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EC number: 200-556-6 | CAS number: 63-37-6
- 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
- Study period:
- 1983
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 983
Materials and methods
- Objective of study:
- bioaccessibility (or bioavailability)
- distribution
- excretion
- toxicokinetics
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- Deviations:
- yes
- Remarks:
- 2 animals/dose
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Citicoline
- EC Number:
- 213-580-7
- EC Name:
- Citicoline
- Cas Number:
- 987-78-0
- Molecular formula:
- C14H26N4O11P2
- IUPAC Name:
- (2-{[({[(2R, 3S, 4R, 5R)-5-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl] methyl phosphonato}oxy)(hydroxy)phosphoryl]oxy}ethyl)trimethylazanium
- Details on test material:
- Synonym: CDP-Choline
Constituent 1
- Specific details on test material used for the study:
- RADIOLABELLING INFORMATION
CDP-choline was prepared by the Radiochemical Center of Amercham by an enzymatic process from phosphoryl (14C-methyl) choline and cytidine 5'-triphosphate.
- Radiochemical purity: It was purified by ionic exchange chormatography and the radiochemical purity was determied to be 99%.
- Specific activity: it was 50 mCi/mol
- Locations of the label: (14C-methyl) choline
- Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: own colony
- Weight at study initiation: 175-225 g
- Housing: metabolic cages
- Diet: fasted up to 24h after administration and then with free access to food
- Water: ad libitum
- Fasting period: 16-h prior to administration.
Administration / exposure
- Route of administration:
- intravenous
- Vehicle:
- other: in a solution not specified
- Duration and frequency of treatment / exposure:
- Administered only in one occasion into jugular vein.
Doses / concentrations
- Dose / conc.:
- 4 mg/kg bw (total dose)
- Remarks:
- with an activity of 10 microCi per animal
- No. of animals per sex per dose / concentration:
- 2
- Control animals:
- not specified
- Details on dosing and sampling:
- TOXICOKINETIC / PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled:
Blood samples (about 100 ml) were obtained by means of small cuts in the tail at the scheduled times and evaluated by weighing.
Urine and feces produced in the periods of 0-24h and 24-72h were collected.
The organs studied were brain, lung, kidney, liver and heart. The animals used fo the determination of organ levels were collected under anesthesia with ether before the extraction of the respective organ. The organs were immediatelly and carefully removed. Aliquot parts of 100 mg of tissue were digested and decolorised. Then, they were measured in the scintillation counter.
- Other:
Blood was put to digest decolorise in a mixture of hydrogen peroxide and Packard soluene-isopropanol before being counted in a liquid scintillation counter LS-7500 Beckman in the presence of 10 ml of Instagel-0.5 N HCl, according to the programme for 14C-counting.
Urines were diluted in to water up to a volume of 50 ml.
Feces were homogenized and diluted up to a volume of 250 ml.
From the diluted urine and feces, sampels of 1 ml were taken as to evaluate them with scintillation counter in the presence of Instagel, according to the prgramme for 14C.
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine, faeces, blood, brain, lung, kidney, liver and heard tissues.
- Method type(s) for identification: The samples were counted with a liquid scintillation counter LS-750, according to the programme for 14C.
Results and discussion
Main ADME resultsopen allclose all
- Type:
- distribution
- Results:
- CDP-choline and metabolites are widely distributed
- Type:
- excretion
- Results:
- inestimable by fecal route and low by urinary route
Toxicokinetic / pharmacokinetic studies
- Details on distribution in tissues:
- A fall in values of the radioactivity corresponding to CDP-choline administered by intravenous route is observed between 1/2 and 1 hour after administration. Later, on the blood concentration shows a trend to come back slowly to the initial values. Thus, a redistribution phase is made evident.
CDP-Choline or its labelled metabolites are widely distributed, the cerebral radioactivity evolving in a different way from the blood which would confirm the inclusion of the product in the pool of phospholipids.
- Details on excretion:
- The elimination is inestimable by fecal route and low by urine route, giving rise to the high hematic levels obtained at long times.
The values obtained ranged between 6-7% of total recovery, corresponding to a large degreee to the urinary elimination. An important percentage is eliminated in the form of CO2. Moreover, it seems taht there is a fixation of CDP- Choline or its metabolites in the structure components of the blood such as a red blood corpuscles and leukocytes, because these products are problably included in the metabolic processes of inclusion in cellular structures.
Toxicokinetic parameters
- Key result
- Test no.:
- #1
- Toxicokinetic parameters:
- AUC: 77.42
- Remarks:
- 0-24 h
Metabolite characterisation studies
- Metabolites identified:
- not measured
Bioaccessibility (or Bioavailability)
- Bioaccessibility (or Bioavailability) testing results:
- The CDP-choline is completely absorbed when administered by intravenous route. The bioavailability is practically complete.
Any other information on results incl. tables
Table 1: Bood kinetics of the total radioactivity after intravenous administration of 4 mg/kg of CDP-Choline to male rats, expressed as percentage of radioactivity per 10 ml of blood, as average and standard deviation:
Time |
Average |
Standard deviation |
10 min |
3.05 |
0.24 |
20 min |
2.59 |
0.31 |
30 min |
1.47 |
0.22 |
1 h |
1.40 |
0.02 |
2 h |
2.84 |
0.02 |
3 h |
2.50 |
0.05 |
4 h |
2.77 |
1.00 |
5 h |
3.37 |
0.31 |
6 h |
3.68 |
0.02 |
7 h |
- |
- |
24 h |
3.12 |
0.19 |
Table 2: Urinary and fecal recovery of radioactivity after the administration of 4 mg/kg of CDP-choline intravenously, as percentage related to the administered dose, expressed as the average with standard deviation:
Urine/fecal collection period |
Average |
Standard deviation |
0-24 |
1.78 |
0.38 |
24-72 |
4.84 |
0.61 |
0-24 |
0.12 |
0.10 |
24-72 |
0.56 |
0.23 |
Table 3: Organic distribution of CDP-Choline and labelled metabolites, expressed as percentage of total dose, after intravenous administration of 4 mg/kg of labelled CDP-choline:
Time |
5 h |
24 h |
||
|
Average |
Standard Deviation |
Average |
Standard Deviation |
Brain |
0.26 |
0.03 |
0.23 |
0.18 |
Lung |
2.27 |
0.29 |
2.32 |
1.68 |
Liver |
2.32 |
6.82 |
15.52 |
6.81 |
Kidney |
5.86 |
1.61 |
1.45 |
0.98 |
Heart |
0.85 |
0.72 |
1.03 |
0.87 |
Applicant's summary and conclusion
- Conclusions:
- The CDP-choline administered by intravenous route on rats is widely distributed in the organs and eliminated very slowly. The value of AUC (0-24h) is 77.42.
- Executive summary:
The bioavailability of radiollableled CDP-choline was studied by intravenous route on Sprague-Dawley rats. The amount of 4 mg/kg bw (total dose) was administered in a solution into jugular vein and the absortion, distribution on brain, lung, kidney, liver and heart and excretion of the substance was evaluated. The product was widely distributed in the organs and a very low urinary and fecal elimination was observed, thus producing mantained blood levels. The AUC (0-24h) was determined to be 77.42.
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