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EC number: 205-003-2 | CAS number: 130-95-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study is not done according to OECD guideline, but it is a well documented study.
Data source
Reference
- Reference Type:
- publication
- Title:
- The reproducibility of quinine bioavailability.
- Author:
- Paintaud, G., Alván, G. and Ericsson, Ö.
- Year:
- 1 993
- Bibliographic source:
- Br J Clin Pharmacol. 35(3):305-307
Materials and methods
- Objective of study:
- toxicokinetics
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Six subjects, three males and three females, participated in the study. Their mean age (range) was 31 (21-40) years and their mean body weight was 72 (52-85) kg. All were found to be healthy by routine clinical examination and laboratory tests. They had taken no drugs for at least 1 week before the study. One female subject and two male subjects were smoking between 15 to 20 cigarettes per day. The subjects were given two identical oral doses of quinine on two separate occasions. The subjects took the oral doses of quinine after a light breakfast had been taken at home. The other oral intakes were a coffee (from 0.33 to 2 h after the dose) and lunch (from 3 to 5 h after the dose), after which there were no dietary restrictions. The subjects were resting during the first 3 h after dosing. Following the oral doses, blood samples (2 ml) were collected in heparinised tubes at the time of drug intake, every 20 min until 3 h, every hour from 3 to 12 h and at 24, 28 and 32 h. Plasma was separated within 1 h after collection by centrifugation for 7 min at 2000 g. The samples were stored at -20° C until assay. Quinine was measured by a reversed phase HPLC method with fluorescence detection. The excitation and emission wavelengths of the detector were set at 350 and 446 nm, respectively. Plasma samples (100 µl) were alkalinized with sodium hydroxide, extracted with toluene and reextracted with phosphate buffer. The column was an Ultrasphere ODS 3 µm, 75 x 4.6 mm. The eluent was prepared by mixing 480 ml phosphate buffer 0.1 mol/L, pH 1.9, 30 ml acetonitrile, 10 ml tetrahydrofuran and 8 ml triethylamine and adjusting pH to 3.5 with NaOH 5 mol-1. The flow rate was 1.0 ml/min. The within-assay coefficient of variation was 2-4%, and the day-to-day coefficient of variation was less than 4% during the study. The limit of determination was 2 nmol/L plasma. Peak plasma concentrations (Cmax) and the time to reach peak concentrations (tmax) of quinine were noted. The terminal elimination rate constant (λz) was estimated by linear regression of the log linear portion of the terminal elimination phase. Areas under the plasma drug concentration-time curve (AUC) were calculated by the linear trapezoidal method with extrapolation to infinity. The mean percentage of the AUC extrapolated beyond the last data point was 13% for the oral doses and 16% for the infusion.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- 6119-47-7
- Cas Number:
- 6119-47-7
- IUPAC Name:
- 6119-47-7
- Test material form:
- other: tablet
- Details on test material:
- - Name of test material (as cited in study report): Quinine hydrochloride dihydrate- other: tablet obtained from KabiVitrum, Stockholm, Sweden
Constituent 1
- Radiolabelling:
- no
Test animals
- Species:
- human
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: unspecified
- Vehicle:
- unchanged (no vehicle)
- Duration and frequency of treatment / exposure:
- The subjects were given two identical oral doses of quinine on two separate occasions. The median (range) interval between the two oral doses was 11.5 (6-60) days.
Doses / concentrations
- Remarks:
- Doses / Concentrations:The subjects were given two identical oral doses of quinine on two separate occasions. The oral dose was as close as possible to 15 mg/kg and it was administered using 100 mg and 250 mg tablets of quinine hydrochloride dihydrate. The quinine salt has a molecular weight of 397 and the intended dose was equivalent to 12.24 mg/kg of quinine base. The actual mean oral dose was 12.06 mg/kg of quinine base.
- No. of animals per sex per dose / concentration:
- Six subjects, three males and three femalesTheir mean age (range) was 31 (21-40) years and their mean body weight was 72 (52-85) kg. All were found to be healthy by routine clinical examination and laboratory tests. They had taken no drugs for at least 1 week before the study. One female subject and two male subjects were smoking between 15 to 20 cigarettes per day.
- Control animals:
- not specified
- Details on study design:
- The subjects took the oral doses of quinine after a light breakfast had been taken at home. The other oral intakes were a coffee (from 0.33 to 2 h after the dose) and lunch (from 3 to 5 h after the dose), after which there were no dietary restrictions. The subjects were resting during the first 3 h after dosing. Following the oral doses, blood samples (2 ml) were collected in heparinised tubes at the time of drug intake, every 20 min until 3 h, every hour from 3 to 12 h and at 24, 28 and 32 h. Plasma was separated within 1 h after collection by centrifugation for 7 min at 2000 g. The samples were stored at -20° C until assay.
- Details on dosing and sampling:
- PHARMACOKINETIC STUDY (Absorption, distribution, excretion)- Tissues and body fluids sampled (delete / add / specify): blood and plasma- Time and frequency of sampling: oral doses: every 20 min until 3 h, every hour from 3 to 12 h and at 24, 28 and 32 h. Plasma was separated within 1 h after collection
Results and discussion
Toxicokinetic / pharmacokinetic studies
Toxicokinetic parametersopen allclose all
- Test no.:
- #1
- Toxicokinetic parameters:
- AUC: 248 µmol/L* h
- Test no.:
- #1
- Toxicokinetic parameters:
- Cmax: 15.2 µmol/L
- Test no.:
- #1
- Toxicokinetic parameters:
- Tmax: 1.84 h
- Test no.:
- #1
- Toxicokinetic parameters:
- half-life 1st: 10.7 h
- Test no.:
- #2
- Toxicokinetic parameters:
- AUC: 245 µmol/L* h
- Test no.:
- #2
- Toxicokinetic parameters:
- Cmax: 15.7 µmol/L
- Test no.:
- #2
- Toxicokinetic parameters:
- Tmax: 2.01 h
- Test no.:
- #2
- Toxicokinetic parameters:
- half-life 1st: 10.9 h
Metabolite characterisation studies
- Metabolites identified:
- not specified
Any other information on results incl. tables
Pharmacokinetic parameters of quinine calculated from plasma concentrations after oral dosing
First oral dose | Second oral dose | CVw(%) | CVB(%) | |
tmax (h) | 1.84 (1.02-3.00) | 2.01 (1.67-2.33) | 27.4 | 13.9 |
Cmax (µmol/L) | 15.2 (2.8) | 15.7 (1.7) | 9.2 | 11.7 |
AUC (µmol*h/L) | 248 (62) | 245 (65) | 9.7 | 23.7 |
F | 0.76 (0.11) | 0.76 (0.11) | 9.8 | 10.6 |
t1/2,z (h) | 10.7 (2.88) | 10.9 (3.70) | 12.4 | 27.4 |
Values are expressed as mean (± s.d.) except tmax: median (range).
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study resultsQuinine had an absorption rate of 76 % after oral administration. The AUC was about 248 µmol/L *h. The half-life of quinine in plasma was about 10 hours.
- Executive summary:
In the study published by Paintaud, 1993 the pharmacokinetic of quinine was determined after oral administration. Quinine had an absorption rate of 76 %. The AUC was about 248 µmol/L *h and the peak plasma concentration was about 15.2 µmol/L. The half-life of quinine in plasma was about 10 hours. It can be conclude that the oral absorption of quinine is extensive and fast in healthy subjects.
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