Registration Dossier

Administrative data

Description of key information

The substance is not considered irritating to the skin and 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:
not specified
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
other: 59 NohSan No. 4200
Version / remarks:
1985
GLP compliance:
yes
Species:
rabbit
Strain:
other: Japanese white female rabbits
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation:15 weeks old
- Weight at study initiation: 2.50 to 2.71 kg
- Housing: animals were housed individually in aluminium cages with wire mesh bottoms
- Diet: RC4 pellet diet ad libitum
- Water: Tap water ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 5
- Humidity (%): 50 ± 20
- Air changes: at 8 to 10 times per hour
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: Start: 20 Oct. 1995; End: 31 May 1996
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
10 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm2 lint (6.3 cm2)
- % coverage: not specified
- Type of wrap if used: The application site was covered with oil-paper followed by the semi-occlusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressing was removed after the exposure period and the skin was wiped with absorbent cotton soaked in ‘water for injection’ to clean the application site so that any reactions (erythema) were clearly visible at that time
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
- 1, 24, 48 and 72 hours and 7 and 10 days after patch removal

SCORING SYSTEM:
Method of calculation: the skin was scored according to the OECD scoring system (see Table 1 in 'any other information on materials and methods incl. tables'). Mean values of scores from 24-48-72 hours per animal were taken for the classification. The interpretation of the results is based on table 2 in 'any other information on materials and methods incl. tables'.

CLINICAL SIGNS
Clinical signs were observed periodically for 6 hours after application and then once daily thereafter at the same time as dermal observation.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
With a single application of the test substance to the rabbit skin, no irritant dermal reactions were observed and the primary dermal irritation index was zero.
Other effects:
No abnormalities in the clinical signs any of the animals.
Interpretation of results:
GHS criteria not met
Conclusions:
With a single application of the test substance to the rabbit skin, no irritant dermal reactions were observed.
Executive summary:

In a primary dermal irritation study, six 13 week old Japanese white female rabbits were dermally exposed to 0.5 g of the test substance (98.6%) for 4 hours to the previously clipped skin of the rabbits dorsal area. Animals then were observed for up to 72 hours after removal of the test material. Irritation was scored by a table for evaluation of dermal reactions. Based on the results and under the conditions of this study, it was concluded that the test substance has no irritant effect on the rabbit skin according to the Draize classification criteria.

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:
not specified
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
other: Japanese white rabbits
Remarks:
female
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: approximately 15 weeks old
- Weight at study initiation: not specified
- Housing: Individually in aluminium cages
- Diet: RC4 pellet, diet ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 5
- Humidity (%): 50 ± 20
- Air changes (per hr): 8 to 10
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 20 Oct. 1995, To: 31 May 1996
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
other: washed control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 g of the test substance
Duration of treatment / exposure:
Single application
Observation period (in vivo):
72 hours

Number of animals or in vitro replicates:
6 (3 washed and 3 remained unwashed after application)
Details on study design:
ANIMAL TREATMENT AND REMOVAL OF TEST SUBSTANCE
- Unwashed group: The animals in the unwashed group were held in a restrainer, and 0.1 g of the test article was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower eyelid away from the eyeball. Both lids were gently held together for about 1 second to prevent loss of the test article. The right eye served as an untreated control
- Washed group: For the washed group, 0.1 g of the test article was applied in the same way and 2 to 3 minutes after application, the eyes were washed with 200 mL of physiological saline for 1 minute. The right eye was washed with 200 mL of physiological saline and served as a washed control.

SCORING SYSTEM:
- Method of calculation: the eye damage was scored according to the Draize scale scoring system (see Table 1 in 'any other information on materials and methods incl. tables').

TOOL USED TO ASSESS SCORE:
- The eyes were examined by ophthalmoscope
- A drop of 2% fluorescein sodium solution was instilled in the eyes of all animals 24 hours after application, and after immediately rinsing with water for injection, the cornea was examined for the presence or absence of stained marks resulting from corneal damage.

OBSERVATION
Observation for other ocular reactions and clinical signs was made periodically for 6 hours after application and once daily thereafter at the time of eye examination.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
On a single application of the test substance to the rabbit eye, only grade 1 conjunctival redness and conjunctival oedema were observed in the washed and unwashed groups and eye closure or more than normal discharge were observed as other changes in the eye, but all observed effects disappeared within 24 hours.
Other effects:
There were no abnormalities in the clinical signs in either of the groups.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on this study, it was concluded that the test substance did not cause irritant effects
Executive summary:

In a primary eye irritation study, 0.1 g of test substance (98.6%) was instilled into the conjunctival sac of the left eye (13 week old, white, 6 female rabbits) for 24 hours. (3 rabbits were observed for the effectiveness of eye washing.) Animals then were observed for 3 days. Irritation was classified according to the Federal Register. In the observation of irritation, grade 1 conjunctival redness and conjunctival oedema were observed in the unwashed group but positive effects were not observed. Eye closure and more than normal discharge were observed as other changes. These changes disappeared by 24 hours after application. On the other hand, in the washed group, the same changes as those in the unwashed group were observed except for eye closure. There were no abnormalities in the clinical signs in either of the groups. Based on the study’s results and under the conditions of this study, it was concluded that the test substance was tested negative for irritant effects on 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

In a primary dermal irritation study (Shibata, 1996), six 13 weeks old Japanese white female rabbits were dermally exposed to 0.5 g of the test substance (98.6%) for 4 hours to the previously clipped skin of the rabbits' dorsal area. Animals then were observed for up to 72 hours after removal of the test material. Irritation was scored by a table for evaluation of dermal reactions. Based on the results and under the conditions of this study, it was concluded that the test substance has no irritant effect on the rabbit skin according to the Draize classification criteria.

Eye irritation

In a primary eye irritation study (Chibata, 1996), 0.1 g of test substance (98.6%) was instilled into the conjunctival sac of the left eye (13 weeks old, white, 6 female rabbits). The eyes of three animals remained untreated after application of the test substance. The eyes of another three animals were thoroughly washed with 200 mL physiological saline, 2 to 3 minutes after instillation of the test substance. Animals then were observed for 3 days. Irritation was classified according to the Federal Register. In the observation of irritation, grade 1 conjunctival redness and conjunctival oedema were observed in the unwashed group but positive effects were not observed. Eye closure and more than normal discharge were observed as other changes. These changes disappeared by 24 hours after application. On the other hand, in the washed group, the same changes as those in the unwashed group were observed except for eye closure. There were no abnormalities in the clinical signs in either of the groups. Based on the study’s results and under the conditions of this study, it was concluded that the test substance was tested negative for irritant effects on the rabbit eye.

Justification for classification or non-classification

Based on the available information, classification for skin and eye irritation is not warranted in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. (EC) 1272/2008.