Fipronil (Ref: BAS 350l)

Fipronil (Ref: BAS 350l)	Last updated: 06/03/2024
(Also known as: RPA 030)

SUMMARY

A broad-spectrum insecticide with both crop and animal health applications. It has a low aqueous solubility, a low volatility and is not greatly mobile in the environment. It can be quite persistent in soil systems but is less so in aquatic and sediment systems. It is highly toxic to humans and may bio-accumulate. It is considered a neurotoxicant and both an eye and skin irritant. Fipronil is highly toxic to mammals, birds and bees but slightly less so to fish, aquatic invertebrates, aquatic plants and earthworms.

GENERAL INFORMATION

Description

A phenylpyrazole insecticide used in veterinary medicine

Availability status

Current

Introduction & key dates

1987, discovered; 1992, first reported

Examples of veterinary uses

Mainly used as a spot-on treatment for the eradication of fleas

Examples of species treated

Domestic pets including Dogs & Cats

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved

EU Regulatory approval status

Approved

Chemical structure

Isomerism

A chiral molecule, fipronil is an isomeric mixture of two enantiomers (+/-; S/R)

Chemical formula

C₁₂H₄Cl₂F₆N₄OS

Canonical SMILES

C1=C(C=C(C(=C1Cl)N2C(=C(C(=N2)C#N)S(=O)C(F)(F)F)N)Cl)C(F)(F)F

Isomeric SMILES

International Chemical Identifier key (InChIKey)

ZOCSXAVNDGMNBV-UHFFFAOYSA-N

International Chemical Identifier (InChI)

InChI=1S/C12H4Cl2F6N4OS/c13-5-1-4(11(15,16)17)2-6(14)8(5)24-10(22)9(7(3-21)23-24)26(25)12(18,19)20/h1-2H,22H2

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
fipronil	Unstated isomer

General status

Veterinary substance type

Antiparasitic, Insecticide

Substance groups

Phenylpyrazole insecticide; Phenylpyrazole acaricide; Pyrazole insecticide; Prazole acaricide

Minimum active substance purity

950 +/- 25 g kg⁻¹

Known relevant impurities

EU dossier - None declared

Substance origin

Synthetic

Mode of action

Broad-spectrum with contact and stomach action. GABA-gated chloride channel antagonist.

Molecular targets

CAS RN

120068-37-3

EC number

424-610-5

CIPAC number

581

US EPA chemical code

129121

PubChem CID

3352

CLP index number

608-055-00-8

Therapeutic Class

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

ATCvet Code

QP53AX15

Controlled Drug?

Regulation 37/2010 MRL Classification

Molecular mass

437.15

PIN (Preferred Identification Name)

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethanesulfinyl)-1H-pyrazole-3-carbonitrile

IUPAC name

5-amino-1-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)-4-trifluoromethylsulfinylpyrazole-3-carbonitrile

CAS name

5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-((trifluoromethyl)sulfinyl)-1H-pyrazole-3-carbonitrile

Other status information

Relevant Environmental Water Quality Standards

Physical state

White to beige coloured powder

Formulations

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Example products (past and present) using this active

Alfamed Cutaneous Spray

Alfamed S.A.S

GB National authorisation

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

Amflee Cuaneous Spray

Krda D.D. Novo Mesto

GB National authorisation

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

Chanonil Spot-on Solution

EU Pharmaceuticals Ltd

UK National authorisation

Authorised veterinary medicine for general sale (AVM-GSL)

Dixie Spot-on Solution

Quimica S.A.

UK National authorisation

Authorised veterinary medicine for general sale (AVM-GSL)

Formulation and application details

Available in a variety of formulations including solutions fo injection and topical produ ts such as spot-ons and cutaneous sprays

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

3.78

Low

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

Hexane

3000

Toluene

137500

Methanol

545900

Acetone

Melting point (°C)

203

Boiling point (°C)

Decomposes before boiling

Degradation point (°C)

230

Flashpoint (°C)

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

5.62 X 10⁰³

Calculated

Log P

3.75

High

Fat solubility of residues

Solubility

Soluble

Data type

Regulatory data - observed in metabolism and farm animal feeding studies

Density (g ml⁻¹)

1.71

Dissociation constant pKa) at 25 °C

Not applicable

No dissociation

Vapour pressure at 20 °C (mPa)

0.002

Low volatility

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

2.31 X 10^-04

Non-volatile

Volatilisation as max % of applied dose lost

From plant surface

From soil surface

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

203nm = 48385, 286nm = 7281, 291nm = 6008

Surface tension (mN m⁻¹)

72.5

at 20°C

Refractive Index

Environmental release

Degradation

Property

Value

Source; quality score; and other information

Interpretation

Soil degradation (days) (aerobic)

DT₅₀ (typical)

142

Persistent

DT₅₀ (lab at 20 °C)

142

Persistent

DT₅₀ (field)

Moderately persistent

DT₉₀ (lab at 20 °C)

DT₉₀ (field)

Note

EU dossier lab studies DT₅₀ range 32-346 days, geometric mean 142, field studies range 5.6-135 days 4 European sites; Other sources: 96 days (DW4)

Manure DT₅₀ (days)

Aqueous photolysis DT₅₀ (days) at pH 7

Value

0.33

Fast

Note

Rapid in artifical light

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

Value

Stable

Note

Stable pH 5 to pH 7, some hydrolysis occurs at pH 9 - DT₅₀ circa 11 days at 50 °C

Water-sediment DT₅₀ (days)

Moderately fast

Water phase only DT₅₀ (days)

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

11.85

Slightly mobile

K_foc

727

¹/_n

0.95

Notes and range

EU dossier K_f range 4.19-20.7 mL g⁻¹, K_foc range 427-1248 mL g⁻¹, Soils=5

pH sensitivity

Fate indices

Property

Value

Source; quality score; and other information

Interpretation

GUS leaching potential index

2.06

Calculated

Transition state

Bio-concentration factor

BCF (l kg⁻¹)

321

Whole fish (Other literature Log BCF range 1.0-1.8 (R3))

Threshold for concern

CT₅₀ (days)

Known soil metabolites

Metabolite

Major/Minor fraction

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

Estimated maximum occurrence fraction

Notes

5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfonylpyrazole-3-carboxylic acid (Ref: RPA 200761)

Aerobic

5-amino-1-(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyl)-4-trifluoro-methylpyrazole-3-carbonitrile (Ref: MB 46513)

Aerobic, Photolysis

5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl) pyrazole-4-sulfonic acid, potassium (Ref: RPA 104615)

Photolysis

fipronil amide (Ref: RPA 200766)

Major fraction

0.384

fipronil sulfone (Ref: MB 46136)

Major fraction

0.343

fipronil sulfide (Ref: MB 45950)

Major fraction

0.170

Known groundwater metabolites

None

Other known metabolites

Metabolite name and reference

Aliases

Formation medium / Rate

Estimated maximum occurrence fraction

Metabolising enzymes

5-amino-1-(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyl)-4-trifluoro-methylpyrazole-3-carbonitrile (Ref: MB 46513)
Note: Low mobility

Water; Plant

5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl) pyrazole-4-sulfonic acid, potassium (Ref: RPA 104615)
Note: Rat oral LD50 > 2000 mg/kg bw

Plant

5-amino-1-(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyl)-1H-pyrazole-3-carbonitrile (Ref: MB 45897)

Rat

1-(2,6-dichloro-4-trifluoromethylphenyl)-3-amino-5-amino-4-trifluoromethylsulfonylpyrazole (Ref: RPA 105048)
Note: Rat oral LD50 467 mg/kg bw

Water

5-amino-3-carbamyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-rifluoromethylsulfonylpyrazole (Ref: RPA 105320)
Note: Rat oral LD50 > 2000 mg/kg bw

Plant

5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfonylpyrazole-3-carboxylic acid (Ref: RPA 200761)
Note: Persistent

Plant

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

Rat

High

Mammals - Short term dietary NOEL

(mg kg⁻¹)

0.35

Rat

High

(ppm diet)

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

2.53

Rat Reproductive NOAEL

High

Birds - Acute LD₅₀ (mg kg⁻¹)

11.3

Colinus virginianus

High

Birds - Short term dietary (LC₅₀/LD₅₀)

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

0.88

Colinus virginianus NOEL

High

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

> 500

Eisenia foetida corr

Moderate

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

500

Eisenia foetida corr

Low

Soil micro-organisms

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

Dose: 0.67 mg kg⁻¹ soil 28 Day

Collembola

Acute LC₅₀ (mg kg⁻¹)

0.32

Folsomia candida

Chronic NOEC (mg kg⁻¹)

Non-target plants

Honeybees (Apis spp.)

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

0.0059

Apis mellifera

High

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

0.00417

Apis mellifera

High

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)

0.004

Megachile rotundata

High

Mode of exposure

Contact

Other bee species (2)

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

0.0004

Melipona scutellaris

High

Mode of exposure

Contact

Beneficial insects (Ladybirds) as % Mortality at dose 100 g ha⁻¹

100

Coccinella septempunctata

Beneficial insects (Lacewings)

Beneficial insects (Parasitic wasps) as Mortality LR₅₀ g ha⁻¹ 48 hr

0.01

Aphidius rhopalosiphi Adult

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

0.101

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)

0.248

Oncorhynchus mykiss

Moderate

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

0.015

Oncorhynchus mykiss

Moderate

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

> 0.152

Danio rerio

Moderate

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

0.19

Daphnia magna

Moderate

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

0.068

Daphnia magna

Moderate

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

> 0.0006

Ceriodaphnia dubia

High

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

0.00014

Americamysis bahia

High

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

0.0037

Chironomus sancticaroli

High

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

0.0001

Chironomus riparius

High

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

0.0002

Chironomus riparius

High

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

0.16

Lemna gibba

Moderate

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

0.068

Scenedesmus subspicatus

Moderate

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

Mesocosm study data

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)

Rat

High

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

354

Rabbit

Mammals - Inhalation LC₅₀ (mg l⁻¹)

0.36

Rat

Other Mammal toxicity endpoints

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

0.0002

Dog SF=100

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

0.009

Rat SF=100

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

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

0.0035

Dog SF=100

Dermal penetration studies (%)

1.0

Dangerous Substances Directive 76/464

List II

Exposure Routes

Public

Negligible risk to bystanders as pesticide as normally used as seed treatment

Occupational

Risk of exposure acceptable under label recommendations for use for personal protection clothing and equipment

Mammalian dose elimination route and rate

Literature reports less than 1% of the applied dose was absorbed by rats after 24hrs when applied topically. The whole-blood half-life ranged from about 6.2-8.3 days after a single dose. Excreted via faeces and urine

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

Thyroid, kidney and liver toxicant
Highly toxic
Bioaccumulates
US EPA - possible human carcinogen

Handling issues

Property

Value and interpretation

General

Not explosive
IMDG Transport Hazard Class 6.1
Not expected to auto-ignite; Not highly flammable

CLP classification 2013

Health: H301, H311, H331, H372
Environment: H400, H410

WHO Classification

II (Moderately hazardous)

UN Number

UN2811

Waste disposal & packaging

Packaging Group III (minor danger)

Shelf-life, storage, stability and reactivity

Chemically stable under standard ambient conditions. Limited shelf-life. Store at 2-8 DegC

TRANSLATIONS

Language

Name

English

fipronil

French

fipronil

German

Fipronil

Danish

fipronil

Italian

fipronil

Spanish

fipronil

Greek

Polish

fipronil

Swedish

Hungarian

fipronil

Dutch

fipronil

Norwegian

Record last updated:	06/03/2024
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