N-amidinosarcosine

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1997-9-10 to 1997-8-27

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:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

route of dosing intraperitoneal instead of oral

Principles of method if other than guideline:

Route of dosing intraperitoneal instead of oral.

GLP compliance:

yes

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 %
- Purity test date: 1997-7-29
- Lot/batch No.: CRT 197
- Expiration date of the lot/batch: 1998-6-19
- Stability under test conditions: at least 96 h
- Storage condition of test material: at room temperature in the dark

Test animals

Species:

mouse

Strain:

CD-1

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 old
- Weight at study initiation: male mean: 31 g; female mean 26 g
- Housing: group housing of 3 animals per sex per cage
- Diet (e.g. ad libitum): free access
- Water (e.g. ad libitum): free access
- Acclimation period: at least 5 days before start of treatment under laboratory conditions

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:

intraperitoneal

Vehicle:

water

Details on exposure:

- Concentration in vehicle: 1 g of the ground substance was dissolved in 9 ml distilled water
- Justification for choice of vehicle: the vehicle was selected based on information provided by the sponsor
DOSAGE PREPARATION: the test substance was ground and filled in a syringe; 9 ml of water was drawn into the syringe and thoroughly shaken to prepare the suspension; the formulation was administered immediately after preparation
- MAXIMUM DOSE VOLUME APPLIED: 0.66 ml
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: limit test

Doses:

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: 15 days
- Frequency of observations and weighing: body weights were determined on day 1 (pre-adminsitration) and on day 8 and 15; observations of clinical signs was monitored in periodic intervals on the day of dosing (day 1) and once daily thereafter
- Necropsy of survivors performed: yes

Statistics:

no statistical analysis was performed (the method is not intended to allow the calculation of a precise LD50 value)

Results and discussion

Effect levels

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 (anhydride)

Mortality:

No mortality occurred

Clinical signs:

No clinical signs of toxicity were noted in the animals

Body weight:

The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals

Other findings:

none

Any other information on results incl. tables

Table 1: Body weights and individual dose volume (ml)

Group/sex	Animal	Day 1	Dose volume	Day 8	Day 15
Group 1/ Males (2000 mg/kg)	1	30	0.60 ml	33	36
	2	33	0.66 ml	36	39
	3	31	0.62 ml	33	34
	Mean	31		34	36
	St. Dev.	2		2	3
	n	3		3	3
Group 1/ Females (2000 mg/kg)	4	26	0.52 ml	29	33
	5	25	0.50 ml	28	30
	6	27	0.54 ml	28	30
	Mean	26		28	31
	St. Dev.	1		1	2
	n	3		3	3

Applicant's summary and conclusion

Conclusions:

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 of Creatine Monohydrate is 2000 mg/kg body weight. This equals to 1758.36 mg/kg bw Creatine (anhydride).

Executive summary:

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. Creatine monohydrate was administered once as a suspension in deionized water by intraperitoneal injection to three mice of each sex at a dose of 2000 mg/kg body weight. Animals were subjected to daily observation and weekly determinations of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). No mortality occurred and no clinical signs were observed. Body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found in the animals at macroscopic post mortem examination. 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.