Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin irritation (OCED TG 404): not classified at a concentration of 50%; inconclusive for the neat substance

Eye irritation (OECD TG 405): causes irreversible effects to 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:
17 Aug 2010 - 20 Aug 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline Study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted in 1981
Deviations:
yes
Remarks:
occluded dressing, 24 h treatment, abraded sites included and dilution of liquid test substance
GLP compliance:
yes
Species:
rabbit
Strain:
other: NZW (Yac:NZW(KBL)),SPF
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Cheonan Yonan College, Laboratory Animal Center, Korea.
- Age at study initiation: 16 weeks
- Weight at study initiation: 2.38-2.49 kg
- Housing: stainless wire mesh cages, 450W x 600D x 360H (mm). One animal per cage
- Diet: Purina experimental diet for rabbit 38302AF, ad libitum
- Water: public tap water in Cheongju-si was filtered and irradiated by ultraviolet light and provided ad libitum via an automatic watering system
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.0 - 21.6
- Humidity (%): 47.4 - 69.6
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2010-08-09 To: 2010-08-20
Type of coverage:
occlusive
Preparation of test site:
other: shaved and abraded sites
Vehicle:
water
Controls:
other: sites treated with water of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): 10 and 50%

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): neat
- Lot/batch no.: GBA0001
Duration of treatment / exposure:
24 h
Observation period:
72 h
Reading time points: 24, 48 and 72 h
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: six sites (2.5x2.5 cm) below the suprascapular area, on each side of the midline. Three areas were assigned to the intact sites and the others served as the abraded sites.
- % coverage: not stated
- Type of wrap if used: all application sites were covered with a gauze patch (3M Tegaderm Transparent Dressing, Orginal Frame Style, 3M Co., Ltd., U.S.A.) and dressed with Lint cloth plaster (Soft Cloth Tape With Liner, width 10 cm, 3M Co., Ltd., Korea). Both sides were fixed with paper masking tape (DAESUN Com., Korea) and held in contact with the skin by an occlusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was removed using absorbent cotten moistened with tepid water
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize (1959) scoring system
Irritation parameter:
erythema score
Basis:
other: mean out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 10% test substance on intact sites
Irritation parameter:
edema score
Basis:
other: mean out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 10% test substance on intact sites
Irritation parameter:
erythema score
Basis:
animal: mean out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: 50% test substance on intact sites
Irritation parameter:
edema score
Basis:
animal: mean out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 50% test substance on intact sites
Irritant / corrosive response data:
On the 10% test substance sites, no skin reactions were evident on abraded sites at 24, 48 and 72 hours after application. On the 50% test substance sites, erythema (score 1) was evident on abraded sites at 24 and 48 hours after application. The erythema (score 1) seen was then fully reversed within 72 hours after application on the abraded sites. On the control sites, no skin reactions were seen on abraded sites at 24, 48 and 72 hours after application.
Other effects:
No abnormal clinical signs or symptoms were evident in any animals throughout the duration of the study. All animals exhibited normal body weight gains. Mean body weight gains was 0.06 kg.

Table 1: Individual skin irritation scores

 

Animals ID

Erythema/edema scores

Intervals (hours)

24

48

72

Intact skin

Intact skin

Intact skin

10% Test substance

1101

0/0

0/0

0/0

1102

0/0

0/0

0/0

1103

0/0

0/0

0/0

Mean over 24, 48 and 72 h

0

50% Test substance

1101

1/0

1/0

0/0

1102

1/0

1/0

0/0

1103

1/0

1/0

0/0

Mean over 24, 48 and 72 h

0.7

Water

1101

0/0

0/0

0/0

1102

0/0

0/0

0/0

1103

0/0

0/0

0/0

Mean over 24, 48 and 72 h

0

Interpretation of results:
other: not irritating at a concentration of 10 and 50%
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified for 10% and 50% test substance concentration
DSD: not classified for 10% and 50% test substance concentration
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:
17 Aug 2010 - 07 Sep 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted in 1981
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: NZW (Yac:NZW(KBL)), SPF
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Cheonan Yonan College, Laboratory Animal Center, Korea.
- Age at study initiation: 16 weeks
- Weight at study initiation: 2.28-2.70 kg
- Housing: stainless wire mesh cages, 450W x 600D x 360H (mm). One animal per cage
- Diet: Purina experimental diet for rabbit 38302AF, ad libitum
- Water: public tap water in Cheongju-si was filtered and irradiated by ultraviolet light and provided ad libitum via an automatic watering system
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.0 - 21.7
- Humidity (%): 47.1 - 69.6
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2010-08-09 To: 2010-09-07
Vehicle:
water
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 10 and 50%

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): neat
- Lot/batch no.: GBA0001
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
21 days
Reading time points: 1, 24, 48, 72 and 96h (10% test substance)
Reading time points: 1, 24, 48, 72 h and once daily thereafter for upto 21 days (50% test substance)
Number of animals or in vitro replicates:
3 males per concentration group
Details on study design:

SCORING SYSTEM: Draize scoring system (1959)

TOOL USED TO ASSESS SCORE: hand-slit lamp (Kowa SL-15, Kowa Co., Ltd., Japan) and fluorescein
Irritation parameter:
cornea opacity score
Basis:
other: mean out of 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21 d in one out of 3 animals
Remarks on result:
other: 50% test substance
Irritation parameter:
iris score
Basis:
animal: mean out of 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: 50% test substance
Irritation parameter:
conjunctivae score
Basis:
other: mean out of 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
1.8
Max. score:
3
Reversibility:
not fully reversible within: 21 d in one out of 3 animals
Remarks on result:
other: 50% test substance
Irritation parameter:
chemosis score
Basis:
other: mean out of 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 21 d in two out of 3 animals
Remarks on result:
other: 50% test substance
Irritation parameter:
cornea opacity score
Basis:
other: mean out of 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Remarks on result:
other: 10% test substance
Irritation parameter:
iris score
Basis:
other: mean out of 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Remarks on result:
other: 10% test substance
Irritation parameter:
conjunctivae score
Basis:
other: mean out of 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0.4
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: 10% test susbtance
Irritation parameter:
chemosis score
Basis:
animal: mean out of 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0.4
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: 10% test substance
Irritant / corrosive response data:
50% test substance group:
Redness of the conjunctiva (score 1) was evident in the eye of one animal on day 21. The corneal opacity (score 2), area of the opacity (score 2), redness of the conjunctiva (score 1) and chemosis in conjunctiva (score 1) were evident in the eye of one animal. No adverse effects on the conjunctiva, cornea and iris were evident in the eyes of one animal. Corneal vascularisation was evident from day 7 to day 21 in one animal as well as other eye irritations. In conclusion, irreversible effects to the conjunctiva and corneal were observed following instillation of the 50% test substance into the eyes of rabbits. See table 2 for more detail.
Other effects:
No abnormal clinical signs or symptoms were evident in any animals throughout the duration of the study. All animals exhibited normal body weight gains. Mean body weight gains were 0.09 kg and 0.41 kg in the 10 and 50% test substance groups, respectively.

Table 1. Results of eye irritation from the 10% test substance.

Rabbit #

Time

conjunctivae

iris

cornea

 

 

redness

swelling

 

 

1

1 h

1

1

0

0

24 h

1

1

0

0

48 h

1

1

0

0

72 h

0

0

0

0

96 h

0

0

0

0

Mean

24+48+72 h

0.7

0.7

0.0

0.0

2

1 h

1

1

0

0

24 h

1

1

0

0

48 h

0

0

0

0

72 h

0

0

0

0

96 h

0

0

0

0

Mean

24+48+72

0.3

0.3

0.0

0.0

3

1 h

1

1

0

0

24 h

1

1

0

0

48 h

0

0

0

0

72 h

0

0

0

0

96 h

0

0

0

0

Mean

24+48+72 h

0.3

0.3

0.0

0.0

Mean out of all 3 animals

24+48+72 h

0.4

0.4

0.0

0.0

Table 2. Results of eye irritation scores from the 50% test substance.

Rabbit #

Time

conjunctivae

iris

cornea

 

 

redness

swelling

 

 

1

1 h

1

3

0

0

24 h

2

2

1

1

48 h

2

2

0

1

72 h

2

1

0

1

14 d

1

1

0

0

21 d

0

0

0

0

Mean

24+48+72 h

2.0

1.7

0.3

1.0

2

1 h

1

3

0

0

24 h

2

2

1

1

48 h

2

2

0

1

72 h

2

2

0

1

14 d

1

1

0

2

21 d

1

1

0

2

Mean

24+48+72 h

2.0

2

0.3

1.0

3

1 h

1

3

0

0

24 h

2

2

1

1

48 h

2

2

0

1

72 h

2

1

0

1

14 d

1

1

0

0

21 d

1

0

0

0

Mean

24+48+72 h

2.0

1.7

0.3

1.0

Mean out of all 3 animals

24+48+72 h

2

1.8

0.3

1

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information at a concentration of 50% Criteria used for interpretation of results: EU
Conclusions:
CLP: Eye irrit 1, H318 for 50% test substance concentration; not classified for 10% test substance concentration
DSD: Xi; R41 for 50% test substance concentration; not classified for 10% test substance concentration
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion

 

The test item was investigated for skin irritation/corrosion according to OECD TG 404 and in compliance with GLP (Yang, 2012a). 0.5 mL of the test material at 10 and 50% concentration was occlusively applied to shaved, intact and abraded sites of 3 male New Zealand White rabbits, respectively. After 24 h of exposure the test material was removed and the animals were maintained for a 72 h observation period. The skin reaction was examined 1, 24, 48 and 72 h after removal of the patch. At the 10% test substance sites no skin reactions such as erythema or edema were observed in intact skin. However, mild erythema (score 1) was evident at 24 and 48 h after application on the 50% test substance sites, but was fully reversed within 72 h. The mean erythema score for the 50% test substance was calculated to be 0.5. During the observation period, no clinical signs or effect on the body weights were observed in any of the animals. Hence, the test item was considered non-irritating to the skin at concentrations of 10 and 50%.

In a further study the test substance was applied for 14 consecutive days to investigate the potential of cumulative skin irritation (Yang, 2012b). 0.3 mL of the test material at 10 and 50% concentration was applied to shaved open sites of 3 male New Zealand White rabbits once daily for 14 consecutive days, respectively. Observation for cumulative skin response was performed at daily intervals commencing approximately 24 hours following application. On the 10% test substance sites, erythema (score 1) was evident from day 1 to day 5 in all animals. Erythema (score 1) was evident from day 6 to day 14 in one animal. On the 50% test substance sites, erythema (score 2) was evident from day 1 to day 10 in all animals. Erythema (score 1) was evident from day 11 to 14 in all three animals. In conclusion, 10 and 50% of the test substance produced slight skin irritation in New Zealand white rabbits for a short period of time. However, this skin irritation reduced with cumulative application and therefore was concluded that the test substance had no cumulative skin irritation potential.

 

Eye irritation/corrosion

 

The test item was investigated for eye irritation/corrosion according to the OECD TG 405 and in compliance with GLP (Yang, 2012b). Three male New Zealand White rabbits each received 0.1 mL of the 10 and 50% test substance as a single treatment into the conjunctival sac of the right eyes, respectively. Eye reactions of the cornea, iris and conjunctiva were recorded at 1, 24, 48, 72 and 96 h after application for both doses. As eye irritation was evident at 96 h after application of the 50% test substance, observations were continued up to day 21. In the 10% test substance group, redness and chemosis of the conjunctiva (score 1) was evident from 1 h after application, but were fully reversed within 72 h. However, in the 50% test substance group, redness of the conjunctiva (score 1) was evident in the eye of one animal on day 21. The corneal opacity (score 2), area of the opacity (score 2), redness and chemosis of the conjunctiva (score 1) was evident in the eye of one animal. No adverse effects on the conjunctiva, cornea and iris were evident in the eyes of one further animal treated with 50% test substance concentration. The cornea vascularisation was evident from day 7 to day 21 in one animal as well as other eye irritations. Mean scores of all three animals over 24, 48, and 72 h were 1.0 for corneal damage, 0.3 for iritis, 1.8 for conjunctivae scores, and 2.0 for chemosis, respectively. The effects were not fully reversible at the end of the 21-day observation period. In conclusion, the 50% test substance is concluded to be a category 1 (irreversible effects on the eye) eye irritant.

Justification for selection of skin irritation / corrosion endpoint:

The key study was selected for assessment

Justification for selection of eye irritation endpoint:

There is only one study available.

Effects on eye irritation: corrosive

Justification for classification or non-classification

The available data on skin irritation of the test substance do not meet the criteria for classification according to Regulation 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification for the 50% test substance concentration.

The available data on skin irritation/corrosion is however insufficient for the classification or non-classification of the neat substance.

 

The available data on eye irritation/corrosion of the test substance meets the criteria to be classified for irreversible effects in the eye (Cat 1, H318) according to Regulation 1272/2008/EC and as Irritant (X, R41) according to Directive 67/548/EEC for the 50% test substance concentration.

Categories Display