Metronidazole

Metronidazole	Last updated: 18/05/2024
(Also known as: metronidazol ; MTZ)

GENERAL INFORMATION

Description

An imadazole veterinary drug active against both gram-positive and gram-negative bacteria and protozoa

Availability status

Current

Introduction & key dates

1957, introduced

Examples of veterinary uses

Often used to treat diarrhea and other intestinal problem. Effective against Giardia; Trichomonas; Balantidium coli

Examples of species treated

Cattle; Dogs; Cats; Horses; Donkeys; Birds; Reptiles

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved

EU Regulatory approval status

Approved

Chemical structure

Isomerism

Chemical formula

C₆H₉N₃O₃

Canonical SMILES

CC1=NC=C(N1CCO)[N+](=O)[O-]

Isomeric SMILES

No data

International Chemical Identifier key (InChIKey)

VAOCPAMSLUNLGC-UHFFFAOYSA-N

International Chemical Identifier (InChI)

InChI=1S/C6H9N3O3/c1-5-7-4-6(9(11)12)8(5)2-3-10/h4,10H,2-3H2,1H3

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
metronidazole	-

General status

Veterinary substance type

Antibiotic, Antibacterial, Antiprotozoal

Substance groups

Imidazole

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Systemic. Metronidazole is reduced as it enters the target cell where it interacts with bacterial or protozoal DNA causing a loss of helical structure and strand breakage in the DNA leading to eventual death of the cell

Molecular targets

[DNA, Binder], [Oxygen-insensitive NADPH nitroreductase, potentiator], [Periplasmic (Fe) hydrogenase 1, Antagonist]

CAS RN

443-48-1

EC number

207-136-1

CIPAC number

US EPA chemical code

120401

PubChem CID

Therapeutic Class

Antiinfectants for systemic use: Antibacterials for systemic use

ATCvet Code

QJ01RA04

Controlled Drug?

Regulation 37/2010 MRL Classification

Prohibited

Molecular mass

171.15

PIN (Preferred Identification Name)

IUPAC name

2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethanol

CAS name

1-(β-hydroxyethyl)-2-methyl-5- nitroimidazole

Other status information

Evidence of use in third world countries

Relevant Environmental Water Quality Standards

Physical state

White to pale yellow crystalline solid

Formulations

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Example products (past and present) using this active

Eradia Oral Suspension

Virbac

GB National authorisation

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

Metrobactin Tablets

Dechra Regulatory B.V.

GB National authorisation

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

Stomorgyl 20 Film-coated Tablets

Boehringer Ingelheim Animal Health UK Ltd

UK National authorisation

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

Spizobactin Chewable Tablets

Le Vet Beheer B.V.

GB National authorisation

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

Formulation and application details

Usually supplied as oral suspensions or tablets

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

9500

High

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

5000

Ethanol

500

Ether

500

Chloroform

Melting point (°C)

158

Boiling point (°C)

Degradation point (°C)

Flashpoint (°C)

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

9.55 X 10^-01

Calculated

Log P

-0.02

Low

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

2.38

Strong acid

Vapour pressure at 20 °C (mPa)

0.04

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

No absorption >290 nm

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)

16.1

soil-manure slurry mix Slightly persistent DT₅₀ range 9.7–26.8 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)

Mobile

K_oc (mL g⁻¹)

Notes and range

General literature states K_d range 0.54-0.67 mL g⁻¹, K_oc range 39-56 mL g⁻¹, soils=4

Freundlich

K_f (mL g⁻¹)

0.77

Mobile

K_foc (mL g⁻¹)

56.1

¹/_n

1.35

Notes and range

General literature K_f range 0.74-0.80 mL g⁻¹, K_foc range 50.0-71.8 mL g⁻¹, 1.n range 1.27-1.43, soils=4

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

2-hydroxy metronidazole

Humans/Animals (Liver)

1-acetic acid-2-methyl-5-nitroimidazole

1-(2-hydroxyethyl)-2-carboxylic acid-5-nitroimidazole salt

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

> 500

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)

> 5000

Anas platyrhynchos

Low

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)

> 100

Oncorhynchus mykiss

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)

> 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)

182

Americamysis bahia

Low

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)

40.4

Pseudokirchneriella subcapitata

Low

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)

> 500

Rat

Moderate

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

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Subcutaneous LD₅₀ = 3640 mg kg⁻¹

Mouse

Intraperitoneal LD₅₀ = 870 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

Eliminated with some hepatic metabolism mainly in the faeces but some also lost with 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 headaches, nausea and diarrhoea
Associated with the development of leukopenia, neutropenia and increased risk of peripheral neuropathy
Published studies suggest substance is potentially carcinogenic; WHO & IARC - possible carcinogen; CLP data - inadequate epidemiological evidence so substance is not considered as a risk factor for cancer in humans; US NTP - suspected carcinogen; OSHA - Anticipated human carcinogen

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

metronidazole

French

German

Danish

Italian

Spanish

metronidazol

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	18/05/2024
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