Public Release Summary
on the evaluation of the new active mandestrobin
in the product Intuity Fungicide
APVMA Product Number 69787
JULY 2016
© Australian Pesticides and Veterinary Medicines Authority 2016
ISSN: 1443-1335 (electronic)
ISBN: 978-1-925390-41-4 (electronic)
Ownership of intellectual property rights in this publication
Unless otherwise noted, copyright (and any other intellectual property rights, if any) in this publication is owned by the Australian Pesticides and Veterinary Medicines Authority (APVMA).
Creative Commons licence
With the exception of the Coat of Arms and other elements specifically identified, this publication is licensed under a Creative Commons Attribution 3.0 Australia Licence. This is a standard form agreement that allows you to copy, distribute, transmit and adapt this publication provided that you attribute the work.
A summary of the licence terms is available from www.creativecommons.org/licenses/by/3.0/au/deed.en. The full licence terms are available from www.creativecommons.org/licenses/by/3.0/au/legalcode.
The APVMA’s preference is that you attribute this publication (and any approved material sourced from it) using the following wording:
Source: Licensed from the Australian Pesticides and Veterinary Medicines Authority (APVMA) under a Creative Commons Attribution 3.0 Australia Licence.
In referencing this document the Australian Pesticides and Veterinary Medicines Authority should be cited as the author, publisher and copyright owner.
Use of the Coat of Arms
The terms under which the Coat of Arms can be used are set out on the Department of the Prime Minister and Cabinet website (see www.dpmc.gov.au/pmc/publication/commonwealth-coat-arms-information-and-guidelines).
Disclaimer
The material in or linking from this report may contain the views or recommendations of third parties. Third party material does not necessarily reflect the views of the APVMA, or indicate a commitment to a particular course of action.
There may be links in this document that will transfer you to external websites. The APVMA does not have responsibility for these websites, nor does linking to or from this document constitute any form of endorsement.
The APVMA is not responsible for any errors, omissions or matters of interpretation in any third-party information contained within this document.
Comments and enquiries regarding copyright:
Director Public Affairs and Communication
Australian Pesticides and Veterinary Medicines Authority
PO Box 6182
KINGSTON ACT 2604 Australia
Telephone: +61 2 6210 4812
Email:
This publication is available from the APVMA website: www.apvma.gov.au.
JULY 2016
Contents iii
Contents
Preface v
About this document v
Making a submission v
Further information vi
1 Introduction 1
1.1 Applicant 1
1.2 Details of the product 1
1.3 Resistance management 1
1.4 Overseas registrations 1
2 Chemistry and manufacture 2
2.1 Active constituent 2
2.2 Product 6
3 Toxicological assessment 8
3.1 Evaluation of toxicology 8
3.2 Public health standards 10
4 Residues assessment 11
4.1 Introduction 11
4.2 Metabolism 11
4.3 Analytical methods 14
4.4 Residue definition 14
4.5 Residue trials 15
4.6 Animal commodity MRLs 15
4.7 Estimated dietary intake 15
4.8 Fat solubility and bioaccumulation potential 15
4.9 Spray drift 15
4.10 Recommendations 16
5 Assessment of overseas trade aspects of residues in food 17
5.1 Commodities exported 17
5.2 Destination of exports 17
5.3 Proposed use pattern 18
5.4 Comparison of Australian MRLs with Codex and International MRLs 19
5.5 Potential risk to trade 19
Contents iii
6 Occupational health and safety assessment 20
6.1 Health hazards 20
7 Environmental assessment 22
7.1 Introduction 22
7.2 Environmental fate 22
7.3 Environmental effects 23
7.4 Risk Assessment 24
8 Efficacy and safety assessment 25
8.1 Proposed product use pattern 25
8.2 Summary of evaluation of efficacy and crop safety 25
8.3 Conclusions 26
9 Labelling requirements 27
Abbreviations 31
Glossary 35
References 36
List of tables
Table 1: Major destinations for Australian stone fruit exports 18
Preface v
Preface
The Australian Pesticides and Veterinary Medicines Authority (APVMA) is the Australian Government regulator with responsibility for assessing and approving agricultural and veterinary chemical products prior to their sale and use in Australia.
In undertaking this task, the APVMA works in close cooperation with advisory agencies, including the Department of Health and Ageing, Office of Chemical Safety (OCS), Department of the Environment, and State Departments of Primary Industries.
The APVMA has a policy of encouraging openness and transparency in its activities and of seeking community involvement in decision making. Part of that process is the publication of Public Release Summaries for products containing new active constituents.
The information and technical data required by the APVMA to assess the safety of new chemical products, and the methods of assessment, must be consistent with accepted scientific principles and processes. Details are outlined in the APVMA’s website at: www.apvma.gov.au.
This public release summary is intended as a brief overview of the assessment that has been conducted by the APVMA and of the specialist advice received from its advisory agencies. It has been deliberately presented in a manner that is likely to be informative to the widest possible audience thereby encouraging public comment.
About this document
This is a public release summary.
It indicates that the APVMA is considering an application for registration of an agricultural or veterinary chemical. It provides a summary of the APVMA’s assessment, which may include details of:
· the toxicology of both the active constituent and product
· the residues and trade assessment
· occupational exposure aspects
· environmental fate, toxicity, potential exposure and hazard
· efficacy and target crop or animal safety.
Comment is sought from interested stakeholders on the information contained within this document.
Making a submission
In accordance with sections 12 and 13 of the Agvet Code, the APVMA invites any person to submit a relevant written submission as to whether the application for approval of mandestrobin and registration of Intuity Fungicide should be granted. Submissions should relate only to matters that the APVMA is required, by legislation, to take into account in deciding whether to grant the application. These matters include aspects of public health, occupational health and safety, chemistry and manufacture, residues in food, environmental safety, trade, and efficacy and target crop or animal safety. Submissions should state the grounds on which they are based. Comments received that address issues outside the relevant matters cannot be considered by the APVMA.
Submissions must be received by the APVMA by close of business on Tuesday 9 August 2016 and be directed to the contact listed below. All submissions to the APVMA will be acknowledged in writing via email or by post.
Relevant comments will be taken into account by the APVMA in deciding whether the active constituent should be approved and/or whether the product should be registered and in determining appropriate conditions of registration and product labelling.
When making a submission please include:
· contact name
· company or group name (if relevant)
· email or postal address (if available)
· the date you made the submission.
All personal information, and confidential information judged by the APVMA to be confidential commercial information (CCI)[1] contained in submissions will be treated confidentially.
Written submissions on the APVMA’s proposal to grant the application for registration that relate to the grounds for registration should be addressed in writing to:
Case Management and Administration Unit
Australian Pesticides and Veterinary Medicines Authority
PO Box 6182
Kingston ACT 2604
Phone: +61 2 6210 4701
Fax: +61 2 6210 4721
Email:
Further information
Further information can be obtained via the contact details provided above.
Further information on public release summaries can be found on the APVMA website: www.apvma.gov.au
Introduction 1
1 Introduction
This publication provides a summary of the data reviewed and an outline of the regulatory considerations for the proposed registration of Intuity Fungicide, and approval of the new active constituent, mandestrobin.
1.1 Applicant
Sumitomo Chemical Australia Pty Limited.
1.2 Details of the product
The APVMA is considering the proposal to register Intuity Fungicide, containing 250 g/L mandestrobin, as a suspension concentrate formulation. It is intended for control of blossom blight and brown rot in stone fruit. Intuity will be applied at a rate of 120 mL/100 L. A maximum of two applications are allowed on stone fruit per season.
The active constituent mandestrobin is a racemic mixture of two stereoisomers. It has been demonstrated that only the R-isomer has significant fungicidal activity.
1.3 Resistance management
Mandestrobin, a new active to the Australian market, is a strobilurin fungicide, belonging to the sub-class methoxy-acetamide. Mandestrobin is a Quinone outside Inhibitor (QoI) of fungal pathogens. The Fungicide Resistance Action Committee (FRAC), a specialist technical group of CropLife International, has designated mandestrobin as a Group 11 fungicide.
The maximum number of applications that may be applied per season is two, with a minimum interval of 14days between applications.
1.4 Overseas registrations
Health Canada’s Pest Management Regulatory Agency (PMRA) has granted full registration for mandestrobin and four associated end-use products for the management of various fungal diseases in canola and other oilseed crops, corn, grape, legume vegetables, strawberry and other low growing berries, as well as turfgrass.
The European Commission has authorised the use of mandestrobin in the European Union for the management of sclerotinia rot in winter oilseed (canola).
Chemistry and manufacture 7
2 Chemistry and manufacture
2.1 Active constituent
Chemical characteristics of active constituent
Common Name (ISO): / MandestrobinIUPAC Name: / (RS)-2-methoxy-N-methyl-2-[α-(2,5-xylyloxy)-o-tolyl] acetamide
2-[2-(2,5-Dimethylphenoxymethyl)phenyl]-2-methoxy-N-methylacetamide
CAS Name: / 2-[(2,5-dimethylphenoxy)methyl]-α-methoxy-N-methylbenzeneacetamide
Manufacturer’s code/s / S-2200
CAS Registry Number: / 173662-97-0
MINIMUM PURITY: / 940 g/kg
MOLECULAR Formula: / C19H23NO3
Molecular Weight: / 313.39
Chemical characteristics of active constituent, continued
STRUCTURE: / S-2200 R isomer S-2200 S-isomerCHEMICAL FAMILY: / Strobilurin—methoxy-acetamide
Physico-chemical properties of active constituent
Physical Form: / Crystalline powdery solidColour: / White
Odour: / Odourless
MELTING POINT: / 1020C (mean of three determinations)
BOILING Point: / 2960C (mean of three determinations)
RELATIVE Density: / 1.205 (range 1.2009 to 1.2026) at 200C
SOLUBILITY : / 15.8 mg/L at 200C
SOLVENT SOLUBILITY at 200C / Acetone 310 g/L
Dichloromethane 480 g/L
Ethyl acetate 186 g/L
Hexane 2.49 g/L
Methanol 217 g/L
n-Octanol 30.8 g/L
Toluene 128 g/L
Vapour Pressure at 20oC: / 3.36 x 10-8 Pa
HYDROLYSIS RATE: / Both the R-isomer and S-isomer were stable to hydrolysis at pH 4, 7 and 9. No degradation products were detected and no interconversion between the R and S isomers was observed.
DT50 at pH 4, 7 and 9 at 250C: >1 year, as <10% of each isomer degrades for 5days at 500C.
uv: / Solution λmax (nm) ε (L/cm·mol)
Acidic 273 1920
Neutral 273 1740
Basic 273 1880
dissociation constant (pKa): / No spectral shift was observed TGAC peak maxima at 273 nm. Solutions ranged from pH 2 to pH 10. It can be concluded the active has no dissociative activity in this pH range.
Physico-chemical properties of active constituent, continued
stability: / Does not decompose or sublime. Expected to remain in compliance with its specifications under normal conditions and is unlikely to be adversely affected by the presence of metals or metal ions from the packaging material.Octanol/water Partition coefficient (KOW): / Log POW at 250C = 3.51 (POW = 3240)
(effect of pH on partition coefficient was not determined as S-2200 S-isomer and S-2200 R-isomer do not dissociate under acidic or basic conditions)
Volatility (henry’s law constant): / 6.66 x 10-7 Pa.m3/mol at 200C
direct photo-transformation: / Photodegradation of R-isomer in sterile pH 7 buffer at 250C
Label / DT50 (days) / DT75 (days) / DT90 (days)
Benzyl / 5.3 or 4.6 / 10.5 or 9.2 / 17.5 or 15.3
Phenoxy / 3.6 / 7.2 / 12.0
S-2200-OR and S-2200-ORC were identified as the major degradation products at maximum levels of 23% and 14% of applied radioactivity, respectively.
Two other degradation products, S-2200-PR and De-Xy-2200, were present in the approximate range of 5 to 10%. A large number of minor unknowns were present at <10% of applied radioactivity.
The DT50’s for two of the degradation products were calculated to be:
Analyte / DT50 (days)
S-2200-OR / 5.1 or 4.0
S-2200-PR / 2.5 or 2.2
quantum yield: / R-isomer quantum yield in pH 7 buffer: 0.283
S-isomer quantum yield in pH 7 buffer: 0.269
photo-chemical oxidative degradation: / The decomposition rate constant in air following reaction with hydroxyl radicals was calculated to be 96.3802 x 10-12 cm3 molecule-1 s-1. Assuming that the 12hour daytime hydroxyl radical concentration is 1.5 x 106 molecules.cm-3, the half-life was calculated to be 0.111 days (12 hour day) or 1.332 hours.
No ozone reaction could be estimated.
Physico-chemical properties of active constituent, continued
flammability: / Not flammableauto-flammability: / No auto-ignition temperature was observed up to 4000C
oxidising properties: / Not oxidising.
Maximum burn rate was 0.44 mm/s for a 50% mixture with cellulose.
Burn rate of 60% mixture of barium nitrate reference material with cellulose was 0.55 mm/s.
explosive properties: / Not explosive
thermal stability: / A sharp endothermic event was observed for S-2200 TGAC at 100.50C using DSC analysis. The endothermic event corresponds to the melting point of the test substance and is not due to thermal instability Therefore, the test substance was determined to be thermally stable within the temperature range of
20 to 5000C.
STABILITY: / The test substance was found to be stable when stored at ambient temperature in commercial packaging for one year. The appearance of polyethylene bag (packaging material) did not change during the storage period.
Did not decompose under storage at ambient temperature or at 540C for 14days.
AQUEOUS PHOTOLYSIS (QUANTUM YIELD) / The photolytic half-life values of S-2200 at north latitudes 100 to 800 in the four seasons have been determined from the calculation results (S-2167 and S-2354 i.e. R-isomer and S-isomer respectively) using the GCSOLAR programme. The conclusion was that the half-life values of S-2200 at north latitudes 300, 400 and 500 in summer were calculated to be 1.20–3.03 days.
APVMA active constituent standard
On the basis of the data provided, and the toxicological assessment, it is proposed that the following APVMA Active Constituent Standard be established for mandestrobin active constituent:
Constituent / Specification / LevelMandestrobin / Mandestrobin / 940 g/kg minimum
Based on a review of the data provided by the applicant, the APVMA proposes to be satisfied that the chemistry and manufacturing details of mandestrobin are acceptable.