Tilmicosin

Tilmicosin	Last updated: 15/09/2025
(Also known as: 20-deoxy-20-(3,5-dimethylpiperidin-1-yl)-desmycosin ; AH0230 / AH0470; tilmicosina)

GENERAL INFORMATION

Description

A semi-synthetic macrolide antibiotic

Examples of veterinary uses

Used for the treatment and prevention of pneumonia associated with Pasteurella haemolytica, P. multocida, Actinobacillus pleuropneumoniae, mycoplasma species and other microorganisms

Examples of species treated

Cattle; Sheep; Pigs; Poultry; Rabbits; Fish

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved - usually approved as a prescription only medicine to be authorised by a veterinarian (POM-V)

EU Regulatory approval status

Approved

Chemical structure

Isomerism

Tilmicosin exhibits geometrical isomerism, specifically cis-trans isomerism, due to the configuration around its double bonds and bulky substituents. The compound exists as a mixture of cis and trans isomers, with the cis-isomer being the predominant and pharmacologically active form. Typically, the technical material contains approximately 82–88% cis-isomers and 12–18% trans-isomers.

Chemical formula

C₄₆H₈₀N₂O₁₃

Canonical SMILES

CCC1C(C=C(C=CC(=O)C(CC(C(C(C(CC(=O)O1)O)C)OC2C(C(C(C(O2)C)O)N(C)C)O)CCN3CC(CC(C3)C)C)C)C)COC4C(C(C(C(O4)C)O)OC)OC

Isomeric SMILES

CC[C@@H]1[C@H](/C=C(/C=C/C(=O)[C@@H](C[C@@H]([C@@H]([C@H](C(CC(=O)O1)O)C)O[C@H]2[C@@H]([C@H]([C@@H]([C@H](O2)C)O)N(C)C)O)CCN3CC(CC(C3)C)C)C)\C)CO[C@H]4[C@@H]([C@@H]([C@@H]([C@H](O4)C)O)OC)OC

International Chemical Identifier key (InChIKey)

JTSDBFGMPLKDCD-SWSPHLSKSA-N

International Chemical Identifier (InChI)

InChI=1S/C46H80N2O13/c1-13-36-33(24-57-46-44(56-12)43(55-11)40(53)31(8)59-46)19-25(2)14-15-34(49)28(5)20-32(16-17-48-22-26(3)18-27(4)23-48)42(29(6)35(50)21-37(51)60-36)61-45-41(54)38(47(9)10)39(52)30(7)58-45/h14-15,19,26-33,35-36,38-46,50,52-54H,13,16-18,20-24H2,1-12H3/b15-14+,25-19+/t26-,27+,28-,29+,30-,31-,32+,33-,35-,36-,38+,39-,40-,41-,42-,43-,44-,45+,46-/m1/s1

2D structure diagram/image available?

Yes

General status

Veterinary substance type

Antibiotic, Antibacterial, Antimicrobial, Medicinal drug, Medicated feed additive

Substance groups

Macrolide

Minimum active substance purity

Known relevant impurities

Substance origin

Semi-synthetic

Mode of action

Interferes with protein synthesis

Molecular targets

[50S rRNA, Antagonist]

CAS RN

108050-54-0

EC number

CIPAC number

US EPA chemical code

PubChem CID

5282521

Therapeutic Class

Antiinfectants for systemic use: Antibacterials for systemic use

ATCvet Code

QJ01FA91

Controlled Drug?

Regulation 37/2010 MRL Classification

Allowed substance (Table 1: All food producing species)

Molecular mass

869.15

PIN (Preferred Identification Name)

IUPAC name

(4R,5S,6S,7R,9R,11E,13E,15R,16R)-6-[(2R,3R,4S,5S,6R)-4-(dimethylamino)-3,5-dihydroxy-6-methyloxan-2-yl]oxy-7-[2-[(3R,5S)-3,5-dimethylpiperidin-1-yl]ethyl]-16-ethyl-4-hydroxy-15-[[(2R,3R,4R,5R,6R)-5-hydroxy-3,4-dimethoxy-6-methyloxan-2-yl]oxymethyl]-5,9,13-trimethyl-1-oxacyclohexadeca-11,13-diene-2,10-dione

CAS name

4A-O-de(2,6-dideoxy-3-C-methyl-α-L-ribo-hexopyranosyl)-20-deoxy-20-(3,5-dimethyl-1-piperidinyl)-(20(cis: trans)) tylosin

Forever chemical

Other status information

Relevant Environmental Water Quality Standards

Physical state

Related substances & organisms

tilmicosin phosphate

Commercial

Property

Value

Availability status

Current

Introduction & key dates

Late 1980s, first synthesised; 1990s, introduced commercially

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

Nimrod Veterinary Products Ltd
Industrial Veterinaria S.A.
Huvepharma N.V.

Example products using this active

Apotil Solution for Injection
Hymantil Solution for Injection
Tilmovet Oral Granules

Formulation and application details

A wide variety of formulations are available including solutions for injection, granules and premixed medicated feeds

Commercial production

The production of tilmicosin begins with tylosin fermentation broth, which serves as the primary raw material. This broth is first pretreated and filtered to isolate tylosin, which then undergoes a series of chemical transformations including extraction, ammoniation, hydrolysis, and acidification to convert it into tilmicosin base. A key step involves reacting tylosin with 3,5-dimethylpiperidine, forming the tilmicosin molecule through structural modification of the macrolide ring. The crude tilmicosin is then purified and dried, and optionally converted into tilmicosin phosphate via phosphorylation and spray drying for improved solubility and stability

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, broad estimates suggest that typically emissions are likely to be below 5 kg CO₂e/kg. However, the semi-synthetic nature of the production process for this substance is likely to increase emissions.

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

566000

High

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

Melting point (°C)

107

Boiling point (°C)

Degradation point (°C)

Flashpoint (°C)

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

1.23 X 10⁰⁵

Calculated

Log P

5.09

High

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

13.16

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

UV max: 283nm = 22643

Surface tension (mN m⁻¹)

Refractive Index

Environmental release

Substance may enter the environment via the faeces of treated animals or by leaching from spilt medicated feed.

Degradation

Property

Value

Source; quality score; and other information

Interpretation

Soil degradation (days) (aerobic)

DT₅₀ (typical)

Moderately persistent

DT₅₀ (lab at 20 °C)

730

Very persistent

DT₅₀ (field)

DT₉₀ (lab at 20 °C)

DT₉₀ (field)

Note

USEPA data: suggests soil DT₅₀ >2 years; Literature variable & sparse (i) 45.9% decline in loam soil after 1 year, no decline in clay loam after 1 year (E3); (ii) >64 days (R3)

Manure DT₅₀ (days)

Aqueous photolysis DT₅₀ (days) at pH 7

Value

0.82

Fast

Note

Not pH sensitive

Aqueous hydrolysis DT₅₀ (days) at 20 °C and pH 7

Value

Stable

Note

Stable at pH 5 & 7, DT₅₀ 156 days at pH 9

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)

178.5

Non-mobile

K_oc (mL g⁻¹)

16319

Notes and range

USEPA data: K_d range 86-318 mL g⁻¹, K_oc range 4244-36150 mL g⁻¹, Soils=4

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

-0.61

Calculated

Low leachability

Bio-concentration factor

BCF (l kg⁻¹)

450

Estimated

Threshold for concern

CT₅₀ (days)

Not available

Known soil and groundwater metabolites

None

Other known metabolites

Metabolite name and reference

Aliases

Formation medium / Rate

Estimated maximum occurrence fraction

tilmicosin sulphate

Rat

N-desmethyl tilmicosin

Animal

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

> 800

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)

Birds - Short term dietary (LC₅₀/LD₅₀)

> 4710 mg kg feed⁻¹

Anas platyrhynchos

Birds - Chronic 21d NOEL (mg kg⁻¹ bw d⁻¹)

Earthworms - Acute 14 day LC₅₀ (mg kg⁻¹)

> 918

Eisenia foetida 28 day

Moderate

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)

851

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)

57.3

Daphnia magna

Moderate

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) (ErC₅₀)

0.35

Raphidocelis subcapitata

Moderate

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)

> 800

Rat

Moderate

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

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

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

Very little metabolism, excreted unchanged predominately in the faeces

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

Severe allergen
Cardiovascular toxicant

Handling issues

Property

Value and interpretation

General

May emit toxic fumes when heated to decomposition

CLP classification 2013

WHO Classification

Not listed (Not listed)

UN Number

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

tilmicosin

French

tilmicosine

German

Danish

Italian

Spanish

tilmicosina

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	15/09/2025
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