erma new zealand evaluation and review report …...2009/05/11 · erma new zealand evaluation and...

ERMA New Zealand

Evaluation and Review Report

Application for Approval to Import or

Manufacture Firebird for Release

Application Number: HSR08057

Prepared for the Environmental Risk Management

Authority

ERMA New Zealand Evaluation and Review Report: Application HSR08057 of 140

EXECUTIVE SUMMARY

Background information

Bayer New Zealand Ltd. is seeking approval to import Firebird for release.

Firebird is a herbicide containing 400 g/L flufenacet and 200 g/L diflufenican in the

form of a suspension concentrate.

Firebird is proposed to be used for the control of certain broad-leaf and grass weeds

winter wheat and barley.

Firebird will be applied as a herbicide at a maximum product application rate of

300 mL/ha., once per season.

The applicant advises that the method of application will be ground based

application via mechanical spraying equipment.

Diflufenican is present in other herbicides currently available in New Zealand.

Flufenacet is a new active ingredient to New Zealand.

Key issues

The key issues for this application are:

The Agency and the applicant have independently classified Firebird based on the

available information on Firebird and its components. The classifications are

summarised in the table below:

Hazardous Property Applicant’s Assessment The Agency’s

Assessment

Acute Toxicity (Oral) 6.1D (overall) 6.1D

Dermal Sensitisation 6.5B 6.5B

Target Organ Toxicity 6.9B 6.9B

Aquatic Ecotoxicity 9.1A 9.1A

Soil Ecotoxicity - 9.2A

Ecotoxicity to terrestrial vertebrates - 9.3C

The Agency’s classifications differ from the applicant’s due to plant toxicity and

terrestrial vertebrate classifications generated from formulation test data;

Although no EEL has been set for Firebird, the Agency proposes setting the

application rate of 300 mL Firebird / ha. (flufenacet 126.3 g/ha., diflufenican 61.9

g/ha), once per season as the application rate for Firebird. This application rate was

used in the toxicological and ecological risk assessment;

The flufenacet metabolite, FOE 5043 sulfonic acid, has the potential to leach into

and persist in the aquatic environment and ground water. However, it has been

demonstrated that FOE 5043 sulfonic acid is not of ecotoxicological concern. In

addition, flufenacet does not appear to be associated with any metabolites of

toxicological concern (US EPA Fact Sheet, 1998).


The Agency’s ecological risk assessment performed on Firebird has resulted in the

following findings:

o High acute risk for aquatic algae. Based on this risk, the Agency considers it is

appropriate to retain the approved handler control for Firebird when it is used

in a wide dispersive manner, or by a commercial contractor.

o The data on diflufenican gathered in HSNO Chemical Classification

Information Database (CCID) is inadequate for aspects of the ecotoxicological

risk assessment of:

Aquatic (acute and chronic) risk;

Terrestrial (plants) risk;

Avian risk;

Environmental fate.

Quantitative modeling carried out by the Agency indicates that, when applied at a

rate of 300 mL Firebird/ha. and in compliance with HSNO controls, the substance

will not pose any significant risks to the health and safety of operators or bystanders.

On this basis, the Agency considers that any risks to human health and safety will be

adequately managed by the default controls which are triggered by the substance’s

hazard classifications. The Agency notes that this evaluation is consistent with the

findings of the EFSA review of diflufenican and products containing this active

ingredient, which included a similar substance to Firebird.

The Agency proposes that, as required by control T1, the following Acceptable

Daily Exposure (ADE) and Potential Daily Exposure (PDE) values are set for

flufenacet:

o ADE = 0.012 mg/kg bw/day;

o PDEfood = 0.008 mg/kg bw/day; and

o PDEdrinking water = 0.002 mg/kg bw/day.

The Agency also proposes that an acute reference dose (ARfD) of 0.017 mg/kg

bw/day for flufenacet is adopted, in case a value is required by the NZ Food Safety

Authority.

The Agency proposes adopting a WES value for Component C of Firebird (Control

T2) as listed in Appendix 8.

Key issues from current reviews:

The Agency notes that diflufenican and products containing diflufenican have been

recently reviewed by EFSA, 2006 (Draft Assessment Report). This report has

highlighted that;

o under the EU use pattern and conditions a no-spray zone of 5-10 m is required

to protect non-target aquatic and terrestrial plants.

o the AOEL previously identified by the Agency for diflufenican (1mg/kg

bw/day) is significantly greater than that which has been established by EFSA

(0.012 mg/kg bw/day).

The data supplied by the applicant and any new information from other regulatory

agencies, such as EFSA, should diflufenican be reassessed.

The Agency has proposed that the default controls for Firebird be modified, such

that:


o no Environmental Exposure Limits (control E1) or maximum application rates

(control E2) are set at the present time and any default values are deleted

(however, a maximum application rate is applied under section 77A);

o an approved handler control is added, but modified to apply to use only;

o further controls regarding stationary containment systems and pipework are

added;

o a control which prohibits application of Firebird onto or into water is added;

o a control which restricts the application method to ground-based only is added.

The Agency’s assessment of the risks posed by Firebird to the environment and to

human health, during the substance’s lifecycle, is based on qualitative assessment

and quantitative modelling using the GENEEC2 and German BBA models.

The Agency considers that the risk assessments indicate that the risks associated

with Firebird are negligible with the proposed controls in place.

The Agency has evaluated information supplied by the applicant about the benefits

of Firebird and considers that significant benefits are likely to be realised through

the release of this substance.

In conclusion, the Agency considers that there are negligible risks to human health

and to the environment and significant benefits associated with the release of

Firebird. Therefore, the Agency considers that it is evident that the benefits of

releasing Firebird outweigh the costs and the application may be approved in

accordance with clause 26.


TABLE OF CONTENTS

1 Application Details ........................................................................................................................... 6

2 Legislative Criteria for the Application ....................................................................................... 6

3 Application Process .......................................................................................................................... 6

4 Notification and Consultation ........................................................................................................ 7

5 Application Synopsis and Information Review .......................................................................... 8

6 Hazardous Properties, Thresholds and Classification ............................................................... 9

7 Default Controls .............................................................................................................................. 10

8 Risk Assessment ............................................................................................................................. 10

9 Assessment of Beneficial Effects ................................................................................................ 17

10 Controls ............................................................................................................................................ 18

11 Overall Evaluation of Risks, Costs and Benefits ..................................................................... 20

12 Conclusion ....................................................................................................................................... 21

Appendix 1: Decision Path .................................................................................................................... 22

Appendix 2: Hazard Classification ...................................................................................................... 23

Appendix 3: Risk Assessment ............................................................................................................... 90

Appendix 4: Discussion on Controls ................................................................................................. 117

Appendix 5: List of Proposed Controls for Firebird ...................................................................... 125

Appendix 6: Scales for Qualitative Risk Assessment .................................................................... 131

Appendix 7: Government Departments, Crown Entities and Interested Parties Notified ...... 134

Appendix 8: Confidential Material .................................................................................................... 137

Appendix 9: Confidential Material (not to be disclosed to applicant) ................................... 140


1 APPLICATION DETAILS

Application Code HSR08057

Application Type To import or manufacture for release any hazardous

substance under Section 28 of the Hazardous Substances

and New Organisms Act 1996 (“the Act”)

Applicant Bayer New Zealand Ltd.

Date Application Received 28 August 2008

Submission Period 11 September 2008 – 23 October 2008

To be considered by A Committee of the Authority (‘the Committee”)

Purpose of the Application To import or manufacture Firebird, an agricultural

herbicide containing 400 g/l flufenacet, plus 200 g/l

diflufenican, in the form of a suspension concentrate, for

the control of annual grass and broad-leaved weeds in

winter wheat and barley (Category C).

2 LEGISLATIVE CRITERIA FOR THE APPLICATION

2.1 The application was lodged pursuant to section 28.

2.2 This report takes into account matters to be considered in section 29; matters

specified under Part II of the Act; and the relevant provisions of the Hazardous

Substances and New Organisms (Methodology) Order 1998 (“the

Methodology”). Unless otherwise stated, references to section numbers in this

report refer to sections of the Act and clauses to clauses of the Methodology.

3 APPLICATION PROCESS

3.1 Evaluation of the application was undertaken by the ERMA New Zealand

project team (“the Agency”) which comprised the following staff members:

Matthew Allen Advisor (Hazardous Substances)

Elizabeth Morgan Advisor (Hazardous Substances)

Tonderai Kaitano Advisor (Hazardous Substances)

Eugene Georgiades Advisor (Hazardous Substances)

Patrick Gemmell Senior Advisor (Kaupapa Kura Taiao).

3.2 The report was reviewed and signed out by:

Noel McCardle Senior Advisor (Hazardous Substances).


3.3 Timeline

Application formally

received

28 August 2008

Application notified 11 September 2008

Submission closing date 23 October 2008.

3.4 Due to delays in completing this E&R Report, the Authority postponed the

consideration under section 58(3) until 28 May 2009.

4 NOTIFICATION AND CONSULTATION

4.1 The Minister for the Environment was advised of the application1 and given the

opportunity to “call-in” the application2. This action was not initiated.

4.2 The Department of Labour (Workplace Group), the New Zealand Food Safety

Authority (Agricultural Compounds and Veterinary Medicines (ACVM) Group)

and the Department of Conservation were identified as having a specific interest

in the application and were provided with a copy of the application (excluding

the confidential information but with the opportunity to access this if necessary).

4.2.1 No comments or submissions were received.

4.3 Other Government departments, Crown agencies and other interested parties, as

listed in Appendix 7, were provided with a copy of the application summary and

given the opportunity to comment or to make a submission.

4.3.1 No comments or submissions were received.

4.4 The application was publicly notified on the ERMA New Zealand website on 11

September 2008 and subsequently advertised in The Dominion Post, the New

Zealand Herald, the Christchurch Press and the Otago Daily Times3.

4.4.1 No submissions were received.

1 section 53(4)(a))

2 section 68

3 section 53


5 APPLICATION SYNOPSIS AND INFORMATION

REVIEW

Information supplied by the applicant

5.1 The applicant supplied the following documents:

the application;

a confidential appendix (including full formulation data and a draft

label).

Information review

5.2 The confidential information on the composition of Firebird has been withheld

at the request of the applicant for reasons of commercial sensitivity. The

information is provided for the Committee in Confidential Appendix 8.

5.3 The Agency notes that diflufenican and products containing diflufenican have

been recently reviewed by EFSA, 2006 (Draft Assessment Report). This report

has highlighted that;

under the EU use pattern and conditions a no-spray zone of 5-10 m is

required to protect non-target aquatic and terrestrial plants.

the AOEL previously identified by the Agency for diflufenican (1mg/kg

bw/day) is significantly greater than that which has been established by

EFSA (0.012 mg/kg bw/day).

The data supplied by the applicant and any new information from other

regulatory agencies, such as EFSA, will be assessed by the Agency, should a

reassessment of diflufenican be undertaken at a future time.

5.4 The Agency notes that uncertainties exist in aspects of the aquatic, terrestrial

and avian risk assessment, due to the quality and availability of relevant data in

the HSNO Chemical Classification Inventory Database (CCID) for diflufenican

(see paragraph 8.18). However, the Agency considers that these uncertainties

are not sufficient to influence decision making in the scientific and technical

information relating to the potential adverse effects of Firebird4. Therefore, the

Agency considers that the information constitutes an adequate and appropriate

basis for considering the application5.

Description and use of the substance

5.5 Firebird is a herbicide containing 400 g/L flufenacet, and 200 g/L diflufenican

in the form of an suspension concentrate. Firebird is proposed to be used for the

control of certain broadleaf and grass weeds in winter wheat and barley.

4 clauses 29 and 30

5 clause 8


Lifecycle

Manufacture/Importation

5.6 The applicant has indicated that Firebird will be imported fully formulated,

packed for retail sale.

5.7 While Firebird will be manufactured overseas, it is possible that the substance

could be manufactured in New Zealand in the future. Consequently, the risks

associated with the manufacture of Firebird have been evaluated, so that

approval of this substance will be applicable to both the import and manufacture

of Firebird.

Transport, storage and packaging

5.8 Firebird will be packaged in UN approved HDPE 3L containers. Firebird will be

stored on arrival by Bayer New Zealand Ltd. at a dedicated chemical storage

facility.

5.9 Firebird will be distributed by agricultural distributors, with expertise in

handling pesticide chemicals, and dedicated pesticide storage facilities.

5.10 Firebird will be stored in facilities which meet the requirements of the Act (e.g.

signage, emergency plans) and the Resource Management Act 1991.

Use

5.11 Firebird will be applied as a herbicide at a product application rate of 300

mL/ha. (active ingredient application rates: flufenacet 120 g /ha; diflufenican 60

g/ha), once per season.

5.12 The applicant advises that the method of application will be ground-based

application via mechanical spraying equipment.

Disposal

5.13 The applicant advises that the normal method of disposal will be via use as

detailed on the product label, unused product can be retained for use in the

following season. Used containers should be triple rinsed and residue added to

the spray tank. Empty containers should be taken to an Agrecovery point.

5.14 In all cases, the substance and its packaging will be disposed of in accordance

with the Hazardous Substances (Disposal) Regulations 2001 and the Resource

Management Act 1991.

6 HAZARDOUS PROPERTIES, THRESHOLDS AND

CLASSIFICATION

6.1 The Agency has evaluated the information supplied by the applicant and also

referred to other data sources in assessing the hazardous properties of Firebird.

This assessment is attached as Appendix 2.


6.2 The applicant’s and the Agency’s classification of the hazard profiles of Firebird

are listed in Table 6.1.

Table 6.1: Summary of applicant’s and Agency’s HSNO classification of Firebird

Hazardous Property Applicant’s

Assessment

The Agency’s

Assessment

Acute Toxicity (Oral) 6.1D (overall) 6.1D

Dermal Sensitisation 6.5B 6.5B

Target Organ Toxicity 6.9B 6.9B

Aquatic Ecotoxicity 9.1A 9.1A

Soil Ecotoxicity - 9.2A

Ecotoxicity to terrestrial

vertebrates

- 9.3C

6.3 The Agency’s classifications differ from the applicant’s due to plant toxicity and

terrestrial vertebrate classifications generated from formulation test data.

6.4 The risk assessment in Section 8 of this report is based on the Agency’s

classification of Firebird.

7 DEFAULT CONTROLS

7.1 Based on the hazard classification shown in Table 6.1, the set of associated

controls has been identified. These default controls are listed in Appendix 4.

7.2 The Authority is able to vary the default controls and impose controls under

sections 77 and 77A to produce a set of controls relevant to Firebird. Variations

and additional controls for Firebird are considered in Section 10 of this report.

8 RISK ASSESSMENT

Identification of potentially non-negligible risks and costs

8.1 Potentially non-negligible risks were identified for evaluation following clauses

9 and 11, which incorporate sections 5, 6 and 8.

8.2 A “cost” is defined in Regulation 2 of the Methodology as “the value of a

particular adverse effect expressed in monetary or non-monetary terms”. Thus,

these have been assessed in an integrated fashion together with the risks of the

adverse effects in the following assessment.

8.3 The applicant has identified potential sources of risk to the environment and to

human health and safety through release, spillage or exposure throughout the

lifecycle of the substance. The Agency has also identified potential sources of

risk and these, along with those identified by the applicant, are tabulated in

Table 8.1.


Table 8.1: Potential sources of risks associated with Firebird

Lifecycle Activity Associated Source of Risk

Manufacture / Import An incident during the manufacture or importation of Firebird resulting

in spillage and subsequent exposure of people or the environment to

the substance.

Packing An incident during the packing of Firebird resulting in spillage and

subsequent exposure of people or the environment to the substance.

Transport or storage An incident during the transport or storage of Firebird resulting in

spillage and subsequent exposure of people or the environment to the

substance.

Use Application of Firebird resulting in exposure of users or bystanders or

the environment; or an incident during use resulting in spillage and

subsequent exposure of users or the environment to the substance.

Disposal Disposal of Firebird or packaging resulting in exposure of people or

the environment to the substance.

Assessment of potentially significant risks 8.4 In accordance with sections 5 and 6 and clauses 9 and 12, the Agency has

assessed the potentially non-negligible risks of this substance in terms of risks to

the environment, to human health and safety, to the relationship of Māori to the

environment, to society and the community, to the market economy, and to New

Zealand’s international obligations.

8.5 The Agency notes that the evidence provided by the applicant and additional

evidence found by the Agency, relating to the hazardous properties of Firebird,

is largely scientific in nature6. However, as some of the evaluation of risks, costs

and benefits has been carried out on a qualitative basis, it is recognised that

there is a degree of uncertainty in the risk analysis.

8.6 The analysis of risk takes into account the controls that derive from the HSNO

Regulations (in particular the default controls identified in Appendix 4) and

from other legislation such as the Resource Management Act 1991 and the

Health and Safety in Employment Act 1992. That is, the analysis assumes

controls are in place.

8.7 A quantitative risk assessment has been carried out to evaluate the level of risk

to operators and the environment arising from the use of Firebird (see

Appendix 3).

8.8 A qualitative assessment has been undertaken for all other stages of the

lifecycle. In these cases, the level of risk has been evaluated on the basis of the

magnitude and likelihood of adverse effects occurring to people or the

environment (see Appendix 3).

6 clause 25(1)


Assessment of the risks to human health and safety

8.9 The Agency has classified Firebird as an acute oral toxicant (6.1D), a skin

sensitiser (6.5B) and a target organ toxicant (6.9B).

8.10 In the Agency’s opinion, chronic hazards normally require repeated exposure to

the substance for the adverse effects to occur and are therefore most relevant to

the end-users.

8.11 The Agency assessed the health risk to operators on the basis of the German

BBA model predictions for exposure estimates. The quantitative modelling

indicates that at a product application rate of 300 mL / ha., the exposure to

Firebird, when used as recommended on the label, is not likely to present a high

health risk to the mixers or applicators, even with no personal protective

equipment (PPE). However, the Agency considers that is appropriate to retain

requirements for PPE since the use of PPE when handling agrichemicals is good

practice. the Agency notes that the HSNO PPE requirements are not prescriptive

allowing users to select an appropriate level of PPE.

8.12 The Agency notes that the requirement for PPE is triggered as a default control

for Firebird as a result of its 6.9B classification. The Agency, therefore,

concludes that the health risk to operators, with controls in place, is negligible.

Further details on this quantitative assessment are given in Appendix 3.

8.13 Bystanders may be exposed to Firebird by spray-drift during application and are

likely to be further away from the application area than the operators.

Bystanders should not be exposed to Firebird during mixing and loading. The

Agency notes the levels of risk to bystanders posed by mixing, loading and

ground-based application and considers that it is unlikely that an unacceptable

risk will be posed to bystander health. The Agency, therefore, concludes that the

health risk to bystanders is negligible.

8.14 The risks of Firebird to human health and safety (with controls in place) at

various stages of the lifecycle are summarised below in Table 8.3 and discussed

more fully in Appendix 3.

Table 8.3: Level of risk of Firebird to human health and safety.

Lifecycle stage Potential

Adverse Effect

Likelihood of

Adverse

Effect

Occurring

Magnitude of

Adverse

Effect

Level of Risk

Manufacture/packing Acute oral toxicity

Highly

improbable

Moderate Negligible

Contact sensitiser Highly

improbable

Minor -

Moderate

Negligible

Target organ

toxicity

Quantitative assessment indicates that the chronic risks

to human health and safety are acceptable.


Lifecycle stage Potential

Adverse Effect

Likelihood of

Adverse

Effect

Occurring

Magnitude of

Adverse

Effect

Level of Risk

Importation,

transport or storage

Acute oral toxicity

Highly

improbable

Moderate Negligible


improbable

Minor -

Moderate

Negligible

Target organ

toxicity

Not addressed

Use Acute effects: operators & bystanders (qualitative assessment)

Acute oral toxicity Highly

improbable

Moderate Negligible

Contact sensitiser

Highly

improbable

Minor -

Moderate

Negligible

Chronic effects: operators (quantitative assessment)

Target organ

toxicity

Quantitative assessment indicated that the chronic risks

to human health and safety are acceptable and the level

of risk is considered to be negligible.

Chronic effects: bystanders (quantitative assessment)

Target organ

toxicity

Quantitative assessment indicated that the chronic risks

to bystander human health and safety are acceptable

and the level of risk is considered to be negligible.

Disposal Acute oral toxicity Highly

improbable

Moderate Negligible


improbable

Minor -

Moderate

Negligible

Target organ

toxicity

Quantitative assessment indicates that the chronic risks

to human health and safety during disposal are

acceptable and the level of risk is considered to be

negligible.

Assessment of the risks to the environment

8.15 The Agency has classified Firebird as being highly toxic in the aquatic

environment (9.1A), highly toxic in the terrestrial environment (9.2A) and

harmful to terrestrial vertebrates (9.3C). Flufenacet is considered to be

persistent in the aquatic and terrestrial environments. Diflufenican is considered

to be bioaccumulative. Thus, a range of organisms in the environment may be

adversely affected over a prolonged period if exposed to Firebird.

8.16 The Agency considers that the likelihood of exposure to the environment is

greatest during use of the substance.

8.17 This quantitative assessment of the environmental risks associated with the use

of Firebird at a rate of 300 mL / ha. shows that it presents a low acute risk to fish

and crustacean, low chronic risk to algae, and a high acute risk to algae. The

Agency considers also that, although the risk to soil invertebrates was quantified

as unacceptable, provided Firebird was applied once a year, at a time where its


impact on the positive effects of beneficial invertebrates is minimised, this risk

can be reduced to negligible (see Appendix 3).

8.18 The Agency notes that the quality and availability of the data contained in the

HSNO Chemical Classification Information Database (CCID) for diflufenican

gives rise to a degree of uncertainty in aspects of the aquatic, terrestrial, avian

and environmental fate risk assessment for Firebird. However, the Agency notes

the results of the quantitative modelling and considers that application of the

following controls will address the uncertainty arising from the assessment of

diflufenican, and reduce the level of risk to the environment by use of Firebird

to negligible:

Retaining the approved handler controls will minimise the risks

associated with exposure to the aquatic environment;

Setting a maximum application rate of 300 mL / ha., once per year;

Restricting application of Firebird to ground-based methods only;

and

Prohibiting the application of Firebird into or onto water.

8.19 The risks of Firebird to the environment (with controls in place) at various

stages of its lifecycle are summarised below in Table 8.2 and discussed more

fully in Appendix 3.

Table 8.2: Level of risk of Firebird to the environment.

Lifecycle Stage Potential

Adverse

Effect

Likelihood of

Adverse Effect

Occurring

Magnitude of

Adverse

Effect

Level of Risk

Manufacture/packing,

importation, transport

and storage

Spillage

resulting in

death or

adverse effects

to aquatic or

terrestrial

organisms in

the

environment.

Highly improbable Moderate Negligible

Use

Use resulting

in death or

adverse effects

to aquatic

organisms in

the

environment.

Quantitative assessment indicated that

the acute risk to fish and crustacea in

the aquatic environment is low during

use. Quantitative assessment indicated

that the acute risk to algae is high

during use. Flufenacet is considered to

be persistent in the aquatic

environment.

Quantitative assessment indicated that

the chronic risk to fish and crustacea in

the aquatic environment is low during

use.

The Agency

notes the

results of this

quantitative

assessment

and considers

that the

application of

controls will

reduce this

risk to

negligible.

Use resulting

in death or

adverse effects

to terrestrial

Quantitative assessment indicated an

acceptable risk to beneficial insects

during use. Diflufenican is considered

The Agency

notes the

results of this

quantitative


Lifecycle Stage Potential

Adverse

Effect

Likelihood of

Adverse Effect

Occurring

Magnitude of

Adverse

Effect

Level of Risk

organisms in

the

environment.

to be persistent in the soil environment. assessment

and considers

this risk to be

negligible

Use resulting

in death or

adverse effects

to beneficial

invertebrates in

the terrestrial

environment

Quantitative assessment indicated an

unacceptable risk to beneficial insects

during use, within the field

environment. Quantitative assessment

indicated an acceptable risk to

beneficial insects during use, outside of

the field environment. Diflufenican is

considered to be persistent in the soil

environment. The application frequency

of once a year, applied early-season

reduces the risk of impacting on the

positive effects of beneficial

invertebrates.

The Agency

notes the

results of this

quantitative

assessment

and considers

this risk to be

negligible.

Use resulting

in death or

adverse effects

to terrestrial

vertebrates.

Highly

improbable

Minor Negligible

Use resulting

in death or

adverse effects

to birds.

Quantitative assessment indicated that Firebird is unlikely

to be an avian chronic toxicant and considers this risk to

be negligible.

Disposal Disposal

resulting in

death or

adverse effects

to aquatic or

terrestrial

organisms in

the

environment

Highly

improbable

Minor Negligible

Relationship of Māori to the Environment

8.20 The Agency has considered this application in accordance with the clauses

9(b)(i) and 9(c)(iv) and sections 6(d) and 8. In addition, the framework

contained in the Agency user guide “Working with Māori under the HSNO Act

1996” has been used to assess the effects of this application on the relationship

of Māori to the environment.

8.21 The Agency notes that Firebird triggers a number of hazardous properties giving

rise to the potential for cultural risk including the deterioration of the mauri of

taonga flora and fauna species, the environment and the general health and well-

being of individuals and the community.

8.22 In addition, the introduction and use of this substance has the potential to inhibit

the ability of iwi/Māori to fulfil their role as kaitiaki, particularly in relation to


the guardianship of waterways given the highly ecotoxic nature of the substance

to aquatic species, and potential risks to the mauri ora of human health under

prolonged exposure to this substance.

8.23 On considering the information outlined here and elsewhere in this report, the

Agency considers a minimal impact from Firebird on the relationship of Māori

and their culture and traditions with their ancestral lands, water, sites, wāhi tapu,

valued flora and fauna and other taonga to be highly improbable. In addition

there is no evidence to suggest that the controlled use of Firebird will breach the

principles of the Treaty of Waitangi.

8.24 The overall level of risk is therefore considered to be negligible assuming that

the substance will be handled, stored, transported, used, and disposed of, in

accordance with the explicitly stated default and additional controls proposed in

this report, and any other controls required by other legislation.

8.25 However, the Agency notes that should inappropriate use, or accident, result in

the contamination of waterways or the environment generally, that users notify

the appropriate authorities including the relevant iwi authorities in that region.

This action should include advising them of the contamination and the measures

taken to contain and remediate.

Assessment of the risks to society and the community

8.26 There are not expected to be any significant adverse impacts on the social

environment with the controlled use of Firebird, apart from the health effects

and environmental effects already discussed. Consequently, the Agency

considers that this aspect of potential risk need not be considered further.

Assessment of the risks to the market economy

8.27 Taking into account the level of risk to the environment and to human welfare,

no sources of additional risk have been identified that could result in an adverse

economic impact on a community.

8.28 The Agency notes that direct economic costs will be borne by the applicant and

users of the substance. The HSNO default controls intentionally do not manage

direct economic effects. These are for suppliers and users of the substance to

address.

New Zealand’s international obligations

8.29 The Agency does not anticipate that Firebird will pose any risks to New



9 ASSESSMENT OF BENEFICIAL EFFECTS

Potentially non-negligible benefits

9.1 A “benefit” is defined in Regulation 2 of the Methodology as “the value of a

particular positive effect expressed in monetary or non-monetary terms”.

Benefits that may arise from any of the matters set out in clauses 9 and 11 were

considered in terms of clause 13.

9.2 The applicant claims that the approval of Firebird will provide the following

benefits:

9.2.1 Firebird is a unique combination of diflufenican and flufenacet, and

provides an alternative to isoproturon-based herbicides for control of

annual grasses and broadleaf weeds;

9.2.2 Application of Firebird can be carried out from pre-emergence to early

post emergence of crop and weeds, providing flexibility of use;

9.2.3 Firebird is safe to use on all varieties of winter wheat and winter

barley;

9.2.4 The low dose rate, 300 ml Firebird / ha., reduces the environmental

pesticide burden and packaging waste.

9.3 The Agency considers that the economic and related benefits to be derived from

the use of Firebird are potentially significant.

Likely effects of the substance being unavailable

9.4 In accordance with section 29, consideration has been given to the likely effects

of Firebird being unavailable.

9.5 The Agency notes that there are currently no other products containing the same

combination of active ingredients as Firebird. Herbicide products with a similar

hazard profile are available in New Zealand designed to target the grasses and

broadleaf weeds.

9.6 The likely effects of Firebird being unavailable would thus be a reduction in

consumer choice for end-users, and the potential benefits arising from the

introduction of Firebird would not be realised.

Risk reduction implications

9.7 The applicant has indicated that the low use rates required for Firebird will

reduce the chemical burden on the environment, and reduce the amount of

packaging required to be disposed of.


10 CONTROLS

Setting of exposure limits and application rates

10.1 Control T1 relates to the requirement to limit public exposure to toxic

substances by the setting of Tolerable Exposure Limits (TELs), which are

derived from Acceptable Daily Exposure (ADE) values. The Agency is not

proposing that any TEL values be set for Firebird until implementation of a

pending review of setting such values under section 77B (See Appendix 4).

However, as flufenacet is a new active to New Zealand, the following

Acceptable Daily Exposure (ADE) and Potential Daily Exposure (PDE) values

have been set for flufenacet:

ADE = 0.012 mg/kg bw/day;

PDEfood = 0.008 mg/kg bw/day; and

PDEdrinking water = 0.002 mg/kg bw/day.

The Agency proposes that an acute reference dose (ARfD) of 0.017 mg/kg

bw/day for flufenacet is adopted, in case a value is required by the New Zealand

Food Safety Authority.

10.2 Control T2 relates to the requirement to limit worker exposure to toxic

substances by the setting of Workplace Exposure Standards (WESs). It is

proposed that WES values for Component C of Firebird are adopted (See

Appendix 4). The Agency considers that the Department of Labour WES values

for components H and I should not be applied, due their low concentrations in

Firebird.

10.3 Control E1 relates to the requirements to limit exposure of non-target organisms

in the environment through the setting of Environmental Exposure Limits

(EELs). It is proposed that no EELs are set at this time for Firebird and the

default values are deleted (see Appendix 4).

10.4 Control E2 relates to the requirement to set an application rate for a class 9

substance that is to be sprayed on an area of land (or air or water) and for which

an EEL has been set. As no EEL has been proposed for Firebird, the Agency is

not able to propose the setting of a maximum application rate under this

regulation. However, the Agency notes that the risk quotient derived from the

environmental exposure modelling indicates that Firebird may cause adverse

environmental effects when used according to the specific parameters of the risk

assessment. The Agency therefore considers it is appropriate to set a maximum

application rate under section 77A (see paragraph 11.8).

Proposed additions and modifications to controls

10.5 The Agency notes that the risk quotients derived from the quantitative

modelling indicate that use of Firebird could cause acute adverse effects to the

aquatic environment if the substance was to move off target, and restrictions on

use are necessary to manage the risks to the environment (refer Appendix 3).

Accordingly, the Agency considers that the application of controls addressing

these risks will be more effective than the specified (default) controls in terms of


their effect on the management, use and risks of the substance (section

77A(4)(a)). Consequently, the following additional controls are proposed for

Firebird to restrict the level of risk to the environment:

10.5.1 “Firebird shall not be applied onto or into water.”

10.5.2 “The maximum application rate for Firebird shall be 300 mL/ha., with

a frequency of application of once per year.”

10.5.3 “The method of application shall be limited to ground-based

application only”.

10.6 Controls E7 and AH1 relate to requirements for ecotoxic substances to be under

the control of an approved handler. The Agency considers that these controls

should be modified for Firebird so as to apply only during use. Accordingly, the

Agency is proposing that the following control be substituted for Regulation

9(1) of the Hazardous Substances (Classes 6, 8, and 9 Controls) Regulations

2001:

“(1). Firebird must be under the personal control of an approved handler when

the substance is –

(a) applied in a wide dispersive manner; or

(b) used by a commercial contractor.”

10.7 The Agency notes that the specified controls do not address the risks associated

with stationary container systems, nor do they allow for dispensation where it is

unnecessary for any associated pipework to have secondary containment.

Accordingly, the Agency considers that the application of controls addressing

these risks will be more effective than the specified (default) controls in terms of

their effect on the management, use and risks of the substance7. The proposed

controls are shown in Table 5.1 of Appendix 5.

10.8 Control EM12 relates to the requirements for secondary containment of pooling

substances8. The EM12 secondary containment requirements have been

triggered for Firebird as a result of its 6.1D, 6.5B and 9.1A classifications. The

Agency considers that the risks associated with the containment of substances

which are not class 1 to 5 substances (i.e. do not ignite or explode) are different

to those associated with class 1 to 5 substances. Consequently the Agency

considers that the secondary containment requirements can be reduced. The

Agency considers that these reduced secondary containment measures are

adequate to manage the risks of a spillage of Firebird. Therefore, the proposed

additional control, which varies the EM12 control, is more cost-effective in

terms of managing the risks of the substance. The proposed controls are shown

in Table 5.1 of Appendix 5.

10.9 Control TR1 relates to the requirements for a substance to be tracked and is

triggered for Firebird only by virtue of its ecotoxicity. Consequently, the

Agency considers that tracking the substance would be unduly onerous, as the

key risks can be managed through other controls such as approved handler,

7 section 77A(4)(a)

8 Regulations 35 – 41 of the Hazardous Substances (Emergency Management) Regulations 2001


packaging, labelling and emergency management requirements. Thus, this

control may be deleted.

10.10 The Agency considers that the following controls may be combined9 for

Firebird as they relate to the same requirements:

10.10.1 Controls T4 and E6 which relate to requirements for equipment used to

handle hazardous substances.

10.10.2 Controls P13 and P15 which relate to requirements for packaging

hazardous substances.

10.10.3 Controls D4 and D5 which relate to requirements for disposal of

Firebird.

Control precedents

10.11 The Agency considered the Authority’s approvals given to pesticides under Part

5 of the Act as well as those transferred to the Act under the Hazardous

Substances (Pesticides) Transfer Notice 2004 (as amended).

Summary of controls

10.12 The Agency considers that the customised controls listed in Appendix 5 should

apply to Firebird.

Environmental user charges

10.13 Section 96 provides that the Authority may identify and report to the Minister

where it considers that a reduction in the likely occurrence of adverse effects

similar to that achieved by the controls attached to any substance could be

achieved by any environmental user charge, or a combination of an

environmental user charge and controls.

10.14 The Agency considers that use of controls is the most effective means of

managing the risks throughout the lifecycle of Firebird. The imposition of an

environmental user charge instead of, or in combination with controls, is

therefore not required at this time.

11 OVERALL EVALUATION OF RISKS, COSTS AND

BENEFITS

11.1 The Agency considers the risks of Firebird to human health to be negligible.

11.2 While the Agency’s use quantitative and qualitative assessments identified a

high acute risk to the algae during the use of Firebird, the Agency considers that

the use of approved handlers, restricting the method of application to ground-

based only, the setting of a maximum application rate, and prohibiting the

9 section 77(5)


application of the substance into or onto water, will be sufficient to manage

these risks, and reduce their level to negligible.

11.3 The Agency does not consider there to be significant risks to Māori cultural

wellbeing, society and the community, the market economy, or to New


11.4 The Agency has taken the type and severity of the risks, and the characteristics

of such risks into account, and considers that the overall level of risk posed by

the substance is negligible.

11.5 The Agency considers that there are potentially significant benefits associated

with the release of Firebird as are specified in Section 9 of this report.

11.6 Thus, the Agency considers that it is evident that the benefits of releasing

Firebird outweigh the costs.

12 CONCLUSION

12.1 Bayer New Zealand Ltd. has applied for approval to import for release in New

Zealand the substance identified as Firebird.

12.2 The Agency considers Firebird triggers the following hazard classifications:

6.1D Acute oral toxicity

6.5B Contact Sensitisation

6.9B Target organ systemic toxicity

9.1A Aquatic ecotoxicity

9.2A Soil ecotoxicity

9.3C Terrestrial vertebrate ecotoxicity.

12.3 The Agency considers that there are negligible risks to the environment and

human health and significant benefits associated with the release of Firebird.

Therefore, the Agency considers that it is evident that the benefits of releasing

Firebird outweigh the costs and the application may be approved in accordance

with clause 26.

12.4 The Agency considers the controls listed in Appendix 5 should apply to

Firebird.


APPENDIX 1: DECISION PATH

1

Review the content of the

application and all relevant

information

2

Is this information sufficient

to proceed?

5

Identify the composition of the substance,

classify the hazardous properties of the

substance, and determine default controls

6

Identify all risks, costs and benefits that are

potentially non-negligible

7

Assess each risk assuming controls in place.

Add, substitute or delete controls in

accordance with clause 35 and sections77,

77A, 77B

8

Undertake combined consideration of all risks

and costs, cognisant of proposed controls

9

Are all risks with controls in place

negligible?

10

Review controls for cost-effectiveness in

accordance with clause 35 and sections 77,

77A, 77B

11

Is it evident that benefits outweigh

costs?

16

Confirm and set controls

Approve

(section 29(1)(a))

3

Seek additional

information

4

Sufficient?

Decline (section 29(1)(c))

12

Establish position on risk averseness

and appropriate level of caution

13

Review controls for cost-effectiveness

in accordance with clause 35 and

sections 77, 77A, 77B

14

Assess benefits

15

Taking into account controls,

do positive effects outweigh adverse

effects?

Decline

(section 29(1)(b))

Clause 27

Clause 26

No

No

No

No

Yes

Yes

Yes

Yes

Yes

No


APPENDIX 2: HAZARD CLASSIFICATION

Classification of Firebird

Formulation test data were not provided for all endpoints of Firebird. For endpoints

for which formulation test data were not provided, classification was estimated using

mixture rules based on information on the components. Details of the key substance

components and the methods used to derive the classifications are presented in Table

A2.1. The relevant sections of the User Guide to the Thresholds and Classifications in

the HSNO Act (ERMA 2008a) that describes the mixture rules are listed in Table

A2.2.

The active ingredient, flufenacet, is a new pesticide active ingredient to New Zealand.

The Agency has provided a summary of the toxicity, ecotoxicity and environmental

fate data in Tables A2.5 to A2.12a.

Data quality – overall evaluation

The Agency has adopted the Klimisch et al (2001) data reliability scoring system for

evaluating data used in the hazard classification and risk assessment of flufenacet and

Firebird (section 1.2.4 in ERMA 2008a). Scores for individual studies, as evaluated

by the Agency, are included in the data assessment tables A2.5 to A2.12a. Overall,

data provided for flufenacet and Firebird were of high quality (Klimisch scores 1 or

2). Data on components of Firebird were generally of lower quality (Klimisch scores

3 or 4). However, the effect of the lower quality data on the overall evaluation of the

effects of Firebird was not significant because of the amount of high quality

formulation test data supplied.

The lower quality or absence of chronic data on diflufenican has lead to some data

gaps, which affects the prediction of the long-term effects in the environment.

The Agency acknowledges that there are frequently data gaps in the hazard

classification for chemicals which have been in use internationally for a long time.

International programmes such as the OECD High Production Volume programme

(OECD 1990) and REACH (EU 2006) are progressively working towards filling these

data gaps. As new information becomes available, and resources permit, the Agency

will endeavour to update the HSNO classifications for those substances.

Table A2.0: Physical and chemical properties of Firebird. Test Firebird Method Reference

Appearance Beige white, suspension Visual Güldner (2001).

Report No.

14 1050 5201

GLP

Klimisch score: 1

Disk 13

00000469

Odour weak, characteristic Güldner (2001).


Report No.

14 1050 5201

GLP

Klimisch score: 1

Disk 13

00000469

Density at 20°C 1.25 OECD 109 Güldner (2001).

Report No.

14 1050 5201

GLP

Klimisch score: 1

Disk 13

00000469

Surface tension 40.6 mN/m OECD 115 Güldner (2001).

Report No.

14 1050 5201

GLP

Klimisch score: 1

Disk 13

00000469

pH 5.5 According to CIPAC MT

75.3 : Electrometric

determination (pH-meter)

of the sample (undiluted)

under nitrogen atmosphere

and room temperature.

Güldner (2001).

Report No.

14 1050 5201

GLP

Klimisch score: 1

Disk 13

00000469

5.4 According to CIPAC MT

75.3 : Electrometric

determination (pH-meter)

of the sample (1%) in

CIPAC D water under

nitrogen atmosphere and

room temperature.

Güldner (2001).

Report No.

14 1050 5201

GLP

Klimisch score: 1

Disk 13

00000469

Dynamic viscosity η = 185x 10-3

Pa.s OECD 114 Güldner (2001).

Report No.

14 1050 5201

GLP

Klimisch score: 1

Disk 13

00000469

Flash point No flash point up to the

boiling point (105°C)

according to DIN EN

22719

DIN EN 22719 Heitkamp (2002).

Report No.

01/00493

GLP

Klimisch score: 1

Disk 13

00000472

Auto flammability Auto ignition temperature

445°C

DIN EN 51794

EC Guideline A 15

Heitkamp (2002).

Report No.

01/00493

GLP

Klimisch score: 1

Disk 13

00000472

Explosive

properties

Not explosive according to

Guideline A 14

EEC-method A14 Heitkamp (2002).

Report No.


01/00493

GLP

Klimisch score: 1

Disk 13

00000472

Table A2.1: Summary of the toxicity and ecotoxicity hazard classifications of

Firebird. Hazardous Property The Agency’s

Classification

Classification Method Component(s) driving

classification

6.1 oral 6.1D Formulation test data N/A

6.1 dermal No Formulation test data N/A

6.1 inhalation No Formulation test data N/A

6.3/8.2 Skin

irritation/corrosion No Formulation test data N/A

6.4/8.2 Eye

irritation/corrosion No Formulation test data N/A

6.5 Respiratory

sensitization ND Mixture rules N/A

6.5 Contact

sensitization 6.5B Formulation test data N/A

6.6 Mutagenicity ND Mixture rules N/A

6.7 carcinogenicity ND Mixture rules N/A

6.8 Reproductive

developmental toxicity ND Mixture rules N/A

6.9 Target organ

systemic toxicity 6.9B Mixture rules Flufenacet

9.1 Aquatic ecotoxicity 9.1A Formulation test data N/A

Aquatic Persistence Yes Mixture Rules Flufenacet

Bioaccumulation Yes Mixture Rules Diflufenican

9.2 Soil ecotoxicity 9.2A Formulation test data N/A

Soil Persistence Yes Metabolite data Flufenacet

9.3 Terrestrial

vertebrate ecotoxicity 9.3C Formulation test data N/A

9.4 Terrestrial

invertebrate ecotoxicity No Formulation test data N/A


Table A2.2: Location of mixture rules within the HSNO Thresholds and

Classifications User Guide (V2.0. March 2008).

Hazard User Guide to HSNO

Thresholds and

Classifications Reference

Subclass 6.1 Acute Toxicity Part V, Chapter 10, Page 12

Subclass 6.3/8.2 Skin Irritancy/Corrosivity Part V, Chapter 11, Page 7

Subclass 6.4/8.3 Eye Irritancy/Corrosivity Part V, Chapter 12, Page 9

Subclass 6.5 Contact and Respiratory Sensitisation Part V, Chapter 13, Page 8

Subclass 6.6 Mutagenicity Part V, Chapter 14, Page 5

Subclass 6.7 Carcinogenicity Part V, Chapter 15, Page 8

Subclass 6.8 Reproductive Developmental Toxicity Part V, Chapter 16, Page 11

Subclass 6.9 Target Organ Systemic Toxicity Part V, Chapter 17, Page 10

Subclass 9.1 Aquatic Ecotoxicity Part VI, Chapter 19, Page 18

Subclass 9.2 Soil Ecotoxicity Part VI, Chapter 20, Page 8

Subclass 9.3 Terrestrial Vertebrate Ecotoxicity Part VI, Chapter 21, Page 7

Subclass 9.4 Terrestrial Invertebrate Ecotoxicity Part VI, Chapter 22, Page 5


Identity of flufenacet

As this is the first full Part V application considered for this active ingredient, general

data about flufenacet are provided in the Tables A2.3D and A2.4.

Table A2.3D: Identification of flufenacet10

.

CAS number

IUPAC name N-(4-Fluoro-phenyl)-N-isopropyl-2-(5-

trifluoromethyl-[1,3,4]thiadiazol-2-

yloxy)-acetamide

Common name Flufenacet

CAS Number 142459-58-3

Molecular formula C14H13F4N3O2S

Molecular weight 363.3 g/mole

Structural formula See Figure 1

Purity 95.0% (minimum)

Significant impurities/additives

(% concentration)

See Confidential Appendix 8

Known uses Herbicide

HSNO classification 6.1D (oral), 6.1E (inhalation), 6.5B, 6.9B,

9.1A, 9.2A, 9.3C

Other classification & labelling N/A

Figure 1: Structural formula of flufenacet.

Physical and chemical properties of flufenacet relevant to the interpretation of

ecotoxicity tests, environmental fate and exposure assessment are summarized in

Table A2.4.

Table A2.4: Physical and chemical properties of flufenacet. Property Flufenacet Test method Reference

Vapour pressure 9 x 10-7

h Pa (20°C)

2 x 10-6

h Pa (25°C)

OECD 104

EEC method A4

Krohn (1994)

Report No.

14 200 0812

GLP

Klimisch score: 1

Disk 2

00000009

Henry’s Law constant 0.0912 Pa x m3/Mole

(20°C)

Calculated

Krohn (1994)

GLP

Klimisch score: 1

Disk 2

00000010

10

In the Tables below FOE 5043 is the company code name for flufenacet.


Thiadone (Metabolite)

0.72 Pa m3/Mole

(25°C)

Calculated using

HenryWIN

Hellpointner

(1995)

GLP

Report No.

107282

Klimisch score: 1

Disk 2

00000153

Melting range Two modifications of FOE

5043 can be observed with a

melting point of 76 – 79°C,

respectively.

OECD 102 Krohn (1992)

Report No.

14 155 0749

GLP

Klimisch score: 1

Disk 2

00000005

Relative Density 1.45 g/mL (20°C)

OECD 109

EEC method A3

Krohn (1995)

Report No.

14 200 0883

GLP

Klimisch score: 1

Disk 2

00000008

Water Solubility pH 4: 56 mg/L (20°C)

pH 7: 56 mg/L

pH 9: 53 mg/L

OECD 105 Krohn (1992)

Report No.

14 410 0746

GLP

Klimisch score: 1

Disk 2

00000016

Solvent Solubility

(20°C)

n-hexane 8700 mg/L

toluene >200000 mg/L

dichloromethane

>200000 mg/L

2-propanol 170000 mg/L

1-octanol 88000 mg/L

polyethylene glycol

74000 mg/L

polyethylene glycol +

ethanol 160000 mg/L

acetone >200000 mg/L

dimethylformamide

>200000 mg/L

acetonitrile

>200000 mg/L

dimethylsulfoxide

>200000 mg/L

OECD 105 (adapted

for organic solvents)

EPA 63-8

Krohn (1992)

Report No.

14 500 0745

GLP

Klimisch score: 1

Disk 2

00000017

pH pH 9.4 (2%)

OECD 112

Method

2005-0002801-91D

Method

2187/5140000/14

Stupp (1992)

Report No.

14 400 0748

GLP

Klimisch score: 1

Disk 2

00000022

Surface tension 60 mN/m

(Weakly surface active)

OECD 115

EC method A5

Krohn (1995)

Report No.

14 442 0870

GLP

Klimisch score: 1


Flammability Not highly flammable

(Test substance melted when

approached by ignition

flame)

EC method A10 Mix (1995)

Report No.

95/00139

GLP

Klimisch score: 1

Disk 2

00000024

Autoflammability Does not undergo

spontaneous combustion

EC method A16

Explosive properties Not explosive EC method A14

Oxidizing properties A test according to EC

method A17 was omitted as

the test substance melted in a

test using to EC method 10.

Thermal stability DTA: Exothermic reaction

occurred > 160°C

TGA: Weight loss observed

under air and nitrogen >

150°C

Conclusion

FOE 5043 is thermally stable

at room temperature

OECD 113 Eberz and Berg

(1993)

Report No.

93/10262

GLP

Klimisch score: 1

Disk 2

00000006

Partition Coefficient

log Pow

3.20 (24°C) OECD 107

EEC method A8

Krohn (1992)

Report No.

14 700 0744

GLP

Klimisch score: 1

Disk 2

00000018


Biological Hazards: Class 6 Toxicity

Flufenacet is a new pesticidal active ingredient to New Zealand. In addition to acute

and chronic toxicity studies for this active ingredient (summarized in Table A2.5), the

applicant has provided acute toxicity studies on FOE 5043 400 SC & DFF 200 (a

formulation containing flufenacet and diflufenican) which are summarized in Table

A2.6. A summary of the studies taken into consideration in the determination of the

Acceptable Operator Exposure Level (AOEL) and Acceptable Daily Exposure (ADE)

is provided in Table A2.7.

Table A2.5: Summary of toxicity data on flufenacet and its metabolites. ACUTE TOXICITY

Acute oral toxicity Acute dermal toxicity Acute inhalation toxicity

TYPE OF STUDY: Acute oral

toxicity in rats.

SPECIES: Rat

STRAIN: Sprague-Dawley

NUMBER/SEX/GROUP: 5

TEST SUBSTANCE: FOE 5043

DOSE LEVELS: 0, 46, 138,

600, 1146 and 4560 mg/kg bw

for males and 0, 46, 325, 514,

664 and 1294 mg/kg bw for

females.

ENDPOINT: LD50

VALUE: 589 mg/kg females,

1617 mg/kg males

REMARKS: Deaths: 3/5 and

4/5 male rats died in the 1146

and 4560 mg/kg bw doses

respectively, within 5 days after

dosing.

2/5, 4/5 and 5/5 female rats died

in the 514, 664, and 1292 mg/kg

bw doses respectively within 24

hours of dosing.

Clinical signs: ataxia, laboured

breathing, decreased activity,

salivation, clear and red

lacrimation, urine stain, perianal

stain, red nasal stain, red lacrimal

stain, oral stain, red tinged fur on

forelimb.

Evidence of lacrimation,

salivation and nasal stain were

considered treatment-related

gross lesions in males found

dead.

Evidence of salivation, nasal

TYPE OF STUDY: Acute

dermal toxicity in rats.

SPECIES: Rat (Sprague-

Dawley)

ENDPOINT: LD50 (limit dose

test)

VALUE: >2000 mg/kg for

males and females

REMARKS: Clinical signs:

two females out of 5 showed

treatment-related urine stains

that persisted through days 2-5.

No treatment related clinical

signs in males. No deaths.

No treatment-related gross

lesions were observed at

necropsy for consistency.

REFERENCE SOURCE:

Sheets, L.P. (1992). Acute

Dermal Toxicity Study with

Technical Grade FOE 5043 in

Rats. Study Number 90-022-

FN (Unpublished report).

Miles Inc., Agriculture

Division Toxicology, 17745

South Metcalf, Stilwell,

Kansas 66085-9104.

GLP: Yes

TEST GUIDELINES:

US-EPA-FIFRA, Guideline

81-2, Nov 1984.

US-EPA-TSCA, 40 CFR

Section 798.1100, July 1988.

OECD Guideline 402,

February 1987.

Japan, 59 NohSan No 4200,

TYPE OF STUDY: Acute

inhalation toxicity in rats.

SPECIES: Rat (Sprague-

Dawley)

DOSE LEVELS: 3.74 mg/L

under nose-only exposure.

ENDPOINT: LC50

VALUE: 3.74 mg/L for males

and females

REMARKS: LC50 not

specifically identified by study

(no mortalities observed).

Clinical signs: ataxia, tilted

head, lacrimation, moribundity,

Nasal discharge, rales, urine

stain and rough coat.

These signs were first observed

shortly after exposure (Day 0)

and a complete recovery in both

sexes was observed by Day 4.

Gross pathology: no treatment-

related effects observed

following necropsy.

REFERENCE SOURCE:

Warren, D. L. (1990). Acute

Four-Hour Inhalation Toxicity

Study with Technical Grade

FOE 5043 in Rats. Study

Number 90-042-FV

(Unpublished report). Mobay

Corporation Health,

Environment, Safety and Plant

Management; Corporate

Toxicology Department, 17745

South Metcalf, Stilwell, KS

66085-9104.


stain, ocular stain, ventral/urine

stain, and reddened lungs were

considered treatment-related

gross lesions in females found

dead.

In the surviving animals there

was no effect on body weight or

body weight gain except for a

slight decrease in the surviving

top dose male. All clinical signs

of toxicity had resolved by day

14except for a red lacrimal stain

in one male animal (600 mg/kg

bw).

No gross lesions were observed

in animals that survived to Day

14 (termination).

GLP: Yes

TEST GUIDELINES:

US-EPA-FIFRA, 81-1, Nov 1984

US-EPA-TSCA, 40 CFR section

798.1175, July 1990

OECD Test Guideline 401, Feb

1987

Japan, 59 NohSan No 4200, Jan

1985.

REFERENCE SOURCE:

Astroff, A. B. and Fitzpatrick,

T. L. (1993). Acute Oral

Toxicity Study with Technical

Grade FOE 5043 in Rats.

(Supplemental Submission to

EPA MRID No. 43441104

(Supplement 1996). Bayer

Corporation, Agriculture

Division. Report No. 102699)

RELIABILITY (KLIMISCH

SCORE): 1

The Agency notes that the

applicant submitted other acute

oral toxicity data for FOE 543 in

rats and mice, but the above

study documents the lowest LD50

value (female rats). The other

values were:

Rats (male) 683 mg/kg

bw

Mice: 1331 and 1756

mg/kg bw for male and

females respectively.

the Agency also notes that

although 3/5 males died at 1146

mg/kg bw, the calculated LD50

was given as 1617 mg/kg bw due

January 1985.


SCORE): 1

The Agency notes that no

significant toxic effects seen

when tested at 2000 mg/kg bw

so no classification for 6.1

dermal applied.

GLP: Yes

TEST GUIDELINES:

US-EPA-FIFRA,

Guideline 81-3,

November 1984.

US-EPA-TSCA, 40 CFR

Section 798.1150, July 1988.

OECD Guidelines Section 4,

Guideline 403,

May 1981.

Japan, 59 NohSan No. 4200,

January 1985.

10


SCORE): 1

The Agency’s view is that while

no death occurred at the highest

concentration tested, significant

signs of toxicity occurred at this

concentration which is below

the highest cut off for 6.1D. The

Agency assigned the substance a

6.1E classification in accordance

with the ERMA, 2008 (p10-6)


to use of a modified probit

analysis program.

The Agency concluded the

substance classified as 6.1D

based on the female rat data.

Conclusion: Classification of

6.1D for acute oral toxicity

Conclusion: no classification

assigned

Conclusion: Classification for

6.1E for inhalation toxicity

IRRITATION

Eye irritation Skin irritation

TYPE OF STUDY: Eye irritation in rabbits.

SPECIES: Rabbits

STRAIN: New Zealand White

NO./GROUP: 6 males

TEST SUBSTANCE: FOE5043 (flufenacet)

approx 93%

APPLICATION: Instillation of 54 mg (1mL) into

the left eye of each animal.

RESULTS:

Mean Draize Scores:

Corneal opacity: 0/18 = 0

Iritis: 0/18 = 0

Conjunctival redness. 13/18 = 0.72

Conjunctival chemosis: 5/18 = 0.28

Conjunctival oedema not recorded; however

conjunctival discharge was recorded and reported

as 0/18 when calculated using the same method as

applied to the scoring of redness and chemosis.

REVERSIBILITY OF EFFECT: Conjunctival

redness was reported for 2/6 rabbits at 72 hours,

but all observed effects had reversed by 7 days.

GLP; Yes

TEST METHOD:

1) US-EPA-FIFRA, Pesticide Assessment

Guidelines, Subdivision F, Hazard

Evaluation: Human and Domestic Animals,

Guideline 81-4, November 1984.

2) US-EPA-TSCA, Health Effects Testing

Guidelines, 40 CFR Section 798.4500, July 1989.

3) OECD Guidelines for Testing of chemicals,

Section 4, Guideline 405,

February 1987.

4) Japan, Ministry of Agriculture, Forestry and

Fisheries, Guidance on Toxicology Study Data for

Application of Agricultural Chemical

Registration, 59 NohSan No. 4200, January 1985.

REFERENCE SOURCE:

Sheets, L.P. and Philips, S.D. (1992). Primary

Eye Irritation Study with Technical Grade FOE

5043 in Rabbits. Study Number 91-335-IU.

TYPE OF STUDY: Skin irritation in rabbits.

SPECIES: Rabbits

STRAIN: New Zealand White

NO./GROUP: 3 males

TEST SUBSTANCE: FOE5043 (flufenacet)

APPLICATION: Semi-occluded dermal

application of 0.5 g/animal.

RESULTS:

Mean Draize Score for erythema: 0/18 = 0

Mean Draize Score for oedema: 0/18 =0

REVERSIBILITY OF EFFECT: Not applicable

as no effects observed.

GLP: Yes

TEST METHOD:


Guidelines, Subdivision F, Hazard Evaluation:

Human and Domestic Animals, Guideline 81-5,

November 1984.



3) OECD Guidelines for Testing of Chemicals,

Section 4, Guideline 404, May 1981.


Fisheries, Guidance on Toxicology Study Data

for Application of Agricultural Chemical


REFERENCE SOURCE:

Sheets, L.P. and Philips, S.D. (1992). Primary

Dermal Irritation Study with Technical Grade

FOE 5043 in Rabbits. Study Number 91-325-IV.

Mobay Corporation Health, Environment, Safety

and Plant Management; Corporate Toxicology

Department, 17745 South Metcalf, Stilwell,

Kansas 66085-9104.

RELIABILITY (KLIMISCH SCORE): 1


Miles Inc., Agriculture Division, Toxicology;

17745 South Metcalf, Stilwell, Kansas 66085-

9104


Conclusion on classification: Flufenacet does

not trigger classification as an eye

irritant/corrosive.

Conclusion on classification: Flufenacet does

not trigger classification as a skin

irritant/corrosive.

SENSITIZATION

Respiratory sensitization Contact sensitization

No information provided. TYPE OF STUDY: Contact sensitization in

guinea pigs (Buehler test).

SPECIES: Guinea Pigs

STRAIN: Hsd Win:DH

NO./GROUP: 15 males in test group, 15 males

in non-induced control group, 5 males in

dichloronitrobenzene DNCB positive control

group and 5 males in DNCB non-induced control

group)

RESULTS: No erythema observed in any of the

FOE5043 test or non-induced control animals or

DNCB non-induced control animals.

Sensitization was observed in the DNCB positive

control group. Therefore, under the conditions of

this study, FOE 5043 does not cause dermal

sensitization.

TEST SUBSTANCE: FOE5043 (0.4g solid

flufenacet moistened with deionised water)

GLP: Yes

TEST METHOD: Buehler Topical Closed-Patch

Technique. This study was conducted in

accordance with:


Guidelines, Subdivision F, Hazard Evaluation:

Human and Domestic Animals, Guideline 81-6,

November 1984.



3) OECD Guidelines for Testing of Chemicals,

Section 4, Guideline 406, May 1981.


Fisheries, Guidance on Toxicology Study Data

for Application of Agricultural Chemical


REFERENCE SOURCE:

Sheets, L.P. and Philips, S.D. (1992). Dermal

Sensitization Study with Technical Grade FOE

5043 in Guinea Pigs. Miles Inc., Agriculture

Division; Toxicology. 17745 South Metcalf,

Stilwell, KS 66085-9104. Study Number 91-324-

JD


TYPE OF STUDY: Contact sensitization in

guinea pigs (Magnusson-Kligman Maximization


Method).

SPECIES: Guinea Pigs

STRAIN: Hsd Win:DH

DOSES:

Intradermal induction – 5%

Topical induction – 50%

Challenge – 50% and 25%

The test substance was formulated in sterile

physiological saline containing 2% v/v

Cremophor EL® to yield a suspension.

RESULTS: The 50% formulation caused “slight

localized” to “moderate confluent” redness and in

65% in 65% of the animals, whilst the 25% test

substance formulation caused “slight localized”

redness in 70% of the test animals. No skin

reaction was observed in the control animals.

Therefore, FOE 5043 exhibits skin sensitization

potential under the conditions of this test.

GLP: Yes

TEST SUBSTANCE: FOE5043

TEST METHOD: Magnusson-Kligman

Maximization Method carried out in accordance

with GLP. This study was conducted in

accordance with:

1) OECD Guideline for Testing of Chemicals;

Section 4: Health Effects, No. 406: “Skin

Sensitization”.

2) EC Guideline 92/69 (17th

Adaptation of the

Guideline 67/548/EEC): Classification,

Packaging and Labeling of Hazardous Materials,

“Skin Sensitisation”, Method B.6.

Pesticide Assessment Guidelines, Subdivision F,

Hazard Evaluation: Human Domestic Animals, §

81-6.

REFERENCE SOURCE:

Vohr, H.W. (1994). Study For The Skin

Sensitization Effect In Guinea Pigs

(Maximization Test of Nagnusson and Kligman).

Report No: 23560. BAYER AG, Fachbereich

Toxikologie, Friedrich-Ebert-Strasse 217-333 D-

42096 Wuppertal


The Agency notes that although the Buehler test

returned a negative result, FOE 5043 elicited skin

reactions in >30% of the animals in the

Magnusson-Kligmann test. This triggers a 6.5B

classification.

Conclusion on classification: No data provided,

therefore no classification assigned.

Conclusion on classification: Flufenacet

triggers a 6.5B classification.

MUTAGENICITY

In vitro studies


STUDY TYPE: Ames test (salmonella/microsome test)

CELL TYPE: Bacteria. Salmonella typhimurium strains TA 1535, TA 1537, TA 100 and TA 98.

TEST SUBSTANCE: Flufenacet (96.8%)

DOSE RATE: 0, 16,50, 158, 500, 1571, 5000 µg/plate with and without S9.

RESPONSE: negative

GLP: Yes

GUIDELINE: OECD Guideline 471

REFERENCE SOURCE:

Herbold, B. (1995). Salmonella/Microsome Test - Plate Incorporation And Preincubation Method.

Study No.: T 4054104. Bayer A G, Fachbereich Toxicology, Friedrich-Ebert-Strafie 217-333, D-

42096 Wuppertal, F.R.G.


STUDY TYPE: Mammalian chromosome aberration test

CELL TYPE: Mammalian. Chinese Hamster Ovary Cells


DOSE RATE: 0, 8, 40, 200 µg/mL (with and without S9mix) applied to the culture medium

RESPONSE: No statistically significant or biologically relevant increases of numbers of metaphases

with aberrations were detected 8, 24 or 30 hours after the beginning of the four hour treatment with the

test substance with and without S9 mix. Authors concluded substance is not clastogenic for

mammalian cells, with and without metabolic activation in vitro.

GLP: Yes

GUIDELINE: OECD Guideline 473

REFERENCE SOURCE:

Gahlmann, R. (1995). In Vitro Mammalian Chromosome Aberration Test With Chinese Hamster

Ovary (CHO) Cells. Study No.: T 2039172. Bayer A G, Fachbereich Toxicology, Friedrich-Ebert-

Strafie 217-333, D-42096 Wuppertal, F.R.G.


STUDY TYPE: Unscheduled DNA synthesis study

CELL TYPE: Rat Liver Primary Cells


DOSE RATE: 2.5, 5.0, 10.0, 20.0, 40.0, 60.0 and 80μg/ml

RESPONSE:

There was no evidence of unscheduled DNA synthesis following treatment with the test article. The

positive control article (2-Acetylaminofluorene) produced a clearly positive effect in the assay.

GUIDELINE:

EEC Directive 87/302/EEC: – Mutagenicity. DNA Damage and Repair - Unscheduled DNA


Synthesis -Mammalian Cells - In vitro

OECD Guidelines for Testing of Chemicals. "Genetic Toxicology: DNA Damage and

Repair/Unscheduled DNA Synthesis in Mammalian Cells in vitro". Adopted: 23 Oct 86, No.

482.

New and Revised Health Effects Test Guidelines October 1984. (U.S.) Environmental

Protection Agency, Washington DC (PB 84-233295); HG - DNA - Unsched Syn, October

1983

REFERENCE SOURCE:

Brendler-Schwaab, S. (1992). Test On Unscheduled DNA Synthesis In Rat Liver Primary Cell

Cultures In Vitro. Study No.: T 3039551. Bayer A G, Fachbereich Toxicology, Friedrich-Ebert-Strafie

217-333, D-42096 Wuppertal, F.R.G.


STUDY TYPE: V79-HGPRT assay in vitro.

CELL TYPE: Chinese hamster lung cells (V79)


DOSE RATE: 7.8, 15.6, 31.3, 62.5, 125, 180, 250 and 500 μg/ml with and without S9.

RESPONSE:

No significant dose-related or reproducible increase in mutant frequency above that of the negative

controls. In contrast, the positive controls ethylmethanesulfonate (without S-9 mix) and

dimethylbenzanthracene (with S-9 mix) produced a clearly mutagenic effect in the assay. The test

substance is thus considered to be nonmutagenic in the V79-HGPRT Forward Mutation Assay, both

with and without metabolic activation.

GUIDELINE:

EEC Directive 87/302/EEC – Mutagenicity. In vitro Mammalian Cell - Gene Mutation Test

OECD Guidelines for Testing of Chemicals. "Genetic Toxicology: In vitro Mammalian Cell

Gene Mutation Assay". Adopted: 4 April 84, No. 475.


Protection Agency, Washington DC (PB 84-233295). HG - Gene Muta - Somatic Cells,

October 1984.

Reference Source:

Brendler-Schwaab, S. (1994). Mutagenicity Study For The Detection Of Induced Forward Mutations

In The V79-Hgprt Assay In Vitro. Study No.: T 0044066. Bayer A G, Fachbereich Toxicology,

Friedrich-Ebert-Strafie 217-333, D-42096 Wuppertal, F.R.G.


In vivo studies

STUDY TYPE: Bone Marrow Micronucleus Test

SPECIES: Mice

STRAIN: Bor: NMRI (SPF Han)

NO/SEX/DOSE: 5 males and 5 females



DOSE RATE: Pilot study (intraperitoneal administration of 0, 250, 300, 350, 500 m/kg) identified 250

mg/kg as maximum tolerated dose (MTD). This was the dose used in the study

RESPONSE: No significant increase in the number of micronucleated normochromatic erythrocytes in

any of the groups. The ratio of polychromatic to normochromatic erythrocytes was not altered by

treatment.

GLP: Yes

GUIDELINE:

EEC Directive 84/449/EEC B.12. Other Effects – Mutagenicity: Micronucleus Test.

OECD Guidelines for Testing of Chemicals - "Genetic Toxicology: Micronucleus Test", No.

474.


Protection Agency Washington, DC (PB 84-233295). HG - Chromo - Micronuc, October

1983.

REFERENCE SOURCE:

Herbold, B. (1993). Micronucleus Test On The Mouse. Study No.: T 8044217. Bayer A G,

Fachbereich Toxicology, Friedrich-Ebert-Strafie 217-333, D-42096 Wuppertal, F.R.G.


Conclusion on classification: No classification for mutagenicity assigned to the substance

CARCINOGENICITY

See carcinogenicity studies reported under the ‘Target Organ Systemic Toxicity’ section of this table.

Conclusion on classification: The Agency considers that the data does not trigger any 6.7

classification.

REPRODUCTIVE/DEVELOPMENTAL TOXICITY

Developmental studies

STUDY TYPE: Developmental toxicity study

SPECIES: Rat

STRAIN: Charles River Crl:CD®(SD)BR rats

NUMBER/GROUP: 30 inseminated dams

DOSE: 0, 5, 25, 125 mg/kg/day (by gavage) once daily from days 6 to 15 of gestation (total of 10

consecutive doses)

TEST SUBSTANCE: FOE5043 (97.2%)

TEST GUIDELINE: U.S. EPA-FIFRA, Section 158.135, Guideline No. 83-3 (a)

REMARKS:

Authors note that for the dams, FOE 5043 promoted a significant reduction in mean body

weight gain, actual body weight gain (terminal body weight minus the weight of the intact

uterus) and overall maternal body weight gain during the study for the 125 mg/kg bw/day

group. There was also a statistically significant reduction in food consumption following the

initiation of treatment for the 125 mg/kg bw/day group. However, food consumption returned

to normal by the end of the study.

Histopathological evaluations of liver and thyroid from control and high-dose animals, as well

as those tissues which exhibited gross anatomical abnormalities, revealed no treatment-related

findings.


There were no adverse treatment-related effects on any measured maternal reproductive

parameter. Resorption/postimplantation losses were comparable with the control for the 3

treatment groups. The test article has no teratogenic potential at doses up to and including 125

mg/kg, as the incidence of malformations was comparable between the 3 treatment groups and

the control and well within historical control ranges.

The authors note that the only evidence of developmental toxicity was a decrease in fetal

weights and an increase in delayed ossification and/or increased variation in some skeletal

elements for the 125 mg/kg group. Lower doses did not promote any form of developmental

toxicity.

MATERNAL TOXICITY

NOAEL: 25 mg/kg bw/day

LOAEL: 125 mg/kg bw/day, due to reduced body weight gain and food consumption.

FOETAL TOXICITY


LOAEL: 125 mg/kg bw/day, due to reduced fetal weight, increase in delay ossification and/or an

increase in some skeletal variations.

REFERENCE SOURCE:

Stewart, P.D. (1997). A Developmental Toxicity Study With Orally Administered FOE 5043

Technical in the Rat. [Supplemental Submission to Bayer Report No. 106835 of the same title by

Clemens, G.R., Leeling, J.L., Rinke, M. and Hartnagel Jr, R.E. 1995]. Toxicology – Healthcare, Miles

Inc., P.O. Box 40, Elkhart, IN 46515.


The Agency considers that although treatment-related developmental effects were observed in foetuses

from the high dose group, these findings appear to be secondary to maternal toxicity and do not

support 6.8A/B classification.

STUDY TYPE: Developmental toxicity study in rabbits

TEST SUBSTANCE: FOE5043 (98.5%)

SPECIES: Rabbit.

STRAIN: New Zealand White Rabbits

NO/GROUP: 20 does

DOSE: 0, 5, 25, 125, 200 mg/kg bw/day, administered by oral gavage on days 6 to 18 of gestation.

TEST METHOD: U.S. EPA-FIFRA Section 158.135 Guideline No. 83-3

REMARKS:

Signs of maternal toxicity were observed at 125 and 200 mg/kg bw/day according to

researchers. The main effects related to stool changes, reduction in mean body weight gain

during the treatment interval, and an increase in histopathological changes of the liver.

Histopathological changes characterized by vacuolar change in hepatocytes in liver observed

at 25, 125 and 200 mg/kg bw/day, although no changes to absolute or relative liver weight

were seen. In most cases there were associated changes of hypertrophy and a ground-glass

appearance of the hepatocytic cytoplasm reflective of increased endoplasmic reticulum.

No adverse effects on maternal reproductive parameters were observed.

There was a significant decrease in fetal weight and a consequential increase in incidence of

delayed ossification of the skull for the 200 mg/kg bw/day group. There was an increase in

skeletal variations (e.g., supernumerary ribs) for the 125 and 200 mg/kg bw/day groups, some

of which occurred at incidences above historical control incidences.

There were no statistically significant increases in the foetal and/or litter incidences of

external, soft tissue, skeletal or combined malformations for any group.

There were no statistically significant changes in the sex ratio.


MATERNAL


LOAEL: 25 mg/kg/day due to histopathological changes (vacuolation in the hepatocytes) in the liver

DEVELOPMENTAL


LOAEL: 125 mg/kg bw/day due to an increase in skeletal variations (supernumerary ribs). (Reduced

fetal weight, increased skeletal ossification delays were seen at higher doses.)

REFERENCE SOURCE:

Clemens, G.R., Jasty, V., Grosso, D.S. and Hartnagel Jr., (1995). A developmental toxicity study

with orally administered FOE 5043 technical in the rabbit. Study report MTD9313. Toxicology –

Healthcare, Miles Inc., P.O. Box 40, Elkhart, IN 46515


The Agency considers that developmental effects seen in the foetuses may have been secondary to

maternal toxicity. Therefore, these findings do not support any 6.8 classification.

Reproductive studies

STUDY TYPE: Two-generation dietary reproduction study

SPECIES: Rats


NO/SEX/GROUP: 30

DOSE: 0, 20, 100, 500 ppm in diet. These dietary intakes are equivalent to 1.4, 7.4 and 37.4 mg/kg

bw/day for males (pre-mating). For females, these intakes are respectively: 1.5, 8.2 and 41.4 mg/kg

bw/day (pre-mating), 1.3, 6.9 and 36.2 mg/kg bw/day (during gestation) and 2.4, 13.3 and 68.7 mg/kg

bw/day during the first two weeks of lactation.

TEST METHOD:

P and F1 animals were fed test compound throughout the course of the study, starting at 7

weeks of age for P generation and from weaning for F1 generation.

During the study, adult animals were evaluated for the effect of the test compound on body

weight, food consumption, clinical signs, estrous cycling, mating, fertility, gestation length,

and litter size.

Offspring were evaluated for compound-related effects on sex ratio, pup viability, body

weight gain, and clinical signs.

Gross necropsy evaluations were performed on all adults and pups. Histopathological

evaluation of reproductive organs, the pituitary, liver, and gross lesions was performed on all

P and F1 adults.

TEST SUBSTANCE: FOE5043 (95.2 – 99% purity)

GUIDELINE: OECD No. 416. US EPA 40 CFR Section 798.4700

REMARKS:

No significant compound-related effects on gestation or lactation in P or F1 dams

No compound-related effects on estrous cycle, insemination length, mating index, fertility

index, gestation index, gestation length, birth index, number of implantation sites

Gross pathology – no compound-related effects in adults or pups

Organ weights – there was increased absolute and relative liver weight and morphologic

evidence of hepatocellular hypertrophy in P high-dose females and F1 mid- and high-dose

females.

Morphological evidence of hepatocellular hypertrophy was noted in the P and F1 high-dose

group males, in the F1 high-dose group females, and in the F1 mid-dose group males (clearing

of cytoplasm, granular texture of cytoplasm and/or enlargement of hepatocytes in

centrilobular region). Authors considered these compound-induced changes to be due to

induction of metabolic enzymes as a result of treatment with FOE 5043. Authors considered


this to be an adaptive change. Effects in liver are consistent with observations in general

toxicity (6.9) studies.

PARENTAL TOXICITY

NOAEL: 100ppm (equivalent to pre-mating doses of 7.4 mg/kg bw/day for males and 8.2 mg/kg

bw/day for females) based on the argument that the observed increase in liver weights and

hepatocellular hypertrophy is an adaptive rather than adverse response.

LOAEL: 500ppm (equivalent to pre-mating doses of 37.4 mg/kg bw/day for males and 41.4 mg/kg

bw/day for females)

REPRODUCTIVE EFFECTS

NOAEL: 500ppm (equivalent to pre-mating doses of 37.4 mg/kg bw/day for males and 41.4 mg/kg

bw/day for females)

LOAEL: Not determined as NOAEL was the highest test dose

REFERENCE SOURCE: Eigenberg, D A., 1995 (with a supplement, 1997). A two generation dietary

reproduction study in rats using technical grade FOE 5043. Bayer Corporation, Agriculture Division,

Toxicology, 17745 South Metcalf, Stilwell, KS, USA. Unpublished company report No 106891-2


The Agency notes that delayed ossification and an increase in minor variations were found as possibly

compound-related developmental effects in both the rat and rabbit studies, however, this occurred

above maternally toxic doses and no increase malformations were seen. The Agency considers the

findings do not support any 6.8 classification for developmental or reproductive toxicity.

Conclusion on classification: No classification

TARGET ORGAN SYSTEMIC TOXICITY

Sub-chronic toxicity – oral

TYPE OF STUDY: sub-chronic 90-day feeding study

SPECIES: Rat

STRAIN: CDF[F-344]/BR

NO.ANIMALS/SEX/GROUP: 15 animals/dose/sex

TEST SUBSTANCE: FOE5043 (Flufenacet) 94.8%

DOSE LEVELS: 0, 100, 400, 1600, 3000ppm equivalent to 0, 6.0, 24.3, 109.1 and 191.2 mg/kg bw/day

in males and 0, 7.2, 28.8, 127.2 and 224.5 mg/kg bw/day in females.

ROUTE: oral (dietary; in feed). Acetone/corn oil mixture used as vehicle

GLP: Yes

TEST GUIDELINES: OECD Guideline 408

REMARKS:

Decrease in body weight observed in 1,600 ppm females and 3,000 ppm males and females,

but these changes were less than 10%.

Authors considered that the toxicological response of the rat could be broadly categorized as

involving structural and/or functional alternations in liver, kidney, haematological

system/spleen, and thyroid-related endpoints.

Haematological changes observed were as follows:

o increased reticulocyte numbers at 1600-ppm (males and females);

o decreased erythrocyte count and hematocrit at 400 ppm (males) and 1600 and 3000

ppm (males and females);

o decreased hemoglobin at 100 ppm (males) and 400, 1600, and 3000 ppm (males and

females);

o increased platelet count at 3000 ppm (males and females); and


o Increased white blood cell count at 400- and 1600-ppm (males) and 3000-ppm (males

and females).

Clinical chemistry changes included:

o increased serum potassium concentration in 3000-ppm females;

o decreased serum glucose concentration in 400- and 1600-ppm females and 3000-ppm

males and females;

o increased serum uric acid concentration in 400-ppm females and 1600-and 3000-

ppm males and females;

o increased serum phosphate concentration in 3000-ppm males;

o increased serum cholesterol concentration in 1600- and 3000-ppm males and

females;

o increased total serum protein, albumin, and globulin concentrations in 3000-ppm

males;

o decreased serum triglyceride concentration in 400-, 1600-, and 3000-ppm males;

o increased serum γ-glutamyltransferase activity in 1600- and 3000-ppm females;

o decreased total serum thyroxine concentration in 100-ppm males and 400-, 1600-,

and 3000-ppm males and females; and

o Decreased total serum triiodothyronine concentration in 400-, 1600-, and 3000-ppm

males and increased total serum triiodothyronine concentration in 3000-ppm females.

Principal organ weight changes following exposure to FOE 5043 included:

o increased liver weight in 400, 1600, and 3000 ppm males and females;

o increased spleen weight in 3000-ppm.males; and

o Increased thyroid weight in 400, 1600 and 3000 ppm males and females.

Histopathological changes were:

o Liver: increased incidence of hepatocellular swelling, characterized by both

cytomegaly and karyomegaly in 400-, 1600-, and 3000-ppm males and females; and

increased incidence of individual liver cell degeneration or necrosis in 400-, 1600-,

and 3000-ppm males and females;

o Spleen: increased incidence and severity of brown granular pigment accumulation

within the red pulp in 400-, 1600-, and 3000-ppm males and females;

o Kidney: increased incidence of mild proximal tubule injury in 400-, 1600-, and

3000-ppm males and females.

Decreased total serum thyroxine was observed at 100ppm in males but this is not considered

to be biologically significant as most of the values for the test subjects are within the ranges

displayed by the control group. Effects at 400 ppm and above in both sexes appear to be

significant however.

The authors proposed a NOEL of 7.2mg /kg bw/day for the female rat at the lowest dose

tested of 100ppm. [A further 3-week study was carried out to examine the effect of the

substance on circulating thyroid hormone concentrations in the male rat at exposure levels

below 100ppm (see details of study below)].

LOAEL: 400ppm (equivalent to 24.3mg/kg bw/day for the male rat and 28.8mg/kg bw/day for the

female rat) based on cellular degeneration and necrosis, changes in haematological and other

parameters as discussed above.

NOAEL: 100ppm (equivalent to 6.0 mg/kg bw/day for the male rat and 7.2 mg/kg bw/day for the

female rat.

REFERENCE SOURCE: Christensen, W.R. and Wahle, B.S. (1995). Technical Grade FOE 5043:

Subchronic Toxicity Testing study in rats. Bayer Corporation, Agriculture Division, Toxicology, 17745

South Metcalf, Stilwell, KS, USA. Unpublished company report No 106857.


TYPE OF STUDY: 13-week Range-Finding Toxicity Study in the Mouse

SPECIES: Mouse

STRAIN: CD-1

NO.ANIMALS/SEX/GROUP: 15 animals/dose/sex

TEST SUBSTANCE: FOE5043 (Flufenacet) 94.8%


DOSE LEVELS: 0, 100, 400, 1600, or 4000 ppm

ROUTE: Dietary

GLP: Yes

TEST GUIDELINES: None given

REMARKS:

Declines in erythrocyte and platelet count, haemoglobin and haematocrit concentration were observed

in 4000-ppm males and females. Decrease in thyroid hormone (400-4000 ppm), alkaline phosphatase

(1600-4000 ppm), and aspartate transaminase (4000 ppm) activity at 13 weeks. alterations in absolute

and/or relative liver (400-4000 ppm), kidney (100-4000 ppm), ovary (4000 ppm) , and spleen (400-

4000 ppm) weight. Cytomegaly of the liver, pigmentation of the spleen, and thyroid hyperplasia in

400-4000-ppm males and females. A top dose of 400 ppm was thus selected at which to conduct

the follow-up oncogenicity testing study with FOE 5043 in the mouse.

REFERENCE SOURCE:

Christenson, W.R. and Wahle, B.S. (1995). Technical Grade FOE 5043: A 13-week Range-Finding

Toxicity Study in the Mouse. Bayer Corporation, Agriculture Division – Toxicology, 17745 South

Metcalf, Stilwell, KS 66085-9104.

RELIABILITY (KLIMISCH SCORE):

TYPE OF STUDY: 13 week subchronic feeding study in beagles

ROUTE: Oral (dietary).

TEST SUBSTANCE: FOE5043 (flufenacet) 94.8% (3/90); 93.8% (10/90)

SPECIES: Dogs

STRAIN: Beagle

NO.ANIMALS/SEX/GROUP: 4

DOSE LEVELS: 0, 50, 200, 800, 2400 ppm (equivalent to 0, 1.67, 7.20, 27.21 and 96.91 mg/kg

bw/day in males and 0, 1.70, 6.90, 28.00 and 93.23 mg/kg bw/day in females respectively.)

GLP: Yes

TEST GUIDELINES:

1) US-EPA-FIFRA, Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and

Domestic Animals, Guideline 82-1, November 1984;

2) OECD Guidelines for Testing of Chemicals, Section 4, Guideline 409, May 1981; and

3) Japan, Ministry of Agriculture, Forestry and Fisheries, Guidance on Toxicology Study Data for

Application of Agricultural Chemical Registration, 59 NohSan No. 4200, January 1985.

REMARKS:

Soft faeces and thin body condition were considered treatment-related clinical signs at the

2400 ppm level in both sexes.

Clinical chemistry changes included increased lactate dehydrogenase (LD) and alkaline

phosphatase (ALP) levels, and decreased alanine aminotransferase (ALT) and aspartate

aminotransferase (AST). LD was increased in male dogs at 2400 ppm and in females at 200,

800 and 2400 ppm. ALP was increased in males and females at 2400 ppm. ALT was

decreased in both sexes at 200, 800 and 2400 ppm. AST was decreased at all doses, but

researchers only considered this compound- related in both sexes at 800 and 2400 ppm

because the decrease at 200 ppm was less clear. There was also a decrease in albumin in males

at 200, 800 and 2400 ppm, and in females at 800 and 2400 ppm. Globulin levels were

considered increased in a compound-related manner in females only at 200, 800 and 2400

ppm.

The authors concluded that hepatic enzyme induction resulted in secondary thyroid organ

changes. A treatment related decrease in serum thyroxine (T4) was found in both sexes at

200, 800 and 2400 ppm. A decreased triiodothyronine (T3) was likely to be compound-related

in both sexes at 800 and 2400 ppm. This decline in both hormones, without corresponding

cholesterol and triglyceride increases, and without accompanying myxedema-like clinical

signs (signs of prolonged hypothyroidism), suggests to the Authors an extrathyroidal

mechanism due to increased hepatic clearance of thyroid hormones. [The Agency notes that


with the exception of the top dose females, no histopathology findings were seen in the

thyroid.]

The Authors claim calcium and glucose levels were decreased due to the metabolic effect of

the compound on the liver, and secondary to thyroid hormone loss. Serum glucose was

decreased in males at 800 and 2400 ppm, and females at 200, 800 and 2400 ppm. Calcium

was decreased in males at 2400 ppm, and in females at 800 and 2400 ppm.

Decreased red blood cell count (RBC), haemoglobin (Hgb), haematocrit (Hct), mean cell

volume (MCV), and mean cell haemoglobin concentration (MCHC) in both sexes at the 2400

ppm dose.

There were no urinalysis findings or gross pathology observations related to compound

administration.

There was a compound-related decrease in terminal body weights in the 2400 ppm males and

a similar l trend in females. Treatment-related organ weight increases were found in absolute

and relative liver weights in both sexes at 2400 ppm, and in the 800 ppm females.

The relative kidney weights were increased in the 2400 ppm males and in the 200, 800 and

2400 ppm females.

Principle histological findings consisted of:

a. Bone marrow: hyperplasia in 2400 ppm males and females,

b. Spleen: pigment in 200, 800 and 2400 ppm females and in 800 and 2400 ppm

males,

c. Kidney: hyperplasia of epithelial cells in 800 and 2400 ppm males and in 2400

ppm females, and cytoplasmic vacuolization in collecting tubules in 800 and 2400

ppm females,

d. Liver: Moderate diffuse hepatomegaly in 2400 ppm males and females, and

pigment in liver in 2400 ppm females,

e. Brain: Vacuolization of the cerebral cortex in 2400 ppm males and females;

f. Thyroid: Hypertrophy of thyroid follicular cells in 2400 ppm females.

Authors concluded that a clear NOAEL of 50 ppm was present, intermediate progression of

toxicity was represented at 200 and 800 ppm, and a maximum tolerated dose of 2400 ppm was

defined by this study.

LOAEL: 200ppm (7.2mg/kg bw/day for the male beagle and 6.9mg/kg bw/day for the female

beagle) based on increases in lactate dehydrogenase, alkaline phosphatase and globulin levels,

decreases in alanine aminotransferase, aspartate aminotransferase, albumin and serum thyroxine (T4).

NOAEL: 50 ppm for both sexes (1.67 mg/kg bw/day in the male beagle, 1.7 mg/kg bw/day in the

female beagle).

REFERENCE: Jones, R.D, and Lake S.G. 1995. (Addendum, 1997) FOE 5043: 13 week subchronic

feeding study in beagle dogs. Miles Inc [later: Bayer Corporation], Agriculture Division, Toxicology,

17745 South Metcalf, Stilwell, KS, USA. Unpublished company report No 106851-2.


TYPE OF STUDY: Chronic toxicity feeding study in the beagle dog [for one year]

ROUTE: Oral (dietary).

TEST SUBSTANCE: Technical grade FOE5043 (flufenacet)

SPECIES: Dog

STRAIN: Beagle


DOSE LEVELS: 0, 40, 800, 1600 ppm.(equivalent to 0, 1.29, 27.75, and 62.24 mg/kg bw/day for

males and 0, 1.14, 26.84, and 58.79 mg/kg bw/day for females). [The Agency notes the poorly spaced

dose intervals in this study which makes interpretation difficult. The report indicates that the doses

were selected based on findings of 13-week feeding study in beagles (doses in that study were 0, 50,

200, 800 and 2400 ppm)].

GLP: Yes

TEST GUIDELINES:

1) US-EPA-FIFRA, Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and

Domestic Animals, Guideline 83-1, November 1984;

2) US-EPA-TSCA, Health Effects Testing Guidelines, 40 CFR Section 798.3320, July 1988;

3) OECD Guidelines for Testing of Chemicals, Section 4, Guideline 452, May 1981;

4) Japan, Ministry of Agriculture, Forestry and Fisheries, Guidance on Toxicology Study Data for


Application of Agricultural Chemical Registration, 59 NohSan No. 4200, January 1985; and

5) US-FDA, Toxicological Principles for the Safety Assessment of Direct Food Additives and Color

Additives Used in Food, Appendix II Guidelines For Toxicological Testing, October 1982.

REMARKS:

There were no significant changes in food consumption or body weight during the study, but

at termination body weight decreases were found at 1,600 ppm (both sexes) and 800 ppm

(females) [The Agency notes the inconsistency regarding the fact that no significant weight

changes were observed in-life and yet significant decreases in terminal weights were

reported].

Clinical observation included head tilting at 1,600 ppm in both sexes.

No ophthalmologic abnormalities were found during in-life examinations (but see effect on

eyes reported at necropsy).

Authors considered the liver to be the primary target organ.

Neurological effects observed primarily the highest dose groups (1600 ppm, both sexes) just

prior to termination [The Agency notes the late investigation of these findings but observes

that histological findings in the nervous system were also seen]: (1) abnormal behaviour -

hypo-reactivity in two high dose animals, reduced reaction to movement and sound (1 animal)

and hyper-reactivity/ hypertonia; (2) postural abnormalities - deficits in wheel-barrowing,

hemi-walking, hemi-hopping, hemi-standing and proprioception (both sexes); (3) gait/body

position - deficits in stride width, being stiff legged and reluctant to walk (both sexes), with

stride width deficits in two mid-dose dogs (what sex) [Note: This is the only finding at 800

ppm.] Body position deficits in the high dose dogs consisted of wide stance, head tilt, being

flat footed and being unsteady; and (4) optic nystagmus/strabismus/ placement - abnormal

physiologic nystagmus.

The authors noted differences in organ weights in the two highest dose groups. The changes

were :

o an increase in relative heart weights (800 and 1,600 ppm in both sexes), an increase in

absolute heart weights (1,600 ppm in both sexes and 800 ppm males)

o an increase in relative kidney weights (800 and 1,600 ppm in both sexes) and increased

absolute kidney weights (1,600 ppm in both sexes and 800 ppm males)

o an increase in relative and absolute liver weights (800 and 1,600 ppm in both sexes)

o increased relative adrenal weights in 1,600 ppm females

o increased relative and absolute thyroid weights (1,600 ppm in both sexes)

Histopathology differences noted at necropsy that were compound-related occurred in the

liver, kidney, eye, brain, spinal column and sciatic nerve, and were limited to 800 and/or 1,600

ppm dose levels in both sexes. The principle observations were:

o Liver: slight hepatocytomegally in 1600 ppm males and in 800 and 1600 ppm females.

Slight hepatocyte vacuolization in 800 and 1600 ppm males and females

o Kidney: minimal to slight hyperplasia of the epithelium lining the renal pelvis in 800 and

1600 ppm male and female dose groups

o Eye: minimal to moderate vacuolization of the ciliary body epithelium and cystic

vacuolization of the peripheral optic retina in both sexes at 800 and 1600 ppm.

o Brain, spinal column and sciatic nerve: minimal to moderate axonopathy. Electron

microscopy identified enlarged myelin and/or non myelinated membrane lining around

the organelles (primarily mitichondria). Effects on the sciatic nerve were at 1,600 ppm

both sexes, whilst the brain and spinal cord effects were present in both sexes at 800 and

1,600 ppm.

The main clinical chemistrychanges that were considered compound related were: (1)

decreased glucose (800 and 1600 ppm, both sexes), (2) increased cholesterol (800 and 1600

ppm, both sexes), (3) decreased thyroxine and triiodothyronine (800 and 1600 ppm, both

sexes), (4) decreased alanine aminotransferase (800 and 1600 ppm, both sexes), increased

alkaline phosphatase (800 and 1600 ppm, both sexes), and (5) decreased albumin (800 ppm,

females; 800 and 1600 ppm, males).

Authors concluded NOEL was 40ppm with intermediate toxic effects at the two highest dose

groups.

LOAEL: 800ppm (27.75 mg/kg bw/day for the males and 26.82 mg/kg bw/day for the females). Based

on a combination of clinical chemistry (liver enzymes), organ weight and histopathology changes with

neurological symptoms at the top two doses. The brain and spinal cord effects were the most


significant findings at this level.

NOAEL: 40ppm (1.29 mg/kg bw/day for the male beagle, 1.14 mg/kg bw/day for the female beagle).

REFERENCE: RD Jones (1995)

RELIABILITY (KLIMISCH SCORE): 2 (reliable with restrictions)

The Agency review of this study noted that the ratio between dosage intervals were too high to enable

the accurate identification of the NOAEL and LOAEL in this study, particularly when the dose levels

are compared to those used in the subchronic study in dogs (above).

Chronic toxicity/carcinogenicity

TYPE OF STUDY: Chronic toxicity and Carcinogenicity study (2-year duration).

SPECIES: Rat

STRAIN: CDF[F-344]/BR

NO.ANIMALS/SEX/GROUP: 50 (with additional 20 in control and top dose group, and 10 in mid

dose group for 1 year interim sacrifice).

TEST SUBSTANCE: FOE5043 (flufenacet) 95.2-99% purity

DOSE LEVELS: 0, 25, 400, 800 ppm (equivalent to 0, 1.2, 19.3 and 39.0 mg/kg bw/day in males and

0, 1.5, 24.4 and 49.8 mg/kg bw/day in females respectively)

ROUTE: Oral (dietary)

GLP: Yes

TEST GUIDELINES: FIFRA Guideline No. 83-5 Combined Chronic Toxicity/Oncogenicity Studies

OECD Guideline No. 453 Combined Chronic Toxicity/Oncogenicity Studies

TSCA Guideline No. 798.3320 Combined Chronic Toxicity/Oncogenicity Studies

MAFF Guideline 59 NohSan No. 4200 Combined Chronic Toxicity/Oncogenicity Studies

REMARKS:

For the males, survival rates at termination were as follows: Control group – 70%; 25 ppm

group – 70%; 400 ppm group – 46%; 800 ppm group – 44%.

Female survival rates at termination were as follows: Control group – 72%; 25 ppm group –

70%; 400 ppm group – 50%; 800 ppm group – 50%.

There was an 8% decline in body weight gain in 400-ppm females while 10 and 17% declines

in body weight gain were recorded in 800-ppm males and females, respectively.

Findings at 400ppm dose level appear to be generally consistent with the findings of the 90-

day rat study:

o Haematology observations:

increased methaemoglobin content in 400 and 800 ppm males and females;

increased platelet count in 800 ppm males; and

increased white blood cell count in 400 ppm males and 800 ppm males and

females.

o Clinical chemistry observations:

increased serum cholesterol concentration in 400 and 800 ppm females

(changes observed from 95 days onwards);

increased total serum protein and globulin concentration in 800 ppm females

(from 95 days onwards);

decreased serum triglyceride concentration in 400 and 800 ppm males (from

95 days onwards);

increased serum calcium concentration in 800 ppm animals (from day 179

in males and day 368 onwards in females); and

increased serum γ-glutamyltransferase (GGT) activity in 400 and 800ppm

males at 12 month interim sacrifice and at termination, although statistical

significance was not reached at all time points for these dose levels.

o Organ weight observations:

weight changes in the heart (increase), liver (increase), spleen (increase),

and thyroid (increase) of 1-year 400 and 800-ppm males and females; and

weight changes in the brain (relative weight increase), heart (relative weight

increase), kidney (reduction), liver (increase), lung (increase), ovary

(reduction), spleen (increase), and thyroid (increase) of 2-year 400 and/or

800 ppm males and females. [The Agency notes the report refers to changes

in testis weight, but the Appendix tables do not identify this.]

o Histopathological observations:


Liver: increased incidence of hepatocytomegaly in 1- and 2-year 400 and

800 ppm males and females;

Liver: increased incidence of hepatic individual cell necrosis in 1-year

800ppm males and females and 2-year 800-ppm males;

Liver: increased incidence of hepatic biliary hyperplasia/fibrosis in 2-year

400 and 800 ppm males;

Liver: decreased incidence of hepatic tigroid basophilic foci/areas of

alteration in 2-year 400 ppm females and 2-year 800 ppm males and

females;

Eyes: exacerbation of the common background change of ocular sclera

mineralization in 1-year 800 ppm females and 2-year 400 and 800 ppm

males and females; and increased incidence of cataracts in 2-year 800-ppm

females;

Spleen: increased incidence of splenic pigmentation in 1-year 400 ppm

females and 1-year 800 ppm males and females;

Kidney: exacerbation of the common background change of renal pelvic

mineralization in 2-year 25, 400, and 800 ppm males and 2-year 400 and

800-ppm females;

Kidney: exacerbation of the common background change of renal pelvic

epithelial hyperplasia in 2-year 400 and 800 ppm males;

Uterus: increased incidence of uterine cystic endometrial hyperplasia in 2-

year 400- and 800-ppm females;

Lung: increased incidence of granulomatous pneumonia in 2-year 400 ppm

males

Upper Respiratory tract: and 2-year 800 ppm males and females; and

increased incidence of suppurative inflammation of the skull (nasal

turbinates, nasolacrimal duct, and/or middle ear) in 2-year 800 ppm males.

Authors concluded there was no evidence of a chemically-induced neoplastic response in any

tissue examined [The Agency concurs with this conclusion].

Chronic toxicity

LOAEL: 400 ppm (equivalent to 19.3 mg/kg bw/day in males and 24.4 mg/kg bw/day in females)

based primarily on increased incidence of methaemoglobin content, hepatic biliary hyperplasia/fibrosis,

ocular sclera mineralisation and renal pelvic epithelial hyperplasia in both sexes and endometrial

hyperplasia in females.

NOAEL: 25 ppm (equivalent to 1.2 mg/kg bw/day in males and 1.5 mg/kg bw/day in females)

Neoplasia

LOAEL: None established (no increase in tumours seen).

NOAEL 800 ppm (equivalent to 39.0 mg/kg bw/day and 49.8. mg/kg bw/day for male and female rats,

respectively) (the highest dose tested).

REFERENCE SOURCE: Christensen, W. R and Wahle B.S., 1995 (Addendum 1997). Technical

Grade FOE 5043: A combined chronic toxicity/oncogenicity toxicity testing study in the rat. Bayer

Corporation, Agriculture Division, Toxicology, 17745 South Metcalf, Stilwell, KS, USA. Unpublished

company report No 106859-1


TYPE OF STUDY: Oncogenicity study in mice over 20 months

SPECIES: Mice

STRAIN: CD 1



DOSE LEVELS: 0, 50, 200, 400 ppm in the diet, equivalent to 0, 7.4, 30.4 and 62.2 mg/kg bw/day in

males and 0, 9.4, 38.4 and 77.2 mg/kg bw/day in females.

ROUTE: Oral in diet

GLP: Yes

TEST GUIDELINES: OECD No 451. FIFRA No 83-2.


REMARKS:

Food consumption and body weight was unaffected in treated groups in comparison to controls in both

sexes and at all the treated dose levels.

There was no effect on survival in either sex.

Clinical observations: There was an increase in the incidence of opacity of the eye in both males and

females at 400 ppm. There was an increase in the incidence of paleness of the eye in both males and

females at 200 and 400 ppm.

There was an increase in blood methaemoglobin content in 200 and 400 ppm males and females.

There was no evidence of any treatment-related effect on organ weights in the study.

At necropsy there was an increase incidence of ocular cataracts in 50, 200 and 4000 ppm males and

females. The researchers suggest that a possible mechanism for producing the eye effects is related to

the raised methaemoglobin levels, which may be reflected in depletion of glutathione and subsequent

oxidative injury. [The Agency notes that this is at this stage only a hypothesis.]

There was no indication of a treatment-related increase in neoplasia at any site.

Chronic toxicity

LOAEL: 50 ppm, equivalent to 30.4 mg/kg bw/day in males and 38.42 mg/kg bw/day in females, based

on ocular cataracts in both males and females and other eye changes.

NOAEL: No NOAEL determined for chronic toxicity.

Neoplasia

LOAEL: None established (no increase in tumours seen).

NOAEL: 400 ppm equivalent to 62.2 mg/kg bw/day in males and 77.4 mg/kg bw/day in females (Note:

this was the highest dose)

REFERENCE SOURCE: Christensen W.R. and Wahle, B.S, 1995 (amendment 1996). Technical

Grade FOE 5043: An oncogenicity toxicity testing study in the mouse. Bayer Corporation, Agriculture

Division, Toxicology, 17745 South Metcalf, Stilwell, KS, USA. Unpublished company report No

106860-1


Further investigations – thyroid effects

TYPE OF STUDY: Supplementary study to investigate the compounds effects on the thyroid

SPECIES: rat

STRAIN: male Fischer rats [CDF (F-344)/B strain]

NO.ANIMALS/SEX/GROUP: 5 per dose group


DOSE LEVELS: 0, 25, 1,000, 3,000 ppm

ROUTE: oral (dietary)

TEST GUIDELINES: supplementary study - no guideline

REMARKS: 3 week study. Authors observed dose-related decline in T4 levels over three weeks; also

alterations on thyroid stimulating hormone as well as total, free and reverse serum T3 but these changes

were less consistent than the T4 changes. Authors conclude that the study supports the conclusion that

the changes in T4 levels (free and total serum levels) in the rat are the result of compound related

effects on the liver. The authors note increased liver size and weight with proliferation of the

endoplasmic reticulum.

REFERENCE SOURCE: Christenson & Wahle (1995) Extrathyroidally Mediated Changes in

Circulating Thyroid Hormone Concentrations in the Male Rat Following Administration of an

Experimental Oxyacetamide (FOE 5043)

RELIABILITY (KLIMISCH SCORE): 2 (supplementary study, not conducted to a guideline)

The Agency’s conclusion is that the thyroid changes in the rat are not relevant to the likely human

toxicological response to the compound.


Further investigations – neurotoxicity studies

TYPE OF STUDY: Further investigation to examine potential neurotoxic effects in the rat

SPECIES: rat

STRAIN: Fischer 344

NO.ANIMALS/SEX/GROUP: 12 females/dose group


DOSE LEVELS: 0, 25, 48 mg/kg

ROUTE: Oral by gavage (single dose)

GLP: Yes

TEST GUIDELINES: No guideline (supplemental study)

REMARKS:

Functional Observation Battery testing conducted at least 3 hours after dosing. No

compound-related effects observed at either dose.

NOEL: 48 mg/kg (female)

REFERENCE SOURCE: Sheets L. P. 1995 (Addendum 1998). An acute oral neurotoxicity screening

study with Technical Grade FOE 5043 in Fischer 344 rats. Bayer Corporation, Agriculture Division,

Toxicology, 17745 South Metcalf, Stilwell, KS, USA. Unpublished company report No 106897-1


Further investigations – neurotoxicity studies

TYPE OF STUDY: Further investigation to examine potential neurotoxic effects in the rat (sub

chronic, 13 week study)

SPECIES: Rat

STRAIN: Fischer 344



DOSE LEVELS: 0, 120, 600, 3000 ppm (for 13 weeks)

ROUTE: dietary administration

GLP: Yes

TEST GUIDELINES: No guideline (supplemental study)

REMARKS:

Clinical observations: mortality, body weight, food consumption, automated measurements of

activity (figure-eight maze), functional observational battery, quantitative

electroencephalography (qEEG), brain weight, and a gross necropsy. Skeletal muscle,

peripheral nerves, eyes (with optic nerves) and tissues from the central nervous system were

examined microscopically for lesions

No compound-related effects or clinical signs

Body weight and food consumption reduced for males and females in high treatment dose

group

Function Observation Battery (FOB) test: effects noted in males and females in high dose

group.

o FOB results for males: forelimb grip strength reduction, slightly uncoordinated

righting response.

o FOB results for females: reduced forelimb grip strength, decreased body temperature,

increased hind-limb foot-splay.

Evidence of cumulative neurotoxicity in high dose group from weeks 8 to 13, demonstrated

through effects on motor and locomotor activity

NOAEL for clinical signs: 3000ppm (219 mg/kg bw/day for male rat, 247 mg/kg bw/day female rat)

NOAEL for FOB: 600 ppm (38.1 mg/kg bw/day for male rat, 42.6 mg/kg bw/day female rat)

REFERENCE SOURCE: Sheets L.P. (1995) A Subchronic Dietary Neurotoxicity Screening Study

with Technical Grade Thiafluamide (FOE 5043) in Fischer 344 Rats. Bayer Corporation, Agriculture

Division, Toxicology, 17745 South Metcalf, Stilwell, KS, USA. Unpublished company report No 94-

46-72-YQ


Conclusion on classification:

The Agency considers that the short-term feeding studies indicate that the substance does effect the

liver, although over the short-term these effects do not appear to be of toxicological significance. The

2 year feeding study suggests, however, that longer term exposure to the substance may cause

irreversible changes in the liver such as hepatic biliary hyperplasia and increased individual cell

necrosis. The male rat appeared to be more sensitive to these effects over the long term, than the

female rat.


Compound related effects on thyroid hormones were reported in rats and beagles; however, the authors

have concluded that these are secondary to the compound’s effects on the liver. The Agency considers

that there is sufficient evidence to support this conclusion in the rat, although the mechanism that is

described as the pathway the for secondary thyroid effects in beagles is not correct. Nevertheless, the

Agency considers that the effect is unlikely to be relevant to humans.

Further investigative studies indicate neurotoxic effects in the rat. The NOAEL for these effects

appears to be higher than the NOAEL for the compound-related effects on the liver. In the dog,

neurotoxicity was also seen at high dose, and this was associated with histopathology findings in brain

optic nerve and sciatic nerve and these effects appeared to progress. Finally, the Agency notes that no

NOAEL value was established for the eye effects in mice in the oncogenicity study, but due to the

duration of this study (20 months) did not consider this supports a 6.9A classification.

The Agency considers that there is sufficient evidence of an effect on the liver in the rat and the beagle

to support the 6.9B classification. The LOAEL in the 90 day rat study (24.3 mg/kg bw/day) is below

the threshold for classification (ERMA, 2008, p17-9, Table 17-2), and is supported by the 2 year study

in rats. There is support for the classification in the dog studies from the 13 week study. (The Agency

does not consider the LOAEL in the chronic (1 year) study in dogs reliable). In addition, the substance

may have neurotoxic effects at doses higher than those required to elicit adverse effects on the liver.

The Agency concludes that the substance triggers the 6.9B classification.

Metabolism

TYPE OF STUDY: Metabolism study in rats

SPECIES: Rats


DOSE: For preliminary and low dose experiments animals received 1 mg/kg bw of the labeled FOE

5043.

GLP: Yes

TEST GUIDELINES: Researchers investigated the metabolism using the molecule with a label in

three separate positions: one on the fluorophenyl (fluorophenyl UL- 14

C) portion and and two involving

the thiadizole ring (thiodiazole 2-14

C and 5-14

C, respectively).

FOE 5043 was rapidly absorbed and metabolized. At all dose levels at least 91% of the administered

radioactivity was recovered in excreta or respired gases within 72 hours. Urinary excretion was the

major route of excretion at all doses tested, with smaller amounts excreted in faeces. A maximum of

7% of the administered dose was found in the tissue and residual carcass.

All unidentified residues in excreta were characterized as polar and being of low molecular weight.

REFERENCE SOURCE: Krolski et al, 1995. The metabolism of FOE 5043 in rats. Miles Inc.

[subsequently Bayer Corporation], Agriculture Division, Toxicology, 17745 South Metcalf, Stilwell,

KS, USA. Unpublished company report No 106665.


The Agency notes that the authors used Sprague-Dawley rats here and F344 for all but one of the

toxicological studies. This is not a preferred approach as metabolism can vary between strains;

however, this is considered not to have an impact on the overall toxicity assessment.

Repeat dermal toxicity

TYPE OF STUDY: 21 day dermal toxicity in the rat

SPECIES: Rat


NO.ANIMALS/SEX/GROUP: 8. (An additional 8 rats of each sex in the top and control groups were

included to assess recovery over 2 weeks.)

TEST SUBSTANCE: Technical grade FOE 5043

DOSE LEVELS: 0, 20, 150, or 1,000 mg/kg bw/day. The substance was applied as a solid softened

with tap water.

ROUTE: Dermal application to the shorn back of the animals.

GLP: Yes

TEST GUIDELINES: US EPA FIFRA 82-2. OECD No 411.


REMARKS: There were no compound-related clinical signs or mortality. Body weight gain and

terminal weights and food consumption were not affected by treatment.

Thyroxine (T4) and free thyroxine (FT4) were both significantly decreased at 1,0000 mg/kg bw in both

sexes and reductions in FT4 were seen in males at 150 mg/kg bw. Liver weights were significantly

increased in males treated with either 150 or 1,000 mg/kg bw/day, but no change was seen in females.

Centrilobular hepatocytomegaly was seen as the only histopathological change and was only seen in

females at 1,000 mg/kg bw/day.

The animals previously dosed at 1,000 mg/kg bw/day showed a complete recovery following 2 weeks

without treatment.

LOAEL: The researchers proposed the LOAEL was >1,000 mg/kg bw/day for both sexes.

NOAEL: The researchers proposed a NOAEL of 1,000 mg/kg bw/day for both sexes.

REFERENCE SOURCE: Warren D.L. and Zorbas, M.A. 1995. Repeat dose 21 day dermal toxicity

study with technical grade FOE 5043 in rats. Bayer Corporation, Agriculture Division, Toxicology,

17745 South Metcalf, Stilwell, KS, USA. Unpublished company report No 93-112-SZ


The Agency notes that while the researchers propose there were no adverse effects, they proposed the

no observed effect level (NOEL) was 20 mg/kg bw for males and 150 mg/kg bw/day for females,

giving a lowest observed effect level (LOEL) of 150 mg/kg bw/day in males and 1,000 mg/kg bw/day

in females. The cut off for 6.9B by the dermal route is a LOAEL ≤200 mg/kg bw/day (although this is

for a 90 day rather than a 28 day study).

In conclusions, the Agency does not consider that these data demonstrate toxic effects from repeat

dermal exposure which justify classification for 6.9 (dermal). The Agency notes that while the liver

weights were increased in males histological changes were only seen in females and these were

reversible and were not associated with liver enzyme changes. With respect to the disturbance in the

thyroid hormone levels the Agency does not consider these to be of biological importance as there were

no treatment-related effects on T3, TSH or thyroid pathology.

Additional studies: Toxicity of Thiadone (a metabolite)

SPECIES: Rat

STRAIN: Sprague Dawley

NO/SEX/DOSE: 5

TEST SUBSTANCE: FOE 6457 (thiadone, a metabolite of FOE 5043)

ENDPOINT: LD50

VALUE: <1,650 mg/kg (males) and < 600 mg/kg (females)

REMARKS: The substance was administered by gavage at 1,650 mg/kg bw in the male group and 600

mg/kg bw in the female group. These doses were selected based on the proposed LD50 values for the

parent compound. All animals died within 10 minutes of dosing.

The only clinical sign seen was tremors in one female animal prior to death.

The only gross finding at necropsy was white mucosa of the glandular stomach which extended to the

duodenum in male rats.

The metabolite appears more toxic than the parent compound.

GLP: Yes

TEST GUIDELINES: OECD, No 401. US EPA FIFRA Guideline 81-1.

REFERENCE SOURCE: Zorbas, M. A. and Phillips, S,D., 1993. Acute toxicity of FOE 6457

(thiadone, a metabolite of FOE 5043) in rats. Miles Inc. [subsequently Bayer Corporation], Agriculture

Division, Toxicology, 17745 South Metcalf, Stilwell, KS, USA. Unpublished company report No

930012-TC.


The Agency notes that though the metabolite appears more toxic than the parent compound, no

classification of the substance is required, since it is a metabolite.


Table A2.6: Summary of toxicity data on FOE 5043 400 SC & DFF 200 (a

formulation containing flufenacet and diflufenican). ACUTE TOXICITY

Acute oral toxicity Acute dermal toxicity Acute inhalation toxicity

SPECIES: Rat

STRAIN: Wistar Hsd Cpb: WU

(SPF)


400 SC & DFF 200

DOSE LEVELS: 3 females at

2000 mg/kg bw, 3 females and 3

males at 500 mg/kg bw.

ENDPOINT: LD50 (limit dose

test)

VALUE: >500 <2,000 mg/kg bw

REMARKS: 2 groups of 3

female rats were tested at doses

of 500 and 2,000 mg/kg bw. 1

group of 3 male rats was tested at

500 mg/kg.

Clinical observations:

3/3 of the female animals dosed

at 2000 mg/kg bw died between 2

and 5 hours after dosing.

Summary noted that at 500

mg/kg gait was uncoordinated

and breathing laboured in both

sexes. Additionally, in males

motility was decreased, and in

females gait high legged.

At 2000 mg/kg in females

motility and reactivity were

decreased, gait uncoordinated

and spastic, position abdominal,

breathing laboured, and in one

female atony and in one

increased salivation were

observed. The signs observed

started 45 minutes after

administration and lasted up to

Day 4.

Body weight and body weight

gain of male rats were not

affected by treatment. The gross

pathology investigations

performed at the end of the post-

treatment observation period did

not afford any treatment-related

findings.

At necropsy the female animals

SPECIES: Rats

STRAIN: Wistar Hsd Cpb:

WU (SPF)

NO/SEX/DOSE: 5

TEST SUBSTANCE: FOE

5043 400 SC & DFF 200

ENDPOINT: LD50

VALUE: >4,000 mg/kg bw

REMARKS: Study tested

males and females at 4,000

mg/kg bw.

Clinical observations: At 4000

mg/kg in two males and two

females gait was

uncoordinated on Day 2. It

was claimed by researchers

this was possibly due to the

occlusive dressing.

Locally, the treatment area had

a yellowish discoloration. The

discoloration started on Day 2

and lasted up to Day 15 (the

end of the study). Body

weight and body weight gain

of males were not affected by

treatment. A slight, transient

decrease in body weight was

observed on Day 8 of the study

in one female, the study

authors considered this to be

probably caused by the

occlusive dressing. The body

weight reduction was

reversible by the end of the

post-treatment period. The

gross pathology investigations

performed at the end of the

post-treatment observation

period did not afford any

treatment-related findings. In

one male (animal no. 8) a

diminution of both testes was

observed.

GLP: Yes

TEST GUIDELINE: OECD

No. 402

REFERENCE SOURCE: Dr F

Krötlinger, F., 2002, “Study

for acute dermal toxicity in

rats” Study number T4071312.

SPECIES: Rats

STRAIN: Wistar Hsd Cpb: WU

(SPF)

NO/SEX/DOSE: 5

TEST SUBSTANCE: FOE

5043 400 SC & DFF 200.

ENDPOINT: LC50

DOSE CONCENTRATION:

2,078 mg/m3 air (2.078 mg/L) as

a nose only exposure for 4

hours.

The mass mean aerodynamic

diameter (MMAD) was < 4 µm

(MMAD 3.58 µm, geometric

standard deviation approx.

2.14)

VALUE: NOAEL and LC50

> 2,078 mg/m3 air (> 2.078

mg/L)

REMARKS: Clinical

observations: Exposure to the

maximum technically attainable

concentration of the formulation

as a mist did not result in any

mortality. The only clinical sign

was hypothermia. Mean rectal

temperature of 33.0°C vs 38.2°C

in males and 34.6° C vs 38.3° C

in females. These temperatures

were taken immediately after

cessation of exposures (within

approximately ½ hour).

Necropsy findings were

unobtrusive. In summary, the

test substance (liquid aerosol)

proved to have essentially no

acute inhalation toxicity to rats.

GLP: Yes

TEST GUIDELINE: OECD No.

403

REFERENCE SOURCE:

Pauluhn, J, 2002. “Study on

acute inhalation toxicity in rats

according to OECD No. 403.”

Study No T7071306. Bayer AG

PH PD T Toxicology Friedrich-

Ebert Str. 217–333. D-42096

Wuppertal.


that died had pale discolouration

of the liver and spleen and

slightly collapsed lungs with

spotted dark red discolouration.

GLP: Yes

TEST GUIDELINE: OECD

Guideline No 423. 67/548/EEC

B1. US EPA OPPTS 870.1100.

REFERENCE SOURCE:

Krötlinger, F., 2002, “Study for

acute oral toxicity in rats.” Study

number T5071313. Bayer AG

Toxicology Friedrich-Ebert Str.

217–333. D-42096 Wuppertal.


SCORE): 2

The Agency notes that the study

used both male and female rats,

but no explanation of this was

given. (No evidence was

presented that males were more

sensitive than females.)

[Guidelines assume that females

are more sensitive.] Also, there

was no justification given for the

use of these doses levels.

[OECD Guideline No 23,

following 2-3 deaths at 2000

mg/kg bw would then test the

substance at 300 mg/kg bw.]

Since 3/3 female animals died

after dosing with 2000 mg/kg bw,

the LD50 is clearly <2000 mg/kg

bw, so the classification is 6.1D.

Bayer AG Toxicology

Friedrich-Ebert Str. 217–333.

D-42096 Wuppertal.


SCORE): 2

The Agency notes that clinical

signs were reversible by the

end of the study with the

exception of the finding of

discolouration at site of

application, which was not

considered a toxicologically

significant finding. Testicular

abnormalities in a single male

were considered a chance

finding not related to

treatment.


SCORE): 1

The Agency assigned no

classification on the basis that

the highest achievable

concentration as a mist was not

associated with deaths or

significant toxicity. Although

hypothermia was observed, this

is not considered significant

enough to trigger classification.

Conclusion: 6.1D classification

assigned

Conclusion: No classification

is assigned

Conclusion: No classification is

assigned

IRRITATION

Eye irritation Skin irritation

TEST SUBSTANCE: Flufenacet: 406.52 g/l

Diflufenican: 205.76 g/l

TEST METHOD: EC guideline B.5. and OECD

No 405

ANIMALS: 3 male Himalayan rabbits

APPLICATION: single instillation of 0.1 mL into

the conjunctival sack of the right eye of each

animal.

RESULTS:

One animal showed conjunctival redness one hour

after application (score of 1), but this was not

observed in at subsequent time periods.

TEST SUBSTANCE: Flufenacet: 406.52 g/l

Diflufenican: 205.76 g/l

TEST METHOD: EC guideline B.4.

OECD No. 404

ANIMALS: 3 male Himalayan rabbits

APPLICATION: acute skin irritation, Patch-Test,

in rabbits, semi-occlusive, 0.5mL/animal.

RESULTS:

Mean Draize Score for erythema: 0

Mean Draize Score for oedema: 0

REVERSIBILITY OF EFFECT: Not applicable


Mean Draize Scores (at 24, 48 and 72 hours) were:

Corneal opacity: 0/9 = 0

Iritis: 0/9 = 0.

Conjunctival redness. 0/9 = 0

Conjunctival oedema: 0/9 = 0

REVERSIBILITY OF EFFECT: Not applicable as

no effects observed.

REFERENCE: Dr PJ Leuschner (2001)


as no effects observed.

REFERENCE: Dr PJ Leuschner (2001)


Conclusion on classification: The formulation

does not trigger classification as an eye

irritant/corrosive.

Conclusion on classification: the formulation

does not trigger classification as a skin

irritant/corrosive.

SENSITIZATION

Respiratory sensitization Contact sensitization

No information available.

TEST SUBSTANCE: FOE 5043 (flufenacet) :

409.02 g/l; DFF (diflufenican): 207.00 g/l

TEST METHOD: Guinea pig maximization test

according to Magnusson & Kligman.

OECD Guideline No. 406, EC Guideline

96/54/EC, Health Effects Test Guidelines,

OPPTS 870.2600.

ANIMALS: 30 female guinea pigs (20 in test

group, 10 in control group).

STRAIN: Hsd Poc:DH

DOSES:

Intradermal induction: 2.5% (= 10 mg test

item/animal)

Topical induction: 100% (= 500 mg test

item/animal)

1st challenge: 100% (= 500 mg test item/animal)

2nd

challenge: 50% (= 250 mg test item/animal)

RESULTS: After the intra-dermal induction the

animals in the control group and in the test item

group showed strong effects including

encrustation at the injection sites of the first

induction.

The 1st challenge with the 100% test item

concentration led to skin effects (grade 1- 3) in

20 of 20 animals (100%) in the test item group

and in 6 animals (60%) of the control group

(grade 1). The 2nd challenge with the 50% test

item formulation led to skin effects (grade 1-

3) in 18 of 20 animals (90%) in the test item

group and to no skin effects in the control group.

The authors concluded that test formulation

exhibited skin-sensitisation potential.

REFERENCE: Dr HW Vohr (2002)



The Agency noted that in the Magnusson &

Kligman test the proportion of test animals

showing skin reactions following the challenge

dose was > 30% and is therefore sufficient to

trigger classification as a 6.5B contact sensitiser.

The effects observed following the second

challenge ranged from slight localised redness to

severe redness and swelling with some test

subjects’ skin squamous in places and showing

hardness and/or encrustation.

Conclusion on classification: No classification. Conclusion on classification: The substance

triggers classification as a contact sensitizer

(6.5B).

Table A2.7 Summary of toxicity studies considered in determining the

Acceptable Operator Exposure Level (AOEL) and Acceptable Daily Exposure

(ADE) for flufenacet

Study NOEL LOAEL Critical effect Developmental study in rats. Maternal

25 mg/kg bw/day

Developmental

25 mg/kg bw/day

Maternal

125 mg/kg bw/day

Developmental

125 mg/kg bw/day

Reduced maternal body

weight gain and food

consumption.

Reduced fetal weight,

increase in delayed

ossification and/or in

some skeletal variations.

Developmental study in

rabbits.

Maternal

5 mg/kg bw/day

Developmental

25 mg/kg bw/day

Maternal

25 mg/kg bw/day

Developmental

125 mg/kg bw/day

Histopathological

changes (vacuolation in

the hepatocytes) in the

liver.

Due to increases in

skeletal variations

(supernumary ribs).

Reduced fetal weight and

ossification delays at

higher dose levels.

2 generation reproductive

toxicity in rats

Parental

100 ppm

(7.4 mg/kg bw/day

males and 8.2

mg/kg bw/day

females)

Reproductive

500 ppm

(37.4 mg/kg

Parental

500 ppm

(37.4 mg/kg

bw/day males and

41.4 mg/kg bw/day

females)

Reproductive

>500 ppm

(37.4 mg/kg

Increased liver weights

and hepatocellular

hypertrophy.

No reproductive or

developmental effects


bw/day males and

41.4 mg/kg bw/day

females)

bw/day males and

41.4 mg/kg bw/day

females)

seen.

90 day study in rats 100 ppm

(6.0 mg/kg bw/day

males and 7.2

mg/kg bw/day

females)

400 ppm

(24.3 mg/kg

bw/day males and

28.8 mg/kg bw/day

females)

Increased liver weight

and associated

histological changes

(hypertrophy and

hepatocellular necrosis),

also changes in clinical

chemistry parameters

and histological changes

pigmentation in the

spleen and proximal

tubule injury in the

kidney.

13 week study in dogs 50 ppm

(1.67 mg/kg

bw/day males and

1.7 mg/kg bw/day

females)

200 ppm

(7.2 mg/kg

bw/day males and

6.9 mg/kg bw/day

females)

Effects on lactate

dehydrogenase,

alkaline phosphatase,

globulin, alanine

aminotransferase,

aspartate

aminotransferase,

albumin and serum

thyroxine.

Chronic study in dogs (1 year) 40 ppm

(1.29 mg/kg

bw/day males and

1.14 mg/kg bw/day

females)

800 ppm

(1.29 mg/kg

bw/day males and

1.14 mg/kg bw/day

females)

Clinical chemistry (liver

enzymes) with

neurological symptoms

at the top dose.

2 year rat chronic

toxicity/carcinogenicity

study

Chronic toxicity

25 ppm

(1.2 mg/kg

bw/day males and

1.5 mg/kg bw/day

females)

Neoplastic

800 ppm

(39.0 mg/kg

bw/day males and

49.8 mg/kg

bw/day females)

Chronic toxicity

400 ppm

(19.3 mg/kg

bw/day males and

24.4 mg/kg

bw/day females)

Neoplastic

>800 ppm

(>39.0 mg/kg

bw/day males and

>49.8 mg/kg

bw/day females).

Increased

methaemoglobin

content, hepatic biliary

hyperplasia/fibrosis,

ocular sclera

mineralisation, renal

pelvic epithelial

hyperplasia in both

sexes, and endometrial

hyperplasia in females

No increase in

neoplasia seen.

20 month chronic

carcinogenicity study in mice

Chronic toxicity

No NOAEL

established for

chronic toxicity in

this study. (The

lowest dose was 50

ppm, equivalent to

7.4 and 9.4 mg/kg

bw/day in males

and females

respectively.)

Neoplastic

Chronic toxicity

50 ppm

(30.4 mg/kg

bw/day males and

38.4 mg/kg bw/day

females)

Neoplastic

Ocular cataracts in both

males and females and

other eye changes.


400 ppm

(62.2 mg/kg

bw/day males and

77.4 mg/kg bw/day

females)

>400 ppm

(>62.2 mg/kg

bw/day males and

>77.4 mg/kg

bw/day females)

No neoplasia seen.

Acceptable Operator Exposure Level (AOEL)

The NOAEL of 1.67 mg/kg bw/day identified in the male beagle (13 week sub-chronic study) was

selected for derivation of the AOEL and an uncertainty factor (UF) of 100 applied (10 for interspecies

extrapolation, 10 for intraspecies uncertainty). No correction for the percentage of absorption in the

study which is consistent with the rapid absorption of the compound. The calculation (rounding to two

significant figures) gives:

AOEL = {NOAEL x absorption fraction}/UF = {1.67x 1.0}/100

AOEL = 0.017 mg/kg bw/day.

Acceptable Daily Exposure (ADE)

The Agency notes that an ADI (0.005 mg/kg bw/day) has been set by the EFSA for flufenacet. The

EFSA have established this ADI based on their LOAEL of 1.2 mg/kg bw/day established in the two-

year rat study (increased incidence of renal pelvic mineralisation was identified as the critical effect).

A uncertainty factor of 250 was applied in determining the ADI.

The UF of 250 is higher than usual as it takes into account that a LOAEL has been used a no NOAEL

was established in the study. The uncertainty factor consisted of 10 for interspecies extrapolation, 10

for intraspecies uncertainty and 2.5 due to the use of an LOAEL rather than a NOAEL.

The Agency notes that in its review of the data a NOAEL was established, as the Agency did not

consider the renal effects to be of sufficient toxicological significance at this 1.2 mg/kg bw/day dose

level. Therefore, the Agency did not use an additional 2.5 uncertain factor to account for the use of a

LOAEL in place of a NOAEL. The Agency’s calculation is:

ADE = NOAEL/LOAEL/{Uncertain factors} = 1.2/100 = 0.012 mg/kg bw/day

Rounding gives: ADE = 0.012 mg/kg bw/day.

[The Agency also notes that the US EPA (US EPA, 1998) established a chronic reference dose of

0.0004 mg/kg bw/day. The US EPA also considered the value was a LOAEL, but used a factor of 3 to

take into account the use of the LOAEL in place of a NOAEL (so their uncertainty factor was 300).]

The Agency has agreed with the New Zealand Food Safety Authority that we will set an acute

reference dose (ARfD), for new active ingredients. In the case of flufenacet the Agency notes that the

EU has proposed a value of 0.017 mg/kg bw/day which is based on the same calculation as the AOEL

(above). The Agency has proposed that this value is proposed for flufenacet in New Zealand.


Class 9 Ecotoxicity and environmental fate

Sub-class 9.1 Aquatic ecotoxicity, fate and degradation Classification under this sub-class requires consideration of the acute and chronic

aquatic toxicity of the substance and the bioaccumulative and persistence properties

of the components of the substance.

Aquatic fate and degradation of flufenacet and its metabolites

Information on aquatic fate and degradation is summarised in Table A2.7.

Table A2.7: Summary of aquatic fate and degradation of flufenacet (FOE 5043)

and its metabolites.

Study type Test results Test method

[reference number] Flufenacet (FOE 5043) Metabolites Abiotic degradation

Hydrolysis

Sterile Aqueous Buffer

pH 5: Stable (25°C)

pH 7: Stable

pH 9: Stable

Zeng and Wood (1992)

EPA 161-1 Hydrolysis

Report No.

102623

GLP

Klimisch score: 1

Disk 2

00000019

Photolysis Sterile Aqueous Buffer

pH 5 (25°C)

GLP

Stable

DT50:

3203 days

(irradiated samples)

DT50:

3237 days

(dark control samples)

Non-GLP (25°C)

Pond water 1 (Howe, IN)

DT50: 433 days

Pond water 2 (Stillwell, KS)

DT50: 1386 days

Pure water + 15 ppm humic

material

(natural photosensitizer)

DT50: 433 days

Pure water + 50 ppm KNO3

(generates hydroxyl radicals)

DT50: 95 days

DT50: 130 - > 365 days

The results of the model

studies indicate that direct

photodegradation in water

contributes to the overall

elimination of FOE5043 to a

low extent only.

Kasper and Shadrick

(1995)

EPA 161-2 Photolysis

Report No.

106246

GLP

Klimisch score: 1

Disk 2

00000020

Hellpointner and Schild

(1993)

ECETOC –method in

polychromatic light

Report No.

M 112 0566 - 1

GLP

Klimisch score: 1

Disk 2



[reference number] Flufenacet (FOE 5043) Metabolites 00000021

Biodegradation (laboratory)

Aerobic

(water and

sediment

systems)

Rate 0.750 kg/ha

Duration 157 days

Temperature: 20°C

System I

Water – Lawrence KS

(pH 7.5)

Silty clay loam

(pH 7.9, OC 0.7%)

DT50 (water): 61.7 days

DT50 (total water/sediment):

84.6 days


284.5 days

System II

Water – Stilwell KS

(pH 7.5)

Silty clay loam

(pH 7.8, OC 1.4%)

DT50 (water): 47 days


78.1 days


260.5 days

Bound residues increased

steadily with each successive

sampling interval. For the

157 - day sampling interval

28.5%, and 46.4% of the

applied radioactivity was

tightly bound to the sediment

in System I, and System II,

respectively.

Kelley et al. (1995)

BBA Guideline Part IV,

5-1

Report No.

106928

GLP

Klimisch score: 1

Disk 5

00000151

Anaerobic Pond water/Sandy loam

(pH 6.2 OM 0.6%)

Temperature: 21°C

DT50: 447 days*

Most abundant metabolite,

thiadone (16%)*

*Calculated from 0 to 99

days as anaerobic conditions

were not maintained for the

study duration (388 days

post-treatment).

Pangilinan and Smith

(1995)

EPA 162-3

Report No.

106440

GLP

Klimisch score: 2*

Disk 5

00000150

Bioaccumulation

Bluegill

Lepomis

macrochirus

Uptake rate constant (k1):

165 ± 23

Depuration Rate Constant

(k2):

Gagliano (1994)

FIFRA Guideline 72-6

FIFRA Guideline 165-4

Report No. 106760

GLP



[reference number] Flufenacet (FOE 5043) Metabolites 2.3 ± 0.3

Time to 50% Clearance:

0.30 ± 0.04 days

Steady State BCF:

71.4 ± 1

Time to 90% of BCF:

0.99 ± 0.13 days

Radioactive residues from

sunfish, exposed to [14C]FOE

5043.

Rate of 100 µg/L

Duration: 21 and 28 days

Total radioactive residues

(Fillet)

21 days: 1.79 ppm

28 days: 1.76 ppm

Total radioactive residues

(Viscera)

21 days: 10.97 ppm

28 days: 10.22 ppm

Major metabolite

cysteine conjugate of 4'-

fluoro-N-isopropyl

acetanilide

Fillet: 37%

Viscera: > 50%

(total radioactivity)

Mercapturic acid conjugate

Fillet: 24%

Viscera: 16%


FOE 5043

Fillet: 4.7%

Viscera: 17.8%


Glucuronide conjugate of

hydroxylated FOE 5043

Viscera: 5%


Minor metabolites

glutathione conjugate of 4'-

fluoro-N-isopropyl

acetanilide and the sulfoxides

of both the cysteine and

mercapturic acid conjugates.

Klimisch score: 1

Disk 5

00000170

Leimkuehler and Moore

(1994)

EPA 165-4

Report No. 106577

GLP

Klimisch score: 1

Disk 5

00000171


Conclusion

Flufenacet is not considered bioaccumulative based on the results of the study in fish

(BCF = 71.4) and is considered not rapidly degradable.

Aquatic toxicity

The toxicity of flufenacet and Firebird to aquatic organisms is summarized in Tables

A2.8 and A2.8A.

Table A2.8: Summary of aquatic toxicity data for flufenacet and its metabolites.

Test species

Test type

&

duration

Test resultsa, b

Test methodc

[reference number] Flufenacet

(FOE 5043)

Metabolites

Fish

Rainbow trout

Oncorhynchus

mykiss

96 h Static

96 h Static

96 h Static

LC50

5.84 mg/L

95% CI:

3.84 – 7.14 mg/L

[measured] > 80% of

[nominal]

FOE 5043-Sulfonic

acid

LC50

> 86.7 mg/L

[Lowest lethal]

> 86.7 mg/L

Limit test

[measured] > 80% of

[nominal]

Thiadone

LC50

9.1 mg/L

95% CI:

5.0 – 10.3 mg/L

[measured] > 80% of

[nominal]

Bowers and Frank

(1995)

FIFRA 72-1

Report No. 106673

GLP

Klimisch score: 1

Disk 5

00000162

Dorgerloh (1992)

OECD 203

Report No. 95031

GLP

Klimisch score: 1

Disk 5

00000144

Bowers and Lam

(1998)

FIFRA 72-1

Report No. 108738

GLP

Klimisch score: 1

Disk 5

00000165

Bluegill

Lepomis

macrochirus

96 h Static

96 h Static

LC50

2.13 mg/L

95% CI:

1.84 – 2.49 mg/L

[measured] > 80% of

[nominal]

Temperature below

specified range for 4

h (min 20.7°C)

Thiadone

LC50

18.6 mg/L

Bowers (1995)

FIFRA 72-1

Report No. 106674

GLP

Klimisch score: 1

Disk 5

00000163

Hall and Lam (1999)

FIFRA 72-1

Report No. 108455


Test species

Test type

&

duration

Test resultsa, b

Test methodc


(FOE 5043)

Metabolites

95% CI:

14.9 – 28.0 mg/L

[measured] > 80% of

[nominal]

Light intensity below

guideline

Hardness above

guideline

GLP

Klimisch score: 1

Disk 5

00000166

Sheephead Minnow

Cyprinodon

variegatus

96 h Static

renewal

LC50

3.31 mg/L

95%CI:

2.73 – 4.02 mg/L

*[measured] range

79 - 106% [nominal]

[DO] < 60% day 2

Temperature outside

of acceptable range

Gagliano and

Bowers (1994)

FIFRA 72-3 (a)

Report No. 106421

GLP

Klimisch score: 2*

Rainbow trout

Oncorhynchus

mykiss

97 day ELS

Flow-

through

NOEC:

0.179 mg/L

(% swim up)

LOEC:

0.334 mg/L

(% swim up)

[measured]

Problems with

diluter (day 81 for

5.5h)

Hardness above

guideline (day 42)

Gagliano (1995)

FIFRA 72-4

Report No. 106978

GLP

Klimisch score: 1

Disk 5

00000167

Invertebrates

Waterflea

Daphnia magna

48 h Static

48 h Static

EC50:

30.9 mg/L

95%CI:

29.0 – 47.9 mg/L

[measured] > 80% of

[nominal]

FOE 5043-Sulfonic

acid

EC50

> 87.3 mg/L

[Lowest lethal]

> 87.3 mg/L

Limit test

Bowers (1994)

FIFRA Guideline

72-2

Report No.

106597

GLP

Klimisch score: 1

Disk 5

00000172

Heimbach (1995)

OECD 202

Report No.

HBF/Dm 145

GLP

Klimisch score: 1

Disk 5

00000145


Test species

Test type

&

duration

Test resultsa, b

Test methodc


(FOE 5043)

Metabolites

48 h Static

[measured] > 80% of

[nominal]

Thiadone

31.7 mg/L

95%CI:

26.5 – 38.2 mg/L

[measured] > 80%

and < 120% of

[nominal]

Bowers and Lam

(1998)

FIFRA 72-2

Report No.

108464

GLP

Klimisch score: 1

Disk 5

00000175

Hyalella azteca 96 h Static LC50

2.45 mg /L

95%CI: 1.80 – 3.15

mg/L

*[measured] lower

than 70% [nominal]

[measured] used to

calculate LC50.

Bowers (1995)

FIFRA 72-2

Report No. 106908

GLP

Klimisch score: 1*

Disk 5

106908

Waterflea

Daphnia magna

21 d Static NOEC:

3.26 mg/L

(mean time to first

brood, no. of

offspring)

LOEC:

6.33 mg/L

[measured] > 90% of

[nominal]

*

Temperature out of

range for 32 h

(21.8°C > 21.0°C).

Daphnids did not

receive specified

feed on day 3.

Hardness out of

range

(184 > 180 mg/L).

Gagliano and

Bowers (1994)

FIFRA 72-4

Report No.

106762

GLP

Klimisch score: 1*

Disk 5

00000176

Algae/Aquatic Plants

Algae

Selenastrum

capricornutum

(Pseudokirchneriella

subcapitata)

96 h Static

120 h

ErC50

0.00310 mg/L

95% CI:

Not determined*

EbC50

0.00306 mg/L

95% CI:

0.00284 – 0.00328

mg/L

[measured] > 95%

Dorgerloh (1998)

OECD 201

Report No.

DOM 98092

GLP

Klimisch score: 2*

Disk 5

00000179


Test species

Test type

&

duration

Test resultsa, b

Test methodc


(FOE 5043)

Metabolites

and < 106% of

[nominal]

*pH variance > 1.5

(7.1 – 9.5)

Algae

Scenedesmus

subspicatus

72 h Static FOE 5043-Sulfonic

acid

ErC50

> 86.7 mg/L

LOErC

> 86.7 mg/L

[measured] > 80% of

[nominal]

pH values > than

recommended in all

concentrations.

Anderson (1995)

OECD 201

Report No.

E 323 0971-5

GLP

Klimisch score: 1

Disk 5

00000146

Algae

Pseudokirchneriella

subcapitata

72 h Static

72 h Static

FOE 5043-

Methylsulfide

ErC50

83.8 mg/L

*No 95% CI given

[measured] > 85%

and < 110% of

[nominal]

Thiadone

ErC50

15.0 mg/L

95% CI:

10.7 – 21.0 mg/L

[measured] > 100%

and < 110% of

[nominal]

Dorgerloh (1998)

OECD 201

Report No.

E 323 1346-2

GLP

Klimisch score: *2

Disk 5

00000182

Hall and Lam (1998)

FIFRA 123-2 Tier 2

Report No.

E 108823

GLP

Klimisch score: 1

Disk 5

00000183

Algae

Anabaena

flos-aquae

120 h Static

EbC50

32.5 mg/L

95% CI:

26.9 – 39.3 mg/L

[measured] > 84%

and < 107% of

[nominal]

Hughes and

Alexander (1993)

FIFRA 123-2

Report No.

105199

GLP

Klimisch score: 1

Disk 5

00000180

Freshwater Diatom

Navicula pelliculosa

120 h Static EC50:

2.07 mg/L

95% CI:

0.56 – 3.56 mg/L

(Cell Density)

Bowers and Dobbs

(1995)

USEPA 123-2

Report No.

107113


Test species

Test type

&

duration

Test resultsa, b

Test methodc


(FOE 5043)

Metabolites

[measured] > 80%

and < 120% of

[nominal]

GLP

Klimisch score: 1

Disk 5

00000178

Marine Diatom

Skeletonema

costatum

120 h Static EC50:

0.00559 mg/L

95% CI:

0.00547 – 0.00578

mg/L

(Cell Density)

[measured] > 92% of

[nominal]

*pH variation > 1.5

units

Bowers and Dobbs

(1995)

USEPA 123-2

Report No.

107115

GLP

Klimisch score: 1*

Aquatic Plants

Lemna gibba

14 d ErC50:

0.0318 mg/L

95% CI:

0.0160 – 0.154 mg/L

[measured] > 75.6%

of [nominal] day 0

[measured] > 51% of

[nominal] day 14

*pH variation > 1.5

units

FOE 5043-Sulfonic

acid

EC50

> 75.9 mg/L

(no. of fronds)

LOAErC

> 75.9 mg/L

[measured]

concentrations used

Dorgerloh (1998)

USEPA 123-2

Report No.

105198

GLP

Klimisch score: 1*

Disk 5

00000184

Dorgerloh (1995)

USEPA 123-2

Report No.

DOM 95072

GLP

Klimisch score: 1

Disk 5

00000147

Other

Oxygen

Consumption in

Activated Sludge

FOE 5043

EC50

> 10000 mg/L

Kanne (1989)

ISO 8192-1986/B

Report No.

89238067

Non-GLP

Klimisch score: 3*

Disk 5

00000205 a Results are reported on the basis of nominal concentrations except where otherwise stated, Standard

test guidelines provide for reporting of results on a nominal basis where measurements indicate the test

substance remains within 20% of nominal. b 95% confidence intervals are stated where available


c Unless otherwise stated, the tests were conducted according to the test method identified

Conclusion

Flufenacet is classified as 9.1A due to its toxicity to algae.

Table A2.8A: Summary of aquatic toxicity data for Firebird.

Test species

Test type

&

duration

Test resultsa, b

Test method

c

[reference number]

Rainbow trout

Onchorynchus

mykiss

Static

96 h

LC50

12.3 mg/L

95% CI:

9.31 – 16.4 mg/L

Measured FOE 5043 (flufenacet): 70% - 85%

Measured diflufenican: 1 and 4%*

(*Low solubility in water)

[Nominal] used.

Dorgerloh (1996)

OECD 203

Report No.

DOM 95081

GLP

Klimisch score: 1

Disk 14

00000553

Waterflea

Daphnia magna

Static

48 h

Limit test

EC50

> 100 mg/L

NOEC:

> 100 mg/L

Measured FOE 5043: 55%*

Measured Diflufenican: 0.87%*


[Nominal] used.

Heimbach (1996)

OECD 202

Report No.

HBF/Dm 151

GLP

Klimisch score: 1

Disk 14

00000554

Algae

Selenastrum

capricornutum

Static

72 h

ErC50

0.00663 mg/L

Measured FOE 5043: 45 - 178%*

Measured diflufenican: 0.87%*


[Nominal] used.

Dorgerloh and

Sommer (2001)

OECD 203

Report No.

DOM 20073

GLP

Klimisch score: 1

Disk 14

00000555

Algae

Scenedesmus

subspicatus

Static

72 h

ErC50

0.01704 mg/L

[Measured] FOE 5043 > 90% and < 111% of

[Nominal] in cell free culture medium.

*pH above guideline.

Anderson (1996)

OECD 201

Report No.

E 323 0975-9

GLP

Klimisch score: 1*

Disk 14

00000556

Aquatic Plants

Lemna gibba

Static

7 d

ErC50

0.307 mg/L

(frond number)

Test medium modified to reach a sufficient

doubling time.

Dorgerloh and

Sommer (2001)

OECD 221

Report No.

DOM 20074

GLP

Klimisch score: 1

Disk 14




c Unless otherwise stated, the tests were conducted according to the test method identified


Conclusion

Firebird is classified as 9.1A due to its toxicity to algae.

Sub-class 9.2 Soil ecotoxicity and terrestrial fate Classification under this sub-class requires consideration of the persistence of the

components of the substance in soil, and the toxicity of the substance to soil-dwelling

invertebrates (e.g. earthworm), soil microbial function and terrestrial plants resulting

from soil based exposure.

Data on the adsorption, mobility and field dissipation of the active ingredient is used

in the ecological risk assessment for the substance. Refer to Appendix 3.

Terrestrial fate and degradation of flufenacet.

Information of terrestrial fate and degradation is summarised in Tables A2.9 and

A2.9A.

Table A2.9: Terrestrial fate and degradation of flufenacet (FOE 5043) and its

metabolites.

Test type Test results Test method

a

[reference number] Flufenacet Metabolites Abiotic degradation Soil Photolysis

Sandy Loam

(pH 6.4, OC 1.16%)

Rate 6.2 ppm

(1 kg/ha)

Temperature 25°C

Irradiated Samples

DT50: 248 days

(First order kinetics)

Dark control samples

DT50: 167 days


Photolysis is not a

primary route of

degradation

Kasper and Shadrick

(1995).

EPA Guidelines N,

Section 161-3

Report No. 106247

GLP

Klimisch score: 1

Disk 4

00000121

Biodegradation

(Laboratory)

Aerobic

Phenyl Labelled

Sandy Loam

(pH 6.2, OC 0.6%)

Temperature 21°C

Rate: 1 ppm

(1 x application rate)

DT50: 33.8 days

(r = 0.9948, First order)

14 metabolic products

Only FOE oxalate >10%

Aerobic

Thiadiazole Labelled

Sandy Loam

(pH 6.2, OC 0.6%)

Temperature 21°C


(1994).

EPA Guidelines N,

Section 162-1

Report No. 106408

GLP

Klimisch score: 1

Disk 4

00000119


(1994).

EPA Guidelines N,

Section 162-1

Report No. 106420



a

[reference number] Flufenacet Metabolites Rate: 2.9 ppm

(3 X application rate)

DT50: 63.6 days

(r = 0.9922, First order)

>6 metabolic products

Major metabolite

Thiadone < 4%

Rate: 0.750 kg/ha

Temperature: 20°C

Loamy sand

(pH 6.2, OC 2.58%)

DT50: 25.5 days

DT90: 132 days

1.5 order kinetics

Rate: 0.750 kg/ha

Temperature: 20°C

Silt loam

(Laacherhof)

(pH 7.3, OC 0.9%)

DT50: 10.1 days

DT90: 52.6 days

1.5 order kinetics

Rate: 1.5 kg/ha

Temperature: 20°C

Silt loam

(Hofchen im Tal)

(pH 5.8, OC 2.4%)

DT50: 27.1 days

DT90: 90 days

First order kinetics

FOE – Sulfonic Acid

Temperature 20°C

Rate 750 g/ha.assuming

a 40% transformation

rate to sulfonic acid.

Sand

(pH 5.3, OC 0.57%)

DT50: 270 days

Loamy sand

(pH 6.3, OC 2.48%)

DT50: 189 days

Silt Loam

(Laacherhof)

(pH 7.3, OC 0.9%)

DT50: 247 days

FOE oxalate

Calculated values based

on experimental DT50

values of FOE sulfonic

acid.

Loamy sand

DT50: 5 days

GLP

Klimisch score: 1

Disk 4

00000120


BBA Guidelines Part

IV, 4-1

General Directorate

for Agriculture

VI B II-1

Report No. 106664

GLP

Klimisch score: 1

Disk 4

00000123

Hellpointner (1996)

Report No.

MR-1313/95

BBA Guidelines Part

IV, 4-1

SETAC 1995

Disk 5

00000129

Schafer (1998)

Report No.

MR-037/98

(amendment to report

MR 1085/95)

Calculation method

Disk 5

00000128



a

[reference number] Flufenacet Metabolites Silt loam

(Laacherhof)

DT50: 17 days

Silt loam

(Hofchen im Tal)

DT50: 12 days

Biodegradation

(Field)

Product applied

FOE 5043 60 WG

Without vegetation

D-23881 Breitenfide

Silty sand

(pH 6.2 OC 1.69%)

Rate 0.8 kg/ha

Agrotop Spraying Boom

DT50: 30.5 days

DT90: 101 days

Order of function: 1*

D-96166 Kirchlauter

Heavy sandy loam

(pH 7.1 OC 0.61%)

Rate 0.8 kg/ha


DT50: 53.1 days

DT90: 177 days

Order of function: 1

D-40789 Monheim

loamy sand

(pH 6.7 OC 1.45%)

Rate 0.8 kg/ha


DT50: 53.7 days

DT90: 178 days

Order of function: 1

D-51399 Burscheid

heavy loamy silt

(pH 6.5 OC 0.97%)

Rate 0.8 kg/ha


DT50: 15.4 days

DT90: 51.0 days


With vegetation

F-27700

Fresne-L’Archeveque

Crop: Maize

Loamy silt

(pH 6.0 OC 1.11%)

Rate 1.0 kg/ha

Knapsack

DT50: 16 days

Sommer (1995)

Report No.

RA-2112/93

BBA Guidelines Part

IV, 4-1

GLP

Klimisch score: 1

Disk 5

00000130

The results of

following single trials

are presented in this

report:

Trial No.: 30159/0

Trial No.: 30162/0

Trial No.: 30163/9

Trial No.: 30164/7

Trial No.: 30248/1

Trial No.: 30250/3

Trial No.: 30251/1

Trial No.: 30253/8



a

[reference number] Flufenacet Metabolites DT90: 177 days

Order of function: √1

F-27700


Crop: Maize

Loamy silt

(pH 5.2 OC 1.86%)

Rate 1.0 kg/ha

Knapsack

DT50: 37.9 days

DT90: 198 days

Order of function: 1.5

F-30290 Laudun

Crop: Sunflower

Sandy loamy silt

(pH 7.6 OC 0.62%)

Rate 1.0 kg/ha

Knapsack

DT50: 29.5 days

DT90: 98.1 days


F-13150

St Etienne du Gres

Crop: Sunflower

Sandy loamy silt

(pH 7.7 OC 0.80%)

Rate 1.0 kg/ha

Knapsack

DT50: 33.7 days

DT90: 112 days

Order of function: 1*,**

*Calculated without values of last sampling days

**Calculated without a value for day 7 of

degradation

During the whole test duration nearly all residues

remained in the 0 - 10 cm layers of soil.

The results of the lower layers of all eight trials

show that all concentrations of FOE 5043, FOE

5043-alcohol, FOE 5043-oxalate and FOE 5043-

sulfonic acid in deeper soil layers (20 - 30 cm) are

below the limit of determination of 10 µg/kg.

No mobility of FOE 5043 or the metabolites FOE


sulfonic acid was observed.

Product

FOE 5043 60 WG

Rate 0.4 kg/ha


Sommer (1995)

Report No.

RA-2116/93

BBA Guidelines Part

IV, 4-1



a

[reference number] Flufenacet Metabolites D-51399 Burscheid

Silt Loam

(pH 6.5, OC 0.97%)

DT50: 37.6* days

DT90: 125* days


D-40789 Monheim

Sandy Loam

(pH 6.7, OC 1.45%)

DT50: 43.2 days

DT90: 144 days


*calculated without the values of the last sampling

day.

Product

FOE 5043 60 WG

With vegetation

Rate 0.4 kg/ha

Knapsack

F-27150

Saussay-la-Campagne

Silt Loam

(pH 7.4, OC 0.92%)

DT50: 16 days

DT90: 52 days


F-27700


Silt Loam

(pH 6.6, OC 1.00%)

DT50: 13 days

DT90: 43 days



day.

The results of the lower layers of both trials showed

that all concentrations of FOE 5043, FOE 5043-

alcohol, FOE 5043-oxalate and FOE 5043-sulfonic

acid in deeper soil layers (10-20 cm, 20 - 30 cm, 30

- 40 cm and 40 - 50 cm) are below the limit of

detection of 3 µg/kg corresponding to < 2 % of the

initial concentration of the active ingredient.




Product

FOE 5043 60 WG

With vegetation

Rate 1 kg/ha

GLP

Klimisch score: 1

Disk 5

00000131

Sommer (1995)

Report No.

RA-2051/93

BBA Guidelines Part

IV, 4-1

GLP

Klimisch score: 1

Disk 5

00000132

Sommer (1995)

Report No.

RA-2019/94



a

[reference number] Flufenacet Metabolites

F-30290 Laudun

Silty clay loam

0 – 30 cm

(pH 7.7, OC 1.28%)

30 – 50 cm

(pH 7.8, OC 0.70%)

Knapsack

DT50: 36.2 days

DT90: 120 days


F-13103

St. Etienne du Gres

Silty loam

0 – 30 cm

(pH 7.7, OC 0.96%)

30 – 50 cm

(pH 7.8, OC 0.60%)

Knapsack

DT50: 41.8 days*

DT90: 139 days*


I-48100

Ravenna

Sandy loamy silt

0 – 30 cm

(pH 7.8, OC 0.0.98%)

Silty sand

30 – 50 cm

(pH 7.8, OC 0.57%)

Wheelbarrow applicator

DT50: 37.9 days

DT90: 126 days


I-48020

Romauldo

loamy clay

0 – 30 cm

(pH 7.8, OC 1.11%)

30 – 50 cm

(pH 7.8, OC 0.96%)

Wheelbarrow applicator

DT50: 47.5 days

DT90: 158 days



day.

The results of the lower layers (10 - 20 cm, 20 - 30

cm, 30 - 40 cm and 40 - 50 cm) of all four trials

showed that, except one value of FOE 5043 in the

10 - 20 cm layer between the limit of detection and

the limit of determination, all concentrations of

FOE 5043, FOE 5043-alcohol, FOE 5043-oxalate

BBA Guidelines Part

IV, 4-1

GLP

Klimisch score: 1

Disk 5

00000133



a

[reference number] Flufenacet Metabolites and FOE 5043-sulfonic acid are below the limit of

detection of 3 μg/kg.




Soil accumulation

Adsorption/desorption FOE 5043

Kelley and Wood

(1992)

EPA Guideline 163-1

Report No. 103903

GLP

Klimisch score: 1

Disk 5

00000136

Christensen and Yen

(1994).

Canadian guideline

T-1-225 #6.2, B.

Report No. 106578

GLP

Klimisch score: 2*

Disk 5

00000137

Blumhorst et al. 1994

Canadian guideline

T-1-225 #6.2, B.

Report No. 106578

GLP

Klimisch score: 1

Disk 5

00000137

Soil Kd Koc

Silt loam

pH 5.9 OC 2.9%

Ad 3.2

Des 3.9

Ad 213

Des 254

Clay loam

pH 6.4 OC 2.2%

Ad 2.7

Des 3.1

Ad 233

Des 264

Loamy sand

pH 6.4 OC 0.4%

Ad 1.6

Des 2.1

Ad 742

Des 1016

Sand

pH 5.0 OC 0.3%

Ad 1.0

Des 0.9

Ad 613

Des 554

Sandy loam

pH 6.4 OC 1.4%

Ad 4.8

Des 5.3

Ad 354

Des 395

Kd

Koc

Loam

pH 7.1 OC 4.3%

Ad 4.9

Des 10.5

Ad 113

Des 245

Silt Loam

pH 7.3 OC 2.8%

Ad 4.0

Des 6.6

Ad 144

Des 238

Characterised as mobile in loam and silt loam with

a potential for high mobility in the environment.

*There were some minor deviations from

guidelines such as temperature range and pH

measures.

Metabolites

Kd Koc

FOE Methyl Sulfoxide

Sand

pH 5.8, OC 0.27%

Ad 0.13

Des 0.08

Ad 49

Des 31

Sandy Loam

pH 6.3, OC 0.75%

Ad 0.35

Des 0.29

Ad 46

Des 39

Silty Clay Loam

pH 6.6, OC 2.13%

Ad 2.05

Des 2.59

Ad 96

Des 121

Silty Clay

pH 6.0, OC 1.21%

Ad 5.60

Des 6.12

Ad 463

Des 506

Mobility class

very high/medium

FOE Sulfonic Acid

Sand

pH 5.8, OC 0.27%

Ad 0.05

Des -

Ad 19

Des -

Sandy Loam

pH 6.3, OC 0.75%

Ad 0.11

Des -

Ad 15

Des -

Silty Clay Loam

pH 6.6, OC 2.13%

Ad 0.20

Des -

Ad 10

Des -

Silty Clay

pH 6.0, OC 1.21%

Ad 0.07

Des -

Ad 6

Des -

Mobility class very high



a

[reference number] Flufenacet Metabolites

FOE Oxalate

Sand

pH 5.8, OC 0.27%

Ad 0.06

Des -

Ad 23

Des -

Sandy Loam

pH 6.3, OC 0.75%

Ad 0.1

Des -

Ad 13

Des -

Silty Clay Loam

pH 6.6, OC 2.13%

Ad 0.15

Des -

Ad 7

Des -

Silty Clay

pH 6.0, OC 1.21%

Ad 0.16

Des -

Ad 13

Des -

Mobility class

very high

FOE Alcohol

Sand

pH 5.8, OC 0.27%

Ad 0.23

Des 0.4

Ad 0.35

Des 147

Sandy Loam

pH 6.3, OC 0.75%

Ad 0.78

Des 1.38

Ad 1.42

Des 184

Silty Clay Loam

pH 6.6, OC 2.13%

Ad 2.02

Des 3.20

Ad 1.56

Des 150

Silty Clay

pH 6.0, OC 1.21%

Ad 3.80

Des 3.94

Ad 2.10

Des 326

Mobility class

high/medium

Thiadone

Sand

pH 5.8, OC 0.27%

Ad 0.12

Des 0.35

Ad 43

Des 128

Sandy Loam

pH 6.3, OC 0.75%

Ad 0.33

Des 1.42

Ad 44

Des 189

Silty Clay Loam

pH 6.6, OC 2.13%

Ad 0.61

Des 1.56

Ad 29

Des 73

Silty Clay

pH 6.0, OC 1.21%

Ad 0.71

Des 2.10

Ad 58

Des 174

Mobility class

very high/high

It can be concluded that all metabolites have the

potential to be quite mobile in soil. However, with

regard to the quantities being found in soil, only

FOE oxalate or FOE sulfonic acid are expected to

have a potential to leach into deeper soil layers in

significant amounts.

Table A2.9A: Terrestrial fate (mobility and leaching) of flufenacet and its

metabolites. Mobility/

Leaching

Leaching of Aged 5043 through Soil Columns

Rate: 1.76 mg ai/kg soil

Between 26.7% and 29.0% of the applied radioactivity was collected in

the leachates from 30-day columns and 34.7% to 44.3% was collected

in the leachate from the 90-day columns. Only 17.4% of the applied

radioactivity from the 30-day incubation system was due to

metabolites, whereas 42.3% of the applied radioactivity was due to

metabolites in the 90-day incubation system.

Kelley and Wood

(1993)

BBA Guideline Part

IV, 4-2

Report No. 105018

GLP

Klimisch score: 1

Disk 5

00000139


Analysis of the leachates from the 30-day and 90-day incubation

periods indicates that the metabolites leach more readily than the

parent compound.

Comparison of extracts from the 30-day and 90-day incubation periods

with the 30-day and 90-day leachates reveals that all of the identified

metabolites and several unknown radioactive components (maximum

percent = 1.8% combined) moved through the soil columns with the

leachates.

Lysimeter study on the translocation of FOE 5043 into the

underground after 2-year application as pre-emergence herbicide

in corn (1st year of study)

Over a period of 1 year after the application the leaching behaviour of

[phenyl-UL-14C] FOE 5043 and it's degradation products was

investigated under practice-relevant German corn growing field

conditions

Rate: 480 g ai/ha

The preliminary results of this study proved that even under worst case

conditions a contamination of soil layers below 1.2 m or of

groundwater by the parent after recommended use of FOE 5043 can be

precluded with a probability bordering certainty.

One metabolite, FOE sulfonic acid, may be contained in soil pore

water below 1.2 m depth at a peak concentration of about 1.2 µg/L and

a 1st year's annual mean of about 0.5 µg/L.


underground after 2-year application as pre-emergence herbicide

in corn (2nd

year of study)

Rate: 480 g ai/ha.(First application – May 1993)

Rate: 480 g ai/ha.(Second application – May 1994)

The measured values of total radioactive residue (TRR) in the

leachates showed a typical break-through curve and comparable results

for both lysimeters. The maximum TRR of 1.04 ug and 0.69 ug a.i.

equivalents/L was each reached in February 1995.

The mean residue of FOE 5043 in total 2nd year's leachate was

measured to be less than 0.005 µg/L, but the parent compound could

not be positively detected. The mean concentration of each known

FOE 5043-metabolite was lower than 0.02 µg/L, except the findings of

sulfonic acid. The mean residues of sulfonic acid in AL-95 were

measured to be 0.24 µg/L (lys. #15) and 0.15 µg/L (lys. #16),

respectively.

These contents were significantly lower than those found in the annual

leachates of the 1st year, despite the repeated application after one

year.

Despite the repeated application after one year, the TRR in the

leachates of the 2nd year was generally lower than that of the 1st year.

These findings indicate that the outflow of radioactivity resulting from

the 1st application of FOE 5043 was more or less completed after one

year. Therefore, a longer lasting leaching of metabolites into deeper

soil layers is not to be expected from a single use of FOE 5043.

Hellpointner (1995)

BBA Guideline Part

IV, 4-3

Report No. PF-4024

GLP

Klimisch score: 1

Disk 5

00000140

Hellpointner (1995)

BBA Guideline Part

IV, 4-3

Report No. PF-4081

GLP

Klimisch score: 1

Disk 5

00000143


It is indicated that a lower portion of mobile metabolites (i. e. sulfonic

acid) was able to leach out of the soil cores in the subsequent year after

repeated use. This may partly be due to an enhanced overall

degradation (i. e. mineralization) in the year of repeated application,

probably caused by better adapted soil microorganism populations or

by the slightly higher soil temperatures. The other marginal conditions

of study were not differing so much.

Only a total of 0.50% and 0.32% of the radioactivity applied leached

through each of the two soil cores during the 2nd year of study. These

portions correspond to 0.25% and 0.16% of total applied radioactivity,

only. Only a total of 0.66% and 0.59% of the total applied radioactivity

leached through each of the two soil cores during the 2 years of

lysimeter study.

Again, the residues found in the harvested corn materials of the 2nd

year were at a rather low level (TRR < 6.5 ppb in kernels and TRR <

11.7 ppb in cobs & hulls) and were well comparable to those

determined in the materials of the 1st year. These findings indicate that

a repeated use of FOE 5043 should not cause increasing total residues

in the harvested crop materials.


conditions a contamination of soil layers below 1.2 m depth or of

groundwater by the parent after recommended use of FOE 5043 in

corn can be precluded with a probability bordering certainty. One

metabolite, the 4-fluoro-N- methylethylanilinesulfoacetamide (FOE

5043-sulfonic acid) may be contained for short term in soil pore water

below 1.2 m depth. In this study a peak concentration of about 1.2

µg/L was measured in the 1st winter and the annual mean of the 1st

year's leachate amounted to about 0.5 µg/L . But in the subsequent

year, including a repeated application of FOE 5043, the values were

found to be lower (yearly mean of about 0.2 µg/L).


underground after the use as pre-emergence herbicide in a corn /

winter wheat crop rotation

Over a period of 1 year the leaching behaviour of [phenyl-UL-14C]

FOE 5043 and it's degradation products was investigated under

practice-relevant German corn (silage) / winter wheat growing field

conditions.

Rate 480 g ai/ha.(First application – May 1993)

Rate 180 g ai/ha.(Second application – November 1993)

The maximum residue of FOE 5043 in single leachate was measured to

be lower than 0.01 µg/L. The maximum concentration of FOE-

metabolites (including unknowns) was each lower than 0.08 µg/L,

except the findings of FOE-sulfonic acid and, only for lys. #18, the

FOE alcohol.

The maximum residues of FOE-sulfonic acid found in the leachates

were measured to be 3.4 µg/L and 3.7 µg/L. The FOE-alcohol was

positively detected in lys. #18, only (maximum residues of 0.16 µg/L).

The detection of FOE-alcohol in the leachates of lysimeter #18 was the

only significant difference in the two tested soil cores.

The mean residue of FOE 5043 in total 1st year's leachate was lower

than 0.01 µg/L. The mean concentration of FOE-metabolites

Hellpointner (1995)

BBA Guideline Part

IV, 4-3

Report No. PF-4025

GLP

Klimisch score: 1

Disk 5

00000141


(including unknowns) was each lower than 0.06 ng/L, except the

findings of FOE sulfonic acid. The mean residues of FOE -sulfonic

acid in the total 1st year's leachates were 1.42 µg/L and 1.69 ng/L,

respectively. A total of 1.43% and 1.56% of applied radioactivity

leached through the two soil cores during 1st year of study.


conditions a contamination of soil layers below 1.2 m or of ground

water by the parent after recommended use of FOE 5043 can be

precluded with a probability bordering certainty.

One metabolite, FOE-sulfonic acid, may be contained in soil pore

water below 1.2 m depth at a peak concentration of about 3.5 µg/L and

a 1st year's annual mean of about 1.6 µg/L.

Lysimeter study on the translocation of FOE 5043 into the subsoil

after use as pre-emergence herbicide in a maize / winter wheat

crop rotation The leaching behaviour of [phenyl-UL-

14C]FOE 5043 and its

degradation products was investigated in a maize-winter wheat crop

rotation under practice-relevant German field conditions.

Rate 480 g ai/ha.(First application – May 1993)

Rate 180 g ai/ha.(Second application – November 1993)

The measured total radioactive residue (TRR) in the individual

leachates showed a typical break-through curve and well comparable

results for both lysimeters. For both lysimeters the TRRmax. was

reached in February 1994 (after 38 weeks) at about 5 ug a.i. equivalent/

L. However, in the subsequent period until February 1995 the TRR

decreased about 20-fold to a range of less than 0.25 ug a.i.

equivalent/L.

These findings indicated that the use of FOE 5043 should not have a

longer-lasting influence on the water relevant for groundwater recharge

below agricultural soils.

A concrete peak of parent compound could not be observed in the

analyses of leachates. The content of FOE 5043 in individual leachate

was found to be lower than 0.01 µg/L. The maximum concentration of

metabolites (including unknowns) was each lower than 0.04 µg/L,

except that of FOE 5043 sulfonic acid (SAC) and, in case of lys. #18,

the FOE 5043 alcohol (ALC). The maximum content of SAC found in

the leachates of Feb. 94 was measured to be 3.4 µg/L (lys. #17) and 3.7

µg/L (lys. #18), respectively. The ALC was observed in lys. #18, only

(maximum content of 0.095 ng/L in an early leachate taken in Oct. 93).

The FOE 5043 in annual leachate of the 1st year was much lower than

0.01 µg/L. The content of metabolites (including unknowns) was each

lower than 0.04 µg/L, except that of SAC. On average, the content of

SAC in annual leachate of the 1st year was 1.5 µg/L. The FOE 5043 in

annual leachate of the 2nd year was significantly lower than 0.005

µg/L and the content of metabolites (including unknowns) was at the

most 0.022 µg/L. Compared to the annual leachate of the 1st year the

mean content of SAC had decreased 100-fold to about 0.015 µg/L,

already. Until the end of study, the leaching of [14C]material out of the

soil monolith was approaching the background level. It is quite

plausible that some radioactivity is passing the soil monoliths further,

because a comparatively high portion of radioactively labelled carbon

was applied to the soil in a quite stable [14C]labelling position

Hellpointner (1996)

BBA Guideline Part

IV, 4-3

Report No. PF-4184

GLP

Klimisch score: 1

Disk 5

00000142


(phenyl-UL). It is conceivable that the unknown radioactively labelled

compounds (TRR) in the leachate might consist of humic and/or biotic

substances into which liberated radioactively labelled carbon dioxide

and/or radioactive fragments of the a.i. or metabolites had been

incorporated.

The comparatively low mobility of FOE 5043 and its metabolites in

soil was supported by the measured distribution of radioactivity in the

processed soil monoliths. The main portion of recovered radioactivity

was still located in the upper soil layers.

Furthermore, the main portion of TRR still contained there was not

extractable (bound) residue. The recoveries of parent compound (less

than 0.8% of total applied) and of relevant metabolites in the processed

soil layers were quite low. Obviously, relevant portions (55.6% and

44.8%) of radioactivity once applied to the soil monolith had been

mineralised and released into the air.

The results of this study proved that even under worst case conditions a

contamination of soil layers below 1.2 m depth by the parent (after

recommended use of FOE 5043) can be precluded with a probability

bordering certainty. Most of its relevant degradation products in soil

showed a similar behaviour. It should be considered that only a total

portion of 1.56% and 1.72% of applied radioactivity was extracted

from the soil monoliths of lysimeter #17 and #18 by all the leachates

during 2.5 years of study. One individual metabolite, SAC, may be

contained in soil pore water below 1.2 m depth at a short-term peak

concentration of about 3.5 µg/L, a 1st year's annual mean of at about

1.5 µg/L and a 2nd year's annual mean of about 0.015 µg/L, only. The

SAC represents a metabolite formed in soil from one part (half) of the

parent compound molecule. Furthermore, the data confirmed that the

herbicide FOE 5043 is a well degradable parent compound.

The Agency’s Conclusion

The flufenacet metabolite, FOE 5043 sulfonic acid, has the potential to

leach into and persist in the aquatic environment and ground water.

FOE 5043 sulfonic acid has appeared in mean concentrations

exceeding 0.1 µg/L (designated EU cut-off). However, it has been

demonstrated that FOE sulfonic acid has no toxicological or

ecotoxicological relevance.

a unless otherwise stated, the tests were conducted in accordance with the named test guideline

NA= Not applicable

ND= No data provided

Figure 2: Degradation pathway of FOE 5043 (Schafer 1998, MR-037/98).


Conclusion

Based on these data flufenacet is considered to not meet the HSNO criteria for

degradability in soil < 30 days. This is primarily due to the degradability of the major

metabolite FOE 5043-sulfonic acid, DT50 range 189 – 270 days. As a result, Firebird

is considered to be not rapidly degradable in soil.

Soil toxicity

A summary of the toxicity of flufenacet and Firebird to soil dwelling macro-

organisms, soil microbial function and terrestrial plants is provided in Tables A2.10

and A2.10A.

Table A2.10: Summary of terrestrial toxicity data for flufenacet.

Test species Test type &

duration

Test resultsa, b

Test methodc

[reference

number] Flufenacet Metabolites

Soil-dwelling invertebrates

Earthworm

Eisenia fetida

Acute

14 day

Acute

14 day

LC50

226 mg/kg dry weight

95% CI:

208 – 246 mg/kg

EC50

22.6 mg/kg dry

weight

NOEC

< 10 mg/kg dry

weight

[Lowest Lethal]

178 mg/kg dry weight

FOE 5043

- Sulfonic acid

LC50

> 1000 mg/kg dry

weight

NOEC

> 1000 mg/kg dry

weight

*temperature

outside of range for

1 day

(22°C < 22.5°C)

*Humidity outside

of range on 0 – 4

days

(94% > 90%)

FOE 5043

- Oxalate

LC50

> 1000 mg/kg dry

weight

Heimbach (1995)

OECD 207

Report No.

HBF/Rg 202

GLP

Klimisch score: 1

Disk 5

00000197

Heimbach (1999)

OECD 207

Report No.

99-005-1022

GLP

Klimisch score: 2*

Disk 5

00000198

Heimbach (1999)

OECD 207

Report No.

1022.006.630

GLP

Klimisch score: 2*

Disk 5

00000199


NOEC

> 1000 mg/kg dry

weight

*temperature

outside of range for

1 day

(22°C < 22.5°C)

*Humidity outside

of range on days 5-6

and days 8-12 (98%

> 90%)

d 6-8 (54% < 60%)

Earthworm

Eisenia fetida

Reproduction

56 days

Reproduction

56 days

FOE 5043 WG 60

Rate:

1 kg/ha.formulation

2 kg/ha.formulation

5 kg/ha.formulation

LC50

> 5 kg/ha

NOEC

2 kg/ha.formulation

(Weight reduction)

*This reduction in

weight was not

considered as

biologically

significant.

(p = 0.043 < 0.050).

The numbers of

offspring were not

reduced.

FOE 5043 WG 60

Rate:

1 kg/ha.formulation

2 kg/ha.formulation

5 kg/ha.formulation

1 kg/ha.formulation

Total biomass of

offspring significantly

higher (36 %).

2 kg/ha.formulation

No. of offspring was

significantly higher

(27%).

5 kg/ha.formulation

Total biomass of

offspring significantly

higher (27%).

It can be anticipated,

Heimbach (1997)

ISO/DIS 11268-2

BBA Part VI, 2-2

Report No.

HBF/Rg 251

GLP

Klimisch score: 1

Disk 5

00000200

Heimbach (1997)

ISO/DIS 11268-2

BBA Part VI, 2-2

Report No.

HBF/Rg 213

GLP

Klimisch score: 1

Disk 5

00000201


that FOE 5043 WG

60 did not affect

reproduction of

earthworms up to the

highest tested rate of

5 kg/ha.

Terrestrial plants

Monocotyledons

4 species

Dicotyledons

6 species

Seed

Germination

Seedling

Emergence

21 d

FOE 5043 Dry

Flowable 61.0% ai

No significant

difference between

treated and control

plants.

EC50

Sorghum

0.054 lb ai/A

(0.061 kg ai/ha)

(lowest EC50 of 10

spp.)

NOEC

0.0039 lb ai/A

(0.0044 kg ai/ha)

(Height/Weight)

Johns (1994)

Report No.

106780

EPA 122-1

EPA 123-1

GLP

Klimisch score: 1

Disk 5

00000204

Monocotyledons

4 species

Dicotyledons

6 species

Vegetative

vigour

21 d

Risk

assessment

only

EC50

Sorghum

0.058 lb ai/A

0.065 kg ai/ha

Height

EC50

Sorghum

0.041 lb ai/A

0.046 kg ai/ha

Weight

(lowest EC50 of 10

spp.)

NOEC

0.0078 lb ai/A

0.0087 kg ai/ha

Height/Weight

Johns (1994)

Report No.

106780

EPA 122-1

EPA 123-1

GLP

Klimisch score: 1

Disk 5

00000204

Soil microbial function

Nitrogen

Mineralisation

28 d FOE 5043

Rate:

0.62 kg/ha

(0.83 mg/kg dry wt soil)

3.1 kg/ha


EC25

> 4.15 mg/kg dry wt

soil

FOE 5043 should not

Anderson (1994)

BBA Part VI, 1-1

ISO/DIS 1036-6

Report No.

E 337 0885-4

GLP

Klimisch score: 1

Disk 5

00000202


negatively influence the

turnover of Nitrogen in

soil.

Glucose

Stimulated

Respiration in

Soil

FOE 5043

Rate:

0.62 kg/ha


3.1 kg/ha


EC25

> 4.15 mg/kg dry wt

soil

FOE 5043 should not

influence the

degradation of organic

carbon in soils.

Anderson (1994)

BBA Part VI, 1-1

ISO/DIS 1036-6

Report No.

E 337 0887-9

GLP

Klimisch score: 1

Disk 5

00000203

a Results are reported on the basis of nominal concentrations except where otherwise stated, Standard



cUnless otherwise stated, the tests were conducted according to the test method identified

NA= Not applicable

ND= No data provided

Conclusion

Flufenacet is classified as 9.2A due to it’s’ toxicity to non-target plants and its

degradation half-life in soil.

Table A2.10A: Summary of terrestrial toxicity data for Firebird.

Test species Test type &

duration

Test resultsa, b

Test method

c

[reference

number]

Soil-dwelling invertebrates

Earthworm

Eisenia fetida

Acute

14 d

Reproduction

56 d

LC50

> 1000 mg/kg dry weight

NOEC

32 mg/kg dry weight

(weight)

NOEC

> 4 mg/kg dry weight

(3000 g formulation/ha)

Meisner (2001)

OECD 207

Report No.

MPE/Rg 362/01

GLP

Klimisch score: 1

Disk 5

00000565

Heimbach (1998)

BBA VI, 2-2

Report No.

MPE/Rg 280

GLP

Klimisch score: 1

Disk 5

00000566

Terrestrial plants

Monocotyledons

2 species

Dicotyledons

4 species

Seedling

emergence

21 days after

50%

emergence of

Allium cepa

(Onion)

Survival

EC50

331.52 g/ha

Kalsch (2002)

Report No.

P2PA

OECD 208A

GLP


controls 0.44 mg/kg dry soil

NOEC

103.4 g/ha

0.14 mg/kg dry soil

Shoot length

Allium cepa

(Onion)

EC50

308.96 g/ha

0.41 mg/kg dry soil

Brassica napus

(Oilseed rape)

NOEC

3.2 g/ha

0.0043 mg/kg dry soil

Fresh weight

Allium cepa

(Onion)

EC50

190.43 g/ha

0.25 mg/kg dry soil

Brassica napus

(Oilseed rape)

NOEC

3.2 g/ha

0.0043 mg/kg dry soil

Klimisch score: 1

Disk 5

00000570

Monocotyledons

2 species

Dicotyledons

4 species

Vegetative

vigour

21 days after

50%

emergence of

controls

Risk

assessment

only

Fresh weight

Cucumis sativus

(Cucumber)

EC50

27.75 g/ha

Glycine max

(Soybean)

Cucumis sativus

(Cucumber)

NOEC

3.2 g/ha

Kalsch (2002)

Report No.

P3PB

OECD 208A

GLP

Klimisch score: 1

Disk 14

00000570

Soil microbial function

Nitrogen

Mineralisation

Rate:

0.6 kg product /ha.

(0.80 mg product/kg dry wt soil)

3.0 kg product/ha


EC25

> 4.00 mg/kg dry wt soil

Anderson (1995)

BBA Part VI, 1-1

ISO/DIS 1036-6

Report No.

E 337 1025-1

GLP

Klimisch score: 1

Disk 5

00000569

Glucose

Stimulated

Respiration in

Soil

Rate:

0.6 kg product /ha.


3.0 kg product/ha


Anderson (1995)

BBA Part VI, 1-1

ISO/DIS 1036-6

Report No.

E 330 1024-3

GLP


EC25

> 4.00 mg/kg dry wt soil

Klimisch score: 1

Disk 5

00000568

a Results are reported on the basis of nominal concentrations except where otherwise stated, Standard




Conclusion

Firebird is classified as 9.2A due to its’ toxicity to non-target plants.

Sub-class 9.3 Terrestrial vertebrate ecotoxicity The mammalian toxicity of flufenacet has been addressed under sub-class 6. Key

endpoints for both mammalian and avian toxicity are summarized in Table A2.11.

Table A2.11: Summary of terrestrial vertebrate toxicity data for flufenacet.

Test

species

Test type

&

duration

Test resultsa, b

Test method

c

[reference number]

Mammals

Rat

(Sprague

Dawley)

Acute oral LD50:

589 mg/kg body weight (females)

Astroff and

Fitzpatrick

US FIFRA 81-1

OECD 401

Report No.

102699

Klimisch score: 1

Birds

Bobwhite

quail

Colinus

virginianus

Acute oral

14 day

observation

LD50:

1608 mg ai/kg

body weight

NOEC:

125 mg/kg body weight

LOEC:


Stafford (1992)

FIFRA 71-1

Report No.

102642

GLP

Klimisch score: 1

Disk 5

00000156

Mallard

duck

Anas

platyrhynchos

Acute oral

14 day

observation

LD50:

>2000 mg ai/kg

body weight

NOEC:


LOEC:


(mortality)

*Two females at the 1000 mg a.i./kg dose level

and one female at the 2000 mg a.i./kg dose level

were found dead the day after dosing.

Downs and Hancock

(1997)

FIFRA 71-1

Report No.

107700

GLP

Klimisch score: 2*

Disk 5

00000157


Postmortem examinations revealed no

compound related findings. No consistent, dose

related symptoms were noted in any birds. None

of the birds that died exhibited any toxic

symptoms. No effects on bodyweight or feed

consumption were noted at any dose level.

Bobwhite

quail

Colinus

virginianus

Subacute

dietary

5 day

exposure

3 day

observation

LC50:

> 5317 ppm

NOEC:

1280 ppm

(Symptoms of intoxication –

ataxia, hyporeactivity)

LOEC:

2469 ppm

(Symptoms of intoxication –

ataxia, hyporeactivity)

Feed aversion observed at 4970 ppm. Death

attributed to food avoidance rather than direct

effect of compound.

Toll (1994)

FIFRA 71-2

OECD 205

Report No.

106583

GLP

Klimisch score: 1

Disk 5

00000159

Mallard

duck

Anas

platyrhynchos

Subacute

dietary

5 day

exposure

3 day

observation

LC50:

> 4970 ppm

NOEC:

<164 ppm

(Symptoms of intoxication - diarrhoea)

LOEC:

164 ppm

(Symptoms of intoxication - diarrhoea)

Feed aversion observed at 4970 ppm. Death

attributed to food avoidance rather than direct

effect of compound.

Stafford (1994)

FIFRA 71-2

Report No.

103814

GLP

Klimisch score: 1

Disk 5

00000158

Bobwhite

quail

Colinus

virginianus

Reproduction

Study

NOEC

(number of eggs laid per hen)

1890 ppm

NOEL

291.58 mg ai/kg bw/day

NOEC

(mean eggshell thickness)

1890 ppm

NOEL


NOEC

(proportion of fertile eggs per eggs set per hen

or number viable embryos over number of eggs

set)

1890 ppm

NOEL


NOEC

Schmuck (1994)

OECD 206

FIFRA 71-4

Report No.

SXR/REP 03

GLP

Klimisch score: 1

Disk 5

00000160


(proportion of hatching per fertile eggs per hen

or percent hatching of viable embryos)

441 ppm

NOEL


(% of self hatched chicks, rel. to viable 18-d

embryos)

NOEC

(proportion of 14-day old juveniles per number

of hatchlings)

1890 ppm

NOEL


NOEC

(14-day juvenile weights per hen)

1890 ppm

NOEL


Mallard

duck

Anas

platyrhynchos

Reproduction

Study

NOEC

(number of eggs laid per hen)

211 ppm

NOEL


NOEC

(mean eggshell thickness)

544 ppm

NOEL


NOEC

(proportion of fertile eggs per eggs set per hen

or number viable embryos over number of eggs

set)

211 ppm

NOEL


(Viable eggs of eggs set)

NOEC

(proportion of hatching per fertile eggs per hen

or percent hatching of viable embryos)

88 ppm

NOEL


(Normal hatchlings of live 3-week embryos)

NOEC

(proportion of 14-day old juveniles per number

of hatchlings)

544 ppm

NOEL


(14-day old survivors of normal hatchlings)

NOEC

(14-day juvenile weights per hen)

Hancock and

Reynolds (1994)

FIFRA 71-4

Report No.

106594

GLP

Klimisch score: 1

Disk 5

00000161


88 ppm

NOEL

12.02 mg ai/kg bw/day a Results are reported on the basis of nominal concentrations except where otherwise stated, Standard




Conclusion

Flufenacet is classified as 9.3C due to its toxicity to mammals and birds.

Table A2.11A: Summary of terrestrial vertebrate toxicity data for Firebird.

Test

species

Test type

&

duration

Test resultsa, b

Test method

c

[reference number]

Mammals

Rat

(Wistar)

Acute oral LD50:

> 500 < 2000 mg/kg body weight

Krötlinger

OECD 423

Report No.

T5071313

Klimisch score: 2

Conclusion

Firebird is classified as 9.3C due to its toxicity to mammals.

Sub-class 9.4 Terrestrial invertebrate ecotoxicity A summary of the data on the toxicity of flufenacet and Firebird to honeybees and

other non-target terrestrial invertebrates is provided in Tables A2.12 and A2.12A,

respectively.

Table A2.12: Summary of terrestrial invertebrate toxicity data for flufenacet.

Test

species

Test type &

duration

Test resultsa, b

Test methodc

[Reference number]

Flufenacet Metabolites


Honey bee

Apis

mellifera

Contact

24 h

Contact

48 h

Contact

48 h

LD50

> 25 µg/Bee

LD50

> 200 µg/Bee

LD50

> 400 µg/Bee

Mayer (1996)

FIFRA 141-1

Study no.

107517

GLP

Klimisch score: 1

Disk 5

00000189

Nengel (1995)

EPPO Guideline 170

Study no.

B-94137/01-BLEU

GLP

Klimisch score: 1

Disk 5

00000188

Tornier (1994)

EPPO Guideline 170

Study no.

B-958264

Non-GLP

Klimisch score: 3

Disk 5

00000187

Honey bee

Apis

mellifera

Oral

48 h

Oral

48 h

LD50

> 175.56 µg/Bee

LD50

> 340.4 µg/Bee

Nengel (1995)

EPPO Guideline 170

Study no.

B-94137/01- BLEU

GLP

Klimisch score: 1

Disk 5

00000188

Tornier (1994)

EPPO Guideline 170

Study no.

B-958264

Non-GLP

Klimisch score: 3

Disk 5





Conclusion

Based on the information (Table A2.12), flufenacet does not trigger the threshold for

toxicity to terrestrial invertebrates.

Table A2.12A: Summary of terrestrial invertebrate toxicity data for Firebird.

Test species

Test type

&

duration

Test resultsa, b

Test method

c

[reference number]


Honey bee

Apis mellifera

48 h Oral

48 h Contact

72 h

Respiration

LD50

> 198 µg/bee

(40% mortality observed)

LD50

> 200 µg/bee


LD50

> 0.6 kg/ha.in 200 L/ha


Heimbach (1996)

EPPO 170

BBA VI 23-1

Report No.

95 10 48 508

GLP

Klimisch score: 1

Disk 14

00000558

Honey bee

Apis mellifera

48 h Oral

48 h Contact

LD50

> 199 µg/bee


LD50

> 200 µg/bee


Hennig-Pusch (1996)

EPPO 170

Report No.

95 10 48 508

GLP

Klimisch score: 1

Disk 14





Conclusion

Based on the information (Table A2.12A), Firebird does not trigger the threshold for

toxicity to terrestrial invertebrates.

Table A2.13: Summary of ecotoxicity classifications for flufenacet, diflufenican

and Firebird

Sub-class Flufenacet Diflufenican Firebird 9.1 Aquatic ecotoxicity 9.1A highly

ecotoxic to the

aquatic

environment

9.1A highly

ecotoxic to the

aquatic

environment

9.1A highly ecotoxic to

the aquatic environment

9.2 Soil ecotoxicity 9.2A highly

ecotoxic to the

soil environment

9.2C harmful

to the soil

environment

9.2A highly ecotoxic to

the soil environment

9.3 Terrestrial vertebrate

ecotoxicity

9.3C harmful

to terrestrial

vertebrates

No Data 9.3C harmful

to terrestrial

vertebrates

Note: the Agency’s classifications differ from the applicant’s due to plant toxicity and

terrestrial vertebrate classifications generated from both flufenacet and formulation

(Firebird) data.

References

ERMA New Zealand 2008a. User Guide to HSNO Thresholds and Classifications.

ERMA New Zealand, Wellington.

European Union 2006. Regulation (EC) No 1907/2006 of the European Parliament

and of the Council of 18 December 2006 concerning the Registration, Evaluation,

Authorisation and Restriction of Chemicals (REACH), establishing a European


Chemicals Agency, amending Directive 1999/45/EC and repealing Council

Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as

Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC,

93/105/EC and 2000/21/EC. http://reach.jrc.it/

Klimisch, HJ, Andreae, E, Tillman, U 1997. A systematic approach for evaluating the

quality of experimental and ecotoxicological data. Regulatory Toxicology and

Pharmacology 25: 1–5.

OECD 1990. Manual for Investigation of HPV Chemicals.

http://www.oecd.org/document/21/0,3343,en_2649_34379_1939669_1_1_1_1,00.htm

l Retrieved 23 January 2008.

http://reach.jrc.it/

http://www.oecd.org/document/21/0,3343,en_2649_34379_1939669_1_1_1_1,00.html

http://www.oecd.org/document/21/0,3343,en_2649_34379_1939669_1_1_1_1,00.html


APPENDIX 3: RISK ASSESSMENT

Introduction

Quantitative risk assessments have been carried out to evaluate the level of risk to operators,

bystanders and the environment arising from the use of Firebird.

Qualitative assessments have been undertaken for all other stages of the lifecycle. In these

cases, the level of risk has been evaluated on the basis of the magnitude and likelihood of

adverse effects occurring to people or the environment (see Appendix 6 for a description of

the scales used for qualitative assessment).

Human health risk assessment

Assessment of risks to human health - manufacture

The Agency has qualitatively assessed the risks of Firebird to human health and safety during

manufacture and considers the risks to be negligible.

This assessment is based on the following considerations:

The Agency considers that, while Firebird has the potential to cause a major adverse

effect through its oral toxicity, workers handling the substance will be aware of the

hazards and the measures that need to be undertaken to ensure their own safety and

will not ingest sufficient substance to result in a major adverse effect. Even a

moderate effect is highly improbable.

The Agency considers that it is highly improbable that workers will suffer contact

sensitisation from exposure to Firebird, given requirements for personal protective

equipment (PPE), and compliance with HSNO information provisions (e.g. labels,

advertising, Safety Data Sheets (SDS)). The magnitude of skin sensitisation is

considered minor to moderate, based on the sensitivity of the exposed parties.

Quantitative assessment of the chronic risks to human health associated with exposure

to Firebird during use, indicated an acceptable level of risk as long as PPE was used.

As workers involved in manufacture of Firebird will be required to comply with the

requirements for PPE as well as comply with Department of Labour (DoL)

requirements for health and safety, the Agency considers the level of risk to workers

to be negligible.

The Agency considers the risk of repeated exposure to bystanders during manufacture

is sufficiently remote that it is not necessary to address, given that the general public

are normally excluded from manufacturing facilities.


Assessment of risks to human health – importation, storage and transport

The Agency has qualitatively assessed the risk of Firebird to human health and safety during

importation, transportation and storage and considers the risks to be negligible.


Workers and bystanders could only be exposed to the substance during transport and

storage in isolated incidents where spillage occurs.

In these circumstances, the Agency considers it highly improbable that workers or

bystanders will ingest sufficient Firebird to result in a moderate adverse effect.

The Agency considers that it is highly improbable that a spillage of Firebird will

occur during importation, transport or storage and workers or bystanders will suffer

contact sensitisation, given adherence to the HSNO controls (e.g. packaging,

identification and emergency management) and the Land Transport Rule 45001, Civil

Aviation Act 1990 and Maritime Transport Act 1994 (as applicable). The magnitude

of skin sensitisation is considered minor to moderate, based on the sensitivity of the

exposed parties.

The Agency considers the risk of target organ effects from Firebird during

importation, transport or storage to be sufficiently remote that it is not necessary to

address, given that exposure could only occur in isolated spillage incidents.

Assessment of risks to human health - disposal

The Agency has qualitatively assessed the risk to human health and safety during disposal of

Firebird, and considers the risks to the health and safety of people to be negligible.


If Firebird is disposed of by means other than use, this will be in accordance with the

requirements of the Hazardous Substances (Disposal) Regulations 2001 and the

Resource Management Act 1991.

The Agency considers that it is highly improbable that users or bystanders could

inadvertently ingest sufficient Firebird during disposal to result in an acute moderate

effect, given that Firebird will generally be disposed of by use or in accordance with

HSNO controls for disposal (e.g. disposal information requirements on labels and

SDS).

The Agency considers that it is highly improbable that workers will suffer contact

sensitisation from exposure to Firebird during disposal, given that Firebird will

generally be disposed of by use. The Agency considers it even less likely that workers

or bystanders will suffer contact sensitisation from exposure to Firebird, disposed of

by means other than use. The magnitude of skin sensitisation is considered minor to

moderate, based on the sensitivity of the exposed parties.


The Agency notes that a quantitative assessment of the chronic risks to operators

associated with exposure to Firebird during use indicated an acceptable level even if

PPE was not used. This assessment includes the possibility of prolonged and repeated

exposure to Firebird during use. The Agency considers it is even less likely that users

or bystanders could be repeatedly exposed to Firebird during disposal to such an

extent that target organ toxicity effects occur and therefore considers the chronic risk

to human health during disposal of Firebird to be negligible.

Assessment of risks to human health - use

The Agency has qualitatively assessed the acute risks of Firebird to human health and safety

during use and considers the risks to be negligible.


The Agency considers that it is highly improbable that users or bystanders could

inadvertently ingest sufficient Firebird during use to result in an acute moderate

effect, given that Firebird will be used in accordance with HSNO controls (e.g. PPE,

approved handlers).

The Agency considers that it is highly improbable that users will suffer contact

sensitisation from Firebird, given the HSNO requirements for PPE, approved handlers

and provision of hazard and precautionary information on the product label. The

magnitude of skin sensitisation is considered minor to moderate, based on the

sensitivity of the exposed parties.

Operator exposure assessment

The Agency has undertaken an assessment of risks to operator health using the United

Kingdom Pesticide Safety Directorate’s interpretation of the German BBA Model to estimate

operator exposure to the active ingredients flufenacet and diflufenican, during the use of

Firebird. This model estimates the exposure of workers to a pesticide during mixing, loading

and spray application, in mg/kg person/day (http://www.pesticides.gov.uk/index.htm). The

derived values consider both dermal and inhalation exposure routes.

The BBA model can use either the geometric mean or the 95th percentile model - the

geometric mean was used for assessing Firebird. The BBA model provides for a range of

different spray applications (tractor-mounted/trailed sprayers and hand-held sprayers) and

formulation types (liquid, wettable powder and wettable granule). Additionally, the BBA

model also allows flexibility to vary protective clothing (hands, head and body and respiratory

protection).

Five different scenarios were modelled for each of the two active ingredients, as shown in

Table A3.6.

The applicant has indicated that Firebird will be applied at a maximum rate of 300 mL

product/ha.(equivalent to 126.3 g/ha. flufenacet; 61.9g/ha. diflufenican)

The Agency has used this maximum application rate for conducting an operator exposure

assessment.


The applicant has provided modelling to estimate operators exposure to Firebird, using the

BBA model; however, this modelling is based on an application rate of 600 mL/ha. i.e. twice

the rate proposed for Firebird.

Table A3.6 details the estimated exposure for each scenario modelled. The following points

have been taken into account for the purposes of calculating the estimated exposure. For each

model only the conservative scenario as described below, has been addressed:

the concentration of active ingredients in Firebird (400g/L flufenacet and 200 g/L

diflufenican)

0.3 L of Firebird is applied per hectare

the substance is sprayed using a tractor mounted/trailed broadcast sprayer with

hydraulic nozzles;

a work rate of 20 hectares per day (the default value for boom sprayers used in the

German BBA model) is used in the absence of specific work rate data in the New

Zealand context;

a 10% percutaneous absorption value was used (the default value for the German BBA

model, and the value which has been used in the applicant’s modeling) in the absence

of specific value for flufenacet; and

the bodyweight for operators is set at 70 kg.

Table A3.6a: Estimated exposure to flufenacet for 70 kg operator under five different

exposure scenarios as predicted from the UK PSDs interpretation of the BBA Model

Exposure scenario Estimated operator Exposure (mg/kg

bw/day)

No personal protective clothing and

equipment (PPE) during mixing, loading

and application

0.016

Gloves only during mixing and loading 0.008

Gloves only during application 0.015

Full PPE during mixing, loading and

application (excluding respirator)

0.00046


application (including respirator)

0.00040

Table A3.6b: Estimated exposure to diflufenican for 70 kg operator under five different

exposure scenarios as predicted from the UK PSDs interpretation of the BBA Model

Exposure scenario Estimated operator Exposure (mg/kg

bw/day)

No personal protective clothing and

equipment (PPE) during mixing, loading

and application

0.0079

Gloves only during mixing and loading 0.0037

Gloves only during application 0.0072



0.00022




0.00020

Calculation of Acceptable Operator Exposure Level (AOEL)

The toxicological endpoint for assessment of occupational (worker) and bystander risks is the

AOEL (Acceptable Operator Exposure Level). The AOEL is the maximum daily dose

considered to be without adverse health effect for operators, workers and bystanders. It is

based on the most appropriate NOAEL/NOEL from relevant studies and is calculated by

dividing the NOAEL/NOEL by one or more uncertainty (safety) factors selected on the basis

of the extent and quality of the available data, the species for which data are available and the

nature of the effects observed.

AOEL = NOAEL (most relevant study)

Safety Factors

Selection of NOAEL:

With respect to assigning an appropriate NOAEL to calculate the AOEL, the Agency has

taken the likely duration and frequency of worker exposure into consideration. The Agency

has applied a NOAEL of 1.67 mg/kg bw/day for flufenacet. This value was obtained from the

13 week sub-chronic toxicity study in the beagle. Selection of this value as the NOEL for

flufenacet is indicated in the EFSA Draft Assessment Report (2006).

In calculating the AOEL, the Agency has used a combined safety factor of 100 to account for

intra- and interspecies variation. In the absence of specific oral absorption data for flufenacet,

the Agency has assumed 100% oral absorption.

AOEL [flufenacet] = 1.67 mg/kg bw/day x 100% = 0.017 mg/kg bw/day.

100

The active ingredient diflufenican is currently approved in several formulations. The Agency

notes that the substance has previously undergone full Part 5 assessment (refer to application

HSR04066) and an AOEL of 1 mg/kg bw/day was established. The Agency notes that this

AOEL is significantly greater than that which has been established by the EFSA (0.12 mg/kg

bw/day). The Agency has applied the more conservative AOEL, established by ESFA, to

calculate the risk quotients given below for diflufenican. The AOEL was based on highest

NOAEL of 1.6 – 1.9 mg/kg bw/day for 13 week study in rats (rounded to 2 mg/kg bw/day)

with the use of an uncertainty factor of 100 and using the lower absorption percentage of 58%

in male. (PSD, 2005).

AOEL [diflufenican] = 2.00 mg/kg bw/day x 0.58 = 0.0116 mg/kg bw/day.

100

= 0.012 mg/kg bw/day

Calculation of Risk Quotients and operator risk assessment

To assess the risks to operators the Agency has divided the estimated exposure values as

calculated from the exposure modeling by the AOEL to derive a risk quotient (RQ) for each

exposure scenario modeled (Tables A3.7a and A3.7b). A 10% percutaneous absorption value


was used (the default value for the German BBA model, and the value which has been used in

the applicant’s modeling) in the absence of specific value for diflufenican. (The other model

parameters are given above.)

RQ = Estimated Operator (or Bystander) Exposure

AOEL

A RQ > 1 indicates the likelihood of a risk to the operator (or bystander).

Table A3.7a: Risk quotients determined for each exposure scenario for flufenacet.

Exposure scenario Estimated operator

exposure (mg/kg

bw/day)

RQ

No PPE during mixing, loading and application 0.016 0.94

Gloves only during mixing and loading 0.008 0.47

Gloves only during application 0.015 0.88



0.00046 0.027



0.00040 0.024

Table A3.7b: Risk quotients determined for each exposure scenario for diflufenican.

Exposure scenario Estimated operator

exposure (mg/kg

bw/day)

RQ

No PPE during mixing, loading and application 0.0079 0.66

Gloves only during mixing and loading 0.0037 0.31

Gloves only during application 0.0072 0.605



0.00022 0.0018



0.00020 0.0016

The Agency notes that in all exposure situations modelled, risks to operators are considered to

be at acceptable levels (RQ < 1) for both active ingredients, although for flufenacet the RQ

estimate for use without PPE is close to 1.0. The Agency considers that, while the ‘no PPE’

exposure model leads to an acceptable level of risk, it is appropriate to retain requirements for

PPE since the use of PPE when handling agrichemicals is good practice. The Agency notes

that the HSNO PPE requirements are not prescriptive allowing users to select an appropriate

level of PPE.

The applicant has indicated that Firebird is intended to be applied using ground-based

methods only, therefore any human health risks associated with aerial application of the

substance have not been assessed.

Exposure for re-entry workers has not been estimated because even with no PPE operator

exposures do not indicate a risk for operators. Re-entry workers are not exposed to mixing

and loading operations so their exposures are likely to be lower that those of operators. The

Agency also notes that the nature of the use for Firebird (for winter cereals early in the growth

cycle) is an application type not likely to be associated with re-entry activity.


Public health exposure and risk assessment

The main potential source of exposure to the general public from Firebird (other than via food

residues which will be considered as part of the registration of this substance under the

Agricultural Compounds and Veterinary Medicines (ACVM) Act 1997) is via spray drift.

Given the results of the modelling as outlined above, the Agency considers that the use of

Firebird will not pose a significant risk to bystanders. The modeling above suggests that

bystanders may be at risk from the application of Firebird as they will not be wearing PPE,

however, the Agency notes that bystanders are not exposure during mixing loading and are

likely to be further away from the application area than operators. Therefore, the risk to

bystanders is estimated as acceptable for both active ingredients.

Environmental exposure and risk assessment

Assessment of environmental risks – manufacture/packing, importation, transport and

storage

The Agency has qualitatively assessed the risks to the environment of Firebird during

manufacture, importation, transportation and storage and considers the risks to be negligible.


The magnitude of adverse effects on the environment from a spillage during

manufacture, importation, transport or storage are considered by the Agency to be

moderate, as although the substance is toxic to the aquatic and terrestrial

environments, and harmful to terrestrial vertebrates, any spill would involve small

quantities which would lead to localised effects only.

The Agency also considers such an event to be highly improbable given adherence to

the HSNO controls (e.g. packaging, identification and emergency management) and

the Land Transport Rule 45001, Civil Aviation Act 1990 and Maritime Transport Act

1994 (as applicable).

Assessment of environmental risks – disposal

The Agency has qualitatively assessed the risks to the environment of disposal of Firebird and

considers the risks to be negligible.


Firebird will generally be disposed of by normal use as a herbicide.

If Firebird is disposed of by means other than use, this will be in accordance with the

requirements of the Hazardous Substances (Disposal) Regulations 2001 and the

Resource Management Act 1991. The Agency considers the likelihood of adverse

effects to the environment arising from disposal to be highly improbable and the

magnitude of such effects minor.


Assessment of environmental risks - use

For Class 9 substances, irrespective of the intrinsic hazard classification, the ecological risk

can be assessed for a substance by calculating a risk quotient based on an estimated exposure

concentration. Such calculations incorporate toxicity values, exposure scenarios (including

spray drift, application rates and frequencies), and the half lives of the component(s) in soil

and water. The calculations provide an Estimated Environmental Concentration (EEC) which,

when divided by the LC50 or EC50, gives a risk quotient (RQ).

Acute RQ = EECshort term Chronic RQ = EEClong term

LC50 or EC50 NOEC

If the RQ exceeds a predefined level of concern, this suggests that it may be appropriate to

refine the assessment or to apply the approved handler control (AH) control and/or other

controls to ensure that appropriate matters are taken into account to minimize off-site

movement of the substance. Conversely, if a worst-case scenario is used, and the level of

concern is not exceeded, then in terms of the environment, there is a presumption of low risk

which is able to be adequately managed by such things as label statements (warnings,

disposal). The AH control can then be removed on a selective basis.

Levels of concern (LOC) developed by the USEPA (Urban and Cook 1986) and adopted by

the Agency, to determine whether a substance poses an environmental risk are provided in

Table A3.1.

Table A3.1: Levels of concern as adopted by the Agency.

Endpoint LOC Presumption

Aquatic (fish, invertebrates)

Acute RQ≥ 0.5 High acute risk

Acute RQ 0.1-0.5 Risk can be mitigated through restricted use

Acute RQ< 0.1 Low risk

Chronic RQ≥ 1 High chronic risk

Plants (aquatic and terrestrial)

Acute RQ≥ 1 High acute risk

Birds (EU Guideline, 2008)

Acute dietary

TER ≤

10 High acute risk

Chronic TER ≤ 5 High chronic risk

The Toxicity Exposure Ratios (TER) values are compared with assessment factors (trigger

values, levels of concern) which according EFSA (2008) are < 10 for the acute and short-term

scale and < 5 for the long-term scale. If either of these triggers is met imposition of controls to

reduce exposure or further steps to improve the risk assessment should be considered.


Aquatic risk - Flufenacet

Assessment of Expected Environmental Concentration

The Agency has used the Generic Estimated Environmental Concentration Model v2

(GENEEC2) surface water exposure model (USEPA 2001) to estimate the EEC of flufenacet

in surface water which may potentially arise as a result of spray drift and surface runoff from

the applicant’s proposed New Zealand use pattern.

The parameters used in the GENEEC2 modelling are listed in Table A3.2 and represent the

recommended use on winter wheat (highest rate) as a conservative estimate.

Table A3.2: Input parameters for GENEEC2 analysis. Flufenacet Reference

Application rate 300 mL (0.1263 g) Product label

Application frequency Once per season Product label

Application interval NA

Kd * 3.1 Kelley and Wood (1992)

Report No. 103903

GLP, Klimisch score: 1

Disk 5, 00000136

Aerobic soil DT50** 45.51 days Pangilinan and Smith (1994).

Report No. 106408


Disk 4, 00000119

Pangilinan and Smith (1994).

Report No. 106420


Disk 4, 00000120


Report No. 106664


Disk 4, 00000123

Pesticide wetted in? No Product label

Methods of application Ground-based only Product-label

‘No spray’ zone NA

Water solubility 56 mg/L Krohn (1992) Report No. 14 410 0746


Disk 2, 00000016

Aerobic aquatic DT50*** 84.6 days Kelley et al. (1995)

Report No. 106928


Disk 5, 00000151

Aqueous photolysis DT50 Stable Kasper and Shadrick (1995)

Report No. 106246


Disk 2, 00000020

*The lowest of the Kd values measured in a non-sand textured soil (i.e. not sand, coarse sand,

fine sand, loamy sand) (USEPA, 2001).

**The soil DT50 value of 45.51 for flufenacet follows the GENEEC2 calculation of the upper

90% confidence limit on the mean value (n≥2) of the five aerobic laboratory values measured

at 20°C (USEPA, 2001).

***Longest value taken in accordance with GENEEC2 guidance document (USEPA, 2001).


Output from the GENEEC2 model. RUN No. 1 FOR flufenacet ON Winter whe * INPUT VALUES *

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

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

ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)

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

.112( .112) 1 1 3.1 56.0 GRHIFI( 6.6) .0 .0

FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)

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

METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED

(FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

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

45.51 2 N/A .00- .00 84.60 84.60

GENERIC EECs (IN MICROGRAMS/LITER (PPB)) Version 2.0 Aug 1, 2001

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

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

GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

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

4.55 4.51 4.31 3.88 3.60

The Estimated Environmental Concentration (EEC) for flufenacet as estimated by GENEEC2

are:

Peak EEC: 4.55 µg/L 0.00455 mg/L

Chronic EEC (21 days): 4.31 µg/L 0.00431 mg/L

Table A3.3: Aquatic ecotoxicity endpoints to be used in risk assessment

(formulation test data was used where possible). Exposure Species LC50 or EC50

(mg formulation/L)

LC50 or EC50

(mg a.i./L)

Acute Onchorynchus mykiss 12.3 4.18

Daphnia magna > 100 > 33.95

Selenastrum capricornutum 0.00663 (ErC50) 0.00225 (ErC50)

Chronic Onchorynchus mykiss* 0.18

Daphnia magna* 3.26

* data from active ingredient

Assessment of acute risk

The Estimated Environmental Concentration (EEC) for flufenacet as estimated by GENEEC2

are shown in Table 3.4, along with the aquatic data for flufenacet for the most sensitive

species tested (further details on these toxicity data are included in Table A2.7).

Table A3.4: Acute risk quotients derived from the GENEEC2 model and toxicity data.

Peak EEC from

GENEEC2 (mg/L)

LC50 or EC50

(mg/L)

RQ (Acute)

EEC/ LC50 or EC50

Fish 0.00455 4.18 0.001

Crustacea >33.95 0.0001

Algae 0.00225 2.022


When compared against the relevant acute risk quotients (Table A3.1), the acute RQs derived

from the GENEEC2 modelling for flufenacet indicate the following:

For fish and crustacean: the acute risk is low

For algae: the acute risk is high

Assessment of chronic risk

Table A3.5: Chronic risk quotients derived from the GENEEC2 model and chronic

aquatic toxicity data.

21-day EEC from

GENEEC2 (mg/L)

NOEC

(mg/L)

RQ (Chronic)

EEC/ NOEC

Fish 0.00431 0.18 0.024

Crustacea 3.26 0.001

When compared against the relevant chronic risk quotients (Table A3.1), the chronic RQs

derived from the GENEEC2 modelling for flufenacet indicate the following:

For fish and crustacean: the chronic risk is low

For algae: the levels of concern to estimate chronic risks to algae are not

currently defined

Based on the acute RQs for algae, the Agency considers it is appropriate to retain the

approved handler controls for Firebird when it is used in a wide dispersive manner, or by a

commercial contractor. Further, the Agency considers that the application rate proposed by

the applicant and used in the modelling should be set as a maximum application rate.

Avian Toxicity - Flufenacet

The avian toxicity assessment was performed according to “Risk Assessment to Birds and

Mammals (EFSA 2008)”.

For practical reasons it is useful to conduct the risk assessment in two stages. The screening

step contains simple procedures for the calculation of the TERs (Toxicity Exposure Ratios).

These procedures involve standard scenarios and default values for the exposure estimate

which can be performed with a low input of effort. The tier 1 standard scenarios include

intake via feed and represent a realistic worst case assessment where the exposure scenarios

are selected to reflect a situation where the total daily feed is contaminated. The aim is to

exclude, with sufficient certainty, false negatives (= risk remains undetected).

Acute toxicity

Screening step

Step 1 Identify which of the indicator species listed in Table I.1 (Annex I) is relevant to the crop.

Step 2 Calculate the daily dietary dose (DDD) for a single application by multiplying the shortcut value

presented in Table I.1 with the application rate in kg/ha.


DDD single application = application rate [kg/ha] x short cut value

Step 3 Multiply the daily dietary dose for a single application with an appropriate multiple application

factor for 90th percentile residue data (MAF90) when the substance is applied two or more times.

Or calculate a specific MAF90 according to Appendix 15 for non-standard application intervals.

DDD multiple applications = DDD single application x MAF90

Step 4 Take the appropriate LD50 (mg/kg bw/d) for birds.

Step 5 Calculate the toxicity-exposure-ratio

TER = LD50 / DDD

Step 6 Compare the TER to the respective trigger value.

TER ≥ 10 No refinement required

TER < 10 Go to first-tier risk assessment (step 7)

Table A3.6: Acute avian risk assessment – screening step.

Crop1

Indicator

Species2

Short-cut

value3

(90th percentile RUD)

LD504

Application

rate (kg/ha)

MAF905

TER6

Trigger

value

Cereal Small

omnivorous

bird

158.8 1833.03 0.1263 1 91.4 <10

1

Crop type Table I.1 (Annex 1) and Appendix 10 2

Species type Table I.1 (Annex 1) and Appendix 10 3

Residue Unit Dose (90th

percentile) Table I.1 (Annex 1) 4 Geometric mean if multiple species tested

5 Multiple application factor (90

th percentile) Table 11 and Appendix 15

6 Toxicity-exposure ratio = LD50 / Estimated environmental concentration

Flufenacet, as a component of Firebird, applied according to the manufacturer’s instructions is

unlikely to be acutely toxic to birds. The first-tier risk assessment is not necessary.

Chronic toxicity

Steps to determine the reproductive risk to birds It should be noted that the initial steps are based on worst-case assumptions and should be used to

identify those substances and associated uses that do not pose a risk to birds and for which hence

no further reproductive risk assessment is required.

Step 1


Determine if breeding birds will be exposed to either the active substance or the associated

product.

Step 2 If exposure is possible, the lowest NOAEL from the avian reproduction study/studies should be

determined. It should be noted that the endpoints from the current guidelines are presented as ppm

diet or mg a.s./kg diet. Therefore, it is necessary to convert the endpoints to daily doses, i.e. mg

a.s./kg bw/d. In the first instance a generic factor of 0.1 can be used and applied to the ppm or mg

a.s./kg food endpoint.

Step 3 Identify the appropriate indicator species and mean shortcut value for the crop under assessment

from Table I.1 in Annex 1 and multiply this by the application rate in kg a.s./ha. If multiple

applications are to be made, then the appropriate ‘multiple application factor’ or MAFm should be

used.

DDD = application rate x short-cut value x MAFm

Step 4 Compare the lowest NOAEL to the DDD generated.

TER ≥ 5 No refinement required

TER< 5 Go to phase-specific approach (step 5)

Table A3.7: Chronic avian risk assessment – screening step.

Crop1

Indicator

Species2

Short-cut

value3

(Mean RUD)

NOAEL4

mg ai/kg bw/d Application

rate (kg/ha)

MAFm5

TER6

Trigger

value

Cereal Small

omnivorous

bird

64.8 26.13 0.1263 1 3.19 <5

1

Crop type Table I.1 (Annex 1) and Appendix 10 2

Species type Table I.1 (Annex 1) and Appendix 10 3

Residue Unit Dose (Mean) Table I.1 (Annex 1) 4 Most sensitive reproductive parameter (Geometric mean if multiple species tested)

5 Multiple application factor (Mean) Table 11 and Appendix 15

6 Toxicity-exposure ratio = LD50 / Estimated environmental concentration

Based upon the chronic toxicity screening step, flufenacet as a component of Firebird applied

according to the manufacturer’s instructions, may be chronically toxic to birds. The risk

assessment requires the refinement of a tier 1 assessment.

Chronic avian risk assessment – Refining step (Tier 1)

Step 5

In the phase-specific approach the breeding cycle of birds is divided into five phases,

namely:

1) pair formation and establishing site selection;


2) copulation and egg laying ranging from 5 days pre-laying through to the end of the egg-laying

period;

3) incubation and hatching;

4) juvenile growth and survival until fledging; and

5) post-fledging.

Extract the following toxicity endpoints from the avian reproduction studies:

NOAEL for the number of eggs laid per hen;

NOAEL for mean eggshell thickness;

NOAEL for the proportion of fertile eggs per eggs set per hen or number

viable embryos over number of eggs set;

NOAEL for the proportion of hatching per fertile eggs per hen or percent

hatching of viable embryos;

NOAEL for the proportion of 14-day old juveniles per number of hatchlings;

NOAEL for 14-day juvenile weights per hen.

If more than one avian reproduction study is available, then the above endpoints should be

extracted for each study.

Step 6 Once the above endpoints have been extracted then the endpoints need to be converted to daily

dose using the mean value for food consumption over the whole study and average body weight

over the duration of the study at the NOAEL.

Step 7 If more than one study is available, then the datasets can be either merged or the geometric mean

of the endpoints used.

Step 8 In addition to the above reproductive endpoints, it is also necessary to determine an endpoint to

assess the risk to the phases relevant to chick survival. In order to calculate this endpoint, the LD50

value used in the acute assessment (see section 3.1) should be divided by 10.

Step 9 In order to address uncertainty about the appropriate exposure scenario for the phase-specific

approach, two exposure scenarios are assessed, namely:

1) A scenario where the residue on treated food is assumed to be based on a 1- to 3-day

Period;

2) A scenario where the residue on treated food is assumed to be based on a 21-day period.

For the first scenario, it is assumed that a short exposure could lead to reproductive effects,

whereas in the second scenario it is assumed that long-term exposure could lead to reproductive

effects.

Identify the appropriate crop and generic focal species in Tables I.3 (Annex I). Where more

than one generic focal species is highlighted, the one that is relevant in terms of time of

application or growth stage should be selected. Where there is more than one generic focal species

in terms of timing etc, then it is proposed that risk assessment should be carried out with all

relevant generic focal species and then refined as necessary.

Step 10


Once an appropriate generic focal species has been selected, then the daily dietary dose (DDD)

based on 1-, 2-, 3- and 21-day exposure should be determined. The 1-day DDD uses the initial

exposure estimate. In order to calculate the 2-, 3- and 21-d DDDs it is necessary to multiply by a

time-weighted average (TWA) factor to the initial exposure. For 2 days, the factor is 0.93; for 3

days 0.90 and for 21 days 0.53.

DDD = application x short-cut x TWA x MAFm

Step 11 In order to have an exposure estimate for chick survival stage, it is necessary to calculate a 3-day

DDD assuming a shortcut value of 22.7 for chicks fed foliar dwelling insects, and 3.8 for those

fed ground dwelling insects. In the first instance both scenarios should be assessed, unless it can

be justified that one scenario is not relevant to the proposed use.

Step 12 Compare the above DDD to the relevant phase-specific NOAEL.

Step 13 Interpret the risk assessment following the below table.

Scenario Assessment outcome

1 to 3-day ETE

(Effects are based

on short-term

exposure)

TER < 5 TER < 5 TER < 5

21-day ETE

scenarios (i.e.,

effects are based on

long-term

exposure)

TER ≥ 5 TER ≥ 5 TER < 5

Next steps No further

refinement

required.

Further refinement is

required. The outcome

of the risk assessment

indicates that one

possible refinement

step is to try to

determine if the effects

are the result of short-

term exposure.

Further refinement is required.

However, the outcomes of the risk

assessment indicates that little will

be gained by additional effects

data and hence trying to determine

if the effects are the result of short-

term exposure. It is recommended

that refinements should

concentrate on refining the

exposure as well as the potential

consequences of effects.

Table A3.8: Summary of values applied in the phase specific approach. Short-cut

value (Mean RUD)

Lark

Short-cut

value (Mean RUD)

Goose

Application

rate (kg/ha)

MAFm TWA

2 days

TWA

3 days

TWA

21 days

Chick

short-cut

value

3 days

Chick

short-cut

value

21 days

10.9 26.7 0.1263 1 0.93 0.90 0.53 3.8 22.7

Table A3.9: Summary of toxicity values applied in the phase specific approach.

LD50 NOAEL1 NOAEL

2 NOAEL

3 NOAEL

4 NOAEL

5 NOAEL

6

Geometric 1833.03 88.70 146.49 88.70 26.13 146.49 58.92


Mean

NOAEL1 number of eggs laid per hen

NOAEL2

mean egg shell thickness

NOAEL3

proportion of viable eggs set per hen

NOAEL4

proportion of hatchling per viable eggs per hen

NOAEL5

proportion of 14 day old juveniles per number of hatchlings per hen

NOAEL6

14 day juvenile weights per hen

Note: Geometric mean of data used (where more than one study available).

Table A3.10: Pair formation and establishing site selection.

Short term Long term

LD50/10 and 1 day DDD LD50/10 and 21 day TWA DDD

Lark TER 133.15 251.23

Goose TER 54.36 102.56

Trigger level < 5

Table A3.11: Copulation and egg laying.


NOAEL1 and 1

day DDD

NOAEL2 and 1

day DDD

NOAEL1 and 21

day TWA DDD

NOAEL2 and 21

day TWA DDD

Lark

TER

64.43 106.41 121.57 200.77

Goose

TER

26.30 43.43 49.63 81.96

Trigger

level

< 5

Table A3.12: Incubation and hatching.


LD50/10

and 1 day

DDD

NOAEL3

and 1 day

DDD

NOAEL4

and 1 day

DDD

LD50/10

and 21

day TWA

DDD

NOAEL3

and 21

day TWA

DDD

NOAEL4

and 21

day TWA

DDD

Lark

TER

133.15 64.43 21.09 251.23 121.57 35.81

Goose

TER

54.36 26.30 8.61 102.56 49.63 14.62

Trigger

level

< 5

Table A3.13: Juvenile growth and survival. Short term Long term

LD50/10

and 2

day

TWA

DDD

LD50/10

and 1

day

DDD Chick

ground

dwelling

LD50/10

and 1

day

DDD Chick

foliar

dwelling

NOAEL5

and 3

day

TWA

DDD

LD50/10

and 21

day

TWA

DDD

LD50/10

and 21

day

DDD Chick

ground

dwelling

LD50/10

and 21

day

DDD Chick

foliar

dwelling

NOAEL5

and 21

day

TWA

DDD


insects

value insects

value insects

value insects

value

Lark

TER

143.17 381.93 63.94 118.23 251.23 720.62 120.63 200.77

Goose

TER

58.45 381.93 63.94 48.27 102.56 720.62 120.63 81.96

Trigger

level

< 5

Table A3.14: Post-fledgling survival.


LD50/10 and

1 day DDD Chick ground

dwelling insects

value

LD50/10

and 1 day

DDD Chick foliar

dwelling

insects value

NOAEL6

and 3 day

DDD

LD50/10

and 21

day TWA

DDD Chick ground

dwelling

insects value

LD50/10

and 21

day TWA

DDD Chick foliar

dwelling

insects value

NOAEL6

and 21

day TWA

DDD

Lark

TER

381.93 63.94 47.55 720.62 120.63 80.75

Goose

TER

381.93 63.94 19.41 720.62 120.63 32.96

Trigger

level

< 5

Based upon the refined risk assessment for chronic toxicity (Tier 1), flufenacet as a

component of Firebird applied according to the manufacturer’s instructions, is unlikely to be

chronically toxic to birds.

Aquatic risk - Diflufenican

Assessment of Expected Environmental Concentration

The Agency has used the Generic Estimated Environmental Concentration Model v2

(GENEEC2) surface water exposure model (USEPA 2001) to estimate the EEC of

diflufenican in surface water which may potentially arise as a result of spray drift and surface

runoff from the applicant’s proposed New Zealand use pattern.

The parameters used in the GENEEC2 modelling are listed in Table A3.15 and represent the

recommended use on winter wheat (highest rate) as a conservative estimate.

Table A3.15: Input parameters for GENEEC2 analysis. Diflufenican Reference

Application rate 300 mL (0.0619 g/ha) Product label

Application frequency Once per season Product label

Application interval NA

Koc * 27801 Internal database

Aerobic soil DT50** No laboratory data; field data 311-733

days (mean = 522 days)

Internal database

Pesticide wetted in? No Product label

Methods of application Ground based Product label

‘No spray’ zone No Product label

Water solubility 0.05 mg/L Internal database

Aerobic aquatic DT50*** 1044 days Model default


Aqueous photolysis DT50 0 days Model default

*if neither the Kd nor the Koc are available, use 0.35 times the Kow value (USEPA, 2001).

**Value previously used in HSR04066 assessment

***If unavailable use the default of 2 x aerobic soil input value (USEPA, 2001).

Output from the GENEEC2 model.

RUN No. 1 FOR diflufenican ON winter whe * INPUT VALUES *

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

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

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

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

.055( .055) 1 1 27801.0 50.0 GRHIFI( 6.6) .0 .0

FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)

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

METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED

(FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)

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

522.00 2 N/A .00- .00 ****** 1044.00

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

GEEC AVG GEEC AVG GEEC AVG GEEC AVG GEEC

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

293.25 271.41 174.55 84.80 59.21

The Estimated Environmental Concentration (EEC) for diflufenican as estimated by

GENEEC2 are:

Peak EEC 0.293 µg/L 0.000293 mg/L

Chronic EEC (21 days) 0.175 µg/L 0.000175 mg/L

Table A3.16: Aquatic ecotoxicity endpoints to be used in risk assessment

(formulation test data was used where possible). Exposure Species LC50 or EC50

(mg formulation/L)

LC50 or EC50

(mg a.i./L)

Acute Onchorynchus mykiss 12.3 >2.05

Daphnia magna > 100 > 16.63

Selenastrum capricornutum 0.00663 (ErC50) 0.00110 (ErC50)

Chronic Onchorynchus mykiss* ND

Daphnia magna* 0.03

* data from active ingredient

Assessment of acute risk

The Estimated Environmental Concentration (EEC) for diflufenican as estimated by

GENEEC2 are shown in Table 3.17, along with the aquatic data for diflufenican for the most

sensitive species tested (further details on these toxicity data are included in Table A2.7).

Table A3.17: Acute risk quotients derived from the GENEEC2 model and toxicity data.

Peak EEC from LC50 or EC50 RQ (Acute)


GENEEC2 (mg/L) (mg/L) EEC/ LC50 or EC50

Fish 0.000293 >2.05 *

Crustacea >16.63 *

Algae 0.00110 0.27

*risk to fish not calculated due to low water solubility (0.05 mg/L).

When compared against the relevant acute levels of concern (Table A3.1), the acute RQs

derived from the GENEEC2 modelling for diflufenican indicate the following:

For fish and crustacean: the acute risk is low

For algae: the acute risk is low

Assessment of chronic risk

Table A3.18: Chronic risk quotients derived from the GENEEC2 model and chronic

aquatic toxicity data.

21-day EEC from

GENEEC2 (mg/L)

NOEC

(mg/L)

RQ (Chronic)

EEC/ NOEC

Fish 0.000175 ND --

Crustacea 0.03 0.006

When compared against the relevant chronic levels of concern (Table A3.1), the chronic RQs

derived from the GENEEC2 modelling for diflufenican indicate the following:

For fish and crustacean: the chronic risk is low

For algae: the levels of concern to estimate chronic risks to algae are not

currently defined

Avian toxicity – Diflufenican

The acute and chronic avian toxicity values used in EFSA DAR (2006) were the LD50 of >

2150 mg/kg bw and the NOEC of 91.84 mg/kg bw, respectively. However, since other

formulations containing diflufenican have been assessed without assessment of avian risk

they have not been used in the evaluation of this application. These values reported by EFSA,

as well as the original studies supplied by the applicant, will be assessed by the Agency upon

a reassessment of diflufenican.

It is also noted that the assessment of avian risk carried out in the EFSA DAR (2006) was for

a use rate of diflufenican double that to be used in New Zealand. This assessment showed no

acute or chronic risks to birds.

Terrestrial risk - Firebird

Spray Drift Modelling – Phytotoxicity

Firebird is sprayed at a maximum application rate of 0.372 kg/ha.or 37.2 mg/m2.

Soil-based exposure – seedling emergence

If it assumed that the Firebird is dispersed to a depth of 0.05 m and the density of soil is 1500

kg/m3, then the 37.2 mg/m

2 Firebird will be dispersed within 75 kg of soil/m

2 giving 0.496

mg/kg.


If it is assumed that 6.6% (fine spray, high boom) of the Firebird will reach directly outside

the target area (an assumption based on GENEEC2 modeling), then the concentration of

Firebird adjacent to a sprayed field would be 0.033 mg/kg soil.

Firebird generates an EC50 value of 0.19043 kg/ha.(0.25 mg/kg, see Table A2.10A for further

details of this study) for all plant species tested. Consequently, Firebird (high boom, fine

spray) results in a risk quotient of 0.132.

Foliar exposure – vegetative vigour

Firebird is sprayed at a maximum application rate of 372 g/ha.(300 mL/ha).

If it is assumed that 6.6% (fine spray, high boom) of the Firebird will reach directly outside

the target area (an assumption based on GENEEC2 modeling), then the concentration of

Firebird adjacent to a sprayed field would be 24.55 g/ha.

Firebird generates an EC50 value of 27.75 g/ha., (see Table A2.10 for further details of this

study) for cucumber. Consequently, Firebird (fine spray, high boom) results in a risk quotient

of 0.885.

According to the risk assessment performed by the Agency, Firebird does not pose a risk to

non-target plants when applied via the high boom, fine spray scenario.

Risk to Terrestrial Invertebrates (Bees) - Firebird

Firebird is not toxic to bees, therefore no risk assessment is required.

Table 3.19: Summary of effects of exposure to flufenacet on beneficial invertebrates.

Test species Results

Test methodc

[Reference

number]

Predaceous mite

Typhlodromus pyri

Juveniles (protonymphs) of T. pyri were exposed to fresh

residues of FOE 5043 WG 60 applied on a glass substrate.

FOE 5043 WG 60 – 60% flufenacet

The three treatments were each applied as five separate

replicates.

Rate 6.0 µg a.i./sqcm.

It was found that exposure to FOE 5043 WG 60 led to 100

% juvenile mortality.

As no individuals survived the juvenile exposure to FOE

5043 WG 60, no effect on reproduction could be assessed.

Reproduction of the individuals exposed to the harmless

reference was normal.

No effect of juvenile exposure to FOE 5043 WG 60 on egg-

MITOX (1995)

lOBC-Working

Group "Pesticides

and Beneficial

Arthropods".

Report No.

MB013

GLP

Klimisch score: 1

Disk 5

00000190



Test methodc

[Reference

number]

hatch success has been determined, because of the 100%

juvenile mortality in the treatments with FOE 5043 WG60.

Note: One replicate of the control was not taken into

account, as the numbers of individuals that had escaped,

exceeded 20 %. This did not affect the validity of the whole

test.

Applicant summary:

As predatory mites are not beneficial species relevant to

product use (preemergence/early postemergence herbicide)

there is no risk to affect biological control capacity. Thus,

no further tests under extended laboratory or semi field

conditions have been conducted.

Parasitic Wasp

Aphidius

rhopalosiphi

A. rhopalosiphi were exposed to fresh residues of FOE

5043 WG 60 applied on a glass substrate.


Rate of 1 kg /ha.(200 L water).

No wasps died during the first 24 h and only three out of 30

wasps (10 %) had died after 48 h following exposure to

FOE 5043 WG 60. None of the 30 wasps died in the control

over 48 h and all of the insects in the toxic standard

treatment were dead within 24 h.

Ten females from both the FOE 5043 WG 60 and the

control treatments were then confined individually over pots

of aphid-infested barley seedlings for 24 h. The numbers of

mummies (parasitised aphids) produced was assessed 9 days

later.

The mean numbers of mummies produced was 22.6/female

in the FOE 5043 WG 60 treatment and 41.5/female in the

control (Difference 46% < 50%).

It was concluded from this study that it is unlikely that FOE

5043 WG 60 would be harmful to A. rhopalosiphi when

used under conditions of good agricultural practice.

Agrochemical

Evaluation Unit,

The University of

Southampton

(1995)

ESCORT 1994.

Report No.

BAY-94-7

GLP

Klimisch score: 1

Disk 5

00000191

Parasitic Wasp

Aphidius

rhopalosiphi

Extended Laboratory Test to Evaluate the Side-Effects

of the Herbicide FOE 5043 WG 60 on Adults of the

Parasitic Wasp when applied to barley plants.

Rate of 1 kg /ha.(200 L water).


Over the 48 h confinement period, no wasps died in either

the FOE 5043 WG 60 treatment or in the control. With the

toxic standard treatment, all of the wasps died within 24 h.

Behavioural observations suggested that fresh residues of

the FOE 5043 WG 60 were slightly repellent.

Agrochemical

Evaluation Unit,

The University of

Southampton

(1995)

In house protocol.

Report No.

BAY-95-3

GLP

Klimisch score: 1

Disk 5

00000195



Test methodc

[Reference

number]

In the fecundity assessments, the FOE 5043 WG 60

treatment did not significantly affect the numbers of

offspring produced, with 12.1 mummies produced per

female compared with 15.1 mummies per female in the

control.

Carabid beetles

Poecilus cupreus

FOE 5043 WG 60

Rate 1 kg/ha.


Treatment with 1 kg/ha.FOE 5043 WG 60 had no adverse

effects on the tested ground beetles.

The individual feeding activity was statistically also not

affected by the test compound.

Schmuck (1995)

BBA 23-2.1.8

Report No.

E 371 0852-6

GLP

Klimisch score: 1

Disk 5

00000192

Lycosid spiders

Pardosa agrestis

FOE 5043 WG 60

Rate 1 kg/ha.


The spray treatment with 1 kg/ha.FOE 5043 WG 60 did not

adversely affect the behaviour or survival of exposed

lycosid spiders.

The individual feeding activity was statistically also not

affected by the test compound. If the total number of flies

eaten per viable spider per day in the control plots is used as

a basis for comparison and assumed to be 100%, then the

feeding rates for the 1 kg/ha.FOE 5043 WG 60 treatment

were 89%.

Schmuck (1995)

BBA 23-2.1.9

Report No.

E 382 0854-0

GLP

Klimisch score: 1

Disk 5

00000193

Rove Beetles

Aleochara bilineata

FOE 5043 WG 60

Rate 1 kg/ha.


The observed mortality rates during the 28 day exposure

period were 3%, 0% and 55% for the control, FOE 5043

WG 60 and the reference treatment, respectively.

The reproductive performance of the exposed rove beetles

was not impeded by the test substance. If the total number

of beetles that emerged from pupae in the control chambers

(= 2428) is used as a basis for comparison and assumed to

be 100%, then the offspring emergence rates for the FOE

5043 WG 60 treatments was 99.6%.

Schmuck (1995)

IOBC/WPRS 5.2.5

Report No.

E 380 0953-8

GLP

Klimisch score: 1

Disk 5

00000194

Ladybird beetle

Coccinella

septempunctata

FOE 5043 WG 60

Rate 1 kg/ha.


Control larvae as well as larvae exposed to spray deposits of

FOE 5043 WG 60, entered the pupal stage between day 5

and day 8 (average 6.3 days and 6.7 days) after treatment.

Adult beetles emerged in both groups between day 9 and

day 13 (average: 11.1 days and 11.0 days) following the

application.

Schmuck (1995)

BBA VI, 23-2.1.5

Report No.

E 376 0652 - 2

GLP

Klimisch score: 1

Disk 5

00000196



Test methodc

[Reference

number]

In the controls, 36 ladybird larvae completed successfully

the metamorphosis (= 75%). In the cages which received a

treatment, 31 out of 50 (= 69%) larvae entered the adult

stage.

The number of eggs laid per female in the treatment group

(mean value: 739.9 eggs per female; n= 2) was statistically

significant higher than in the control (mean value: 525.9

eggs per female; n=2). Hatch rate of the eggs laid in the

treatment group (70.5%; n=2) was also statistically

significant higher than those laid by the controls (65.0%;

n=2). If the total number of offspring per female in the

control chambers (339.5; n=2) is used as a basis for

comparison and assumed to be 100%, then the offspring

emergence rate for females exposed to the FOE 5043 WG

60 treatments was 154% (521.8; n=2).

Table 3.20: Summary of effects of exposure to Firebird on beneficial invertebrates.


Test methodc

[Reference

number]

Predaceous mite

Typhlodromus pyri

Tier 1 testing

Effects of Flufenacet & Diflufenican SC 600 on the

Predatory Mite Typhlodromus pyri Scheuten (Acari,

Phytoseiidae) in the Laboratory -Dose Response Design-

LR50 (7 d)

81.8 mL/ha

95% CI:

71.4 – 93.8 mL/ha

NOER:

45.0 mL/ha.(not significantly different to controls)

The reproduction was statistically not affected at rates up to

of 45 mL/ha.Flufenacet & Diflufenican SC 600/ha.(Student

t-test, α = 0.05).

Higher tier testing

The effects of Flufenacet & Diflufenican SC 600 on

Typhlodromus pyri (Acari: Phytoseiidae) on natural

substrate in laboratory (extended laboratory test).

LR50 (7 d)

110.2 mL/ha

95% CI:

30.2 – 402.2 mL/ha

NOER:

83.2 mL/ha.(not significantly different to controls)

Goβmann (2001)

Louis/Ufer 1995

Blummel et al.

2000

Report No.

9352063

GLP

Klimisch score: 1

Disk 14

00000560

Chauzat (2002)

Blummel et al.

2000

Report No.

01TYBYL12

GLP

Klimisch score: 1

Disk 14

00000561



Test methodc

[Reference

number]

The reproduction was statistically not affected at rates up to

of 83.2 mL/ha.Flufenacet & Diflufenican SC

600/ha.(Student t-test, α = 0.05).

Parasitic Wasp

Aphidius

rhopalosiphi

Effects of Flufenacet & Diflufenican SC 600 on the

Parasitoid Aphidius rhopalosiphi in the Laboratory

- Limit Test - LR50 (2 d)

> 700 mL/ha

The reproduction was not affected at rates up to 700

mL/ha.Flufenacet & Diflufenican SC 600/ha.

Moll and Butzler

(2001)

Mead-Briggs et al.

2000

Report No.

9351001

GLP

Klimisch score: 1

Disk 14

00000562

Carabid beetles

Poecilus cupreus

FOE 5043 (40%) + Diflufenican (19%) WG 60: Acute

effects of a spray application on carabid beetles (Poecilus

cupreus) under laboratory conditions

LR50 (14 d)

> 600 g/ha

The spray-application with 600 g FOE 5043 + OFF WG 60 /

ha.caused in no adverse effects on the treated beetles. Only

negligible effects were observed on 3 beetles for 4 - 6 hours

after application.

The individual feeding activity, following a spray

application of 600 g FOE 5043 + OFF WG 60 / ha., was not

statistically (p = 0.05) affected by the test compound.

Hennig-Pusch

(1996)

BBA 23-2.1.8

SETAC 1994

Report No.

HGP/LA PC002

GLP

Klimisch score: 1

Disk 14

00000563

Ladybird beetle

Coccinella

septempunctata

Testing toxicity to beneficial arthropods Ladybird -

Coccinella septempunctata L. / Larvae according to BBA

Guideline VI, 23-2.1.5 (1989): Foe 5043 & Diflufenican

WG 60

Rate: 600 g FOE 5043 + OFF WG 60 / ha

LR50 (18 d)

> 600 g/ha

In the test variant with Foe 5043 & Diflufenican WG 60

there was 2.4 % mortality of the ladybird larvae (corrected

by SCHNEIDER-ORELLI).

A decrease of the fertility was not observed in comparison

with the control. The relative decrease of beneficial

effectivity was E = -49.6 % (i.e., there was an increase).

Hennig-Pusch

(1996)

BBA 23-2.1.5

Report No.

96 10 48 010

GLP

Klimisch score: 1

Disk 14

00000564

Predatory mite

Hypoaspis aculeifer

Flufenacet & Diflufenican SC 600: The effects on

survival and reproduction of the predaceous mite in

standard soil (LUFA 2.1)

LR50:

> 32 mg ai/kg dry soil

Reproduction

Not statistically different from control at 32 mg ai/kg dry

Lechelt-Kunse

(2002).

SECOFASE

Lekke and van

Gestel, 1996

Barrett et al. 1994

Report No.

B094HAE

GLP



Test methodc

[Reference

number]

soil (highest concentration tested). Klimisch score: 1

Disk 14

00000567

Table 3.21: Hazard quotients for in-field scenarios from the use of Firebird.

Species Application rate

(mL/ha)

MAF1 LR50

2

(mL/ha)

HQ Trigger

value Typhlodromus pyri (Tier 1 Test) 300 1 81.8 3.67 2 T. pyri (Extended laboratory test) 300 1 110.2 2.72 2

1MAF Multiple application factor (MAF taken from Appendix III, ESCORT 2)

2LR50 application rate that results in 50% mortality of test species

The in-field assessment shows a non-acceptable risk to beneficial invertebrates from both

tier 1 and the higher tier extended laboratory study using natural substrates.

Table 3.22: Hazard quotients for off-field scenarios from the use of Firebird.

Species Application

rate (mL/ha)

MAF

Drift

factor

Off-field

Rate (g/ha)

LR50

(mL/ha)

HQ Trigger

value T. pyri 300 1 2.77 10.3 110.2 0.09 2

1Drift factor = Drift value/100 (Drift values taken from Appendix IV, ESCORT 2)

The off-field assessment shows an acceptable risk to beneficial invertebrates.

Because the substance is an herbicide sprayed once per season with specific efficacy to plants,

the Agency recommends that the application rate not be changed. However, because the

product is to be applied early in the season (from pre-emergence to early post-emergence of

the crop) the risk of impacting the positive effects of beneficial insects is reduced.

Volatilisation

Hellpointner (1995)

Disk 2: 00000023 PF report No. 4069

Calculation of the chemical lifetime of thiafluamide (FOE5043) in the Troposphere.

Summary

Based on the calculation according to Atkinson the chemical lifetime of thiafluamide

(flufenacet) in the air was assessed to be less than 1 day, with respect to the OH radical

reaction, only. The chemical stability of thiafluamide in air is not determined by an attack at

one single site, but by attacks at different parts of the thiafluamide molecule. This should

result in the formation of various primary radicals leading to secondary oxidation products,

which can be eliminated from the air by wet and/or dry deposition. On account of the

relatively short chemical lifetime of thiafluamide in the air it is not to be expected that the

active ingredient can be transported in gaseous phase over large distances or can accumulate


in the air. This indicates that there should be no difference hi the behaviour between

thiafluamide and other organic substances which are emitted into the air from natural sources

(e.g. from soil or plants).

Hellpointner (1995)

BBA Guideline IV, 6-1

GLP

Disk 2: 00000154 PF report No. 4091

Determination of the Volatilisation Behaviour of FOE 5043 (60 WG) in a Field Trial.

Under the weather conditions being typical for a pre-emergence application of FOE 5043 on

late seeded corn end of May the volatilisation rate of parent compound (including possible

volatile metabolites and/or wind-eroded particles containing radioactivity) was determined to

average 16 % within 24 hours.

Two of the three trials showed well comparable results. The mean losses amounted to about

10 % within 24 hours and the main portions were lost within the first hour after application.

The observed loss in the other trial amounted to 29 % after 24 hours (highest observed rate)

and was longer lasting (for about 3 hours). Obviously, this was caused by comparatively

lower recoveries by means of the soil extracts. No plausible explanation, i. e. climatic

parameter of exposure or soil moisture, could be given for that deviation to the other two

trials.

On account of the low trend of FOE 5043 to volatilise from soil an exposure to relevant

amounts of parent compound or an emission via contaminated air is not to be expected in the

field.

Summary and conclusions of the ecological risk assessment

Based on the risk assessment for the aquatic and terrestrial environment as set out above, risks

to the following species groups have been identified.

Aquatic environment

Algae: Acute risk

See Approved Handler control in Appendix 4.

Terrestrial environment

Beneficial invertebrates: Acute risk (in-field)

However, because the product is to be applied early in the season (from pre-emergence to

early post-emergence of the crop), the risk of impacting the positive effects of beneficial

insects is reduced.

References EFSA 2008. Risk assessment for birds and mammals. Revision of guidance document under

council directive 91/414/EEC (SANCO/4145/2000 – final of 25 September 2002)1. Scientific

opinion of the panel on plant protection products and their residues (PPR) on the science

behind the guidance document on risk assessment for birds and mammals. Question no.

EFSA-Q-2006-064. Adopted on 17 June 2008. The EFSA Journal, 734: 1-181.

EFSA DAR (2006). Draft Assessment Report. Diflufenican.


EPPO 2001. Guideline on the test methods for evaluating the side-effects of plant protection

products. No PP 1/170(3)

EPPO 2002. Environmental risk assessment scheme for plant protection products. Chapter 10

honeybees. EPPO Bulletin 33

http://archives.eppo.org/EPPOStandards/PP3_ERA/pp3-10(2).pdf

ERMA New Zealand 2008a. User Guide to HSNO Thresholds and Classifications. ERMA

New Zealand, Wellington.

European Commission, Guidance Document on terrestrial ecotoxicology under Council

Directive 91/414/EEC, SANCO/ 10329/2002 rev. 2 final, 17 October 2002.

http://ec.europa.eu/food/plant/protection/evaluation/guidance/wrkdoc09_en.pdf

HSNO Chemical Classification Information Database

http://www.ermanz.govt.nz/hs/compliance/chemicals.html

Urban DJ, Cook, NJ 1986. Hazard Evaluation Division Standard Evaluation Procedure:

Ecological Risk Assessment. EPA 540/9-85-001. United States Environmental Protection

Agency Office of Pesticide Programs, Washington DC, USA.

USEPA 2001. Generic Estimated Environmental Concentration Model v2 (GENEEC2).

United States Environmental Protection Agency Office of Pesticide Programs, Washington

DC, USA http://www.epa.gov/oppefed1/models/water/index.htm#geneec2

http://archives.eppo.org/EPPOStandards/PP3_ERA/pp3-10(2).pdf

http://ec.europa.eu/food/plant/protection/evaluation/guidance/wrkdoc09_en.pdf

http://www.ermanz.govt.nz/hs/compliance/chemicals.html

http://www.epa.gov/oppefed1/models/water/index.htm#geneec2


APPENDIX 4: DISCUSSION ON CONTROLS

Based on the hazard classification as shown in Table 6.1, the set of associated controls has

been identified. These default controls, expressed as control codes11

, are listed in Table A4.1.

Table A4.1: List of default controls for Firebird

Toxicity Controls

T1 Limiting exposure to toxic substances through the setting of TELs

T2 Controlling exposure in places of work through the setting of WESs.

T4 Requirements for equipment used to handle substances

T5 Requirements for protective clothing and equipment

T7 Restrictions on the carriage of toxic or corrosive substances on passenger service vehicles

Ecotoxicity Controls

E1 Limiting exposure to ecotoxic substances through the setting of EELs

E2 Restrictions on use of substances in application areas

E5 Requirements for keeping records of use

E6 Requirements for equipment used to handle substances

E7 Approved handler/security requirements for certain ecotoxic substances

Identification Controls

I1 Identification requirements, duties of persons in charge, accessibility, comprehensibility,

clarity and durability

I3 Priority identifiers for ecotoxic substances

I8 Priority identifiers for toxic substances

I9 Secondary identifiers for all hazardous substances

I11 Secondary identifiers for ecotoxic substances

I16 Secondary identifiers for toxic substances

I17 Use of generic names

I18 Requirements for using concentration ranges

I19 Additional information requirements, including situations where substances are in

multiple packaging

I20 Durability of information for class 6.1 substances

I21 General documentation requirements

I23 Specific documentation requirements for ecotoxic substances

I28 Specific documentation requirements for toxic substances

I29 Signage requirements

I30 Advertising corrosive and toxic substances

Packaging Controls

P1 General packaging requirements

P3 Criteria that allow substances to be packaged to a standard not meeting Packing Group I,

II or III criteria

P13 Packaging requirements for toxic substances

P15 Packaging requirements for ecotoxic substances

PG3 Packaging requirements equivalent to UN Packing Group III

PS4 Packaging requirements as specified in Schedule 4

11

Control codes are those assigned by ERMA NZ to enable easy cross reference with the regulations. A

detailed list of these codes is contained in the ERMA New Zealand User Guide to the Controls

Regulations.


Disposal Controls

D4 Disposal requirements for toxic or corrosive substances

D5 Disposal requirements for ecotoxic substances

D6 Disposal requirements for packages

D7 Information requirements for manufacturers, importers and suppliers, and persons in

charge

D8 Documentation requirements for manufacturers, importers and suppliers, and persons in

charge

Emergency Management Controls

EM1 Level 1 information requirements for suppliers and persons in charge

EM6 Information requirements for toxic substances

EM7 Information requirements for ecotoxic substances

EM8 Level 2 information requirements for suppliers and persons in charge

EM11 Level 3 emergency management requirements: duties of person in charge, emergency

response plans

EM12 Level 3 emergency management requirements: secondary containment

EM13 Level 3 emergency management requirements: signage

Tracking Controls TR1 General tracking requirements

Approved handler Controls AH1 Approved Handler requirements (including test certificate and qualification requirements)

Tank Wagon and Transportable Containers Controls

The Hazardous Substance (Tank Wagons and Transportable Containers) Regulations 2004

prescribe a number of controls relating to tank wagons and transportable containers.

Those controls which require calculations, derivations or extended discussion are considered

in the following sections.

Toxicity Controls

Setting of TELs (Control Code T1)

Tolerable Exposure Limits (TELs) are designed to limit the extent to which the general public

is exposed to hazardous (toxic) substances. A TEL represents the maximum concentration of

a substance legally allowable in a particular medium, and can be set as either a guideline

value or an action level that should not be exceeded. For the purposes of setting TELs, an

environmental medium is defined as air, water, soil or a surface that a hazardous substance

may be deposited onto.

TELs are established from PDE (potential daily exposure) values, which are themselves

established from ADE (acceptable daily exposure) values or reference doses (RfD) which are

similar to ADE but are used to protect against a specific toxic effect of concern.

Human exposure may also occur through food or drinking water. Exposure through food is

managed via the establishment of Maximum Residue Limits (MRLs) as set by the Minister of

Food Safety on the advice of the New Zealand Food Safety Authority (NZFSA). Exposure

through drinking water is managed via the establishment of Maximum Acceptable Values

(MAVs) as set by the Ministry of Health. MRLs and MAVs are also established from ADE

values.


Setting of PDEs

If an ADE or RfD value is set for a substance, or component of a substance, a PDE value for

each relevant exposure route must also be set. A PDE is an amount of substance (mg/kg

bodyweight/day), calculated in accordance with Regulation 23, that estimates the relative

likelihood of particular exposures. A PDE for any single exposure route is a fraction of the

ADE or RfD, and the sum of all PDE values from all possible exposures must be less than or

equal to the ADE or RfD.

The main routes of exposure considered are ingestion (food, water, air, soil), inhalation (air)

and skin contact (surface deposition, water, soil).

Setting of ADEs

An ADE is an amount of a hazardous substance (mg/kg bodyweight/day), that, given a

lifetime of daily exposure, would be unlikely to result in adverse human health effects. An

RfD (reference dose) is a similar measure that can be used to protect against a specific toxic

effect of concern.

Regulation 11(1) of the Hazardous Substances (Classes 6, 8 and 9) Controls Regulations 2001

determines when an ADE/RfD is required to be set:

(1) This regulation applies to a class 6 substance if-

(a) it is likely to be present in-

(i) 1 or more environmental media; or

(ii) food; or

(iii) other matter that might be ingested; AND

(b) it is a substance to which a person is likely to be exposed on 1 or more

occasions during the lifetime of the person; AND

(c) exposure to the substance is likely to result in an appreciable toxic

effect.

If all three requirements of regulation 11(1) are met, then an ADE/RfD should be set for the

relevant component(s), and PDE and TEL values subsequently established for each relevant

exposure route.

The toxicity (Class 6) classifications of Firebird that trigger the need to consider setting a

TEL are 6.1D, 6.5B and 6.9B.

The Agency considers that flufenacet meets the requirements of Regulation 11(1)(a), (b) and

(c), and therefore notes that an ADE, and subsequently PDEs and TELs are required to be set

for this component.

However, the Agency is intending to review the setting of ADEs, PDEs and TELs under

section 77B of the Act, and until this review is complete, the Agency proposes not to set

TELs for flufenacet. Noting that Firebird is intended for use on food crops and contains

flufenacet, a new active ingredient to New Zealand, an ADE and PDEfood value are calculated

for this component which will enable the NZFSA to set MRLs if needed.


The Agency notes that the EFSA have set an ADI of 0.005 mg/kg bw/day for flufenacet,

established on the basis of the LOAEL of 1.2 mg/kg bw/day (increased incidence of renal

pelvic mineralisation) in the two two-year studies in the rat, using a safety factor of 250. The

Agency considered this dose level in the study to be a NOAEL, so calculated an ADE for

flufenacet using this value as a NOAEL and an uncertainty factor of 100 (see Appendix 2),

which gave an ADE of 0.012 mg/kg bw/day.

If an ADE is set for a substance, a PDE value for each exposure route must also be set. The

main routes of exposure to be considered are ingestion (from food, water etc), inhalation and

dermal (skin) contact. The sum of all PDE values from each possible exposure route must be

less than or equal to the ADE set for the substance, i.e. the PDE is a fraction of the ADE:

PDE = ADE x n, where “n” = a value between 0 and 1

Exposure to Firebird may occur via inhalation, dermal contact or oral ingestion.

The “n” values for flufenacet are set initially by the Agency at 0.7 for food, 0.2 for drinking

water and 0.1 each for inhalation, dermal contact and non-foodstuffs.

Based on an ADE value for flufenacet of 0.012 mg/kg bw/day (5 µg /kg bw/ day), the Agency

proposes that the following PDE values be adopted:

PDEFOOD = 0.0084, rounded to 0.008 mg/kg bw/day

PDEDRINKING WATER = 0.0024, rounded to 0.002 mg/kg bw/day

The Agency has agreed with the New Zealand Food Safety Authority that we will set an acute

reference dose (ARfD), for new active ingredients. This will provide a basis for the NZ Food

Safety Authority to assess shorter term food residues if this should be required. In the case of

flufenacet the Agency notes that the EU has proposed a value of 0.017 mg/kg bw/day which

is based on the same calculation as the AOEL (in Appendix 3). The Agency proposes that

this value applies to flufenacet in New Zealand.

Setting of WES (Control Code T2)

Workplace exposure standards (WES) are designed to protect persons in the workplace from

the adverse effects of toxic substances. A WES is an airborne concentration of a substance

(expressed as mg substance/m3 of air, or ppm in air), which must not be exceeded in a

workplace and only applies to places of work (Regulation 29(2), Hazardous substances

(Classes 6, 8 and 9 Controls) Regulations 2001).

Regulation 29(1) of the Hazardous Substances (Classes 6, 8 and 9 Controls) Regulations 2001

determines when a WES is required to be set. If all three of the requirements of this regulation

are met then a WES is required to be set.

Regulation 29 states:

(1) This regulation and regulation 30 apply to a class 6 substance if,-

(a) under the temperature and pressure the substance is to be used in, it can become

airborne and disperse in air in the form of inspirable or respirable dust, mists,

fumes, gases or vapours; AND


(b) human exposure to the substance is primarily through the inhalation or dermal

exposure routes; AND

(c) the toxicological and industrial hygiene data available for the substance is

sufficient to enable a standard to be set.

When setting WES, the Authority must either adopt a value already proposed by the

Department of Labour or already set under HSNO or derive a value by taking into account the

matters described in Regulation 30(2) of the Hazardous Substances (Classes 6, 8 and 9

Controls) Regulations.

The Agency typically adopts WES values listed in the Workplace Exposure Standards

(Effective from 2002) document (refer to the link below).

http://www.osh.govt.nz/order/catalogue/pdf/wes2002.pdf

The Agency notes that Department of Labour has set WES values for Components C, H4 and

I in Firebird.

The Agency considers that the Department of Labour WES value for Component C should be

adopted as the HSNO WES value that applies to Component C in Firebird and this is given in

Appendix 8. The Agency considers that the WES values for Components H and I should not

be applied to Firebird due to their low concentration in the formulated substance.

Ecotoxicity Controls

Setting of EELs (Control code E1)

Regulation 33 of the Hazardous Substances (Classes 6, 8 and 9 Controls) Regulations 2001

specify that an environmental exposure limit (EEL) may be set for a class 9 substance for one

or more environmental media if organisms that live in that environment may be exposed to the

substance. An EEL is the (maximum) concentration of a substance in an environmental

medium that will present a negligible risk of adverse environmental effects to organisms

(excluding humans) in non-target areas.

As specified by regulation 32, a default EEL of 0.1 µg/L water is set for any class 9.1

substance, and 1 µg/kg soil (dry weight) for any class 9.2 substance.

For the purposes of setting EELs, an environmental medium is defined as water, soil or

sediment where these are in the natural environment, or a surface onto which a hazardous

substance may be deposited.

An EEL can be established by one of three means:

Applying the default EELs specified in regulation 32

Adopting an established EEL as provided by regulation 35(a)

Calculating an EEL from an assessment of available ecotoxicological data as

provided by regulation 35(b).

The Hazardous Substances and New Organisms (Approvals and Enforcement) Act 2005

added a new section (s77B) to the HSNO Act, which, amongst other things provided the

http://www.osh.govt.nz/order/catalogue/pdf/wes2002.pdf


Authority with the ability to set EELs as guideline values, rather than the previous pass/fail

values.

However, until the Agency has developed formal policy on the implementation of s77B, it

proposes not to set EELs for any components of Firebird at this time. It is also proposed that

the default EEL water and soil values be deleted until the policy has been established.

Approved Handler Controls- Highly ecotoxic substances (AH1, E7)

Approved handler requirements have been triggered for Firebird as a result of its 9.1A and

9.2A classifications. The outcome of the ecological risk assessment (refer Appendix 3)

indicates that there is potential for acute adverse environmental effects on algae if the

substance moves off-target. The Agency considers it is therefore appropriate to retain the

approved handler control.

This approach is consistent with the Authority’s policy on approved handler and tracking

controls for class 9 substances (November 2003).

Tracking control- Highly ecotoxic substances (TR1)

Tracking requirements have been triggered for Firebird as a result of its 9.1A and 9.2A

classifications. However, for substances where the tracking control has been triggered solely

as a result of ecotoxicity, it is considered that any risk that may arise during its life-cycle are

adequately managed by other controls such as approved handler, packaging, labeling and

emergence management requirements. the Agency therefore considers the tracking control

can be deleted as provided by section 77(4)(b).

This approach is consistent with the Authority’s policy on approved handler and tracking

controls for class 9 substances (November 2003).

Setting of Application Rate (Control Code E2) These regulations relate to the requirement to set an application rate for a class 9 substance

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

been set.

Although no EEL has been set for Firebird, the Agency proposes setting the application rate

of 300 mL formulated product/ha. (Flufenacet 126.3 g/ha., Diflufenican 61.9 g/ha), once per

season as the application rate for Firebird. This rate was used in the ecological risk

assessment.

Other controls required as a result of the ecological risk assessment.

This substance is not to be applied onto or into water;

Identification controls

Identification of Toxic Components on Labels/Documentation (SDS)


The Hazardous Substances (Identification) Regulations 2001 specify that certain toxic and/or

corrosive components are required to be specified on the product label and on SDS

documentation.

Identification of toxic components on labels

Regulations 25(e) and 25(f) require that certain toxic components are required to be specified

on the product label.

Regulation 25(e) states:

...a toxic substance must be identified by...

'information identifying, by its common or chemical name, every ingredient, that would,

independently of any other ingredient, give the substance a hazard classification of 6.1A,

6.1B, 6.1C, 6.5, 6.6, 6.7, 6.8 or 6.9, and the concentration of that ingredient in the substance."

Regulation 25(f) states:

...a toxic substance must be identified by...

"information identifying (other than an ingredient referred to in paragraph (E)) that would,

independently of any other ingredient, give the substance a hazard classification of 6.1D, and

the concentration of the ingredient that would contribute the most to that classification."

Identification of toxic components on SDS

Regulation 39(5) of the Hazardous Substances (Identification) Regulations 2001, states that

certain corrosive and toxic components are required to be specified on documentation.

Regulations 39(5) states:

"The requirements of regulation 19(f) or (as the case requires) regulation 25(e) apply to all

documentation; but any ingredient required by that provision to be identified (other than an

ingredient to which regulation 26 applies) must also be identified by any Chemical Abstract

Services number allocated to it."

Concentration cut-offs for component identification

Consistent with the guidance provided by GHS, the Hazardous Substances Standing

Committee (HSSC) agreed that the concentration cut-offs triggering the requirement for

identification of components on labels and documentation are:

HSNO Classification Cut-off for label (% w/w) Cut-off for SDS (% w/w)

6.5A, 6.5B, 6.6A, 6.7A 0.1 0.1

6.6B 1 1

6.7B 1 0.1

6.8A, 6.8C 0.3 0.1

6.8B 3 0.1

6.9A, 6.9B 10 1


Firebird - Components requiring identification

Under these regulations, as determined by the HSSC (March 2006), the name and

concentration of the following components need to be specified on the label and

documentation:

Label & Documentation

Flufenacet


APPENDIX 5: LIST OF PROPOSED CONTROLS FOR

FIREBIRD

Table A5.1: Proposed controls for Firebird – codes, regulations and variations.

Control

Code12

Regulation13

Topic Variations

Hazardous Substances (Classes 6, 8, and 9 Controls) Regulations 2001

T1 11-27 Limiting exposure to toxic

substances

No TEL values are set at this time.

The following ADE and PDE values

are set for flufenacet:

ADE = 0.012 mg/kg bw/day

PDEfood = 0.008 mg/kg bw/day

PDEdrinking water = 0.002 mg/kg bw/day

The following Acute Reference Dose is

set for flufenacet:

ARfD = 0.017 mg/kg bw/day.

T2 29, 30 Controlling exposure in places of

work The DoL WES values for Component

C in Firebird are adopted.

T4/E6 7 Requirements for equipment used to

handle hazardous substances

Controls T4 and E6 are combined.

T5 8 Requirements for protective clothing

and equipment

T7 10 Restrictions on the carriage of toxic

or corrosive substance on passenger

service vehicles

E1 32-45 Limiting exposure to ecotoxic

substances

No EEL values are set at this time and

the default EELs are deleted.

E2 46-48 Restrictions on use within

application area

As no EELs have been set, no

application rate is required to be set

under this control at this time.

However, an application rate is set as

an additional control under Section

77A (see below).

E5 5(2), 6 Requirements for keeping records of

use

E7 9 Approved handler/security

requirements for certain ecotoxic

substances

The following control is substituted for

Regulation 9(1) of the Hazardous

Substances (Classes 6, 8, and 9 Controls)

Regulations 2001:

(1). This subsatnce must be under the

personal control of an approved

12 Note: The numbering system used in this column relates to the coding system used in the ERMA New Zealand Controls Matrix. This links the hazard classification categories to the regulatory controls triggered by each category. It is available from the ERMA New Zealand website www.ermanz.govt.nz/resources and is also contained in the ERMA New Zealand User Guide to the HSNO Control Regulations. 13 These Regulations form the controls applicable to this substance. Refer to the cited Regulations for the formal specification, and for definitions and exemptions.

http://www.ermanz.govt.nz/resources


Control

Code12

Regulation13

Topic Variations

handler when the substance is -

(a) applied in a wide dispersive

manner; or

(b) used by a commercial contractor.

Hazardous Substances (Identification) Regulations 2001

I1 6, 7, 32-35,

36 (1)-(7)

General identification requirements

Regulation 6 – Identification duties

of suppliers

Regulation 7 – Identification duties

of persons in charge

Regulations 32 and 33 –

Accessibility of information

Regulations 34, 35, 36(1)-(7) –

Comprehensibility, Clarity and

Durability of information

I3 9 Priority identifiers for ecotoxic

substances

I8 14 Priority identifiers for toxic

substances

I9 18 Secondary identifiers for all

hazardous substances

I11 20 Secondary identifiers for ecotoxic

substances

I16 25 Secondary identifiers for toxic

substances

I17 26 Use of Generic Names

I18 27 Use of Concentration Ranges

I19 29-31 Alternative information in certain

cases

Regulation 29 – Substances in fixed

bulk containers or bulk transport

containers

Regulation 30 – Substances in

multiple packaging

Regulation 31 – Alternative

information when substances are

imported

I20 36(8) Durability of information for 6.1

substances

I21 37-39, 47- Documentation required in places of


Control

Code12

Regulation13

Topic Variations

50 work

Regulation 37 – Documentation

duties of suppliers


duties of persons in charge of places

of work

Regulation 39 – General content

requirements for documentation

Regulation 47 – Information not

included in approval

Regulation 48 – Location and

presentation requirements for

documentation


requirements for vehicles

Regulation 50 – Documentation to be

supplied on request

I23 41 Specific documentation requirements

for ecotoxic substances

I28 46 Specific documentation requirements

for toxic substances

I29 51-52 Duties of persons in charge of places

with respect to signage

I30 53 Advertising corrosive and toxic

substances

Hazardous Substances (Packaging) Regulations 2001

P1 5, 6, 7 (1), 8 General packaging requirements

Regulation 5 – Ability to retain

contents

Regulation 6 – Packaging markings

Regulation 7(1) – Requirements

when packing hazardous substance

Regulation 8 – Compatibility

Regulation 9A and 9B – Large

Packaging

P3 9 Packaging requirements for

substances packed in limited


Control

Code12

Regulation13

Topic Variations

quantities

P13

P15

19

21

Packaging requirements for Firebird Controls P13 and P15 are combined.

PG3 Schedule 3 The tests in Schedule 3 correlate to

the packaging requirements of UN

Packing Group III (UN PGIII).

PS4 Schedule 4 This schedule describes the

minimum packaging requirements

that must be complied with when a

substance is packaged in limited

quantities

Hazardous Substances (Disposal) Regulations 2001

D4

D5

8

9

Disposal requirements for Firebird Controls D4 and D5 are combined

D6 10 Disposal requirements for packages

D7 11, 12 Disposal information requirements

D8 13, 14 Disposal documentation

requirements

Hazardous Substances (Emergency Management) Regulations 2001

EM1 6, 7, 9-11 Level 1 emergency management

information: General requirements

EM6 8(e) Information requirements for toxic

substances

EM7 8(f) Information requirements for

ecotoxic substances

EM8 12-16, 18-

20

Level 2 emergency management

documentation requirements

EM11 25-34 Level 3 emergency management

requirements – emergency response

plans

EM12 35-41 Level 3 emergency management

requirements – secondary

containment

The following subclauses shall be

added after subclause (3) of regulation

36:

(4) For the purposes of this regulation,

and regulations 37 to 40, where

this substance is contained in

pipework that is installed and operated so as to manage any loss

of containment in the pipework it— (a) is not to be taken into account

in determining whether a place

is required to have a secondary containment system; and

(b) is not required to be located in

a secondary containment system.

(5) In this clause, pipework— (a) means piping that—

(i) is connected to a stationary

container; and


Control

Code12

Regulation13

Topic Variations

(ii) is used to transfer a

hazardous substance into or out of the stationary

container; and

(b) includes a process pipeline or a transfer line.

The following subclauses are added at

the end of regulation 37: (2) If pooling substances which do not

have class 1 to 5 hazard

classifications are held in a place

above ground in containers each of

which has a capacity of 60 litres or

less—

(a if the place’s total pooling

potential is less than 20,000

litres, the secondary containment

system must have a capacity of at

least 25% of that total pooling

potential:

(b) if the place’s total pooling

potential is 20,000 litres or

more, the secondary

containment system must have a

capacity of the greater of—

(i) 5% of the total pooling

potential; or

(ii) 5,000 litres.

(3) Pooling substances to which

subclause (2) applies must be

segregated where appropriate to

ensure that leakage of one substance

may not adversely affect the

container of another substance.

The following subclauses are added at

the end of regulation 38: (2) If pooling substances which do not

have class 1 to 5 hazard

classifications are held in a place

above ground in containers 1 or

more of which have a capacity of

more than 60 litres but none of

which have a capacity of more than

450 litres—

(a) if the place’s total pooling

potential is less than 20,000

litres, the secondary

containment system must have a

capacity of either 25% of that

total pooling potential or 110%

of the capacity of the largest

container, whichever is the

greater:

(b) if the place’s total pooling

potential is 20,000 litres or


Control

Code12

Regulation13

Topic Variations

more, the secondary containment

system must have a capacity of

the greater of—

(i) 5% of the total pooling

potential; or

(ii) 5,000 litres

(3) Pooling substances to which

subclause (2) applies must be

segregated where appropriate to

ensure that the leakage of one

substance may not adversely affect

the container of another substance.

EM13 42 Level 3 emergency management

requirements – signage

Hazardous Substances (Personnel Qualification) Regulations 2001

AH1 4-6 Approved Handler requirements See E7.

Hazardous Substances (Tank Wagons and Transportable Containers) Regulations 2004

Regulations 4 to 43

where applicable

The Hazardous Substances (Tank Wagons and Transportable Containers)

Regulations 2004 prescribe a number of controls relating to tank wagons and

transportable containers and must be complied with as relevant.

Section 77 and 77A Additional Controls

The controls relating to stationary container systems, as set out in Schedule 8 of the Hazardous

Substances (Dangerous Goods and Scheduled Toxic Substances) Transfer Notice 2004 (Supplement to

the New Zealand Gazette, 26 March 2004, No. 35, page 767), as amended, apply to this substance,

notwithstanding clause 1(1) of that schedule.

Addition of subclauses after subclause (3) of Regulation 36, subclause (1) of Regulation 37 and

subclause (1) of Regulation 38 of the Hazardous Substances (Emergency Management Controls)

Regulations, refer control EM12.

Firebird shall not be applied onto or into water.

The maximum application rate for Firebird shall be 300 mL/ha., once per season.

The method of application of Firebird shall be limited to ground-based application only.


APPENDIX 6: SCALES FOR QUALITATIVE RISK

ASSESSMENT

This section describes how the Agency staff and the Authority address the qualitative

assessment of risks, costs and benefits. Risks and benefits are assessed by estimating the

magnitude and nature of the possible effects and the likelihood of their occurrence. For each

effect, the combination of these two components determines the level of the risk associated

with that effect, which is a two dimensional concept. Because of lack of data, risks are often

presented as singular results. In reality, they are better represented by ‘families’ of data which

link probability with different levels of outcome (magnitude).

The magnitude of effect is described in terms of the element that might be affected. The

qualitative descriptors for magnitude of effect are surrogate measures that should be used to

gauge the end effect or the ‘what if’ element. Tables 1 and 2 contain generic descriptors for

magnitude of adverse and beneficial effect. These descriptors are examples only, and their

generic nature means that it may be difficult to use them in some particular circumstances.

They are included here to illustrate how qualitative tables may be used to represent levels of

adverse and beneficial effect.

Table 1 Magnitude of adverse effect (risks and costs)

Descriptor Examples of descriptions - ADVERSE

Minimal Mild reversible short term adverse health effects to individuals in highly localised area

Highly localised and contained environmental impact, affecting a few (less than ten) individuals

members of communities of flora or fauna, no discernible ecosystem impact

Local/regional short-term adverse economic effects on small organisations (businesses,

individuals), temporary job losses

No social disruption

Minor Mild reversible short term adverse health effects to identified and isolated groups

Localised and contained reversible environmental impact, some local plant or animal communities

temporarily damaged, no discernible ecosystem impact or species damage

Regional adverse economic effects on small organisations (businesses, individuals) lasting less

than six months, temporary job losses

Potential social disruption (community placed on alert)

Moderate Minor irreversible health effects to individuals and/or reversible medium term adverse health

effects to larger (but surrounding) community (requiring hospitalisation)

Measurable long term damage to local plant and animal communities, but no obvious spread

beyond defined boundaries, medium term individual ecosystem damage, no species damage

Medium term (one to five years) regional adverse economic effects with some national

implications, medium term job losses

Some social disruption (e.g. people delayed)

Major Significant irreversible adverse health effects affecting individuals and requiring hospitalisation

and/or reversible adverse health effects reaching beyond the immediate community

Long term/irreversible damage to localised ecosystem but no species loss

Measurable adverse effect on GDP, some long term (more than five years) job losses

Social disruption to surrounding community, including some evacuations

Massive Significant irreversible adverse health effects reaching beyond the immediate community and/or

deaths

Extensive irreversible ecosystem damage, including species loss

Significant on-going adverse effect on GDP, long term job losses on a national basis

Major social disruption with entire surrounding area evacuated and impacts on wider community


Table 2 Magnitude of beneficial effect (benefits) Descriptor Examples of descriptions -BENEFICIAL

Minimal Mild short term positive health effects to individuals in highly localised area

Highly localised and contained environmental impact, affecting a few (less than ten) individuals

members of communities of flora or fauna, no discernible ecosystem impact

Local/regional short-term beneficial economic effects on small organisations (businesses,

individuals), temporary job creation

No social effect

Minor Mild short term beneficial health effects to identified and isolated groups

Localised and contained beneficial environmental impact, no discernible ecosystem impact

Regional beneficial economic effects on small organisations (businesses, individuals) lasting less

than six months, temporary job creation

Minor localised community benefit

Moderate Minor health benefits to individuals and/or medium term health impacts on larger (but

surrounding) community and health status groups

Measurable benefit to localised plant and animal communities expected to pertain to medium

term.

Medium term (one to five years) regional beneficial economic effects with some national

implications, medium term job creation

Local community and some individuals beyond immediate community receive social benefit.

Major Significant beneficial health effects to localised community and specific groups in wider

community

Long term benefit to localised ecosystem(s)

Measurable beneficial effect on GDP, some long term (more than five years) job creation

Substantial social benefit to surrounding community, and individuals in wider community.

Massive Significant long term beneficial health effects to the wider community

Long term, wide spread benefits to species and/or ecosystems

Significant on-going effect beneficial on GDP, long term job creation on a national basis

Major social benefit affecting wider community

The likelihood applies to the composite likelihood of the end effect, and not either to the

initiating event, or any one of the intermediary events. It includes:

the concept of an initiating event (triggering the hazard), and

the exposure pathway that links the source (hazard) and the area of impact (public

health, environment, economy, or community).

Thus, the likelihood is not the likelihood of an organism escaping, or the frequency of

accidents for trucks containing hazardous substances, but the likelihood of the specified

adverse effect14

resulting from that initiating event. It will be a combination of the likelihood

of the initiating event and several intermediary likelihoods15

. The best way to determine the

likelihood is to specify and analyse the complete pathway from source to impact.

Likelihood may be expressed as a frequency or a probability. While frequency is often

expressed as a number of events within a given time period, it may also be expressed as the

number of events per head of (exposed) population. As a probability, the likelihood is

dimensionless and refers to the number of events of interest divided by the total number of

events (range 0-1).

14

The specified effect refers to scenarios established in order to establish the representative risk, and may

be as specific as x people suffering adverse health effects, or y% of a bird population being adversely

affected. The risks included in the analysis may be those related to a single scenario, or may be defined as a

combination of several scenarios. 15

Qualitative event tree analysis may be a useful way of ensuring that all aspects are included.


Table 3 Likelihood

Descriptor Description

Highly improbable Almost certainly not occurring but cannot be totally ruled out

Very unlikely Considered only to occur in very unusual circumstances

Unlikely (occasional) Could occur, but is not expected to occur under normal operating conditions.

Likely A good chance that it may occur under normal operating conditions.

Highly likely Almost certain, or expected to occur if all conditions met

Using the magnitude and likelihood tables a matrix representing a level of risk/benefit can be

constructed.

In the example shown in Table 4, four levels of risk/benefit are allocated: A (negligible), B

(low), C (medium), and D (high). These terms have been used to avoid confusion with the

descriptions used for likelihood and magnitude, and to emphasise that the matrix is a tool to

help decide which risks/benefits require further analysis to determine their significance in the

decision making process.

For negative effects, the levels are used to show how risks can be reduced by the application

of additional controls. Where the table is used for positive effects it may also be possible for

controls to be applied to ensure that a particular level of benefit is achieved, but this is not a

common approach. The purpose of developing the tables for both risk and benefit is so that

the risks and benefits can be compared.

Table 4 Level of risk

Magnitude of effect

Likelihood Minor Minor Moderate Major Massive

Highly

improbable A A A B B

Very unlikely A A B B C

Unlikely A B B C C

Likely B B C C D

Highly likely B C C D D


APPENDIX 7: GOVERNMENT DEPARTMENTS,

CROWN ENTITIES AND INTERESTED PARTIES

NOTIFIED

Aakland Chemicals (1997) Limited

AgBio Research Limited

Agcarm Incorporated

AgResearch Limited

Agronica New Zealand Limited

Ancare Scientific Limited

ARPPA

BASF New Zealand Limited

Bayer New Zealand Limited

BOC Limited

Bomac Laboratories Limited

Caltex New Zealand Limited

Central Hawkes Bay District Council

Chancery Green

Chemagro New Zealand Limited

Chemsafety Limited

Crown Public Health

CSD Consultancy Ltd

Donaghys Industries Limited

Dow AgroSciences (New Zealand) Limited.

DuPont (New Zealand) Limited

Environment Southland

Environment Waikato

Far North District Council

Federated Farmers of New Zealand (Incorporated)

Fish and Game Council of New Zealand

Fish and Game Eastern Region

Franklin District Council

GE Free (Wairarapa)

General Cable New Zealand Limited

Greater Wellington - The Regional Council

Green Party of Aotearoa New Zealand

Horticulture and Food Research Institute (HortResearch)

HQ Joint Forces New Zealand

Human Rights Commission

Hunt Agencies Limited

IMCD New Zealand Limited

Intervet Limited

Jordens Nurseries

Kaipara District Council

Kawerau District Council

Landcorp Farming Limited

Lowndes Associates


MackeNew Zealandie District Council

MAF Biosecurity New Zealand (MAFBNew Zealand)

Matamata-Piako District Council

Merial New Zealand Limited

Ministry of Research Science and Technology (MoRST)

Muaupoko Co-operative Society

Napier Health Centre - Public Health Unit

National Aquarium of New Zealand

National Institute of Water and Atmospheric Research Limited (NIWA)

New Plymouth District Council

New Zealand Chemical Industry Council Inc

New Zealand Customs Service

New Zealand Meatworkers Union

New Zealand Press Association

New Zealand Society of Gunsmiths Inc

New Zealand Veterinary Association Inc

New Zeland Bee Industry Group - Federated Farmers

Ngati Kahungunu Iwi Incorporated

Northern Chemical Workers Union

Northland Health

Northland Regional Council

Nufarm New Zealand Limited

Nursery and Garden Industry Association of New Zealand Inc

Otago District Health Board

Pacific Growers Supplies Limited

Pesticide Action Network Aotearoa New Zealand

Pfizer New Zealand Limited

PharmVet Solutions

Physicians and Scientists for Global Responsibility (PSGR)

Rangitikei District Council

Reckitt Benckiser

Royal Forest and Bird Protection Society of New Zealand Inc.

Rural and Associated Contractors Federation of New Zealand

South Taranaki District Council

Spraywatchers Group

Sustainability Council of New Zealand

Syngenta Crop Protection Limited

Tairawhiti District Health

Taranaki Regional Council

Tasman District Council

Te Pataka Matauranga Charitable Trust

Technical Strategy Group Limited

Television New Zealand

Thames Coromandel District Council

The Green Party of Aotearoa New Zealand Inc

The National Beekeepers Association of New Zealand

TMP Consultancy

University of Auckland

Veg-Gro Supplies Limited

ViaLactia Biosciences (New Zealand) Limited


Virbac Laboratories New Zealand Limited

Yates Australia

Zelam Limited

10 Private Individuals


APPENDIX 8: CONFIDENTIAL MATERIAL


APPENDIX 9 CONFIDENTIAL MATERIAL

- NOT TO BE DISCLOSED TO APPLICANT

erma new zealand evaluation and review report …...2009/05/11 · erma new zealand evaluation and...

Documents