Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The test item did not induce skin irritation (in vivo study, rabbits).

The test item did not induce eye irritation (in vivo study, rabbits). Very weak signs of irritation (chemosis, conjunctivae) were fully reversible within 48 and 72 h, respectively.

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:
December 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
other: ETAD test method 14.10.76
Version / remarks:
Hazleton Manual of Standard Operating Procedures as applied to ETAD test method 14.10.76 from Code of Federal Regulations, Title 16, Section 1400.41
Deviations:
no
GLP compliance:
no
Remarks:
Study pre-dates GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Six New Zealand White rabbits, free from any obvious skin lesions and weighing not less than 2.0 kg were used for the study. They were obtained from Buxted Rabbit Co. Ltd., Great Totease Farm, Buxted, Nr. Uckfield, Sussex.

Diet
The animals were allowed unlimited access to mains water and food (Standard Rabbit Diet - BP Nutrition (U.K.) Ltd., Stepfield, Witham, Essex) throughout the study.

Environment
The animals were housed individually in grid floor cages in a single room maintained under conditions of ambient humidity and temperature except that a lower temperature of 14°C is automatically imposed, and exposed to natural lighting conditions.
Type of coverage:
occlusive
Preparation of test site:
abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
24 hours
Observation period:
7 days
Number of animals:
6 animals
Details on study design:
Procedure and observations
The animals were identified by a number stamped on a metal ear tag.
Twenty four hours prior to treatment, the back of each animal was shaved using electric clippers. One side of the shaven area on each animal was left intact. The other side of the shaven area was abraded using a sterile hypodermic needle to scratch a 5 x 5 lattice in an area measuring 2.5 cm x 2.5 cm such that only the stratum corneum was penetrated and bleeding did not occur. The test article (0.5 .g) was applied under gauze pads (2.5 cm x 2.5 cm) to the intact and abraded areas of each rabbit.
The patches were secured by adhesive strapping and the whole trunk further occluded with a stockinette bandage.
Twenty four hours after administration the patches were removed and the skin reactions on both the intact and abraded areas of each rabbit were scored according to Draize, J.H. (1959), Assoc. of Food and Drug Officials of the U.S., Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics.". The evaluation was repeated 48 hours later (72 hours after administration) and finally 7 days after administration if any irritation was apparent at the 72 hour reading.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
8
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The primary irritation index of test article Y0154/001 was 0.0. The test article was therefore classified as a non irritant.
Other effects:
Red/brown staining of the test area and surrounding skin made the irritation assessment difficult.

Skin irritation reactions

Test article/concentration: Y0154/001, as supplied

Rabbit number

Time (hours)

Erythema

Oedema

A

I

A

I

688

24

0

0

0

0

72

0

0

0

0

689

24

0

0

0

0

72

0

0

0

0

691

24

0

0

0

0

72

0

0

0

0

692

24

0

0

0

0

72

0

0

0

0

693

24

0

0

0

0

72

0

0

0

0

694

24

0

0

0

0

72

0

0

0

0

 

Sub total

0

0

0

0

Total

0

0

Sex    Male

Primary irritation index

0/24 = 0.0

A = abraded skinI = intact skin

Interpretation of results:
GHS criteria not met
Conclusions:
The substance did not show any signs of irritation (erythema and edema score: 0.0). The substance is not classifiable according to CLP criteria.
Executive summary:

The study was carried out to determine the primary irritation index of test article in the albino rabbit. The study was performed in accordance with the Standard Operating Procedures as applied to the ETAD test method 14.10.76 from Code of Federal Regulations, Title 16, Section 140041.

 

Six New Zealand White rabbits, free from any obvious skin lesions and weighing not less than 2.0 kg were used for the study.

Twenty four hours prior to treatment, the back of each animal was shaved using electric clippers. One side of the shaven area on each animal was left intact. The other side of the shaven area was abraded using a sterile hypodermic needle. The test article (0.5 .g) was applied under gauze pads to the intact and abraded areas of each rabbit. The patches were secured by adhesive strapping and the whole trunk further occluded with a stockinette bandage.

Twenty four hours after administration the patches were removed and the skin reactions on both the intact and abraded areas of each rabbit were scored. The evaluation was repeated 48 hours later (72 hours after administration) and finally 7 days after administration if any irritation was apparent at the 72 hour reading.

 

Results

The primary irritation index of test article was 0.0. The test article was therefore classified as a non irritant.

Red/brown staining of the test area and surrounding skin made the irritation assessment difficult.

 

Conclusion

A primary skin irritation study was performed in the albino rabbit on the test article.

A primary irritation index of 0.0 was obtained. The test article is therefore classified as a non-irritant.

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:
November 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
other: ETAD test method 14.10.76
Version / remarks:
Hazleton Manual of Standard Operating Procedures as applied to ETAD test method 14.10.76 from Code of Federal Regulations (HLE protocol no. 524/6)
Deviations:
no
GLP compliance:
no
Remarks:
Study pre-dates GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Six New .Zealand White rabbits obtained from Buxted Rabbit Co. Ltd., Great Totease Farm, Buxted, Nr. Uckfield, Sussex were used for the study. At commencement the animals were free from any eye irritation or defects.

Diet
The animals were allowed unlimited access to filtered mains water and food (Standard Rabbit Diet, BP Nutrition (U.K.) Ltd., Stepfield, Witham, Essex) throughout the study.

Environment
The animals were housed individually in grid floor cages in a single room maintained under conditions of ambient humidity and temperature except that a lower temperature of 14°C is automatically imposed.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
100 mg
Duration of treatment / exposure:
72 hours (no washing following installation of test article)
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
6 animals
Details on study design:
The animals were identified by an indelible number marked on the inner surface of the pinna. The test article (100 mg) was placed in one eye of each animal by gently pulling the lower lid away from the eyeball to form a cup into which the test substance was dropped.
The lids were then gently held together for about one second. The other eye, remaining untreated, served as a control. The eyes were not washed following instillation of the test article.
The eyes were examined 1 hour, 24 hours, 48 hours and 72 hours after instillation and the degree of irritation was scored according to: Draize, J.H. (1959), Assoc. of Food and Drug Officials of the U.S., Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics". Where a substance caused irritation within the first three days after administration the ocular reaction was also assessed on the seventh day. This value was not included in the calculation of the irritant score.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.28
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No further details specified in the study report.

Individual total eye irritation scores

 

Individual total scores

Rabbit number

24 hours

(a)

48 hours

(b)

72 hours

(c)

347

348

536

540

579

581

2

4

4

6

8

6

2

2

2

2

2

2

0

0

0

0

0

0

Total

30

12

0

Grand total (a + b + c) = 42

 

Irritation score =          a + b + c

                                   --------------- = 2.3

                                          18

 

Individual conjunctival, iridial, corneal irritation scores

Rabbit No.

TEST ARTICLE Y0154/001

Time

Conjunctivae

Iris

Cornea

(A+B+C) x2

Dx5

(ExF) x5

Total

A

B

C

D

E

F

347

1 hr

24 hr

48 hr

72 hr

7 days

2

1

1

0

-

2

0

0

0

-

2

0

0

0

-

0

0

0

0

-

0

0

0

0

-

0

0

0

0

-

12

2

2

0

-

0

0

0

0

-

0

0

0

0

-

12

2

2

0

-

348

1 hr

24 hr

48 hr

72 hr

7 days

2

1

1

0

-

2

1

0

0

-

2

0

0

0

-

0

0

0

0

-

0

0

0

0

-

0

0

0

0

-

12

4

2

0

-

0

0

0

0

-

0

0

0

0

-

12

4

2

0

-

536

1 hr

24 hr

48 hr

72 hr

7 days

2

1

1

0

-

2

1

0

0

-

2

0

0

0

-

0

0

0

0

-

0

0

0

0

-

0

0

0

0

-

12

4

2

0

-

0

0

0

0

-

0

0

0

0

-

12

4

2

0

-

540

1 hr

24 hr

48 hr

72 hr

7 days

2

1

1

0

-

1

1

0

0

-

1

1

0

0

-

0

0

0

0

-

0

0

0

0

-

0

0

0

0

-

8

6

2

0

-

0

0

0

0

-

0

0

0

0

-

8

6

2

0

-

579

1 hr

24 hr

48 hr

72 hr

7 days

2

1

1

0

-

2

1

0

0

-

2

2

0

0

-

0

0

0

0

-

0

0

0

0

-

0

0

0

0

-

12

8

2

0

-

0

0

0

0

-

0

0

0

0

-

12

8

2

0

-

581

1 hr

24 hr

48 hr

72 hr

7 days

2

1

1

0

-

2

1

0

0

-

2

1

0

0

-

0

0

0

0

-

0

0

0

0

-

0

0

0

0

-

12

6

2

0

-

0

0

0

0

-

0

0

0

0

-

12

6

2

0

-

- = observations not made

Interpretation of results:
GHS criteria not met
Conclusions:
The substance did not cause any signs of irritation in rabbit eyes (cornea opacity, iris). Very weak signs of irritation (chemosis, conjunctivae) were fully reversible within 48 and 72 h, respectively. The substance is not classifiable according to CLP criteria.
Executive summary:

A study was carried out to determine the eye irritation score of test article in the albino rabbit.

The study was performed in accordance with Standard Operating Procedures as applied to ETAD test method 14.10.76 from Code of Federal Regulations.

 

Six New Zealand White rabbits were used for the study. At commencement the animals were free from any eye irritation or defects.

The test article (100 mg) was placed in one eye of each animal by gently pulling the lower lid away from the eyeball to form a cup into which the test substance was dropped. The lids were then gently held together for about one second. The other eye, remaining untreated, served as a control. The eyes were not washed following instillation of the test article.

The eyes were examined 1 hour, 24 hours, 48 hours and 72 hours after instillation and the degree of irritation was scored.

Where a substance caused irritation within the first three days after administration the ocular reaction was also assessed on the seventh day.

This value was not included in the calculation of the irritant score.

 

Result

An eye irritation score of 2.3 was obtained. The test article is therefore regarded as a non irritant.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A study was carried out to determine the primary irritation index of test article in the albino rabbit. The study was performed in accordance with the Standard Operating Procedures as applied to the ETAD test method 14.10.76 from Code of Federal Regulations, Title 16, Section 140041.

 Six New Zealand White rabbits, free from any obvious skin lesions and weighing not less than 2.0 kg were used for the study.

Twentyfour hours prior to treatment, the back of each animal was shaved using electric clippers. One side of the shaven area on each animal was left intact. The other side of the shaven area was abraded using a sterile hypodermic needle. The test article (0.5 g) was applied under gauze pads to the intact and abraded areas of each rabbit. The patches were secured by adhesive strapping and the whole trunk further occluded with a stockinette bandage.

Twentyfour hours after administration the patches were removed and the skin reactions on both the intact and abraded areas of each rabbit were scored. The evaluation was repeated 48 hours later (72 hours after administration) and finally 7 days after administration if any irritation was apparent at the 72 hour reading.

No systemic or local effects were noted during the study. The primary irritation index of test article was 0.0. The test article was therefore classified as a non irritant.

A study was carried out to determine the eye irritation score of test article in the albino rabbit.

The study was performed in accordance with Standard Operating Procedures as applied to ETAD test method 14.10.76 from Code of Federal Regulations.

Six New Zealand White rabbits were used for the study. At commencement the animals were free from any eye irritation or defects.

The test article (100 mg) was placed in one eye of each animal by gently pulling the lower lid away from the eyeball to form a cup into which the test substance was dropped. The lids were then gently held together for about one second. The other eye, remaining untreated, served as a control. The eyes were not washed following instillation of the test article.

The eyes were examined 1 hour, 24 hours, 48 hours and 72 hours after instillation and the degree of irritation was scored.

Where a substance caused slight irritation within the first three days after administration the ocular reaction was also assessed on the seventh day. This value was not included in the calculation of the irritant score.

Slight conjunctival reddening ans swelling was seen up to 48 and 24 hours, respectively.

An eye irritation score of 2.3 was obtained. The test article is therefore regarded as a non irritant.

Justification for classification or non-classification

Due to the lack of irritation signs in both skin and eye irritation in vivo studies, the test item is not classifiable according to CLP criteria.