Tolfenamic acid

Tolfenamic acid	Last updated: 16/09/2025
(Not known by any other names)

GENERAL INFORMATION

Description

A non-steroidal anti-inflammatory drug (NSAID) which is a structural analogue of flunixin

Examples of veterinary uses

Used for fever, postoperative pain, and acute and chronic inflammatory conditions

Examples of species treated

Cattle; Dogs; Cats; Pigs

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved - usually available as a prescription only medicine to be authorised by a veterinarian (POM-V)

EU Regulatory approval status

Approved

Chemical structure

Isomerism

Tolfenamic acid exhibits positional and conformational isomerism but not stereoisomerism. Its structure includes a substituted anthranilic acid core, where variations in the positions of chloro and methyl groups on the aromatic ring can lead to positional isomers. Additionally, the molecule can adopt different conformations due to rotation around single bonds, particularly between its aromatic rings and amide linkage, which may influence its biological activity. At least nine forms of tolfenamic acid have been identified, however, since it lacks any chiral centres, tolfenamic acid does not form enantiomers or diastereomers.

Chemical formula

C₁₄H₁₂ClNO₂

Canonical SMILES

CC1=C(C=CC=C1Cl)NC2=CC=CC=C2C(=O)O

Isomeric SMILES

International Chemical Identifier key (InChIKey)

YEZNLOUZAIOMLT-UHFFFAOYSA-N

International Chemical Identifier (InChI)

InChI=1S/C14H12ClNO2/c1-9-11(15)6-4-8-12(9)16-13-7-3-2-5-10(13)14(17)18/h2-8,16H,1H3,(H,17,18)

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
tolfenamic acid	-

General status

Veterinary substance type

Anti-inflammatory, Analgesic, Medicinal drug

Substance groups

Unclassified substance

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Directly inhibits prostaglandin receptors

Molecular targets

[Prostaglandin G/H Synthase 1, Antagonist]

CAS RN

13710-19-5

EC number

237-264-3

CIPAC number

US EPA chemical code

PubChem CID

Therapeutic Class

Musculo-skeletal system: Non-steroidal anti-inflammatory and antirheumatic products

ATCvet Code

QM01AG02

Controlled Drug?

Regulation 37/2010 MRL Classification

Allowed substance (Table 1: Bovine, Porcine)

Molecular mass

261.71

PIN (Preferred Identification Name)

IUPAC name

2-[(3-chloro-2-methylphenyl)amino]benzoic acid)

CAS name

N-(2-methyl-3-chlorphenyl)-anthranilic acid

Forever chemical

Other status information

Relevant Environmental Water Quality Standards

Physical state

Related substances & organisms

flunixin

Commercial

Property

Value

Availability status

Current

Introduction & key dates

1980s, discovery; 1990s, first European approvals

Example manufacturers & suppliers of products using this active now or historically

Vetoquinol UK

Example products using this active

Tolfedine Solution for Injection
Tolfedine Tablets

Formulation and application details

Usually supplied as a sterile solution for injection or in tablet form for oral administration

Commercial production

Tolfenamic acid is synthesised through a multi-step chemical process involving the condensation of 2-chlorobenzoic acid with 3-chloro-2-methylaniline. Initially, 2-chlorobenzoic acid is reacted with sodium hydroxide in a solvent like methyl isobutyl ketone under reflux conditions. Then, 3-chloro-2-methylaniline is added along with a catalyst such as copper(II) bromide and an acid-binding agent, and the mixture is further heated to promote the formation of the amide bond. After the reaction is complete, the mixture undergoes acidification, typically with hydrochloric acid, to precipitate the crude tolfenamic acid. This is followed by filtration and recrystallisation, often using an ethanol-water mixture, to purify the final product.

Impact on climate of production and use

Published GHG data is not available for most pharmaceuticals. However, according to industry, global averages suggest producing 1 kg of a typical active pharmaceutical ingredient can range from 10 to 100 kg CO₂e for small molecule drugs and potentially up to 1000 kg CO₂e for complex biologicals such as vaccines, depending on the drug type, its formulation, complexity of synthesis, solvent recovery, and energy sources used.

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

0.78

Low

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

Melting point (°C)

206

Boiling point (°C)

Degradation point (°C)

Flashpoint (°C)

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

1.48 X 10⁰⁵

Calculated

Log P

5.17

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)

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)

CT₅₀ (days)

Known metabolites

None

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

225

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

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)

7.4

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 (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)

225

Rat

Moderate

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

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Intraperitoneal LD₅₀ = 238 mg kg⁻¹

Rat

Subcutaneous LD₅₀ = 267 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

Some metabolisim, the unchanged substance and its glucuronides are predominantly excreted into the bile

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 tremor, euphoria, fatigue and gastrointestinal problems
Possible lungs, thorax and respiratory system stimulant

Handling issues

Property

Value and interpretation

General

IMDG TransportHazard Class 6.1

CLP classification 2013

WHO Classification

Not listed (Not listed)

UN Number

UN2811

Waste disposal & packaging

Packaging Group III (minor danger) - may be product specific

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

tolfenamic acid

French

acide tolfenamique

German

Danish

Italian

Spanish

ácido tolfenámico

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	16/09/2025
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