Registration Dossier

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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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 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:
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.
Body weight:
All animals gained weight in both weeks p.a.
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.