Trimethoprim	Last updated: 17/05/2024
(Also known as: TRI; TMP; trimexazole; SMX-TMP)

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GENERAL INFORMATION

Description	A synthetic bacteriostatic antibiotic used as a veterinary medicine active against both gram-positive and gram-negative bacteria
Availability status	Current
Introduction & key dates	circa 1965, discovered; 1973, approved
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
EU Regulatory approval status	Approved

Chemical structure

Isomerism	-
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?	No
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
Other status information	-
Relevant Environmental Water Quality Standards	-
Physical state	White to cream coloured crystalline powder
Related substances & organisms	sulphachlorpyridazine ormetoprim sulphadimethoxine

Formulations

Property	Product	Manufacturer	Authorisation Route	Legal Class (GB/UK)
Example products (past and present) using this active	Bimotrim Solution for Injection	Bimeda Animal Health Ltd	UK National authorisation	Prescription only medicine to be authorised by a veterinarian (POM-V)
	Diatrim Oral Powder	Eurovet Animal Health B.V.	GB National authorisation	Prescription only medicine to be authorised by a veterinarian (POM-V)
	Metaxol Solution for Drinking Water	Eurovet Animal Health B.V.	GB National authorisation	Prescription only medicine to be authorised by a veterinarian (POM-V)
	Norodine Bolus Tablets	Norbrook Laboratories Ltd	UK National authorisation (IC)	Prescription only medicine to be authorised by a veterinarian (POM-V)
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

ENVIRONMENTAL FATE

Property		Value	Source; quality score; and other information	Interpretation
Solubility - In water at 20 °C (mg l⁻¹)		400	R4 R = Peer reviewed scientific publications 4 = Verified data	Moderate
Solubility - In organic solvents at 20 °C (mg l⁻¹)		18200	L3 L = Pesticide manuals and hard copy reference books / other sources 3 = Unverified data of known source Chloroform	-
		25700	L3 L = Pesticide manuals and hard copy reference books / other sources 3 = Unverified data of known source Propylene glycol	-
		30	L3 L = Pesticide manuals and hard copy reference books / other sources 3 = Unverified data of known source Ether	-
		20	L3 L = Pesticide manuals and hard copy reference books / other sources 3 = Unverified data of known source Benzene	-
Melting point (°C)		201	F4 F = U.S. EPA ECOTOX database / U.S. EPA pesticide fate database / Miscellaneous WHO documents / FAO data, IPCS INCHEM data (US EPA Databases Related to Pesticide Risk Assessment ) 4 = Verified data	-
Boiling point (°C)		-	-	-
Degradation point (°C)		-	-	-
Flashpoint (°C)		-	-	-
Octanol-water partition coefficient at pH 7, 20 °C	P	8.13 X 1000	Calculated	-
	Log P	0.91	R4 R = Peer reviewed scientific publications 4 = Verified data	Low
Fat solubility of residues	Solubility	-	-	-
	Data type	-	-	-
Density (g ml⁻¹)		-	-	-
Dissociation constant pKa) at 25 °C		7.12	R4 R = Peer reviewed scientific publications 4 = Verified data	-
		Weak base
Vapour pressure at 20 °C (mPa)		1.31 X 10-03	R4 R = Peer reviewed scientific publications 4 = Verified data	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	R4 R = Peer reviewed scientific publications 4 = Verified data	Persistent
	DT₅₀ (lab at 20 °C)	-	-	-
	DT₅₀ (field)	-	-	-
	DT₉₀ (lab at 20 °C)	-	-	-
	DT₉₀ (field)	-	-	-
	Note	-
Manure DT₅₀ (days)		31.5	R4 R = Peer reviewed scientific publications 4 = Verified data 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	Kd (mL g⁻¹)	-	R4 R = Peer reviewed scientific publications 4 = Verified data	Slightly mobile
	Koc (mL g⁻¹)	2835
	Notes and range	General literature states Koc range 1680-3990 mL g⁻¹
Freundlich	Kf (mL g⁻¹)	-	-	-
	Kfoc (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	F4 F = U.S. EPA ECOTOX database / U.S. EPA pesticide fate database / Miscellaneous WHO documents / FAO data, IPCS INCHEM data (US EPA Databases Related to Pesticide Risk Assessment ) 4 = Verified data 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		-	-	-
		-	-	-
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	R4 R = Peer reviewed scientific publications 4 = Verified data 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	R3 R = Peer reviewed scientific publications 3 = Unverified data of known source 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, growth) - Acute 7 day EC₅₀, biomass (mg l⁻¹)		> 1.0	R4 R = Peer reviewed scientific publications 4 = Verified data Lemna gibba LOEC 7 day	Moderate
Aquatic plants (rooted, growth) - Acute 14 day EC₅₀, biomass (mg l⁻¹)		-	-	-
Algae - Acute 72 hour EC₅₀, growth (mg l⁻¹)		80.3	F4 F = U.S. EPA ECOTOX database / U.S. EPA pesticide fate database / Miscellaneous WHO documents / FAO data, IPCS INCHEM data (US EPA Databases Related to Pesticide Risk Assessment ) 4 = Verified data Selenastrum capricornutum	Low
Algae - Chronic 96 hour NOEC, growth (mg l⁻¹)		25.5	R4 R = Peer reviewed scientific publications 4 = Verified data Selenastrum capricornutum	Low
Mesocosm study data	NOEAEC mg l⁻¹	-	-	-
	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	F4 F = U.S. EPA ECOTOX database / U.S. EPA pesticide fate database / Miscellaneous WHO documents / FAO data, IPCS INCHEM data (US EPA Databases Related to Pesticide Risk Assessment ) 4 = Verified data 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	V3 V = ChemID Online Databases; Chemspider; PubChem. (ChemID ) 3 = Unverified data of known source Rat	-
		Subcutaneous LD₅₀ > 5000 mg kg⁻¹	V3 V = ChemID Online Databases; Chemspider; PubChem. (ChemID ) 3 = Unverified data of known source 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	F4 F = U.S. EPA ECOTOX database / U.S. EPA pesticide fate database / Miscellaneous WHO documents / FAO data, IPCS INCHEM data (US EPA Databases Related to Pesticide Risk Assessment ) 4 = Verified data	-

Health issues

Specific human health issues		Carcinogen Genotoxic Endocrine disruptor No data found A0 A = Chromosome aberration (EFSA database) 0 = No data ; B0 B = DNA damage/repair (EFSA database) 0 = No data ; C0 C = Gene mutation (EFSA database) 0 = No data ; D0 D = Genome mutation (EFSA database) 0 = No data ; E0 E = Unspecified genotoxicity type (miscellaneous data source) 0 = No data No data found Reproduction / development effects Acetyl cholinesterase inhibitor Neurotoxicant ?Possibly, status not identified No data found ?Possibly, status not identified Respiratory tract irritant Skin irritant Skin sensitiser No data found ✓Yes, known to cause a problem No data found Eye irritant Phototoxicant   No data found 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	-

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Record last updated:	17/05/2024
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