Registration Dossier

Administrative data

Description of key information

The substance was not irritating to the skin of rabbits in an in vivo skin irritation study performed according to OECD 404. The substance was corrosive to the eyes of rabbits in an in vivo eye irritation study performed according to OECD 405.

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:
1997-09-11 to 1997-09-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kuiper Rabbitry, Gary, Indiana
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: 1850 - 2320 g
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
Temperature, humidity and light controlled room (DHEW publication No. 86-23 (NIH))

IN-LIFE DATES: From: 1997-09-11 To: 1997-09-25
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: moistened with water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g
Duration of treatment / exposure:
4 hours.
Observation period:
14 days
Number of animals:
6 males
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- Type of wrap if used: 2 layer gauze patch secured with non-irritating Kendall Curity Standard Porus tape covered with a semiocclusive plastic overwrap secured with non-irritating Kendall Curity Standard Porus tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 4.5, 24, 48 and 72 h
Score:
2.09
Max. score:
8
Reversibility:
fully reversible
Remarks:
by 336h observation period.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.6
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48h
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48h
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48h
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7d
Other effects:
No data

Table 1: Individual irritation scores

Rabbit Number

Sex

ER

4.5

ED

4.5

ER

24

ED

24

ER

48

ED

48

ER

72

ED

72

ER

168

ED

168

ER

336

ED

336

ER Mean totals (24, 48, 72 hours)

ED Mean totals (24, 48, 72 hours)

285

M

1

0

1

0

1

0

1

0

0

0

0

0

1

0

286

M

1

1

0

0

0

0

0

0

0

0

0

0

0

0

287

M

1

2

1

1

2

0

2

0

0

0

0

0

1.6

0.3

288

M

1

2

2

1

2

0

2

0

0

0

0

0

2

0.3

289

M

1

2

2

1

2

0

2

0

0

0

0

0

2

0.3

290

M

1

2

2

1

3

1

3

1

1

0

0

0

2.67

1

Mean totals (24, 48, 72 hours)

1.5

0.3

Interpretation of results:
GHS criteria not met
Conclusions:
The test material does not meet the criteria for classification as a skin irritant as defined in the EU CLP Regulation (EC) No. 1272/2008 under the conditions of the study.
Executive summary:

In an OECD 404 Guideline study, 0.5 g of test material moistened with water was applied to the shaved test site on each of six New Zealand white rabbits (male) and covered with a 2 layer gauze patch secured with non-irritating Kendall Curity Standard Porus tape covered with a semiocclusive plastic overwrap secured with non-irritating Kendall Curity Standard Porus tape for 4 hours. After 4 hours the test sites were wiped with a damp cloth. The sites were examined for erythema and edema using Draize method of scoring at 24, 48 and 72 hours, then 168 and 336 hours.

Semi occlusive 4 hour exposure to 0.5g of the test material produced erythema and/or oedema in 5 of the 6 test animals at 24 hours. At 72 hours 5 out of 6 animals still showed signs of erythema but oedema was observed in only one animal . All skin reactions were reversed by the 336 hour observation. The mean erythema score over the 24, 48 and 72 hour period was 1.5 and the mean oedema score over the same period was 0.3.

The test material does not require classification for skin irritation according to EU the CLP Regulation 1272/2008.

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:
1997-09-11 to 1997-10-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kuiper Rabbitry, Gary, Indiana
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: 2010 - 2300 g
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
Temperature, humidity and light controlled room (DHEW publication No. 86-23 (NIH))

IN-LIFE DATES: From: 1997-09-11 To: 1997-10-02
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye acts as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (packed volume)
Duration of treatment / exposure:
Eyes not washed.
21 days
Observation period (in vivo):
1, 24, 48, 72, 168, 336 and 504 hours
Number of animals or in vitro replicates:
Six
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: fluorescein and UV light
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21d
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21d
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14d
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14d
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14d
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7d
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 21d
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 21d
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 72h
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 48h
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 48
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 48h
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 21d
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 21d
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 21d
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 21d
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 21d
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 14d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 21d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 21d
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14d
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14d
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 14d
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 14d
Irritant / corrosive response data:
See Table 1
There were positive eye irritation reactions in all of the six test subjects and the maximum group mean score was 37.0/110.0 at the 24 hour observation. Irreversible effects were observed in at least 1 of the six test animals at the end of the 21 d observation period.
Other effects:
No other effects noted

Table 1: Individual irritation scores

Rabbit #1

 

1 h

24 h

48 h

72 h

7 d

14 d

21 d

Av. 24/48 /72 h

Fully reversible:

Cornea

-

1

1

1

1

2

2

1

No

Iris

1

1

1

1

1

1

0

1

Yes

Conjunctiva

2

2

2

2

1

1

1

2

No

Chemosis

2

2

2

2

1

1

0

2

Yes

 

Rabbit #2

 

1 h

24 h

48 h

72 h

7 d

14 d

21 d

Av. 24/48 /72 h

Fully reversible:

Cornea

-

1

1

1

1

2

3

1

No

Iris

1

1

1

1

1

1

1

1

No

Conjunctiva

2

2

2

2

2

2

2

2

No

Chemosis

3

2

2

2

2

2

1

2

No

 

Rabbit #3

 

1 h

24 h

48 h

72 h

7 d

14 d

21 d

Av. 24/48 /72 h

Fully reversible:

Cornea

-

1

1

1

1

0

0

1

Yes

Iris

0

1

1

0

0

0

0

0.7

Yes

Conjunctiva

2

2

2

2

1

1

0

2

Yes

Chemosis

2

1

1

1

1

0

0

1

Yes

 

Rabbit #4

 

1 h

24 h

48 h

72 h

7 d

14 d

21 d

Av. 24/48 /72 h

Fully reversible:

Cornea

-

1

1

1

1

0

0

1

Yes

Iris

1

1

0

0

0

0

0

0.3

Yes

Conjunctiva

2

2

2

2

2

1

1

2

No

Chemosis

3

2

2

2

2

0

0

2

Yes

 

Rabbit #5

 

1 h

24 h

48 h

72 h

7 d

14 d

21 d

Av. 24/48 /72 h

Fully reversible:

Cornea

-

1

1

1

1

0

0

1

Yes

Iris

0

1

0

0

0

0

0

0.3

Yes

Conjunctiva

2

2

2

1

1

1

0

1.7

Yes

Chemosis

3

2

2

1

1

0

0

1.7

Yes

 

Rabbit #6

 

1 h

24 h

48 h

72 h

7 d

14 d

21 d

Av. 24/48 /72 h

Fully reversible:

Cornea

-

1

1

1

0

0

0

1

Yes

Iris

1

1

0

0

0

0

0

0.3

Yes

Conjunctiva

2

2

2

1

1

0

0

1.7

Yes

Chemosis

2

2

1

1

1

0

0

1.3

Yes

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
There were positive eye irritation reactions in all of the six test subjects and the maximum group mean score was 37.0/110.0 at the 24 hour observation. Effects observed were not fully reversible in at least one animal by the 504 hour (21 day) observation point.
In accordance with EU CLP Regulation (EC) No. 1272/2008, classification of this substance is required for eye irritation. As effects are not reversible in at least one animal, classification as Category 1 serious eye damage is applicable.
Executive summary:

In an OECD Guideline No. 405 0.1 mL of the test material was applied as supplied to the non-irrigated eye of six albino New Zealand rabbits. Irritation was recorded using the Draize scale at 1, 24, 48, 72, 168, 336 and 504 hour time points.

There were positive eye irritation reactions in all of the six test subjects and the maximum group mean score was 37.0/110.0 at the 24 hour observation. Effects observed were not fully reversible in at least one animal by the 504 hour (21 day) observation point.

In accordance with EU CLP Regulation (EC) No. 1272/2008, classification of this substance is required for eye irritation. As effects are not reversible in at least one animal, classification as Category 1 serious eye damage is applicable.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation

One reliable study is available. In this study, performed according to OECD 404 under GLP, 0.5g of the substance was applied to the shaved backs of six male New Zealand White rabbits and covered with a semi-occlusive dressing. After four hours the dressing was removed and any excess substance removed with a damp cloth. The sites were examined for erythema and oedema at 24, 48 and 72 hours and 7 and 14 days. Erythema and/or oedema was observed in 5 of the 6 test animals at 24 hours. At 72 hours 5 out of 6 animals still showed signs of erythema but oedema was observed in only one animal. . All skin reactions were reversed by the 336 hour observation. The mean erythema score over the 24, 48 and 72 hour period was 1.5 and the mean oedema score over the same period was 0.3 [Kukulinski M (1997d)].

Eye irritation

One reliable study is available. In this study, performed according to OECD 405 under GLP, 0.1 mL of the substance was applied to the non-irrigated eye of six New Zealand White rabbits. The eyes were observed at 1, 24, 48 and 72 hours and 7, 14 and 21 days after instillation and effects on the cornea, iris and conjunctiva recorded. Effects were seen in the cornea (maximum individual average score for 24, 48 & 72 h = 1), iris (maximum individual average score for 24, 48 & 72 h = 1), conjunctiva (maximum individual average score for 24, 48 & 72 h = 2) and for chemosis (maximum individual average score for 24, 48 & 72 h = 2). The effects noted in the cornea (2/6 animals) iris (1/6 animals) and conjunctiva (3/6 animals) did not fully reverse by 21 days [Kukulinski M (1997e)].

Justification for classification or non-classification

In a GLP in vivo skin irritation study performed according to OECD TG 404, the substance produced scores of >= 2.3 in 1/6 animals. Based on the results of this study the substance is not classified for skin irritation in accordance with Regulation (EC) No 1272/2008.

In a GLP in vivo eye irritation study performed according to OECD TG 405 the substance produced effects to the cornea and iris that were irreversible within 21 days.On this basis the substance is classified as Category 1 for eye effects in accordance with Regulation (EC) No 1272/2008.