Clotrimazole

Clotrimazole	Last updated: 15/05/2024
(Not known by any other names)

GENERAL INFORMATION

Description

Clotrimazole is a topical triazole broad-spectrum antifungal veterinary compound

Availability status

Current

Introduction & key dates

late-1960s, discovered

Examples of veterinary uses

Used to treat a range of internal and external fungal infections (e.g. ringworm, otitis media). Also exhibits activity against Gram +ve bacteria

Examples of species treated

Dogs; Cats

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved

EU Regulatory approval status

Approved

Chemical structure

Isomerism

None

Chemical formula

C₂₂H₁₇CIN₂

Canonical SMILES

C1=CC=C(C=C1)C(C2=CC=CC=C2)(C3=CC=CC=C3Cl)N4C=CN=C4

Isomeric SMILES

International Chemical Identifier key (InChIKey)

VNFPBHJOKIVQEB-UHFFFAOYSA-N

International Chemical Identifier (InChI)

InChI=1S/C22H17ClN2/c23-21-14-8-7-13-20(21)22(25-16-15-24-17-25,18-9-3-1-4-10-18)19-11-5-2-6-12-19/h1-17H

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
clotrimazole	-

General status

Veterinary substance type

Medicinal drug, Antifungal agent, Antimycotic drug

Substance groups

Imazazole fungicide; Imazazole medicinal drug; Triazole fungicide; Triazole medicinal drug

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Inhibits the biosynthesis of ergosterol

Molecular targets

[Cytochrome P450 51, Antagonist], [Intermediate conductance calcium-activated potassium channel protein 4, Inhibitor], [Ergosterol, Inhibitor], [Nuclear receptor subfamily 1 group I member 2, Activator], [Hydroxycarboxylic acid receptor 2, Agonist]

CAS RN

23593-75-1

Alternative/old CAS RN

117829-71-7

EC number

245-764-8

CIPAC number

US EPA chemical code

PubChem CID

2812

Therapeutic Class

Alimentary tract & metabolism: Antiinfectives and antiseptics; Dermatologicals: Imidazole & triazole derivatives; Genito urinary system & sex hormones: Imidazole derivatives; Antiinfectives for systemic use: Imidazole derivatives

ATCvet Code

QA01AB18; QD01AC01; QG01AF02; QJ02AB90

Controlled Drug?

Regulation 37/2010 MRL Classification

Molecular mass

344.84

PIN (Preferred Identification Name)

1-[(2-chlorophenyl)-diphenylmethyl]imidazole

IUPAC name

1-[(2-chlorophenyl)-diphenylmethyl]imidazole

CAS name

Other status information

Relevant Environmental Water Quality Standards

Physical state

Off-white solid

Formulations

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Example products (past and present) using this active

Aurizon Ear Drops, Suspension

Vetoquinol UK Ltd

GB National authorisation

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

Otomax Ear Drops Suspension

MSD Animal Health UK Limited

GB National authorisation

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

Marbodex Aural Ear Drops, Suspension for Dogs

Norbrook Laboratories Limited

GB National authorisation

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

Formulation and application details

Formulated, often in combination with other medications (e.g. marbofloxacin, dexamethasone), as a suspension solution

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

3.7

Low

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

Melting point (°C)

147

Boiling point (°C)

Degradation point (°C)

141

Flashpoint (°C)

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

1.58 X 10⁰⁶

Calculated

Log P

6.2

High

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

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)

K_oc (mL g⁻¹)

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 metabolites

None

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

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)

> 0.29

Unknown species

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)

0.10

Daphnia magna

Moderate

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

HUMAN HEALTH AND PROTECTION

General

Property

Value

Source; quality score; and other information

Interpretation

Threshold of Toxicological Concern (Cramer Class)

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

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

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

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

Mainly hepatic

Health issues

Specific human health issues

Carcinogen

Genotoxic

Endocrine disruptor

; ; ; ;

No data found

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

No information available

Handling issues

Property

Value and interpretation

General

Combustible
Not corrosive
IMDG Transport Hazard Class 9

CLP classification 2013

Health: H301, H315, H319, H361, H373
Environment: H400, H410

WHO Classification

Not listed (Not listed)

UN Number

UN3077

Waste disposal & packaging

Packaging Group III (minor danger)

Shelf-life, storage, stability and reactivity

Generally stable

TRANSLATIONS

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Name

English

clotrimazole

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Record last updated:	15/05/2024
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