Trimethoprim

Trimethoprim	Last updated: 06/09/2025
(Also known as: TRI; TMP; trimexazole; SMX-TMP)

GENERAL INFORMATION

Description

A synthetic bacteriostatic antibiotic used as a veterinary medicine active against both gram-positive and gram-negative bacteria

Examples of veterinary uses

Used to treat infections of the respiratory tract, urogenital tract, alimentary tract, skin joints and wound

Examples of species treated

Cats; Dogs; Horses; Cattle; Pigs; Turkeys; Sheep

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

Trimethoprim exhibits structural isomerism, specifically positional isomerism, due to the arrangement of its functional groups on the aromatic rings. The molecule consists of a 2,4-diaminopyrimidine ring linked to a 3,4,5-trimethoxybenzyl group. The two known structural isomers of trimethoprim are 2-methoxybenzyl-1,3-diazine and 3-methoxybenzyl-1,2-diazine, which share the same molecular formula but differ in the positions of the methoxy and diazine groups.

Chemical formula

C₁₄H₁₈N₄O₃

Canonical SMILES

COC1=CC(=CC(=C1OC)OC)CC2=CN=C(N=C2N)N

Isomeric SMILES

No data

International Chemical Identifier key (InChIKey)

IEDVJHCEMCRBQM-UHFFFAOYSA-N

International Chemical Identifier (InChI)

InChI=1S/C14H18N4O3/c1-19-10-5-8(6-11(20-2)12(10)21-3)4-9-7-17-14(16)18-13(9)15/h5-7H,4H2,1-3H3,(H4,15,16,17,18)

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
trimethoprim	-

General status

Veterinary substance type

Antibiotic, Antibacterial, Medicinal drug, Medicated feed additive

Substance groups

Diaminopyrimidine

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Interferes with the action of bacterial dihydrofolate reductase, inhibiting synthesis of tetrahydrofolic acid

Molecular targets

[Thymidylate synthase, Antagonist], [Dihydrofolate reductase, Antagonist]

CAS RN

738-70-5

EC number

212-006-2

CIPAC number

US EPA chemical code

PubChem CID

Therapeutic Class

Antiinfectants for systemic use: Antibacterials for intramammary use, Antibacterials for systemic use

ATCvet Code

QJ51EA01; QJ01EA01

Controlled Drug?

Regulation 37/2010 MRL Classification

Allowed substance (Table 1: Equidae, All food producing species)

Molecular mass

290.32

PIN (Preferred Identification Name)

IUPAC name

5-(3,4,5- trimethoxybenzyl) pyrimidine-2,4-diamine

CAS name

2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine

Forever chemical

Other status information

Relevant Environmental Water Quality Standards

Physical state

White to cream coloured crystalline powder

Related substances & organisms

sulphachlorpyridazine

ormetoprim

sulphadimethoxine

Commercial

Property

Value

Availability status

Current

Introduction & key dates

Circa 1965, discovered; 1973, approved

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

GlaxoSmithKline
Novartis
Bimeda Animal Health Ltd
Eurovet Animal Health B.V.

Example products using this active

Proloprim
Monotrim
Triprim
Bimotrim Solution for Injection
Diatrim Oral Powder
Metaxol Solution for Drinking Water

Formulation and application details

Available in a variety of formulations including tablets, oral pastes, medicated premix feeds, additives for drinking water and solutions for injection

Commercial production

The production of trimethoprim involves a multi-step synthetic process based around constructing its core structure: a 2,4-diaminopyrimidine ring linked to a 3,4,5-trimethoxybenzyl group. One common route begins with 3,4,5-trimethoxybenzaldehyde, which undergoes a Knoevenagel condensation with malonic acid derivatives to form an intermediate. This is then partially reduced using hydrogen gas over a palladium on carbon catalyst to yield an enamine. The enamine is reacted with guanidine, initiating a heterocyclisation reaction that forms the pyrimidine ring. In another pathway, the hydroxyl group on the intermediate pyrimidine is replaced with chlorine using phosphorus oxychloride, and then substituted with an amino group via ammonia treatment, yielding the final trimethoprim compound.

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)

400

Moderate

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

18200

Chloroform

25700

Propylene glycol

Ether

Benzene

Melting point (°C)

201

Boiling point (°C)

Degradation point (°C)

Flashpoint (°C)

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

8.13 X 10⁰⁰

Calculated

Log P

0.91

Low

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

7.12

Weak base

Vapour pressure at 20 °C (mPa)

1.31 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

Surface tension (mN m⁻¹)

Refractive Index

Environmental release

Substance may enter the environment via the urine and faeces of treated animals

Degradation

Property

Value

Source; quality score; and other information

Interpretation

Soil degradation (days) (aerobic)

DT₅₀ (typical)

110

Persistent

DT₅₀ (lab at 20 °C)

DT₅₀ (field)

DT₉₀ (lab at 20 °C)

DT₉₀ (field)

Note

Manure DT₅₀ (days)

31.5

Sewage sludge DT59 range 22-41 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)

Slightly mobile

K_oc (mL g⁻¹)

2835

Notes and range

General literature states K_oc range 1680-3990 mL g⁻¹

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

1.12

Calculated

Low leachability

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

1-N-oxide metabolite

Animals

3-N-oxide metabolite

Animals

4-hydroxy metabolite

Animals

3-hydroxy metabolite

Animals

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

4850

Mouse

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)

> 100

Oryzias latipes

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)

123

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

> 1.0

Lemna gibba 7 day

Moderate

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

Algae - Acute (growth rate, fresh; mg l⁻¹) (EC₅₀)

80.3

Raphidocelis subcapitata

Low

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

25.5

Raphidocelis subcapitata

Low

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)

4850

Mouse

Low

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

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Intraperitoneal LD₅₀ = 500 mg kg⁻¹

Rat

Subcutaneous LD₅₀ > 5000 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

Up to 20% of dose is metabolised in the liver and is excreted unchanged in the urine and faeces

Health issues

Specific human health issues

Carcinogen

Genotoxic

Endocrine disruptor

No data found

; ; ; ;

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 nausea and vomiting
May cause disturbance in the production of blood cells
Mmay cause hyperkalaemia

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

trimethoprim

French

trimethoprime

German

Danish

Italian

Spanish

trimetoprima

Greek

Polish

trimetoprim

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	06/09/2025
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