N-amidinosarcosine

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

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

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

Constituent 2

Reference substance name:

Creapure

IUPAC Name:

Creapure

Details on test material:

- Name of test material (as cited in study report): Creatine monohydrate
- Molecular formula (if other than submission substance): C4H11N3O3
- Substance type: organic
- Physical state: solid; colourless, white powder
- Analytical purity: >= 99 %
- Purity test date: 2011-03-21
- Lot/batch No.: 108131
- Expiration date of the lot/batch: 2014-03-21
- Stability under test conditions: According to the sponsor, the stability of the test item is guaranteed throughout the study period when stored under the
conditions stated.
- Storage condition of test material: In the refrigerator (2 – 8°C)

Test animals

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

Administration / exposure

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

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 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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.