Registration Dossier

Administrative data

Description of key information

The test item was not irritating to the skin and the eye.

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:
from 1994-08-09 to 1994-08-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study followed the procedures indicated by internationally accepted guidelines and recommendations as Commission Regulation (EC) No 440/2008 (B.4: Acute Toxicity: Dermal Irritation / Corrosion).
Reason / purpose:
reference to other study
Reference:
Composition 0
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
directive 92/69/EEC
Deviations:
no
Principles of method if other than guideline:
NA
GLP compliance:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: a pprox. 12 weeks
- Weight at study initiation: 2026 - 2195 grams
- Housing: Individually in labelled cages with perforated floors and equipped with an automatic drinking system
- Diet: Standard laboratory rabbit diet (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands) approx. 100 gram per day.
- Water: Free access to tap-water diluted with decalcified water.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 °C
- Humidity: 50 % rel. humidity
- Air changes: approximately 15 air changes per hour
- Photoperiod: 12 hours artificial fluorescent light and 12 hours dark per day.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
The amount of test substance dose was 0.5 mL per animal.
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: surgical gauze patch of 2x3 cm
- Type of wrap if used: patches were mounted on Micropore tape which was wrapped around the abdomen and secured with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: Four hours after the application, the dressing was removed and the remaining test substance removed using a tissue moistened with tap-water and subsequently a dry tissue

SCORING SYSTEM: As stated in the guidelines
TEST SITE
- Area of exposure: 2 x 3 cm
- % coverage: 100
- Type of wrap: semi-occlusive

REMOVAL OF TEST SUBSTANCE
- Washing: with tissue moistened with tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM:
- according to the guidelines
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
- no skin irritation after 4 hours
- no evidence of a corrosive effect
Other effects:
Colouration: No staining of the treated skin by the test substance was observed.
Toxicity symptoms/Mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

no remarks

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item was considered not irritating to the rabbit skin.
Executive summary:

The test item was tested for skin irritation/corrosion to the intact rabbit skin in a test with three New Zealand White albino rabbits according to OECD guideline 404/EU method B.4. 0.5 mL of the test substance was applied to the intact skin of the shaved area on one flank on the shaved skin of the animals. The test area was wrapped with surgical tape. After 4 hours the wrapping was removed, the remaining test substance washed off and the application site observed for any signs of irritation/corrosion for 72 hours. No skin irritation was caused by the test item after 4 hours of exposure in any of the three rabbits. There was no evidence of a corrosive effect on the skin. No staining of the treated skin by the test substance was observed. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

According to the results obtained in this study, the test item was considered not irritating to the rabbit 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:
from 1994-08-15 to 1994-08-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study followed the procedures indicated by internationally accepted guidelines and recommendations as Commission Regulation (EC) No 440/2008 (B.5: Acute Toxicity: Eye Irritation / Corrosion)).
Reason / purpose:
reference to other study
Reference:
Composition 0
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
directive 92/69/EEC
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
24 February 1987
Deviations:
no
GLP compliance:
yes
Test material information:
Composition 1
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: approx. 14 weeks
- Weight at study initiation: 2516 - 2885 grams
- Housing: individually in labelled cages with perforated floors and equipped with an automatic drinking system (ITL, Bergen, The Netherlands)
- Diet: standard laboratory rabbit diet (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, The Netherlands) approx. 100 g per day
- Water: free access to tap-water diluted with decalcified water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 °C
- Humidity: 50 % rel. humidity
- Air changes: approximately 15 air changes per hour
- Photoperiod: 12 hours artificial fluorescent light and 12 hours dark per day
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Amount of test substance: 0.1 mL
Duration of treatment / exposure:
After 24 hour observation, the eyes of the test animals were treated with a solution of 2 % fluorescein in water to quantitatively determine corneal epithelial damage.
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM:
- according to the guidelines

TOOL USED TO ASSESS SCORE:
- fluorescein
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24/48/72 h
Score:
1.5
Max. score:
3
Reversibility:
fully reversible within: 7 - 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
other: 24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
other: 24/48/72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
other: 24/48/72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24/48/72 h
Score:
0.9
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24/48/72
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24/48/72
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24/48/72 h
Score:
0
Max. score:
2
Irritant / corrosive response data:
There was no evidence of ocular corrosion.
Other effects:
Colouration: No staining of peri-ocular tissues by the test substance was observed.
Toxic symptoms/Mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

no remarks

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on results obtained the test item is not classified as eye irritating
Executive summary:

Instillation of 0.1 ml of the test item into one eye of each of the animals resulted in effects on the iris in two animals and on the conjunctivae in all three animals. Iridic irritation, grade 1, was observed on day 1 in the two animals and had resolved within 24 hours. The irritation of the conjunctivae consisted of redness and chemosis of the conjunctival tissues and discharge. The irritation had resolved completely within 7 days in two animals and within 14 days after instillation in the third animal. Treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals. There was no evidence of ocular corrosion. No staining of peri-ocular tissues by the test substance was observed.

The test item was considered as not irritating to the rabbit eye.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation / corrosion

The test item was tested for skin irritation/corrosion to the intact rabbit skin in a test with three New Zealand White albino rabbits according to OECD guideline 404/EU method B.4. 0.5 mL of the test substance was applied to the intact skin of the shaved area on one flank on the shaved skin of the animals. The test area was wrapped with surgical tape. After 4 hours the wrapping was removed, the remaining test substance washed off and the application site observed for any signs of irritation/corrosion for 72 hours. No skin irritation was caused by the test item after 4 hours of exposure in any of the three rabbits. There was no evidence of a corrosive effect on the skin. No staining of the treated skin by the test substance was observed. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. According to the results obtained in this study, the test item was considered not irritating to the rabbit skin.

Eye Irritation

Instillation of 0.1 ml of the test item into one eye of each of the animals resulted in effects on the iris in two animals and on the conjunctivae in all three animals. Iridic irritation, grade 1, was observed on day 1 in the two animals and had resolved within 24 hours. The irritation of the conjunctivae consisted of redness and chemosis of the conjunctival tissues and discharge. The irritation had resolved completely within 7 days in two animals and within 14 days after instillation in the third animal. Treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals. There was no evidence of ocular corrosion. No staining of peri-ocular tissues by the test substance was observed. the test item was considered as not irritating to the rabbit eye.


Justification for selection of skin irritation / corrosion endpoint:
Only one GLP and guideline study available.

Justification for selection of eye irritation endpoint:
Only one GLP and guideline study available.

Justification for classification or non-classification

Based on the results obtained from testing of the supporting substances, the test item was not classified and labeled as skin irritant according to Regulation (EC) No 1272/2008 (CLP) and Directive 67/548/EEC (DSD).