Registration Dossier

Administrative data

Description of key information

The test material was investigated for its irritating potential to skin and eyes in two in vivo tests in rabbits. The two in vivo tests followed or exceeded the requirements of the respective OECD Guidelines.

Skin irritation was studied in rabbits with either abraded or intact skin which were exposed to the test item for 24 hours under occlusive conditions. Based on the results of this study, the test material is not considered to be irritating to the skin.

The potential for eye irritation was investigated in rabbits. Minor initial effects were fully reversible thus indicating that the test material is not irritating to the eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1970
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
This study design follows OECD guideline 404 and extends requirements in certain details (e.g exposure time, number of animals, scarified skin, occlusive instead of semi-occlusive). The conduct and the findings of the study are well reported. However, some individual data were not included in the report.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
increased exposure time, larger number of animals, scarified skin, occlusive instead of semi-occlusive conditions
GLP compliance:
no
Remarks:
performed before OECD GLP regulation became effective
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Six male White New Zealand rabbits were used with either intact (3 animals) or scarified skin (3 animals).

TEST ANIMALS
- Source: E. Merck
- Age at study initiation: no information provided
- Weight at study initiation: mean 2,50 kg (2,32 - 2,80 kg)
- Housing: individual cages (Becker)
- Diet: Altromin, ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature, Humidity, Air changes, Photoperiod: no information provided
Type of coverage:
occlusive
Preparation of test site:
abraded
Vehicle:
water
Controls:
yes, concurrent vehicle
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g

VEHICLE
- Amount applied: low volume to moisten the test material

NEGATIVE CONTROL
- negative control: talcum, moistened with water
- Amount applied: 0.5 g

Duration of treatment / exposure:
24 h
Observation period:
7 d
Number of animals:
6 animals: 3 animals with intact skin (only shaved) and
3 animals with abraded skin (after shaving)
Details on study design:
TEST SITE
- Area of exposure: 4 cm2
- Type of wrap if used: occlusive

REMOVAL OF TEST SUBSTANCE
- Washing: removal of remaining test material with water 24 hours after start of exposure
- Time after start of exposure: 24 hours

OBSERVATION TIME POINTS
Once daily for 1 week

SCORING SYSTEM:
according to Draize /FDA (Appaisal of the Safety of Chemicals in Foods, Drugs, and Cosmetics of the FDA, Baltimore MD, 1959)
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
1
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
0.83
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
0.13
Max. score:
4
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: Scores are evaluated from the findings described in the report
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Directly after removal of the occlusive patches a slight reddening was observed in all rabbits both with intact or scarified skin up to day 2 (5 animals) or day 4 (one animal). Thereafter, all animals were without findings.
Other effects:
no

Skin reactions were evaluated and graded according to FDA appraisal. The scores were assessed from the description of effects provided in the report.

Interpretation of results:
GHS criteria not met
Conclusions:
Based on this study the test material is considered to be not irritating to the skin.
Executive summary:

The skin irritation potential of the test material was investigated in six male White New Zealand rabbits following application either on intact (3 animals) or scarified skin (3 animals). Aliquots of neat test material (0.5 g) were moistened with water and applied to the intact or scarified skin of each rabbit for a 24-hour period under occlusive conditions. The rabbits were examined for skin reactions after removal of the patches daily for seven days. Skin reactions were evaluated and graded according to FDA appraisal. Directly after removal of the occlusive patches a slight reddening was observed in all rabbits both with intact or scarified skin up to day 2 (5 animals) or day 4 (one animal). Thereafter, all animals were without findings.

Based on this study the test material is considered not to be irritating to the skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1970
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Remarks:
performed before OECD GLP regulation became effective
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Three male White New Zealand rabbits were used.

TEST ANIMALS
- Source: E. Merck
- Age at study initiation: no infomation provided
- Weight at study initiation: mean 2,78 kg (2,61 - 2,91 kg)
- Housing: individual cages (Becker)
- Diet: Altromin, ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature, Humidity, Air changes, Photoperiod: no information provided
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
100 mg per animal
Duration of treatment / exposure:
The applied test material was not rinsed off.
Observation period (in vivo):
The rabbits were examined for eye irritation daily up to day 7 of the study.
Number of animals or in vitro replicates:
3 animals
Details on study design:
Aliquots of 0.1 g DHA were applied into the conjunctival sac of the left eye of each rabbit. The right eye remained untreated and served as a control. After treatment the rabbits were examined for eye irritation daily up to one week. Eye reactions were evaluated and graded according to Draize (Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, FDA Baltimore, 1959).

REMOVAL OF TEST SUBSTANCE
- Washing: not performed

SCORING SYSTEM: according to Draize (Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, FDA Baltimore, 1959)

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
erythema
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Remarks:
erythema
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
erythema
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Eye reactions were evaluated and graded according to Draize scale. After instillation of the test material, no irritancy was observed in two animals. One animal showed a slight transient erythema of the conjunctiva from 24 hours after instillation up to day 3 of the observation period. Scores are established from the observations described in the report.The scores are not mentioned in the study report.
Other effects:
No clinical signs were observed. The development of body weight was inconspicious.

No individual scores on eye irritation were provided in the report. However, only one animal showed a slight reddening of the conjunctivae from day 1 to day 3. No irritating effects were observed in the two remaining animals. Therefore, the test material is evaluated as not irritating to the eyes.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: US CPSC / US FDA
Conclusions:
Based on the results of this study, undiluted test item is evaluated as non-irritating to the eyes
Executive summary:

The test material was tested for acute eye irritation in three male rabbits (New Zeeland). Aliquots of 0.1 g were applied into the conjunctival sac of the left eye of each rabbit. The right eye remained untreated and served as a control. The rabbits were examined for eye irritation daily up to day 7 of the study. Eye reactions were evaluated and graded according to Draize scale. After instillation of the test material, no irritancy was observed in two animals. One animal showed a slight transient erythema of the conjunctiva from 24 hours after instillation up to day 3 of the observation period. Based on the results of this study, undiluted test material is evaluated as non-irritating to the eyes.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

In vivo studies in rabbits on skin and eye irritation showed that the test substance exhibits no irritating potential.

Justification for classification or non-classification

Based on the results of in vivo studies, the test material must not be classified to be irritating/corrosive as shown in valid in vivo studies.