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:
other: experimental study on similar substance
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, test procedure in accordance with OECD 406 methods, meets generally accepted scientific principles, acceptable for assessment. Not GLP compliant.
Qualifier:
according to
Guideline:
other: "Hazardous Substances Regulations" - US Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
The rabbits were caged singly in an experimental room maintained at a temperature of 20°C. (± 1°) and a relative humidityof 50-70%. Animals were exposed to artificial light for 10 hours daily from 08.00 - 18.00 hours. A commercial irradiated diet (Styles-Oxoid) was fed ad lib. Sterile filtered water was available at all times.
Type of coverage:
occlusive
Preparation of test site:
other: shaved and abraded
Vehicle:
water
Controls:
other: intact skin was used as control
Amount / concentration applied:
Test solution: 10 g of the test compound in 10 ml of water0.75 ml of the test solution was applied to each test site on a 2.5 square cm gauze pad.
Duration of treatment / exposure:
24 h
Observation period:
up to 14 days
Number of animals:
6 (3 males; 3 females)
Details on study design:
Twenty-four hours prior to the dermal application, the backs of the rabbits were shaved over an area consisting of at least 10% ofthe total body surface. Two test sites lateral to the mid line of the back were used on each rabbit. Immediately before theapplication of the test compound, the right hand site was abraded uith the point of a sterile hypodermic needle. The abrasions weresufficiently deep to penetrate the stratum corneum but not to damage the dermis. The left hand site remained intact.10g. of the test compound was mixed with 10 ml of water to make solution of 15 ml., 0.75 ml of which was applied to each testsite on a 2.5 cm. square gauze pad. These were covered with aluminium foil secured with "Sleek" adhesive tape. The test sites were then covered by a 6" wide "Cohan" self adhesive bandage in order to retain the test substance in close contace with the skin.After 24 hours the dressing was removed and the intact and abraded application sites were assessed for oedema and erythema.A further assessment was made at 72 hours and for any further period considered necessary up to 14 days.
Irritation parameter:
erythema score
Remarks:
Intact
Basis:
mean
Time point:
other: 24h
Score:
ca. 1.17
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Remarks:
Abraded
Basis:
mean
Time point:
other: 24 h
Score:
ca. 1.5
Reversibility:
other: 3 fully reversible within 72 hours
Irritation parameter:
edema score
Remarks:
Intact
Basis:
mean
Time point:
other: 24 h
Score:
ca. 2.67
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Remarks:
Abraded
Basis:
mean
Time point:
other: 24
Score:
ca. 3
Reversibility:
other: 4 fully reversible within 72 hours
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Time point:
24/48/72 h
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Time point:
24/48/72 h
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The primary irritation index as the measure of the acute irritation to the skin of rabbits was found to be 2.29.

Erythema formation

No/sex

Intact

Abraded

24 hours

72 hours

24 hours

72 hours

11 male

1

0

1

0

13

1

0

2

0

15

1

0

2

1

12 female

2

0

2

0

14

1

0

1

1

16

1

0

1

0

Mean

1.17

0

1.5

0.33

Edema Formation

No/sex

Intact

Abraded

24 hours

72 hours

24 hours

72 hours

11 male

3

0

3

0

13

3

0

3

0

15

2

0

3

2

12 female

3

0

3

0

14

3

0

3

1

16

2

0

3

0

Mean

2.67

0

3

0.5

Total: 9.17

Primary irritation index: 2.29

Interpretation of results:
GHS criteria not met
Conclusions:
non-irritant to the skin
Executive summary:

The primary irritation index as the measure of the acute irritation to the skin of rabbits was found to be 1.17 for Erythema and 2.67 for Edema based on US Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965).

Therefore the tested item is to be considered as non-irritant to the skin of rabbits.

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:
other: experimental study on similar substance
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, test procedure in accordance with OECD 406 methods, meets generally accepted scientific principles, acceptable for assessment. Not GLP compliant.
Qualifier:
according to
Guideline:
other: Hazardous substance Labelling Act Sect. 191-12 (february 1965)
Deviations:
yes
Remarks:
slight modifications
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Healthy New Zealand White rabbits (Porton strain) aged 12-16 weeks with average body weights of 2.70 kgs. (males ) and 2.58 kgs (females) bred on the premises and maintained under a semi-barrier system. Six rabbits (3 males and 3 females) were acclimatised in the test area for one week prior to the start of the trial.The rabbits were caged singly in an experimental room maintained at a temperature of 20°C. (_+1°) and a relative humidityof 50-70%. Animals ware exposed to artificial light for 10 hours daily from 08.00 - 18.00 hours. A commercial irradiated diet(Styles-Oxoid) was fed ad lib. Sterile filtered water was available at all times.
Vehicle:
unchanged (no vehicle)
Controls:
other: the right eye served as control
Amount / concentration applied:
100 mg of the test compound were instilled into the conjunctival sac of the left eye. The eyelids were then held closed for 1 second. The right eye served as a control. After 30 seconds the compound was, as far as possible, flushed out of the eyes of three of the rabbits with approximately200 ml. of warm water.
Duration of treatment / exposure:
30 seconds
Observation period (in vivo):
up to 16 days
Number of animals or in vitro replicates:
6 (3 males and 3 females)
Irritation parameter:
cornea opacity score
Basis:
animal: all animals
Time point:
other: 1 h
Score:
1
Reversibility:
fully reversible within: 6 days
Irritation parameter:
iris score
Basis:
animal: 11,13
Time point:
24 h
Score:
1
Reversibility:
fully reversible within: 10 days
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal: all animals
Time point:
other: 1 h
Score:
2
Reversibility:
fully reversible within: 15 days
Irritation parameter:
chemosis score
Basis:
animal: 11,15,16
Time point:
other: 1 h
Score:
1
Reversibility:
fully reversible within: 10 days
Irritation parameter:
chemosis score
Basis:
animal: 13,14
Time point:
other: 1 h
Score:
2
Reversibility:
fully reversible within: 10 days
Irritation parameter:
chemosis score
Basis:
animal: 14
Time point:
other: 1 h
Score:
3
Reversibility:
fully reversible within: 10 days
Irritation parameter:
conjunctivae score
Remarks:
Discharge
Basis:
animal: all animals
Time point:
other: 1 h
Score:
3
Reversibility:
fully reversible within: 6 days
Irritation parameter:
chemosis score
Time point:
24/48/72 h
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Time point:
24/48/72 h
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Time point:
24/48/72 h
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Time point:
24/48/72 h
Remarks on result:
positive indication of irritation

 

Time

Rabbit no.

11

13

15

12

14

16

1 h

Cornea Opacity

1

1

1

1

1

1

Iris

 

 

 

 

 

 

Conjunctivae

Redness

Chemosis

Discharge

 

2

1

3

 

2

2

3

 

2

1

3

 

2

3

3

 

2

2

3

 

2

1

3

 

Time

Rabbit no.

11

13

15

12

14

16

1 day

Cornea Opacity

1

1

 

1

1

1

Iris

1

1

 

 

 

 

Conjunctivae

Redness

Chemosis

Discharge

 

2

2

2

 

2

3

3

 

2

1

 

 

2

3

2

 

2

2

1

 

2

1

 

 

Time

Rabbit no.

11

13

15

12

14

16

3 days

Cornea Opacity

1

1

 

1

 

1

Iris

1

1

 

 

 

 

Conjunctivae

Redness

Chemosis

Discharge

 

3

2

1

 

3

2

2

 

1

 

 

 

3

2

2

 

2

1

 

 

3

 

 

 

Time

Rabbit no.

11

13

15

12

14

16

6 days

Cornea Opacity

1

 

 

 

 

 

Iris

1

1

 

 

 

 

Conjunctivae

Redness

Chemosis

Discharge

 

2

1

 

 

2

2

 

 

1

 

 

 

2

1

 

 

1

 

 

 

1

 

 

 

Time

Rabbit no.

11

13

15

12

14

16

10 days

Cornea Opacity

 

 

 

 

 

 

Iris

 

 

 

 

 

 

Conjunctivae

Redness

Chemosis

Discharge

 

 

1

 

 

1

 

 

Interpretation of results:
GHS criteria not met
Conclusions:
irritant for the eye
Executive summary:

The ocular reactions were scored by the method described in "Appraisal of the Safety of Chemicals in Food Drugs and Cosmetics" page 51, published by the Association of Food and Drug Officials of the U.S.A. (sea appendix I).The tested substance is considered to be irritant for the rabbits eyes.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation: The primary irritation index as the measure of the acute irritation to the skin of rabbits was found to be 1.17 for Erythema and 2.67 for Edema based on US Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965).

The tested item is to be considered as non-irritant to the skin of rabbits.

Eye irritation: The ocular reactions were scored by the method described in "Appraisal of the Safety of Chemicals in Food Drugs and Cosmetics" page 51, published by the Association of Food and Drug Officials of the U.S.A. (sea appendix I).The tested substance is considered to be irritant for the rabbits eyes. The supporting study perfomed based on OECD 405, showed some adverse effects to cornae. Despite for this the CLP criteria for the definition of the calssification does not give any hazard statement, it was decided to classfied Acid Blue 113 based on the consiederation that the key study was performed with a higher purity and based on the fact that some adverse effect were found in the supporting study.


Justification for selection of skin irritation / corrosion endpoint:
The study was performed on a tested substance with a higher content of active ingredient.

Justification for selection of eye irritation endpoint:
The study was performed on a tested substance with a higher content of active ingredient.

Effect on skin: not irritating

Effects on eye: irritating

Justification for classification or non-classification

Skin irritation

Skin irritation has to be considered is following EU test B4, a mean value of ≥2,3 -≤4,0 for erythema/eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions; or Inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or (3) In some cases where there is pronounced variability of response among animals, with very definite positive effects related to chemical exposure in a single animal but less than the criteria above

Based on provided data no classification for skin irritation is warranted under Regulation 1272/2008.

 

Eye irritation

Substances are classified as eye irritant if that have the potential to induce reversible eye irritation according to the following criteria: if, when applied to the eye of an animal, a substance produces:

— at least in 2 of 3 tested animals, a positive response of:

— corneal opacity≥1 and/or

— iritis≥1, and/or

— conjunctival redness≥2 and/or

— conjunctival oedema (chemosis)≥2

— calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days

 

Based on provided data classification for eye irritation/corrosion Cat. 2, H 319 is warranted under Regulation 1272/2008.