Levothyroxine

Levothyroxine	Last updated: 16/09/2025
(Also known as: L-thyroxine; L-T4)

GENERAL INFORMATION

Description

A synthetic thyroid hormone replacement compound used in veterinary medicine, usually used as the sodium salt

Examples of veterinary uses

Used to treat hypothyroidism (low thyroid hormone) and to prevent growth of goiters

Examples of species treated

Dogs; Cats

Approval status

VMR 2013/2033 approval status (GB/UK)

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

EU Regulatory approval status

Approved

Chemical structure

Isomerism

Levothyroxine exhibits optical isomerism, specifically existing as the L-isomer of thyroxine, which is the biologically active form in humans. Thyroxine itself is a chiral molecule due to the presence of an asymmetric carbon atom in its amino acid backbone. This gives rise to two enantiomers: L-thyroxine (levothyroxine) and D-thyroxine (dextrothyroxine). The L-isomer mimics the natural hormone produced by the thyroid gland and is used therapeutically to treat hypothyroidism. In contrast, the D-isomer has significantly reduced biological activity and is not used clinically.

Chemical formula

C₁₅H₁₁I₄NO₄

Canonical SMILES

C1=C(C=C(C(=C1I)OC2=CC(=C(C(=C2)I)O)I)I)CC(C(=O)O)N

Isomeric SMILES

C1=C(C=C(C(=C1I)OC2=CC(=C(C(=C2)I)O)I)I)C[C@@H](C(=O)O)N

International Chemical Identifier key (InChIKey)

XUIIKFGFIJCVMT-LBPRGKRZSA-N

International Chemical Identifier (InChI)

InChI=1S/C15H11I4NO4/c16-8-4-7(5-9(17)13(8)21)24-14-10(18)1-6(2-11(14)19)3-12(20)15(22)23/h1-2,4-5,12,21H,3,20H2,(H,22,23)/t12-/m0/s1

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
Levothyroxine hydrochloride monohydrate	Variant

General status

Veterinary substance type

Medicinal drug: synthetic thyroxime

Substance groups

Synthetic hormone

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Acts as endogenous thyroxine, stimulating metabolism, growth, development and differentiation of tissues

Molecular targets

[Thyroid hormone receptor alpha, Agonist], [Thyroid hormone receptor beta, Agonist]

CAS RN

51-48-9

EC number

200-101-1

CIPAC number

US EPA chemical code

PubChem CID

5819

Therapeutic Class

Synthetic thyroid hormones: Thyroid hormones

ATCvet Code

QH03AA01

Controlled Drug?

Regulation 37/2010 MRL Classification

Molecular mass

776.87

PIN (Preferred Identification Name)

(S)-2-amino-3-(4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl)propanoic acid

IUPAC name

(S)-2-amino-3-(4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl)propanoic acid

CAS name

3,5,3',5'-tetraiodo-L-thyronine

Forever chemical

Other status information

Relevant Environmental Water Quality Standards

Physical state

Crystalline solid

Related substances & organisms

levothyroxine sodium

Commercial

Property

Value

Availability status

Current

Introduction & key dates

1914, first isolated; 1972, commercial introduction; 1980s, vet use begins

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

Zoetis UK Ltd
Virbac Ltd
VetOne
Dechra Pharmaceuticals

Example products using this active

Soloxine
Thyro-Tabs Canine
Thyrosyn
Thyromed
Leventa
Thyroxanil

Formulation and application details

Usually formulated, as the sodium salt, as tablets for oral administration

Commercial production

Levothyroxine is synthesised through a multi-step chemical process that mimics the structure of the natural thyroid hormone thyroxine. The synthesis typically begins with iodinated aromatic precursors, such as 3,5-diiodotyrosine derivatives, which are chemically modified to form the thyronine backbone. A key step involves the iodination of phenolic rings using agents like iodine or sodium iodide in the presence of oxidising agents such as sodium hypochlorite. These reactions are carefully controlled to ensure the correct placement of four iodine atoms, which are essential for biological activity. The intermediate compounds undergo further transformations, including condensation reactions and protective group manipulations, followed by purification through crystallisation or chromatography to remove impurities.

Impact on climate of production and use

Published GHG data is not available for most pharmaceuticals. However, according to industry, global averages suggest producing 1 kg of a typical active pharmaceutical ingredient can range from 10 to 100 kg CO₂e for small molecule drugs and potentially up to 1000 kg CO₂e for complex biologicals such as vaccines, depending on the drug type, its formulation, complexity of synthesis, solvent recovery, and energy sources used.

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

0.1

at 25 °C

Low

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

Melting point (°C)

231

Boiling point (°C)

Degradation point (°C)

235

Flashpoint (°C)

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

1.26 X 10⁰⁴

Calculated

Log P

4.1

High

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

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

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)

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)

CT₅₀ (days)

Known metabolites

None

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

> 20

Rat

High

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

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)

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)

Temperate Freshwater Aquatic invertebrates - Chronic 21 day NOEC (mg l⁻¹)

1.0

Daphnia magna

Moderate

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)

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

> 20

Rat

High

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

Metabolised mainly in liver & kidneys, eliminated via the faeces and urine

Health issues

Specific human health issues

Carcinogen

Genotoxic

Endocrine disruptor

; ; ; ;

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

Blood toxicant
High doses may induce thyrotoxicosis which may cause weight loss, increased appetite, palpitations, nervousness, diarrhoea, abdominal cramps as well as other symptoms

Handling issues

Property

Value and interpretation

General

Will emit toxic fumes when heated to decomposition

CLP classification 2013

WHO Classification

Not listed (Not listed)

UN Number

None allocated

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

levothyroxine

French

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Spanish

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	16/09/2025
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