Clavulanic acid

Clavulanic acid	Last updated: 08/09/2025
(Not known by any other names)

GENERAL INFORMATION

Description

A substance with weak antibacterial activity but used in conjunction with amoxycillin to treat many gram-positive and gram-negative, aerobic and anaerobic microorganisms

Examples of veterinary uses

It is mainly used to treat skin and soft tissue infections and periodontal (gum) disease

Examples of species treated

Cats; Dogs; Cattle; Pigs; Sheep

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved

EU Regulatory approval status

Approved

Chemical structure

Isomerism

Clavulanic acid exhibits stereoisomerism, specifically geometric (cis–trans or E/Z) and optical isomerism, due to its unique beta-lactam structure and substituents. The molecule contains a double bond between the C-2 and C-3 positions, which allows for E/Z isomerism, with the naturally occurring form being the Z-isomer, where the substituents are on the same side of the double bond. Additionally, clavulanic acid has two chiral centres at C-2 and C-5, giving rise to diastereomers. The biologically active form is the (2R,5R,Z)-isomer, which is crucial for its function as a beta-lactamase inhibitor.

Chemical formula

C₈H₉NO₅

Canonical SMILES

C1C2N(C1=O)C(C(=CCO)O2)C(=O)O

Isomeric SMILES

C1[C@@H]2N(C1=O)[C@H](/C(=C/CO)/O2)C(=O)O

International Chemical Identifier key (InChIKey)

HZZVJAQRINQKSD-PBFISZAISA-N

International Chemical Identifier (InChI)

InChI=1S/C8H9NO5/c10-2-1-4-7(8(12)13)9-5(11)3-6(9)14-4/h1,6-7,10H,2-3H2,(H,12,13)/b4-1-/t6-,7-/m1/s1

2D structure diagram/image available?

Yes

General status

Veterinary substance type

Antibiotic, Antibacterial, Medicinal drug

Substance groups

Penicillin related

Minimum active substance purity

Known relevant impurities

Substance origin

Natural

Mode of action

Broad-spectrum. A beta-lactamase inhibitor

Molecular targets

[Beta-lactamase, Inhibitor]

CAS RN

58001-44-8

EC number

261-069-2

CIPAC number

US EPA chemical code

PubChem CID

Therapeutic Class

Antiinfectants for systemic use: Antibacterials for systemic use

ATCvet Code

QJ01CR02

Controlled Drug?

Regulation 37/2010 MRL Classification

Allowed substance (Table 1: Bovine, Porcine)

Molecular mass

199.16

PIN (Preferred Identification Name)

IUPAC name

(2R,5R,Z)- 3-(2-hydroxyethylidene)- 7-oxo- 4-oxa- 1-aza- bicyclo[3.2.0]heptane- 2-carboxylic acid

CAS name

Forever chemical

Other status information

Relevant Environmental Water Quality Standards

Physical state

Off-white crystalline powder

Related substances & organisms

amoxicillin

Commercial

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Availability status

Current

Introduction & key dates

1974, discovered

Example products (past and present) using this active

Cladaxxa Chewable Tablets

Krka D.D. Novo Mesto

GB National authorisation

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

Clavaseptin Palatable Tablets

Vetoiquinol UK Ltd

GB National authorisation

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

Combiclay Suspension for Injection

Norbrook Laboratories Ltd

UK National authorisation

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

Synuclay Tablets 50mg

Norbrook Laboratories Ltd

GB National authorisation

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

Formulation and application details

Usually supplied in chewable/palatable tablet form

Commercial production

Clavulanic acid is produced through a microbial fermentation process using the actinomycete Streptomyces clavuligerus, which naturally synthesises the compound as a secondary metabolite. The production begins with the cultivation of this microorganism in a nutrient-rich medium, where glycerol is typically used as the preferred carbon source due to its efficiency in promoting clavulanic acid biosynthesis. The fermentation is carried out under controlled conditions to optimise yield. Organic nitrogen sources like soybean protein or amino acids are added to enhance production. After fermentation, the broth is subjected to filtration and extraction, often involving ion-exchange resins or solvent systems to isolate clavulanic acid.

Impact on climate of production and use

As microbial-based products tend to use fermentation-based production processes rather than chemical synthesis, they typically have a lower fossil fuel input in formulation and active ingredient creation, and also have reduced downstream emissions due to biodegradability and minimal soil disruption, their life-cycle GHG emissions are expected to be low. Whilst hard and precise data is not available, broad estimates suggest that typically emissions are likely to be below 5 kg CO₂e/kg.

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

300000

High

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

Melting point (°C)

117.5

Boiling point (°C)

Degradation point (°C)

Flashpoint (°C)

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

9.12 X 10^-03

Calculated

Log P

-2.04

Low

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

2.7

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)

Sediment 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)

Low risk

Based on LogP < 3

Low risk

CT₅₀ (days)

Known soil and groundwater metabolites

None

Other known metabolites

Metabolite name and reference

Aliases

Formation medium / Rate

Estimated maximum occurrence fraction

2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid

Human

1-amino-4-hydroxybutan-2-one

Rat; Dog; Human

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

> 2000

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

Vegetative vigour ER₅₀ (g ha⁻¹)

Seedling emergence ER₅₀ (g ha⁻¹)

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

Notes

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)

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 (free-floating, fonds growth, fresh) - 7 day (mg l⁻¹)

Aquatic plants (rooted, growth rate, fresh) - 14 day (mg l⁻¹)

Algae - Acute (growth rate, fresh; mg l⁻¹)

Algae - Chronic (growth rate, fresh; 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)

> 2000

Rat

Low

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

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Subcutaneous LD₅₀ = 1393 mg kg⁻¹

Rat

Intraperitoneal LD₅₀ = 1399 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

Mainly eliminated unchanged in the urine

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

May cause gastrointestinal problems
May cause seizures, chest pain & irregular heartbeat

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

TRANSLATIONS

Language

Name

English

clavulanic acid

French

acide clavulanique

German

Danish

Italian

Spanish

acido clavulanico

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	08/09/2025
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