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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 200-306-6 | CAS number: 57-00-1
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1998-8-12 to 1998-9-10
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 998
- Report date:
- 1999
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- N-(aminoiminomethyl)-N-methyl-Glycine, monohydrate
- Cas Number:
- 6020-87-7
- Molecular formula:
- C4H9N3O2*H2O
- IUPAC Name:
- N-(aminoiminomethyl)-N-methyl-Glycine, monohydrate
- Details on test material:
- - Name of test material (as cited in study report): Creatine Monohydrate
- Substance type: organic
- Physical state: solid; white crystals
- Analytical purity: 101.8 %
- Purity test date: 1997-7-29
- Lot/batch No.: CRT 197/813 603
- Expiration date of the lot/batch: 1999-8-11
- Stability under test conditions: at least 4 hours
- Storage condition of test material: at room temperature in the dark
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: approximately 6 weeks
- Weight at study initiation: +/- 20% of sex mean
- Housing: group housing of 5 animals per sex per cage; during activity monitoring animals were individually housed overnight
- Diet (e.g. ad libitum): free access
- Water (e.g. ad libitum): free access
- Acclimation period: at least 5 days before start of treatment
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 °C
- Humidity (%): 50 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 1 % aqueous CMC
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: Formulations (w/w) were prepared daily within 4 hours prior to dosing. Adjustment was made for specific gravity of vehicle
VEHICLE
- Justification for use and choice of vehicle (if other than water): based on trial formulations performed at NOTOX
- Concentration in vehicle: 0, 250, 500, 1000, 2000 mg/kg body weight per day
- Amount of vehicle (if gavage): 5 ml/kg body weight - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The test substance formulations in 1 % aqueous CMC were noted as stable for at least 4 hours and formed a homogeneous solution at the concentrations tested. Analysis of the accuracy of dose preparations revealed values which were in good conformity with the target values. For group 5 the analytical results differed from the target values by about 10 % which was still considered to represent an acceptable level of accuracy for formulations of this type.
- Duration of treatment / exposure:
- at least 28 days
- Frequency of treatment:
- once daily, approximately the same time each day, 7 days per week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- Control
- Dose / conc.:
- 250 mg/kg bw/day (nominal)
- Dose / conc.:
- 500 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Dose / conc.:
- 2 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: dose levels were selected on the basis of two 5-day dose range finding studies (Notox projects 210522/210533)
- Positive control:
- no positive control
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once daily; once prior to start of treatment and on day 8, 15, 22 and 28 this was also performed outside the home cage in a standard arena; the time of onset, degree and duration was recorded
BODY WEIGHT: Yes
- Time schedule for examinations: on day 1, 8, 15, 22 and 28
FOOD CONSUMPTION
- weekly
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No
WATER CONSUMPTION:
- weekly
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: after urine collection prior to post mortem examination
- Anaesthetic used for blood collection: Yes (Ether)
- Animals fasted: Yes
- How many animals: all animals
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: after urine collection prior to post mortem examination
- Animals fasted: Yes
- How many animals: all animals
URINALYSIS: Yes
- Time schedule for collection of urine: after last treatment on day 28/29 [males] and 29/30 [females]); sampling period approximately 16 hours
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: during week 4 of treatment
- Dose groups that were examined: all animals were tested
- Battery of functions tested: grip strength, hearing ability, pupillary reflex, static righting reflex - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Other examinations:
- Histotechnology: all organ and tissue samples were processed, embedded and cut at a thickness of 2-4 µm and stained with haematoxylin and eosin
- Statistics:
- Univariate one-way analysis of variance was used to assess the significance of intergroup differences. If variables could be assumed to follow a normal distribution, the Dunnett-test (many-to-one-t-test) based on a pooled variance estimate was applied for the comparison of the the treated groups and the control groups for each sex. The Steel-test (many-to-one rank test) was applied when the data could not be assumed to follow a normal distribution. All tests were two-sided and in all cases p < 0.05 was accepted as the lowest level of significance. Group means were calculated for continuous data and medians were calculated for discrete data in the summary tables.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- no effects on urinary crystals, no changes in clinical apperance, functional observations, body weights, food consumption, clinical laboratory investigations, macroscopic examinations, organ weights and microscopic examination
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 2 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- equal to 1758.36 mg/kg body weight Creatine (anhydride)
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical biochemistry
- clinical signs
- food consumption and compound intake
- gross pathology
- haematology
- histopathology: neoplastic
- histopathology: non-neoplastic
- mortality
- organ weights and organ / body weight ratios
- urinalysis
- water consumption and compound intake
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- Oral treatment with creatine monohydrate for 28 days at dose levels up to 2000 mg/kg body weight per day has no effects on urinary crystals, no changes in clinical appearance, functional observations, body weights, food consumption, clinical laboratory investigations, macroscopic examinations, organ weights and microscopic examination. A NOAEL of 2000 mg/kg bw/day could be established. This equals to 1758.36 mg/kg bw/day Creatine (anhydride).
- Executive summary:
In a sub-acute 28-day oral toxicity study which was conducted according the OECD guideline 407 “Repeated Dose 28-day Oral Toxicity Study in Rodents” (1995) creatine monohydrate (in 1% aqueous carboxymethyl cellulose) was administered daily to SPF-bred Wistar rats by oral gavage. Based on the results of two 5-day range finding studies, the dose levels for the 28-day toxicity study were selected to be 0, 250, 500, 1000 and 2000 mg/kg bw/day. One control group and four treated groups were tested, each consisting of 5 males and 5 females. No treatment-related findings were noted. A NOAEL of 2000 mg/kg bw/day was established.
The corresponding calculated NOAEL of creatine is exceeding 1758.36 mg/kg body weight.
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.