E&R Template - Release - EPA · Web viewFood consumption of the parent animals in both the P and F1 generations at 100 and 500 ppm and of the females of the F1 generation at 2000ppm;

ERMA New ZealandEvaluation and Review Report

Application for Approval to Import or Manufacture Frontier-P for Release

Application Number: HSR08124

Prepared for the Environmental Risk Management Authority

EXECUTIVE SUMMARY

Background information

BASF New Zealand Limited is seeking approval to import Frontier-P for release.

Frontier-P is a herbicide containing 720 g/litre dimethenamid-P in the form of an emulsifiable concentrate.

Frontier-P is proposed to be used as a pre-emergence selective herbicide for the control of annual grasses and broadleaf weeds in a number of field crops.

Frontier-P will be applied as a herbicide at a maximum application rate of 1.3 L/ha (0.936 kg dimethenamid-P/ha) with a maximum of 1 application per year.

The applicant advises that application will be by either aerial or ground based methods.

Dimethenamid-P is a new active ingredient to New Zealand.

Classification The Agency and the applicant have independently classified Frontier-P based on the

available information on Frontier-P and its components. The classifications are summarised in the table below:

Hazardous Property Applicant’s Assessment Agency’s Assessment

Acute Toxicity (Oral) 6.1D 6.1D

Acute Toxicity (Inhalation) 6.1D(aspiration hazard)

─

Skin Irritancy 6.3B 6.3BEye Irritancy 6.4A 6.4ASkin Sensitisation 6.5B 6.5BCarcinogenicity 6.7B 6.7BTarget Organ Toxicity 6.9B ─Aquatic Ecotoxicity 9.1A 9.1ASoil Ecotoxicity 9.2A 9.2AEcotoxicity to Terrestrial Vertebrates

9.3C 9.3C

Biocide 9.1D ─

Differences between Agency’s and the applicant’s classifications are:

ERMA New Zealand Evaluation and Review Report: Application HSR08124 Page 2 of 150

o The applicant’s incorrect inclusion of the biocide classification. This has been removed as the substance has triggered ecotoxicity classifications.

o The applicant assigned a 6.9B classification based on the 2-year feeding study in rats. However, results from this study do not support classification of Frontier-P as a target organ toxicant.

o The applicant assigned a 6.1D (aspiration hazard) classification to Frontier-P because component A2 is classified as presenting an aspiration hazard. However, an aspiration hazard only triggers 6.1E classification and furthermore, component A2 is present at below the threshold for triggering aspiration hazard classification. Formulation test data indicates Frontier-P does not trigger classification as an inhalation toxicant.

Risk Assessment The Agency notes that dimethenamid-P has been recently reviewed by APVMA

(2007) and by PMRA-ARLA (Canada) (2009). The outcomes of these reviews have been considered within the Agency’s assessment of Frontier-P.

The Agency’s assessment of the risks posed by Frontier-P 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 Frontier-P are negligible with the proposed controls in place.

The Agency has evaluated information supplied by the applicant about the benefits of Frontier-P and considers that benefits are likely to be realised through the release of this substance.

Controls

The Agency has proposed that the default controls for Frontier-P be modified, such that:

- no Tolerable Exposure Limits (T1), Workplace Exposure Standards (T2) or Environmental Exposure Limits (E1) are set at the present time and any default values are deleted;

- the maximum application rate for Frontier-P shall be 1.3 L/ha (0.936 kg dimethenamid-P/ha) with a maximum application frequency of 1 application per year.

- the maximum quantity for passenger service vehicles (T7) is increased from 0.1 L to 1 L;

- the approved handler (E7, AH1) controls are retained, but modified to apply to use only;

- the tracking control (TR1) is deleted;


- further controls regarding stationary containment systems and pipework are added; and

- a control which prohibits application of Frontier-P onto or into water is added.

Agency Conclusion

In conclusion, the Agency considers that there are negligible risks to human health and to the environment and potential benefits associated with the release of Frontier-P. Therefore, the Agency considers that it is evident that the benefits of releasing Frontier-P outweigh the costs and the application may be approved in accordance with clause 26.


TABLE OF CONTENTS

1 Application Details.............................................................................................................62 Legislative Criteria for the Application..............................................................................63 Application Process............................................................................................................64 Notification and Consultation............................................................................................75 Application Synopsis and Information Review..................................................................86 Hazardous Properties, Thresholds and Classification......................................................107 Default Controls...............................................................................................................128 Risk Assessment...............................................................................................................129 Assessment of Beneficial Effects.....................................................................................1810 Controls............................................................................................................................1911 Overall Evaluation of Risks, Costs and Benefits.............................................................2212 Conclusion........................................................................................................................22

Appendix 1: Decision Path.......................................................................................................24

Appendix 2: Hazard Classification..........................................................................................25

Appendix 3: Risk Assessment................................................................................................101

Appendix 4: Discussion on Controls......................................................................................111

Appendix 5: List of Proposed Controls for Frontier-P...........................................................137

Appendix 6: Scales for Qualitative Risk Assessment............................................................144

Appendix 7: Government Departments, Crown Entities and Interested Parties Notified......147

Appendix 8: Confidential Material........................................................................................149


1 APPLICATION DETAILSApplication Code HSR08124

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 BASF New Zealand Limited

Date Application Received 10 December 2008

Submission Period 20 January 2009 – 4 March 2009

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

Purpose of the Application To import Frontier-P as a pre-emergence selective herbicide for the control of annual grasses and broadleaf weeds in a number of field crops (Category C).

2 LEGISLATIVE CRITERIA FOR THE APPLICATION

3 The application was lodged pursuant to section 28.

4 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.

5 APPLICATION PROCESS

6 Evaluation of the application was undertaken by the ERMA New Zealand project team (“the Agency”) which comprised the following staff members:

Haydn Murdoch Advisor (Hazardous Substances)

Eugene Georgiades Advisor (Hazardous Substances)

Tonderai Kaitano Advisor (Hazardous Substances)

Patrick Gemmell Senior Advisor (Kaupapa Kura Taiao).

7 The report was reviewed and signed out by:

Noel McCardle Senior Advisor (Hazardous Substances).


8 Timeline

Application formally received 10 December 2008

Application notified 20 January 2009

Submission closing date 4 March 2009.

8.1 Due to delays in completing this E&R Report, the Authority postponed the consideration under section 58(3) until 31 July 2009.

9 NOTIFICATION AND CONSULTATION

10 The Minister for the Environment was advised of the application1 and given the opportunity to “call-in” the application2. This action was not initiated.

10.1 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.

11 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.

12 The application was publicly notified on the ERMA New Zealand website on 20 January 2009 and subsequently advertised in The Dominion Post, the New Zealand Herald, the Christchurch Press and the Otago Daily Times3.

12.1.1 No submissions were received.

1 section 53(4)(a)2 section 683 section 53


13 APPLICATION SYNOPSIS AND INFORMATION REVIEW

Information supplied by the applicant

14 The applicant supplied the following documents: the application; a confidential appendix (including full formulation data and a draft

label).

Information review

15 The confidential information on the composition of Frontier-P 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.

16 The Agency notes that dimethenamid-P (Frontier-P) has been recently reviewed by APVMA (2007). This product was assessed at similar use quantities (maximum rate 1.4 L/ha) as are proposed for New Zealand (maximum rate 1.3 L/ha). This report highlighted the following environmental concerns:

Aerial application is prohibited on the label (this route was not considered in the Australian assessment);

The chemical is very toxic to aquatic plants, algae and terrestrial plants. To

protect these plants spray-drift buffers of 20 metres for aquatic plants, or 15 metres for terrestrial plants are required assuming medium spray quality;

If a fine spray is used (or as a default where spray quality is not defined on the label), then the risk is higher and buffers of 50 metres for aquatic plants and 40 metres for terrestrial plants are required;

Risks to algae and terrestrial and aquatic plants have also been identified from run-off events. A clear relationship was established for the time between application and storm events and run-off. It is recommended that restrictions on application be restricted when there is the expectation of heavy rain. This would provide a better chance for dimethenamid to bind/degrade prior to a run-off event and therefore limit the risk from runoff.

17 The Agency notes that dimethenamid-P (Frontier-Max) has been recently reviewed by PMRA-ARLA (Canada) (2009). This report highlighted the following environmental concerns:

Dimethenamid-P has a potential for leaching in soils.


A buffer zone of 3 m is calculated for the use of Frontier Max Herbicide for protection of terrestrial plants.

A buffer zone of 1 m is calculated for the use of Frontier Max Herbicide for protection of aquatic habitats.

18 The outcomes of these reviews have been considered within the Agency’s assessment of the substance.

19 The Agency considers that there are no significant uncertainties sufficient to influence decision making in the scientific and technical information relating to the potential adverse effects of Frontier-P4. Therefore, the Agency considers that the information constitutes an adequate and appropriate basis for considering the application5.

Description and use of the substance19.1 Frontier-P is a herbicide containing 720 g/litre dimethenamid-P in the form of

an emulsifiable concentrate. Frontier-P is proposed to be used as a pre-emergence selective herbicide for the control of annual grasses and broadleaf weeds in a number of field crops.

Lifecycle

Manufacture/Importation

19.2 The applicant has indicated that Frontier-P will be manufactured overseas and imported into New Zealand fully formulated and packaged in the sale packs.

19.3 While Frontier-P 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 Frontier-P have been evaluated, so that approval of this substance will be applicable to both the import and manufacture of Frontier-P.

Transport, storage and packaging

19.4 Packaging for Frontier-P will conform to Packaging Group II. FRONTIER-P will be marketed in mould blown high-density polyethylene (HDPE) containers with inner barrier (e.g. polyamide) and with foil seals. These are protected by screw caps of polypropylene.

19.5 The substance will be transported within New Zealand in accordance with the relevant New Zealand Transport Legislation.

19.6 The substance will be stored in accordance with the requirements of NZS8409:2004 Management of Agrichemicals, the Act and the Resource Management Act 1991.

4 clauses 29 and 305 clause 8


Use

19.7 Frontier-P is a post-plant, pre-emergence selective herbicide applied to prepared ground for the control of annual grasses and broadleaf weeds in maize, squash, sweetcorn, dwarf beans, onions and forage brassica.

19.8 The proposed use rate of Frontier-P for New Zealand conditions is 0.5 to 1.3 litres formulation/ha or 360-936 g a.i./ha. Frontier-P is intended for use only once a year. Frontier-P is not intended for direct use over water.

19.9 The applicant advises that application will be by either aerial or ground based methods.

Disposal

19.10 The applicant advises that the normal method of disposal of the substance will be via use.

19.11 Frontier-P as well as its damaged packaging, contaminated adsorbents, and other materials shall be disposed of in a suitable landfill. Additional methods are described in the GIFAP monograph “Disposal of unwanted pesticide stocks” 1991. Unclean empty containers are to be treated in that context like full ones.

19.12 Empty primary packages of Frontier-P shall be triple rinsed as described in the ECPA “Guidelines for rinsing agrochemical containers”, 1993. That reduces the amount of product to below 0.01% of the original amount. Pressure rinsing or integrated pressure rinsing of the packaging material achieves a similar or better result. The rinsate is to be added to the spray liquid.

19.13 Triple rinsed primary packages shall be rendered unusable, and then they may be disposed off according to local regulations and best available practice. The rinsed container may be offered for recycling under the Agrecovery Rural Recycling Programme.

19.14 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.

19.15 HAZARDOUS PROPERTIES, THRESHOLDS AND CLASSIFICATION

20 The Agency has evaluated the information supplied by the applicant and also referred to other data sources in assessing the hazardous properties of Frontier-P. This assessment is attached as Appendix 2.

21 The applicant’s and the Agency’s classification of the hazard profiles of Frontier-P are listed in Table 6.1.


Table 6.1: Summary of applicant’s and Agency’s HSNO classification of Frontier-P

Hazardous Property Applicant’s Assessment

Agency’s Assessment

Acute Toxicity (Oral) 6.1D 6.1D

Acute Toxicity (Inhalation) 6.1D(aspiration hazard)

─

Skin Irritancy 6.3B 6.3BEye Irritancy 6.4A 6.4ASkin Sensitisation 6.5B 6.5BCarcinogenicity 6.7B 6.7BTarget Organ Toxicity 6.9B ─Aquatic Ecotoxicity 9.1A 9.1ASoil Ecotoxicity 9.2A 9.2AEcotoxicity to Terrestrial Vertebrates

9.3C 9.3C

Biocide 9.1D ─

22 The differences between Agency’s and the applicant’s classifications of Frontier-P are:

6.3.1. The applicant’s incorrect inclusion of the biocide classification. This has been removed, as the substance has triggered ecotoxicity classifications and therefore the biocide rider does not apply.

6.3.2. The applicant assigned 6.9B classification based on the 2-year feeding study in rats. However, results from this study do not support classification of Frontier-P as a target organ toxicant.

6.3.3. The applicant assigned 6.1D (aspiration hazard) classification to Frontier-P because component A2 is classified in as presenting an aspiration hazard. However, aspiration hazard only triggers 6.1E classification and furthermore, component A2 is present at below the threshold for triggering aspiration hazard classification. Formulation test data indicates Frontier-P does not trigger classification as an inhalation toxicant.

23 The risk assessment in section 8 of this report is based on the Agency’s classifications of Frontier-P


24 DEFAULT CONTROLS24.1 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.

24.2 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 Frontier-P. Variations and additional controls for Frontier-P are considered in Section 10 of this report.

24.3 RISK ASSESSMENTIdentification of potentially non-negligible risks and costs

25 Potentially non-negligible risks were identified for evaluation following clauses 9 and 11, which incorporate sections 5, 6 and 8.

26 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.

27 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 Frontier-P

Lifecycle Activity Associated Source of Risk

Manufacture / Import An incident during the manufacture or importation of Frontier-P resulting in spillage and subsequent exposure of people or the environment to the substance.

Packing An incident during the packing of Frontier-P 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 Frontier-P resulting in spillage and subsequent exposure of people or the environment to the substance.

Use Application of Frontier-P 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 Frontier-P or packaging resulting in exposure of people or the environment to the substance.


Assessment of potentially significant risks

28 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.

29 The Agency notes that the evidence provided by the applicant and additional evidence found by the Agency, relating to the hazardous properties of Frontier-P, 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.

30 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.

31 A quantitative risk assessment has been carried out to evaluate the level of risk to operators, bystanders and the environment arising from the use of Frontier-P (see Appendix 3).

32 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).

Assessment of the risks to the environment

33 The Agency has classified Frontier-P as being very toxic in the aquatic environment (9.1A), very toxic to soil organisms (9.2A) and harmful to terrestrial vertebrates (9.3C). Dimethenamid-P is considered persistent in the environment. Thus, a range of organisms in the environment may be adversely affected if exposed to Frontier-P.

34 The Agency considers that the likelihood of exposure to the environment is greatest during use of the substance.

34.1 This quantitative assessment of the environmental risks associated with the use of Frontier-P show that it presents a high acute risk to the aquatic environment and a high risk to non-target plants (see Appendix 3).

34.2 The Agency notes the results of the quantitative modelling and considers that application of the following controls will reduce the level of risk to the environment to negligible:

The approved handler controls (triggered by the 9.1A and 9.2A classification). The Agency considers that requiring people using the

6 clause 25(1)


substance to be approved handlers, will minimise the risks associated with exposure to the aquatic and terrestrial environments; and

Prohibiting the application of Frontier-P into or onto water; and

Setting a maximum application rate and application frequency.

34.3 The risks of Frontier-P 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 Frontier-P to the environment.

Lifecycle Stage Potential Adverse Effect

Likelihood of Adverse Effect Occurring

Magnitude of Adverse Effect

Level of Risk

Manufacture, 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 there was a high risk to the aquatic environment from the use of Frontier-P. The Agency considers that the application of controls will reduce this risk to negligible.

Use resulting in death or adverse effects to non-target plants.

Quantitative assessment indicated that there was a high risk to non-target plants during the use of Frontier-P. The Agency considers that the application of controls will reduce this risk to negligible.

Use resulting in death or adverse effects to terrestrial vertebrates.

Quantitative assessment indicated that there was a low risk to birds during the use of Frontier-P. The Agency considers that the application of controls will reduce this risk to negligible.

Use resulting in death or adverse effects to terrestrial invertebrates

Quantitative assessment indicated that there was a negligible risk to bees and other beneficial insects during the use of Frontier-P.

Disposal Disposal resulting in death or adverse effects to aquatic or terrestrial organisms in the environment

Highly improbable

Minor Negligible


Assessment of the risks to human health and safety

35 The Agency has classified Frontier-P as an acute oral toxicant (6.1D), a skin irritant (6.3B), an eye irritant (6.4A), a skin sensitiser (6.5B) and a suspected carcinogen (6.7B).

36 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.

37 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 the highest application rates the exposure to Frontier-P, when used as recommended on the label, is not likely to present a high health risk to the mixers or applicators, as long as “full” Personal Protective Equipment (PPE) is worn during mixing, loading and applying the substance. The use of respirators is not required.

38 The Agency notes that the requirement for PPE is triggered as a default control for Frontier-P as a result of its 6.1D, 6.3B, 6.4A, 6.5B and 6.7B classifications. 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.

39 The Agency notes that the main potential source of exposure to the general public from Frontier-P (other than via food residues) is via spray drift. The Agency has undertaken an assessment of the risks to public/bystander health using the United Kingdom Chemicals Regulation Directorate’s (CRD) current formula to assess public/bystander exposure for pesticides. The results of this modelling indicate that the risks posed to bystanders from the use of Frontier-P are considered to be at acceptable levels and the default controls triggered by the toxicity hazards associated with the substance are sufficient to mitigate risks. The Agency, therefore, concludes that the health risk to bystanders is negligible. Further details on this quantitative assessment are given in Appendix 3.

39.1 The risks of Frontier-P 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 Frontier-P to human health and safety.

Lifecycle stage Potential Adverse Effect



Level of Risk

Manufacture/packing Acute toxicity Highly improbable

Moderate Negligible

Skin irritancyEye irritancy

Highly improbable

Minimal Negligible


Lifecycle stage Potential Adverse Effect



Level of Risk

Skin sensitisation Highly improbable

Minor to moderate

Negligible

Carcinogenicity Quantitative assessment indicates that the chronic risks to human health and safety are acceptable when PPE is worn. This reduces the level of risk to negligible.

Importation, transport or storage

Acute toxicity Highly improbable

Moderate Negligible


Highly improbable

Minimal Negligible


Minor to moderate

Negligible

Use Acute effects: operators & bystanders (qualitative assessment)

Acute toxicity Highly improbable

Moderate Negligible


Highly improbable

Minimal Negligible


Minor to moderate

Negligible

Chronic effects: operators (quantitative assessment)

Carcinogenicity Quantitative assessment indicated that the chronic risks to human health and safety are acceptable if PPE is worn during mixing, loading and application. The use of PPE reduces the level of risk to negligible.

Chronic effects: bystanders (quantitative assessment)

Carcinogenicity 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 toxicity Highly improbable

Moderate Negligible


Highly improbable

Minimal Negligible


Minor to moderate

Negligible

Carcinogenicity 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.


Relationship of Māori to the Environment39.2 ERMA New Zealand 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 ERMA New Zealand 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.

39.3 The Agency notes that Frontier-P 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.

39.4 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.

39.5 On considering the information outlined here and elsewhere in this report, the Agency considers a minimal impact from Frontier-P 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 Frontier-P will breach the principles of the Treaty of Waitangi.

39.6 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.

39.7 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

40 There are not expected to be any significant adverse impacts on the social environment with the controlled use of Frontier-P, 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


41 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.

42 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 obligations42.1 The Agency does not anticipate that Frontier-P will pose any risks to New

Zealand’s international obligations.

42.2 ASSESSMENT OF BENEFICIAL EFFECTSPotentially non-negligible benefits

42.3 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.

42.4 The applicant claims that the approval of Frontier-P will provide the following benefits:

42.4.1 The active ingredient in Frontier-P belongs to a chemical class of herbicides which has been extensively used on a worldwide scale in different crops and cropping systems for more than 30 years and has experienced very little resistance development. The main reason for the lack of wide spread resistance is to be seen in the complex mode of action of this chemical class.

42.4.2 The change from the racemic active ingredient in the current product Frontier to the resolved active isomer in Frontier-P will result in:-

a 47% reduction in the amount of herbicidal active ingredient applied per hectare;

the total amount of chemistry (litres of substance) applied per hectare being reduced by 35%;

significant savings relative to packaging, storage, transport and disposal (an estimated 36%);

and, linked to this, a significant reduction in the environmental impact of these activities.

42.5 The Agency considers that economic and related benefits are likely to be derived from the use of Frontier-P.


Likely effects of the substance being unavailable42.6 In accordance with section 29, consideration has been given to the likely effects

of Frontier-P being unavailable.

42.7 The Agency notes that there are similar herbicide products already available in New Zealand with a comparable range of hazards, but none that contain the resolved active isomer of dimethenamid-P.

42.8 The likely effects of Frontier-P being unavailable would thus be a reduction in consumer choice for end-users, the use of less effective forms of the active ingredient, resulting in higher quantities of herbicide being applied into the environment.

Risk reduction implications42.9 The applicant has provided information about some potential risk reduction

implications as outlined in section 9.2.2. The Agency also notes that there are herbicides available in New Zealand which contain the racemic active ingredient dimethenamid.

42.10 CONTROLSSetting of exposure limits and application rates

43 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 Frontier-P until implementation of a pending review of setting such values under section 77B. However, the Agency notes that Frontier-P is intended for use on food crops and contains a new active ingredient to New Zealand and, therefore, ADE and PDE values are proposed for dimethenamid-P (see Appendix 4).

43.1 Control T2 relates to the requirement to limit worker exposure to toxic substances by the setting of Workplace Exposure Standards (WESs). No WES values are proposed for any component Frontier-P (See Appendix 4).

43.2 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 Frontier-P and the default values are deleted (see Appendix 4).

43.3 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 Frontier-P, the Agency is not able to propose the setting of a maximum application rate under this regulation. However, the Agency notes that risk quotients derived from the environmental exposure modelling are above the level of concern (refer Appendix 3). This indicates that Frontier-P may cause adverse environmental effects when used according to the specific parameters of the risk assessment.


The Agency, therefore, considers it appropriate to set a maximum application rate under section 77A (see paragraph 10.5).

Proposed additions and modifications to controls43.4 The Agency notes that the risk quotients derived from the quantitative

modelling indicate that restrictions on use are necessary to mitigate 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 control is proposed for Frontier-P to restrict the level of risk to the environment:

43.4.1 The maximum application rate for Frontier-P shall be 1.3 L/ha (0.936 kg dimethenamid-P/ha) with a maximum application frequency of 1 application per year; and

43.4.2 Frontier-P shall not be applied onto or into water.

44 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.

45 Control EM12 relates to the requirements for secondary containment of pooling substances8. The EM12 secondary containment requirements have been triggered for Frontier-P as a result of its 9.1A classification. 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 Frontier-P. 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.

46 Control I169 includes a requirement to identify certain toxic components on product labels. The Agency, consistent with the guidance provided by the Global Harmonised System (GHS), considers that regulation 25(e) should be varied such that the concentration cut-offs that apply to a component with a hazard classification of 6.5, 6.6, 6.7, 6.8 or 6.9, for the purpose of triggering this requirement, should be as follows:

7 section 77A(4)(a)8 Regulations 35 – 41 of the Hazardous Substances (Emergency Management) Regulations 20019 Regulation 25 of the Hazardous Substances (Identification) Regulations 2001


HSNO Classification of Component Concentration Cut-off for Label (%)6.5A, 6.5B 0.110

6.6A, 6.7A 0.16.6B, 6.7B 1

6.8A, 6.8C 0.36.8B 3

6.9A, 6.9B 10

46.1 The Agency considers that the following controls should be varied under section 77(4)(b) for Frontier-P, as the variations will not significantly increase the adverse effects of the substance:

46.1.1 Control T7 relates to restrictions on the carriage of hazardous substances on passenger service vehicles. The Agency notes that the trigger quantity for this control was varied for the sensitisation hazard for pesticides transferred to the Act under the Hazardous Substances (Pesticides) Transfer Notice 2004. Consequently, the Agency considers that the quantity of Frontier-P triggering these requirements should likewise be varied from 0.1 L to 1 L.

46.1.2 Control E7 relates to requirements for ecotoxic substances to be under the control of an approved handler. The Agency considers that this control should be modified for Frontier-P 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). Frontier-P 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.”

46.1.3 Control TR1 relates to the requirements for a substance to be tracked and is triggered for Frontier-P 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, packaging, labelling and emergency management requirements. Thus, this control may be deleted.

10 Identification of sensitising components may be required below the 0.1% level if a lower value has been used for classification.

46.2 The Agency considers that the following controls may be combined11 for Frontier-P as they relate to the same requirements:

46.2.1 Controls T4 and E6 which relate to requirements for equipment used to handle hazardous substances.

46.2.2 Controls P13 and P15 which relate to requirements for packaging hazardous substances.

46.2.3 Controls D4 and D5 which relate to requirements for disposal of Frontier-P.

Control precedents

47 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

48 The Agency considers that the customised controls listed in Appendix 5 should apply to Frontier-P.

Environmental user charges

49 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.

50 The Agency considers that use of controls is the most effective means of managing the risks throughout the lifecycle of Frontier-P. The imposition of an environmental user charge instead of, or in combination with controls, is therefore not required at this time.

51 OVERALL EVALUATION OF RISKS, COSTS AND BENEFITS51.1 The Agency considers the risks of Frontier-P to human health to be negligible.

51.2 The Agency’s quantitative and qualitative assessments identified a high risk to the aquatic environment and non-target plants during the use of Frontier-P. However, the Agency considers that approved handler requirements and the setting of a maximum application rate will reduce the level of this risk to negligible.

11 section 77(5)

51.3 The Agency does not consider there to be significant risks to Māori cultural wellbeing, society and the community, the market economy, or to New Zealand’s international obligations.

51.4 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.

51.5 The Agency considers that there are benefits associated with the release of Frontier-P as are specified in Section 9 of this report.

51.6 Thus, the Agency considers that it is evident that the benefits of releasing Frontier-P outweigh the costs.

51.7 CONCLUSION51.8 BASF New Zealand Limited has applied for approval to import for release in

New Zealand the substance identified as Frontier-P.

52 The Agency considers Frontier-P triggers the following hazard classifications: 6.1D Acute oral toxicity 6.3B Skin irritancy 6.4A Eye irritancy 6.5B Skin sensitisation 6.7B Carcinogenicity 9.1A Aquatic ecotoxicity 9.2A Soil ecotoxicity 9.3C Terrestrial vertebrate ecotoxicity.

52.1 The Agency considers that there are negligible risks to the environment and human health and benefits associated with the release of Frontier-P. Therefore, the Agency considers that it is evident that the benefits of releasing Frontier-P outweigh the costs and the application may be approved in accordance with clause 26.

53 The Agency considers the controls listed in Appendix 5 should apply to Frontier-P.

APPENDIX 1: DECISION PATH

APPENDIX 2: HAZARD CLASSIFICATION Classification of Frontier–PFormulation data were not provided for all endpoints of Frontier–P. Where no data were available classification was estimated using mixture rules based on information on the components. Details of the methods used to derive the classifications are presented in Table A2.1. The relevant sections of the User Guide to Thresholds and Classifications under the HSNO Act (ERMA 2008a) that describe the mixture rules are listed in Table A2.2.

The active ingredient, dimethenamid-P, is a new pesticide active ingredient to New Zealand. The Agency has provided a summary of the physical/chemical properties, the toxicity, ecotoxicity and environmental fate data in Tables A2.4 to A2.15A.

Data quality – overall evaluation

The applicant has proposed the bridging of data between the racemic mixture dimethenamid and the resolved enantiomer dimethenamid-P by providing the original test reports for the former for comparison with the latter. The toxicology, ecotoxicology and environmental fate data appear comparable; therefore this proposition is accepted where there are gaps in the dimethenamid-P data.

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 dimethenamid-P and Frontier–P (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 A2.12. Overall, data provided for dimethenamid-P and Frontier–P were of high quality [Klimisch scores 1 or 2]. Data on components of Frontier–P 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 Frontier–P was not significant because of the volume of high quality data provided.

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. Note:Following submission of the EU dossier for Frontier-P the formulation BAS 656 07 H was immediately modified to BAS 656 08 H for commercialisation. Subsequently BAS 656 08H has also been modified. The changes made are not expected to significantly affect/alter the physic-chemical properties or the toxicological/ecotoxicological properties of the formulated product. For full details see Confidential Appendix 8.


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.html Retrieved 23 January 2008.


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

http://reach.jrc.it/

Table A2.0: Physical and chemical properties of Frontier–P (BAS 656 08H).* Test Frontier–P Method ReferenceCondition Clear liquid Visual inspection

Internal method no.CF/P 062.4

Kästel, 1999Report No. 01951GLPKlimisch score: 1BAS 656 07H

Colour Red brown Visual inspectionInternal method no.CF/P 038.5

Physical state Liquid Visual inspectionInternal method no.CF/P 039.5

Odour Strong aromatic OrganolepticInternal method no.CF/P 040.5

Flash point 105°C Pensky-Martens methodEC A9.1.6.3.2

pH (1%) 3.3 (CIPAC water D)3.2 (pure water)

CIPAC MT 75

Dynamic viscosity20°C

27.9 OECD guideline114

Surface tension(mN/m)

29.5 (0.25%) 29.9 (1.5%)

Internal method no.CF/P 014.12EEC A5 1.6.1

Auto ignition 410°C 92/69/EC A15 Löffler, 1998Report No. SIK-Nr.98/1682GLPKlimisch score: 1

Test substanceBAS 656 07H

*The Agency notes that although the formulation of Frontier is BAS 656 08H, the test substance used was a previous formulation BAS 656 07 H. The Agency has read across the data from the test substance to the new formulation based on similarities between the two substances.

As a result, the Agency has taken the density for Frontier-P® as 1.1271g/cm3 based on the composition of the formulation given in Appendix 8.

Conclusions:Frontier–P (656 08 H) is classified as non flammable as a result of it’s flashpoint of 105°C.


Table A2.1: Summary of the tox and ecotox hazard classifications of Frontier–P.Hazardous Property Agency Classification Classification Method Component(s) driving

classification6.1 oral 6.1D Formulation data N/A6.1 dermal Not triggered Formulation data N/A6.1 inhalation Not triggered Formulation data N/A6.3/8.2 Skin irritation/corrosion

6.3B Formulation data N/A

6.4/8.2 Eye irritation/corrosion

6.4A Formulation data N/A

6.5 contact sensitisation

6.5B Formulation data N/A

6.6 Mutagenicity Not triggered Mixture rules N/A6.7 Carcinogenicity 6.7B Mixture rules A6 and C2

6.8 Reproductive developmental toxicity

Not triggered Mixture rules N/A

6.9 Target organ systemic toxicity

Not triggered Mixture rules N/A

9.1 Aquatic ecotoxicity 9.1A Formulation data N/AAquatic Persistence Not readily degradable Mixture rules Active ingredientBioaccumulative Not bioaccumulative Mixture rules Active ingredient9.2 Soil ecotoxicity 9.2A Formulation data N/ASoil Persistence Not persistent Mixture rules Active ingredient9.3 Terrestrial vertebrate ecotoxicity

9.3C Formulation data N/A

9.4 Terrestrial invertebrate ecotoxicity

Not triggered Formulation 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 12Subclass 6.3/8.2 Skin Irritancy/Corrosivity Part V, Chapter 11, Page 7Subclass 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 8Subclass 6.6 Mutagenicity Part V, Chapter 14, Page 5Subclass 6.7 Carcinogenicity Part V, Chapter 15, Page 8Subclass 6.8 Reproductive Developmental Toxicity Part V, Chapter 16, Page 11Subclass 6.9 Target Organ Systemic Toxicity Part V, Chapter 17, Page 10Subclass 9.1 Aquatic Ecotoxicity Part VI, Chapter 19, Page 18Subclass 9.2 Soil Ecotoxicity Part VI, Chapter 20, Page 8Subclass 9.3 Terrestrial Vertebrate Ecotoxicity Part VI, Chapter 21, Page 7Subclass 9.4 Terrestrial Invertebrate Ecotoxicity Part VI, Chapter 22, Page 5


Identity of the Active IngredientAs this is the first full Part 5 application considered for this active ingredient, general and physico-chemical data about dimethenamid-P are provided in the Tables A2.3 and A2.4.

Table A2.3: Identification of dimethenamid-P (SAN 1289 H).CAS number:163515-14-8

IUPAC name S-2-Chloro-N-(2,4-dimethyl-3-thienyl)-N-(2-methoxy-1-methylethyl)acetamide

Common name Dimethenamid-PMolecular formula C12-H18-Cl-N-O2-SMolecular weight 275.8 Structural formula See Figure 1Purity 94%Significant impurities/additives (% concentration)Known uses HerbicideHSNO classification 6.1D (overall), 6.1D (oral and inhalation), 6.5B,

9.1A, 9.2A, 9.3BOther classification & labelling

Figure 1: Structural formula of dimethenamid-P (SAN 1289 H).http://chem.sis.nlm.nih.gov/chemidplus/

Physical and chemical properties of dimethenamid-P relevant to the interpretation of ecotoxicity test, environmental fate and exposure assessment are summarized in Table A2.4A. For endpoints for which data are lacking on dimethenamid-P, data are given on dimethenamid in Table 2.4B.

Table A2.4A: Physical and chemical properties of dimethenamid-P (SAN 1289 H).Property Dimethenamid-P Test method ReferenceCondition clear liquid Visual inspection


Krohl, 1999Report No.01985GLPKlimisch score: 1

Colour Yellow brown Visual inspectionInternal method no.CF/P 038.5

Physical state Liquid Visual inspection


http://chem.sis.nlm.nih.gov/chemidplus/


Widlak, 1997Report No.97/5193GLPKlimisch score: 1SAN 1289 H

Odour Faint aromatic Organoleptic determinationInternal method no.CF/P 040.5

Surface Tension 0.1%: 52.0 mN/m0.5% : 50.7 mN/m

Internal method no.CF/P 014.12EC A5 1.6.1

Density (20°C) 1.195 - 1.196 g/cm3 Internal method no.CF/P 082.1EC A3 1.4.2AM-7070 ASTMD891AM-7075 ASTM D792

Melting point/Solidification point

-50°C Internal method no.CF/P 58.3EC A1

Boiling Point 122.6°Cat 0.07 mmHg

ASTM D1120ASTM D850ASTM D86

Chen, 1999Report No. 97/5194GLPKlimisch score: 1SAN 1289 H

Vapour pressure 3.47 x 10-3 Pa (20°C)

2.51 x 10-3 Pa (25°C)

T-0338-0296-0Gas saturation method

Chen & Laster, 1996Report No.96/5418GLPKlimisch score: 1SAN 1289 H

Henry’s Law constant 4.72 x 10-9 atm-m3/mole4.80 x 10-4 Pa-m3/mole

Calculation Hsieh, 1999Report No.1999/5002SAN 1289 H

Physical state(Appearance)

Dark brown liquid Visual Observation Chen, 1997Report No.97/5198GLPKlimisch score: 1SAN 1289 H

Odour Strong unpleasant musty odour

Method T-0319 Jones, 1997Report No.97/5186SAN 1289 H

Water Solubility(25°C)

1149 ± 17 mg/L USEPA 40CFR Subdivision D Series 63-8

Laster, 1996Report No.96/5411GLPKlimisch score:1SAN 1289 H

Solvent Solubility (20°C)

Soluble in all proportions in:Tetrahydrofuranisopropyl alcoholacetoneacetonitriledimethyl sulfoxidedichloromethane

USEPA 40CFR Subdivision D Series 63-8

Liu, 1997Report No.97/5196GLPKlimisch score: 1SAN 1289 H


toluenen-octanol

hexane: 24.8/100 mL solventPowLog Pow

77.6 ± 171.89 ± 0.10

OPPTS 830.7550Shake flask method

Lam, 1998Report No.98/5071GLPKlimisch score: 1SAN 1289 H

Hydrolysis (25°C) pH 5 StablepH 7 StablepH 9 Stable

USEPASubdivision NSection 161-1

Guirguis, 1997Report No.97/5184GLPKlimisch score: 1SAN 1289 H

Photolysis DT50: 13.7 + 1.9 days(pH 7, 25°C at 100 ppm) 25.7 noon sunlight at 40°N latitude


Guirguis, 1997Report No.97/5195GLPKlimisch score: 1SAN 1289 H

Flash point 174°C USEPASubdivision NSection 63-15AM-7068ASTM D93-73

Widlak, 1997Report No.94/5177GLPKlimisch score: 1SAN 1289H

Oxidizing properties Moderate reducing agentshould not be mixed or stored in close proximity to strong oxidizing agents such as KMnO4

Does not react with iron.Special precautions against reducing agents are unnecessary.Does not react with MAP.In case of fire, extinguishing agents containing MAP can be used with this product.

OPPTS 830.6314 Jones, 1998Report No.98/5161GLPKlimisch score: 1BAS 656 PHSAN 1289H

Table A2.4B: Physical and chemical properties of dimethenamid (SAN 582 H).Property dimethenamid Test method ReferenceAuto ignition point 395°C EC A15

DIN 51794IEC 79-4

van Helvoirt, 1994Report No.94/11877GLPKlimisch score: 1SAN 582H

Explosive properties No explosion or ignition observed

USEPASubdivision NSection 63-15Stresau Laboratory test FD305

Srnak, 1991Report No.91/11850Non-GLPKlimisch score: 2SAN 582H

Quantum yield 0.007402Lifetime (5.98 days)Spring sunlight at 40°N


Sen & Yu, 1994Report No.94/10636


latitude. GLPKlimisch score: 1SAN 582H

Dissociation constant No indication of dissociation of SAN 582H taking place between pH of 1 and 11 at 25°C.


Rozek, 1988Report No.88/11352GLPKlimisch score: 1SAN 582H

Photochemical oxidative degradation

t1/2 = 2.45 h (12 h day)Rate constant:52.336 x 10-12 cm3/molecules

The rate constant for reactions of dimethenamid with OH radicals in the atmosphere was calculated using the AOPWIN program based on ATKINSON’S increment method.

QSAR estimate Scarf, 1999Report No.99/10075SAN 582H

Biological Hazards: Class 6 Toxicity

The active ingredient dimethenamid-P is a new active ingredient to New Zealand. Dimethenamid-P [also known by the name S-dimethenamid and by the code SAN1289] is the purified, active, R-enantiomer of dimethenamid. The substance dimethenamid [also known by the code name SAN 582 H] was transferred under the HSNO Act in 2004 (Approval number: HSR000673).

Dimethenamid is a racemate containing 50% M- and P-isomers. Frontier-P has been developed because the P-isomer only has herbicidal activity and thus if the M-isomer is removed the amount of dimethenamid applied can be cut by 50%. However the same amount of the active dimethenamid-P is still applied.

Rather than repeat all the mammalian toxicity studies bridging principles were applied along with some limited testing on the P-isomer to demonstrate that the P-isomer was no more toxic than the racemic mixture.

Based on the fact the P-isomer is 50% of the racemic mixture, then 100 mg of the racemate contains 50 mg P-isomer. So if the toxicity of the racemic mixture was purely associated with the P-isomer and the LOAEL for the racemic mixture was 100 mg/kg/day the LOAEL for the P-isomer would be expected to be 50 mg/kg/day.

If the P-isomer alone was more toxic than the racemic mixture then the LOAEL would be expected to be lower. The P-isomer could be more toxic on its own if the M-isomer somehow blocked the expression of toxicity of the P-isomer.

In order to determine whether it was appropriate to read across the toxicity of the racemic mixture to the P-isomer either using mixture rules or formulation test data, the following studies performed on both the racemic and P-isomer were considered:

Acute Toxicity – rat oral; rabbit dermal; inhalation; skin and eye irritation; dermal sensitisation


Repeat dose – 90 day rat Prenatal teratogenicity – rat Mutagenicity – Ames; CHO/HGPRT in vitro; in vitro chromosomal aberration

CHO;

Similar toxicity with respect to these endpoints justifies use of data on the racemic mixture to estimate the effects of dimethenamid-P for carcinogenicity, developmental/reproductive toxicity and target organ effects, including setting AOEL and ADE.

Table A2.5.1: Summary of Acute Oral Toxicity Data on Dimethenamid-P versus Racemic Dimethenamid.Racemic Dimethenamid Dimethenamid-PMaterials and methods:Five fasted Sprague-Dawley rats per sex and dose; test substance administered undiluted; dose levels of 150, 300 and 600 mg/kg bw; observation period of 14 days

Materials and methods:Five fasted Sprague-Dawley rats per sex and dose; test substance administered undiluted; dose levels of 350, 400 and 500 mg/kg bw; observation period of 15 days

LD50 : 371 (186) mg/kg bw (m);427 (214) mg/kg bw (f); 397(200) mg/kg bw (combined)

() – represents amount of P-isomer

LD50 : 429 mg/kg bw (m);531 mg/kg bw (f);466 mg/kg bw (combined)Comment: Comparison of racemate and P-isomer study results - LD50 values similar between two substances i.e. similar ballpark figures which would not result in an alteration of classification class. The LD50 of the P-isomer alone is higher than that of the racemic mixture, suggesting that the M-isomer is contributing to the toxicity of the racemate. The results here indicate that by using read across from racemate to P-isomer would represent a precautionary approach.

Clinical symptoms:Day of dosing - Ocular and oral discharges, and hypoactivity all groups; nasal discharge, wet rales, fecal staining, soft stool and abdominal griping in mid and high dose groups.

Days after dosing –hypoctivity, decreased food consumption and red ocular discharge.

All symptoms reversible by day 4

Clinical symptoms:Day of dosing – Lacrimation and salivation all dose groups, decreased activity at high dose;

Days after dosing – lethargy, decreased food consumption, yellow ano-genital staining, black and/or brown staining on the snout, oral area, buccal area and/or extremities, and decreased fecal volume or stool.

All symptoms reversible by day 5.

Comment: Comparison of racemate and P-isomer study results – there is some concordance. As the studies were run a number of years apart and considering the subjective nature of clinical signs it is inappropriate


Racemic Dimethenamid Dimethenamid-Pto do a detailed analysis.

Macroscopic findings:Animals that died:Stomach/intestine: discoloured and thickened walls, red coloured fluids, test material.

Lungs: discoloured and red foci.

Surviving animals:No macroscopic findings related to treatment.

Macroscopic findings:Animals that died:Stomach: black mucosa, brown fluid.

Lungs: discoloured.

Thymus: discoloured region (red/black)Thoracic cavity: fluidTestes: discoloured (red).

Surviving animals:No macroscopic findings related to treatment.

Comment: Comparison of racemate and P-isomer study results – there is some concordance. As the studies were run a number of years apart and considering the subjective nature of clinical signs it is inappropriate to do a detailed analysis.

Conclusion:The acute oral toxicity studies with racemic dimethenamid and dimethenamid-P resulted in similar outcomes, which supports read-across.

Table A2.5.2: Summary of Acute Dermal Toxicity Data on Dimethenamid-P versus Racemic Dimethenamid.

Racemic Dimethenamid Dimethenamid-P

Materials and methods:Five New Zealand white rabbits per sex and dose; test substance administered undiluted; single dose level - 2000 mg/kg bw; observation period of 14 days

Materials and methods:Five New Zealand white rabbits per sex and dose; test substance administered undiluted; single dose level - 2000 mg/kg bw; observation period of 15 days

LD50 : > 2000 mg/kg bw

LD50 : > 2000 mg/kg bw

Clinical symptoms:None related to treatment.No dermal effects.

Clinical symptoms:None related to treatment.3/10 treated animals had red subcutaneous discoloration foci at treatment site.

Macroscopic findings:None related to treatment.

Macroscopic findings:None related to treatment.

Conclusion:The acute dermal toxicity studies of racemic dimethenamid and dimethenamid-P did not only result in similar LD50 values but also in a similar lack of clinical symptoms and macroscopic findings. This again supports a read-across approach.

Table A2.5.3: Summary of Acute Inhalation Toxicity Data on Dimethenamid-P versus Racemic Dimethenamid.



Materials and methods:Five Wistar rats per sex; head-nose inhalation system; exposure period four hours; liquid aerosol; concentration of 4.99 mg/l; observation period of 14 days

Materials and methods:Five Sprague-Dawley rats per sex and dose; head-nose inhalation system, exposure period four hours; liquid aerosol; concentration of 2.2 mg/l; observation period of 15 days

LC 50 :> 4.99 mg/l (2.5 mg/l P-isomer) (highest concentration tested)

LC 50 : >2.2 mg/l air(highest concentration tested)

Cumulated mortality: No mortalities.

Cumulated mortality: No mortalities.

Clinical symptoms:During exposure: Sedation, dyspnea, curved body position and ruffled fur.Hours after exposure: sedation, dyspnea, curved body position and ruffled fur.

Days after exposure: Sedation, dyspnea, curved body posture, ruffled fur.

No symptoms after day 3.

Body weight gain was normal.

Clinical symptoms:During exposure: Labored breathing during last two hours.Hours after exposure: Secretory effects (lacrimation, chromodacryorrhea, red and clear nasal discharge, dried red facial material) and respiratory responses (labored breathing and moist rales).Days after exposure: dried red material on skin/fur; yellow anogenital stains.

No symptoms after day 3.

Body weight gain was normal.

Macroscopic findings:At sacrifice no findings related to the test substance

Macroscopic findings:At sacrifice no findings related to the test substance.

Conclusion:The acute inhalation exposure of rats to racemic dimethenamid and dimethenamid-P resulted in no deaths at the highest concentrations tested. Minor clinical observations observed in both studies cleared by day 3 after exposure. It can be concluded that both forms have a low acute inhalation hazard and are comparable in toxicity. Supporting appropriateness of read-across.

Table A2.5.4: Summary of Dermal Irritation Data on Dimethenamid-P versus Racemic Dimethenamid.Racemic Dimethenamid Dimethenamid-P

Materials and methods:Six New Zealand white rabbits; 0.5 ml test substance administered undiluted dermally for four hours; observation period of 72 hours.

Materials and methods:Six New Zealand white rabbits; 0.5 ml test substance administered undiluted dermally for four hours; observation period of 72 hours.

Irritation Results:Very slight erythema in 5/6 animals and edema in 1 animal.

Irritation Results : Slight erythema in 3/6 animals, very slight erythema in 2/6 animals; no edema

Irritation cleared:24 hr


Conclusion:Slight dermal irritation that cleared within 72 hr was noted both with racemic dimethenamid and dimethenamid-P. These results demonstrate that both forms present a potential for only slight dermal irritation. The later clearing of the irritation in the P-isomer study may be due to a difference in calling


Racemic Dimethenamid Dimethenamid-Plevels or twice as much P-isomer being present. However the later clearing is considered not to represent a toxicologically important event which indicates that read across is not appropriate.

Table A2.5.5: Summary of Eye Irritation Data on Dimethenamid-P versus Racemic Dimethenamid.Racemic Dimethenamid Dimethenamid-P

Materials and methods:Six New Zealand white rabbits; 0.1 ml test substance administered undiluted to conjunctival sac of one eye; no wash; observation period of 72 hours.

Materials and methods:Six New Zealand white rabbits; 0.1 ml test substance administered undiluted to conjunctival sac of one eye; no wash; observation period of 72 hours.

Irritation Results :

Conjunctiva: redness and mild discharge in all animals; chemosis in 4 animals.Cornea: noneIris: none

Irritation Results :

Conjunctiva: Slight redness and/or chemosis and moderate to severe discharge.Cornea: noneIris: none


Irritation cleared: 48 hr

Conclusion:Both racemic dimethenamid and dimethenamid-P produce mild transient ocular irritation in rabbits which cleared within 72 hr. No significant differences in eye irritation potential were observed between the two forms. Read-across is again supported.

Table A2.5.6: Summary of Dermal Sensitisation Data on Dimethenamid-P versus Racemic Dimethenamid.Racemic Dimethenamid Dimethenamid-P

Materials and methods:Maximization method; 10 guinea pigs in control, 20 in treatment group. Phase 1 induction with 5% test material given intracutaneous, phase 2 one week later with 100% applied dermally for 48 hr. Challenge two weeks later with 100% applied dermally. Skin reactions scored at 24 and 48 hr.

Materials and methods:Buehler method; 20 (10/sex) Dunkin Hartley guinea pigs for treatment group and 10 (5/sex) for control. Induction and challenge with undiluted test material. Induction – dermally, six hours, once a week for three weeks. Challenge - dermally for six hours, 14 days after induction. Dermal scoring at 24 and 48 hr after challenge.

Positive dermal responses:24 hr: 9/19 vs. 0/10 control48 hr: 15/19 vs. 0/10 control

Positive dermal responses:24 hr: 16/20 vs. 0/10 control48 hr: 13/20 vs. 0/10 control

Conclusion:An increased incidence of positive dermal responses was seen with both racemic dimethenamid and dimethenamid-P indicating both compounds are dermal sensitizers. Read across is supported

Table A2.5.7: Summary of Short-term Toxicity Data on Dimethenamid-P versus Racemic Dimethenamid.


Materials and methods:Test substance administration to 10 Sprague-Dawley rats per sex in the diet for 3-months; Concentrations: 0; 50, 150, 500; 1500 and 3,000 ppm

Materials and methods:Test substance administration to 10 Sprague-Dawley rats per sex in the diet for 3-months; Concentrations: 0; 500; 1500; and 3,000 ppm



Mortality and clinical symptoms:no substance-related deaths and no adverse clinical symptoms,

Mortality and clinical symptoms:no substance-related deaths and no adverse clinical symptoms,

Body Weight Gain:Retarded body weight gain at 1500 and 3,000 ppm and slight decrease in 500 ppm males

Body Weight Gain:retarded body weight gain at 1,500 and 3,000 ppm

Food consumption:No effect.

Food consumption:No effect.

Hematology:No effect.

Hematology:Increased activated partial pro-thromin time (APTT) at high dose. No other effects.

Clinical chemistry:Decreased APT and ALT at all levels.Alk Phos. decreased at 1500 and 3000 ppm.GGT increased at 3000.Cholesterol increased at 3000 and in females at 1500 ppm.

Clinical chemistry:Decreased APT and alkaline phosphatase at all levels.

GGT increased at 3000 and in males at 1500 ppm.Cholesterol increased in at 3000 ppm.

Urinalysis:no substance-related effect

Urinalysis:no substance-related effect

Relative Liver weight:Increased at 3000 ppm both sexes and in females at 1500 ppm.

Relative Liver weight:Increased at 1500 and 3000 ppm both sexes and in males at 500 ppm.

Pathology: Hepatocellular hypertrophy:Centrilobular in females at 1500 and 3000 ppm.

Pathology: Hepatocellular hypertrophy:Centrilobular in females at all dose levels. Periportal in males at 1500 and 3000 ppm.

NOAEL:500 ppm (250 ppm P-isomer)

NOAEL:500 ppm

Conclusion:The 3-month feeding studies led to no biologically relevant differences between racemic dimethenamid and dimethenamid-P. The NOAEL is considered to be 500 ppm for both forms. The NOAEL is based on the consideration that minor effects observed with both compounds at 500 ppm were due to a physiological response to the chemical and not due to frank toxicity. Read across is again supported. When considering P-isomer content between the two studies, the M-isomer does appear to contribute to toxicity when the substance is tested as a racemate.

Table A2.5.8: Summary of Prenatal Toxicity Data on Dimethenamid-P versus Racemic Dimethenamid.Racemic Dimethenamid Dimethenamid-PMaterials and methods:Groups of 25 pregnant Sprague-Dawley rats; Test substance administration in 0.5% CMC suspension with HiSil 233.Dose levels: 0; 50 (25), 215 (108) and 425 (213) mg/kg bw once daily by gavage from day 6 through day 15 of gestation. () represents P-isomer content.

Materials and methods:Groups of 25 pregnant Sprague-Dawley rats; Test substance administration in 0.5% aqueous CMC suspension with HiSil 233.Dose levels: 0; 25, 150 and 300 mg/kg bw once daily by gavage from day 6 through day 15 of gestation

Maternal toxicity:425 (213) mg/kg/day: Clinical signs. Body weight loss days 6-9, decreased weight gain days 6-16 (-35%). Decrease in food consumption. Increase in relative liver weight.

215 (108) mg/kg/day: Decreased body weight gain

Maternal toxicity:300 mg/kg/day: Clinical signs. Body weight loss during treatment days 6-9, decreased weight gain days 6-16 (-25%). Decreased food consumption. Increase in relative liver weight. 150 mg/kg/day: Decreased body weight gain days 6-16 (-18%). Decreased food consumption.


Racemic Dimethenamid Dimethenamid-Pdays 6-16 (-16%). Decreased food consumption. Increased liver weight.

50 (25) mg/kg/day: Slightly decreased body weight gain and food consumption (days 6-9 only) – not an adverse effect.

25 mg/kg/day: Slightly decreased body weight gain and food consumption (days 6-9 only). Considering range-find data these changes were spurious and not adverse effects.

Comment: no indication that the P-isomer alone is more toxic than when in the racemate form. Supporting read across

Embryo-/fetotoxicity:425 (213) mg/kg/day: Slight decrease in fetal body weight (-2%). Increased incidence of early resorptions.

215 (108) mg/kg/day: Slight decrease in fetal body weight (-1%). Increased incidence of early resorptions.

50 (25) mg/kg/day: No effect.

Embryo-/fetotoxicity:300 mg/kg/day: Slight decrease in fetal body weight (-3%). Retarded ossifications of 2nd sternal centra and pelvis pubis

150 mg/kg/day: Slight decrease in fetal body weight (-2%). Retarded ossifications of pelvis pubis and 2nd

sterna

25 mg/kg/day: No effect.

Comment: no indication that the P-isomer alone is more toxic then when in the racemate form. Supporting read across

Teratogenic effect: no Teratogenic effect: noNOAEL:Maternal toxicity: 50 (25) mg/ kg bwEmbryo-/fetotoxicity: 50 (25) mg/kg bw

NOAEL:maternal toxicity: 25 mg/kg/dayembryo-/fetotoxicity: 25 mg/kg bw

Conclusion: These studies demonstrate the similarity of the prenatal toxicity of racemic dimethenamid and dimethenamid-P. No teratogenic effects were noted at any dose level with either compound. Only the highest doses that were clearly maternally toxic caused signs of fetotoxicity. The slight and transient decreases in maternal body weight gain seen at the low doses in both studies were not considered to be toxicologically meaningful. The mid doses for both compounds showed some evidence of fetotoxicity. For the racemic mixture, the slight increase in resorptions was not considered to be toxicologically relevant and the mid dose was considered a NOAEL. For the P-isomer, the only fetotoxic effect at the mid dose was an increase in delayed ossifications, but this dose could not be excluded as an effect level resulting in the lowest dose being determined the fetotoxic NOAEL. In terms of P-isomer content the NOAEL’s are comparable between the two studies supporting read-across.

Table A2.5.9: Summary of Mutagenicity Data on Dimethenamid-P versus Racemic Dimethenamid.

Racemic Dimethenamid Dimethenamid-PAmes Assay.Strains tested: TA 98, TA 100, TA 1535, TA 1537 and TA 1538; with and without activation.Levels: 100 (50) to 10000 (5000) µg/plate.Results: Negative

Ames Assay:Test 1 -91.1% technical material.Strains tested: TA 98, TA 100, TA 1535, TA 1537 and E. coli WP2 uvrA with and without activation.Levels: 50 to 6500 µg/plate (non-act.),100 to 10000 µg/plate (with activation)Results: Weakly positive only for TA 100 without activation. Negative for TA 100 with activation and all other strains with and without activation.Tests 2 -and 3


Racemic Dimethenamid Dimethenamid-P91.1% technical material and 99.4% analytical grade materialStrains tested: TA 98, TA 100, TA 1535, TA 1537 and E. coli WP2 uvrA with and without activation.Levels: 4 to 5000 µg/plateResults: Negative for both technical and analytical grade materials.Test 491.1% technical materialStrain tested: TA 100 without activationLevels: 100 to 5000 µg/plateResults: Negative

CHO/HGPRT mammalian cell mutation assay:Dose levels: 33(16) to 333 (166) µg/ml (with and without activation)Cytotoxicity at highest dose levels.Results: Negative

CHO/HGRT mammalian cell mutation assay:Dose levels: 100 -400 µg/ml (without activation); 100 -450 µg/ml (with activation).Cytotoxicity at highest dose levels.Results: Negative

In vitro chromosome aberration:Chinese hamster ovary cells.Dose levels: 10 (5) to 150 (75) µg/ml for 17 hr without activation; 150 (75) to 500 (250) µg/ml for 2 hours with activation.Toxicity evident at high doses.Results: Negative

In vitro chromosome aberration:Chinese hamster ovary cells.Dose levels: 0, 15, 30, 60 and 120 µg/ml for 20 hr without activation; 0, 63, 125, 250 and 500 µg/ml for 4 hours with activation. Toxicity was evident at highest doses tested.Results: Negative

In vitro Unscheduled DNA synthesis (UDS) with rat primary hepatocytes:Test 1.Dose levels 0, 1, 3, 10, 30 and 100 nl/ml.Results: NegativeTest 2.Dose levels trial 1: 0, 0.025, 0.050, 0.10, 0.50, 1.00, 2.50, 5.0 and 10.0 µg/ml.Dose levels trial 2: 0, 0.10, 0.25, 1.00, 2.50, 5.00, and 10.0 µg/ml.Results: Equivocal positive. Test 3.Dose levels trial 1: 0, 0.32, 1.6, 8, 40, 200 µg/ml.Dose levels trial 2: 0, 7.8, 15.6, 31.3, 62.5 and 125 µg/ml.Results: Negative

In vitro Unscheduled DNA synthesis (UDS) with rat primary hepatocytes:

Dose levels 0, 7.8, 15.6, 31.3, 62.5, 125, 250, 500 or 1000 µg/ml.Results: Negative

Mouse micronucleus assay:Test 1.Single oral exposure.Dose levels: 0 and 1000 mg/kg.Results: NegativeTest 2.Two oral exposures.Dose levels: 0 and two doses of 710 mg/kg (50% of LD50).

Mouse micronucleus assay:Intraperitoneal exposure.Dose levels: 0, 103, 205 or 410 mg/kg (67% of LD50).

Results: Negative


Racemic Dimethenamid Dimethenamid-PResults: Negative.

Conclusion: Extensive mutagenicity testing has been conducted both with the racemic and P-isomer forms of dimethenamid. The assays were conducted at comparable dose levels for the racemic and P-isomer forms of dimethenamid. Racemic dimethenamid was negative in all genotoxicity studies except for an equivocal positive in one in vitro UDS assay which could not be reproduced. All other studies were negative. With the P-isomer, a positive effect was noted in one strain without activation in the Ames assay. However, this could not be repeated in three separate studies. Negative results were obtained in all other mutagenicity studies conducted with Dimethenamid-P. Although the route of exposure for the mouse micronucleus assay was different for the two forms (single oral exposure for the racemic mixture and intraperitoneal for the P-isomer), this is not consider to have any material effect on the comparability of the test results, which were both negative.The overall weight of the evidence demonstrates no mutagenic potential for both the racemate and Dimethenamid-P. Thus, read across is again supported.

Having determined that the toxicity profiles of racemic dimethenamid and dimethenamid-P are comparable and thus read-across is acceptable, the toxicity profile of dimethenamid-P is summarised in Table A2.6. Where a test on dimethenamid-P was not carried out, the equivalent test on the racemate is used instead. Specifically, carcinogenicity, reproductive and chronic toxicity studies were not undertaken using dimethenamid-P, so tests using the racemate are used instead (see table A2.7). 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 A2.9.

Table A2.6: Summary of toxicity data on dimethenamid-P and its metabolites.ACUTE TOXICITY

Acute oral toxicity Acute dermal toxicity Acute inhalation toxicity

TEST SUBSTANCE: SAN 1289 (S-dimethenamid technical) Purity 96.3% dimethenamid (91.1% S-dimethenamid)

SPECIES: Rat

STRAIN: Sprague-Dawley CD

NUMBER/SEX/GROUP: 5

DOSE LEVELS: 350, 400 and 500 mg/kg bw

ADMINISTRATION ROUTE: Oral intubation.

ENDPOINT: LD50

VALUE: 466 mg/kg bw (both sexes), 429 mg/kg bw males, 531 mg/kg bw females.

RESULTS: Deaths: 350 mg/kg bw group: 0.

TEST SUBSTANCE: SAN 1289 (S-dimethenamid technical) Purity 96.3% dimethenamid (91.1% S-dimethenamid).

SPECIES: Rabbit

STRAIN: New Zealand White

NUMBER/SEX/GROUP: 5

DOSE LEVELS: 2,000 mg/kg bw

ADMINISTRATION ROUTE: 24-Hour occluded dermal application.

ENDPOINT: LD50

VALUE: >2,000 mg/kg bw

RESULTS: No signs of toxicity observed in-life or at necropsy.

TEST SUBSTANCE: SAN 1289 - 96.3% S-Dimethenamid technical

SPECIES: Rat

STRAIN: Sprague-Dawley CD

NUMBER/SEX/GROUP: 5

DOSE: 2.2 mg/L for four hours. The applicant has not indicated whether or not this was the maximum dose practicable.

ADMINISTRATION ROUTE: Nose-only inhalation exposure to a mist of the substance.

ENDPOINT: LC50

VALUE: >2.2 mg/L

RESULTS: From exposure through the first two days, animals showed lacrimation,


400 mg/kg: 1 male (day 3); 500 mg/kg: All males died

(one within 23 hours of dosing, three on day 3 and the fifth on day 5). Two females died (both within 23hours of dosing).

Signs on day of dosing: Animals in all groups

showed lacrimation and excessive salivation.

All high-dose animals exhibited decreased activity, yellow ano-genital staining, lethargy, decreased food consumption, decreased faecal volume or no stool. [Note that animals were individually housed].

Surviving animals were free of abnormalities by Day 5.

Body weights: 350 mg/kg bw group - all

animals showed body weight gains on days 8 and 15.

400 mg/kg group – one female showed weight loss on day 8 and weight gain by day 15, whilst another showed weight loss on day 8 and no weight change by day 15. All surviving males recorded weight gains on both days.

500 mg/kg group - one female showed weight loss by day 8 but gained weight by day 15. All other surviving animals showed weight gains on both days.

Necropsy findings: Animals found dead during

the study revealed the following: red thymic region, fluid in the thoracic cavity, red lungs, black mucosa and brown fluid in the stomach, and red testes.

No abnormalities were observed in animals sacrificed at study termination.

GLP: Yes.

TEST GUIDELINES: US EPA FIFRA Series 81-1, Acute Oral Toxicity

REFERENCE SOURCE:

GLP: Yes

TEST GUIDELINES: US EPA FIFRA Series 81-2, Acute Dermal Toxicity Study.

REFERENCE SOURCE: Blaszcak, D.L. (1996). Acute Dermal Toxicity Study with SAN 1289 H Technical in Rabbits. Study No.: 96-1405. Sandoz Agro, Inc. 1300 East Touhy Avenue, Des Plaines, IL 60018.

RELIABILITY (KLIMISCH SCORE): 1

chromodacryorrhea, red nasal discharge, laboured breathing and moist rales. No responses were seen after day two. Treatment with the test substance did not produce any adverse effect on body weight gain. There were no abnormal post-mortem findings.

TEST GUIDELINES: US EPA FIFRA Series 81-3, Acute Inhalation Toxicity Study.

REFERENCE SOURCE: Hoffman, G.M. (1996). An Acute (4-hour) Inhalation Toxicity Study of SAN 1289 H Technical In the Rat via Nose-only Exposure. Study No.: 96-5279. Sandoz Agro, Inc. 1300 East Touhy Avenue, Des Plaines, Illinois 60018-3300.


Comments:The threshold for classifying a substance in mist form as an inhalation toxicant is 5 mg/L. In this study, the substance was only tested up to 2.2 mg/L and the applicant did not indicate whether or not this was the maximum possible dose. The effects seen at 2.2 mg/L are sufficient to trigger 6.1D classification. Moreover, these effects could worsen with increasing dose.


Blaszcak, D.L. (1996). Acute Oral Toxicity Study with SAN 1289 H Technical in Rats. Study No.: 96-1404. Sandoz Agro, Inc. 1300 East Touhy Avenue, Des Plaines, IL 60018.


Classification: 6.1D (oral) classification is assigned on the basis of the combined LD50 466 mg/kg).

Classification: The test substance does not trigger classification as an acute dermal toxicant.

Classification: The test substance triggers 6.1D classification as an acute inhalation toxicant.

IRRITATION

Eye irritation Skin irritation

TEST SUBSTANCE: 96.3% dimethenamid (91.1% S-dimethenamid)

SPECIES: Rabbit


NUMBER/SEX/GROUP: 2 males and 4 females

APPLICATION: 0.1 mL of test material into the lower conjunctival sac of one eye.

RESULTS:All six animals exhibited slight conjunctival redness and or chemosis and moderate to severe conjunctival discharge. Four animals were free of all irritation by 24 hours and the remaining two animals were free of all irritation by 48 hours.Mean Draize Scores, 24-72 hours: Corneal opacity: 0/6 = 0Iritis: 0/6 = 0. Conjunctival redness. 0/6 = 0Conjunctival oedema: 0/6 = 0Thus, the substance caused mild, transient ocular irritation.

TEST GUIDELINES: US EPA FIFRA Series 81-4, Primary Eye Irritation Study.

REFERENCE SOURCE: Blaszcak, D.L. (1996). Primary Eye Irritation Study with SAN 1289 H Technical in Rabbits. Study Number 96-1407. Sandoz Agro, Inc. 1300 E. Touhy Avenue, Des Plaines, IL 60018-3300



SPECIES: Rabbit


NUMBER/SEX/GROUP: 3 males and 3 females

APPLICATION: 0.5 mL semi-occluded, 4-hour exposure

RESULTS:Three of the six animals exhibited slight erythema with no oedema; two animals exhibited very slight erythema with no oedema. The sixth animal did not show any signs of irritation.

Mean Draize Score 24-72 hours for erythema: 14/18 = 0.77

Mean Draize Score 24-72 hours for oedema: 0/18 =0

REVERSIBILITY OF EFFECT: erythema reversed within 72 hours in all animals

TEST GUIDELINES: US EPA FIFRA Series 81-5, Primary Dermal Irritation.

REFERENCE SOURCE: Blaszcak, D.L. (1996). Primary Dermal Irritation Study with SAN 1289 H Technical in Rabbits. Study Number 96-1406. Sandoz Agro, Inc. 1300 E. Touhy Avenue, Des Plaines, IL 60018-3300


Conclusion on Classification:The test substance does not trigger classification as an eye irritant.

Conclusion on Classification: The test substance does not trigger classification as a skin irritant.

SENSITISATION


Respiratory sensitization Contact sensitizationNo tests undertaken.


SPECIES: Guinea pig

STRAIN: Dunkin Hartley (albino)

NUMBER/SEX/GROUP: Range finding – 3/sex; Sensitization study – 10/sex; Irritation control – 5/sex.

METHOD: Buehler method (3-Induction)

APPLICATION: Closed patch technique using undiluted test substance.

RESULTS: Induction dose administered once per week for three weeks. All animals showed positive response by third induction dose. Challenge dose administered 14 days later with all animals showing a positive response: 17/20 scored ≥ 1 and the remaining 3/20 scored 0.5. Incidence index of 85%.

TEST GUIDELINES:US EPA FIFRA Series 81-6, Dermal Sensitization Study.

REFERENCE SOURCE: Blaszcak, D.L. (1996). Closed-Patch Repeated Insult Dermal Sensitization Study with SAN 1289 H Technical in Guinea Pigs (Buehler Method). Study No.: 96-1408. Sandoz Agro, Inc. 1300 E. Touhy Avenue, Des Plaines, IL 60018-3300


Conclusion on classification: Conclusion on classificationThe substance triggers 6.5B classification (contact sensitizer).

MUTAGENICITY

In vitro studies In vivo studies

STUDY TYPE: Bacterial Plate Incorporation Mutagenicity Assay with and without S9 Activation

CELL TYPE: Salmonella typhimurium histidine auxotrophs TA98, TA100, TA1535, TA1537 and Escherichia coli tryptophan auxotroph WP2 uvr A.

TEST SUBSTANCE: 96.3% dimethenamid, (91.1% S-dimethenamid)

DOSE RATE: 6.7, 10, 33, 67, 100, 333, 667, 1,000, 3,333 and 5,000 μg per plate.

RESULTS:Precipitate observed at >3,333 μg/plate with no appreciable toxicity. Positive mutagenicity response with tester strain TA100 without S9

STUDY TYPE: Micronucleus cytogenic assay in mice

SPECIES: ICR Mice

TEST SUBSTANCE: S-Dimethenamid (96.45%)

ANIMALS/SEX/GROUP: 15 of each sex in the vehicle only, low

and mid-dose groups; 20 of each sex in the high dose group;

and 5 of each sex in the positive control

group.

DOSE LEVELS: 103, 205 and 410 mg/kg bw by intraperitoneal injection


activation.

GUIDELINE: US EPA FIFRA Series 84-2

REFERENCE SOURCE:Wagner, V.O and Coffman, N. (1996). Salmonella / Escherichia coli Plate Incorporation Mutagenicity Assay. Reg. Doc. #BASF 96/5403. Sandox Agro, Inc. 1300 East Touhy Avenue, Des Plaines, IL 60018.


…………………………………………………...

STUDY TYPE: Bacterial reverse mutation assay with and without S9 Activation.


TEST SUBSTANCE: S-dimethenamid (99.4%)

DOSE RATE: 20 μg – 5,000 µg/plate standard plate test and 4 μg – 2,500 µg/plate pre-incubation test.

RESULTS:No mutagenic response was observed with or without activation. No precipitation of the test substance was found. Toxicity was observed at >500 μg/plate.

GUIDELINE:OECD Nos. 471 and 472.

REFERENCE SOURCE:Engelhardt, G. and Hoffman, H. (1997). Salmonella typhimurium/Escherichia coli Reverse Mutation Assay (Standard Plate Test and Preincubatuion Test) with S-Dimethenamid. Reg. Doc. #BASF 97/10621. Department of Toxicology, BASF Aktiengesellschaft D-67056 Ludwigshafen/Rhein, FRG.


…………………………………………………...



TEST SUBSTANCE: S-dimethenamid technical (91.1%)

RESULTS:No deaths observed. Clinical signs following dosing included lethargy (7/15 males at 205 mg/kg bw, 4/15 females at same dose; all animals in both sexes at 410 mg/kg bw), hyperactivity and aggressiveness in all animals at 205 and 410 mg/kg bw. No significant increase in micronucleated polychromatic erythrocytes in the treated groups relative to the controls at 24, 48 or 72 hours after administration. The substance was thus negative in the mouse micronucleus assay.

GUIDELINE: FIFRA 84-2.

REFERENCE SOURCE: Puman, D.L., Gudi, R., and Poris, S.K. (1996). Micronucleaus cytogenetic Assay in Mice. Microbiological Associates, Inc. 5221 River Road, Bethesda, Maryland 20816 and 9900 Blackwell Road, Rockville, Maryland 20850. Study Number G95CB09.122


Comments:The Agency notes that the signs reported following dosing i.e. lethargy, hyperactivity/aggressiveness contradict each other. The authors have not commented on this.


DOSE RATE: 20; 100; 500; 2,500 and 5,000 µg/plate

RESULTS: Toxicity observed from >500 μg/plate. No test substance precipitation found. Test substance did not cause any increase in the number of revertant colonies either with or without S9 mix. Hence, under these experimental conditions, the test substance is not mutagenic.

GUIDELINE: OECD 471 and 472

REFERENCE SOURCE: Engelhardt, G. and Hoffman, H. (1997). Salmonella typhimurium/Escherichia coli Reverse Mutation Assay (Standard Plate Test and Preincubation Test) with S-Dimethenamid technical. Reg. Doc. #BASF 97/10622. Department of Toxicology, BASF Aktiengesellschaft D-67056 Ludwigshafen/Rhein, FRG.


…………………………………………………...


STRAIN: Salmonella typhimurium histidine auxotroph TA100

TEST SUBSTANCE: 91.1% S-dimethenamid

DOSE RATE: 100; 333; 1,000; 2,000; 3,333; 4,000 and 5,000 µg/plate.

RESULTS:No positive mutagenic response observed. Precipitate was observed at >2,000 g/plate. No appreciable toxicity observed.

GUIDELINE: US EPA 84-2

REFERENCE SOURCE: Wagner, V.O. and Klug, M.L. (1997). Bacterial Reverse Mutation Assay. BASF Reg. Doc # 97/5271. MA BioServices, Inc. 9630 Medical Center Drive, Rockville, MD 20850.


…………………………………………………...

STUDY TYPE: CHO/HGPRT mutation assay.

CELL TYPE: Chinese Hamster Ovary cells CHO-K1-BH4



DOSE RANGE: 50 – 400 µg/ml non-activated cultures; 25 – 450 µg/ml S9 activated cultures.

RESULTS:No positive mutagenic response obtained. No precipitate observed. Toxicity observed at <350 μg/plate without activation and 400 and 450 μg/plate with activation.

GUIDELINE: FIFRA 84-2

REFERENCE SOURCE: San, R.H.C and Clarke, J.J. (1996). CHO/HGPRT mutation assay: SAN1289 H technical. BASF Reg. Doc. #96/5404. Microbiological Associates, Inc. 9900 Blackwell Road, Rockville, MD 20850.


…………………………………………………...

STUDY TYPE: Chromosome aberration test in Chinese hamster ovary (CHO) cells

CELL TYPE: Chinese Hamster Ovary cells CHO-K1


DOSE RANGE: 2 – 120 µg/ml non-activated cultures; 8 - 500 µg/ml S9 activated cultures.

RESULTS:The only positive result obtained was at the 60 μg/plate dose level in the non-activated test system. However, this positive response was within the historical range of the solvent control and not considered biologically significant. Based on this, the authors concluded that the test was negative for the induction of structural aberrations in CHO cells.


REFERENCE SOURCE:Curry, P.T. and Schadly, E. (1996). Chromosome Aberrations in Chinese hamster ovary (CHO) cells. Reg. Doc. #BASF 96/5400. Microbiological Associates, Inc. 9900 Blackwell Road, Rockville, MD 20850.


…………………………………………………...

STUDY TYPE: Unscheduled DNA synthesis.


CELL TYPE: Primary hepatocytes from a male Sprague-Dawley rat.


DOSE LEVELS: 7.8, 15.6, 31.3, 62.5, 125 µg/ml

RESULTS: The test article did not induce a significant increase in the mean number of net nuclear grain counts at any dose level compared to the solvent control. Thus, S-dimethenamid was negative in the UDS assay.


REFERENCE SOURCE: San, R., Sly, J (1996). Unscheduled DNA Synthesis Assay in Rat Primary Hepatocytes. Reg. Doc. #BASF 96/5399. Microbiological Associates, Inc. 9900 Blackwell Road, Rockville, MD 20850.


ERMA New Zealand CommentsERMA notes that although one of the assays returned a positive mutagenicity result with the TA100 tester strain of Salmonella typhimurium, three more assays were subsequently run. All of these gave negative results with all strains used. ERMA therefore concurs with the conclusions drawn by the Authors.

Conclusion on classification: Based on a weight-of-evidence approach, in-vitro and in-vivo studies indicate that the active ingredient is not mutagenic, therefore no classification is assigned.

CARCINOGENICITY

Refer to studies with SAN 582 H (racemic mixture of r and s dimethenamid).

Conclusion on classification: Racemic dimethenamid (and hence dimethenamid-P) does not trigger classification as a carcinogen.

REPRODUCTIVE/DEVELOPMENTAL TOXICITY

Developmental studies

STUDY TYPE: Developmental Toxicity Study

SPECIES: Rat

STRAIN: Sprague-Dawley Crl:CD® BF

TEST SUBSTANCE: SAN 1289 H Technical (S-Dimethenamid Technical).

DOSES: 0, 25, 150 and 300 mg/kg/day


ROUTE: Orally by gavage

TEST GUIDELINE: US EPA Pesticide Assessment Guidelines Subdivision F, 83-3.

RESULTS: Maternal1. No deaths, abortions or premature deliveries in any group;2. Significantly higher number of rats with excess lacrimation, piloerection, salivation, decreased

motor activity, swollen ocular membrane, ptosis, dark pink skin (nose, mouth, forepaws, hindpaws, hindlimbs or ears) and urine stains on abdominal fur in 300 mg/kg/day dose group;

3. Absolute feed consumption significantly reduced in the 150 and 300 mg/kg/day groups throughout the dosing period (days 6 through 15);

4. Absolute and relative feed consumption values significantly reduced in the 150 and 300 mg/kg/day groups for the entire gestation period after dosing was begun,

5. Reduced body weight gain in the 150 mg/kg/day groups and a significant weight loss in the 300 mg/kg/kg group on days of presumed gestation 6 to 9;

6. Maternal body weights for the 150 and 300 mg/kg/day groups significantly less than for the control groups from days 9 and 8 respectively;

7. Percentage liver weight significantly increased in the 300 mg/kg/day group. This observation reflected dosage-dependent but not statistically significant tendencies for increased absolute liver weight and reduced terminal body weight in this group.

Foetal1. Foetal body weights reduced in the 150 and 300 mg/kg/day groups;2. Significant increases in foetal alterations in the 150 and 300 mg/kg/day groups due to retarded

ossifications of sternal centra and pelvic pubes. Occurred at doses where maternal toxicity was evident;

3. Foetal alterations noted were as follows: Umbilical hernia and oedema of head, neck and thoracic regions in one 300mg/kg/day dose

group foetus. Skeletal examination of this foetus identified alterations commonly associated with compression secondary to oedema including incomplete ossification of the tympanic rings, irregular ossification of the left scapulae and absence of the bones in the forelimbs (humerus, radius and ulna) and the right hindlimb (femur) and incompletely ossified pubes.;

Two 300 mg/kg/day foetuses had a depressed eye bulge associated with microphthalmia of the affected eye;

4. Analyses of the average numbers of foetal ossification sites per litter did not reveal biologically important or statistically significant differences among the three dosage groups.

REFERENCE SOURCE: York, R.G. (1996). Oral (Gavage) Developmental Toxicity Study of SAN 1289 H in Rats. Reg.Doc.#BASF 97/5274. Argus Research Laboratories, Inc. 905 Sheehy Drive, Building A, Horsham, Pennsylvania 19044-1297.


DEVELOPMENTAL STUDIES

MATERNAL TOXICITY:NOAEL: 25 mg/kg/day.LOAEL: 150 mg/kg/day due to effects on body weight.

FOETAL TOXICITY NOAEL: >300 mg/kg/dayLOAEL: >300 mg/kg/day

ERMA New Zealand Comments:ERMA New Zealand concurs with the conclusions of the Authors – the maternal LOAEL is 150 mg/kg/day whilst maternal NOAEL is 25 mg/kg/day. As described above, the dams showed reduced food intake and body weight gain at the mid and high doses, which results in poor nutritional status. Therefore, the foetal effects seen at the highest dose


tested were secondary to maternal toxicity. Moreover, foetal effects seen at all the doses tested were neither biologically important nor statistically significant compared with those seen in the control animals. Therefore, both the foetal LOAEL and NOAEL > 300 mg/kg bw/day, the highest dose tested.

Reproductive studiesRacemic dimethenamid (and hence dimethenamid-P) does not trigger classification as a reproductive toxicant (Refer to studies with SAN 582 H, the racemic mixture of R- and S-dimethenamid).

Conclusion on classification: The test substance does not trigger classification as a developmental toxicant because the effects seen at the highest dose were secondary to maternal toxicity.TARGET ORGAN SYSTEMIC TOXICITY

Subchronic toxicity – oral

TYPE OF STUDY: 4-week range-finding study of SAN1289H in rat via dietary administration

SPECIES/STRAIN: Sprague-Dawley CD BR rats

NO.ANIMALS/SEX/GROUP: 5

TEST SUBSTANCE: 94.7% active ingredient (S-dimethenamid)

DOSE LEVELS: 0, 150, 500, 1500 and 3000 ppm corresponding to-

0, 15, 50, 155, 306 mg/kg bw /day (males); 0, 12, 52, 143, 290 mg/kg bw /day (females)

ROUTE: Oral, via the diet

GLP: YES

TEST GUIDELINES: None identified

RESULTS:1. Mean body weights of male animals receiving the highest dose (306 mg/kg bw / day) were lower

than those of the control animals throughout the study (percentage difference from mean control body weight was -7.1%);

2. Slight increase in mean gamma-glutamyl transferase values in the high-dose animals (7+2 IU/L compared to 0 IU/L for the control animals);

3. Relative and absolute liver weights of animals in the high-dose group (both sexes) were significantly increased compared with the control values at the termination of the study;

LOEL: 306 mg/kg bw /day (males), 290 mg/kg bw /day (females) NOEL: 155 mg/kg bw /day (males), 143 mg/kg bw /day (females)

REFERENCE SOURCE: Randall, M et al (1996). A 4-week Range-finding Study of SAN 1289 H in the Rat via Dietary Administration. Study No. 95-2400. Sandoz Agro, Inc. 1300 East Touhy Avenue, Des Plaines, IL 60018.

RELIABILITY (KLIMISCH SCORE): 1.........................................................................................................................................

TYPE OF STUDY: Subchronic (3-month) toxicity study in rats.


SPECIES/STRAIN: Crl: CD® BR Sprague-Dawley rats

NO. ANIMALS/SEX/GROUP: 10

TEST SUBSTANCE: 96.3% dimethenamid, 91.1 % S-dimethenamid

DOSE LEVELS: 0, 500, 1500, 3000 ppm corresponding to 0, 37, 110 and 222 mg/kg bw / day for males and 0, 40, 125 and 256 mg/kg bw / day for females.

ROUTE: oral (dietary)

GLP: yes

TEST GUIDELINES: US EPA FIFRA 82-1

RESULTS: 1. No deaths were recorded during the study;2. Terminal mean body weights for 1500 and 3000 ppm dose males were 5% and 7% lower than

those of control animals respectively. For females, they were 4% and 5% lower than controls respectively. Group mean body weights for treated animals were lower than those of controls beginning week 1 after dosing through the end of the study;

3. Mean activated partial thromboplastin time of 3000 ppm dose animals was higher than that of controls. However, the difference was only statistically significant in females [this is not reported in any other study];

4. Gamma glutamyl transferase (GGT) increased in males in the 1500 and 3000 ppm dose groups and in females in the 3000 dose group;

5. Dose related trend towards decreased serum aspartate aminotransferase (AST) for males in all groups and statistically significant decreases in serum alanine aminotransferase (ALT), and serum alkaline phosphatase (ALP) in the 1500 and 3000 ppm male animals;

6. Trend toward slightly increased cholesterol values in treated animals, statistically significant in high dose males;

7. Increase in absolute and relative liver weights of males in all dose groups and females in the 1500 and 3000 ppm dose groups;

8. Treatment related slight periportal hepatocellular hypertrophy in males in 8/10 mid-dose animals and all high dose animals;

9. Treatment related slight centrilobular hepatocellular hypertrophy in females at an incidence of 3/10, 8/10 and 8/10 for the low, mid and high dose animals respectively which were not seen in controls;

10. The cytoplasm of enlarged hepatocytes had ring-like eosinophilic inclusions of variable sizes in 3/10 and 7/10 males of the mid and high dose groups respectively. These inclusions were not observed in females.

NOAEL: 500 ppm (37 mg/kg bw/day males; 40 mg/kg bw / day females).LOAEL: 1500 ppm (110 mg/kg bw/day males; 125 mg/kg bw / day females) based on presence of eosinophilic cytoplasmic inclusions in hepatocytes and hepatocellular hypertrophy.

REFERENCE SOURCE: Blanset, D (1996). A Subchronic (3-month) Toxicity study of SAN 1289 H in the Rat via Dietary Administration. Reg. Doc. # BASF 96/5420. Sandoz Agro, inc., 1300 East Touhy Avenue, Des Plaines, IL 60018.


Comments:The toxicological significance of decreases of the enzymes ALT, AST and ALP is questionable. Normally, increases in activity of these enzymes indicate liver damage. The LOAEL obtained from the 4-week range-finding study in Sprague-Dawley rats described above was 306 mg/kg/day. It is also noted that in the developmental toxicity study also carried out with Sprague-Dawley rats, the LOAEL for maternal toxicity was 150 mg/kg/day driven by effects on body weight without any other evidence of specific target organ toxicity. Taken together, the weight of evidence suggests that 6.9 classification


is not warranted for dimethenamid-P.Conclusion on ClassificationThe test substance does not trigger classification as a 6.9 target organ toxicant.

Table A2.7: Summary of toxicity data on SAN 582 H (racemic mixture of r/s-dimethenamid).ABSORPTION, DISTRIBUTION AND METABOLISM OF SAN 582

TYPE OF STUDY: Absorption, Distribution And Metabolism in Rats

SPECIES/STRAIN: male and female kfm:WIST rats

TEST SUBSTANCE: SAN 582 H

DOSE LEVELS: 10 mg/kg bw for acute low oral and intravenous administration and 1000 mg/kg bw high oral dose. 10 mg/kg bw for repeated oral doses once a day for 14 days.

RESULTS:After single oral low dose exposure, lowest absorption obtained ~ 90%After single oral high dose exposure, lowest absorption obtained ~ 63%After repeated low doses, absorption was similar to that after a single oral low dose exposure.

REFERENCE SOURCE:Vollmin, S. (1992). Absorption, Distribution Metabolism and Excretion of (14C) SAN 582 H in rat after single and multiple doses (addendum to: SAN 582 H metabolism in rat; BASF RegDoc# 89/11026. SANDOZ Agro, Ltd., Basle, CH. BASF RegDoc.# 92/12428

GLP: Yes...................................................................................................................

TYPE OF STUDY: Dermal Absorption of 14C-R,S-dimethenamid and 14C-S-dimethenamid in rats

SPECIES/STRAIN: Wistar rats

TEST SUBSTANCE: [14C]-Racemic dimethenamid radiochemical purity 99.69% [14C]-Dimethenamid-P radiochemial purity 99.51% Unlabeled racemic dimethenamid purity 99.0% Unlabeled dimethenamid-P purity 93.0%

GUIDELINES: EEC Directive 87/302, part B; OECD 417

EXPERIMENTAL PROCEDURE:The absorption, distribution and excretion of radioactivity was studied in male Wistar rats following a single dermal administration of [14C]-labelled racemic dimethenamid or dimethenamid-P. Racemic dimethenamid was tested dissolved in the neat solvent of a commercial formulation (Frontier 6.0 herbicide) at nominal dose levels of 0.004, 0.04 and 0.4 mg/cm². The doses were selected on the basis of model calculations giving a range of expected field exposure. Animals were exposed for either 4 or 8 hours after which the patches with test substance were removed and the skin was washed with a mild soap solution. Sacrifice was at 4 hours for the 4 hour exposure and at 8, 24 or 72 hours after the 8 hour exposure.Four animals were used per dose group and sacrifice time. In this balance/excretion study animals were placed in metabolism cages in order to collect excreta up to 72 hours. At the end of the various collection periods animals were sacrificed and the following specimens/tissues were checked for remaining radioactivity:

Excreta (urine and faeces), blood cells, plasma, kidney, liver, carcass, treated skin (application site) and non-treated skin surrounding the application site.

The cage wash, skin wash and the application material (protective cover) were also checked for radioactivity.


To compare dermal penetration rates of racemic and dimethenamid-P, a second experiment was performed using [14C]-labelled dimethenamid-P dissolved in the neat solvent of the formulation BAS 656 07 H. The same nominal dose levels were used of 0.004, 0.04 and 0.4 mg/cm2. The animals were exposed for 8 hours and sacrificed at 72 hours after the end of treatment. This exposure and sacrifice time was chosen as it produced the greatest penetration results in the racemic dimethenamid study.

To assess the effect of the formulation on dermal penetration, a third experiment was performed using [14C]-dimethenamid in the BAS 656 07 H formulation. The exposure time was 8 hours and the sacrifice time was 72 hours. This exposure and sacrifice time was chosen as it gave the highest penetration results in the second experiment using dimethenamid-P and the same solvent.

RESULTS: Recoveries of radioactivities from all dose groups were acceptable. The maximum dermal absorption of [14C]-racemic-dimethenamid was 18 % at 72 hours after

an 8 hour exposure with the lowest dose of 0.004 mg/cm². The maximum dermal absorption of [14C]-dimethenamid-P in the proposed BAS 656 07 H

formulation was 27.32% and occurred the 0.04 mg/cm² dose level. After an 8 h-exposure of [14C]-racemic-dimethenamid in BAS 656 07 H at a dose level of 0.4

mg/cm², 24.7 % was absorbed after 72 hours. This is very similar to the 23% absorption observed with dimethenamid-P at the same exposure and sacrifice times using the same formulation.

CONCLUSION:Following a single dermal administration of [14C]-racemic dimethenamid diluted in a commercial formulation (Frontier 6.0 Herbicide) there was a partial dermal absorption which had a maximum of 18% at 72 hours after an 8 hour exposure period. The penetration was increased slightly to 25% when the proposed formulation BAS 656 07 H was used as a carrier. A similar penetration of 27% was observed with dimethenamid-P in the BAS 656 07 H formulation.Overall, the in vivo dermal penetration of dimethenamid or dimethenamid-P is approximately 26%.

REFERENCE SOURCE:Leibold E. (1999). Preliminary information: 14C-R,S-dimethenamid and 14C-S-dimethenamid-study of the dermal absorption in rats. BASF RegDoc.# 99/10283 (unpublished) BASF Aktiengesellschaft, Ludwigshafen, Germany

GLP: yes

.................................................................................................................................

TYPE OF STUDY: Rates of permeation through human and rat epidermis using an in vitro assay

SPECIES/STRAIN: Wistar rats

TEST SUBSTANCE: [14C]-dimethenamid thiophene label; radiochemical purity: > 98%. Unlabeled dimethenamid purity: 97.6%.

Guidelines: None available

EXPERIMENTAL PROCEDURE:An in vitro study was used to compare the dermal penetration rates of racemic [14C]-dimethenamid through human and rat skin. Post mortem human skin was obtained and dermatomed to a thickness of 300 m. Wistar rats were sacrificed, the abdominal region was clipped free of hair and skin samples excised. The excised rat skin was cut free of fatty tissue and resulting samples were approximately 2000 m thick. The excised human and rat skin epidermis and upper dermis were mounted in Franz-type static dermal penetration cells. Each skin sample was checked for integrity using transepithelial electrical resistance. Three different dose solutions were prepared using the [14C]-dimethenamid, cold dimethenamid and an ethanol water solvent. The dose levels used were 2.55, 10.2 and 40.8 mg/cm2.


The test solutions were applied as a single dermal application at a dose volume of approximately 500 µl/cm2 for 24 hours. Three replicates were used for each dose level and skin type, and each experiment was repeated twice giving a total of nine cells tested per dose group and skin type. Samples of the receptor fluid (ethanol and water) were taken at 0, 2, 4, 6, 8, 20, 22 and 24 hours and analyzed for radioactivity. At the end of exposure the skin samples were removed from the cells and washed with ethanol and water. Both the skin samples and the skin wash were analyzed for radioactivity.

RESULTS:Skin penetration rates of [14C]-dimethenamid through human and rat skin as reported for 24 hr are were as follows:

Rate of penetration (g/cm2/hr)Dose level (mg/cm2) Rat Human2.55 3.3 3.210.2 13.2 11.840.8 30.8 67

The rat skin samples used were 6.67 times thicker than human skin. After adjusting the above results for the differences in skin thickness, the following results were obtained:

Penetration rates of [14C]-dimethenamid through human and rat skin corrected for skin thickness.

Dose Level (mg/cm2) Rate Of Penetration (g/cm2/Hr) Relative PenetrationRat/HumanRat Human

2.55 22 3.2 710.2 88 11.8 740.8 205 67 3

Correcting for the difference in skin thickness, the rate of penetration through human skin is 3 to 7 times less than that through rat skin. However, saturation has occurred at the high dose in the rat skin as the penetration rate no longer continues to increase linearly with dose. Human exposure from the mixing, loading and application of dimethenamid has been predicted with worker exposure modes to be at most 0.4 mg/cm2. Therefore, the comparative values of rat/human skin from the lower doses is considered more appropriate for use in predicting human exposure.

CONCLUSION:Dermal penetration studies in rats demonstrated, that the in vivo dermal penetration of dimethenamid or dimethenamid-P is approximately 26%. Based on the results of in vitro penetration comparisons between human and rat skin, it can be concluded that the rate of dermal penetration (µg/cm2/h) through rat skin is 7-fold higher than through human skin. Overall the human dermal penetration of dimethenamid is predicted to be approximately 4%.

REFERENCE SOURCE:Sommer E., Mueller F. (1993). 14C-dimethenamid technical: Rates of permeation through human and rat epidermis using an in vitro assay. SANDOZ Agro Ltd., Department of Toxicology, Muttenz, Switzerland (unpublished). BASF RegDoc.# 93/11759

GLP: yes

TARGET ORGAN TOXICITY

Subchronic toxicity – oral

TYPE OF STUDY: 13 week dose range finding study in CD-1 mice

SPECIES/STRAIN: CD1 mice

NO.ANIMALS/SEX/GROUP: 12/sex/group


TEST SUBSTANCE: 91.5 +/- 1% SAN 582 H

DOSE LEVELS: 0, 300, 700, 2000, 5000 ppm corresponding to 0, 45.9, 104.6, 301.3 and 805.4 mg/kg/ bw/day in males and 0, 59.5, 137.2, 383.4 and 972.3 mg/kg/ bw/day in females.


GLP: YES

RESULTS: 1. No deaths occurred as a result of compound administration;2. 5000 ppm findings: in males – food consumption was decreased and body weight gains were

decreased by 50% compared with controls. Males and females showed an increase in the absolute and relative liver weights and relative kidney weights. No treatment-related microscopic findings in animals of either sex.

3. 2000 ppm findings: males and females showed increased absolute and relative liver weights. Increased relative kidney weights in both sexes, though not statistically significant. No macroscopic changes were reported;

4. 700 ppm findings: increase in relative liver weights observed in males;5. 300 ppm: no treatment-related findings;6. Authors concluded dose-related response to treatment was demonstrated at 700 and 2000 ppm.

NOAEL: 700 ppm (104.6 mg/kg bw / day males, 137.2 mg/kg bw / day females).LOAEL: 2000 ppm (301.3 mg/kg bw / day males, 383.4 mg/kg bw / day females) based on effects on the liver and kidneys

REFERENCE SOURCE: Warren, S., Karapally, J., Ettlin, R., Carpy, S. and Muller, F. (1988). SAN 582 H: 13-Week Dose-Range Finding Study in C D-1 Mice. Reg. Doc. #BASF 88/11360. Sandoz Ltd, Agro Development. Toxicological Department. Basle, Switzerland.

RELIABILITY (KLIMISCH SCORE): 1.......................................................................................................................

TYPE OF STUDY: 13 week oral toxicity study in dogs

SPECIES/STRAIN: Beagle dog

NO. ANIMALS/SEX/GROUP: 4/sex/group

TEST SUBSTANCE: 91.4% SAN 582 H

DOSE LEVELS: 0, 91.5, 750, 2000 ppm corresponding to 0, 5, 37 and 96 mg/kg/day respectively.


GLP: YES TEST GUIDELINES: US EPA Pesticide Assessment Guidelines Subdivision F, 82-1

RESULTS: 1. No deaths occurred at any of the doses tested.2. Body weight gain was reduced in all animals at 2000 ppm and in females at 750 ppm. One high

dose animal lost 1kg over the dosing period whilst another had marginal losses during the first week of dosing;

3. No haematological changes observed;4. Clinical chemistry: increase in blood cholesterol and alkaline phosphatase levels in the high dose

group;5. Organ changes: absolute and relative liver weights significantly increased in 2000 ppm dose group.

Relative liver weights significantly increased for 750 ppm dose group;


6. Gross pathology: one high dose male had a pale liver with a 10mm diameter irregular area on the parietal surface of the median lobe, loosely adhered to the diaphragm. A high dose female showed prominent liver lobulation;

7. Histopathological changes: Periportal cytoplasmic vacuolation of hepatocytes detected in all high dose animals and 2 intermediate dose animals (one of each sex). The vacuoles were negative for fat and glycogen;

8. Dilatation of liver sinusoids in three males and three females from the high dose group, and in one female from the 750 ppm dose group;

9. Conclusion: hepatotoxicity occurred in all animals at 2000 ppm and in individual animals at 750 ppm.

NOAEL: 91.5 ppm (5 mg/kg bw/day both sexes)LOAEL: 750 ppm (37 mg/kg bw/day both sexes) based on decreased body weight gain, cytoplasmic vacuolation and hepatic sinusoidal dilatation.

REFERENCE SOURCE: Greenough, R.J. and Goburdhun, R. (1986). SAN 582 H: 13-Week Oral Toxicity Study in Dogs. Reg. Doc. #BASF 86/11159. Sandoz Ltd., Agro Development, Toxicological Department, Basle, Switzerland.


Comment:Although the results from this study suggest 6.9B classification for the test material, progression of liver effects was not evident in the 52-week oral toxicity study in the same do species summarised below. Therefore, the substance is not considered to trigger 6.9 classification.

Chronic toxicity/carcinogenicity

TYPE OF STUDY: 52-week oral toxicity study in dogs

SPECIES: beagles

NO. ANIMALS/SEX/GROUP: 4/sex/group


DOSE LEVELS: 0, 50, 250, 1250 ppm equivalent to 0, 1.95, 10.1, 48.7 mg/kg bw / day in males and 0, 2.1, 9.1, and 49.3 mg/kg bw /day in females respectively.

ROUTE: dietary

GLP: Yes

TEST GUIDELINES: US EPA Pesticide Assessment Guidelines Subdivision F, 83-1.

RESULTS:1. No unscheduled deaths were recorded throughout the duration of the study.2. Reduced body weight gain in high dose animals (both sexes) and mid-dose males. One mid dose

male dog showed a body weight loss of 0.4 kg over the dosing period whilst a high dose male lost 0.5 kg during the treatment period.

3. There were treatment-related increase in blood cholesterol and alkaline phosphatase levels for the high dose animals. The effect on cholesterol was present in the males up to midway through the study whilst significant increases in alkaline phosphatase were maintained in females throughout the treatment period.

4. Liver weights were significantly increased for the high dose males and all treated females;5. There were no gross pathological lesions that could be related to treatment with the compound;6. Clinical chemistry changes indicate effects on liver function in the high dose group especially.

Dose related increases in blood cholesterol levels were observed in males during weeks 13


and 26. Changes in the high dose group were statistically significant at week 26. High dose males also showed significant increased in alkaline phosphatase levels at week 26.

Females showed increased blood cholesterol at week 13. AP levels increased in the high dose female group and this effect was statistically significant at all measurement points (weeks 13, 26 and 51).

7. Statistically significant increase in liver weights in high dose males and all treated females – authors concluded that this was spurious for 50 and 250 ppm animals as there were neither histopathological effects in the liver nor changes in blood chemistry;

8. Periportal hepatocytes vacuolation in 2/4 males and 4/4 females in the high dose group. The vacuoles contained neither lipid nor glycogen;

9. Minimal to mild hepatocytes enlargement, mid-zonal region, in 2 males and one female from the high dose group.

NOAEL: 50 ppm (1.95 mg/kg bw/day)LOAEL: 250 ppm (10.1 mg/kg bw/day) based on body weight effects.

REFERENCE SOURCE: Greenough, R.J., Goburdhun, R. And Macnaughtan, F. (1988). SAN 582 H: 52 Week Oral Toxicity Study in Dogs. Reg. Doc. # BASF 88/11361. Sandoz AG. CG-4002 Basle, Switzerland.


CommentsThese findings do not support 6.9 classification of dimethenamid.......................................................................................................................................................

TYPE OF STUDY: Chronic Toxicity / Carcinogenicity

SPECIES/STRAIN: Charles River Crl: CD (SD) BR rats

NO.ANIMALS/SEX/GROUP: 50/sex/group for the main group; 20/sex/group for satellite group


DOSE LEVELS: 0, 100, 700, 1500 ppm corresponding to 0, 5.1, 36 and 80 mg/kg bw / day for males ; 0, 6.8, 49 and 109 mg/kg bw / day for females.

ROUTE: dietary

GLP: yes

TEST GUIDELINES: US EPA FIFRA Guideline No. 83-5, OECD and Japanese MAFF Guidelines.

REMARKS:1500ppm treatment group = males: 80 mg/kg/bw/day; females: 108 mg/kg/bw/day1. 62% of the animals (both sexes) survived to study termination.2. Authors concluded no treatment related clinical signs at this dose;3. Reduced food utilisation efficiency (both sexes) during the first 25 weeks of treatment;4. Decrease in bodyweight gain during weeks 0-10 in both males and females. This trend was

maintained in males and increased in females until the end of the main growth phase (week 80). At Week 80, the decrease in absolute mean body weight compared with controls was 10 and 16% in males and females respectively.

5. Ocular lesions were not observed at 53 weeks but at week 104. Increased incidence of posterior capsular lenticular opacities in males and females were considered to be a treatment related exacerbation of a normal age-related change;

6. Clinical biochemistry: Increased GGT for males throughout the whole study; Increased cholesterol in females ;


Decreased glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase noted for females in weeks 13, 26, 52 and males in week 78.

Decreased calcium in males in weeks 52 and 1047. Urinalysis showed marginal increases in detectable urinary ketone content for males in weeks 26,

52 and 78;8. 104 week group: slight increase in the number of animals showing liver masses, liver cysts and

pale areas of the liver compared with control rats;9. Terminal studies showed 17/50 males and 19/50 females with paleness of the liver compared with

6/50 and 10/50 controls respectively;10. Increased liver weights in female rats in the 52 and 104 week groups;11. Neoplastic pathology:

Increased incidence of liver cell tumours in males; Increased incidence of tubular adenomata of the ovaries, considered by the study authors to be

of “equivocal” toxicological significance;12. Non-neoplastic pathology:

Increased incidence of circumscribed areas of altered eosinophilic hepatocytes in the liver (males);

Increased bile duct hyperplasia noted (females); Increased incidence of cystically dilated bile ducts; Increased incidence and severity of epithelial hyperplasia at the limiting ridge of the stomach

(males) but this was considered by the authors to be of “equivocal” toxicological significance.700ppm treatment group = males: 36 mg/kg bw/day; females: 49 mg/kg bw/day 1. 50% of the males and 60% of the females survived to study termination.2. Females showed lower food utilisation efficiency during the first 25 weeks of treatment;3. Marginal increase in gamma-glutamyl transferase (GGT) activities in weeks 78 and 104, Lower

glutamic-oxaloacetic transaminase(GOT) and glutamic-pyruvic transaminase (GPT) activities were noted for females in weeks 13, 26, and 52 and for males in week 78;

4. Organ weight analysis showed increased liver weights for females at the interim kill;5. Terminal studies showed macroscopic difference in treated males compared with controls with

14/50 showing paleness of the liver compared with 6/50 controls;6. Increased incidence of bile duct hyperplasia in females;7. Increased incidence of ovarian tubular hyperplasia;8. Increased incidence of parathyroid hyperplasia was noted for males but was considered to be of

“equivocal” toxicological significance.100ppm treatment group = males: 5.1 mg/kg bw/day; females: 6.8 mg/kg bw/dayNo treatment related findings

a. Non-neoplastic effects NOAEL: 100 ppm (males: 5.1 mg/kg bw/day; females: 6.8 mg/kg bw/day)LOAEL: 700 ppm (males: 36 mg/kg bw/day; females: 49 mg/kg bw/day) based on bile duct hyperplasia, ovarian tubular hyperplasia, and effects on the enzymes GGT, GOT and GPT.

Comment:These findings suggest a 6.9B classification for racemic dimethenamid. However, the effects only became apparent at the terminal kill and may represent an exacerbation of age-related pathologies. They are therefore not considered to drive 6.9 classification.

b. Neoplastic effects Analysis of tubular adenomas – females

Dose Group Control 100 ppm 700 ppm 1500 ppmOriginal diagnosisGranulosa cell tumour 1 1Tubular adenoma 2 1 2 6Tubular hyperplasia 12 7 14 22Review with external pathologistGranulosa cell tumour 1Sertoli tubular adenoma 3 3 4 5Sertoliform tubular hyperplasia 18 12 12 23Sertoliform tubular hyperplasia + adenoma 21 12 14 24


CommentFollowing the initial diagnosis of tubular adenoma by the study pathologist, an external consultant was brought in to offer his own assessment. The results of both the initial and the subsequent reassessment are detailed in the table above. The tubular adenoma was redefined as Sertoli tubular adenoma. Although there was no statistically significant increase in adenomas, there appeared to be a trend of increasing occurrence in higher dose groups. Nevertheless, The combined incidence of sertoliform tubular hyperplasia and adenoma does not show a similar trend. The reviewers further argue that the ovarian adenomas are:

unique to Sprague-Dawleys; rarely found in other rat species; not found in man or domestic animals; do not metastise and their potential for malignancy is doubtful

The reviewers conclude that these lesions have no toxicological significance and have limited relevance to man. The Agency concurs with the conclusions reached by the reviewers. The findings do not support classification of the test substance as a carcinogen or potential carcinogen.

Analysis of Liver Tumours – malesDose Group Control 100 ppm 700 ppm 1500 ppmBenign liver cell tumour 0 1 0 3Malignant liver cell tumour 0 0 0 2

All the above tumours were noted in sacrificed animals, not those dying before end of study. Given that high dose animals showed superior survival (62%) compared with control males ((36%), low dose males (40%) and mid dose males (50%). This superior survival may also result in exaggeration of the difference in tumour incidence between control and high dose animals.

TUMOURS BACKGROUND INCIDENCE: Male Liver Cell Tumour Data: HRC Historical Control – Benign = 0-1.8%, Malignant = 0-

3.6%; Charles River Historical Control (updated 1991, unpublished) – Benign = 0-15.4%; Malignant = 0-7.7%.

Female Tubular Adenoma Data: HRC Historical Control – 0-5.5%; Charles River Historical Control (updated 1991, unpublished) –0-1%.

SURVIVAL: Males: Controls – 36 %; 100 ppm – 40%; 700 ppm – 50%; 1500 ppm – 62%; Females: Controls – 50%; 100 ppm – 44%; 700 ppm – 60%; 1500 ppm – 62%.

NOAEL: 1500 ppm (80 mg/kg bw / day for males and 109 mg/kg bw / day for females)LOAEL: >1500 ppm

REFERENCE SOURCE: Ruckman, S.A., Waterson, L.A., Crook, D., Buist, D., Gopinath, C., Read, R., Gibson, W.A., Anderson, A., Dawe, I.S. and Chanter, D.O. (1990). Potential tumorigenic and toxic effects in prolonged dietary administration to rats. Reg. Doc. #BASF 90/11138. Sandoz Ltd., Agrochemical Toxicology Dept., CH-4002 Basle, Switzerland.


Comments:The Agency notes that although there was an increased incidence of liver tumours amongst rats receiving the 1500 ppm dose, the Authors argued that this was well within the range observed among historical control data. They attributed the increased incidence of malignant liver cell tumours to the incidence of benign liver cell tumours. They further argued that although there were a greater number of ovarian tubular adenomas amongst female rats receiving 1500 ppm, there was no statistically significant effect on pair-wise comparison and on Fisher’s exact method, and so this result is considered to be of equivocal toxicological significance. The explanation given by the Authors is plausible given that the rodent species used here shows a high background tumour incidence. The view that these tumours are not treatment-related is further corroborated by findings from the carcinogenicity study in mice detailed below.


.................................................................................................................................

TYPE OF STUDY: Carcinogenicity

SPECIES/STRAIN: Charles River (UK) Crl: CD-1 (ICR) BR mice

NO.ANIMALS/SEX/GROUP: 52/sex/group for the main group; 16/sex/group for satellite group


DOSE LEVELS: 0, 30, 300, 1500, 3000 ppm corresponding to 3.8, 40.8, 205 and 431 mg/kg/bw/day for males; 4.1, 40.1, 200, 411 mg/kg/bw/day for females

ROUTE: dietary

GLP: yes

TEST GUIDELINES: US EPA FIFRA Guideline No. 83-5, OECD and Japanese MAFF Guidelines.

REMARKS:3000 ppm treatment group (males: 431 mg/kg/bw/day; females: 411 mg/kg/bw/day)1. No apparent treatment-related clinical signs;2. Survival considered unaffected by treatment;3. Lower body weight gain during the first 52 weeks, food consumption unaffected but impaired food

utilisation efficiency apparent in males over weeks 1 to 13;4. Higher liver weights at the interim kill (Week 66) in both sexes and in females at terminal kill

(Week 95). Higher kidney weights in the females at terminal kill but not associated with any specific pathological changes;

5. Neoplastic pathology – no evidence of tumorigenic potential;6. Non-neoplastic pathology:

Interim kill – higher incidence of centrilobular hepatocytes enlargement, both sexes; Minimally increased incidence of hyperkeratosis of the limiting ridge of the stomach, both

sexes.1500 ppm treatment group (males: 205 mg/kg/bw/day; females: 200 mg/kg/bw/day)1. No treatment related clinical signs at this dose;2. Survival considered unaffected by treatment;3. Lower body weight gain was apparent during the first 52 weeks of treatment, food consumption

was unaffected;4. Higher liver and kidney weights in females at the terminal kill. Specific pathological changes only

noted in the liver;5. Neoplastic pathology – no evidence of tumorigenic potential;6. Non-neoplastic pathology:

No treatment related changes at interim kill; Higher incidence of enlarged hepatocytes at terminal kill and for dying animals.

300 ppm treatment group (males: 40.8 mg/kg bw/day; females: 40.1 mg/kg bw/day) 1. No treatment related clinical signs;2. Survival, food consumption, body weight gain, organ weights unaffected;3. Neoplastic pathology - no evidence of tumorigenic potential observed;4. Non-neoplastic pathology – higher incidence of enlarged hepatocytes in the liver for those main

group animals dying or killed;30 ppm treatment group (males: 3.8 mg/kg bw/day; females: 4.1 mg/kg bw/day)No treatment related findings observed.

a. Non-neoplastic effects NOAEL: 300 ppm (males: 40.8 mg/kg bw/day; females: 40.1 mg/kg bw/day)LOAEL: 1500 ppm (males: 205 mg/kg/bw/day; females: 200 mg/kg/bw/day) based on effects on liver, kidney and body weight gain.


b. Neoplastic effects No evidence of tumorigenic potential.

SURVIVAL: Males: Controls – 33%; 30 ppm – 48%; 300 ppm – 48%; 1500 ppm – 37%; 3000 ppm – 46%; Females: Controls – 63%; 30 ppm – 79%; 300 ppm – 79%; 1500 ppm – 65%; 3000 ppm –

73%.

REFERENCE SOURCE: Hooks, W., Chambers, P.R., Majeed, S.K., Gibson, W.A., Gopinath, C. and Dawe, I.S. (1990). SAN 582 H: Potential tumorigenic and toxic effects in prolonged dietary administration to mice. Reg. Doc. #BASF 90/11139. Sandoz Ltd., Agrochemical Toxicology Dept., CH-4002 Basle, Switzerland.


ERMA New Zealand CommentsERMA concurs with the conclusions drawn by the authors regarding the tumorigenic potential of the test compound.Conclusion on classification: The test substance does not trigger 6.7 classification as a carcinogen.REPRODUCTIVE/DEVELOPMENTAL TOXICITYDevelopmental studies

STUDY TYPE: Developmental toxicity (embryo/foetal toxicity and teratogenic potential).

SPECIES/STRAIN: New Zealand White Rabbit

DOSE: 0, 37.5, 75 and 150 mg/kg/day

ROUTE: Oral (stomach tube)

GUIDELINE:U.S. EPA Pesticide Assessment Guidelines Subdivision F, 83-3.

TEST SUBSTANCE: SAN 582 H, 92.0% purity.

RESULTS: Pilot Study:Doses of 0, 37.5, 75, 150, 300 and 425 mg/kg/day administered orally (stomach tube) to four presumed pregnant rabbits per group on days 6 to 18 of gestation. Deaths occurred in the 300 and 425 mg/kg/day dosage groups. Reduced body weight gain and food consumption occurred in animals given 150 mg/kg/day. Developmental StudyBased on the results of the pilot study, dose levels of 0, 62.5, 75, 125 and 250 mg/kg/day administered to 20 rabbits per group on days 6 to 18 of presumed gestation for the Developmental Study. There were 13 deaths and seven abortions in the high dosage group and so the study was terminated prior to scheduled Caesarean-sectioning on day 29 of gestation. Only one pregnant high dose doe survived to day 25 of gestation. Maternal body weight gain and feed consumption were reduced at 125 and 250 mg/kg/day.Second Developmental Study – Maternal Effects1. Dosages of 0, 37.5, 75 and 150 mg/kg/day used at a volume of 10 mL/kg on days 6 through 18 of

presumed gestation;2. No deaths occurred during the study;3. Two does from the 150 mg/kg/day group prematurely delivered/aborted and this was considered to

be treatment-related. Authors considered this to be evidence of maternal and developmental toxicity;

4. Animals from the 150 mg/kg/day and 75 mg/kg/day groups infrequently had dried faeces or no faeces at all as well as decreased food consumption. There was increased incidence of localised


alopecia in the 150 mg/kg/day animals compared with controls. However, there was no statistically significant difference from the control animals;

5. Inhibited maternal body weight gain during the dosage period in the 150 mg/kg/day and 75 mg/kg/day groups. This was statistically significant for the high dose group during days 12 to 15 of gestation. This group experienced remarkable weight loss during days 15 to 19;

6. Reduced absolute food consumption for the high and middle dose group animals, statistically significant for the high dose animals;

7. There were 18, 16, 16 and 17 pregnant does in the control, low, middle and high dose groups respectively. Since two high dose does aborted/prematurely delivered, there were 18, 16, 16 and 15 litters available for evaluation in the control, low, middle and high dose animals at Caesarean;

8. There were 129, 109, 120 and 110 live foetuses in the control, low, middle and high doses respectively;

9. There was one dead foetus in a control litter and two low dose animals with 100% resorption;10. There were no test substance-related effects on implantation, live litter size, foetal sex ratio or

foetal body weight.Second Developmental Study – Foetal Effects1. No external, soft tissue or skeletal foetal alterations considered to be related to treatment with the

test compound;2. Alterations noted in high dose specimens did not occur in more than one foetus;3. Litter incidences for all alterations (malformations and variations) were not significantly increased

compared with control values;4. No ossification delays were noted.

MATERNAL TOXICITY NOAEL: 37.5 mg/kg bwLOAEL: 75 mg/kg bw based on effects on food consumption and body weight gain as well as faecal abnormalities.

DEVELOPMENTAL TOXICITY NOAEL: 75 mg/kg bwLOAEL: 150 mg/kg bw based on premature delivery / abortions.

REFERENCE SOURCE: Hoberman, A.M. (1988). Developmental Toxicity (Embryo/Fetal Toxicity And Teratogenic Potential) Study of SAN 582 H Administered Orally (Stomach Tube) to New Zealand White Rabbits. Reg. Doc. #BASF 88/11376. Argus Research Laboratories, Inc., 935 Horsham Road, Horsham, PA 19044.


CommentsThe abortions seen in 2/20 high dose animals are likely due to the remarkable weight loss seen in the dams during days 15 to 19 and significantly reduced food consumption. One of these animals consumed less than 20 g of feed per day on days 8 to 11 and less than 2 g per day from day 12 through day 28 when it aborted. The other animal consumed less than 2 g per day from day 13 through 26. These two animals showed the lowest food consumption compared to the rest of the group. Furthermore, there were no other significant observations noted in the surviving high dose foetuses. Therefore, the Agency considers that the findings of this study do not justify classification of the test compound as a developmental toxicant.

Reproductive studies

STUDY TYPE: Two-Generation Reproductive Toxicity Study

SPECIES/STRAIN: Wistar/HAN Rat.

DOSES: 0, 100, 500, and 2000 ppm corresponding to 10, 50 and 150 mg/kg bw / day.

ROUTE: Via the diet.


TEST SUBSTANCE: SAN 582 H, 92.6% purity.

GUIDELINES: Reproductive and Fertility Effects, Pesticide Assessment Guidelines, Subdivision F, Hazard

Evaluation: Human and Domestic Animals, No. 83-4, U.S. Environmental Protection Agency; Two –Generation Reproduction Toxicity Study, OECD Guidelines for the Testing of

Chemicals, Section 4, Health Effects, No. 416.

RESULTS: The following effect were considered treatment-related:1. There were no deaths in any of the parent animals;2. Reduced food consumption at 2000 ppm in males of the P generation during pre-pairing and post-

pairing, and in the males of the F1 generation during the pre-pairing period;3. Reduced mean body weights in the males of the P and F1 generations at 2000 ppm;4. Reduced food consumption at 2000 ppm in P generation females during pre-pairing and lactation;5. Reduced mean body weight and body weight gain in both the F1 and F2 pups during the lactation

period at 2000 ppm;6. Statistically significant increase in the absolute and relative liver weight of the P and F1 parent

animals both sexes) at 2000 ppm; 7. Marginally increased relative liver weight, both sexes of both generations at 500 ppm, statistically

significant for females of the P generation;8. No treatment related effects seen at 100 ppm in any of the animals;

The following were considered to be unaffected by treatment with the test substance:1. Viability of the parent animals at all doses tested;2. Food consumption of the parent animals in both the P and F1 generations at 100 and 500 ppm and

of the females of the F1 generation at 2000ppm;3. Body weight gain of the P and F1 parent animals at 100 and 500 ppm and of the females at 2000

ppm;4. Percentage of animals mating, fertility index, conception rate, gestation index, mean pre-coital

time, duration of gestation, mean number of implantation sites per dam, post-implantation loss, mean number of pups per dam, postnatal and breeding loss in the dose groups up to and including 2000 ppm;

5. Appearance of the pups at external examination and sex ratios of the F1 and F2 pups at all doses tested;

6. Mean body weight and body weight gain of the F1 and F2 pups at 100 and 500 ppm;7. Liver weight of the parent animals at 100ppm;

REPRODUCTIVE TOXICITY STUDIES

PARENTAL TOXICITY NOAEL: 500 ppm (50 mg/kg bw)LOAEL: 2000ppm (150 mg/kg bw) based on effects on body and liver weight.

REPRODUCTIVE EFFECTS NOAEL: 2000 ppm (200 mg/kg bw / day).LOAEL: None since the highest dose tested was the NOAEL.

DEVELOPMENTAL TOXICITY NOAEL: 2000 ppmLOAEL: None since the highest dose tested was the NOAEL.

REFERENCE SOURCE: Suter, P, Biedermann, K., Wilson, J.Th., Terrier, Ch. (1989). SAN 582 H: Two-Generation Reproduction Study in the Rat. Part I. Reg. Doc. #BASF 90/11140. Research and Consulting Company AG., P.O. Box CH 4452 Itingen, Switzerland.


Comments


The findings from this study do not support classification of the test compound as a reproductive / developmental toxicant.

Conclusion on classification: The test substance does not trigger 6.8A/B/C classification.

Table A2.8: Toxicity of BAS 656 08 H (current formulation of Frontier®-P) and BAS 656 07 H (previous formulation).BAS 656 08 H (current formulation) BAS 656 07 H (previous formulation)Acute oral toxicity Acute oral toxicity

SPECIES: Rat

STRAIN: Wistar Albino

NUMBER/GROUP: 3 females

TEST SUBSTANCE: BAS 656 08 H

CONTENT OF ACTIVE INGREDIENT: 70.5% (w/v)

DOSE LEVELS: Two groups of 500 mg/kg bw and one of 2,000 mg/kg bw

ADMINISTRATION ROUTE: oral gavage.

ENDPOINT: LD50

VALUE: >500 mg/kg/bw but < 2,000 mg/kg bw (females).

RESULTS: All animals in the 2,000 mg/kg bw group died within day 1 of administration, no deaths in the other groups. Main clinical observations in the 2,000 mg/kg bw group included dyspnoea, staggering, tremor, twitching, piloerection and salivation. Symptoms in the 500 mg/kg groups included impaired general state, dyspnoea, staggering, piloerection, salivation and lacrimation. Mean body weights in the 500 mg/kg bw groups increased throughout the duration of the study. No significant necropsy findings were observed in any of the groups.

GLP: Yes.

TEST GUIDELINES: OECD Guideline for the Testing of

Chemicals No. 423, December 17, 2001 (“Acute Oral Toxicity – Acute Toxic Class Method”);

EC Directive 2004/73, No. L216, B.1 tris. June 16, 2004 (“Acute Oral Toxicity – Acute Toxic Class Method”);

US EPA Health Effects Test Guidelines OPPTS 870.1100, December 2002 (“Acute Oral Toxicity”).

SPECIES: Rat


NUMBER/GROUP/SEX: 5

TEST SUBSTANCE: BAS 656 07 H (previous formulation of Frontier®-P).

CONTENT OF ACTIVE INGREDIENT: 64.0 % (w/w)

DOSE LEVELS: 1000 mg/kg bw, 1414 mg/kg bw, 2000 mg/kg bw

ADMINISTRATION ROUTE: oral gavage.

ENDPOINT: LD50

VALUE: 1473 mg/kg/bw (males); 1686 mg/kg bw (females); 1581 mg/kg bw (combined).

RESULTS:Preliminary assay:Dose levels of 1200, 2000 and 5000 mg/kg were administered. Main clinical signs observed were hypoactivity, piloerection and dyspnoea. Mortality occurred in the female given 1200 mg/kg (day three) and in the male and female given 5000 mg/kg (day 2 and 1 respectively).

Main test:1. At 2000 mg/kg dose level, the main findings

were : Hypoactivity, piloerection and dyspnoea

in all animals on day 1; Lateral recumbency in one animal on

day 1; Mortality occurred in 2/5 males and 4/5

females on day 1. Two other males were found dead on day 2;

Hypoactivity continued in surviving animals through day 2, complete recovery by day 3.

2. At 1414 mg/kg the main findings were: Hypoactivity and piloerection in all


REFERENCE SOURCE: Gamer, A.O. and Landsiedel, R. (2006). BAS 656 08 H Acute Oral Toxicity Study in Rats. BASF DocID 2006/1026825. Experimental Toxicology and Ecology, BASF Aktiengesellschaft, 67056 Ludwigshafen, Germany.


animals on day 1; Death of 1/5 males on day 1 and one

male and one female on day 2; Hypoactivity and piloerection persisted

in surviving animals up to day 4, complete recovery by day 5.

3. At 1000 mg/kg, no clinical signs were observed. One male was found dead on day 2.

Summary of mortality (given as number of animals that died/total number of animals in the group):

1000 mg/kg: Males – 1/5; Females – 0/5; 1414 mg/kg: Males – 2/5; Females – 1/5; 2000 mg/kg: Males – 4/5; Females – 4/5

GLP: Yes.

TEST GUIDELINES: OECD Guideline for the Testing of

Chemicals No. 401, 24 February 1987; EC Directive No. 92/69/EEC, B.1, 31 July

1992;; US EPA FIFRA Guidelines: Subdivision F

Series 81, November 1984.

REFERENCE SOURCE: Manciaux, X. (1998). BAS 656 07 H: Acute Oral Toxicity in Rats. Reg. Doc. #BASF 98/10858. Centre International de Toxicologie, Miserey – 27005 Evreux, France.


Conclusion on ClassificationThe test substance triggers classification as a 6.1D oral toxicant.

Conclusion on ClassificationThe test substance triggers classification as a 6.1D oral toxicant.

Acute dermal toxicity (current formulation) Acute inhalation toxicity (previous formulation)

SPECIES: Rat




ADMINISTRATION ROUTE: Percutaneous

ENDPOINT: LD50

VALUE: >5000 mg/kg bw (both sexes).

RESULTS:No mortalities or clinical signs of toxicity were observed in this study. Very slight erythema (days 1-2) and scaling (days 5-6) at the application site were noted in one male animal. Males gained weight during the 14-day study

SPECIES: Rat


ANIMALS/SEX/GROUP: 5


CONTENT OF ACTIVE INGREDIENT: 64% (w/v)

ADMINISTRATION ROUTE: Inhalation (liquid aerosol of substance, head and nose exposure).

ENDPOINT: LC50

VALUE: > 5.6 mg/l (4 h) (both sexes).

RESULTS:No mortality occurred during the exposure or the 14-day post-exposure observation period. The


period, but females only gained weight during the second week of the observation period. No gross pathological changes were observed at necropsy.

TEST METHOD:1. OECD Guideline 402 (24 Feb 1987); 2. EPA OPPTS 870.1200 (Aug 1998)

GLP: Yes.

Gamer, A.O. and Landsiedel, R. (2006). BAS 656 08 H Acute dermal toxicity study in rats. BASF Aktiengesellschaft unpublished Report No. 2006/1026826. Experimental Toxicology and Ecology, BASF Aktiengesellschaft, 67056 Ludwigshafen, Germany


following symptoms were observed during or after exposure: attempts to escape, irregular and accelerated respiration, respiratory sounds, squatting posture, smeared fur and piloerection. No clinical signs were observed on day 7 and thereafter. Body weight gain was depressed during the first week, but recovered in the second week. Necropsy revealed gray-red discoloration of the lungs in all animals. Histopathological examination was performed on the lungs of two animals, which revealed acute congestion, slight alveolar edema, slight diffuse alveolar histiocytosis and slight multifocal perivascular infiltration of eosinophils (one animal only).

TEST GUIDELINES:1. OECD 403, 2. EEC Annex V, B2

GLP: yes

Gamer A.O., et al (1998). BAS 656 07 H - Acute inhalation toxicity study in Wistar rats. BASF Aktiengesellschaft, Ludwigshafen, Germany. Unpublished BASF RegDoc.#98/10838.


Conclusion on ClassificationThe test substance does not trigger classification as an acute dermal toxicant.

Conclusion on ClassificationThe test substance does not trigger classification as an acute inhalation toxicant.

Dermal Irritation/Corrosion (current formulation)

Eye Irritation/Corrosion (current formulation)

SPECIES: Rabbit




ADMINISTRATION ROUTE: 2.5x2.5 patch under semi-occlusive conditions.

RESULTS:Slight or moderate erythema, partly extending beyond the area of exposure, slight oedema and scaling were observed in the animals during the course of the study. The cutaneous reactions were reversible in one animal within 7 days after removal of the patch. In two animals moderate erythema and scaling were still observed at study termination on day 14. The average score (24 to 72 hours) for irritation was calculated to be 1.8 for erythema and 0.1 for oedema.

SPECIES: Rabbit




ADMINISTRATION DOSE: 0.1 mL into conjunctival sac.

RESULTS: The average score (24 to 72 hours) for irritation was calculated to be 0.6 for corneal opacity, 0.3 for iris, 2.9 for conjunctival redness and 1.7 for chemosis. The findings were reversible in 2 of 3 animals within 14 days, and within 21 days for the third animal. One animal exhibited loss of corneal tissue, while the third animal exhibited discharge of blood and suppuration

TEST METHOD:1. OECD Guideline 405 (24 Feb 1987);


TEST METHOD:1. OECD Guideline 404 2. EPA OPPTS 870.2500 (Aug 1998);

GLP: Yes.

Remmele, M.. and Landsiedel, R. (2006). BAS 656 08 H Acute dermal irritation / corrosion in rabbits. BASF Aktiengesellschaft unpublished Report No. 2006/1026827. Experimental Toxicology and Ecology, BASF Aktiengesellschaft, 67056 Ludwigshafen, Germany.


2. EPA OPPTS 870.2400 (Aug 1998).

GLP: Yes

Wiemann, C. & Hellwig, J. (2000). BAS 656 08 H Acute eye irritation in rabbits. BASF Aktiengesellschaft unpublished Report No. 2000/1012350. Experimental Toxicology and Ecology, BASF Aktiengesellschaft, 67056 Ludwigshafen, Germany.


Conclusion on ClassificationThe test substance triggers 6.3B (skin irritation) classification

Conclusion on ClassificationThe test substance triggers 6.4A (eye irritant) classification.

Contact Sensitisation (current formulation) Respiratory sensitization



SPECIES: Guinea pig

STRAIN: HsdPoc: DH

NUMBER/SEX/GROUP:

METHOD: Buehler method (9-Induction)

APPLICATION: Closed patch technique using undiluted test substance.

RESULTS: The first until third induction did not cause any skin irritation in the test group animals. Discrete or patchy to intense erythema and swelling, scaling and eczematoid skin change were noticed in the animals of the test group after the remaining induction treatments. Due to cumulative skin irritation, the test patch was moved to the middle of the flank in some animals for the eighth and ninth induction. The challenge caused discrete or patchy or moderate and confluent erythema in test group animals. Positive challenges were noted in 11/20 test group animals at 24 hours, and 4/20 at 48 hours, while negative controls gave no responses throughout.

GLP: Yes

TEST GUIDELINES:1. OECD Guideline 406 (17 Jul 1992); 2. EPA OPPTS 870.2600 (Mar 2003).

No tests undertaken.


REFERENCE SOURCE:Gamer, A.O. and Landsiedel, R. (2006). BAS 656 08 H Modified BUEHLER Test (9 inductions) in guinea pigs. BASF Aktiengesellschaft unpublished Report No. 2006/1026828. Experimental Toxicology and Ecology, BASF Aktiengesellschaft, 67056 Ludwigshafen, Germany.


Conclusion on Classification: The substance triggers 6.5B classification (contact sensitizer).

Table A2.9 Summary of toxicity studies considered in determining the Acceptable Operator Exposure Level (AOEL) and Acceptable Daily Exposure (ADE) for dimethenamid-P Study NOAEL LOAEL Critical effectDevelopmental toxicity study in Sprague-Dawley rats with S-Dimethenamid

25 mg/kg bw / day (maternal)

150 mg/kg bw / day (maternal)

Reduced food consumption and body weight gain

Subchronic (3-month) toxicity study in Sprague-Dawley rats with S-dimethenamid

37 mg/kg bw/day males; 40 mg/kg bw / day females

110 mg/kg bw/day males; 125 mg/kg bw / day females

Increase in GGT, decreases in AST, ALT, ALP, lower terminal weight and hepatocellular hypertrophy and eosinophilic inclusions

13 week dose range finding study in CD-1 mice with r/s-dimethenamid

104.6 mg/kg bw / day males, 137.2 mg/kg bw / day females

301.3 mg/kg bw / day males, 383.4 mg/kg bw / day females

Increase in relative liver and kidney weights in both sexes.

13 week oral toxicity study in beagle dogs with r/s-dimethenamid

5 mg/kg bw/day, average for both sexes.

37 mg/kg bw / day average for both sexes.

Decreased body weight gain, cytoplasmic vacuolation and hepatic sinusoidal dilatation.

52-week oral toxicity study in beagle dogs with r/s-dimethenamid

1.95 mg/kg bw/day

10.1 mg/kg bw/day

Reduction in mean body weight gain in males and increased liver weights in females.

Chronic Toxicity / Carcinogenicity (104 weeks) in Sprague-Dawley rats with r/s-dimethenamid

Males: 5.1mg/kg bw/day; Females: 6.8 mg/kg bw/day

Males: 36 mg/kg bw/day; Females: 49 mg/kg bw/day

Bile duct hyperplasia, ovarian tubular hyperplasia, increased GGT activity; decreased activity of GOT, GPT.

Carcinogenicity (104 weeks) in CD-1 mice with r/s-dimethenamid

Males: 40.8 mg/kg bw/day; Females: 40.1 mg/kg bw/day

Males: 205 mg/kg/bw/day; Females: 200 mg/kg/bw/day

Increased liver and kidney weights in females, reduced body weight gain, both sexes.

Developmental toxicity study in rabbits with r/s-dimethenamid

37.5 mg/kg bw (maternal toxicity)

75 mg/kg bw (maternal toxicity)

Based on effects on food consumption and body weight gain as well as faecal abnormalities.

Reproductive toxicity study in Wistar/HAN Rats with r/s-dimethenamid

200 mg/kg bw / day (parental toxicity)

50 mg/kg bw (parental toxicity)

Based on increased liver weight.

Acceptable Operator Exposure Level (AOEL)


NOAEL = 1.95 mg/kg bw/day (from the 52 week oral toxicity study in dogs above); Uncertainty factor = 100 (accounts for intra- and interspecies variation); Oral absorption factor of 90% (see ADME summary in Table A2.7).

AOEL = 1.95 mg/kg bw/day x 90% = 0.018 mg/kg bw/day. 100

Acceptable Daily Exposure (ADE) NOAEL = 1.95 mg/kg bw/day (from the 52 week oral toxicity study in dogs above); Uncertainty factor = 100 (accounts for intra- and interspecies variation); Oral absorption factor of 90% (see ADME summary in Table A2.7).

ADE = 1.95 mg/kg bw/day x 90% = 0.018 mg/kg bw/day. 100

Class 9 Ecotoxicity and Environmental Fate

Sub-class 9.1 Aquatic ecotoxicity, fate and degradationClassification 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 dimethenamid-P and its metabolitesInformation on aquatic fate and degradation is summarised in Tables A2.10 and A2.10B.

Table A2.10: Summary of aquatic fate and degradation of dimethenamid-P (SAN 1289H) and the metabolites N-(2,4-dimethyl-thiopen-3-yl)-N-(2-methoxy-1-methyl-ethyl)-acetamide (M3), dimethenamid oxaloamide (M23) and dimethenamid sulfonate (M27).

Study type Test results Test method [reference number]SAN 1289 H Metabolites

Abiotic degradationHydrolysis (25°C)

pH 5: StablepH 7: StablepH 9: Stable

Guirguis, 1997Report No.97/5184USEPASubdivision NSection 161-1GLPKlimisch score: 1SAN 1289 H

Photolysis DT50: 13.7 ± 1.9 days(pH 7, 25°C at 100 ppm)

DT50: 25.7 days (noon sunlight at 40°N latitude)

Guirguis, 1997Report No.97/5195USEPASubdivision NSection 161-2GLPKlimisch score: 1SAN 1289 H

Biodegradation (laboratory)See Table A2.10B (SAN 582 H)

Bioaccumulation



See Table A2.10B (SAN 582 H)

Octanol/water partition coefficient

No data for SAN 1289 H Metabolite M3Log Kow: 2.58

M3 has no dissociation constant, therefore the log Kow is not dependent on pH

Daum, 1999OECD 117Report No. 99/10261GLPKlimisch score: 1


No data for SAN 1289 H Metabolite M23Log Kow: 2.26 (pH 2.1)

Log Kow: -2.16 (pH 7)



Metabolite M27Log Kow: -2.63(deionised water, pH 5.8)

Log Kow: -1.57 (pH 7)


Table A2.10B: Summary of aquatic fate and degradation of dimethenamid (SAN 582 H).


Abiotic degradationHydrolysis (25°C)

pH 5: StablepH 7: StablepH 9: Stable

Fostiak & Hsieh, 1988Report No.88/11332USEPASubdivision NSection 161-1GLPKlimisch score: 1SAN 582H

Photolysis DT50: 16.4 ± 1.1 days(pH 7, 25°C at 100 ppm)

DT50: 23.9 days (noon sunlight at 40°N latitude)

Sabat & Yu, 1992Report No.92/12388USEPAInternal protocolGLPKlimisch score: 1SAN 582 H

Photolysis Top layer of Aqueous systems

ConditionsLocation:Central EuropeThickness of aqueous layer:1 cmSubstance concentration:1 μg/mL

DT50: 0.3 d (April)DT50: 0.2 d (May)

Scharf, 1999Report No.99/10073Calculation based on Frank& Klopffer, 1985SAN 582 H

Photochemical oxidative

DT50: 2.45 h (12 h day) Scharf, 1999Report No.



degradation(Troposphere)

99/10075QSAR estimateAOPWIN ProgramSAN 582 H

Biodegradation (laboratory)Water/sediment system

Application rate: 0.4834 mg ai/L(Field rate: 1.44 kg ai/ha)

River systempH 7.46, TOC 0.9 (before test)loamy sandDT50 (water): 20.3 daysDT50 (total): 23.4 days

DT90 (water): 67.4 daysDT90 (total): 77.8 days

Pond systempH 7.6, TOC 2.6(before test)sandy loamDT50 (water): 27.7 daysDT50 (total): 33.4 days

DT90 (water): 92.1 daysDT90 (total): 110.9 days

Wyss-Benz&Völkel 1994Report No. 94/10641BBA Part IV: 5-1GLPKlimisch score:1SAN 582 H

Activated SludgeRespiration inhibition Test

< 25% deviation from control at 100 mg/L

Not toxic to wastewater bacteria at a concentration of < 100 mg/L

Desmares-Koopmans, 1996OECD209Report No.95/11327GLPKlimisch score: 1SAN 582 H

BioaccumulationBluegillLepomis macrochirus

BCF = 58

Steady state = 21 days(whole body and inedible tissues)

Steady state = > 28 days(edible tissues)

Elimination DT50: 10.7 days

Sabourin, 1988USEPA Guidelines 1982Report No. 88/11365GLPKlimisch score: 1SAN 582 H

ConclusionDimethenamid-P is not considered bioaccumulative based on the results of the study of dimethenamid in fish (BCF=58) and is considered not readily degradable (DT50 > 16 days). As the value used to determine ready degradability is in this instance for the


loss of parent compound only, the value for ultimate degradation of the substance will be a much longer.


Aquatic toxicityThe toxicity of dimethenamid-P, dimethenamid and Frontier-P® to aquatic organisms is summarized in Tables A2.11, A2.11A, A2.11B and A2.11C.

Table A2.11: Summary of aquatic toxicity data for dimethenamid-P (SAN 1289 H) and the metabolites M3, M23 and M27.

Test speciesTest type & duration

Test results a, b

Test method c

[reference number]SAN 1289 H MetabolitesFishRainbow trout,Oncorhynchus mykiss

96 h Flow-through

LC50:6.3 mg/L95% CI:3.7 – 11 mg/L

[measured] > 80% < 120% of [nominal]

Graves & Swigert, 1996FIFRA 72-1Report No. 96/5417GLPKlimisch score: 1SAN 1289 H

BluegillLepomis macrochirus

96 h Flow-through

LC50:10 mg/L95% CI:7.5 - 12 mg/L


Graves & Swigert, 1996FIFRA 72-1Report No. 96/5414GLPKlimisch score: 1SAN 1289 H

Rainbow trout,Oncorhynchus mykiss

96 h Static Metabolite M3LC50:60.8 mg/L95% CI:49.2 – 75.1 mg/L


Grützner, 1997FIFRA 72-1OECD 203Report No. 97/10271GLPKlimisch score: 1


96 h Static Metabolite M23Limit TestLC50: > 87 mg/L[measured]

Van der Kolk, 1995FIFRA 72-1OECD 203Report No. 95/11318GLPKlimisch score: 1


96 h Static Metabolite M27Limit TestLC50: > 100 mg/L[measured]


InvertebratesDaphnia magna 48 h

Flow-through

EC50:12 mg/L95% CI:10 – 13 mg/L


Graves and Swigert, 1996FIFRA E 72-2Report No. 96/5415GLPKlimisch score: 1SAN 1289 H

Daphnia magna 48 h Static Metabolite M3EC50:

Grützner, 1997OECD 202



Test results a, bTest method c

[reference number]SAN 1289 H Metabolites > 101.6 mg/L


FIFRA E 72-2Report No. 97/10272GLPKlimisch score:1

Daphnia magna 48 h Static Metabolite M23Limit testEC50: > 95 mg/L[measured]

*pH of the test lower than the control range:Test: 6.49- 7.41Control: 7.66 – 7.71

Van der Kolk, 1995FIFRA 72-1OECD 203Report No. 95/11319GLPKlimisch score: 1*

Daphnia magna 48 h Static Metabolite M27Limit testEC50: > 100 mg/L[measured]


Algae/Aquatic plants Green algaSelenastrum capricornutum

120 h Static EC50 (density):0.017 mg/L95% CI:0.0041 – 0.030 mg/L

[measured] > 72 and < 88% [nominal]

* control pH range > 1.5.

Hoberg, 1997FIFRA guidelines122-2, 123-2Report No. 97/5170GLPKlimisch score: 1*SAN 1289 H

Blue-green algaAnabaena flos-aquae



Hoberg, 1997FIFRA guidelines122-2, 123-2Report No. 97/5173GLPKlimisch score: 1SAN 1289 H

Freshwater diatomNavicula pelliculosa




Green algaScenedesmus subspicatus

72 h Static Metabolite M3ErC50:97.4 mg/L*

*Calculated by linear regression analysis. 50% inhibition at

Grützner, 1997OECD 201FIFRA J 122Report No. 97/10274GLPKlimisch score: 2*




[reference number]SAN 1289 H Metabolitesconcentration > than concentrations tested.



72 h Static Metabolite M23Limit testErC50: > 94 mg/L[measured]

*pH of the test lower than the control range:Test: 6.67- 7.32Control: 7.61 – 7.76

van der Kolk, 1995OECD 201FIFRA J 122Report No. 95/11320GLPKlimisch score:1*


72 h Static Metabolite M27ErC50:> 208 mg/L


van der Kolk, 1995OECD 201FIFRA J 122Report No. 95/11332GLPKlimisch score:1

DuckweedLemna gibba

14 d Static EC50 (Frond density):0.016 mg/L95% CI:0.0055 – 0.048 mg/L(dry weight)

EC50 (frond biomass):0.0089 mg/L95% CI:0.0025 – 0.032 mg/L(dry weight)

Test initiation:[measured] > 80 and < 120% [nominal]

*Test completion:[measured] > 10 and < 40% [nominal]

EC50: based on initial [measured] – note this calculation should have been based on the geometric mean of the measured concentrations leading to a lower EC50 than given for the calculation performed.

Hoberg, 1997FIFRA guidelines122-2, 123-2Report No. 97/10742GLPKlimisch score: 2*SAN 1289 H




[reference number]SAN 1289 H Metabolites

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 availablec Unless otherwise stated, the tests were conducted according to the test method identified

Table A2.11A: Summary of aquatic toxicity data for dimethenamid (SAN 582 H).


Test results a, b Test method c

[reference number]

FishRainbow TroutSalmo gairdneri

96h static LC50:2.6 mg/L

95% CI:1.7 – 5.8 mg/L

[measured] > 95% < 105% [nominal]

Bowman, 1988FIFRA 72-1Report No.88/11366GLPKlimisch score: 1SAN 582 H

BluegillLepomis macrochirus

96 h static LC50:6.4 mg/L

95% CI:3.3 – 10 mg/L

[measured] = [nominal]

*DO range: 46 – 100%

Bowman, 1988FIFRA 72-1Report No.88/11368GLPKlimisch score: 2*SAN 582 H


21-dayFlow-through

NOEC:0.63 mg/L

LOEC:1.25 mg/L(pigmentation, loss of co-ordination)


Jenkins, 1991OECD204Report No. 91/11906GLPKlimisch score: 1SAN 582 H


Early Life Stage90-days

NOEC: 0.12 mg/L

LOEC:0.24 mg/L(Growth during first 31 days)

Graves & Smith, 1992FIFRA E 72-4ASTM E 1241-88Report No. 92/12456GLPKlimisch score: 1SAN 582 H

InvertebratesDaphnia magna 48 h static LC50:

16 mg/L

95% CI:12 – 22 mg/L

Frazier, 1988FIFRA 72-2Report No.95/11367GLP




[reference number]

[measured] > 85% < 95% [nominal]Klimisch score: 1SAN 582 H

Daphnia magna 21 dayFlow-through

NOEC:1.36 mg/L

LOEC:2.51 mg/L(survival, 1st generation)(weight, 2nd generation)


Holmes& Swigert, 1992FIFRA 72-2Report No. 92/12455GLPKlimisch score: 1SAN 582 H

Algae/Aquatic plants Freshwater algaAnabaena flos-aquae

120 h static ErC50:1.2 mg/L95% CI:0.11-65.0 mg/L

EbC50:0.45 mg/L95% CI:0.072-3.0 mg/L

[measured] > 55% , < 95% of [nominal]calculations based on [measured]

Hoberg, 1992FIFRA 122-2, 123-2Report No.92/12457GLPKlimisch score: 1SAN 582 H

Freshwater diatomNavicula pelliculosa

120 h static Limit testErC50:> 1.2 mg/L

EbC50:>1.2 mg/L[measured]

Hoberg, 1992FIFRA 122-2, 123-2Report No.92/12458GLPKlimisch score: 1SAN 582 H

Freshwater algaSelenastrum capricornutum

120 h ErC50:0.096 mg/L

95% CI: 0.049 – 0.112 mg/L[measured]

Thompson & Peters, 1991FIFRA 123-2Report No. 91/11907GLPKlimisch score: 1SAN 582 H

DuckweedLemna gibba

14 d IC50 (mean % inhibition):0.028 mg/L

95% CI: 002 – 0.074 mg/L

[measured] used

Thompson et al. 1991FIFRA 123-2Report No. 91/11907GLPKlimisch score: 1SAN 582 H

Table A2.11B: Summary of aquatic toxicity data for Frontier–P (BAS 656 07 H).Test species Test type

& duration

Test resultsa, b Test methodc

[reference number]BAS 656 07 H

FishRainbow trout, 96 h static LC50: Zok, 1999


Test species Test type & duration


[reference number]BAS 656 07 H

Oncorhynchus mykiss

7.94 mg/L

[measured] > 100%, < 115% [nominal]

FIFRA 72-1OECD 201Report No. 99/10317GLPKlimisch score: 1BAS 656 07 H

InvertebratesDaphnia magna 48 h static LC50:

17.1 mg/L

95% CI:16 – 18.3 mg/L[measured] > 100%, < 120% [nominal]

Jatzek, 1999OPPTS 850.1010OECD 202Report No. 99/10316GLPKlimisch score: 1BAS 656 07 H

Algae/Aquatic plants Scenedesmus subspicatus

72 h static ErC50:0.1327 mg/L


Reuschenbach, 1999OPPTS 850.1010OECD 202Report No. 99/10315GLPKlimisch score: 1BAS 656 07 H

DuckweedLemna gibba

14 d ErC50:0.054 mg/L

95% CI:0.038 – 0.075 mg/L


Dohmen, 1999OPPTS 850.44Report No. 99/10314GLPKlimisch score: 1BAS 656 07 H


Table A2.11C: Summary of aquatic toxicity data for the leachates of Frontier-P.



[reference number]

FishRainbow trout,Oncorhynchus mykiss

96 h static No clinical signs nor mortality were observed in the fish exposed to the control and treated leachate over the 96 hour exposure period.

Mixed leachates of the 2nd year of lysimeter study number: 321726 with 14C-SAN 582 H (Lysimeter 2).

The leachate tested appears to be non-toxic to fish.

Wüthrich, 1995OECD 203Report No.95/11351GLPKlimisch score: 1

InvertebratesDaphnia magna 48 h static No immobility was observed in the daphnia

exposed to the control and treated leachate over the 48 hour exposure period.

Wüthrich, 1995OECD 202Report No.




[reference number]

Note: the immobility of a single animal was noted after 48 h in one replicate of treated leachate – not considered to have occurred as an effect of the treated leachate mixture.

Mixed leachates of the 2nd year of lysimeter study number: 321726 with 14C-SAN 582 H (Lysimeter 2).

The leachate tested appears to be non-toxic to daphnia.

95/11326GLPKlimisch score: 1

Algae/Aquatic plants Pseudokirchneriella subcapitata

72 h static Test mixture

Growth rate% inhibition

Biomass% inhibition

OECD medium

-- --

Tap water control

93.8 96.7

Control leachate

72.9 79.9

Treated leachate

24.0 53.8

Toxicity of the SAN 582H leachates is inconclusive based on the failure of the controls.

Wüthrich, 1995OECD 201Report No.95/11326GLPKlimisch score: 1


ConclusionDimethenamid-P is classified as 9.1A due to its toxicity to aquatic plants (Hoberg, 1997, Report No. 97/10742).Frontier-P is classified as 9.1A due to its toxicity to aquatic plants (Dohmen, 1999,Report No. 99/10314).The leachates of Frontier-P® tested did not trigger a 9.1 classification (Wüthrich, 1995, Report No. 95/11326 ).

Notes: Comparison of fish and invertebrate acute toxicity values of dimethenamid

and dimethenamid-P shows similar concentrations causing effects. On this basis the chronic toxicity of dimethenamid has been extrapolated to dimethenamid-P.

The algal toxicity of dimethenamid-P appears greater than that of dimethenamid to an extent that cannot be explained by the concentration of the S-isomer in dimethenamid.


Sub-class 9.2 Soil ecotoxicity and terrestrial fateClassification under this sub-class requires consideration of the persistence of the components of the Frontier-P in soil, and the toxicity 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 dimethenamid-P, dimethenamid and Frontier–PInformation of terrestrial fate and degradation is summarised in Table A2.12, Table A2.12A, respectively.

Table A2.12: Terrestrial fate and degradation of dimethenamid-P (SAN 1289 H) and its metabolites.

Test typeTest results Test method a

[reference number]Active Metabolites

Abiotic degradationPhotolysisBridging studySAN 582H and SAN 1289H

Elliot clay loam soil(pH 6.4, OM 4.1%)

SAN 1289H (P)DT50: 44.71 daysCorrected for spring 40°NDT50: 56.8 days

Major degradation product:CO2 10%

SAN582HDT50: 29.87 daysCorrected for spring 40°NDT50: 40 days

Major degradation product:CO2 12%

Nietschmann & Yu, 1997Report No. 97/5181USEPASubdivision NSection 161-2GLPKlimisch score: 1

Biodegradation - aerobic(Laboratory)Bridging studySAN 1289H (P) and SAN 582H

Elliot clay loam soil(pH 6.4, OM 4.1%, 23°C)

SAN 1289H (P)DT50: 10 daysSAN582HDT50: 10 days

Pathways of degradation were also identical.

Wendt, 1997Report No. 97/5257USEPA 162-1GLPKlimisch score: 1


Conclusion:No metabolic differences will occur regarding the fate of dimethenamid –P (S) versus the dimethenamid R,S-enantiomer mixture.

Soil accumulation Ad DesAdsorption/desorptionSAN 1289H

Soil Kd Koc Kd Koc Tong & Su, 1997Report No. 97/5180OECD 106USEPA guidelineGLPKlimisch score: 1

Clay(pH 8.00, OC 0.99%)

2.09 211 3.24 328

Clay loam(pH 6.40, OC 2.38%)

2.51 105 3.31 139

Loam sediment(pH 7.30, OC 1.22%)

3.02 247 3.89 319

Sandy loam(pH 7.00, OC 0.35%)

1.38 395 1.40 401

Silt loam(pH 6.70, OC 1.51%)

1.95 129 2.09 138

Sandy clay loam(pH 5.6, OC 1.40%)

6.61 474 8.32 596


2.51 123 2.4 118


2.14 90 2.63 110


1.23 101 2.63 215

Sand(pH 3.9, OC 3.43%)

13.49 393 20.89 609

Conclusion:Dimethenamid-P is expected to have high to medium mobility in soil.Koc values 50-150 high mobility, Koc values 150-500 medium mobility

Soil accumulation Oxalamide Ads DesAdsorption/desorptionOxalamide (M23)Sulfonate (M27)

Soil Kd Koc Kd Koc Mamouni, 1995Report No. 95/101821OECD 106GLPKlimisch score: 1

AmendmentTong, 1999Report No. 99/5014

Loamy sand(pH 6.4, OC 1.6%)

0.06 3.48 - -


0.24 17.22 - -

Silty clay(pH 7.8, OC 2.9%)

0.11 3.88 - -

Loam(pH 7.9, OC 1.1%)

0.05 4.13 - -


0.09 9.61 - -

Silt loam(pH 7.1 CaCl2, OC 4.39%)

0.35 7.91 - -

Sulfonate Kd Koc Kd KocLoamy sand(pH 6.4, OC 1.6%)

0.23 14.38 - -


0.14 10.29 - -


0.10 3.52 - -

Loam 0.00 0.00 - -


(pH 7.9, OC 1.1%)Sandy loam(pH 7.5, OC 0.9%)

0.02 2.23 - -

Silt loam(pH 7.1 CaCl2, OC 4.39%)

0.43 9.87 - -

Conclusion: The metabolites M23 and M27 are characterised as highly mobile compounds.

a unless otherwise stated, the tests were conducted in accordance with the named test guideline

Table A2.12A: Terrestrial fate and degradation of dimethenamid (SAN 582 H).

Test typeTest results Test methoda

[reference number]

Active

Abiotic degradationPhotolysisSAN 582 H

Kenyon loam soil(pH 7.4, OM 3.2%)DT50: 5.3 ± 0.3 daysCorrected for spring 40°NDT50: 7.8 days

Sabat & Yu, 1992Report No. 92/12387USEPASubdivision NSection 161-3GLPKlimisch score: 1

Biodegradation - aerobic(Laboratory)SAN 582

Kenyon Loam soil(pH 6.2, OM 3.8%, 25°C)DT50: 38 days

Major metabolite:oxalamide (M23)

Krueger & Bade, 1990Report No. 90/11105USEPA 162-1GLPKlimisch score: 1

Biodegradation - aerobic(Laboratory)SAN 582 H

SAN 582 HLoamy sand(pH 5.8, OC 2.29%, 20°C)DT50: 13 days

Major metabolitesOxalic acid (M23) 8.86%Sulfonic acid (M27)10.87%

Sandy loam(pH 6.6, OC 1.34%, , 20°C)DT50: 13 days

Major metabolitesOxalic acid (M23)10.17%Sulfonic acid (M27)12.69%

MetabolitesLoamy sandM23DT50: 41 dM27DT50: 140 d

Sandy loamM23DT50: 24 dM27DT50: 60 d

König, 1995Report No. 95/10128BBA Part IV, 4-1GLPKlimisch score: 1

Biodegradation - aerobic(Laboratory)SAN 582H

SAN 582 HSandy clay loam(pH 7.95, OC 1.34%, , 20°C)DT50: 7.8 days

MetabolitesM23DT50: 25.9 daysM27DT50: 40 days

König, 1996Report No. 96/11006BBA Part IV, 4-1GLP


Klimisch score: 1Extrapolation to different soil temperaturesSAN 582H

SAN 582 H10°CDT50: 17.2 28.628.6123.226.428.6 days

20°CDT50: 7.81313561213 days

Metabolites10°CM23DT50: 57.290.252.8days

M27DT50: 88308132 days

20°CM23DT50: 25.94124 days

M27DT50:4014060 days

Gottesbüren, 1999Report No. 99/10071Non-GLP (calculation)Klimisch score: 1

Biodegradation – anaerobicSAN 582H

Kenyon loam soil(pH 6.2, OM 3.8%)DT50: 53.8 days

Major metabolitesOxalic acid (M23)8.7%

Bade, 1990Report No. 90/11111USEPA 162-2

Soil accumulation Ad DesAdsorption/desorptionSAN 582 HLinear Isotherm model

Freundlich model

Soil Kd Koc Kd Koc Völlmin, 1995Report No. 95/10123OECD 106GLPKlimisch score: 1

Sand(pH, OC 0.5%)

0.3 61 - -

Loamy sand(pH, OC 1.4%)

1.59 144 4.36 311

Clay loam(pH, OC 1.1%)

0.65 59 - -

Silt loam(pH, OC 1.0%)

0.62 62 - -

Silty clay(pH, OC 2.9%)

1.10 38 2.38 82

Sand(pH 6.9, OC 0.5%)

0.32 64 - -


1.6 114 4.19 299


0.73 67 - -


0.62 62 - -


1.15 40 2.59 89


Conclusion:SAN 582 H is adsorbed weakly by soils of low organic carbon content. This compound is predicted to have high to medium mobility in these soils.

Soil accumulation Ads DesAdsorption/desorptionSAN 582 H

Soil Kd Koc Kd Koc Tong, 1991Report No. 91/118819OECD 106GLPKlimisch score: 1

Loam (Kenyon)(pH 7.1, OC 2.2%)

3.3 150 3.7 168


3.5 121 3.9 135

Silt Loam(pH 7.4, OC 0.3%)

0.7 233 0.7 233

Sandy clay loam(pH 6.4, OC 1.7%)

2.0 118 2.1 124

Conclusion: SAN 582H is predicted to have high to medium soil mobility.

Mobility/leaching LaboratorySAN 582 H

Rate: 2.82 ppm soil

Sandy soil (pH 6.90, OC 0.5%)Cumulative radioactivity in leachate (%AR):Column A: 24.15% (AI: 0.09%, M23: 16.66%, M27: 0.96%, M31:1.13%)

Column B: 23.54%(AI: --%, M23:16.65%, M27:0.45%, M31: 0.79%)

M31: Thioglycolic acid

The maximum extractable radioactive residues in soil layer: Column A: 0-5 cm 14.05%Column B: 0-5 cm15.36%

Conclusions: Residues of dimethenamid were only found in one column (0.09% of AR). Therefore the groundwater contamination potential of dimethenamid is low.

Oxalamide (M23) was the only transformation product of significance in the leachate – approximately 17% of AR in both columns. Therefore the potential for ground water contamination exists by M23.

König, 1995Report No.95/10101BBA Part IV, 4-2GLPKlimisch score: 1


Rate: 2.82 ppm soil

Loamy sand soil (pH 5.8, OC 2.3%)Cumulative radioactivity in leachate (%AR):Column A: 22.41% (AI: --%, M23: 10.73%, M27: 2.17%, M31: 2.20%)

Column B: 22.89%(AI: --%, M23:11.10%, M27:2.54%, M31: 2.34%)

The maximum extractable radioactive residues in soil layer: Column A: 0-5 cm 19.13%Column B: 0-5 cm 24.57%

Conclusions: No residues of dimethenamid were found in the leachates

König, 1994Report No.94/10635BBA Part IV, 4-2GLPKlimisch score: 1


(LOD = 0.1%). Therefore the groundwater contamination potential of dimethenamid is low.

Oxalamide (M23) was the only transformation product of significance in the leachate – approximately 11% of AR in both columns. Therefore a potential for ground water contamination exists for M23.


Rate: 1.6 L/ha (1440 g ai/ha) König, 1994Report No.95/10122BBA Part IV, 4-2GLPKlimisch score: 1

Volume Leachate (mL)

Total amounts (%) of radioactivity in leachate

Soil A B A BSand(pH 7.6, OM 0.3%)

365 370 43 37

Loamy sand(pH 7.0, OM 2.5%)

370 375 5.3 4.5

Sandy loam(pH 7.9, OM 1.2%)

380 380 11 6.4

Silt loam(pH 7.0, OM 1.6%)

375 375 5.8 4.5

Sandy clay loam(pH 8.3, OM 1.3%)

375 370 4.9 1.8

The maximum extractable radioactive residues in soil layer: Sand 25-30 cm: Column A 24%, Column B 24%Loamy Sand 10-15 cm: Column A 32%: Column B 40%Sandy loam 20-25 cm: Column A 28%, Column B 25%Silt loam 20-25 cm: Column A 34%, Column B 34%Sandy clay loam 20-25 cm: Column A 20%, Column B 21%

Conclusions:In the case of sand soil 37% and 30% of the initially applied amount of dimethenamid had leached whereas no detectable residues were found in the leachates of the Loamy sand soil (LOD 0.002% applied amount). Only one of the two leachates from each of the other soils contained dimethenamid residues Sandy loam (column A: 3.27% of the applied amount), Silt loam (column A: 0.59%) and Sandy clay loam (column A: 1.69%), respectively.

Detectable quantities of metabolites M23, M27 and M31 were measured in the leachates. This observation is attributed to degradation of the parent molecule in the test soil.

There is a potential for the metabolites M23, M27 and M31 to leach into groundwater.

Mobility/leaching Outdoor LysimetersSAN 582 H

Application rate: 1.44 kg ai/haLysimeter 1: one applicationLysimeter 2: two applications one year apart

Burgener, 1996Report No.96/10707BBA IV, 4-3


Soil Type: Sandy soilParameter Horizon (cm)

0-30 30-60 60-90 90-120pH (KCl) 6.1 5.9 6.1 7.3OC% 1.05 0.49 0.14 0.00

Determination of movement and degradation of dimethenamid and its degradation products in a soil profile of 120 cm and leaching as a function of the precipitation and vegetation. Normal agricultural practices such as soil cultivation, crop protection fertilization and crop rotation were followed.

Distribution of radioactivityLeachatesFirst year:Lysimeter 1: 30.3 μg parent equivalents/L.Lysimeter 2: 31.5 μg/L

Second year:Lysimeter 1: 8.9 μg/LLysimeter 2: 35.3 μg/L (second treatment)

Third year:Lysimeter 1: 4.5 μg/LLysimeter 2: 15.4 μg/L (second treatment of third year)

Plants - RapeFirst year:Lysimeter 1: 0.41 ppm ARLysimeter 2: 0.53 ppm ARPredominantly found in straw (grain 0.05 ppm)

Second year:Lysimeter 1: 0.03 ppm ARLysimeter 2: 0.15% AR

Third year:< 0.01 ppm AR

SoilLysimeter 1: 22.71% AR present after 3 years12.3% AR localized in the top 8 cm.1.62% found below 57 cm.

Lysimeter 2: 26.17% AR present after 3 years14.65% AR localized in the top 8 cm.1.64% found below 57 cm.

Total recovery:Lysimeter 1: 34.72% AR recoveredLysimeter 2: 40.16% AR recovered

Loss of radioactivity attributed to total degradation to CO2, conversion to volatile products and biodegradation.

Characterisation of radioactivityMetabolitesLysimeter 1: Average annual yieldU1: 3.63AR (6.2 μg/L)

GLPKlimisch score: 1


U8: 0.97 AR (1.7 μg/L)M27: 0.70 AR (1.2 μg/L)M23: 0.14 AR (0.2 μg/L)Dimethenamid was not detected in any leachate.

Lysimeter 2: Average annual yieldU1: 3.34% (5.0 μg/L)U2: 1.82% (2.9 μg/L)U5: 1.39% (2.1 μg/L)U6: 1.67% (2.5 μg/L)U8: 0.99% (1.5 μg/L)U10: 1.12% (2.0 μg/L)M27: 1.61% (2.6 μg/L)M23: 0.47% (0.7 μg/L)Dimethenamid was not detected in any leachate.

The chromatographic profile of the leachates changes throughout the course of the study indicating an increased formation of polar degradation products with time. No parent compound was found in the percolation water.

At least 17 unknown and two known metabolites (M23 and M27) showed a high mobility in the sandy soil of the lysimeters.

Conclusions:The metabolites of dimethenamid show the potential to leach into ground water.

Mobility/leaching FieldSAN 582 H

Bare soil treated once with 1.6 L/ha (1440 g ai/ha)Two sites (Germany)

Site 1: R10283Soil texture (Loamy sand)Organic matter (%)0-30 cm: 1.530-60 cm: 0.6pH0-30 cm: 6.530-60 cm: 6.7

Site 2: R10284Soil texture (Silty loam)Organic matter (%)0-30 cm: 2.130-60 cm: 0.8pH0-30: 7.630-60: 7.4

DimethenamidDT50: 3.5 days (R10283)4.7 days(R10284)At both sites, dimethenamid was localized exclusively in the top 10 cm of the soil with the exception of the samples collected 0, 3 and 7 days after application of one of the sites (R10283).

Fricker & Hertl, 1995Report No. 95/10130BBA IV, 4-1GLPKlimisch score: 1


“The findings were demonstrated to be due to cross contamination during sample collection rather than leaching of the parent molecule.”

OxalamideDT50: 45 days (R10283)18 days (R10284)

SulfonateDT50: 76 days (R10283)22 days (R10284)

The major fraction of the metabolites was confined to the uppermost soil layer (0-10 cm). At Site R10283, traces of oxalamide (0.009 μg/g) were detected at day 90 in the 20-30 cm soil layer indicating possible mobility. This finding was not confirmed by residues in earlier or later samples.

Significant quantities of metabolites oxalamide and sulfonate were measured in the day 0 samples. This observation is attributed to degradation of the parent in the time interval between application and freezing.

Conclusions:Although there is some evidence of oxalamide leaching to the 20-30 cm soil layer, the incidence appears to be isolated.


Bare soil treated once with 1.6 L/ha (1440 g ai/ha)Two sites (France)

Site 1: R10242Soil texture (Sandy loam)Organic carbon (%)0-25 cm: 1.50 25-50 cm: 0.70pH0-25 cm: 5.925-50 cm: 5.6

Site 2: R10243Soil texture (Sandy silt loam)Organic carbon (%)0-25 cm: 1.1025-50 cm: 0.50pH0-25 cm: 6.0025-50 cm: 6.50

DimethenamidDT50

1.8 days (R10242)34.7 days (R10243)

The major fraction of dimethenamid was localised in the upper 10 cm of the soil. Some samples collected during the first two weeks of the study contained residues (< 0.058 μg/g) in the 10-30 cm layer. No residues were

Fricker & Hertl, 1995Report No. 95/10133BBA IV, 4-1GLPKlimisch score: 1


detected at depths below 10 cm in any of the samples collected at day 28 and at the subsequent sampling dates. No residues were detected below 30 cm throughout the entire study period. OxalamideDT50: Not determined (R10242)41.5 days (R10243)

SulfonateDT50: 25.4 days (R10242)41.7 days (R10243)

Site R10242Oxalamide residues were detected on four occasions during the first month of study in the 0-10 cm soil layer (< 0.031 μg/g). One week after the application 0.012 μg/g were found in the 10-20 cm layer. After day 28, no residues were detected below 20 cm throughout the entire study period.

Sulfonate residues were found on 3 occasions during the study: day 15 (0.011μg/g in the 10-20 cm layer, day 28 (0.015 μg/g in the 0-10 cm layer) and day 86 (0.010 μg/g in the 20-30 cm layer). Residues (< 0.01 μg/g were occasionally detected in the 0-50 cm layer from day 0 to 120 – no sulfonate was detected on the last sampling date (day 181).

Site R10243The major fraction of metabolites was found in the 0-10 cm layer. Oxalamide (0.01 μg/g) was found in the 10-20 cm layer at day 21. No residues were detected below 20 cm throughout the entire study period.

Three samples from deeper layers contained sulfonate residues: two of them in the 10-20 cm layer (0.007 μg/g and 0.006 μg/g on days 3 and 28, respectively) and one in the 40-50 cm horizon (0.01 μg/g on day 60). On day 91 and on the subsequent sampling dates no residues were detected below 10 cm.

Absolute concentrations of metabolites reached approximately 7% of the initial concentration of dimethenamid.

Conclusions:Although potential for leaching has been shown for the metabolites, oxalamide and sulfonate, they appear to be present at low concentrations (Max: 0.011μg/g soil).


Bare soil treated once with 1.6 L/ha (1440 g ai/ha)Two sites (France)

Site 1: R10244Soil texture (loam)Organic carbon (%)0-25 cm: 0.525-50 cm: 0.3

Carrier and Blanz, 1997Report No. 97/11507BBA IV, 4-1GLPKlimisch score: 1


pH0-25 cm: 6.525-50 cm: 6.7

Site 2: R10245Soil texture (sand)Organic carbon (%)0-25 cm: 1.225-50 cm: 1.1pH0-25 cm: 5.925-50 cm: 5.7

DimethenamidDT50

16.3 days (R10244)13.3 days (R10245)

Site R10244No residues were detected below 10 cm. 98% of residues were detected in the 0-10 cm layer.

Site R1024581.7% of residues were detected in the 0-10 cm layer. Residues were located in the 10-20 cm (11.9%) and 20-30 cm (6.4%) layers, respectively.

Residues above the quantitation limit were found in the layers of 10-20 cm and 20-30 cm depth in the samples taken at day 0, 57 and 90 and in the layer of 10-20 cm depth on day 30.

MetabolitesSite R10244The dissipation of dimethenamid is accompanied by the transient formation of oxalamide and sulfonate. Formation is less evident at site R10245, where metabolites were only detected in trace amounts.

Absolute concentrations of the total of both metabolites reached approximately 5% of the initial concentration of dimethenamid.

Conclusions:Dimethenamid showed the potential to leach beyond both the 10 cm and 20 cm soil layers.


Bare soil treated once with 1.6 L/ha (1440 g ai/ha)Three sites (Italy)

Site 1: R10246Soil texture (sandy loam)Organic carbon (%)0-30 cm: 0.7 30-50 cm: 0.4pH0-30 cm: 7.930-50 cm: 8.1

Site 2: R10247

Carrier, 1997Report No. 97/11508BBA IV, 4-1GLPKlimisch score: 2*


Soil texture (sandy loam)Organic carbon (%)0-30 cm: 0.430-50 cm: 0.4pH0-30 cm: 8.130-50 cm: 8.1

Site 3: R10248Soil texture (loam)Organic carbon (%)0-30 cm: 0.930-50 cm: 0.9pH0-30 cm: 7.930-50 cm: 7.9

DimethenamidDT50

4.8 days (R10246)8.3 days (R10247)15.2 days (R10248)

Site 1: R10246At days 0, 3 and 7, some residues of dimethenamid were detected in the 10 – 40 cm soil layers. No residues were detected below 10 cm in the samples taken 15 days after the application – with the exception of the layer 20-30 cm on day 21 (0.003 μg/g).

Site 2: R10247Samples collected at days 0 and 3 showed residues of dimethenamid detected down to 50 cm depth.

No dimethenamid above the limit of quantitation was measured in soil level below 10 cm in any sample taken after 7 days.

Site 3: R10248Dimethenamid residues were detected to 30 cm between days 0 and 7. Day 3 dimethenamid was detected at the 40-50 cm level. No residues were detected below 10 cm after 14 days – with the exception of the 20-30 cm layer (day 30).

*Note (Klimisch scoring):“Since at day 0, the soil was dry and no rain was recorded in the 24 hours following application and since the presence of residues of dimethenamid was not confirmed at later sampling dates and did not increase with increasing rainfall, the apparent mobility of dimethenamid to deeper soil layers observed during the first week at each of the three sites is judged to be an artefact due to cross-contamination during sampling and transport of the samples.

These levels were judged to be an artefact due to cross-contamination during sampling and transport of the samples.”


OxalamideDT50: 97.8 days (R10246)52.8 days (R10247)158.5 days (R10248)

SulfonateDT50: 24.4 days (R10246)74.1 days (R10247)136.6 days (R10248)

Site 1: R10246Oxalamide was detected only in the upper 10 cm of the horizon between 14 and 122 days at concentrations ranging between 0.012 to 0.021 μg/g.

Sulfonate was first detected at day 3. Its concentration was 0.022 μg/g 14 days after the application and then decreased to a non-detectable concentration at 93 days. Concentrations below the limit of quantitation were measured in the 10-20 cm level 30 and 60 days which may indicate a slight tendency to migrate to deeper layers while degrading.

Site 2: R10247Oxalamide and sulfonate were found only in the upper 10 cm of the soil horizon. Oxalamide was detected at concentrations above the limit of determination on days 21 and 30. Sulfonate residues were only detected on 4 sampling dates, the concentration increases from 0.03 μg/g (21 days) to 0.039 μg/g (day 30). Residues were non-detectable 122 days after application.

Site 3: R10248Oxalamide was only detected in the upper 10 cm level. The maximum concentration was 0.037 μg/g (5.5% of the initial concentration of dimethenamid) 122 days after application. No oxalamide was detected later.

Sulfonate residues were first found only at the 0-10 cm soil level. The concentration increased from 0.02 μg/g 25 days after application to a maximum concentration of 0.049 μg/g (7.2% of the initial dimethenamid concentration) 60 and 93 days after initial application. The concentration decreased following sampling at 186 and 246 days. Sulfonate residues were detected below the limit of quantitation in the 10-20 cm and 20-30 cm soil layers, indicating a tendency to migrate deeper with increasing time whilst degrading. The peak concentration of both metabolites accounted for 8.2 to 12.7% of the initial concentration of dimethenamid.

Conclusions:The data regarding dimethenamid should be treated with caution with regard to the potential of cross contamination. The metabolites appear to be not rapidly degradable for the majority of tested soil types. The


sulfonate metabolite shows the potential for leaching during the degradation process.

Mobility/DissipationSwitzerland 1994-1997

Application rate: 1.6 L/ha (1440 g ai/ha) per yearSoil type: Sandy loam (0-30 cm, pH 7.75, OC 1.1%)Crop: Corn

Pore waterNo dimethenamid residues above 0.1 μg/L were detectable in any of the pore water samples collected in suction cups installed at a depth of 1.0-1.2 m or 2.6 – 3.0 m and taken at monthly intervals up to 36 months after the first application.

Soil1994The concentration of dimethenamid found in soil samples decreased from a maximum concentration of 0.90 μg/g just after application to < 0.01 μg/g five months after application.

1995The concentration of dimethenamid found in soil samples decreased from a maximum concentration of 0.89 μg/g just after application to < 0.01 μg/g two months after application.

MetabolitesOxalamide19940 – 10 cmRange 0.01 – 0.03 μg/g (between 3 and 65 days)Maximum at 65 days

19950 – 10 cmRange 0.01 – 0.02 μg/g (between 0 and 29 days)Maximum at 16 and 29 days

10-30 cm0.01 μg/g (16 days)

Sulfonate19940 – 10 cmRange 0.02 – 0.05 μg/g (between 3 and 65 days)Maximum at 30 days

19950 – 10 cmRange 0.01 – 0.05 μg/g (between 3 and 29 days)Maximum at 16 days

10-30 cm0.03 μg/g (16 days)

Conclusions:Dimethenamid is not expected to accumulate in soil.Dimethenamid residues were located in the upper 0 – 10 cm soil layers, no leaching effect could be observed.Although metabolite residues were found below the 10

Gasser, 1998Report No. 98/10384GLPKlimisch score: 1


cm layer of soil , concentrations are expected to dissipate to < 0.01 μg/g after 5 months.

Residues in cropped fieldFrance

Application rate: 1.4 – 1.6 L/ha (1260 – 1440 g ai/ha)Soil:Crop: Corn

Ground water samplesNo dimethenamid residues were detectable in any of the ground water samples taken between 5 to 6 months after application.

SoilSite 1The concentration of dimethenamid found in soil samples decreased from a maximum concentration of 0.67 μg/g just after application to < 0.01 μg/g three months after application.

Site 2The concentration of dimethenamid found in soil samples decreased from a maximum concentration of 0.68 μg/g just after application to < 0.01 μg/g three months after application.

Dimethenamid residues were located in the upper 0 -12.5 cm soil layers (*Klimisch score: residues found in 4 deeper layers attributed to cross contamination). No leaching effect was observed during 3 months following application.

Conclusions:Data concerning the leaching of dimethenamid to layers below 12.5 cm should be viewed with caution due to cross contamination. However, no residues were found in groundwater samples taken between 5 to 6 months.

Gasser, 1998Report No. 98/10385GLPKlimisch score: 2*

Agency’s conclusions:With regard to ground water contamination, the active ingredient dimethenamid applied at a rate of 1.6 L/ha shows no leaching potential. The metabolites, oxalamide and sulfonate, appear to be mobile in the soil and therefore have the potential to leach into groundwater.

ConclusionBased on these data dimethenamid-P is considered to meet the HSNO criteria for degradability in soil < 30 days. The metabolites M23 and M27 are not considered to meet the HSNO criteria for degradability in soil < 30 days (10°C).

Soil toxicityA summary of the toxicity of dimethenamid-P, dimethenamid, and Frontier-P to soil dwelling macro-organisms, soil microbial function and terrestrial plants is provided in Table A2.13, Table A2.13A and table A2.13B, respectively.

Table A2.13: Summary of terrestrial toxicity data for dimethenamid-P (SAN 1289 H).Test species

Test type & duration


[reference number]SAN 1289 H MetabolitesSoil-dwelling invertebratesEarthwormEisenia

Acute14 d

Metabolite M23LC50:

Krieg, 1998OECD 207


foetida > 1264 mg/kg soil dry wt

NOAEC:1264 mg/kg soil dry wt

Report No. 98/10299GLPKlimisch score: 1

EarthwormEisenia foetida

Metabolite M27LC50:1264mg/kg soil dry wt

NOAEC:632 mg/kg soil dry wt

Krieg, 1998OECD 207Report No. 98/10300GLPKlimisch score: 1

Terrestrial plantsSeedling emergence

Vegetative vigour(Used for Risk Assessment only)

Acute14 d

EC50

(Shoot length - lettuce):0.020 lb ai/A95% CI:0.0032 – 0.18 lb ai/A

EC50 equivalent to: 0.022 kg/ha0.029 mg/kg soil d. wt

EC50 (Shoot weight - ryegrass):0.082 lb ai/A95% CI:0.01 – 0.72 lb ai/A

EC50 equivalent to: 0.092 kg/ha


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 availablec Unless otherwise stated, the tests were conducted according to the test method identifiedNA= Not applicableND= No data provided

Table A2.13A: Summary of terrestrial toxicity data for dimethenamid (SAN 582 H).Test species



[reference number]Active MetabolitesSoil-dwelling invertebratesEarthwormEisenia foetida

Acute14 d

LC50:294.4 mg/kg soil dry wt

95% CI:260.6 – 339.9 mg/kg soil dry wt

NOEC:125

van Dijk, 1988OECD 207 (2)Report No. 88/11372GLPKlimisch score: 1SAN 582 H


mg/kg soil dry wt

Soil microbial function

Carbon mineralisation

Nitrogen mineralisation

28 d Application rate:2.4 mg/kg soil(1.8 kg/ha)12 mg/kg soil(9 kg/ha)

Soil 1 - Sandy(pH 6.84, %OC 1.34)Soil 2 - loamy(pH 5.50, %OC 3.91)

Soils 1 & 2< 25% deviation from control at both application rates

Soil 1> 25% deviation from control (increased nitrogen in soil) at both application rates

Soil 2< 25% deviation from control at both application rates

Danneberg, 1991Report No. 91/11908GLPKlimisch score:1SAN 582 H

Bacterial inhibition

16 hCell multiplication

EC50: > 400 mg/L

Scholtz, 1994GuidelineISO 10712:1990 (E)Report No. 94/11901NonGLPSAN 582 H

Table A2.13B: Summary of terrestrial toxicity data for Frontier-P (BAS 656 H).Test species



[reference number]FormulationSoil-dwelling invertebratesEarthwormEisenia foetida

Acute14 d

LC50:596.3mg/kg soil dry wt

95% CI:544.65 – 650.7mg/kg soil dry wt

NOEC:316.5mg/kg soil dry wt

Krieg, 1999OECD 207 (2)Report No. 99/10287GLPKlimisch score: 1SAN 656 H

Soil microbial functionSoilNitrogen Turnover

28 d% - deviation from control

Soil 1.4 L/ha 7.0 L/haLoamy sand + 1.7 + 0.4

Krieg, 1999BBA Part VI, 1-1Report No. 99/10134GLPKlimisch score: 1


ALoamy sand B

- 0.5 - 0.5

Negligible effects.

SAN 656 H

Soil Respiration % - deviation from control

Soil 1.4 L/ha 7.0 L/haLoamy sand A

- 1.5 - 3.0

Loamy sand B

- 2.4 - 3.6

Negligible effects.

Krieg, 1999BBA Part VI, 1-1Report No. 99/10265GLPKlimisch score: 1SAN 656 H

Terrestrial plantsSeedling emergence

Vegetative vigour(Used for Risk Assessment only)

Acute14 d

EC50

(Shoot length - lettuce):0.020 lb ai/A95% CI:0.0032 – 0.18 lb ai/A

EC50 equivalent to: 0.022 kg/ha0.029 mg/kg soil d. wt

EC50

(Shoot weight - ryegrass):0.082 lb ai/A95% CI:0.01 – 0.72 lb ai/A

EC50 equivalent to: 0.092 kg ai/ha

Hoberg, 1997FIFRA guidelines122-1, 123-1Report No. 97/5175GLPKlimisch score: 1SAN 1289 HFormulation

Conclusion Dimethenamid-P and Frontier-P® are classified as 9.2 A due to their toxicity to non-target plants (Hoberg 1997, Report no. 97/5175).

Sub-class 9.3 Terrestrial vertebrate ecotoxicityThe mammalian toxicity of dimethenamid-P, dimethenamid and Frontier-P has been addressed under sub-class 6. Key endpoints for both mammalian and avian toxicity are summarized in Tables A2.14, A2.14A andA2.14B.

Table A2.14: Summary of terrestrial vertebrate toxicity data for dimethenamid-P (SAN 1289 H).

Test species



[reference number]SAN 1289 H

MammalsRatSprague-Dawley rats

Oral intubation

LD50: 429 mg/kg bw (males)

Blaszcak, D (1996)FIFRA Guideline 81-


LD50:531 mg/kg bw (females)

1GLPKlimisch score: 1SAN 1289

BirdsNorthernBobwhite QuailColinus virginianus

Acute Oral14 days

LD50:1068 mg/kg95% CI: 845 – 1356 mg/kg

NOEC:< 292 mg/kg

Palmer & Beavers, 1996FIFRA 71-1Report No. 96/5419GLPKlimisch score: 1SAN 1289H

NorthernBobwhite QuailColinus virginianus

Acute Dietary8 days

LC50:> 5620 ppm

NOEC:1780 ppm

Palmer et al, 1996FIFRA 71-2OECD 205Report No. 96/5412GLPKlimisch score: 1SAN 1289H

Mallard duckAnas platyrhynchos

Acute Dietary8 days

LC50:> 5620 ppm

NOEC:1780 ppm

Palmer et al, 1996FIFRA 71-2OECD 205Report No. 96/5419GLPKlimisch score: 1SAN 1289H


Table A2.14A: Summary of terrestrial vertebrate toxicity data for dimethenamid (SAN 582 H).

Test species



[reference number]SAN 582 H

BirdsNorthernBobwhite QuailColinus virginianus

Acute Oral14 days

LD50:1908 mg/ kg95% CI: 1486 – 3229 mg/kgNOEC:< 292 mg/kg

Grimes & Jaber, 1988FIFRA 71-1Report No. 88/11373GLPKlimisch score: 1SAN 582 H

NorthernBobwhite QuailColinus virginianus

Acute Dietary8 days

LC50:> 5620 ppm

NOEC:1780 ppm

Hinken et al. 1988FIFRA 71-2Report No. 88/11370GLPKlimisch score: 1SAN 582 H


Acute Dietary8 days

LC50:> 5620 ppm

NOEC:562 ppm

Grimes & Jaber, 1988FIFRA 71-2Report No. 88/11369GLPKlimisch score: 1


SAN 582 HNorthernBobwhite QuailColinus virginianus

Reproduction20 weeks

NOEC (number of eggs laid per hen)1800 ppmNOEL220.75 mg ai/kg bw/day

NOEC(mean eggshell thickness)900 ppmNOEL113.52 mg ai/kg bw/day

NOEC (proportion of eggs set that are fertile eggs per hen or number viable embryos over number of eggs set)1800 ppmNOEL220.75 mg ai/kg bw/day

NOEC (proportion of fertile eggs hatching per hen or percent hatching of viable embryos)1800 ppmNOEL220.75 mg ai/kg bw/day

NOEC (proportion of 14-day old juveniles per number of hatchlings)1800 ppmNOEL218.05 mg ai/kg bw/day

NOEC (14-day juvenile weights per hen)1800 ppmNOEL218.05 mg ai/kg bw/day

Beavers et al, 1992FIFRA 71-4OECD 206Report No. 94/11900GLPKlimisch score: 1SAN 582 H


Reproduction20 weeks

NOEC (number of eggs laid per hen)1800 ppmNOEL257.86 mg ai/kg bw/day

NOEC(mean eggshell thickness)1800 ppmNOEL268.83 mg ai/kg bw/day

NOEC (proportion of eggs set that are fertile per hen or number viable embryos over number of eggs set)1800 ppmNOEL257.86 mg ai/kg bw/day

Beavers et al, 1994FIFRA 71-4OECD 206Report No. 94/11899GLPKlimisch score: 1SAN 582 H


NOEC (proportion of fertile eggs that hatch per hen or percent hatching of viable embryos)1800 ppmNOEL257.86 mg ai/kg bw/day

NOEC (proportion of 14-day old juveniles per number of hatchlings)1800 ppmNOEL268.83 mg ai/kg bw/day

NOEC (14-day juvenile weights per hen)1800 ppmNOEL268.83 mg ai/kg bw/day


Table A2.14B: Summary of terrestrial vertebrate toxicity data for Frontier-P® (BAS 656 08 H).

Test species



[reference number]BAS 656 08 H Metabolites

MammalsRatWistar rats Oral LD50:

> 500 - < 2000 mg/kg bw*

Gamer, A. O. and R. Lansiedel (2006).OECD 423EC Directive 2004/73 No. 1216 B.1 tris.USEPA OPPTS 870.1100GLPKlimisch score: 1BAS 656 08H

*Note: Acute toxicity studies with a previously tested but very similar formulation of Frontier-P (BAS 656 07H) have shown an LD50 of 1581 mg/kg bw (See Table A2.8). As a result, instead of a 9.3B classification being assigned to the product based on the conservative 500 mg/kg bw value, a 9.3C has been assigned based on the read-across from the aforementioned data.

Conclusion Dimethenamid-P is classified as 9.3B due to its toxicity to mammals (Blaszcak, D (1996), Report No.96-1404).Frontier-P® is classified as 9.3C due to its toxicity to mammals (Gamer and Landsiedel, 2006, Table A2.8).


Sub-class 9.4 Terrestrial invertebrate ecotoxicityA summary of the data on the toxicity of dimethenamid-P (dimethenamid) and Frontier-P to honeybees and other non-target terrestrial invertebrates is provided in Table A2.15 and Table A2.15A.

Table A2.15: Summary of terrestrial invertebrate toxicity data for dimethenamid.

Test species Test type & duration


[Reference number]Active Metabolites

Honey beeApis melliferacarnica

Acute Oral Toxicity24 h

AcuteContact Toxicity24 h

Oral LD50:> 1000 μg/bee

Contact LD50:94 μg/bee

Donat, 1986Report No. 86/11170Not GLP*Klimisch score: 4*

Donat, 1990Report No. 90/11149Amendment


Table A2.15A: Summary of terrestrial invertebrate toxicity data for Frontier-P (BAS 656 07 H).Honey beeApis melliferacarnica

Acute Oral Toxicity48 h

AcuteContact Toxicity48 h

Oral LD50:> 200 μg/bee (205 μg/bee)

NOEC:< 124.76 μg/bee

Note: The actual uptaken test substance in the highest dose was 200 μg/bee and caused 53.3% mortality after 48h. At 150 μg/bee mortality was 36.7% after 48 h.

Contact LD50:> 200 μg/bee (1373 μg/bee)

NOEC:< 200 μg/bee

Note: In this test neither the highest dose nor lower doses caused relevant bee mortality (i.e., > 50%). At 200 μg/bee 16.7%, at 150 μg/bee 36.7%.

In the limit test (200 μg/bee) and the multiple dose tests all bees in the highest doses were negatively affected 24h. The test bees at the doses of 200, 150 and 100 μg/bee appeared wet and moved only their legs, unable to reach the feeding tube. They did not recover until the end of the trial.

Sack, 1999EPPO No. 170Report No. 99/10373GLPKlimisch score: 1BAS 656 07 H



Conclusion Based on the information (Table A2.12 and Table A2.12A), dimethenamid-P and Frontier–P do not trigger the threshold for toxicity to terrestrial invertebrates.

Table A2.16: Summary of ecotoxicity classifications for dimethenamid-P and Frontier–PSub-class dimethenamid-P Frontier–P9.1 Aquatic ecotoxicity 9.1A highly ecotoxic to the

aquatic environment9.1A highly ecotoxic to the aquatic environment

9.2 Soil ecotoxicity 9.2A highly ecotoxic to the soil environment

9.2A highly ecotoxic to the soil environment

9.3 Terrestrial vertebrate ecotoxicity

9.3B ecotoxic to the terrestrial vertebrates

9.3C harmful to terrestrial vertebrates

9.4 Terrestrial invertebrate ecotoxicity

No classification triggered No classification triggered


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 Frontier-P.

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 and packaging

The Agency has qualitatively assessed the risks of Frontier-P to human health and safety during manufacture and packaging and considers the risks to be negligible.

This assessment is based on the following considerations:

Manufacturing and packaging facilities for Frontier-P will be required to meet the HSNO requirements for equipment, emergency management and provision of information (e.g. Safety Data Sheets (SDS)) as well as the requirements of Good Manufacturing Practice (GMP) and the Health and Safety in Employment Act (H&SE Act).

The Agency considers that, while Frontier-P has the potential to cause a major adverse effect through its acute 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 skin or eye irritancy from Frontier-P, given requirements for personal protective equipment (PPE), and compliance with HSNO information provisions (e.g. labels, advertising, SDS). Furthermore, the magnitude of skin and eye irritancy is considered minimal, given the temporary nature of effects.

The Agency considers that it is highly improbable that workers will receive skin sensitisation from Frontier-P, given requirements for PPE and compliance with the HSNO information provisions (e.g. labels, advertising and 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 Frontier-P during use, indicated an acceptable level of risk as long as PPE was used. As workers involved in manufacture and packing of Frontier-P 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 Frontier-P 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 Frontier-P to result in a moderate adverse effect.

The Agency considers that it is highly improbable that a spillage of Frontier-P will occur during importation, transport or storage and workers or bystanders will suffer skin or eye irritancy, 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). Furthermore, the magnitude of skin and eye irritancy is considered minimal, given the temporary nature of effects.

The Agency considers that it is highly improbable that a spillage of Frontier-P will occur during importation, transport or storage and workers or bystanders will suffer skin 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 carcinogenic effects from Frontier-P 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 Frontier-P, and considers the risks to the health and safety of people to be negligible.



If Frontier-P 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 Frontier-P during disposal to result in an acute moderate effect, given that Frontier-P 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 skin or eye irritancy from Frontier-P during disposal, given that Frontier-P will generally be disposed of by use. Furthermore, the magnitude of skin and eye irritancy is considered minimal, given the temporary nature of effects.

The Agency considers that it is highly improbable that workers will suffer skin sensitisation from Frontier-P during disposal, given that Frontier-P will generally be disposed of by use. The magnitude of skin sensitisation is considered minor to moderate based on the sensitivity of the exposed parties.

The Agency notes that quantitative assessment of the chronic risks to operators associated with exposure to Frontier-P during use indicated an acceptable level of risk as long as PPE is used. This assessment includes the possibility of prolonged and repeated exposure to Frontier-P during use. The Agency considers it is less likely that workers or bystanders could be repeatedly exposed to Frontier-P during disposal to such an extent that carcinogenic effects occur and therefore considers the chronic risk to human health during disposal of Frontier-P to be negligible.

Assessment of risks to human health - use

The Agency has qualitatively assessed the acute risks of Frontier-P 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 Frontier-P during use to result in an acute moderate effect, given that Frontier-P 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 skin or eye irritancy from Frontier-P, given the HSNO requirements for PPE, approved handlers and provision of hazard and precautionary information on the product label. Furthermore, the magnitude of skin and eye irritancy is considered minimal, given the temporary nature of the effects.


The Agency considers that it is highly improbable that users will suffer skin sensitisation from Frontier-P, 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’s Chemicals Regulation Directorate (Pesticides) interpretation of the German BBA Model to estimate operator exposure to dimethenamid-P during the use of Frontier–P. This model estimates the exposure of workers to a pesticide during mixing, loading and during spray application, in mg/kg person/day (http://www.pesticides.gov.uk/approvals.asp?id=697). The derived values consider both dermal and inhalation exposure routes.

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). Six different scenarios were modelled for Frontier–P as shown in Table A3.1.

The applicant states that the maximum application rate of Frontier–P is as follows: 1.3 litres formulation/ha, equivalent to 936 g ai/ha pure dimethenamid-P

However, the Agency has considered the purity of the technical grade active ingredient used in the formulation of Frontier-P so as to take into account the toxicity of the impurities. This leads to the following application rate:

1.3 litres formulation/ha, equivalent to 999.7 g a.i./ha technical dimethenamid-P

The Agency has used this maximum application rate for conducting an operator exposure assessment. Table A3.1 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 technical grade dimethenamid-P in Frontier–P = 769 g/L 1.3 L of Frontier–P is applied per hectare the substance is sprayed using a tractor mounted boom 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 4% percutaneous absorption value was used for dimethenamid-P (see dermal penetration studies summary, Table A2.7) from both the formulated product and the diluted spray; and

the bodyweight for operators is set at 70 kg.


http://www.pesticides.gov.uk/approvals.asp?id=697

Table A3.1: Estimated exposure to dimethenamid-P for 70 kg operator under five different exposure scenarios as predicted from the UK CRD’s interpretation of the BBA ModelExposure scenario Estimated operator Exposure

(mg/kg bw/day)No personal protective clothing and equipment (PPE) during mixing, loading and application

0.051

Gloves only during mixing and loading

0.024

Gloves only during application 0.047Gloves during mixing/loading and application

0.020

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

0.002

Full PPE during mixing, loading and application (including respirator)

0.001

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 from relevant studies and is calculated by dividing the NOAEL 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 = NOEL (most relevant study)Safety Factors

Selection of NOEL:

The Agency has established the following NOAEL to consider as the basis for the AOEL for dimethenamid:

13 week oral toxicity study in beagle dogs, 5 mg/kg bw/day 52 week oral toxicity study in beagle dogs, 1.95 mg/kg bw/day

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. Given these factors, the Agency considers it appropriate to use the NOAEL of 1.95 mg/kg bw/day from the study detailed above.

In calculating the AOEL, the Agency has used a combined safety factor of 100 to account for intra- and interspecies variation. Additionally, an oral absorption factor of 90% (see ADME summary in Table A2.7) has been applied by the Agency.


AOEL = 1.95 mg/kg bw/day x 90% = 0.018 mg/kg bw/day. 100

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 modelling by the AOEL to derive a risk quotient (RQ) for each exposure scenario modelled (Table A3.2).

RQ = Estimated Operator (or Bystander) ExposureAOEL

A RQ > 1 indicates the likelihood of a risk to the operator (or bystander).

Table A3.2: Risk quotients determined for each exposure scenario for Frontier–P.Exposure scenario Estimated operator

Exposure (mg/kg bw/day)RQ

No personal protective clothing and equipment (PPE) during mixing, loading and application

0.051 2.83

Gloves only during mixing and loading

0.024 1.33

Gloves only during application

0.047 2.61

Gloves during mixing/loading and application

0.020 1.11

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

0.002 0.11

Full PPE during mixing, loading and application (including respirator)

0.001 0.06

The only exposure situations in which risks to operators is considered to be acceptable (RQ < 1) is when full PPE is worn during mixing, loading and applying the substance, either with or without a respirator. This indicates full PPE should be worn by operators when mixing, loading and/or applying Frontier–P. The Agency notes that PPE is triggered as a default control for Frontier–P as a result of its 6.1D, 6.5B and 6.7B classifications.

Re-entry exposures In respect of potential re-entry exposures, these were not estimated for Frontier–P. Since the substance is applied pre-emergence or early post-emergence, there is no likelihood of extensive contact between a re-entry worker and treated foliage during re-entry operations.

Public health exposure and risk assessmentThe main potential source of exposure to the general public from Frontier–P (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.


The results from the quantitative modelling of operator exposure indicate there is an unacceptable risk to operators from Frontier–P unless full PPE (with or without respirator) is worn. The Agency notes that although any potential bystanders will not be wearing PPE, they will not be directly handling the substance.

By-stander ExposureThe Agency has undertaken an assessment of risks to public/bystander health using the United Kingdom Chemicals Regulation Directorate, Pesticides (CRD) current formula to assess public/bystander exposure for pesticides which are of low volatility and which are typically applied as sprays either by boom sprayers, broadcast air assisted sprayers or hand held sprayers http://www.pesticides.gov.uk/applicant_guide.asp?id=1246&link=%2Fuploadedfiles%2FWeb%5FAssets%2FPSD%2FBystander%2520exposure%2520guidance%5Ffinal%2520version%2Epdf

The CRD guidance document considers a number of scenarios for bystander exposure. The Agency has undertaken the assessment of risks to public/bystander health using the formula that estimates the exposure of the public/bystanders at the time of application (spray drift) which is:

Systemic exposure = {(PDE x SC x %absorbed) + (PIE x SC x 100%)}/BW

PDE (potential dermal exposure)

SC (concentration of dimethenamid-P in spray)

% absorbed (percentage dermal absorption)

PIE (potential inhalation exposure)

BW (bodyweight 70 kg).

Tractor-mounted/trailed boom sprayer: hydraulic nozzles

0.1 ml spray 3.33 mg/ml 4% 0.006 ml spray 70 kg

SC calculation: recommended maximum application rate = 1300 ml product/ha with 300 L of

water/ha; concentration of technical grade dimethenamid-P technical in Frontier-P = 769 g/l,

therefore amount in 1.3 L = 1.3 X 769 = 999.7 g; This implies that 300 L of spray contains 999.7g dimethenamid-P technical; Therefore, concentration of dimethenamid-P technical in spray = 999.7/300 g/L =

3.33 mg/ml

The following measurements are default values used by the CRD and have been adopted by the Agency for the purposes of calculating the estimated exposure from spray drift:

For boom spray, the average potential dermal exposure for a bystander, positioned 8 meters downwind from the sprayer and the average estimated amount of spray passing through the breathing zone are 0.1 and 0.006 ml spray/person, respectively.

Using these data, exposure to dimethenamid-P from the use of FRONTIER-P can be estimated as follows assuming no protection from clothing and 100% inhalation, retention and absorption of PIE:

Systemic exposure = [(PDE x SC x % absorbed) + (PIE x SC x 100%)]/BW = [(0.1 x 3.33 x 0.04) + (0.006 x 3.33 x 1)]/70


http://www.pesticides.gov.uk/applicant_guide.asp?id=1246&link=%2Fuploadedfiles%2FWeb_Assets%2FPSD%2FBystander%2520exposure%2520guidance_final%2520version.pdf



= 0.0005 mg/kg bw/day

RQ = Bystander Exposure/AOEL = 0.0005/0.018 = 0.03

Therefore, risks to the general public are considered to be at acceptable levels (RQ < 1) from ground based applications.

Risks from Aerial ApplicationThe Chemicals Registration Directorate (CRD)’s Bystander Model does not consider risk arising from aerial application of a substance. The Agency acknowledges that spray drift from aerial applications is likely to be greater than for ground based applications, potentially increasing bystander exposure. The Agency notes that although any potential bystanders will not be wearing PPE, they will not be directly handling the substance. Applying a drift factor of 13% (aerial spray - default) determined in the GENEEC 2 environmental exposure modeling, the Agency estimates the exposure of bystanders to be 13% of the calculated operator exposure (no PPE) given in Table A3.2:

Exposure from aerial application = 0.13 x 0.051= 0.007 mg/kg bw

RQ = Bystander Exposure/AOEL = 0.007/0.018 = 0.37.

Since RQ < 1, the Agency considers that aerial application of Frontier-P is unlikely to pose unacceptable risk to bystanders.

Exposure of Children

It is also possible that spray drift fallout from applications may be deposited in gardens adjacent to treated areas and individuals in such locations may become exposed through contact with such deposits. Total children’s exposure is estimated using the CRD Bystander Exposure Guidance as detailed below.

a) Spray Drift fallout:Allowing for an untreated headland of 1 m, the fallout from spray drift at the boundary with a neighboring area is predicted to be equivalent to 2.77% of the applied dose, declining to 0.57% at a distance of 5m from the boundary. The total level of fallout over the whole area from boundary to a point 3 m outside is estimated to be about 1%.

b) Children’s Dermal Exposure:Systemic dermal exposure SE(d) can be calculated using the fallout values and the equation

SE(d) = (AR x DF x TTR x TC x H x DA)/BWWhere, Field application rate (AR) = 0.9997 kg/ha or ~1 kg / 10,000 m2 = 1kg/108 cm2

= 1000000000 / 108 mg cm-2

= 10 μg / cm2

Drift fallout (DF) is assumed to average 1% from field crop (boom) sprayer applications Turf transferable residues (TTR) is estimated at 5%, the EPA default value Transfer coefficient (TC) = 5200 cm2/h, the standard EPA value


Exposure duration (H) in hours for a typical day is assumed to be 2 hours, which matches the 75th percentile for toddlers playing on grass in the EPA Exposure Factors Handbook

DA = percent dermal absorption BW = body weight – assumed to be 15kg for a 2-3 year old toddler

Therefore,SE(d) = (10 x 0.01 x 0.05 x 5200 x 2 x 0.04)/15

= 0.14 μg /kg bw

c) Children’s hand-to-mouth exposure:Systemic dermal exposure via the hand-to-mouth route, SE(h), can be calculated using the fallout values and the equation

SE(h) = (AR x DF x TTR x SE x SA x Freq x H)/BW

Where, Field application rate (AR) = 10 μg / cm2

Drift fallout (DF) is assumed to average 1% from field crop (boom) sprayer applications

Turf transferable residues (TTR) is estimated at 5%, the EPA default value Saliva extraction factor (SE) = 50%, the default value SA = surface area of the hands, the assumption used here is that 20 cm2 of skin area is

contacted each time a child puts a hand into their mouth (this is equivalent to the palmer surface of three fingers and is also related to the next parameter)

Freq = frequency of hand to mouth events per hour – for short term exposures the value of 20 events /hour is used, this is the 90th percentile of observations that range from 0 to 70 events / hour

Exposure duration (H) in hours for a typical day is assumed to be 2 hours, which matches the 75th percentile for toddlers playing on grass in the EPA Exposure Factors Handbook

BW = body weight – assumed to be 15kg for a 2-3 year old toddler

Therefore,SE(h) = (10 x 0.01 x 0.05 x 0.5 x 20 x 20 x 2)/15

= 0.13 μg /kg bw

d) Children’s object-to-mouth exposure:Systemic exposure arising from object to mouth events, SE(o), can be calculated using the equation

SE(o) = (AR x DF x TTR x IgR)/BWWhere,

Field application rate (AR) = 10 μg / cm2

Drift fallout (DF) is assumed to average 1% from field crop (boom) sprayer applications

Turf transferable residues (TTR) is estimated at 5%, the EPA default value IgR is the ingestion rate for mouthing grass/day. This was assumed to be equivalent to

25cm2 of grass / day BW = body weight – assumed to be 15kg for a 2-3 year old toddler

Therefore,


SE(h) = (10 x 0.01 x 0.05 x 25)/15= 0.008 μg /kg bw

e) Children-as-bystander’s total exposure:Children’s total exposure (TE) is estimated as the sum of the dermal, hand-to-mouth and object to mouth exposures i.e.

TE = SE(d) + SE(h) + SE(o)= 0.14 + 0.13 + 0.008 μg /kg bw= 0.28 μg /kg bw

Risk quotient for children = Total Exposure / AOEL= 0.00028 mg/kg bw / 0.018 mg/kg bw/day= 0.02

Therefore, the Agency considers that the risk to children as bystanders arising out of Frontier-P application is low.

Summary and conclusions of the human risk assessmentThe outcome of the quantitative assessment of risks posed to operators and bystanders from the use of Frontier-P indicates that there is a significant risk to operators if full personal protective clothing is not used. This risk is addressed by appropriate labeling requirements and the T5 control.

Bystander risk assessment indicates that Frontier-P, when used as directed on the draft label, does not pose a significant risk to members of the public.

Environmental exposure and risk assessment

Assessment of environmental risks - manufacture, importation, transport and storage

The Agency has qualitatively assessed the risks to the environment of Frontier-P 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 very toxic to the aquatic environment, very toxic to the soil environment 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 Frontier-P and considers the risks to be negligible.


Frontier-P will generally be disposed of by normal use as a herbicide.

If Frontier-P 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 ERMA New Zealand, to determine whether a substance poses an environmental risk are provided in Table A3.3.

Table A3.3: Levels of concern as adopted by ERMA New Zealand.Endpoint LOC PresumptionAquatic (fish, invertebrates)Acute RQ≥ 0.5 High acute riskAcute RQ 0.1-0.5 Risk can be mitigated through restricted useAcute RQ< 0.1 Low risk


Chronic RQ≥ 1 High chronic risk

Plants (aquatic and terrestrial)Acute RQ≥ 1 High acute risk

Mammals and birdsAcute dietary RQ≥

0.5 High acute risk

Acute oral dose [granular products] RQ≥

0.5 High acute risk

Chronic RQ≥ 1 High chronic risk

Aquatic riskAssessment 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 dimethenamid-P 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 A3.4 and represent the recommended use on maize (highest rate) as a conservative estimate.

Table A3.4: Input parameters for GENEEC2 analysis.Dimethenamid-P Reference

Application rate 1.3 L/ha(1 kg ai/ha)

Product label

Application frequency 1 Product label

Application interval N/A

Kd 1.23* Tong & Su, 1997Report No. 97/5180

Aerobic soil DT50 28.69** Sabat & Yu, 1992Report No. 92/12387Krueger & Bade, 1990Report No. 90/11105König, 1995Report No. 95/10128Nietschmann & Yu, 1997Report No. 97/5181

Pesticide wetted in? No Product label

Methods of application AerialGround – (low boom)

Product label

‘No spray’ zone NA

Water solubility 1149 Laster, 1996Report No.96/5411


Aerobic aquatic DT50 33.4 days*** Wyss-Benz & Völkel 1994Report No. 94/10641

Aqueous photolysis DT50

25.7(noon sunlight at 40°N latitude)

Guirguis, 1997Report No.97/5195

*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 28.69 for dimethenamid-P follows the GENEEC2 calculation of the upper 90% confidence limit on the mean value (n≥2) of the four aerobic laboratory values (USEPA, 2001).***Longest value taken in accordance with GENEEC2 guidance document (USEPA, 2001).

Output from the GENEEC2 model.

Aerial application

RUN No. 1 FOR DimethenamidP ON maize * INPUT VALUES * -------------------------------------------------------------------- RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORP ONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN) -------------------------------------------------------------------- .890( .890) 1 1 1.2 1149.0 AERL_B( 13.0) .0 .0

FIELD AND STANDARD POND HALFLIFE VALUES (DAYS) -------------------------------------------------------------------- METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED (FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND) -------------------------------------------------------------------- 28.69 2 N/A 25.70- 3186.80 33.40 33.05

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 -------------------------------------------------------------------- 44.41 43.68 39.56 31.92 27.39

Low boom application

RUN No. 2 FOR DimethenamidP ON Maize * INPUT VALUES *--------------------------------------------------------------------RATE (#/AC) No.APPS & SOIL SOLUBIL APPL TYPE NO-SPRAY INCORPONE(MULT) INTERVAL Kd (PPM ) (%DRIFT) ZONE(FT) (IN)--------------------------------------------------------------------.890( .890) 1 1 1.2 1149.0 GRLOFI( 2.9) .0 .0

FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)--------------------------------------------------------------------METABOLIC DAYS UNTIL HYDROLYSIS PHOTOLYSIS METABOLIC COMBINED(FIELD) RAIN/RUNOFF (POND) (POND-EFF) (POND) (POND)--------------------------------------------------------------------28.69 2 N/A 25.70- 3186.80 33.40 33.05

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--------------------------------------------------------------------41.15 40.43 36.60 29.52 25.33

The Estimated Environmental Concentration (EEC) for dimethenamid-P as estimated by GENEEC2 are: Aerial applicationPeak EEC: 0.04441 mg/LChronic EEC: 0.03956 (21 days)Chronic EEC: 0.02739 (90 days)

Low boom applicationPeak EEC: 0.04115 mg/LChronic EEC: 0.03660 (21 days)Chronic EEC: 0.02533 (90 days)

Assessment of acute risk

Table A3.5: Aquatic ecotoxicity endpoints to be used in risk assessment ( formulation data was used where possible ). Exposure Species LC50 or EC50

(mg formulation/L)LC50 or EC50 (mg a.i./L)

Acute Onchorynchus mykiss 7.94 5.40Daphnia magna 17.1 11.63Lemna gibba 0.054 0.037

Chronic Onchorynchus mykiss* 0.12Daphnia magna* 1.36

*data from active ingredient

The Estimated Environmental Concentration (EEC) for dimethenamid-P as estimated by GENEEC2 are shown in Table 3.6, along with the aquatic data for dimethenamid-P for the most sensitive species tested (further details on these toxicity data are included in Table A2.7). Table A3.6: Acute risk quotients derived from the GENEEC2 model and toxicity data (Aerial application).

Peak EEC from GENEEC2 (mg/L)

LC50 or EC50

(mg ai/L)RQ (Acute)EEC/ LC50 or EC50

Fish 0.04441 5.40 < 0.01Crustacea 11.63 < 0.01Algae 0.037 1.20

Table A3.6A: Acute risk quotients derived from the GENEEC2 model and toxicity data (Low boom application).

Peak EEC from GENEEC2 (mg/L)

LC50 or EC50

(mg ai/L)RQ (Acute)EEC/ LC50 or EC50

Fish 0.04115 6.11 < 0.01Crustacea 13.15 < 0.01


Algae 0.037 1.11

When compared against the relevant acute levels of concern (Table A3.1), the acute RQs derived from the GENEEC2 modeling for dimethenamid-P indicate the following:

Aerial applicationFor fish and crustacean: the acute risk is lowFor algae and aquatic plants: the acute risk is high

Low boomFor fish and crustacean: the acute risk is lowFor algae and aquatic plants: the acute risk is high

Assessment of chronic riskTable A3.7: Chronic risk quotients derived from the GENEEC2 model and chronic aquatic toxicity data (Aerial application).

EEC from GENEEC2 (mg/L)

NOEC(mg/L)

RQ (Chronic)EEC/ NOEC

Fish 0.02739 (90 days) 0.12 0.23Crustacea 0.03956 (21 days) 1.36 0.03

Table A3.7A: Chronic risk quotients derived from the GENEEC2 model and chronic aquatic toxicity data (Low boom application).

EEC from GENEEC2 (mg/L)

NOEC(mg/L)

RQ (Chronic)EEC/ NOEC

Fish 0.02533 (90 days) 0.12 0.21Crustacea 0.03660 (21 days) 1.36 0.03

When compared against the relevant chronic levels of concern (Table A3.3), the chronic RQs derived from the GENEEC2 modelling for dimethenamid-P indicate the following:

Aerial applicationFor fish and crustacean: the chronic risk is lowFor algae: the levels of concern to estimate chronic risks to algae are not

currently defined

Low boomFor fish and crustacean: the chronic risk is lowFor algae: the levels of concern to estimate chronic risks to algae are not

currently defined

Terrestrial risk - Aerial Application

Soil exposure - Seedling EmergenceDimethenamid-P is sprayed at a maximum application rate of 1 kg a.i./ha or 100 mg a.i./m2.


If it assumed that the dimethenamid-P is dispersed to a depth of 0.05 m and the density of soil is 1500 kg/m3, then the 100 mg a.i./m2 dimethenamid-P will be dispersed within 75 kg of soil/m2 giving 1.333 mg/kg.

If it is assumed that 13% of the dimethenamid-P will be uniformly distributed over a 1 ha area outside the target area (an assumption based on GENEEC2 modelling), then the concentration of dimethenamid-P adjacent to a sprayed field would be 0.1733 mg/kg soil.

Dimethenamid-P generates an EC50 value of 0.029 mg/kg, (see Table A2.13B for further details of this study) for lettuce. Consequently, dimethenamid-P results in a risk quotient of 5.98. The risk to non-target plants is high.

Foliar deposition – Vegetative VigourDimethenamid-P is sprayed at a maximum application rate of 1 kg a.i./ha.

If it is assumed that 13% of the dimethenamid-P will be uniformly distributed over a 1 ha area outside the target area (an assumption based on GENEEC2 modelling), then the concentration of dimethenamid-P adjacent to a sprayed field would be 0.13 kg ai/ha.

Dimethenamid-P generates an EC50 value of 0.092 kg ai/ha, (see Table A2.13B for further details of this study) for lettuce. Consequently, dimethenamid-P results in a risk quotient of 1.41. The risk to non-target plants is high.

Terrestrial risk – Low Boom

Soil exposure - Seedling EmergenceDimethenamid-P is sprayed at a maximum application rate of 1 kg a.i./ha or 100 mg a.i./m2.

If it assumed that the dimethenamid-P is dispersed to a depth of 0.05 m and the density of soil is 1500 kg/m3, then the 100 mg a.i./m2 dimethenamid-P will be dispersed within 75 kg of soil/m2 giving 1.333 mg/kg.

If it is assumed that 2.9% of the dimethenamid-P uniformly distributed over a 1 ha area outside the target area (an assumption based on GENEEC2 modelling), then the concentration of dimethenamid-P adjacent to a sprayed field would be 0.039 mg/kg soil.

Dimethenamid-P generates an EC50 value of 0.029 mg/kg, (see Table A2.13B for further details of this study) for lettuce. Consequently, dimethenamid-P results in a risk quotient of 1.333. The risk to non-target plants is high.

Foliar deposition – Vegetative VigourDimethenamid-P is sprayed at a maximum application rate of 1 kg a.i./ha.

If it is assumed that 2.9% of the dimethenamid-P will be uniformly distributed over a 1 ha area outside the target area (an assumption based on GENEEC2 modelling), then the concentration of dimethenamid-P adjacent to a sprayed field would be 0.029 kg ai/ha.

Dimethenamid-P generates an EC50 value of 0.092 kg ai/ha, (see Table A2.13B for further details of this study) for lettuce. Consequently, dimethenamid-P results in a risk quotient of 0.32. The risk to non-target plants is low.


Avian Toxicity - Dimethenamid-P

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 avoid doing detailed evaluations for low risk scenarios while excluding, with sufficient certainty, false negatives (= risk remains undetected).

Acute toxicity

Screening stepStep 1Identify which of the indicator species listed in Table I.1 (Annex I) is relevant to the crop.

Step 2Calculate 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.

The DDD is defined by the food intake rate of the species of concern (i.e., the indicator species, the generic focal species or the focal species), the body weight of the species of concern, the concentration of a substance in/on fresh diet (appendix 14) and the fraction of the diet obtained in the treated area.

The estimated food intake rates are based on the daily energy expenditure of the species of concern, the energy in the food, the ‘energy’ assimilation efficiency of the species of concern, and the moisture content of the food.

The above information is combined into a single value for a specific species-crop-combination and termed a ‘short cut value’.

DDD single application = application rate [kg/ha] x short cut value

Step 3Multiply 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 4Take the appropriate LD50 (mg/kg bw/d) for birds.

Step 5Calculate the toxicity-exposure-ratio


TER = LD50 / DDD

Step 6Compare the TER to the respective trigger value.TER ≥ 10 No refinement requiredTER < 10 Go to first-tier risk assessment (step 7)

Acute toxicityTable A3.8: Acute avian risk assessment – screening step.Crop1 Indicator

Species2Short-cut value3

(90th percentile RUD)

LD504

(mg/kg)Application rate (kg/ha)

MAF905 TER6 Trigger

value

Bulbs and onion like crops

Small granivorous bird

24.7 1068 0.9997 1 43.25 <10

Small omnivorous bird

158.8 6.73 <10

1 Crop type Table I.1 (Annex 1) and Appendix 102 Species type Table I.1 (Annex 1) and Appendix 103 Residue Unit Dose (90th percentile) Table I.1 (Annex 1)4 Geometric mean if multiple species tested5 Multiple application factor (90th percentile) Table 11 and Appendix 156 Toxicity-exposure ratio = LD50 / Estimated environmental concentration

Based upon the acute toxicity screening step, dimethenamid-P as a component of Frontier-P applied according to the manufacturer’s instructions, may be acutely toxic to birds. The risk assessment requires the refinement of a tier 1 assessment.

First-tier risk assessmentStep 7Identify all of the generic focal species listed in Table I.3 (annex I) that are relevant for the crop.

Step 8Calculate the daily dietary dose (DDD) for a single application for each generic focal species by multiplying the shortcut value presented in Table I.3 with the application rate in kg/ha.

DDD single application = application rate [kg/ha] x short cut value

Step 9Multiply the DDD 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 (see Table 11). Or calculate a specific MAF90 according to Appendix 15 for non-standard application intervals.

DDD multiple applications = DDD single application x MAF90

Step 10Take the appropriate LD50 for birds (as in step 4).


Step 11Calculate the toxicity exposure ratio:

TER = LD50 / DDD

Step 12Compare the TER to the respective trigger.

All TERs ≥ 10 No refinement requiredOne or more of the TERs < 10 Higher tier risk assessment required.

Acute avian risk assessment – Refining step (Tier 1)Table A3.9: Summary of values applied in the phase specific approach (bulbs and onion-like crops).CropStage

IndicatorSpecies

Short-cut value(Mean RUD)

LD504

(mg/kg)Application rate (kg/ha)

MAF905 TER6 Trigger

value

BBCH 10-39

Finch 24.7 1068 0.9997 1 43.25 <10

BBCH10-19

Lark 24 44.51 <10

BBCH10-19

Wagtail 26.8 39.86 <10

Based upon the refined risk assessment for acute toxicity (Tier 1), dimethenamid-P as a component of Frontier-P applied according to the manufacturer’s instructions, is unlikely to be acutely toxic to birds.

Chronic toxicitySteps to determine the reproductive risk to birdsIt 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 hence for which no further reproductive risk assessment is required.

Step 1Determine if breeding birds will be exposed to either the active substance or the associated product.

Step 2If 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 3Identify 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 4Compare the lowest NOAEL to the DDD generated.

TER ≥ 5 No refinement requiredTER< 5 Go to phase-specific approach (step 5)

Chronic toxicityTable A3.10: Chronic avian risk assessment – screening step.Crop1 Indicator

Species2Short-cut value3

(Mean RUD)

NOAEL4

mg ai/kg bw/dApplication rate (kg/ha)

MAFm5 TER6 Trigger

value

Bulbs and onion like crops

Small granivorous bird

11.4 174.69 0.9997 1 15.33 <5

Small omnivorous bird

64.8 2.69

1 Crop type Table I.1 (Annex 1) and Appendix 102 Species type Table I.1 (Annex 1) and Appendix 103 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 156 Toxicity-exposure ratio = LD50 / Estimated environmental concentration

Based upon the chronic toxicity screening step, dimethenamid-P as a component of Frontier-P 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 5In 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; and5) 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 6Once 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 7If more than one study is available, then the datasets can be either merged or the geometric mean of the endpoints used.

Step 8In 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 9In 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-dayPeriod;

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 10Once 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 rate x short-cut x TWA x MAFm

Step 11In 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 12Compare the above DDD to the relevant phase-specific NOAEL.

Step 13Interpret the risk assessment following the below table.

Scenario Assessment outcome1 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.

Chronic avian risk assessment – Refining step (Tier 1)Table A3.11: Summary of values applied in the phase specific approach.Species Short-cut

value (Mean RUD)

Application rate (kg/ha)

MAFm TWA2 days

TWA 3 days

TWA 21 days

Chick short-cut value3 days

Chick short-cut value21 days

Finch 11.4 0.9997 1 0.93 0.9 0.53 3.8 22.7Lark 10.9Wagtail 11.3

Table A3.12: Summary of toxicity values applied in the phase specific approach.LD50 NOAEL1 NOAEL2 NOAEL3 NOAEL4 NOAEL5 NOAEL6

GeometricMean

1068 238.58 174.69 238.58 238.58 242.11 242.11

NOAEL1 number of eggs laid per hen NOAEL2 mean egg shell thicknessNOAEL3 proportion of viable eggs set per henNOAEL4 proportion of hatchling per viable eggs per henNOAEL5 proportion of 14 day old juveniles per number of hatchlings per henNOAEL6 14 day juvenile weights per hen

Note: Geometric mean of data used (where more than one study available).


Table A3.13: Pair formation and establishing site selection. Short term Long termLD50/10 and 1 day DDD LD50/10 and 21 day TWA DDD

Finch TER 9.37 17.68Lark TER 9.80 18.49Wagtail TER 9.45 17.84Trigger level < 5

Table A3.14: Copulation and egg laying. Short term Long termNOAEL1 and 1 day DDD

NOAEL2 and 1 day DDD

NOAEL1 and 21 day TWA DDD


Finch TER

20.93 15.33 39.50 28.92

Lark TER

21.90 16.03 41.31 30.25

Wagtail TER

21.12 15.46 39.85 29.18

Trigger level

< 5

Table A3.15: Incubation and hatching. Short term Long termLD50/10 and 1 day DDD



LD50/10 and 21 day TWA DDD



Finch TER

9.37 20.93 23.26 17.68 39.5 39.5

Lark TER

9.80 21.90 24.33 18.49 41.31 41.31

Wagtail TER

9.45 21.12 23.47 17.84 39.85 39.85

Trigger level

< 5

Table A3.16: Juvenile growth and survival. Short term Long termLD50/10 and 2 day TWA DDD

LD50/10 and 1 day DDDChick ground dwelling insects value

LD50/10 and 1 day DDDChick foliar dwelling insects value

NOAEL5

and 3 day TWA DDD

LD50/10 and 21 day TWA DDD

LD50/10 and 21 day DDDChick ground dwelling insects value


NOAEL5

and 21 day TWA DDD

Finch TER

10.08 28.11 4.71 23.60 17.68 53.04 8.88 40.08

Lark 10.54 28.11 4.71 24.69 18.49 53.04 8.88 41.92


TERWagtail TER

10.17 28.11 4.71 23.81 17.84 53.04 8.88 40.44

Trigger level

< 5

Table A3.17: Post-fledgling survival. Short term Long termLD50/10 and 1 day DDDChick ground dwelling insects value



LD50/10 and 21 day TWA DDDChick ground dwelling insects value

LD50/10 and 21 day TWA DDDChick foliar dwelling insects value


Finch TER

28.11 4.71 23.60 53.04 8.88 40.08

Lark TER

28.11 4.71 24.69 53.04 8.88 41.92

Wagtail TER

28.11 4.71 23.81 53.04 8.88 40.44

Trigger level

< 5

Based upon the refined risk assessment for chronic toxicity (Tier 1), dimethenamid-P as a component of Frontier-P applied according to the manufacturer’s instructions, may be chronically toxic to chicks and post-fledgling birds. However, the use pattern of the product is limited to one application per year and output of the modelling shows that the risk appears to be evident for a short duration only. It has been noted by the Agency that the TERs for short-term juvenile survival and short-term fledgling survival feeding exclusively on foliar dwelling insects are based on the daily dietary dose (DDD) which assumes the initial exposure estimate.

To calculate the 2 day DDD it is necessary to multiply the initial exposure (DDD) by a time-weighted average (TWA) factor. For 2 days, the factor is 0.93 – when this value is factored into the equation the TER for the above-described scenarios is > 5 indicating no risk to juvenile or fledgling birds. This calculation indicates that the risk to these birds is transient to the day of application only.

In addition, the above calculation assumes that the proportion of an animal’s daily diet obtained in habitat treated with pesticide = 1. In reality, birds may visit a variety of habitats may obtain their food from a variety of fields rather than the specifically treated field. Given the closeness of the TER to the cut-off, it is not unreasonable to assume that a small variation in dietary source will also equate to the low risk threshold being achieved.

Further, registrations in other jurisdictions (EU, USA, Australia and Canada), using different assessment modelling, have not predicted any chronic effects to birds. However, as a precautionary measure, the Agency considers that the application rate proposed by the applicant and used in the modelling should be set as a maximum application rate.


Risk to Terrestrial Invertebrates (Bees)

The terrestrial invertebrate risk assessment for agricultural pesticides determines whether or not the proposed application poses an unacceptable risk to terrestrial invertebrates (bees).

The following European model has been adopted by ERMA New Zealand to assess the risk to bees [Guidance Document on terrestrial ecotoxicology under Council Directive 91/414/EEC, SANCO/ 10329/2002 rev. 2 final, 17 October 2002].

Hazard Quotient (HQ) = Application Rate / LD50

4.88 = 1000 / 205

Application rate: the maximum single application rate (g active ingredient/ha).

LD50: µg active ingredient/bee.

Conclusion:Based on the HQ, when dimethenamid-P is applied at 1 kg a.i./ha the risk to bees will be negligible.

Risk to Beneficial InvertebratesTable A3.18: Summary of terrestrial invertebrate (beneficial insects) toxicity data for Frontier-P (BAS 656 07 H).

Test species Test resultsa, b Test methodc

[Reference number]Formulation

Predatory miteTyphlodromus pyri

BAS 656 07 H [L/ha]Effect Control 0.0084 0.14 1.4Mortality [%] 9.0 9.0 10.0 19.0Mortality corrected [%]

- 0.0 1.1 11.0

Mean no. offspring/female(+7 to +14)

8.3 7.4 6.4 6.1

Mean no. offspring/female/day

1.19 1.06 0.91 0.87

Total Effect [%] 10 20.9 37.7

Conclusion:Not expected to cause adverse effects up to 1.4 L/ha application rate.

Kühner, 1998Louis/Ufer 1995(ESCORT 1994)Report No. 98/1127GLPKlimisch score: 1

Ground beetlePoecilus cupreus BAS 656 07 H

[L/ha]Effect Control 1.4Mortality [%] 0 0Mortality corrected [%]

- 0

Feeding capacity 4.40 3.93

Kühner, 1998BBA VI 23-2.1.8ESCORT 1994Report No. 98/1127GLPKlimisch score: 1


Test speciesTest resultsa, b

Test methodc

[Reference number]

(Mean/replicate)R in % - 10.61


Green lacewingChrysoperla carnea

BAS 656 07 H [L/ha]

Effect Control 1.4Mortality [%] 4.4 8.9Mortality corrected [%]

- 4.7

Mean no. fertile eggs/female/day

23.8 25.5

Reproductive effect in %

-7.1

Total Effect [%] -2.0


Kühner, 1998Bigler 1988ESCORT 1994Report No. 98/11334GLPKlimisch score: 1

Wolf spiderPardosa spec. BAS 656 07 H

[L/ha]Effect Control 1.4Mortality corrected [%]

6.7 -7.2

Food consumption [%]

100 106


Schmitzer, 1999BBA draft 1994Report No. 99/10751GLPKlimisch score: 1

Staphylinid beetleAleochara bilineata

BAS 656 07 H [L/ha]

Effect Control 1.4Mean no offspring per replicate

680 + 33.8 659 + 75.9

Reproductive effect [%]

- 3


Kemmeter, 1999Moreth & Naton 1992ESCORT 1994Report No. 99/10856GLPKlimisch score: 1

Parasitic waspAphidius rhopalosiphiTier 1 Test

BAS 656 07 H [L/ha]

Effect Control 1.4Mortality [%] 2.5 100

Kühner, 1998Polgar 1988Mead-Briggs1992ESCORT 1994Report No. 98/11334


Test speciesTest resultsa, b

Test methodc

[Reference number]Mortality corrected

[%]- 100

Conclusion: Frontier-P has significant effects on the mortality of the parasitic wasp Aphidius rhopalosiphi. Due to the high mortality a reproductive test was not conducted.

GLPKlimisch score: 1

Parasitic waspAphidius rhopalosiphiTier 2 Test

BAS 656 07 H [L/ha]Effect Control 0.14 1.4

Mortality [%] 5.0 2.8 5.0Mortality corrected [%]

- -2.3 0

Mean no. mummies /female

10.0 7.7 5.41

Reproduction factor - 0.77 0.54

1significantly different to the control (p<0.05)

46 % reduction in reproductive potential. Conclusion:As the reduction in reproductive potential is < 50%, Frontier-P is not expected to cause adverse effects up to 1.4 L/ha (1 kg ai/ha) application rate.

Schuld, 1999Mead-Briggs (1996)ESCORT 1994Report No. 99/10669GLPKlimisch score:

Risk assessmentIn tier 1 testing, Frontier-P caused 100% mortality to the parasitic wasp, Aphidius rhopalosiphi at the maximum recommended application rate of 1.4 L/ha. Higher tier testing using a natural substrate resulted in < 10% mortality and < 50% reduction in reproductive potential. Therefore, Frontier-P is not expected to cause significant adverse effects to beneficial insects at the New Zealand application rates of 1.4 1.3 L/ha (1 kg a.i/ha).

Tier 1 testing of Typhlodromus pyri, Poecilus cupreus, Chrysoperla carnea, Pardosa spec., and Aleochara bilineata at application rates ≤ 1.4L/ha showed negligible adverse effects.

Volatilisation/EvaporationFinal remaining soil radioactivity (SAN 582 H) at the end of the pre-plant incorporated study was 97.7%. 0.84% of the applied labeled dimethenamid volatilised from the soil (30 days).

Final remaining soil radioactivity at the end of topical (surface applied) study was 96.6%. 1.18% of the applied labeled dimethenamid volatilized from the soil (30 days).

Volatility is an insignificant route in the degradation and environmental dissipation of SAN 582 H.

Chen & Hsieh, 1993


Report No. 93/11472Internal protocolGLPKlimisch score: 1

The volatilisation rate of dimethenamid (SAN 582 H) from soil or plants was below 20% of the applied dose. The total amount of volatilised test substance amounted to 6.61% of applied radiocarbon for soil, and 14.1% of applied radiocarbon for plants. The main portion of evaporated dimethenamid was found in the condensate, 4.95% and 13.01%, respectively.

Jonas, 1994Report No. 94/10642BBA Part IV, 6-1GLPKlimisch score: 1

Conclusion:Based on the above studies the risk of long range transport of dimethenamid would be negligible.

Summary and conclusions of the ecological risk assessmentBased on the risk assessment for the aquatic and terrestrial environment as set out above, risks to the following species groups have been identified.

Aerial applicationAquatic plants (Acute risk)Based on the acute RQs for algae, the Agency considers it is appropriate to retain the approved handler controls for Frontier–P when it is used in a wide dispersive manner, or by a commercial contractor for aerial operations.

Terrestrial plants (Soil and foliar deposition)Based on the RQs for both soil and foliar deposition on plants, the Agency considers it is appropriate to retain the approved handler controls for Frontier–P when it is used in a wide dispersive manner, or by a commercial contractor for aerial operations.

Low boom applicationAquatic plants (Acute risk)Based on the acute RQs for algae, the Agency considers it is appropriate to retain the approved handler controls for Frontier–P when it is used in a wide dispersive manner, or by a commercial contractor for ground applications.

Terrestrial plants (Soil deposition)Based on the RQs for soil deposition effects on plants, the Agency considers it is appropriate to retain the approved handler controls for Frontier–P when it is used in a wide dispersive manner, or by a commercial contractor for ground applications.

Further to the approved handler control, the Agency considers that the application rate proposed by the applicant and used in the modelling should be set as a maximum application rate.


For specific information on the controls set see Appendix 4.

ReferencesEPPO 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 33http://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

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://www.epa.gov/oppefed1/models/water/index.htm#geneec2

http://ec.europa.eu/food/plant/protection/evaluation/guidance/wrkdoc09_en.pdf

http://archives.eppo.org/EPPOStandards/PP3_ERA/pp3-10(2).pdf

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 codes12, are listed in Table A4.1.

Table A4.1: List of default controls for Frontier-PToxicity ControlsT1 Limiting exposure to toxic substances through the setting of TELsT2 Controlling exposure in places of work through the setting of WESsT4 Requirements for equipment used to handle substancesT5 Requirements for protective clothing and equipmentT7 Restrictions on the carriage of toxic or corrosive substances on passenger service vehiclesEcotoxicity ControlsE1 Limiting exposure to ecotoxic substances through the setting of EELsE2 Restrictions on use of substances in application areasE5 Requirements for keeping records of useE6 Requirements for equipment used to handle substancesE7 Approved handler/security requirements for certain ecotoxic substancesIdentification ControlsI1 Identification requirements, duties of persons in charge, accessibility, comprehensibility,

clarity and durabilityI3 Priority identifiers for ecotoxic substancesI8 Priority identifiers for toxic substancesI9 Secondary identifiers for all hazardous substancesI11 Secondary identifiers for ecotoxic substancesI16 Secondary identifiers for toxic substancesI17 Use of generic namesI18 Requirements for using concentration rangesI19 Additional information requirements, including situations where substances are in

multiple packagingI20 Durability of information for class 6.1 substancesI21 General documentation requirementsI23 Specific documentation requirements for ecotoxic substancesI28 Specific documentation requirements for toxic substancesI29 Signage requirementsI30 Advertising corrosive and toxic substancesPackaging ControlsP1 General packaging requirementsP3 Criteria that allow substances to be packaged to a standard not meeting Packing Group I,

II or III criteriaP13 Packaging requirements for toxic substancesP15 Packaging requirements for ecotoxic substancesPG3 Packaging requirements equivalent to UN Packing Group IIIPS4 Packaging requirements as specified in Schedule 4Disposal ControlsD4 Disposal requirements for toxic or corrosive substances

12 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.


D5 Disposal requirements for ecotoxic substancesD6 Disposal requirements for packagesD7 Information requirements for manufacturers, importers and suppliers, and persons in

chargeD8 Documentation requirements for manufacturers, importers and suppliers, and persons in

chargeEmergency Management ControlsEM1 Level 1 information requirements for suppliers and persons in chargeEM6 Information requirements for toxic substancesEM7 Information requirements for ecotoxic substancesEM8 Level 2 information requirements for suppliers and persons in chargeEM11 Level 3 emergency management requirements: duties of person in charge, emergency

response plans EM12 Level 3 emergency management requirements: secondary containmentEM13 Level 3 emergency management requirements: signageTracking ControlsTR1 General tracking requirementsApproved Handler ControlsAH1 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.

Where a substance is a pesticides or veterinary medicines active ingredient that is new to New Zealand and it is intended for use on a food crop or animal, the Agency will propose an ADE regardless of whether the requirements of Regulation 11 are met as this information may be of use to NZFSA in setting MRLs.

The Agency considers that the active 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 Frontier–P. Noting that Frontier–P is intended for use on food crops and contains dimethenamid-P, 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 is needed.


On review of the relevant toxicology data, the Agency considers that an ADE of 0.018 mg/kg bw/day should be adopted for dimethenamid-P. Based on this value, and considering the main ingestion exposure to dimethenamid-P would be via food stuff (70%), drinking water (20%) and other non-foodstuffs (10%), the Agency proposes that PDEfood = 0.013 mg/kg bw/day and PDEdrinking water = 0.004 mg/kg bw/day should be set for dimethenamid-P.

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 at this time Department of Labour WES values have been set for components C2 and C6 in Frontier–P. Both values are set at 52 mg/m3 air (time-weighted average). However, the Agency notes that these WES values are of little relevance to Frontier-P as their concentration is too low for the WES to be applicable. The Agency further notes that a WES value of 100 mg/m3 has bee set in the European Union for component A3. Again this WES is not relevant to Frontier-P as the component is present at a low concentration.No WES values have been set for the active by any overseas body monitored by the Agency.

Setting of EELs (Control code E1)


http://www.osh.govt.nz/order/catalogue/pdf/wes2002.pdf

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 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 Frontier–P 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 Frontier–P 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 adverse environmental effects on aquatic and terrestrial plants 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 Frontier–P as a result of its 9.1A and 9.2A classifications. However, for substance 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, labelling 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 Frontier–P, the Agency proposes setting the application rate of 1 kg ai/ha*, once per season as the application rate for Frontier–P. This rate was used in the ecological risk assessment.

*Note: the Agency has assumed that the purity of the active ingredient to be 100% to take the toxicity of any impurities into account considered the purity of the technical grade active ingredient used in the formulation of Frontier-P so as to take into account the toxicity of the impurities.

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 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 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 0.16.6B 1 16.7B 1 0.16.8A, 6.8C 0.3 0.16.8B 3 0.16.9A, 6.9B 10 1

Frontier–P - 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 DocumentationDimethenamid-P, Dimethenamid-P, A6


APPENDIX 5: LIST OF PROPOSED CONTROLS FOR FRONTIER-PTable A5.1: Proposed controls for Frontier-P – codes, regulations and variations.Control Code13

Regulation14

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 dimethenamid-P:

ADE = 0.018 mg/kg bw/day

PDEfood = 0.013 mg/kg bw/ day

PDEwater = 0.004 mg/kg bw/day T2 29, 30 Controlling exposure in places of

workNo WES values are set for components in this substance at this time.

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

The maximum quantity of substance allowed is varied from 0.1 L to 1 L.

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.

E5 5(2), 6 Requirements for keeping records of use.

E7 9 Approved handler requirements The following control is substituted for Regulation 9(1) of the Hazardous Substances (Classes 6, 8, and 9 Controls) Regulations 2001:

(1). The substance must be under

13 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.14 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 Code

Regulation Topic Variations

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.

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

Revised cut-offs for component labelling required by Regulation 25(e)

HSNO Classification of Component

Concentration Cut-off for Label (%)

6.5A, 6.5B 0.115

6.6A, 6.7A 0.1

6.6B, 6.7B 1

6.8A, 6.8C 0.3

I17 26 Use of Generic Names

I18 27 Use of Concentration Ranges

15 Identification of sensitising components may be required below the 0.1% level if a lower value has been used for classification.


Control Code


6.8B 3

6.9A, 6.9B 10

For more information about this variation see paragraph 10.8 of the main document.

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 class 6.1 substances

I21 37-39, 47-50

Documentation required in places of work

Regulation 37 – Documentation duties of suppliers

Regulation 38 – Documentation 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

Regulation 49 – Documentation requirements for vehicles

Regulation 50 – Documentation to be supplied on request

I23 41 Specific documentation requirements for ecotoxic substances

I28 46 Specific documentation


Control Code


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 quantities

P13P15

1921

Packaging requirements for Frontier-P

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

D4D5

89

Disposal requirements for Frontier-P

Controls D4 and D5 are combined

D6 10 Disposal requirements for packagesD7 11, 12 Disposal information requirementsD8 13, 14 Disposal documentation

requirementsHazardous 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- Level 2 emergency management


Control Code


20 documentation requirementsEM11 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

(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.


(2) If pooling substances that 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


Control Code


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.


(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:


Control Code


(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 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.

Frontier-P shall not be applied onto or into water.

The maximum application rate for Frontier-P shall be 1.3 L/ha (0.936 kg dimethenamid-P/ha) with a maximum application frequency of 1 application per year.


APPENDIX 6: SCALES FOR QUALITATIVE RISK ASSESSMENT

Qualitative descriptors are indicative only and they are primarily intended to be used to rank risks and benefits for the purposes of balancing risks and costs against benefits, and so that risks can be prioritised for management. The ‘descriptor’ words should not be seen in any absolute senses – they are simply a means of differentiating levels of significance.

Assessing risks, costs and benefits qualitativelyThis 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).

Describing the magnitude of effectThe 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 A6.1 and A6.2 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 A6.1: Magnitude of adverse effect (risks and costs)Descriptor Examples of descriptions - ADVERSEMinimal 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 groupsLocalised 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 lossesSocial disruption to surrounding community, including some evacuations

Massive Significant irreversible adverse health effects reaching beyond the immediate community and/or deathsExtensive 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 A6.2: Magnitude of beneficial effect (benefits).

Descriptor Examples of descriptions -BENEFICIALMinimal 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 impactLocal/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 groupsLocalised 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 communityLong 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 ecosystemsSignificant on-going effect beneficial on GDP, long term job creation on a national basis Major social benefit affecting wider community

Determining the likelihood of the end effectLikelihood in this context 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 the likelihood of the specified adverse effect16 resulting from that initiating event. It will be a combination of the likelihood of the initiating event and several

16 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.


intermediary likelihoods17. 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). (See Table A6.3).Table A6.3: Using magnitude and likelihood to construct the level of risk and benefit

Descriptor Description

Highly improbable Almost certainly not occurring but cannot be totally ruled outVery unlikely Considered only to occur in very unusual circumstancesUnlikely (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 effect can be constructed.

Determining the level or risk/benefitIn the example shown in Table 6.4, 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 A6.4: Level of risk.

Magnitude of effect

Likelihood Minimal Minor Moderate Major MassiveHighly improbable A A A B BVery unlikely A A B B CUnlikely A B B C CLikely B B C C DHighly likely B C C D D

17 Qualitative event tree analysis may be a useful way of ensuring that all aspects are included.


APPENDIX 7: GOVERNMENT DEPARTMENTS, CROWN ENTITIES AND INTERESTED PARTIES NOTIFIED Aakland Chemicals (1997) LimitedAgBio Research LimitedAgcarm IncorporatedAgResearch LimitedAgronica New Zealand LimitedARPPABALDWINSBASF New Zealand LimitedBayer New Zealand LimitedBOC LimitedChancery GreenChemagro New Zealand LimitedChemsafety LimitedCrown Public HealthCSD Consultancy LtdDuPont (New Zealand) LimitedFar North District CouncilFederated Farmers of New Zealand (Incorporated)Fish and Game Eastern RegionGreater Wellington - The Regional CouncilGreen Party of Aotearoa New ZealandHawkes Bay Regional CouncilIMCD New Zealand LimitedKaipara District CouncilKawerau District CouncilLandcorp Farming LimitedLowndes AssociatesMAF Biosecurity New Zealand (MAFBNZ)Ministry of Research Science and Technology (MoRST)Napier Health Centre - Public Health UnitNew Zealand Bee Industry Group - Federated FarmersNew Zealand Chemical Industry Council IncNew Zealand Customs ServiceNew Zealand Meatworkers UnionNew Zealand Press AssociationNew Zealand Society of Gunsmiths IncNgati Kahungunu Iwi IncorporatedNorthland HealthNufarm New Zealand LimitedPacific Building Steel GroupPacific Growers Supplies Limited


Pesticide Action Network Aotearoa New ZealandPharmVet SolutionsPhysicians and Scientists for Global Responsibility (PSGR)Rangitikei District CouncilReckitt BenckiserSouth Taranaki District CouncilSustainability Council of New ZealandSyngenta Crop Protection LimitedTaranaki Regional CouncilTasman District CouncilTechnical Strategy Group LimitedTelevision New ZealandThe National Beekeepers Association of New ZealandThe New Zealand Institute for Plant and Food Research LimitedTMP ConsultancyWellington City CouncilZelam Limited6 Private Individuals


APPENDIX 8: CONFIDENTIAL MATERIAL


Documents

E&R Template - Release - EPA · Web viewFood consumption of the parent animals in both the P and F1 generations at 100 and 500 ppm and of the females of the F1 generation at 2000ppm;