Griseofulvin

Griseofulvin	Last updated: 25/04/2024
(Also known as: grisovin; delmofulvina; grisefuline; (+)-griseofulvin)

GENERAL INFORMATION

Description

Natural substance used to treat fungal infections which has some veterinary applications

Availability status

Considered obsolete but may be available in some countries

Introduction & key dates

1939, first reported

Examples of veterinary uses

Used to treat ringworm and other skin, hair, and nail fungal infections

Examples of species treated

Horses

Approval status

VMR 2013/2033 approval status (GB/UK)

Not approved

EU Regulatory approval status

Not approved

Chemical structure

Isomerism

Griseofulvin is a chiral molecule. Substance is racemic.

Chemical formula

C₁₇H₁₇ClO₆

Canonical SMILES

CC1CC(=O)C=C(C12C(=O)C3=C(O2)C(=C(C=C3OC)OC)Cl)OC

Isomeric SMILES

C[C@@H]1CC(=O)C=C([C@]12C(=O)C3=C(O2)C(=C(C=C3OC)OC)Cl)OC

International Chemical Identifier key (InChIKey)

DDUHZTYCFQRHIY-RBHXEPJQSA-N

International Chemical Identifier (InChI)

InChI=1S/C17H17ClO6/c1-8-5-9(19)6-12(23-4)17(8)16(20)13-10(21-2)7-11(22-3)14(18)15(13)24-17/h6-8H,5H2,1-4H3/t8-,17+/m1/s1

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
griseofulvin	Unstated isomer
griseofulvin	-

General status

Veterinary substance type

Fungicide, Antifungal, Antibiotic

Substance groups

Benzofuran fungicide

Minimum active substance purity

97%

Known relevant impurities

Substance origin

Natural

Mode of action

Acts by binding to keratin in keratin precursor cells making them resistant to fungal infections.

Molecular targets

[Tubulin beta chain, Antagonist], [Tubulin alpha chain, Antagonist], [Keratin, type I cytoskeletal 12]

CAS RN

126-07-8

EC number

204-767-4

CIPAC number

308

US EPA chemical code

471400

PubChem CID

441140

CLP index number

No data found

Therapeutic Class

Dermatologicals: Antifungals for dermatological use

ATCvet Code

QD01BA01

Controlled Drug?

Regulation 37/2010 MRL Classification

Molecular mass

352.77

PIN (Preferred Identification Name)

IUPAC name

(2S,6'R)-7-chloro-2',4,6-trimethoxy-6'-methyl-3H,4'H-spiro [1-benzofuran-2,1'-cyclohex[2]ene]-3,4'-dione

CAS name

7-chloro-4,6-dimethoxycoumaran-3-one-2-spiro-1'-(2'-methoxy-6'-methylcyclohex-2'-en-4'-one)

Other status information

Relevant Environmental Water Quality Standards

Physical state

White to pale cream-coloured, odourless crystalline powder

Formulations

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Example products (past and present) using this active

Grisol V Granules 7.5%

Vetoquinol UK Limited

Not licensed

Grisol V Powder 7.5% w/w oral powder

Vetoquinol UK Limited

Not licensed

Formulation and application details

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

8.64

Low

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

Melting point (°C)

218

Boiling point (°C)

570

Degradation point (°C)

210

sublimes

Flashpoint (°C)

228

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

2.29 X 10⁰²

Calculated

Log P

2.36

Low

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

1.43

Dissociation constant pKa) at 25 °C

Vapour pressure at 20 °C (mPa)

1.28 X 10^-03

Low volatility

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

Max 286nm and 325nm

Surface tension (mN m⁻¹)

Refractive Index

1.5403

at 25°C

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 soil and groundwater metabolites

None

Other known metabolites

Metabolite name and reference

Aliases

Formation medium / Rate

Estimated maximum occurrence fraction

6-dimethylgriseofulvin

Mammals (Urine)

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

> 10000

Rat

Low

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)

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)

> 1000

Daphnia magna

Low

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)

High (class III)

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

> 10000

Rat

Low

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

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Intraperitoneal LD₅₀ > 5000 mg kg⁻¹

Rat

Subcutaneous LD₅₀ > 12000 mg kg⁻¹

Mouse

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

Excreted mainly in the urine and faeces. Deposited in varying concentrations in the keratin layer of the skin, hair, and nails

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

General human health issues

IARC Group 2B carcinogen; CLP data - suspected carcinogen
May cause nausea, diarrhoea, hives, hives and fatigue
Possible blood and liver toxicant

Handling issues

Property

Value and interpretation

General

When heated to decomposition it emits toxic fumes of halogen gases

CLP classification 2013

Health: H317, H351, H360
Environment: H411

WHO Classification

Not classified: Obsolete (Not classified: Obsolete)

UN Number

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

griseofulvin

French

griseofulvine

German

Danish

Italian

Spanish

griseofulvina

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	25/04/2024
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