Lufenuron (Ref: CGA 184699)

Lufenuron (Ref: CGA 184699)	Last updated: 16/03/2024
(Not known by any other names)

GENERAL INFORMATION

Description

Lufenuron, often combined with milbemycin, is an insect growth regulator used as a veterinary antiparasitic agent

Availability status

Current

Introduction & key dates

1989, first reported; 1990, first introduced

Examples of veterinary uses

Used for the control of fleas and other parasitic infections on animals

Examples of species treated

Cats; Dogs

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved

EU Regulatory approval status

Approved

Chemical structure

Isomerism

Lufenuron consists of a pair of enantiomers. A chiral centre exists at the 2-position of the hexafluoropropoxy side-chain.

Chemical formula

C₁₇H₈Cl₂F₈N₂O₃

Canonical SMILES

C1=CC(=C(C(=C1)F)C(=O)NC(=O)NC2=CC(=C(C=C2Cl)OC(C(C(F)(F)F)F)(F)F)Cl)F

Isomeric SMILES

International Chemical Identifier key (InChIKey)

PWPJGUXAGUPAHP-UHFFFAOYSA-N

International Chemical Identifier (InChI)

InChI=1S/C17H8Cl2F8N2O3/c18-6-5-11(32-17(26,27)14(22)16(23,24)25)7(19)4-10(6)28-15(31)29-13(30)12-8(20)2-1-3-9(12)21/h1-5,14H,(H2,28,29,30,31)

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
lufenuron	-

General status

Veterinary substance type

Insecticide, Antiparasitic, Acaricide

Substance groups

Benzoylurea insecticide; Benzoylphenylurea insecticide

Minimum active substance purity

>95%

Known relevant impurities

EU dossier - None declared

Substance origin

Synthetic

Mode of action

Systemic, selective, stomach acting. Inhibitor of chitin biosynthesis affecting CHS1.

Molecular targets

[Chitin synthesis, Inhibitor]

CAS RN

103055-07-8

EC number

410-690-9

CIPAC number

704

US EPA chemical code

PubChem CID

71777

CLP index number

616-050-00-7

Therapeutic Class

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

ATCvet Code

QP53BC01

Controlled Drug?

Regulation 37/2010 MRL Classification

Molecular mass

511.16

PIN (Preferred Identification Name)

IUPAC name

(RS)-1-[2,5-dichloro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-3-(2,6-difluorobenzoyl)urea

CAS name

N-(((2,5-dichloro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl)amino)carbonyl)-2,6-difluorobenzamide

Other status information

Relevant Environmental Water Quality Standards

Physical state

Off-white to pale beige solid

Formulations

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Example products (past and present) using this active

Program 40mg Suspension for Injection

Elanco Europe Ltd

UK National authorisation (IC)

Prescription only medicine to be authorised by a veterinarian (POM-V)

Program Tablets 204.9 mg

Elanco Europe Ltd

UK National authorisation

Authorised veterinary medicine for general sale (AVM-GSL)

Formulation and application details

Usually formulated as suspension solutions for injection or in tablet form for oral administration

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

0.046

Low

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

460000

Acetone

330000

Ethyl acetate

100

Hexane

66000

Toluene

Melting point (°C)

169.1

Boiling point (°C)

Decomposes before boiling

Degradation point (°C)

242

Flashpoint (°C)

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

1.32 X 10⁰⁵

Calculated

Log P

5.12

at 25 °C

High

Fat solubility of residues

Solubility

Soluble

Data type

Regulatory data - observed in metabolism and farm animal feeding studies

Density (g ml⁻¹)

1.63

Dissociation constant pKa) at 25 °C

10.2

Very weak acid

Vapour pressure at 20 °C (mPa)

4.00 X 10^-03

Low volatility

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

3.41 X 10^-02

Non-volatile

Volatilisation as max % of applied dose lost

From plant surface

From soil surface

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

Neutral solution: 210nm = 37293
Acidic solution: 210nm = 30588
Basic solution: 295nm = 4871
No absorption between 295-750nm

Surface tension (mN m⁻¹)

68.3-72.8

at 20°C

Refractive Index

Environmental release

Degradation

Property

Value

Source; quality score; and other information

Interpretation

Soil degradation (days) (aerobic)

DT₅₀ (typical)

16.3

Non-persistent

DT₅₀ (lab at 20 °C)

20.8

Non-persistent

DT₅₀ (field)

256

Persistent

DT₉₀ (lab at 20 °C)

100.3

Persistent

DT₉₀ (field)

937

Note

EU dossier lab studies DT₅₀ range 11.1-75.7 days, DT₉₀ range 45.2-276.1 days; field studies DT₅₀ range 151-434 days, DT₉₀ range 503-1444 days

Manure DT₅₀ (days)

Aqueous photolysis DT₅₀ (days) at pH 7

Value

0.75

Fast

Note

DT₅₀ 111-1781 days in natural light, summer to winter 40 deg N

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

Value

Stable

Note

Stable pH 5 to pH 9

Water-sediment DT₅₀ (days)

112

Slow

Water phase only DT₅₀ (days)

112

Stable

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.

Soil adsorption and mobility

Property

Value

Source; quality score; and other information

Interpretation

Linear

K_d

K_oc

Notes and range

Freundlich

K_f

1056

Non-mobile

K_foc

41182

¹/_n

0.98

Notes and range

EU dossier K_f range 166-2350 mL g⁻¹, K_foc range 11888-74833 mL g⁻¹, ¹/_n range 0.81-1.06, Soils=5

pH sensitivity

Fate indices

Property

Value

Source; quality score; and other information

Interpretation

GUS leaching potential index

-1.48

Calculated

Low leachability

Bio-concentration factor

BCF (l kg⁻¹)

5300

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

(2,5-dichloro-4-(1,1,2,3,3,3-hexafluoro-propoxy)-phenyl)-urea (Ref: CGA 238277)

Major fraction

0.318

2,5-dichloro-4-(1,1,2,3,3,3-hexafluoro-propoxy)-phenylamine (Ref: CGA 224443)

Major fraction

0.328

2,6-difluorobenzamide (Ref: CGA 149772)

Aerobic; Mol wt = 157; DT50 = 4.4 days

Known groundwater metabolites

None

Other known metabolites

None

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

> 2000

Rat

Low

Mammals - Short term dietary NOEL

(mg kg⁻¹)

Rat 2 yr

High

(ppm diet)

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

Birds - Acute LD₅₀ (mg kg⁻¹)

2000

Anas platyrhynchos

Moderate

Birds - Short term dietary (LC₅₀/LD₅₀)

966 mg kg bw⁻¹ day⁻¹

Colinus virginianus

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)

Soil micro-organisms

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

Dose: 1.5 kg ha⁻¹ 28 Day

Collembola

Acute LC₅₀ (mg kg⁻¹)

Chronic NOEC (mg kg⁻¹)

0.2

Folsomia candida

Non-target plants

Honeybees (Apis spp.)

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

> 200

Apis mellifera

Low

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

> 197

Apis mellifera

Low

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 7 day

Coccinella septempunctata

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

0.4

Chrysoperla carnea Larva

Beneficial insects (Parasitic wasps)

Beneficial insects (Predatory mites) as Mortality LR₅₀ g ha⁻¹ 7 day

> 100

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)

> 29

Lepomis macrochirus

Moderate

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

0.02

Pimephales promelas

Moderate

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

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

0.0013

Daphnia magna

High

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

0.0001

Daphnia magna

High

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

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

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

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

0.002

Chironomus riparius

High

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

0.04

Chironomus riparius

High

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

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

8.8

Pseudokirchneriella subcapitata Growth

Moderate

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

Mesocosm study data

NOEAEC mg l⁻¹

0.0001

NOEAEC 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)

> 2000

Rat

Low

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

2000

Rat

Mammals - Inhalation LC₅₀ (mg l⁻¹)

> 2.35

Rat 4 hr (nose only aerosol)

Other Mammal toxicity endpoints

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

0.015

Dog SF=100

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

None allocated

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

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

0.01

Dog SF=100

Dermal penetration studies (%)

2-13

concentration dependent

Dangerous Substances Directive 76/464

List II

Exposure Routes

Public

Negligible risk to bystanders

Occupational

Farm workers should use protective clothing and equipment

Mammalian dose elimination route and rate

Major route of elimination was via faeces, with very little degradation

Health issues

Specific human health issues

Carcinogen

Genotoxic

Endocrine disruptor

; ; ; ;

Reproduction / development effects

Acetyl cholinesterase inhibitor

Neurotoxicant

Respiratory tract irritant

Skin irritant

Skin sensitiser

Eye irritant

Phototoxicant

No data found

General human health issues

Possible liver and thyroid 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: H317
Environment: H400, H410

WHO Classification

III (Slightly hazardous)

UN Number

UN3077

Waste disposal & packaging

Packaging Group III (minor danger)

Shelf-life, storage, stability and reactivity

Limited shelf-life. Store at -20 DegC

TRANSLATIONS

Language

Name

English

lufenuron

French

lufenuron

German

Lufenuron

Danish

lufenuron

Italian

lufenuron

Spanish

lufenuron

Greek

Polish

lufenuron

Swedish

Hungarian

lufenuron

Dutch

Norwegian

Record last updated:	16/03/2024
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