Public Release Summary
on the evaluation of the active constituent fluopicolide in the product Infinito SC Fungicide
APVMA Product Number 80625
november 2016
© Australian Pesticides and Veterinary Medicines Authority 2016
ISSN: 1443-1335 (electronic)
ISBN: 978-1-925390-56-8 (electronic)
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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.
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Director Public Affairs and Communication
Australian Pesticides and Veterinary Medicines Authority
PO Box 6182
KINGSTON ACT 2604 Australia
Telephone: +61 2 6210 4988
Email:
This publication is available from the APVMA website: www.apvma.gov.au.
november 2016
Contents iii
Contents
Preface 1
About this document 1
Making a submission 1
Further information 2
1 Introduction 3
1.1 Applicant 3
1.2 Details of the product 3
1.3 Overseas registrations 3
2 Chemistry and manufacture 4
2.1 Active constituent 4
2.2 Formulated product 6
2.3 Recommendations 6
3 Toxicological assessment 8
3.1 Chemical class 8
3.2 Toxicokinetics and metabolism 8
3.3 Dermal absorption 9
3.4 Toxicity of fluopicolide 9
3.5 Toxicity of metabolites 9
3.6 Toxicity of Infinito SC Fungicide 9
3.7 Public health standards 10
4 Residues assessment 12
4.1 Introduction 12
4.2 Metabolism 12
4.3 Analytical methods 19
4.4 Stability of the pesticides in stored analytical samples 20
4.5 Residue definition 20
4.6 Residue trials 21
4.7 Rotational crops 25
4.8 Animal commodity MRLs 26
4.9 Estimated dietary intake 29
4.10 Bioaccumulation potential 29
4.11 Spray drift 30
4.12 Recommendations 30
5 Assessment of overseas trade aspects of residues in food 33
6 Occupational health and safety assessment 34
6.1 Use pattern 34
6.2 Exposure during use and recommended Safety Directions/First Aid Instructions 34
6.3 Post-application exposure 35
6.4 Conclusion 35
7 Environmental assessment 36
7.1 Introduction 36
7.2 Environmental fate and behaviour 36
7.3 Environmental effects 37
7.4 Risk assessment 41
7.5 Conclusion 41
8 Efficacy and safety assessment 42
8.1 Proposed product use pattern 42
8.2 Summary of evaluation of efficacy and crop safety 42
8.3 Conclusions 44
9 Labelling requirements 45
Abbreviations 52
Glossary 55
References 56
List of tables
Table 1: Nomenclature, chemistry and key identifiers of fluopicolide 4
Table 2: Summary of key physico-chemical properties of fluopicolide 5
Table 3: Key aspects of the identity of the product Infinito SC Fungicide 6
Table 4: Summary of key physico-chemical properties of the product Infinito SC Fungicide 6
Table 5: APVMA active constituent standard proposed for the active constituent fluopicolide 7
Introduction 1
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, Department of Agriculture and Water Resources, 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 on the APVMA 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 Australian Pesticides and Veterinary Medicines Authority (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.
Introduction 1
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 the active constituent Fluopicolide and registration of the product Infinito SC 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 12 December 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 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.
1 Introduction
1.1 Applicant
Bayer CropScience Pty Ltd.
1.2 Details of the product
It is proposed to register Infinito SC Fungicide, containing 62.5 g a.i./L of fluopicolide and 625 g a.i./L of propamocarb hydrochloride, as a suspension concentrate for the control of downy mildew and late blight in bulb vegetables (onions, spring onions and leeks), lettuce, poppies, cucurbits and potatoes. The proposed use for Infinito SC Fungicide will involve ground application at 1.6 L/ha and a maximum of 3 applications per crop at a minimum interval of 7 days.
Fluopicolide is a fungicide used in agriculture to control oomycetes (Phycomycete) caused diseases including downy mildews (Plasmopara, Pseudoperonospora, Peronospora, Bremia), late blight (Phytophthora), and some Pythium species. The mode of action of fluopicolide is unique and yet it is not well characterised. However, recent reports stated that it acts via inducing perturbation of a spectrin-like protein in the cytoskeleton of oomycetes. It affects the motility of zoospores, the germination of cysts, the growth of the mycelium and sporulation. Resistant oomycetes to phenylamides, strobilurin, dimethomorph and iprovalicarb are labile to fluopicolide. Since fluopicolide translocates toward the stem tips via the xylem, it has a systemic action but it does not translocate toward the roots. Chemically, it classed as an acylpicolide.
1.3 Overseas registrations
Infinito SC Fungicide (fluopicolide at 62.5 g a.i./L and propamocarb hydrochloride at 625 g a.i./L) as a suspension concentrate is currently registered for use on various crops in Algeria, Argentina, Austria, Azerbaijan, Belarus, Belgium, Brazil, Colombia, France, El Salvador, Germany, Guyana, Japan, Morocco, New Zealand, Nicaragua, Peru, Poland, Spain, Switzerland, Trinidad and Tobago, Tunisia, Ukraine and Uruguay.
Infinito SC Fungicide is registered in the United Kingdom and New Zealand for control of late blight (Phytophthora infestans) in potatoes and in other countries for the control of downy mildew in cucurbits.
This publication provides a summary of the data reviewed and an outline of the regulatory considerations for the proposed registration of Infinito SC Fungicide, and approval of the new active constituent, fluopicolide.
Chemistry and manufacture 7
2 Chemistry and manufacture
2.1 Active constituent
The chemical active constituent fluopicolide is manufactured by Bayer CropScience. Tables 1 and 2 summarise key properties of this chemical.
Table 1: Nomenclature, chemistry and key identifiers of fluopicolide
Common Name (ISO): / fluopicolideIUPAC Name: / 2,6-dichloro-N-[3-chloro-5-(trifluoromethyl)-2-pyridylmethyl] benzamide
CAS Registry Number: / 239110-15-7
MOLECuLAR Formula: / C14H8Cl3F3N20
Molecular Weight: / 383.6 g/mol
Structural Formula: /
CHEMICAL FAMILY: / Benzamide
Chemistry and manufacture 7
Physico-chemical properties of the active constituent
Table 2: Summary of key physico-chemical properties of fluopicolide
PHYSICAL FORM: / Fine crystalline beige—coloured powderOdour: / No characteristic odour
molecular weight: / 383.59
pH: / 6.5 at 22.0oC
Melting Point: / 150oC
RELATIVE Density at 20oC: / 1.65
water solubility at 20oC: / 2.86 mg/l at pH 4
2.80 mg/L at pH 7
2.80 mg/L at pH 9
solvent solubility at 20oC: / n-Hexane: 0.20 g/L
Ethanol: 19.2 g/L
Toluene: 20.5 g/L
Ethyl acetate: 37.7 g/L
Acetone: 74.7 g/L
Dichloromethane: 126 g/L
Dimethyl sulfoxide: 183 g/L
vapour pressure at 25oC / 8.3 x 10-7 Pa
DISSOCIATION CONSTANT (PKa): / No evidence of ionization in the pH range 1.9–9.8
surface tension (90% SATURATED SOLUTION): / 71.3 mN/M at 20oC
octanol/water partition co-efficient log(Kow): / Log Kow = 3.26 at pH 7.8 and 22 ± 1oC
Log Kow = 2.9 at pH 4.0, 7.3 and 9.1 and 40oC
uv/visible absorption spectrum: / Absorption maxima wavelengths (nm):
In methanol: 203 and 271
In methanol/HCL: 202 and 270
In methanol/NaOH: 219 and 271
stability: / Not degraded over 14 days at 54oC
After 12 months at ambient temperature in polypropylene containers, no degradation was observed: the impurity profile did not change
2.2 Formulated product
The product, Infinito SC Fungicide will be manufactured in Australia and overseas and will be available in 1L, 2.5 L, 3 L, 5 L, 7 L, 7.5 L, 10 L, 15 L, 20 L, 60 L and 110 L HDPE containers.
Table 3: Key aspects of the identity of the product Infinito SC Fungicide
distinguishing name: / Infinito SC Fungicideformulation type: / Suspension Concentrate (SC)
active constituents concentration: / 62.5 g/L fluopicolide and 625 g/L propamocarb hydrochloride
Physical and chemical properties of product
Table 4: Summary of key physico-chemical properties of the product Infinito SC Fungicide
physical form: / beige suspensionPH value: / 7.0 @ 23oC
Relative density: / 1.130 g/mL @ 20oC
Surface tension: / 31 mN/m @ 20oC
Viscosity: / η (20°C, 20s- ) - 221 mPa.s
η (20°C, 100s-) - 100 mPa.s
FlasH Point: / Not applicable.
Oxidising properties: / No oxidising properties
Explosive properties: / No explosive properties
flammability: / Auto-inflammable with a self-ignition temperature of 420 °C
corrosive hazard: / Not corrosive to HDPE containers
2.3 Recommendations
The APVMA Chemistry and Manufacture Section has evaluated the chemistry aspects of fluopicolide and Infinito SC Fungicide (manufacturing process, quality control procedures, stability, batch analysis results and analytical methods) and found them to be acceptable.
On the basis of the data provided, and the toxicological assessment, it is proposed that the following APVMA active constituent standard be established for fluopicolide:
APVMA Active constituent standard for fluopicolide
Table 5: APVMA active constituent standard proposed for the active constituent fluopicolide
CONSTITUENT / SPECIFICATION / LEVELFluopicolide / fluopicolide / Not less than 970 g/kg
2,6-dichlorobenzamide / Not more than 4 g/kg
Toxicological assessment 11
3 Toxicological assessment
The product Infinito SC Fungicide contains a new active constituent, fluopicolide (62.5 g/L), and the existing active constituent propamocarb hydrochloride (625 g/L). The following summary focuses on the toxicity of fluopicolide with additional information on the toxicity of Infinito SC Fungicide.
The toxicity database of fluopicolide is extensive and consists primarily of toxicity studies conducted in laboratory animals. In interpreting the data, it should be noted that toxicity tests generally use doses that are high compared with likely human exposures. The use of high doses increases the likelihood that potentially significant toxic effects will be identified.