Apramycin

Apramycin	Last updated: 05/09/2025
(Also known as: nebramycin II)

GENERAL INFORMATION

Description

An antibiotic and antibacterial compound used in veterinary medicine

Examples of veterinary uses

Typically used for the treatment of colibacillosis and salmonella in calves and bacterial enteritis in pigs and lambs

Examples of species treated

Pigs; Lambs; Cattle; Chickens; Rabbits

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

Apramycin exhibits stereoisomerism, particularly due to its multiple chiral centres and unique bicyclic sugar moiety. As an aminoglycoside antibiotic, it contains a 2-deoxystreptamine (DOS) core that is singly substituted, unlike the more common 4,5- or 4,6-disubstituted DOS types found in other aminoglycosides. The molecule’s complexity arises from its octodialdose ring system, which includes several stereocentres that define its three-dimensional shape and biological activity. One notable isomer is 6′-epiapramycin, which differs in the configuration of the 6′-hydroxy and 7′-methylamino groups. This epimer forms a weaker intramolecular hydrogen bond, resulting in reduced binding affinity to the bacterial ribosomal A-site and diminished antibacterial potency. These stereochemical variations are crucial because they influence apramycin’s resistance profile and its ability to evade common aminoglycoside-modifying enzymes.

Chemical formula

C₂₁H₄₁N₅O₁₁

Canonical SMILES

CNC1C(C2C(CC(C(O2)OC3C(CC(C(C3O)O)N)N)N)OC1OC4C(C(C(C(O4)CO)N)O)O)O

Isomeric SMILES

CN[C@H]1[C@H]([C@@H]2[C@H](C[C@H]([C@H](O2)O[C@@H]3[C@H](C[C@H]([C@@H]([C@H]3O)O)N)N)N)O[C@@H]1O[C@@H]4[C@@H]([C@H]([C@@H]([C@H](O4)CO)N)O)O)O

International Chemical Identifier key (InChIKey)

XZNUGFQTQHRASN-XQENGBIVSA-N

International Chemical Identifier (InChI)

InChI=1S/C21H41N5O11/c1-26-11-14(30)18-8(33-20(11)37-21-16(32)13(29)10(25)9(4-27)34-21)3-7(24)19(36-18)35-17-6(23)2-5(22)12(28)15(17)31/h5-21,26-32H,2-4,22-25H2,1H3/t5-,6+,7-,8+,9-,10-,11+,12+,13+,14-,15-,16-,17-,18+,19+,20-,21-/m1/s1

2D structure diagram/image available?

Yes

General status

Veterinary substance type

Antibiotic, Antimicrobial, Antibacterial

Substance groups

Aminoglycoside

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Inhibitor of protein synthesis in bacteria both in vivo and in vitro

Molecular targets

[16S rRNA]

CAS RN

37321-09-8

EC number

253-460-1

CIPAC number

US EPA chemical code

PubChem CID

3081545

Therapeutic Class

Antiinfectants for systemic use: Antibacterials for intramammary use; Alimentary tract & metabolism: Intestinal antiinfectants; Antiinfectants for systemic use: Antibacterials for systemic use

ATCvet Code

QJ51GB90; QA07AA92; QJ01GB90

Controlled Drug?

Regulation 37/2010 MRL Classification

Allowed substance (Table 1: Bovine, Ovine, Pocine, Chicken, Rabbit)

Molecular mass

539.58

PIN (Preferred Identification Name)

IUPAC name

(2R,3R,4S,5S,6S)-2-[[(2R,3S,4R,4αR,6S,7R,8αS)-7-amino-6-[(1R,2R,3S,4R,6S)-4,6-diamino-2,3-dihydroxycyclohexyl]oxy-4-hydroxy-3-(methylamino)-2,3,4,4α,6,7,8,8α-octahydropyrano[3,2-β]pyran-2-yl]oxy]-5-amino-6-(hydroxymethyl)oxane-3,4-diol

CAS name

D-Streptamine,O-4-amino-4-deoxy-a-D-glucopyranosyl-(1®8)-O-(8R)-2-amino-2,3,7-trideoxy-7-(methylamino)-D-glycero-a-D-allo-octodialdo-1,5:8,4-dipyranosyl-(1®4)-2-deoxy-

Forever chemical

Other status information

Relevant Environmental Water Quality Standards

Physical state

Colourless, needle-shaped crystals

Related substances & organisms

apramycin sulfate

Commercial

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Availability status

Current

Introduction & key dates

1980s, first clinical use

Example products (past and present) using this active

Apravet Premix medicated feed

Huvepharma N.V.

GB National authorisation

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

Formulation and application details

Often formulated as medicated feeds or as powders to be added to feed or drinking water

Commercial production

Apramycin is produced through a microbial fermentation process using the actinomycete Streptoalloteichus tenebrarius. The biosynthesis begins with the formation of the aminocyclitol core, followed by the assembly of its unique octodialdose sugar moiety. Key enzymes, including glycosyltransferases and methyltransferases like AprI, play crucial roles in tailoring the molecule, AprI specifically catalyses the methylation of demethyl-aprosamine to aprosamine, a vital step in forming active apramycin. The fermentation broth contains apramycin along with impurities such as demethyl-apramycin and carbamyltobramycin, which are removed through downstream purification. Genetic engineering strategies, such as disruption of the aprK gene and overexpression of biosynthetic genes, have been employed to enhance yield and reduce by-products.

Impact on climate of production and use

As microbial-based products tend to use fermentation-based production processes rather than chemical synthesis, they typically have a lower fossil fuel input in formulation and active ingredient creation, and also have reduced downstream emissions due to biodegradability and minimal soil disruption, their life-cycle GHG emissions are expected to be low. Whilst hard and precise data is not available, some broad estimates suggest that typically emissions are likely to be below 5 kg CO₂e/kg of substance.

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

300000

High

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

Melting point (°C)

189

Boiling point (°C)

823

Degradation point (°C)

Flashpoint (°C)

451.6

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

5.01 X 10^-04

Calculated

Log P

-3.3

Low

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

1.56

Dissociation constant pKa) at 25 °C

8.5

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

Main route into the environment from treated pigs is via animal urine and faeces.

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)

Non-mobile

K_oc (mL g⁻¹)

500755

Notes and range

Literature values K_oc range 341900 - 659609 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

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)

> 4160

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)

1669

Colinus virginianus

Moderate

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)

> 100

Eisenia foetida

Low

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)

300

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)

101.6

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)

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)

> 4160

Rat as sulphate variant

Low

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

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Intravenous LD₅₀ = 280 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

Apramycin is rapidly absorbed when administered orally and is excreted via the kidneys without metabolisation

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

Possible kidney toxicant

Handling issues

Property

Value and interpretation

General

When heated to decomposition it emits acrid smoke and irritating fumes
Corrosive

CLP classification 2013

Health: H315
Environment: H410

WHO Classification

Not listed (Not listed)

UN Number

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

apramycin

French

apramycine

German

Danish

Italian

Spanish

apramicina

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	05/09/2025
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