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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
Endpoint summary
Administrative data
Description of key information
Four reliable acute toxicity studies on Creatine monohydrate are available.
Two oral studies in rats, one dermal study in the rat and one intraperitoneal study in mice. All studies are indicating no acute effect up to 2000 mg/kg body weight. A LD50 exceeding 2000 mg/kg body weight could be established. The corresponding calculated LD50 of creatine is exceeding 1758.36 mg/kg body weight. As none of the animals died during the studies the LD0 of creatine is exceeding 1758.36 mg/kg body weight. Therefore the LD50 of Creatine is expected to be above 2000 mg/kg bw.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1997-8-27 to 1997-9-10
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- acute toxic class method
- Limit test:
- yes
- 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: approx. 6 weeks old
- Weight at study initiation: female: average 145 g; male: average 180 g
- Fasting period before study: overnight prior to dosing until approximatetly 3-4 hours after administration of the test substance
- Housing: 3 animals per sex per cage
- Diet (e.g. ad libitum): free access
- Water (e.g. ad libitum): free access
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- distilled
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: 1 g test substance per 9 ml of water
- Justification for choice of vehicle: The vehicle was selected based on information provided by the sponsor
DOSAGE PREPARATION (if unusual): substance was ground into fine powder and 1 g was filled into the tube of a syringe; 9 ml water was drawn in; the syringe was shaken thoroughly to prepare the suspension; the suspension was administered immediately after preparation - Doses:
- 2000 mg/kg (20ml/kg) body weight
- No. of animals per sex per dose:
- 3
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 15 days
- Frequency of observations and weighing: observations of clinical signs once daily; body weight: day 1 (pre-administration, 8 and 15)
- Necropsy of survivors performed: yes - Statistics:
- no statistical analysis was performed
- Preliminary study:
- n.a.
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD0
- Effect level:
- 2 000 mg/kg bw
- Based on:
- test mat.
- Remarks:
- equals 1758.36 mg/kg bw Creatine (anhydrous)
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Remarks:
- equals 1758.36 mg/kg bw Creatine (anhydrous)
- Mortality:
- No mortality occurred
- Clinical signs:
- other: No clinical signs were detected
- Gross pathology:
- No abnormalities were found
- Other findings:
- none
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The oral LD50 value of creatine monohydrate in Wistar rats was established as exceeding 2000 mg/kg body weight. The corresponding LD50 of creatine is > 1758.36 mg/kg body weight.
- Executive summary:
To assess the oral toxicity of creatine monohydrate a limit test based on the OECD guideline No. 423 "Acute oral toxicity-Acute toxic class method" was carried out. Creatine monohydrate in distilled water (1 g per 9 ml) was administered by oral gavage to three approx. 6 week old, fasted Wistar rats of each sex at a dose of 2000 mg/kg body weight. The animals were observed for 15 days. Macroscopic examination was performed after terminal sacrifice (day 15).
No mortality occurred and no clinical signs were noted. Body weight gain was considered as normal. No abnormalities were found at the macroscopic post mortem examination. The oral LD50 value of creatine monohydrate in Wistar rats was established as exceeding 2000 mg/kg body weight.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 2004-10-5 to 2004-10-28
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- acute toxic class method
- Limit test:
- no
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Remarks:
- IGS BR
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland GmbH, D-97633 Sulzfeld
- Age at study initiation: approximately 8 weeks
- Weight at study initiation (mean): group 1 (dose 300 mg/kg b.w.): 175.3 g; group 2 (dose 300 mg/kg b.w.): 179.0 g; group 3 (dose 2000 mg/kg b.w.): 187.0 g; group 4 (dose 2000 mg/kg b.w.) 197.0 g
- Fasting period before study: evening before the administration and about 3 hours afterwards
- Housing: single caging
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): average: 22.1 °C
- Humidity (%): average 55.9 %
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- deionised
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: dependent on body weight; administration of 10 ml per kg b.w.; doses: 300 mg/kg and 2000 mg/kg b.w.
- Amount of vehicle (if gavage): 10 ml per kg b.w.
- Justification for choice of vehicle: the test substance could be disolved in water and water shall be used preferably, according to the guideline
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: as no prior information on the toxicity of the test substance was available, a starting dose of 300 mg/kg b.w. was chosen. The further proceeding was in accordance with the guideline. - Doses:
- Starting dose: 300 mg/kg body weight
Second dose: 2000 mg/kg body weight - No. of animals per sex per dose:
- 3
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations were performed within the periods 0-0.5, 0.5-1, 1-2, 2-4, 4-6 hours after administration and then at least once a day for a total of 2 weeks; body weights were determined before administration, 7 days p.a. and 14 days p.a.
- Necropsy of survivors performed: yes - Statistics:
- no statistical analysis was performed
- Preliminary study:
- none
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Remarks:
- equal to 1758.36 mg/kg bw Creatine anhydride
- Mortality:
- All animals survived until the scheduled termination of the study
- Clinical signs:
- other: All animals were normal during the entire observation period
- Gross pathology:
- All animals were normal at the necroscopy 14 days after administration
- Other findings:
- no other findings
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- No toxic effects of the test substance were noted by signs in life and post mortem. No mortality occurred.
- Executive summary:
To assess the oral toxicity of creatine monohydrate a limit test based on the OECD guideline No. 423 "Acute oral toxicity-Acute toxic class method" was conducted. Creatine monohydrate was administered once as a suspension in deionized water by oral gavage to groups of three fasted, approx. 8 weeks old animals (female Crl:CD(SD)IGS BR rats). A starting dose of 300 mg per kg body weight and a second dose of 2000 mg/kg body weight were given. The animals were observed for 14 days. No toxic effects of the test substance were noted. No mortality occurred. The oral LD50 value of creatine monohydrate in rats was established as exceeding 2000 mg/kg per body weight.
Referenceopen allclose all
Table 1: Body weights (gram)
Group/Sex |
Animal |
Day 1 |
Day 8 |
Day 15 |
Group 1/ Males (2000 mg/kg) |
1 |
184 |
245 |
284 |
2 |
188 |
243 |
292 |
|
3 |
169 |
218 |
252 |
|
Mean |
180 |
235 |
276 |
|
Standard deviation |
10 |
15 |
21 |
|
n |
3 |
3 |
3 |
|
Group 1/ Females (2000 mg/kg) |
1 |
147 |
177 |
203 |
2 |
144 |
178 |
194 |
|
3 |
144 |
192 |
223 |
|
Mean |
145 |
182 |
207 |
|
Standard deviation |
2 |
8 |
15 |
|
n |
3 |
3 |
3 |
Table 1: Synopsis of the results
Dose (mg/kg) |
Step No. |
Animal Nos. |
Exposed animals |
Affected animals |
Deceased animals |
300 |
1 |
111, 112, 113 |
3 |
0 |
0 |
300 |
2 |
114, 115, 116 |
3 |
0 |
0 |
2000 |
3 |
121, 122, 123 |
3 |
0 |
0 |
2000 |
4 |
124, 125, 126 |
3 |
0 |
0 |
Table 2: Body weight and body weight gain
Dose mg/kg (Step No.) |
Animal No. |
Body weight |
Body weight gain |
||||
|
Before administration |
7 days p.a. |
14 days p.a. |
death |
0-7 days p.a. |
7-14 days p.a. |
|
300 (1) |
111 |
170 |
203 |
231 |
- |
33 |
28 |
|
112 |
174 |
204 |
225 |
- |
30 |
21 |
|
113 |
182 |
217 |
239 |
- |
35 |
22 |
|
Mean |
175.3 |
208.0 |
231.7 |
- |
32.7 |
23.7 |
|
SD |
6.1 |
7.8 |
7.0 |
- |
2.5 |
3.8 |
300 (2) |
114 |
181 |
213 |
229 |
- |
32 |
16 |
|
115 |
177 |
214 |
246 |
- |
37 |
32 |
|
116 |
179 |
205 |
228 |
- |
26 |
23 |
|
Mean |
179.0 |
210.7 |
234.3 |
- |
31.7 |
23.7 |
|
SD |
2.0 |
4.9 |
10.1 |
- |
5.5 |
8.0 |
2000 (3) |
121 |
180 |
205 |
210 |
- |
25 |
5 |
|
122 |
184 |
212 |
227 |
- |
28 |
15 |
|
123 |
197 |
227 |
239 |
- |
30 |
12 |
|
Mean |
187.0 |
214.7 |
225.3 |
- |
27.7 |
10.7 |
|
SD |
8.9 |
11.2 |
14.6 |
- |
2.5 |
5.1 |
2000 (4) |
124 |
197 |
222 |
249 |
- |
25 |
27 |
|
125 |
198 |
224 |
236 |
- |
26 |
12 |
|
126 |
196 |
227 |
244 |
- |
31 |
17 |
|
Mean |
197.0 |
224.3 |
243.0 |
- |
27.3 |
18.7 |
|
SD |
1.0 |
2.5 |
6.6 |
- |
3.2 |
7.6 |
Observations in life: normal at any time
Necroscopy findings: normal
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Data waiving:
- other justification
- Justification for data waiving:
- other:
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2011-09-13 to 2011-09-27
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.3 (Acute Toxicity (Dermal))
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland GmbH, D-97633 Sulzfeld.
- Age at study initiation: Approximately 8 weeks (males) and 12 weeks (females) at the time of administration.
- Weight at study initiation: males (mean): 282.2 g; females (mean): 230.4 g
- Fasting period before study: not reported
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 7 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): Mean of 20.92 °C
- Humidity (%): Mean of 56.72 %
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12 - Type of coverage:
- semiocclusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- TEST SITE
- Area of exposure: 10 % of the estimated body surface
- % coverage: 10
- Type of wrap if used: cellulose patch (Pehazell, Hartmann AG), non irritating tape (Blenderm Wundpflaster, 3M), semi-occlusive dressing (Fixomull Stretch, Fa. Beiersdorf)
REMOVAL OF TEST SUBSTANCE
- Washing (if done): none; Residual test substance was wiped off using wet cellulose tissue, if necessary.
- Time after start of exposure: 24 h
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The amounts of the test substance were calculated and weighed for each individual using the body weight determined on the day of the administration.
- For solids, paste formed: no - Duration of exposure:
- 24 h
- Doses:
- 2000 mg/kg
- No. of animals per sex per dose:
- 5 males and 5 females
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: before administration, 7 days p.a., 14 days p.a.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, body weight gain; changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions - Statistics:
- none
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Remarks:
- equals to 1758.36 mg/kg body weigh Creatine (anhydride)
- Mortality:
- All animals survived until the scheduled termination of the study.
- Clinical signs:
- other: General findings: All animals did not show any clinical signs during the entire observation period. Observations of skin condition: Exposed skin was not found to be altered by the test substance.
- Gross pathology:
- No abnormal findings were made in the animals at terminal necropsy.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- No local or systemic toxic effects related to administration of the test substance were noted from clinical observations or post-mortem-examination at a dose of 2000 mg of the test substance per kg body weight. No mortality occurred.
- Executive summary:
In an acute dermal toxicity study according the OECD guideline 402 groups of young adult rats (Crl:CD(SD)) (5/sex) were dermally exposed to Creatine Monohydrate (>=99 %) for 24 hours to 10 % of the body surface area at doses of 2000 mg/kg bw (limit test). Animals then were observed for 14 days. No local or systemic test substance related effects were noted from clinical observations or post-mortem examination at a dose of 2000 mg test substance per kg body weight. No mortality occurred. A dermal LD50 (males/females) > 2000 mg/kg body weight was determined. From the results of this study no classification is derived for Creatine Monohydrate according to the Directive 2001/59/EC.
Reference
Table 1: Body weights and body weight gain.
Individual data, mean and standard deviation SD.
Dose sex |
Animal No. |
Body weight (g) |
Body weight gain (g) |
||||
2000 mg/kg male |
before administr |
7 days p.a. |
14 days p.a. |
death |
0-7 days p.a. |
7-14 days p.a. |
|
121 |
283 |
323 |
366 |
- |
40 |
43 |
|
122 |
295 |
335 |
378 |
- |
40 |
43 |
|
123 |
271 |
300 |
348 |
- |
29 |
48 |
|
124 |
277 |
296 |
334 |
- |
19 |
38 |
|
125 |
285 |
318 |
352 |
- |
33 |
34 |
|
Mean |
282.2 |
314.4 |
355.6 |
- |
32.2 |
41.2 |
|
SD |
9.0 |
16.3 |
16.9 |
- |
8.8 |
5.4 |
|
2000 mg/kg female |
126 |
226 |
251 |
269 |
- |
25 |
18 |
127 |
240 |
245 |
258 |
- |
5 |
13 |
|
128 |
232 |
233 |
240 |
- |
1 |
7 |
|
129 |
226 |
230 |
239 |
- |
4 |
9 |
|
130 |
228 |
243 |
252 |
- |
15 |
9 |
|
Mean |
230.4 |
240.4 |
251.6 |
- |
10.0 |
11.2 |
|
SD |
5.9 |
8.7 |
12.6 |
- |
9.9 |
4.4 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
Additional information
The acute oral toxicity of creatine monohydrate was assessed in two limit tests based on the OECD guideline No. 423 "Acute oral toxicity-Acute toxic class method" . No mortality occurred and no clinical signs were noted. The oral LD50 value of creatine monohydrate in Wistar rats was established as exceeding 2000 mg/kg body weight.
The acute dermal toxicity of Creatine Monohydrate was assessed in a limit test according the OECD guideline 402. No local or systemic test substance related effects were noted from clinical observations or post-mortem examination at a dose of 2000 mg test substance per kg body weight. A dermal LD50 (males/females) > 2000 mg/kg body weight was determined.
The intraperitoneal toxicity of Creatine Monohydrate was assessed in a limit test based on the OECD guideline 423 in mice (strain CD-1) except the route of dosing which was intraperitoneal instead of oral. No mortality occurred and no clinical signs were observed. The intraperitoneal LD50 value of creatine monohydrate in mice was established as exceeding 2000 mg/kg body weight.
As none of the animals died the LD0 is exceeding 2000 mg/kg body weight.
Toxicity by inhalation was not assessed as in case of the test substance Creatine the oral and dermal route are considered as likely routes of human exposure for workers and consumers. Besides that, Creatine has a very low vapor pressure and a high melting point, so the potential for the generation of inhalable forms is low. The particle size of Creatine is considered to be 114.02 µm. Therefore the particles are not considered to be inhalable (cut off size > 100 µm) and no acute inhalation test was performed.
Justification for classification or non-classification
No mortalities or clinical signs were observed at appropriate dose levels.
According Regulation (EC) No 1272/2008 LD50-doses of more than 2000 mg/kg are not considered to indicate oral or dermal acute toxicity.
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