Tramadol

Tramadol	Last updated: 26/04/2021
(Not known by any other names)

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
		Human health High alert: Neurotoxicant Warning: Significant data are missing

GENERAL INFORMATION

Description

A synthetic codine analogue used to control acute and chronic pain of moderate to severe intensity

Availability status

Current

Introduction & key dates

1977, launched Germany; 1962, first synthesised

Examples of species treated

Dogs

Chemical structure

Isomerism

Tramadol is a chiral molecule. The technical material is an isomeric mixture of both R- and S-stereoisomers

Chemical formula

C₁₆H₂₅NO₂

Canonical SMILES

CN(C)CC1CCCCC1(C2=CC(=CC=C2)OC)O

Isomeric SMILES

CN(C)C[C@H]1CCCC[C@@]1(C2=CC(=CC=C2)OC)O

International Chemical Identifier key (InChIKey)

TVYLLZQTGLZFBW-ZBFHGGJFSA-N

International Chemical Identifier (InChI)

InChI=1S/C16H25NO2/c1-17(2)12-14-7-4-5-10-16(14,18)13-8-6-9-15(11-13)19-3/h6,8-9,11,14,18H,4-5,7,10,12H2,1-3H3/t14-,16+/m1/s1

2D structure diagram/image available?

Yes

General status

Veterinary substance type

Medicinal drug: Analgesic

Substance groups

Opoid

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Multiple activity routes

Molecular targets

[µ-opioid receptor, Agonist], [Sodium-dependent noradrenaline transporter, Inhibitor], [Sodium-dependent serotonin transporter, Inhibitor], [5-hydroxytryptamine receptor 2C, Antagonist], [Kappa-type opioid receptor, Agonist], [Delta-type opioid receptor, Agonist]

CAS RN

27203-92-5

EC number

248-319-6

CIPAC number

US EPA chemical code

PubChem CID

ATCvet Code

QN02AX02

Therapeutic Class

Controlled Drug?

Yes

Regulation 37/2010 MRL Classification

Molecular mass

263.38

PIN (Preferred Identification Name)

2-((dimethylamino)methyl)-1-(3-methoxyphenyl)cyclohexanol

IUPAC name

(1R,2R)-2-((dimethylamino)methyl)-1-(3-methoxyphenyl)cyclohexan-1-ol

CAS name

(+/-)-cis-(2-dimethylaminomethyl)-1-(3-methoxyphenyl)-cyclohexanol

Other status information

Relevant Environmental Water Quality Standards

Physical state

Formulations

Property

Product

Manufacturer

Authorisation Route

UK Legal Class

Example products using this active

Ultram

Janssen Pharmaceuticals

No approved directly for animals - used under the 'prescribing cascade'

Formulation and application details

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

39.5

Low

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

Melting point (°C)

180

as the HCl salt

Boiling point (°C)

Degradation point (°C)

Flashpoint (°C)

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

2.24 X 10⁰¹

Calculated

Log P

1.35

Low

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

9.41

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

K_d

K_oc

Notes and range

Freundlich

K_f

K_foc

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 soil and groundwater metabolites

None

Other known metabolites

Metabolite name and reference

Aliases

Formation medium / Rate

Estimated maximum occurrence fraction

Metabolising enzymes

O-desmethyltramadol

Human liver

N-desmethyltramadol

Human liver

O-desmethyl-tramado glucuronide

Human liver

N,O-didesmethyltramadol

Human liver

N,N-didesmethyltramadol

Human liver

N,N,O-tridesmethyl-tramadol

Human liver

N,N,O-tridesmethyl-tramadol

Human liverl

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

350

Mouse

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)

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)

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

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)

350

Mouse

Moderate

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

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Intraperitoneal LD₅₀ = 150 mg kg⁻¹

Rat

Subcutaneous LD₅₀ = 286 mg kg⁻¹

Rat

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

Extensively metabolised in the liver. (0% eliminated in the urine, 10% in faeces

Health issues

Specific human health issues

Carcinogen

Genotoxic

Endocrine disruptor

No data found

; ; ; ;

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

CNS depressant
May depress respiratory function
Some incidences of adverse reactions recorded including headache, diarrhoea, vomiting & cardiovascular irregularities

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

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

tramadol

French

German

Danish

Italian

Spanish

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	26/04/2021
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