Ivermectin

Ivermectin	Last updated: 02/02/2024
(Also known as: 22,23-dihyroavermectin B1)

GENERAL INFORMATION

Description

A common veterinary antiparasitic medication for the treatment of certain internal and external parasites

Availability status

Current

Introduction & key dates

mid 1980s, introduced as an anthelmintic.

Examples of veterinary uses

Traditionally used against worms (except tapeworms) but more recently found to be effective against many species of mites and lice

Examples of species treated

Cattle; Pigs; Sheep; Horses

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved

EU Regulatory approval status

Approved

Chemical structure

Isomerism

Chiral molecules. Technical substance contains a mixture of 90% of 5-O-demethyl-22,23-dihydroavermectin A1b (B1a) and about 10% of 5-O-demethyl-25-de(1-methylpropyl)-22,23-dihydro 25–(1-methylethyl)avermectin (B1b)

Chemical formula

C₄₈H₇₄O₁₄ + C₄₇H₇₂O₁₄

Canonical SMILES

CCC(C)C1C(CCC2(O1)CC3CC(O2)CC=C(C(C(C=CC=C4COC5C4(C(C=C(C5O)C)C(=O)O3)O)C)OC6CC(C(C(O6)C)OC7CC(C(C(O7)C)O)OC)OC)C)C

Isomeric SMILES

CC[C@H](C)[C@@H]1[C@H](CC[C@@]2(O1)C[C@@H]3C[C@H](O2)C/C=C(/[C@H]([C@H](/C=C/C=C/4\CO[C@H]5[C@@]4([C@@H](C=C([C@H]5O)C)C(=O)O3)O)C)O[C@H]6C[C@@H]([C@H]([C@@H](O6)C)O[C@H]7C[C@@H]([C@H]([C@@H](O7)C)O)OC)OC)\C)C

International Chemical Identifier key (InChIKey)

AZSNMRSAGSSBNP-XPNPUAGNSA-N

International Chemical Identifier (InChI)

InChI=1S/C48H74O14.C47H72O14/c1-11-25(2)43-28(5)17-18-47(62-43)23-34-20-33(61-47)16-15-27(4)42(26(3)13-12-14-32-24-55-45-40(49)29(6)19-35(46(51)58-34)48(32,45)52)59-39-22-37(54-10)44(31(8)57-39)60-38-21-36(53-9)41(50)30(7)56-38;1-24(2)41-27(5)16-17-46(61-41)22-33-19-32(60-46)15-14-26(4)42(25(3)12-11-13-31-23-54-44-39(48)28(6)18-34(45(50)57-33)47(31,44)51)58-38-21-36(53-10)43(30(8)56-38)59-37-20-35(52-9)40(49)29(7)55-37/h12-15,19,25-26,28,30-31,33-45,49-50,52H,11,16-18,20-24H2,1-10H3;11-14,18,24-25,27,29-30,32-44,48-49,51H,15-17,19-23H2,1-10H3/b13-12+,27-15+,32-14+;12-11+,26-14+,31-13+/t25-,26+,28+,30+,31+,33-,34?,35+,36+,37+,38?,39+,40-,41+,42+,43-,44+,45-,47-,48-;25-,27-,29-,30-,32+,33?,34-,35-,36-,37?,38-,39+,40-,41+,42-,43-,44+,46+,47+/m10/s1

2D structure diagram/image available?

Yes

General status

Veterinary substance type

Insecticide, Acaricide, Antihelmintic

Substance groups

Avermectin

Minimum active substance purity

Known relevant impurities

Substance origin

Semi-synthetic

Mode of action

Broad spectrum, Glutamate-gated chloride channel (GluCl) allosteric modulator. Induces flaccid paralysis in parasitic nematodes, in vitro.

Molecular targets

[Glycine receptor subunit alpha-3, Agonist], [Gamma-aminobutyric-acid (GABA) receptor subunit beta-3, Agonist]

CAS RN

70288-86-7

Alternative/old CAS RN

71827-03-7

EC number

274-536-0

CIPAC number

US EPA chemical code

PubChem CID

Therapeutic Class

Antiparasitic products, insecticides & repellents: Endectocides; Sensory organs: Otologicals

ATCvet Code

QP54AA01; QS02QA03

Controlled Drug?

Regulation 37/2010 MRL Classification

Allowed substance (Table 1: Mammalian food species)

Molecular mass

861.1

PIN (Preferred Identification Name)

IUPAC name

ivermectin (22,23-dihydroavermectin B1a + 22,23-dihydroavermectin B1b)

CAS name

ivermectin

Other status information

Relevant Environmental Water Quality Standards

UK Environment Agency non-statutory standard for the protection of aquatic life in fresh surface water: 0.0001 µg l⁻¹ as annual average, 0.001 µg l⁻¹ as max acceptable conc.
UK Environment Agency non-statutory standard for the protection of aquatic life in salt water: 0.001 µg l⁻¹ as annual average, 0.01 µg l⁻¹ as max acceptable conc.

Physical state

Off-white coloured, slightly hydroscopic powdery solid

Related substances & organisms

propylene glycol

Formulations

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Example products (past and present) using this active

Alomec Oral Paste

Virbac

UK National authorisation (IC)

Prescription only medicine to be authorised by suitably qualified person (POM-VPS)

Animec Pour-on Solution

Chanelle Animal Health Ltd

GB National authorisation

Prescription only medicine to be authorised by suitably qualified person (POM-VPS)

Bimectin Solution for Injection

Bimeda Animal health Ltd

UK National authorisation

Prescription only medicine to be authorised by suitably qualified person (POM-VPS)

Enovex 0.5% Pour-on Solution for Cattle

Norbrooks Labs

UK National authorisation (IC)

Prescription only medicine to be authorised by suitably qualified person (POM-VPS)

Formulation and application details

Available in a variety of formulations including solutions for injection, orals pastes and gels, and pour-on products

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

4.0

Low

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

30000

Butanol

Melting point (°C)

155

Boiling point (°C)

Degradation point (°C)

Flashpoint (°C)

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

Log P

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

Vapour pressure at 20 °C (mPa)

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

Volatilisation as max % of applied dose lost

From plant surface

From soil surface

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

In methanol: 238nm = 27100, 245nm = 30100

Surface tension (mN m⁻¹)

Refractive Index

Environmental release

Enviornmental releases of parent and metabolites is possible via faeces, urine and manure of treated animals

Degradation

Property

Value

Source; quality score; and other information

Interpretation

Soil degradation (days) (aerobic)

DT₅₀ (typical)

112

Persistent

DT₅₀ (lab at 20 °C)

DT₅₀ (field)

DT₉₀ (lab at 20 °C)

DT₉₀ (field)

Note

General literature states DT₅₀ range 7 to 240 days

Manure DT₅₀ (days)

>45

Other data; DT₅₀ 6 days dung; 7-14 days soil/faeces mix; USEPA: Soil/faeces mix DT₅₀ 100-200 days

Aqueous photolysis DT₅₀ (days) at pH 7

Value

Moderately fast

Note

DT₅₀ range 12hrs to 39hrs, temp dependent

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

Value

Note

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.

Soil adsorption and mobility

Property

Value

Source; quality score; and other information

Interpretation

Linear

K_d

Non-mobile

K_oc

14150

Notes and range

K_oc range 12600-15700 mL g⁻¹

Freundlich

K_f

K_foc

¹/_n

Notes and range

pH sensitivity

Fate indices

Property

Value

Source; quality score; and other information

Interpretation

GUS leaching potential index

-0.31

Calculated

Low leachability

Bio-concentration factor

BCF (l kg⁻¹)

CT₅₀ (days)

Known soil and groundwater metabolites

None

Other known metabolites

Metabolite name and reference

Aliases

Formation medium / Rate

Estimated maximum occurrence fraction

Metabolising enzymes

24-hydroxymethyl ivermectin

Cattle

3”-O-desmethyl ivermectin

Cattle

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

29.5

Rat

High

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)

Anas platyrhynchos

High

Birds - Short term dietary (LC₅₀/LD₅₀)

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

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

315

Eisenia foetida 28 day

Moderate

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

Moderate

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)

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)

Beneficial insects (Parasitic wasps)

Beneficial insects (Predatory mites)

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)

3.0

Oncorhynchus mykiss

Moderate

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

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

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

0.000025

Daphnia magna

High

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

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)

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)

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

< 0.001

Chlorella pyrenoidosa 14 day

High

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)

29.5

Rat

High

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

660

Rat

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Intraperitoneal LD₅₀ = 55 mg kg⁻¹

Rat

Intravenous TDLo = 0.571 mg kg⁻¹

Human

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

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

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

May be absorbed through the skin

Mammalian dose elimination route and rate

Ivermectin excreted in faeces of treated cattle with little metabolism

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

No data found

Eye irritant

Phototoxicant

No data found

General human health issues

May cause swollen lymph glands, dizziness, hypotension, fever and myalgia
Posible liver toxicant

Handling issues

Property

Value and interpretation

General

No information available

CLP classification 2013

WHO Classification

Not listed (Not listed)

UN Number

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

Stable for around 6 months when stored under ambient conditions

TRANSLATIONS

Language

Name

English

ivermectin

French

ivermectine

German

Danish

Italian

Spanish

ivermectino

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	02/02/2024
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