Colistin sulphate

Colistin sulphate	Last updated: 23/02/2024
(Also known as: colistin; belcomycin; colistin sulfate; coly-mycin; colimycin sulfate; polymixin E sulphate)

GENERAL INFORMATION

Description

A broad spectrum antibiotic produced by certain strains of Bacillus polymyxa var. colistinus and effective against most gram-negative bacteria. It is normally formulated as the sulphate.

Availability status

Current

Introduction & key dates

1950s, first veterinary use

Examples of veterinary uses

Used for the prevention and control of gastrointestinal diseases such as Escherichia coli and Salmonella spp.

Examples of species treated

Cattle; Poultry; Pigs; Sheep; Goats; Rabbits

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved

EU Regulatory approval status

Approved

Chemical structure

Isomerism

Isomeric

Chemical formula

C₅₃H₁₀₂N₁₆O₁₇S

Canonical SMILES

CCC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC1=O)CCN)CC(C)C)CC(C)C)CCN)CCN)C(C)O.OS(=O)(=O)O

Isomeric SMILES

CCC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](NC(=O)[C@@H](NC1=O)CCN)CC(C)C)CC(C)C)CCN)CCN)[C@@H](C)O.OS(=O)(=O)O

International Chemical Identifier key (InChIKey)

VEXVWZFRWNZWJX-NBKAJXASSA-N

International Chemical Identifier (InChI)

InChI=1S/C52H98N16O13.H2O4S/c1-9-29(6)11-10-12-40(71)59-32(13-19-53)47(76)68-42(31(8)70)52(81)64-35(16-22-56)44(73)63-37-18-24-58-51(80)41(30(7)69)67-48(77)36(17-23-57)61-43(72)33(14-20-54)62-49(78)38(25-27(2)3)66-50(79)39(26-28(4)5)65-45(74)34(15-21-55)60-46(37)75;1-5(2,3)4/h27-39,41-42,69-70H,9-26,53-57H2,1-8H3,(H,58,80)(H,59,71)(H,60,75)(H,61,72)(H,62,78)(H,63,73)(H,64,81)(H,65,74)(H,66,79)(H,67,77)(H,68,76);(H2,1,2,3,4)/t29?,30-,31-,32+,33+,34+,35+,36+,37+,38+,39-,41+,42+;/m1./s1

2D structure diagram/image available?

Yes

General status

Veterinary substance type

Antibiotic, Antibacterial, Antimicrobial, Feed additive

Substance groups

Polymixin mix

Minimum active substance purity

Known relevant impurities

Substance origin

Natural

Mode of action

Distrupts the bacterial cell membrane changing its permeability.

Molecular targets

[Bacterial outer membrane]

CAS RN

1264-72-8

EC number

215-034-3

CIPAC number

US EPA chemical code

PubChem CID

91885449

Therapeutic Class

Alimentary tract & metabolism: Intestinal anti-infectives

ATCvet Code

QA07AA10

Controlled Drug?

Regulation 37/2010 MRL Classification

Allowed substance (Table 1: All food producing species)

Molecular mass

1267.54

PIN (Preferred Identification Name)

IUPAC name

N-((1S)-3-amino-1-(((1S,2R)-1-(((1S)-3-amino-1-(((3S,6S,9S,12S,15R,18S,21S)-6,9,18-tris(2-aminoethyl)-3-(1-hydroxyethyl)- 12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19- heptazacyclotricos-21-yl)carbamoyl)propyl) carbamoyl)-2-hydroxy-propyl) carbamoyl)propyl)-6-methyl-octanamide sulfuric acid

CAS name

Other status information

Relevant Environmental Water Quality Standards

Physical state

White crystalline powder

Formulations

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Example products (past and present) using this active

Coliplus 2,000,000 IU/ml concentrate

Divasa-Farmavic S.A.

GB National

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

Colibird Poultry solution for drinking water

Ceva Animal Health Ltd

UK National authorisation

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

Hidrocol Solution for Drinking Water

SP Veterinaria S.A.

GB National authorisation

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

Formulation and application details

Often formulated, as the sulphate, as oral solutions and powders for drinking water

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

5640

High

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

Melting point (°C)

Boiling point (°C)

1537

Degradation point (°C)

Flashpoint (°C)

883.5

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

3.98 X 10^-03

Calculated

Log P

-2.4

Low

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

12.1

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

1.575

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)

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 metabolites

None

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

> 5450

Rat as sulphate variant

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

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)

3.5

Danio rerio Embryo

Moderate

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 - Acute 7 day EC₅₀, biomass (mg l⁻¹)

Algae - Acute 72 hour EC₅₀, growth (mg l⁻¹)

Algae - Chronic 96 hour NOEC, growth (mg l⁻¹)

Mesocosm study data

NOEAEC mg l⁻¹

Marine bivalves – Acute EC₅₀ development (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)

> 5450

Rat as sulphate variant

Low

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

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Subcutaneous LD₅₀ = 72.2 mg kg⁻¹

Rat

Intraperitoneal LD₅₀ = 10.6 mg kg⁻¹

Rat

ADI - Acceptable Daily Intake (mg kg⁻¹ bw day⁻¹)

0.004

Rat SF=200

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

Poisonous by intraperitoneal and intravenous routes

Mammalian dose elimination route and rate

Largely (~80%) excreted via the urine, no significant metabolism

Health issues

Specific human health issues

Carcinogen

Genotoxic

Endocrine disruptor

; ; ; ;

Reproduction / development effects

Acetyl cholinesterase inhibitor

Neurotoxicant

Respiratory tract irritant

Skin irritant

Skin sensitiser

No data found

Eye irritant

Phototoxicant

No data found

General human health issues

May cause respiratory muscle paralysis leading to apnea, respiratory arrest and death
Possible kidney toxicant

Handling issues

Property

Value and interpretation

General

IMDG Transport Hazard Class 6.1

CLP classification 2013

WHO Classification

Not listed (Not listed)

UN Number

UN2811

Waste disposal & packaging

Packaging Group III (minor danger)

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

colistin sulphate

French

German

Colistin sulfat

Danish

Italian

Spanish

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	23/02/2024
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