Levothyroxine	Last updated: 24/06/2022
(Also known as: L-thyroxine; L-T4)

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Data alerts

The following alerts are based on the data in the tables below. An absence of an alert does not imply the substance has no implications for human health, biodiversity or the environment but just that we do not have the data to form a judgement.

Environmental fate	Ecotoxicity	Human health
	Ecotoxicity Moderate alert: Daphnia chronic ecotoxicity: Moderate Warning: Significant data are missing	Human health High alert: Mammals acute toxicity: High; Endocrine disrupter

GENERAL INFORMATION

Description	A veterinary medicine used to treat hypothyroidism (low thyroid hormone) and to prevent growth of goiters
Availability status	Current
Introduction & key dates	-
Examples of species treated	Dogs; Cats

Chemical structure

Isomerism	Levethyroxine is the S-isomer of thyroxine
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
ATCvet Code	QH03AA01
Therapeutic Class	Synthetic thyroid hormones: Thyroid hormones
Controlled Drug?	No
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
Other status information	-
Relevant Environmental Water Quality Standards	-
Physical state	Crystalline solid

Formulations

Property	Product	Manufacturer	Authorisation Route	UK Legal Class
Example products using this active	Soloxine	Virbac Ltd, Suffolk UK	UK National authorisation	Prescription only medicine to be authorised by a veterinarian (POM-V)
	Forthyron 200 mg Tablet	Eurovet Animal Health B.V.	EU Mutually recognised procedure	Prescription only medicine to be authorised by a veterinarian (POM-V)
	Leventa 1 mg/ml Oral Solution for Dogs	Intervet UK Ltd	EU Mutually recognised procedure	Prescription only medicine to be authorised by a veterinarian (POM-V)
	Thyforon Flavoured 600 Microgram Tablets for Dogs	Eurovet Animal Health B.V	EU Mutually recognised procedure	Prescription only medicine to be authorised by a veterinarian (POM-V)
Formulation and application details	-

ENVIRONMENTAL FATE

Property		Value	Source; quality score; and other information	Interpretation
Solubility - In water at 20 °C (mg l⁻¹)		0.1	V3 V = ChemID Online Databases; Chemspider; PubChem. (ChemID ) 3 = Unverified data of known source at 25 °C	Low
Solubility - In organic solvents at 20 °C (mg l⁻¹)		-	-	-
Melting point (°C)		231	Q3 Q = Miscellaneous data from online sources 3 = Unverified data of known source	-
Boiling point (°C)		-	-	-
Degradation point (°C)		235	V3 V = ChemID Online Databases; Chemspider; PubChem. (ChemID ) 3 = Unverified data of known source	-
Flashpoint (°C)		-	-	-
Octanol-water partition coefficient at pH 7, 20 °C	P	1.26 X 1004	Calculated	-
	Log P	4.1	V3 V = ChemID Online Databases; Chemspider; PubChem. (ChemID ) 3 = Unverified data of known source	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)		-	-	-
Maximum UV-vis absorption L mol⁻¹ cm⁻¹		-	-	-
Surface tension (mN m⁻¹)		-	-	-
Refractive Index		-	-	-

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)		-	-	-

Soil adsorption and mobility

Property		Value	Source; quality score; and other information	Interpretation
Linear	Kd	-	-	-
	Koc	-
	Notes and range	-
Freundlich	Kf	-	-	-
	Kfoc	-
	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	F4 F = U.S. EPA ECOTOX database / U.S. EPA pesticide fate database / Miscellaneous WHO documents / FAO data, IPCS INCHEM data (US EPA Databases Related to Pesticide Risk Assessment ) 4 = Verified data 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		-	-	-
		-	-	-
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
Fish - Acute 96 hour LC₅₀ (mg l⁻¹)		-	-	-
Fish - Chronic 21 day NOEC (mg l⁻¹)		-	-	-
Aquatic invertebrates - Acute 48 hour EC₅₀ (mg l⁻¹)		-	-	-
Aquatic invertebrates - Chronic 21 day NOEC (mg l⁻¹)		1.0	F4 F = U.S. EPA ECOTOX database / U.S. EPA pesticide fate database / Miscellaneous WHO documents / FAO data, IPCS INCHEM data (US EPA Databases Related to Pesticide Risk Assessment ) 4 = Verified data daphnia magna	Moderate
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	-	-	-
	NOEAEC mg l⁻¹	-	-	-

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	F4 F = U.S. EPA ECOTOX database / U.S. EPA pesticide fate database / Miscellaneous WHO documents / FAO data, IPCS INCHEM data (US EPA Databases Related to Pesticide Risk Assessment ) 4 = Verified data 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	V3 V = ChemID Online Databases; Chemspider; PubChem. (ChemID ) 3 = Unverified data of known source	-

Health issues

Specific human health issues		Carcinogen Genotoxic Endocrine disruptor XNo, known not to cause a problem A0 A = Chromosome aberration (EFSA database) 0 = No data ; B0 B = DNA damage/repair (EFSA database) 0 = No data ; C0 C = Gene mutation (EFSA database) 0 = No data ; D0 D = Genome mutation (EFSA database) 0 = No data ; E3 E = Unspecified genotoxicity type (miscellaneous data source) 3 = Negative ✓Yes, known to cause a problem Reproduction / development effects Acetyl cholinesterase inhibitor Neurotoxicant No data found XNo, known not to cause a problem XNo, known not to cause a problem Respiratory tract irritant Skin irritant Skin sensitiser XNo, known not to cause a problem XNo, known not to cause a problem No data found Eye irritant Phototoxicant   XNo, known not to cause a problem 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	-
German	-
Danish	-
Italian	-
Spanish	-
Greek	-
Polish	-
Swedish	-
Hungarian	-
Dutch	-
Norwegian	-

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Record last updated:	24/06/2022
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