Amitraz (Ref: ENT 27967)

Amitraz (Ref: ENT 27967)	Last updated: 22/08/2024
(Also known as: amitraze; amitrazum ; BTS 27419; BAAM; U-36059)

SUMMARY

Amitraz is an amidine acaricide and insecticide. It is volatile, almost insoluble in water and, based on its chemical properties, is only slightly mobile with a low potential for leaching to groundwater. It is not persistent in soil systems, degradation being very rapid and would also not be expected to persistent in surface water under normal conditions. Amitraz has a moderate mammalian toxicity and there is some concern regarding its potential for bioaccumulation. It is considered to be a neurotoxin. Amitraz has a high to moderate toxicity to most terrestrial and aquatic species, the main exception being algae for which amitraz has a low level of toxicity.

GENERAL INFORMATION

Description

An amidine topically applied insecticide

Availability status

Current

Introduction & key dates

circa 1972, introduced

Examples of veterinary uses

Once used to treat demodicosis mange. It is also used as a topical treatment for flea and tick infestations; and in-hive to control honeybee varroa mite infestations

Examples of species treated

Dogs; Pigs; Cattle; Sheep; Bees

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved (bees only)

EU Regulatory approval status

Approved (bees only)

Chemical structure

Isomerism

None

Chemical formula

C₁₉H₂₃N₃

Canonical SMILES

CC1=CC(=C(C=C1)N=CN(C)C=NC2=C(C=C(C=C2)C)C)C

Isomeric SMILES

International Chemical Identifier key (InChIKey)

QXAITBQSYVNQDR-UHFFFAOYSA-N

International Chemical Identifier (InChI)

InChI=1S/C19H23N3/c1-14-6-8-18(16(3)10-14)20-12-22(5)13-21-19-9-7-15(2)11-17(19)4/h6-13H,1-5H3/b20-12+,21-13+

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
amitraz	-

General status

Veterinary substance type

Antiparasitic

Substance groups

Amidine insecticide; Formamidine insecticide

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Non-systemic having contact and respiratory action. Acts on nervous system. Octopamine receptor agonist.

Molecular targets

[Alpha-2A adrenergic receptor], [5-hydroxytryptamine receptor 7], [Cytochrome P450 1A2], [Interleukin-1 alpha], [Urokinase plasminogen activator surface receptor], [Cytochrome P450 2C19], [C-C motif chemokine 2], [Cytochrome P450 1A1

CAS RN

33089-61-1

EC number

251-375-4

CIPAC number

362

US EPA chemical code

106201

PubChem CID

36324

CLP index number

612-086-00-2

Therapeutic Class

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

ATCvet Code

QP53AD51 / QP53AD01

Controlled Drug?

Regulation 37/2010 MRL Classification

Allowed substance (Table 1: Bovine, Ovine, Porcine, Caprine, Bees)

Molecular mass

293.41

PIN (Preferred Identification Name)

N'-(2,4-dimethylphenyl)-N-{[(2,4-dimethylphenyl)imino]methyl}-N-methylmethanimidamide

IUPAC name

N,N'-[(methylimino)dimethylidyne]di-2,4-xylidine

CAS name

N'-(2,4-dimethylphenyl)-N-[[(2,4-dimethylphenyl)imino]methyl]-N-methylmethanimidamide

Other status information

PAN Bad Actor Chemical; Cannot be used on horses

Relevant Environmental Water Quality Standards

Physical state

Straw coloured crystalline solid

Formulations

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Example products (past and present) using this active

Aludex 50g/l Conc

Intervet Ltd

Not licensed

Promeris Duo Spot on for small dogs

Pfizer Ltd

Not licensed

Apivar 500 mg bee-hive strips for honey bees

Laboratories Calier SA

GB National authorisation

Authorised veterinary medicine for general sale (AVM-GSL)

Apivar Bee-hive strips

Veto-Pharma

GB National authorisation

Authorised veterinary medicine for general sale (AVM-GSL)

Formulation and application details

Currently only licensed for use in bee hives to treat Varroa destructor parasites. Supplied as impregnated strips for suspending inside the hive

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

0.1

Low

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

Melting point (°C)

Boiling point (°C)

Decomposes before boiling

Degradation point (°C)

Flashpoint (°C)

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

3.16 X 10⁰⁵

Calculated

Log P

5.5

High

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

1.13

Dissociation constant pKa) at 25 °C

9.8

Weak acid

Vapour pressure at 20 °C (mPa)

0.051

Low volatility

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

1.06

Moderately volatile

Volatilisation as max % of applied dose lost

From plant surface

From soil surface

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

Surface tension (mN m⁻¹)

Refractive Index

Environmental release

Degradation

Property

Value

Source; quality score; and other information

Interpretation

Soil degradation (days) (aerobic)

DT₅₀ (typical)

0.2

Non-persistent

DT₅₀ (lab at 20 °C)

0.2

Non-persistent

DT₅₀ (field)

Non-persistent

DT₉₀ (lab at 20 °C)

DT₉₀ (field)

Note

Literature DT₅₀ studies range 0.1-2 days

Manure DT₅₀ (days)

Aqueous photolysis DT₅₀ (days) at pH 7

Value

Note

Stable in UV light

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

Value

Non-persistent

Note

pH sensitive: DT₅₀ 2hrs at pH 5, 1.1 days at pH 9, rapid hydrolysis

Water-sediment DT₅₀ (days)

Water phase only DT₅₀ (days)

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)

Slightly mobile

K_oc (mL g⁻¹)

1000

Notes and range

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

0.00

Calculated

Low leachability

Bio-concentration factor

BCF (l kg⁻¹)

1838

Threshold for concern

CT₅₀ (days)

Not available

Known soil metabolites

Metabolite

Major/Minor fraction

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

Estimated maximum occurrence fraction

Notes

N'-(2,4-dimethylphenyl)-N-methyl-methanimidamide

Minor fraction

Aerobic

N-(2,4-dimethylphenyl)formamide

Minor fraction

Anaerobic

semiamitraz hydrochloride (Ref: BTS-27271)

Major fraction

2,4-dimethylformanilide (Ref: BTS 27919)

Minor fraction

2,4-dimethylbenzenamine

Minor fraction

Anaerobic

2,4-dimethylaniline

Minor fraction

Aerobic

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)

800

Rat

Moderate

Mammals - Short term dietary NOEL

(mg kg⁻¹)

Rat 2 yr

(ppm diet)

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

Birds - Acute LD₅₀ (mg kg⁻¹)

788

Colinus virginianus

Moderate

Birds - Short term dietary (LC₅₀/LD₅₀)

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

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

1000

Moderate

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

Soil micro-organisms

Collembola

Acute LC₅₀ (mg kg⁻¹)

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)

Apis mellifera

Moderate

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

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)

Beneficial insects (Lacewings)

Moderately harmful at dose 360 g ha⁻¹

Chrysoperla carnea

Beneficial insects (Parasitic wasps)

Beneficial insects (Predatory mites)

Harmful at dose 360 g ha⁻¹

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)

0.74

Oncorhynchus mykiss

Moderate

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

> 0.00353

Pimephales promelas

High

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

4.25

Danio rerio

Moderate

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

0.035

Daphnia magna

High

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

0.002

Daphnia magna LOEC

High

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

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

4.7

Americamysis bahia

Moderate

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

> 8.0

Chironomus riparius 48 hr

Moderate

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

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)

Raphidocelis subcapitata

Low

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

Mesocosm study data

NOEAEC mg l⁻¹

Marine bivalves

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)

800

Rat

Moderate

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

200

Rabbit

Mammals - Inhalation LC₅₀ (mg l⁻¹)

65.0

Rat

Other Mammal toxicity endpoints

Intraperitoneal LD₅₀ = 800 mg kg⁻¹

Rat

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

0.003

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

0.01

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

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

Dermal penetration studies (%)

Dangerous Substances Directive 76/464

Exposure Routes

Public

Occupational

Occupational exposure may occur through inhalation and dermal contact

Mammalian dose elimination route and rate

In mammals urine is the major route of excretion. 55-74% of the dose was excreted after dosing within first 24hrs

Health issues

Specific human health issues

Carcinogen

Genotoxic

Endocrine disruptor

; ; ; ;

Reproduction / development effects

Acetyl cholinesterase inhibitor

Neurotoxicant

No data found

Respiratory tract irritant

Skin irritant

Skin sensitiser

Eye irritant

Phototoxicant

No data found

General human health issues

Ingestion may cause slow heart beat, low blood pressure, sedation and low body temperature
US EPA - possible human carcinogen

Handling issues

Property

Value and interpretation

General

Not expected to auto-ignite; Not highly flammable

CLP classification 2013

Health: H302, H317, H373
Environment: H400, H410

WHO Classification

II (Moderately hazardous)

UN Number

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

amitraz

French

amitraze

German

Amitraz

Danish

amitraz

Italian

amitraz

Spanish

amitraz

Greek

amitraz

Polish

amitraz

Swedish

Hungarian

amitraz

Dutch

amitraz

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