that the risks are less than the LOC for both threatened and non-threatened species.

The results of the acute risk assessment for soil organisms are summarised in Table 22. In this case

the EPA has only considered the worst-case scenario, given that the risks are less than the LOC no

other scenarios have been considered. For the reproductive toxicity assessment no adverse effects were observed on earthworm populations in a field study following an application of up to 33 kg ai/ha

in one year (EC 2003). This is significantly higher than the rates used in New Zealand, hence it can

be concluded that chronic risks are less than the LOC for both threatened and non-threatened species.

Table 22: Acute TER values for soil organisms

Species

LC50

(mg/kg

soil)

Drift (%)

PEC

(mg/kg

soil)

TER

acute Conclusion

Scenario – 2200 g/ha – “in-field”

Non-selective

weed control > 1000 NA 2.93 >341

Below LOC for threatened/non-

threatened species

Conclusions of the soil organism risk assessment

Acute and chronic risks to soil organisms applicable to paraquat following the application of paraquat-

containing formulations are below the LOC.

Soil micro-organisms

For paraquat, the data indicate that there are no effects on the nitrogen and carbon transformation at

application rates up to 720 kg ai/ha (highest concentration tested). The application rates in New

Zealand are significantly lower and therefore the risks are considered to be below the LOC.

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January 2019

Non-target plant risk assessment The non-target plant risk assessment is based on a comparison of the PEC with toxicity values for the substance. 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 RQ is used when an EC25 is available). For

threatened non-target plants an RQ is calculated by comparing the PEC with a NOEC. The risk assessment approach is explained in the EPA risk assessment methodology (EPA 2018). The

different LOC assigned to specific TER/RQ values are listed in Appendix K.

RQ/TER values for non-threatened non-target plants are shown in Table 23. TER values for threatened non-target plants are shown in Table 24. It was assumed that there would be no crop

interception in the risk assessment.

For this risk assessment the EPA did not have sufficient information to consider the impact of multiple applications, therefore only the impact of one application at the different application rates has been

considered. Given the persistence of paraquat in the soil environment, this is considered a data gap.

Ideally submitters will provide further information to understand the impact of multiple applications. In this case the EPA has modelled a number of use scenarios with one application ranging from best to

worst-case scenarios and including some key use patterns.

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.

Table 23: RQ/TER value for non-target plant – edge of field ie 1 m downwind

Scenarios

Exposure

(g ai/ha) *

drift factor

EC25

(g ai/ha) RQ Conclusion

paraquat-containing formulations – 202.5 g ai/ha

Broccoli, cabbage and cauliflower

202.5 * 2.77% = 5.5

14.6 g/ha

(vegetative

vigour,

cocklebur)

0.38 Below LOC for non-threatened species

paraquat-containing formulations – 400 g ai/ha ground-based application

Lucerne 400 * 2.77% = 11.08

14.6 g/ha

(vegetative

vigour,

cocklebur)

0.76 Below LOC for non-threatened species

paraquat-containing formulations – 400 g ai/ha aerial application assuming application made using coarse to very coarse droplets as per the ASABE standard

Lucerne 400 * 42% = 168

14.6 g/ha

(vegetative 11.5 Above LOC for non-threatened

species

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January 2019

vigour,

cocklebur)


Lucerne 600 * 2.77% = 16.62

14.6 g/ha

(vegetative

vigour,

cocklebur)

1.1 Above the LOC for non-threatened species

paraquat-containing formulations – 600 g ai/ha aerial application assuming application made using coarse to very coarse as per the ASABE standard

Lucerne 600 * 42% = 252

14.6 g/ha

(vegetative

vigour,

cocklebur)

17.3 Above the LOC for non-threatened species


Non-selective weed control

2200 * 2.77% = 60.94

14.6 g/ha

(vegetative

vigour,

cocklebur)

4.17 Above LOC for non-threatened species

paraquat-containing formulations – 2200 g ai/ha aerial based application assuming application made using coarse to very coarse as per the ASABE standard


2200 * 42% = 924

14.6 g/ha

(vegetative

vigour,

cocklebur)

63.4 Above LOC for non-threatened species

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January 2019

Table 24: TER value for threatened non-target plants

Scenarios

Exposure (g

ai/ha)

* drift factor

NOEL

(g ai/ha) RQ Conclusion

paraquat-containing formulations – 202.5 g ai/ha


202.5 * 2.77% = 5.5

4.48 1.2 Below LOC for threatened species


Lucerne 400 * 2.77% = 11.08

4.48 2.5 Above LOC for non-threatened species

paraquat-containing formulations – 400 g ai/ha aerial application assuming application made using coarse to very coarse droplets as per the per the ASABE standard

Lucerne 400 * 42% = 168

4.48 37.5 Above LOC for threatened species


Lucerne 600 * 2.77% = 16.62


paraquat-containing formulations – 600 g ai/ha aerial application assuming application made using coarse to very coarse droplets as per the ASABE standard

Lucerne 600 * 42% = 252




2200 * 2.77% = 60.94


paraquat-containing formulations – 2200 g ai/ha aerial application assuming application made using coarse to very coarse droplets as per the per the ASABE standard


2200 * 49% = 1078

4.48 241 Above LOC for threatened species

Conclusion for non-target plant risk assessment

RQs to non-target plants calculated for paraquat are above the LOC for the majority of uses. The

relationship between distance from the edge of the application area and spraydrift can be expressed

in terms of spraydrift curves. For non-target plants, the EPA has used the BBA spray drift data and the AGDISP model (with the inputs as per Table C5 of the EPA risk assessment methodology (EPA

54


January 2019

2018); aerial agricultural herbicide coarse to very coarse droplets) to predict spray drift at different

distances downwind. Based on the risk assessment, the EPA proposes that the downwind non-target buffer zones to be added to the product label so that users are aware of how to protect non-target

non-threatened and threatened plants.

Table 25: Buffer zones required to protect non-target plants

Crop Application

rate g ai/ha

Application

method

Proposed

buffer

zone to

protect

non-

threatened

plants (m)

Rounded

buffer

zone to

protect

non-

threatened

plants (m)

Proposed

buffer

zone to

protect

threatened

plants (m)

Rounded

Proposed

buffer

zone to

protect

threatened

plants (m)


202.5 Ground-based

0 0 5 5

Lucerne 400 Ground-

based 0 0 5 5

Lucerne 400 Aerial 26 40 64 60

Lucerne 600 Ground-

based 5 5 5 5

Lucerne 600 Aerial 34 40 94 100


2200 Aerial 106 100 232 250

The buffer zones for aerial application at the highest application rate may not be practical. It is

therefore proposed that application rate be limited to 600 g ai/ha once per year and that there be advisory downwind buffer zones to protect non-target plants which vary depending on the use

scenario. In addition the following controls are recommended:

For ground-based application the spray droplet size should be coarse spray droplets as per the ASABE S572 standard. This information should be required on the label so that users are

aware of this control.

For aerial based application the spray droplet size should be coarse to very coarse spray droplets as per the ASABE S572 standard. This information should be required on the label

so that users are aware of this control.

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January 2019

There should be a label statement stating the following wording (or equivalent) “DO NOT

apply when wind speeds are less than 3 km/hr or more than 20 km/hr as measured at the application site”

Bird risk assessment The bird risk assessment is based on a comparison of the PEC with toxicity values for the substance. The toxicity value is divided by the PEC to give a TER. The methodology is explained in the EPA risk

assessment methodology for hazardous substances (EPA 2018).The LOC that the EPA uses for risk

assessment are outlined in Appendix K.

For this risk assessment the EPA did not have any information about the rate of residue decline on

foliage over time. Consequently the EPA were not able to determine an appropriate DT50 value,

therefore the EPA has only assessed the impact of one application. For this assessment, the EPA has looked at the impact of using paraquat at 100, 200, 300, 400 and 600 g ai/ha on different crops. As

risks were all above the LOC at these rates no further analysis has been carried out.

Screening assessment

Based on the low ecotoxicity endpoint values and an assessment that was carried out for another

paraquat formulation (EPA 2016), the results of the screening assessment are not presented here

since they were all above the LOC, consequently this report will present the results of the Tier 1 assessment.

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 risk assessment methodology for

hazardous substances (EPA 2018). The EPA did not have the exact information about the crop

growth stage so all scenarios were included in the assessment. The indicator species mentioned in Table 26 (acute) and Table 27 (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 26: TER values for acute risk assessment – Tier 1 assessment

Crops &

BBCH class Focal species

Short-

cut

value2

(90th %)

Toxicity

endpoint

(mg/kg bw)

TER

ratio Conclusion

Paraquat – Bare soil 100 g ai/ha

Bare soil BBCH<10

Small granivorous bird “finch” Small seeds 100% weed seeds

24.7 54 21.9 Below LOC for non-threatened species

Below LOC for threatened species

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Bare soil BBCH<10

Small insectivorous bird “wagtail” ground invertebrates without interception 100% soil dwelling invertebrates



Bare soil BBCH<10

Small omnivorous bird “lark” Combination (ground invertebrates without interception) 50% seeds, 50% ground arthropods

17.4 54 31 Below LOC for non-threatened species



Bare soil BBCH<10


24.7

54 10.9 Below LOC for non-threatened species

Above LOC for threatened species

Bare soil BBCH<10




Bare soil BBCH<10





Bare soil BBCH<10


24.7 54 7.3 Above LOC for non-threatened species


Bare soil BBCH<10




Bare soil BBCH<10




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Paraquat – Legume 300 g ai/ha

Legume forage BBCH ≥ 20

Small insectivorous bird “wagtail” ground invertebrates with interception 50% ground arthropods, 50% foliar arthropods





7.4

54 24.3 Below LOC for non-threatened species



Small omnivorous bird “lark” Combination (invertebrates without interception) 25% crop leaves 25% weed seeds 50% ground arthropods

7.2 54 25 Below LOC for non-threatened species


Legume forage BBCH 10 - 19

Small insectivorous bird “wagtail” ground invertebrates without interception 50% ground arthropods, 50% foliar arthropods









24 54 7.5 Above LOC for non-threatened species


Legume forage Leaf development BBCH 21-49

medium herbivorous/granivorous bird "pigeon" Non-grass herbs 100% crop



Paraquat – Pasture 300 g ai/ha

Grassland Growing shoots

Large herbivorous bird "goose" Grass + cereals 100% grass leaves


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Grassland Late season (seed heads)

Small granivorous bird "finch" Small seeds 100% weed seeds



Grassland New sown grass seeds

Small granivorous bird "Sparrow" Small seeds 100% grass seeds




Bare soil BBCH < 10




Bare soil BBCH < 10




Bare soil BBCH < 10









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Table 27: TER values for chronic risk assessment – Tier 1 assessment

Crops &

BBCH class Focal species

Short-

cut

value2

(mean%)

Toxicity

endpoint

(mg/kg bw)

TER

ratio Conclusion


Bare soil BBCH<10


11.4 1.7 2.8 Above LOC for non-threatened species


Bare soil BBCH<10

Small insectivorous bird “wagtail” ground invertebrates without

5.9 1.7 5.4 Below LOC for non-threatened species

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interception 100% soil dwelling invertebrates


Bare soil BBCH<10





Bare soil BBCH<10




Bare soil BBCH<10




Bare soil BBCH<10





Bare soil BBCH<10




Bare soil BBCH<10




Bare soil BBCH<10





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Paraquat – Pasture 300 g ai/ha


Large herbivorous bird "goose" Grass + cereals 100% grass leaves



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Grassland Late season (seed heads)

Small granivorous bird "finch" Small seeds 100% weed seeds



Grassland New sown grass seeds

Small granivorous bird "Sparrow" Small seeds 100% grass seeds




Bare soil BBCH < 10




Bare soil BBCH < 10




Bare soil BBCH < 10













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9.7

1.7 0.6 Above LOC for non-threatened species







Small omnivorous bird “lark” Combination (invertebrates without interception) 25% crop



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leaves 25% weed seeds 50% ground arthropods














Medium herbivorous/granivorous bird "pigeon" Non-grass herbs 100% crop



Conclusion for bird risk assessment (Tier 1)

The Tier 1 risk assessment indicates risks above the LOC to both threatened and non-threatened

birds from the use of paraquat-containing formulations for all use scenarios.

Acute risks for both threatened and non-threatened bird species are only less than the LOC for the lowest application rate 100 g ai/ha. Acute risks are less than the LOC for non-threatened bird species

at 200 g ai/ha, however the risks for threatened species are above the LOC at this application rate.

There are acute risks for all other use scenarios. It should be noted that for this risk assessment the EPA has used a different endpoint from the value in previous risk assessments of paraquat-containing

formulations [APP202697; (EPA 2016)]. A value of 54 mg/kg bw has been used in this risk

assessment whereas in APP202697 a value of 35 mg/kg bw was used. The value used in the current assessment was provided by a submitter in response to the call for information and was used in

preference to the old value as the new value came from a study carried out according to recognised

test guidelines and using Good Laboratory Practice (GLP), unlike the older study. The study on which the acute risk assessment is based is summarised in Appendix J.

All use scenarios have chronic risks above the LOC for both threatened and non-threatened species.

During the call for information a submitter has suggested that there should be a significantly higher No Observed Effect Level (NOEL) value used in the risk assessment (NOEL = 30 mg/kg diet), however,

no explanation was provided about why this should be used. The EPA has used a value also used by

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the Canadian regulator in their 2015 review (PMRA 2015) (NOEL = 1.7 mg/kg diet). Use of a

significantly higher NOEL would allow to refine the risks but currently there is no reason to use a different value from the Canadian regulator.

The EPA notes that the Canadian regulator’s risk assessment (PMRA 2015) also identified chronic

risks to birds as being a potential concern, however, the fact that paraquat binds so strongly to biological material means that paraquat is not bioavailable, hence they concluded that chronic risks

were not a concern (PMRA 2015). They also stated that fields treated with paraquat were unlikely to

be significant sources of food for birds. Currently the EPA does not have sufficient information to support such a conclusion and risks to birds are considered to be above the LOC.

Based on the current risk assessment, there are no risk mitigation measures to fully manage the risks

to birds. Should paraquat-containing formulations be reapproved the application rate should be kept as low as possible. Furthermore only one application should be permitted per year since the impact of

multiple applications on bird risks is unknown.

Secondary poisoning

Using the criteria under the Hazardous Substances and New Organisms (HSNO) Act paraquat is not

considered to be bioaccumulative (BCF < 500). Therefore, no risk assessment of secondary

poisoning is performed.

Conclusions for bird risk assessment

Toxicity Exposure Ratio (TER) values for birds calculated for paraquat are above the LOC, and any

risks are non-negligible. Paraquat is not bioaccumulative therefore there are no concerns about secondary poisoning.

Pollinator risk assessment The basis for the pollinator risk assessment is a comparison of the EEC with toxicity endpoints to which safety factors have been applied. The EEC is divided by the toxicity endpoint to calculate a RQ

value. The methodology for the pollinator risk assessment is included in the EPA risk assessment

methodology (EPA 2018). The LOC ascribed to specific RQ values, is described in detail in Appendix K. The EPA has assessed the risks to bees from all of the use scenarios, however, for practical

reasons only a limited number of scenarios ranging from the best to the worst-case scenario have

been presented in the result in Table 28.

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Table 28: Bee exposure estimates and RQ values

Use scenario Application

rate (g ai/ha)

EEC (µg

ai/bee)

Toxicity

endpoint

value (µg

ai/bee)

RQ Conclusion

Acute / Adult bees – contact

Kumara 100 0.24 9.26 0.03 Below the LOC


202.5 0.486 9.26 0.05 Below the LOC

Lucerne/clover seed

400 0.96 9.26 0.1 Below the LOC


2200 5.28 9.26 0.5 Above the LOC

Acute / Adult bees – oral

Kumara 100 2.86 9.06 0.32 Below the LOC


202.5 5.79 9.06 0.64 Above the LOC

Lucerne/clover seed

400 11.45 9.06 1.26 Above the LOC


2200 62.96 9.06 6.95 Above the LOC

Conclusions of the pollinator risk assessment

RQs to bees are above the LOC for all use scenarios with the exception of the lowest application rate

100 g ai/ha. Although a risk is identified, application of paraquat-containing formulations for use in some situations such as a pre-emergence herbicide where exposure to bees is expected to be

minimal.

As paraquat has a 9.4B hazard classification then the HPC Notice 58 will apply. This means that the person who applies the substance must ensure the application plot does not contain any bees that

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are foraging or plants (including trees and weeds) that are likely to be visited by non-target

invertebrate pollinators. As such, risks to pollinators are considered to be mitigated.

Non-target arthropod risk assessment The EPA did not have any information on non-target arthropods in its substance database.

Consequently information has been taken from the EC review in 2003 [(EC 2002) and (EC 2003)]. The EPA’s standard non-target arthropod risk assessment requires median Lethal Rate (LR50) values.

In this case these were not available for some of the standard test species such as Aphidius

rhopalosiphi and Typhlodromus pyri . A qualitative approach has, therefore, been used for the risk assessment and it has been assumed that the ecotoxicity to surface-dwelling species covered in the

EC review (EC 2003) would also be appropriate for other types of non-target arthropods such as

predatory mites and parasitic wasps. The EPA notes that the reviews of paraquat by other regulators have not highlighted this as an issue and welcomes feedback on this approach.

Based on the information in Table 28, in general there appears to be no permanent effects at any of

the application rates tested, although there does appear to be some temporary effects at some of the different application rates. Consequently, the EPA believes that the risks to non-target arthropods can

be considered less than the LOC provided the application rates are less than 1.2 kg ai/ha. If

application rates higher than 1.2 kg ai/ha are permitted there may be a requirement to apply a control requiring a label statement to advise that there may be some impacts on arthropods.

Table 29: Summary of tests on surface-dwelling species

Species Lab/field Application rate

equivalent Endpoint(s)

Pterostichus melanarius

(Carabidae)

Lab 1 kg ai/ha No statistically significant lethal

or sub-lethal effects after five

days

Aleochara bilineata

(Staphylinidae)

Lab 0.6 kg ai/ha 20% reduction in beneficial

capacity, but not statistically

significant

Pardosa spp.

(Lycosidae)

Field 0.6 kg ai/ha applied

over two complete

seasons

Linyphiid spiders adversely

affected but recovered by six

weeks (most likely through

immigration).

Erigonine spiders showed no

significant effect.

Collembola adversely affected

at one site post application, but

recovered within two months

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Species Lab/field Application rate

equivalent Endpoint(s)

Various surface-dwelling

arthropods

Field A number of treatment

regimes over several

years including doses

up to 1700 kg ai/ha

Results difficult to interpret, but

no effects observed that could

be attributed to direct effects of

active substance.

Various surface-dwelling

arthropods

Field 1.2 kg ai/ha. Effects

monitored over 1 year

Microarthropods in general not

adversely affected but two

families of mites were reduced

in numbers up to four months

following treatment

Various soil dwelling micro-

arthropods, including Collembola

Field 480 mg ai/kg soil

(calculated by the EPA

to be equivalent to 360

g ai/ha)

Some statistically significant

differences between treated and

untreated plots, but no

consistent treatment effects.

Conclusion for non-target arthropod risk assessments

Risks to non-target arthropods are below the LOC for both off-field and in-field provided application rates are less than 1.2 kg ai/ha. If application rates higher than 1.2 kg ai/ha are permitted there should

be a label statement to advise users of the unknown risks to arthropods.

Conclusions of the ecological risk assessment The EPA assessed the risks from the use of paraquat-containing formulations. An overview for the

different risks is provided in Table 3. It is considered that the risks to the environment from the

proposed use of paraquat-containing formulations are above the LOC as the identified risks to birds cannot be mitigated even with the prescribed, modified and additional controls. Further information

from submitters could help refine this risk assessment. While risks to the aquatic environment, non-

target plants, bees and beneficial insects were identified there are potential controls which could mitigate these risks.

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Appendix H: Standard terms and abbreviations

Abbreviation Definition

ai active ingredient

AOEL Acceptable Operator Exposure Level

APVMA Australian Pesticides and Veterinary Medicines Authority

ASABE American Society of Agricultural and Biological Engineers

BBA Biologische Bundesanstalt für Land- und Forstwirtschaft

Federal Biological Research Centre for Agriculture and Forestry

BBCH Biologische Bundesanstalt, Bundessortenamt und CHemische Industrie

BCF BioConcentration Factor

Bw body weight

CAS # Chemical Abstract Service Registry Number

cm centimetres

CMR Carcinogenic, Mutagenic, Reprotoxic

CRfD Chronic Reference Dose

DT50 Dissipation Time (days) for 50% of the initial residue to be lost

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

EFSA European Food Safety Authority

EPA New Zealand Environmental Protection Authority

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

EU European Union

FAO Food and Agriculture Organization

g grams

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GENEEC Generic Estimated Environmental Concentration

GI Gastro Intestinal

GLP Good Laboratory Practice

ha hectare

HPC Hazardous Property Controls

HSNO Hazardous Substances and New Organisms

JMPR Joint FAO/WHO Meeting on Pesticide Residues

Kd partition (distribution) coefficient

Koc organic carbon adsorption coefficient

Kg Kilogram

L litres

LC50 Lethal Concentration that causes 50% mortality

LD50 Lethal Dose that causes 50% mortality

LOAEL Lowest Observable Adverse Effect Level

LOC Levels of Concern

LR50 Lethal Rate that causes 50% mortality

m3 cubic metre

mg milligram

NOAEL No Observed Adverse Effect Level

NOEC No Observed Effect Concentration

NOEL No Observed Effect Level

OECD Organisation for Economic Cooperation and Development

OPPTS Office of Prevention, Pesticides & Toxic Substances

PEC Predicted Environmental Concentration

ppb parts per billion (10-9)

PPE Personal Protective Equipment

ppm parts per million (10-6)

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RED Re-registration Eligibility Decision

REI Restricted Entry Interval

RQ Risk Quotient

SD Standard Deviation

STOT Specific Target Organ Toxicity

TER Toxicity Exposure Ratio

UNEP United Nations

US United States

US EPA United States Environmental Protection Agency

WHO World Health Organization

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Appendix I: References

APVMA (2010). "Protective no-spray zones." APVMA (2010). "Standard spray drift risk assessment scenarios." APVMA (2016). Review of the mammalian toxicology and metabolism/toxicokinetics of Paraquat - Summary Report, APVMA: 45. EC (2002). Opinion of the scientific committee on plants on specific questions from the commission regarding the evaluation of paraquat in the context of council directive 91/414/EEC. Brussels, European Commission, Health & Consumer Protection Directorate-General. EC (2003). Review report for the active substance paraquat. Brussels, European Commission, Health & Consumer Protection Directorate-General. EFSA (2015). "Conclusion on the peer review of the pesticide risk assessment of the active substance diquat." EFSA Journal 13(11): 4308. Abstract The conclusions of the European Food Safety Authority (EFSA) following the peer

review of the initial risk assessments carried out by the competent authority of the rapporteur Member State the United Kingdom, for the pesticide active substance diquat are reported. The context of the peer review was that required by Commission Regulation (EU) No 1141/2010 as amended by Commission Implementing Regulation (EU) No 380/2013. The conclusions were reached on the basis of the evaluation of the representative uses of diquat as a desiccant on potato, oilseed rape, sunflower, pulses and as a herbicide on apple, citrus, pome fruit, stone fruit, tree nut, olive, grapevine, tomato, potato, carrot, chicory, sugar beet, onion. The reliable endpoints concluded as being appropriate for use in regulatory risk assessment, derived from the available studies and literature in the dossier peer reviewed, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified.

EFSA (2017). "Guidance on dermal absorption." EFSA Journal 15(6): e04873. Abstract This guidance on the assessment of dermal absorption has been developed to assist

notifiers, users of test facilities and Member State authorities on critical aspects related to the setting of dermal absorption values to be used in risk assessments of active substances in Plant Protection Products (PPPs). It is based on the ‘scientific opinion on the science behind the revision of the guidance document on dermal absorption’ issued in 2011 by the EFSA Panel on Plant Protection Products and their Residues (PPR). The guidance refers to the EFSA PPR opinion in many instances. In addition, the first version of this guidance, issued in 2012 by the EFSA PPR Panel, has been revised in 2017 on the basis of new available data on human in vitro dermal absorption for PPPs and wherever clarifications were needed. Basic details of experimental design, available in the respective test guidelines and accompanying guidance for the conduct of studies, have not been addressed but recommendations specific to performing and interpreting dermal absorption studies with PPPs are given. Issues discussed include a brief description of the skin and its properties affecting dermal absorption. To facilitate use of the guidance, flow charts are included. Guidance is also provided, for example, when there are no data on dermal absorption for the product under evaluation. Elements for a tiered approach are presented including use of default values, data on closely related products, in vitro studies with human skin (regarded to provide the best estimate), data from experimental animals (rats) in vitro and in vivo, and the so called ‘triple pack’ approach. Various elements of study design and reporting that reduce experimental variation and aid consistent interpretation are presented. A proposal for reporting data for assessment reports is also provided. The issue of nanoparticles in PPPs is not addressed. Data from volunteer studies have not been discussed since their use is not allowed in EU for risk assessment of PPPs.

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EPA (2016). Final Science Memo - APP202697 – Para-Ken 250 Herbicide. Wellington, EPA: 72. EPA (2018). Risk Assessment Methodology for Hazardous Substances ; Draft for Consultation. HSNO. JMPR (2003). Pesticides residues in food - 2003: toxicological evaluations. Geneva, Switzerland, Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group on Pesticide Residues. JMPR (2004). Pesticides residues in food - 2004: report 2004. Geneva, Switzerland, Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group on Pesticide Residues. 178: 383. Klimisch, H. J., et al. (1997). "A systematic approach for evaluating the quality of experimental toxicological and ecotoxicological data." Regul Toxicol Pharmacol 25(1): 1-5. The evaluation of the quality of data and their use in hazard and risk assessment as a

systematic approach is described. Definitions are proposed for reliability, relevance, and adequacy of data. Reliability is differentiated into four categories. Criteria relating to international testing standards for categorizing reliability are developed. A systematic documentation of evaluating reliability especially for use in the IUCLID database is proposed. This approach is intended to harmonize data evaluation processes worldwide. It may help the expert in subsequent assessments and should increase the clarity of evaluation.

McCall P.J., et al. (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. PMRA (2015). Special Review of Paraquat: Proposed Decision for Consultation. Ottawa, Pest Management Regulatory Agency: 16. UNEP/FAO (2012). Draft Decision Guidance Document - Liquid formulations (EC and SL) containing paraquat dichloride at or above 276 g/L, corresponding to paraquat ion at or above 200 g/L. Rome, Secretariat of the Rotterdam Convention on the Prior Informed Consent Procedure for Certain Hazardhous Chemicals and Pesticides in International Trade. US EPA (1997). R.E.D. Facts - Paraquat Dichloride. P. A. T. S. W. Prevention: 13.

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Appendix J: Study summaries The studies in this section have been summarised as they are included in the risk assessment and used to assist with hazard classification.

Table 30: Acute terrestrial vertebrate toxicity (bird)

Study type Acute oral LD50

Flag Key study

Test Substance Paraquat dichloride technical concentrate

Exposure Single oral dose with a 14-day observation

Test species Mallard duck (Anas platyrhynchos)

Endpoint LD50 and NOEL

Value LD50 = 54 mg paraquat ion/kg bw

Reference Johnson (1998). Paraquat acute oral LD50 to the mallard duck. Huntington Life Science Ltd, Cambridgeshire, England ISN 399

Klimisch Score 1

Amendments/Deviations None

GLP Yes

Test Guideline/s US EPA Subdivision E, Guideline 71-1

Dose Levels 78, 109, 153, 214, 300 mg paraquat dichloride technical concentrate/kg bodyweight

Analytical measurements No

Study Summary

The aim of the study was to determine the acute oral toxicity of Paraquat dichloride technical concentrate to the mallard duck (Anas platyrhynchos).

Groups of 5 male and 5 female birds were given a single oral dose by incubation of 78, 109, 153, 214, 300 mg paraquat dichloride technical concentrate/kg bodyweight. A similar sized control group were given distilled water alone. Subsequently a further control group together with groups at 56 and 78 mg/kg were also dosed. Birds were observed for 14 days following dosing. Observations included mortality, clinical signs, bodyweight and food consumption.

There were mortalities in all groups exposed to 78 mg/kg bw and over. The LD50 was calculated to be 166 mg paraquat dichloride technical

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concentrate/kg (equivalent to 54 mg paraquat/kg bodyweight) (95% Cl values were between 129-219 mg/kg). The NOEL was determined to be 56 mg/kg.

There was no clear evidence of any treatment related effects on food consumption or bodyweight. There were no mortalities in the control.

Conclusion LD50 = 166 mg paraquat dichloride technical concentrate/kg (equivalent to 54 mg paraquat/kg bodyweight).

Table 31: Acute toxicity to the freshwater diatom

Study type Acute ecotoxicity

Flag Key study

Test Substance Paraquat dichloride technical concentrate

Exposure 5 day

Test species Freshwater diatom (Navicula pelliculosa)

Endpoint EC50 and NOEC

Value EC50 >290 µg paraquat ion/L

Reference

Smyth and Shikkabeer (2000). Paraquat dichloride: Toxicity to the freshwater diatom Navicula pelliculosa Brixham Environmental Laboratory Report Number BL6800/B

Klimisch Score 2 (see comments)

Amendments/Deviations Sediment has been added to the test system

GLP Yes

Test Guideline/s OECD 201

Dose Levels 0.9, 3, 9, 30, 90, 300 and 900 µg paraquat dichloride/L

Analytical measurements Yes by High Performance Gas Chromatography

Study Summary

The toxicity of paraquat dichloride technical to the freshwater diatom Navicula

pelliculosa was determined in the presence of a bottom layer of sediment. The test substance paraquat dichloride technical contained 32.6% paraquat ion. A four day old culture of the diatom in the growth phase was used as inoculum for the test. The OECD test guideline 201 was modified by the addition of sediment to the test vessel. The sediment used was from a field

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soil in the UK classified as a sandy loam. 3 g of field soil was dispensed to each test replicate vessel.

Six replicate cultures of the culture medium control and triplicate replicate cultures of each concentration of paraquat dichloride were used. The following test concentrations were dosed 0.9, 3, 9, 30, 90, 300 and 900 µg paraquat dichloride/L. The test vesssels were borosilicarte glass conical flasks of 250 mLs nominal capacity closed with polyurethane foam bungs. Each flask contained 100 mLs of test solution. The culture were incubated at 24 +/- oC under constant illumination with orbital shaking at approximately 120 rpm, in a orbital incubator. This level of shaking was required to maintain the diatom in suspension and allow growth. Due to the shaking some of the sediment was in suspension during the test.

All growth rates were determined by fluorometric response. After 24, 48, 72, 96 and 120 hours samples were removed from each test and blank vessel for fluorescence determination. The concentration of the test substance was determined at the beginning of the test only. This indicated that there was less than 80% of the nominal concentration at some of the concentrations tested (but not at the two highest concentrations). The test was continued for 120 hours, however, after 96 hours the diatoms effectively stopped growing as the algal medium was spent.

There were no significant differences between the growth rate of the control and any of the concentrations tested. The NOEC was calculated to be 900 µg paraquat dichloride/L (equivalent to 290 µg paraquat ion/L) and the EC50 > 900 µg paraquat dichloride/L (equivalent to >290 µg paraquat ion/L).

Comments

There was no analysis of sediment concentrations or of water concentrations at the end of the test.

The actual concentation of paraquat were less than 80% of the nominal concentration at some of the concentrations tested, however, the concentration at the highest two concentrations were 86 and 97% of the nominal concentrations.Despite these limitations the study is still considered appropriate to use for risk assessment.

Conclusion NOEC = 290 µg paraquat ion/L

EC50 >290 µg paraquat ion/L

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Appendix K: Levels of concern used by the EPA Levels of concern used by the EPA

Aquatic (fish, invertebrates, algae, aquatic plants) – non-threatened

Acute RQ ≥ 0.1

Chronic RQ ≥ 1

Aquatic (fish, invertebrates, aquatic plants) threatened species

Acute RQ ≥ 0.05

Chronic RQ ≥ 0.1

Non-threatened Plants (terrestrial)

Acute RQ /TER RQ ≥ 1 calculated on the basis of EC25 or TER ≤ 5 calculated on the basis of EC50

Threatened plants species (terrestrial)

Acute RQ ≥ 1 calculated on the basis of the NOEC or EC05

Non-threatened earthworm/ birds

Acute TER < 10

Chronic TER < 5

Threatened bird species

Acute TER < 20

Chronic TER < 10

Threatened soil organisms species

Acute TER < 100

Chronic TER < 50

Bees

Acute RQ oral/contact > 0.4

Chronic RQ > 1

Terrestrial invertebrates

Hazard Quotient (HQ) in-field/off-field ≥ 2

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