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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1997-11-17 to 1997-11-20
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:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
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
- Storage condition of test material: at room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: at least 6 weeks
- Weight at study initiation: less than 3.5 kg
- Housing: individually in labelled cages
- Diet (e.g. ad libitum): free access
- Water (e.g. ad libitum): free access
- Acclimation period: at least 5 days before start of the treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 °C
- Humidity (%): 50 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 69.8 +/- 0.5 mg (a volume of approximately 0.1 ml)
Duration of treatment / exposure:
upon application eye closed for one second and subsequently not rinsed
Observation period (in vivo):
The eyes of each animal were examined approximately 1, 24,48 and 72 h after instillation of the test substance
Number of animals or in vitro replicates:
3 animals of either sex
Details on study design:
SCORING SYSTEM: numerical scoring
TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
1492
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
1494
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
1510
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
1492
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
1494
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
1510
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
1492
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
1492
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
1510
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Eyelids, Nictitating membrane
Basis:
animal #1
Remarks:
1492
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Eyelids, Nictitating membrane
Basis:
animal #2
Remarks:
1494
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
1510
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Other effects:
There was no evidence of ocular corrosion. Remnants of the test substance were present in the eye of one animal and on the outside of the eyelid of another animal on day 1.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Table 1: Mean values of eye irritation scores (24, 48 and 72 h after instillation)

Animal No.

Mean 24 – 72 hours

 

Corneal opacity

Iris

Conjunctivae Redness

Conjunctivae Chemosis

1492

0

0

0.3

0

1494

0

0

0.3

0

1510

0

0

0

0

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations, creatine monohydrate does not have to be classified and has no obligatory labelling for eye irritation.0
Creatine monohydrate is not irritating.
Executive summary:

In a primary eye irritation study according to the OECD guideline 405 "Acute Eye Irritation/Corrosion" single samples of approximately 70 mg creatine monohydrate (a volume of approximately 0.1 ml) which is equivalent to 61.54 mg creatine (or 0.088 ml respectively) were instilled into the conjunctival sac of one eye of each of three male albino rabbits (New Zealand White; Source: Broekman Institute; at least 6 weeks old; body weight < 3.5 kg). The eyes were not washed. Observations were made 1, 24, 48 and 72 hours after instillation. Irritation was scored with a numerical scoring system. The irritation consisted of redness, chemosis and/or discharge, and had completely resolved within 24 hours in one animal and within 48 hours in the two other animals. Iridic irritation grade 1 was observed in two animals on day 1 only. In this study creatine monohydrate is not an eye irritant and does not have to be classified.