Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 200-493-4 | CAS number: 60-93-5
- 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 an i.v. infusion dose of quinine. The infusion was started at 08.00 h, after a light breakfast had been taken at home. The 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. For the i.v. infusion dose, blood samples (2 ml) were collected in heparinised tubes at the time of drug intake, every 20 min until 3 h, every 30 min 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. Plasma clearance (CL), fraction of the dose absorbed (F), mean residence time (MRT) and volume of distribution at steady state (Vss) were calculated after intravenous administration by standard equations (Gibaldi &Perrier, 1982).
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Quinine dihydrochloride
- EC Number:
- 200-493-4
- EC Name:
- Quinine dihydrochloride
- Cas Number:
- 60-93-5
- Molecular formula:
- C20H24N2O2.2ClH
- IUPAC Name:
- 6'-methoxycinchonan-9-ol dihydrochloride
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- - Name of test material (as cited in study report): Quinine dihydrochloride
- other: obtained from Apoteksbolaget, Sweden
Constituent 1
- Radiolabelling:
- no
Test animals
- Species:
- human
- Sex:
- male/female
Administration / exposure
- Route of administration:
- intravenous
- Vehicle:
- other: solution of quinine dihydrochloride in isotonic NaCl
- Duration and frequency of treatment / exposure:
- The subjects were given an intravenous infusion dose of quinine.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
The subjects were given an i.v. infusion dose of quinine dihydrochloride. The i.v. dose was 15 mg/kg and was administered as a constant rate infusion over 6 h. The infusion was prepared by dissolution of quinine dihydrochloride powder in isotonic NaCl to obtain a final concentration of 2.5 mg/ml. The quinine salt has a molecular weight of 397 and the intended dose was equivalent to 12.24 mg/kg of quinine base. Five subjects received an i.v. dose of 11.97 mg/kg and one subject received 6.03 mg/kg of quinine base over 3 h.
- No. of animals per sex per dose / concentration:
- Six subjects, three males and three females
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. - Control animals:
- no
- Details on study design:
- The infusion was started at 08.00 h, after a light breakfast had been taken at home. The 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. For the i.v. infusion dose, the blood samples (2 ml) were collected in heparinised tubes at the time of drug intake, every 20 min until 3 h, every 30 min from 3 to 12 h and at 24 h, 28 h 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 30 min 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: 321 µmol/L* h
- Test no.:
- #1
- Toxicokinetic parameters:
- half-life 1st: 11.3 h
- Test no.:
- #1
- Toxicokinetic parameters:
- other: MRT i.v. 14.9 h
Metabolite characterisation studies
- Metabolites identified:
- not measured
Any other information on results incl. tables
Pharmacokinetic parameters of quinine dihydrochloride calculated from plasma concentrations
AUC (µmol*h/L) | t1/2,z(h) | MRT i.v. (h) | Vss(1/kg) | CL (ml*min-1*kg-1) | CVw (%) | |
Quinine dihydrochloride | 321 (71) | 11.3 (3.1) | 14.9 (4.3) | 1.72 (0.38) | 2.00 (0.5) | 10 |
(normalised to a 6 h infusion for subject 4),
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
The AUC of quinine dihydrochloride was 321 µmol/L *h. The half-life of quinine dihydrochloride in plasma was 11.3 hours. - Executive summary:
In the study published by Paintaud, 1993 the pharmacokinetic of quinine dihydrochloride was determined after intravenous infusion. The AUC of quinine diydrochloride was 321 µmol/L *h and the half-life in plasma was 11.3 hours.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.