2-imino-1-methylimidazolidin-4-one

Acute Toxicity: oral

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

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%
- Lot/batch No.: CRT 197
- Expiration date of the lot/batch: 1998-6-19
- Storage condition of test material: at room temperature in the dark
- Stability under test conditions: at least 96 h

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: 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

Administration / exposure

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

Results and discussion

Preliminary study:

n.a.

Effect levels

Effect levels 1

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)

Effect levels 2

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

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.