Registration Dossier

Administrative data

Description of key information

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:
16 to 30 July 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to current OECD test guidelines and GLP principles.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kitayama Labes Co., Ltd.
- Age at study initiation: 10 weeks
- Weight at study initiation: 1840 g to 2015 g
- Housing: Aluminium cages (W318xH358xD498) with stainless steel cascade racks, one animal per cage.
- Diet (ad libitum):Pellet diet (LRC4, Oriental yeast Co., Ltd.), analysed per lot: contaminants confirmed to be within acceptable limits establised by the test facility.
- Water (ad libitum): well water admixed with sodium hypochlorite (about 0.2 ppm), analysed every 6 months: contaminants confirmed to be within acceptable limits in compliance with waterworks law, Japan.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24-26.1
- Humidity (%): 50.6-73,.2
- Air changes (per hr): 10-20
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.4 ml
Duration of treatment / exposure:
4 h
Observation period:
1, 24, 48 and 72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5x2.5 cm
- Type of wrap: before applilcation, an Elizabeth collar was installed. The test substance (moistened with water) was placed on a patch (lint cloth) and placed on application area. The patch was fixed with a non-woven adhesive bandage and occluded by the adhesive elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Cleaned with absorbent cotton moisturised with lukewarm water. Then the Elizabeth collar was removed.
- Time after start of exposure: 4 hours

SCORING SYSTEM: According to OECD 404 for erythema and eschar formation and oedema formation. In addition the Primary Irritation Index (PII) was calculated according to Draize.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal #1
Time point:
24 h
Score:
0
Max. score:
4
Remarks on result:
other: 1 h
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal #2
Time point:
24 h
Score:
0
Max. score:
4
Remarks on result:
other: 1 h
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal #3
Time point:
24 h
Score:
0
Max. score:
4
Remarks on result:
other: 1 h
Irritation parameter:
erythema score
Remarks:
erythema and eschar formation and oedema formation
Basis:
animal #1
Remarks:
#2,.#3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 1 h
Irritant / corrosive response data:
All individual animals at any point in time did not show any irritation.
Other effects:
No clinical signs, no abnormal body weight gain were observed in any animal throughout the observation period.
Interpretation of results:
GHS criteria not met
Conclusions:
E-C104 had no irritation or corrosion potential on the rabbit skin under the conditions of this study (OECD 404).
Executive summary:

The acute dermal irritation or corrosion potential of E-C104 was assessed in three male New Zealand White rabbits according to OECD test guideline 404. The test substance (0.5 g) was moistened with 0.4 ml of vehicle. As a result of the 4 -hour exposure (semi-occluded application) no skin reactions were observed in any animal at any observation time. Therefore, primary irritation index (PII) was 0 and evaluated as not irritating. In conclusion, E-C104 had no irritation or corrosion potential on the rabbit skin under the conditions of the study.

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:
16 to 31 July 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to current OECD test guidelines and GLP principles.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kitayama Labes CO., Ltd.
- Age at study initiation: 10 weeks
- Weight at study initiation: 1920 to 2102 g
- Housing: Aluminium cages (W318xH358xD498) with stainless steel cascade racks, one animal per cage.
- Diet (ad libitum): Pellet diet (LRC4, Oriental Yeast Co., Ltd.), each lot was analysed: contaminants were confirmed to be within acceptable limits established by the test facility.
- Water (ad libitum): Well water admixed with sodium hypochlorite (about 0.2 ppm). Analysed every 6 months: contaminants were confirmed to be within acceptable limits in compliance with the waterworks law, Japan.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24-26.1
- Humidity (%): 50.6-73.2
- Air changes (per hr): 10 to 20
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
Once dosed, the treated eye was left unwashed in three animals, while in three other animals about 30 seconds after administration the treated eye was washed with distilled water.
Observation period (in vivo):
1, 24, 48, 72 and 96 hours after administration
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: in 3 of 6 animals, the eye was washed with about 20 ml/eye of distilled water for 30 seconds at a flow rate not damaging to the eye.
- Time after start of exposure: 30 sec.

SCORING SYSTEM: Draize evaluation criteria (acc to OECD 405), Kay & Calandra's ocular irritation evaluation criteria.

TOOL USED TO ASSESS SCORE: at observations 24 hours after administration, the treated eye was observed first by a slit lamp. One drop of fluorescein sodium solution prepared with water for injection to 2 w/v% was then instilled into the cornea and 2-3 seconds later the cornea was washed with about 20 ml of distilled water. The presence or absence of any injury in the cornea was examined again by a slit lamp.
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal: eye unwashed animals
Time point:
other: 1 hr
Score:
8
Max. score:
110
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: In eye washed animals the score was 7.3 indicating no effect of washing.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
#2, #3, #4, #5, #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: Effect in unwashed and washed eyes.
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
#2, #3, #4, #5, #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: Effect in unwashed and washed eyes.
Irritation parameter:
conjunctivae score
Remarks:
redness, chemosis and discharge
Basis:
animal #1
Remarks:
#2, #3, #4, #5, #6
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: Effect in unwashed and washed eyes.
Irritant / corrosive response data:
Conjunctival redness and discharge of score 1 and chemosis of score 2 were observed in all animals of eye unwashed animals at 1 hour after administration. These changes disappeared by 24 hours after administration in all animals. In eye washed animals, conjunctival redness and discharge of score 1 and chemosis of score 2 were observed in two animals, and conjunctival redness, chemosis and discharge of score 1 was observed in one animal at 1 hour after administration. These changes disappeared by 24 hours after administration in all animals. Maximum mean total score (MMTS according to Kay & Calandra)) for unwashed and washed eyes was 8 and 7.3, respectively. 24 hours after administration and onward, pigmentation of conjunctiva and partial cornea considered to be test substance related was noted in all animals. The pigmentation in the partial cornea disappeared by 96 hours after administration.
Other effects:
No clinical signs or abnormal body weight gain was observed in any animal throughout the observation period. Observation of the cornea using fluorescein sodium solution revealed no stain spot in any animal.
Interpretation of results:
GHS criteria not met
Conclusions:
E-C104 had a minimal irritation potential to the rabbit eye under the conditions of this study (OECD 405): irritation occured only after 1 hr and was fully reversible within 24 hours.
Executive summary:

The acute eye irritation or corrosion potential of E-C104 was assessed in six (3 eye unwashed and 3 eye washed animals) male New Zealand White rabbits. The test substance (0.1 g) was instilled into the right eye of the animal. As a result, conjunctival redness and discharge of score 1 and chemosis of score 2 was observed in all animals of eye unwashed animals at 1 hour after administration. These changes were fully reversible within 24 hours. In the eye washed animals conjuncitval redness and discharge of score 1 and chemosis of score 2 were observed in two animals, and conjunctival redness, chemosis and discharge of score 1 were observed in one animal at 1 hour after administration. These effects were also fully reversible within 24 hours. The MMTS of the eye unwashed and washed animals was 8 and 7.3, respectively, showing no effect of the eye washing. Pigmentation of the conjunctivae was noted in all animals. In conclusion, E-C104 had minimal eye irritation potential to the rabbit eye under the conditions of this study.

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

Additional information

Justification for classification or non-classification