Metaflumizone (Ref: BAS 320l)

Metaflumizone (Ref: BAS 320l)	Last updated: 22/08/2024
(Also known as: NNI 0250)

SUMMARY

Metaflumizone is a semicarbazone broad-spectrum insecticide. It has a low aqueous solubility, is non-volatile and a low potential for leaching to groundwater based on its chemical properties. It is persistent in soil and in water-sediment systems. It has a low mammalian toxicity and considered to have potential negative reproduction/developmental effects. It also has a high potential for bioaccumulation. It has a low to moderate toxicity to most birds, aquatic species, honeybees and earthworms.

GENERAL INFORMATION

Description

A semicarbazone insecticide used as a veterinary parasite treatment

Availability status

Current

Introduction & key dates

2008, developed

Examples of veterinary uses

Indicated for the treatment of fleas and ticks

Examples of species treated

Dogs; Cats

Approval status

VMR 2013/2033 approval status (GB/UK)

Not approved

EU Regulatory approval status

Not approved

Chemical structure

Isomerism

Optical isomeric mixture in the ratio E:Z of 90:10

Chemical formula

C₂₄H₁₆F₆N₄O₂

Canonical SMILES

C1=CC(=CC(=C1)C(F)(F)F)C(=NNC(=O)NC2=CC=C(C=C2)OC(F)(F)F)CC3=CC=C(C=C3)C#N

Isomeric SMILES

C1=CC(=CC(=C1)C(F)(F)F)/C(=N\NC(=O)NC2=CC=C(C=C2)OC(F)(F)F)/CC3=CC=C(C=C3)C#N

International Chemical Identifier key (InChIKey)

MIFOMMKAVSCNKQ-QNKGDIEWSA-N

International Chemical Identifier (InChI)

InChI=1S/C24H16F6N4O2/c25-23(26,27)18-3-1-2-17(13-18)21(12-15-4-6-16(14-31)7-5-15)33-34-22(35)32-19-8-10-20(11-9-19)36-24(28,29)30/h1-11,13H,12H2,(H2,32,34,35)/f/h32,34H

2D structure diagram/image available?

Yes

General status

Veterinary substance type

Insecticide

Substance groups

Semicarbazone compound; Unclassified pesticide

Minimum active substance purity

945 g kg⁻¹

Known relevant impurities

EU dossier - hydrazine <1mg kg⁻¹; toluene <2mg kg⁻¹; 4-(trifluoromethoxy)phenyl isocyanate < 100mg kg⁻¹

Substance origin

Synthetic

Mode of action

Broad-spectrum, attacks insect nervous system causing paralysis. Voltage-dependent sodium channel modulator.

Molecular targets

[Sodium channel, Blocker]

CAS RN

139968-49-3

EC number

604-167-6

CIPAC number

779

US EPA chemical code

281250

PubChem CID

20056430

CLP index number

616-227-00-9

Therapeutic Class

Antiparasitic products, insecticides & repellents: Ecoparasiticides, insecticides & repellents

ATCvet Code

QP53AX25

Controlled Drug?

Regulation 37/2010 MRL Classification

Molecular mass

506.40

PIN (Preferred Identification Name)

IUPAC name

(EZ)-2'-[2-(4-cyanophenyl)-1-(α,α,α-trifluoro-m-tolyl)ethylidene]-4-(trifluoromethoxy)carbanilohydrazide

CAS name

2-(2-(4-cyanophenyl)-1-(3-(trifluoromethyl)phenyl)ethylidene)-N-(4-(trifluoromethoxy)phenyl)hydrazinecarboxamide

Other status information

PAN listed Highly Hazardous Chemical

Relevant Environmental Water Quality Standards

Physical state

White powder

Formulations

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Example products (past and present) using this active

Promeris 160mg Spot-on Solution for Small Cats

Pfizer Ltd

Not licensed

Promeris Duo Spot-on Solution for Large Dogs

Fort Dodge Animal Health

Not licensed

Formulation and application details

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

Solubility - In water at 20 °C (mg l⁻¹)

0.0018

Low

Solubility - In organic solvents at 20 °C (mg l⁻¹)

n-Hexane

4000

Toluene

153300

Acetone

14100

Methanol

Melting point (°C)

133

Isomer specific

Boiling point (°C)

Decomposes before boiling

Degradation point (°C)

232

Flashpoint (°C)

Octanol-water partition coefficient at pH 7, 20 °C

3.98 X 10⁰⁴

Calculated

Log P

4.6

mean of isomers

High

Fat solubility of residues

Solubility

Soluble

Data type

Regulatory data

Density (g ml⁻¹)

1.46

Dissociation constant pKa) at 25 °C

n/a

No dissociation

Vapour pressure at 20 °C (mPa)

1.24 X 10^-05

mean of isomers

Low volatility

Henry's law constant at 25 °C (Pa m³ mol⁻¹)

0.11

Z-isomer

Moderately volatile

Volatilisation as max % of applied dose lost

From plant surface

3.0

24 hr

Volatilisation is not considered critical for air pollution

From soil surface

3.3

24 hr

Volatilisation is not considered critical for air pollution

Maximum UV-vis absorption L mol⁻¹ cm⁻¹

Max @ 234nm=38100, 280nm=19300

Surface tension (mN m⁻¹)

70.5

0.01% solution

Refractive Index

Environmental release

Degradation

Property

Value

Source; quality score; and other information

Interpretation

Soil degradation (days) (aerobic)

DT₅₀ (typical)

141

Persistent

DT₅₀ (lab at 20 °C)

141

Persistent

DT₅₀ (field)

13.8

Non-persistent

DT₉₀ (lab at 20 °C)

362

Persistent

DT₉₀ (field)

67.8

Note

EU dossier lab studies DT₅₀ range 65-376 days, DT₉₀ range 153-728 days, Field studies DT₅₀ range 3.9-53.3 days, DT₉₀ range 9.9-114 days; Manufacturers published data DT₅₀ range 4.3-27 days

Manure DT₅₀ (days)

Aqueous photolysis DT₅₀ (days) at pH 7

Value

3.28

Moderately fast

Note

EU dossier states DT₅₀ 2.43-4.12 days

Aqueous hydrolysis DT₅₀ (days) at 20 °C and pH 7

Value

Note

EU dossier States DT₅₀ 5-6 days at pH 4

Water-sediment DT₅₀ (days)

451

Stable

Water phase only DT₅₀ (days)

1.0

Moderately fast

Air degradation

As this parameter is not normally measured directly, a surrogate measure is used: ‘Photochemical oxidative DT₅₀’. Where data is available, this can be found in the Fate Indices section below.

Decay in stored produce DT₅₀

Soil adsorption and mobility

Property

Value

Source; quality score; and other information

Interpretation

Linear

K_d (mL g⁻¹)

529

Non-mobile

K_oc (mL g⁻¹)

30714

Notes and range

EU dossier K_d range 299-1030 mL g⁻¹, K_oc range 16500-51000 mL g⁻¹

Freundlich

K_f (mL g⁻¹)

K_foc (mL g⁻¹)

¹/_n

Notes and range

pH sensitivity

Fate indices

Property

Value

Source; quality score; and other information

Interpretation

GUS leaching potential index

-0.56

Calculated

Low leachability

Bio-concentration factor

BCF (l kg⁻¹)

7800

Lepomis macrochirus

High potential

CT₅₀ (days)

Known soil metabolites

Metabolite

Major/Minor fraction

$Click here for further information on Major/Minor fraction$

Estimated maximum occurrence fraction

Notes

2-(2-oxo-2-(3-trifluoromethyl)phenyl)ethyl)-benzonitrile (Ref: CL397864)

trifluoro-methoxy aniline (Ref: CL65504)

4-(5-hydroxy-3-oxo-4(4-(trifluoromethoxy)phenyl)-6-(3-trifluoromethyl)phenyl)-2,3,4,5-tetrahydro-1,2,4-triazine-5-yl)benzonitrile (Ref: M320I23)

Minor fraction

0.081

Very persistent

benzonitrile carboxylic acid (Ref: M320I06)

Major fraction

0.084

3-trifluoromethylbenzoic acid (Ref: RE-54488)

Major fraction

0.211

Ref: M320I07, CL1500789

N-[4-(trifluoromethoxy)phenyl]hydrazinecarboxamide (Ref: M320I08, CL952480)

Ref: M320I09, CL397865

Known groundwater metabolites

Metabolite

EC SANCO/221/2000 relevancy

ADI (mg kg⁻¹ bodyweight day⁻¹)

WHO drinking water guidance value (μg L⁻¹ day⁻¹)

4-(5-hydroxy-3-oxo-4(4-(trifluoromethoxy)phenyl)-6-(3-trifluoromethyl)phenyl)-2,3,4,5-tetrahydro-1,2,4-triazine-5-yl)benzonitrile (Ref: M320I23)

Not relevant

Other known metabolites

Metabolite name and reference

Aliases

Formation medium / Rate

Estimated maximum occurrence fraction

M320I22

Animal

M320I24

Animal

M320I25

Animal; Hen

M320I26

Animal; Hen

M320I27

Hen

2-(2-oxo-2-(3-trifluoromethyl)phenyl)ethyl)-benzonitrile
Note: CAS no: 146653-56-7

M320I04

Rat; Animal; Plant

trifluoro-methoxy aniline (Ref: CL65504)

M320I05

Rat; Plant

4-(5-hydroxy-3-oxo-4(4-(trifluoromethoxy)phenyl)-6-(3-trifluoromethyl)phenyl)-2,3,4,5-tetrahydro-1,2,4-triazine-5-yl)benzonitrile (Ref: M320I23)

M320I23

Surface water; Sediment

benzonitrile carboxylic acid (Ref: M320I06)

M320I06

Surface water; Sediment

3-trifluoromethylbenzoic acid (Ref: RE-54488)

M320I29

Surface water; Sediment

4-{2-oxo-2-[3-(trifluoromethyl)phenyl]ethyl}benzonitrile

M320I04

Surface water; Sediment

Ref: CL1500789

M320I07

Rat; Animal; Plant

Ref: CL1023720

M320I10

Rat; Animal

Ref: CL1023721

M320I11

Rat

Ref: CL1023722

M320I12

Rat

Ref: CL269463

M320I13

Rat; Animal

Ref: CL1023723

M320I14

Rat

Ref: CL1023724

M320I15

Rat

Ref: CL1023725

M320I16

Rat

Ref: CL1023726

M320I17

Rat; Animal

M320I18

Rat

M320I19

Rat

M320I20

Rat

M320I21

Rat

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

> 5000

Rat

Low

Mammals - Short term dietary NOEL

(mg kg⁻¹)

(ppm diet)

Mammals - Chronic 21d NOAEL (mg kg⁻¹ bw d⁻¹)

Birds - Acute LD₅₀ (mg kg⁻¹)

> 2025

Colinus virginianus

Low

Birds - Short term dietary (LC₅₀/LD₅₀)

Birds - Chronic 21d NOEL (mg kg⁻¹ bw d⁻¹)

Earthworms - Acute 14 day LC₅₀ (mg kg⁻¹)

> 500

Eisenia foetida corr

Moderate

Earthworms - Chronic NOEC, reproduction (mg kg⁻¹)

3.46

Eisenia foetida corr

Moderate

Soil micro-organisms

Nitrogen mineralisation: No significant adverse effect
Carbon mineralisation: No significant adverse effect

Dose: 0.2 mg kg⁻¹ soil 28 Day

Collembola

Acute LC₅₀ (mg kg⁻¹)

Chronic NOEC (mg kg⁻¹)

> 110

Folsomia candida corr

Non-target plants

Honeybees (Apis spp.)

Contact acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

1.65

Apis mellifera

Moderate

Oral acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

2.43

Apis mellifera

Moderate

Unknown mode acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Chronic

Bumblebees (Bombus spp.)

Contact acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Oral acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Mason bees (Osmia spp.)

Contact acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Oral acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Other bee species (1)

Acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg insect⁻¹)

Mode of exposure

Other bee species (2)

Acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg insect⁻¹)

Mode of exposure

Beneficial insects (Ladybirds) as Mortality LR₅₀ g ha⁻¹

Coccinella septempunctata

Beneficial insects (Lacewings) as Mortlity LR₅₀ g ha⁻¹

> 780

Chrysoperla carnea

Beneficial insects (Parasitic wasps) as Mortality LR₅₀ g ha⁻¹

3.48

Aphidius rhopalosiphi

Beneficial insects (Predatory mites) as Mortality LR₅₀ g ha⁻¹

> 780

Typhlodromus pyri

Beneficial insects (Ground beetles)

Aquatic ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Temperate Freshwater Fish - Acute 96 hour LC₅₀ (mg l⁻¹)

> 0.228

Oncorhynchus mykiss

Moderate

Temperate Freshwater Fish - Chronic 21 day NOEC (mg l⁻¹)

0.0011

Cyprinodon variegatus

High

Tropical Freshwater Fish - Acute 96 hour LC₅₀ (mg l⁻¹)

Temperate Freshwater Aquatic invertebrates - Acute 48 hour EC₅₀ (mg l⁻¹)

> 0.331

Daphnia magna

Moderate

Temperate Freshwater Aquatic invertebrates - Chronic 21 day NOEC (mg l⁻¹)

1.47

Daphnia magna

Moderate

Tropical Freshwater Aquatic invertebrates - Acute 48 hour EC₅₀ (mg l⁻¹)

Aquatic crustaceans - Acute 96 hour LC₅₀ (mg l⁻¹)

> 289

Americamysis bahia

Low

Sediment dwelling organisms - Acute 96 hour LC₅₀ (mg l⁻¹)

1.8

Chironomus riparius

Moderate

Sediment dwelling organisms - Chronic 28 day NOEC, static, water (mg l⁻¹)

0.0256

Chironomus riparius

Moderate

Sediment dwelling organisms - Chronic 28 day NOEC, sediment (mg kg⁻¹)

Aquatic plants - Acute 7 day EC₅₀, biomass (mg l⁻¹)

Algae - Acute 72 hour EC₅₀, growth (mg l⁻¹)

> 0.311

Pseudokirchneriella subcapitata

Moderate

Algae - Chronic 96 hour NOEC, growth (mg l⁻¹)

Mesocosm study data

NOEAEC mg l⁻¹

Marine bivalves – Acute EC₅₀ development (mg l⁻¹)

HUMAN HEALTH AND PROTECTION

General

Property

Value

Source; quality score; and other information

Interpretation

Threshold of Toxicological Concern (Cramer Class)

High (class III)

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

> 5000

Rat

Low

Mammals - Dermal LD₅₀ (mg kg⁻¹ body weight)

5000

Rat

Mammals - Inhalation LC₅₀ (mg l⁻¹)

> 5.2

Rat

Other Mammal toxicity endpoints

ADI - Acceptable Daily Intake (mg kg⁻¹ bw day⁻¹)

0.01

ARfD - Acute Reference Dose (mg kg⁻¹ bw day⁻¹)

0.13

AAOEL - Acute Acceptable Operator Exposure Level (mg kg⁻¹ bw day⁻¹)

Not applicable

AOEL - Acceptable Operator Exposure Level - Systemic (mg kg⁻¹ bw day⁻¹)

0.01

Dermal penetration studies (%)

0.2-0.4

concentration dependent

Dangerous Substances Directive 76/464

List II

Exposure Routes

Public

Occupational

Mammalian dose elimination route and rate

Administered metaflumizone is excreted by rats principally via the faeces. The proprtion absorbed is extensively metabolised.

Health issues

Specific human health issues

Carcinogen

Genotoxic

Endocrine disruptor

; ; ; ;

Reproduction / development effects

Acetyl cholinesterase inhibitor

Neurotoxicant

Respiratory tract irritant

Skin irritant

Skin sensitiser

No data found

Eye irritant

Phototoxicant

No data found

General human health issues

Liver toxicant

Handling issues

Property

Value and interpretation

General

Not explosive or oxidising
IMDG Transport Hazard Class 9
Not expected to auto-ignite; Not highly flammable

CLP classification 2013

Health: H373
Environment: H400, H410

WHO Classification

U (Unlikely to present an acute hazard)

UN Number

UN3077

Waste disposal & packaging

Packaging Group III (minor danger)

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

metaflumizone

French

metaflumizone

German

Metaflumizon

Danish

metaflumizon

Italian

metaflumizone

Spanish

metaflumizon

Greek

Polish

metaflumizon

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	22/08/2024
Contact:	aeru@herts.ac.uk
Please cite as:	Lewis, K.A., Tzilivakis, J., Warner, D. and Green, A. (2016) An international database for pesticide risk assessments and management. Human and Ecological Risk Assessment: An International Journal, 22(4), 1050-1064. DOI: 10.1080/10807039.2015.1133242