Levamisole

Levamisole	Last updated: 09/02/2024
(Also known as: tetramisole ; levomysol; L-tetramisole)

GENERAL INFORMATION

Description

A veterinary antiparasitic drug of the imidazothiazole class which is usually used as the hydrochloride salt

Availability status

Current

Introduction & key dates

1966, discovered

Examples of veterinary uses

Used mainly as a dewormer in livestock and for freshwater tropical fish

Examples of species treated

Cattle; Pigs; Sheep; Freshwater tropical fish; Elephants

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved

EU Regulatory approval status

Approved

Chemical structure

Isomerism

Levamisole is the biologically active isomer of the isomeric tetramisole

Chemical formula

C₁₁H₁₂N₂S

Canonical SMILES

C1CSC2=NC(CN21)C3=CC=CC=C3

Isomeric SMILES

C1CSC2=N[C@H](CN21)C3=CC=CC=C3

International Chemical Identifier key (InChIKey)

HLFSDGLLUJUHTE-SNVBAGLBSA-N

International Chemical Identifier (InChI)

InChI=1S/C11H12N2S/c1-2-4-9(5-3-1)10-8-13-6-7-14-11(13)12-10/h1-5,10H,6-8H2/t10-/m1/s1

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
levamisole	-
levamisole hydrochloride	Variant

General status

Veterinary substance type

Dewormer, Antiparasitic, Anthelmintic

Substance groups

Imidazothiazole

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Works by causing parasitic paralysis allowing it to be expelled. Nicotinic receptor agonist.

Molecular targets

[Neuronal acetylcholine receptor subunit alpha-3, Agonist], [Alkaline phosphatase, placental-like, Antagonist]

CAS RN

14769-73-4

EC number

238-836-5

CIPAC number

US EPA chemical code

PubChem CID

Therapeutic Class

Antiparasitic products, insecticides & repellents: Anthelmintics

ATCvet Code

QP52AE01

Controlled Drug?

Regulation 37/2010 MRL Classification

Allowed substance (Table 1: Bovine, Ovine, Porcine, Poultry)

Molecular mass

204.29

PIN (Preferred Identification Name)

IUPAC name

(S)-6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole

CAS name

Other status information

Relevant Environmental Water Quality Standards

Physical state

White solid

Related substances & organisms

tetramisole hydrochloride

levamisole hydrochloride

Formulations

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Example products (past and present) using this active

Formulation and application details

Usually formulated, as the hydrochloride, as solutions for oral administration or injections

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

1120

High

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

Melting point (°C)

Boiling point (°C)

Degradation point (°C)

Flashpoint (°C)

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

6.92 X 10⁰¹

Calculated

Log P

1.84

Low

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

1.31

Dissociation constant pKa) at 25 °C

Vapour pressure at 20 °C (mPa)

14.76

Highly volatile. If applied directly to plants or soil, drift is a concern & mitigation is advisable

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

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)

DT₅₀ (lab at 20 °C)

DT₅₀ (field)

DT₉₀ (lab at 20 °C)

DT₉₀ (field)

Note

Manure DT₅₀ (days)

Aqueous photolysis DT₅₀ (days) at pH 7

Value

Note

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.

Decay in stored produce DT₅₀

Soil adsorption and mobility

Property

Value

Source; quality score; and other information

Interpretation

Linear

K_d (mL g⁻¹)

Non-mobile

K_oc (mL g⁻¹)

8652

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

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

Ref: R92535

Rat; Dog, Monkey (Urine)

4-[(6S)-2,3,5,6-tetrahydroimidazol[2,1-b)thiazol-6-yl]phenol (Ref: R9313)

p-hydroxylevamisole; p-OH-levamisole

Humans; Rat; Dog; Monkey (Urine)

Ref: R43837

Dog; Monkey (Urine)

Ref: R43037

Dog (Urine)

Ref: R8418

Dog

Ref: R9280

Dog

Ref: R45714

(RS)-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine
Note: Pharmaceutically active

Aminorex

Horse (Urine)

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

180

Rat

Moderate

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)

Birds - Short term dietary (LC₅₀/LD₅₀)

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

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

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)

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)

> 1750

Anguilla spp.

Low

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)

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)

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)

180

Rat

Moderate

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

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Subcutaneous LD₅₀ = 120 mg kg⁻¹

Rat

Intravenous LD₅₀ = 24 mg kg⁻¹

Rat

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

Mammalian dose elimination route and rate

High level of metabolism, less than 6% excreted unchanged in urine, metabolites excreted in both urine and faeces

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

Possible immune system and blood toxicant
May cause stomatitis, nausea, vomiting and adbominal pain

Handling issues

Property

Value and interpretation

General

IMDG Transport Hazard Class 6.1

CLP classification 2013

WHO Classification

Not listed (Not listed)

UN Number

UN2811

Waste disposal & packaging

Packaging Group III (minor danger)

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

levamisole

French

German

Danish

Italian

Spanish

levamisol

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	09/02/2024
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