Registration Dossier

Administrative data

Description of key information

Skin irritation

The dermal irritation potential of test chemical was assessed in various experimental studies conducted on rabbits. Based on the available data for the key and supporting studies, it can be concluded that the test chemical is unable to cause skin irritation and thus considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Eye irritation

An ocular irritation potential of target chemical was assessed in various experimental studies conducted on rabbits. Based on the available data for the key and supporting studies, it can be concluded that the test chemical is able to cause severe eye damage and thus can be considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2”.

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:
February 1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
data is from experimental reports
Qualifier:
according to
Guideline:
other: "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO).
Principles of method if other than guideline:
To measure of the acute irritation provoked by the test chemical on the skin of the rabbits
GLP compliance:
not specified
Species:
rabbit
Strain:
other: Russian breed
Details on test animals and environmental conditions:
TEST ANIMALS
- Sex: Male/female
- Weight at study initiation: 1.5 to 2 kgs
- Housing: In order to prevent injuries by bites the rabbits were kept separately in V2A wire cages.
- Diet (e.g. ad libitum): food (NAFAG, Gossau SG, rabbit food) ad libitum
- Water (e.g. ad libitum): ad libitum
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
C.I. Pigment Red 169 was applied to each side in quantities of 0.5 g. Before application a 50 % polyethylene glycol trituration (PEG 400) was made.
Duration of treatment / exposure:
24 hours
Observation period:
24 hrs and 72 hrs
Number of animals:
Six rabbits (3 males/3 females)
Details on study design:
PROCEDURE:
Six rabbits (3 males/3 females) of the Russian breed were shaved on the whole back and flanks two days before treatment with an electric clipper. The shaven skin on the left side was slightly scarified immediately before treatment.

TEST SITE
- Area of exposure: A gauze patch 2.5 x 2.5 cm was soaked with the test substance and immediately applied to the prepared skin
- Type of wrap if used: The patch was covered with a plastic film 5 x 5 cm, which was fixed to the body with adhesive tape.

REMOVAL OF TEST SUBSTANCE
The gauze patches were removed 24 hours after the application. The reaction of the skin was appraised upon removal and 72 hours after it, on the basis of the following evaluation scheme.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The primary irritation index of C.I. Pigment Red 169 was 0.

Evaluation of Skin reactions:

Animal number, sex

Skin reaction

24 hours after application

72 hours after application

Intact skin

Scarified skin

Intact skin

Scarified skin

1, male

Erythema

 

 

 

 

Edema

 

 

 

 

2, male

Erythema

0

0

0

0

Edema

0

0

0

0

3, male

Erythema

0

0

0

0

Edema

0

0

0

0

4, female

Erythema

0

0

0

0

Edema

0

0

0

0

5, female

Erythema

0

0

0

0

Edema

0

0

0

0

6, female

Erythema

0

0

0

0

Edema

0

0

0

0

Interpretation of results:
other: not irritating
Conclusions:
The Primary Irritation Index of test chemical was 0. Hence, the test chemical can be considered to be not irritating to rabbit skin.
Executive summary:

The purpose of the test was to determine the primary-irritation index, which serves as a reassure of the acute irritation, provoked by test chemical on the skin of the rabbits. The procedure adopted was the patch-test technique described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (19 59) of the US Association of Food and Drug Officials (AFDO). Six rabbits (3 males/3 females) of the Russian breed, were shaved on the whole back and flanks two days before treatment with an electric clipper. The shaven skin on the left side was slightly scarified immediately before treatment. A gauze patch 2.5 x 2.5 cm was soaked with the test substance and immediately applied to the prepared skin. The patch was covered with a plastic film 5 x 5 cm, which was fixed to the body with adhesive tape. The chemical was applied to each side in quantities of 0.5 g. Before application a 50 % polyethylene glycol trituration (PEG 400) was made. The patch was kept intact till 24 hours. The reaction of the skin was appraised upon removal and 72 hours after patch removal. The observed reactions were scored and Primary Irritation Index was calculated. The Primary Irritation Index of test chemical was 0. Hence, the test chemical can be considered to be not irritating to rabbit skin.

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:
February 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
data is from experimental reports
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
Assessment of a possible irritating potential of CI Pigment Red 169 to the eye and to the eye mucosa of rabbits
GLP compliance:
not specified
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Sex: Male and female
- Source: Gaukler; D-6050 Offenbach 1 Main, Frg
- Weight At Study Initiation: Mean Weight (Kg) Male: 3.27 , Female: 3.23
- Housing: Cage made of stainless steel with wire mesh walk floors.
- Floor Area: 40 Cm X 51 Cm
- Diet (E.G. Ad Libitum): KLIBA 341, 4 mm (About 130 G per animal per day)
- Water (E.G. Ad Libitum): About 250 mL tap water per animal per day
- Acclimation Period: At least 8 days before the beginning of the study; same housing conditions as during the study
- Bedding: No Bedding in the cages; sawdust in the waste trays

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Day/Night Rhythm: 12 H/12 H (6.00 - 18.00 Hours/18.00 - 6.00 Hours)
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml bulk volume (about 20 mg of the comminuted test substance)
Duration of treatment / exposure:
Single exposure
Observation period (in vivo):
1 hr, 24hr, 48hr, 72hr, 8 Day, 15 Day and 21 Day after application
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
MALE : 3
FEMALE : 3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not washed
- Time after start of exposure: not washed

SCORING SYSTEM: ACCORDING TO 83/467/EEC CRITERIA OF JULY 29TH, 1983

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: no data
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.1
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.1
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
swelling
Basis:
mean
Time point:
24/48/72 h
Score:
1.4
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.9
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Following symptoms appeared:
after 24 hours of exposure: small retractions in the eyelid, pupil contracted, irritation index could not be read because of staining due to the color of test substance.
after 72 hours: Suppuration
after 8 days: Loss of hair at margins of eyelid
after 15 days: Marginal vascularization of the cornea
after 21 days: Pannus

Calculation of the mean was done according to 83/467/EEC criteria of July 29th, 1983 (for calculation of the means of opacity, iris, redness and swelling, only the readings of 24, 48 and 72 hours are used).

RESULTS ACUTE EYE IRRITATION (OECD)

Serial number

1

2

3

4

5

6

Animal number

0821

0846

0884

0912

0906

0907

Animal weight(kg)

3.46

3.31

3.32

2.91

3.09

3.10

Sex

Fe

Ma

Fe

Fe

Ma

Ma

 

Readings

Animal

Cornea

Iris

Conjunctivae

Symptoms

OP

AR

RED

SW

DI

1 hour

1

0

0

0

1

1

2

S00

S00

2

0

0

0

2*

1

3

3

0

0

0

2*

1

2

4

0

0

0

2

1

2

5

0

0

0

1

1

2

6

0

0

0

2

1

2

24 hour

1

0

0

0

2

1

1

RE

PC/S00

2

0

0

0*

2*

2

3

3

0

0

0

1

2

2

4

0

0

0

2

1

1

5

0

0

0

2

1

1

6

0

0

0

2

1

3

48 hours

1

0

0

0

1

0

0

RE

2

1

2

1

2

2

3

3

0

0

0

1

1

1

4

0

0

0

2

1

0

5

0

0

0

2

0

0

6

0

0

0

2

1

2

72 hours

 

1

0

0

0

0

0

0

RE/S06

PC/S

2

1

4

1

2

2

3

3

0

0

0

0

0

1

4

0

0

0

1

1

0

5

0

0

0

1

0

0

6

0

0

0

1

1

2

8 days

1

 

 

 

 

 

 

 

PC/LH

 

 

 

RE

2

1

4

1

2

2

2

3

0

0

0

0

0

0

4

0

0

0

0

0

0

5

0

0

0

0

0

0

6

0

0

0

1

1

2

15 days

1

 

 

 

 

 

 

 

PC/LH/MV/RE/S

 

 

 

RE/MV/PC

2

2

2

1

2

1

3

3

0

0

0

0

0

0

4

0

0

0

0

0

0

5

0

0

0

0

0

0

6

1

2

0

0

0

0

21 days

1

 

 

 

 

 

 

LC/MV/RE/S/PA

 

 

 

 

LC/MV/RE/PC

2

2

2

1

2

1

2

3

0

0

0

00

0

0

4

0

0

0

0

0

0

5

0

0

0

0

0

0

6

1

2

1

0

0

0

ME

1

0.0

0.0

1

0.3

 

2

0.7

0.7

2

2

3

0

0

0.7

1

4

0

0

1.7

1

5

0

0

1.7

0.3

6

0

0

1.7

1.0

ME

 

0.1

0.1

1.4

0.9

 

KEY: MA = MALE

FE = FEMALE

ME = MEAN

H = HOUR

0 = DAY

EXPLANATIONS OF SYMPTOMS:

S00 - IRRITATION INDEX COULD NOT BE READ BECAUSE OF STAINING DUE - TO THE COLOR OF THE TEST SUBSTANCE

S06 - FIRST STUDY DISCONTINUED AFTER 72 H BECAUSE NO IRRITATION COULD BE OBSERYED AT THAT TIME

LH - LOSS OF HAIR AT MARGINS OF EYELIDS

LC - LOSS OF CORNEAL TISSUE

MV - MARGINAL VASCULARIZATION OF THE CORNEA

PC - PUPIL CONTRACTED

PA - PANNUS

RE - SMALL RETRACTIONS IN THE EYELIDS

S - SUPPURATION

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
The mean scores for cornea, iris, conjunctival swelling and chemosis were 0.1,0.1,1.4 and 0.9 respectively. Also,redness and contracted pupils loss of corneal tissue, marginal vascularization was observed in the treated eyes till 21 days of observation.
Based on these observations and scores, the test chemical can be considered to be irritating to rabbit eyes.
Executive summary:

A study was performed for assessment of a possible irritating potential of CI Pigment Red 169 to the eye and to the eye mucosa of rabbits. The study was conducted according to OECD 405 Guidelines. 6 (3 male, 3 female) Vienna White rabbits were used for the study. 0.1 ml bulk volume (about 20 mg of the comminuted test substance) was instilled into the right eyelid of the test animals. Untreated eyes served as negative control. The treated eyes remained unwashed throughout the study. The treated eyes were observed for signs of irritation and scored at 1 hr, 24hr, 48hr, 72hr, 8 Day, 15 Day and 21 Day after application. The mean scores for cornea, iris, conjunctival swelling and chemosis were 0.1,0.1,1.4 and 0.9 respectively. Also, redness and contracted pupils loss of corneal tissue, marginal vascularization was observed in the treated eyes till 21 days of observation. Based on these observations and scores, the test chemical can be considered to be irritating to rabbit eyes.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

Various studies has been investigated for the test chemical to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical that have been summarized as below;

 

The skin irritation study of test chemical was conducted on rabbit’s skin. The purpose of the test was to determine the primary-irritation index, which serves as a reassure of the acute irritation, provoked by test chemical on the skin of the rabbits. The procedure adopted was the patch-test technique described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (19 59) of the US Association of Food and Drug Officials (AFDO). Six rabbits (3 males/3 females) of the Russian breed, were shaved on the whole back and flanks two days before treatment with an electric clipper. The shaven skin on the left side was slightly scarified immediately before treatment. A gauze patch 2.5 x 2.5 cm was soaked with the test substance and immediately applied to the prepared skin. The patch was covered with a plastic film 5 x 5 cm, which was fixed to the body with adhesive tape. The chemical was applied to each side in quantities of 0.5 g. Before application a 50 % polyethylene glycol trituration (PEG 400) was made. The patch was kept intact till 24 hours. The reaction of the skin was appraised upon removal and 72 hours after patch removal. The observed reactions were scored and Primary Irritation Index was calculated. The Primary Irritation Index of test chemical was 0. Hence, the test chemical can be considered to be not irritating to rabbit skin.

 

The above study was supported by another skin irritation study performed for test chemical on rabbit’s skin. About 50% solution of the test chemical in distilled water was applied to backs and ears of the 2 male rabbits in the following manner- a) Rabbit back: Lapping test (2.5 * 2.5 cm large cotton roll loaded with the substance) b) Rabbit ear: application of a cotton ball loaded with the substance. The treated sites were observed and scored for signs of irritation 24 hours till 8 days after dosing. The Red substance remained on the back of the test animals, hence redness (erythema) not recognizable. The test chemical does not cause any primary skin irritation even on prolonged exposure. Hence, test chemical can be considered to be not irritating to skin.

Based on the available data for key and supporting study, it can be concluded that test chemical is unable to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Eye irritation:

In different studies, the test chemical has been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical that have been summarized as below;

 An eye irritation study was performed for assessment of a possible irritating potential of test chemical to the eye and to the eye mucosa of rabbits. The study was conducted according to OECD 405 Guidelines. 6 (3 male, 3 female) Vienna White rabbits were used for the study. 0.1 ml bulk volume (about 20 mg of the comminuted test substance) was instilled into the right eyelid of the test animals. Untreated eyes served as negative control. The treated eyes remained unwashed throughout the study. The treated eyes were observed for signs of irritation and scored at 1 hr, 24hr, 48hr, 72hr, 8 Day, 15 Day and 21 Day after application. The mean scores for cornea, iris, conjunctival swelling and chemosis were 0.1,0.1,1.4 and 0.9 respectively. Also, redness and contracted pupils loss of corneal tissue, marginal vascularization was observed in the treated eyes till 21 days of observation. Based on these observations and scores, the test chemical can be considered to be irritating to rabbit eyes.

 

The above result was supported by another ocular irritation study conducted for test chemical to measure the acute irritation provoked by test chemical after instillation into the rabbit eyes. The procedure adopted was the technique described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO). The substance was tested on 6 rabbits (3 males/3 females) of the Russian breed. Amounts of 0.1 g of the test substance were introduced into the conjunctival sac of the left eye with a spatula. After application, the eyelids were held open for a few seconds. The right eye served as a control. The treated eyes of three rabbits were each rinsed with 10 ml lukewarm water about 30 seconds after treatment and the remaining treated eyes remained unwashed through out the test. The reactions were appraised with a slit-lamp after 24 hours and after 2, 3, 4 and 7 days on the basis of the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the AFDO. The primary-irritation index, which serves as a measure of the acute irritation provoked by the substance, was found to be 1 for the cornea, 0 for the iris and 1.7 for the conjunctivae. Therefore, the test chemical can be considered as a minimal irritant to the eye of rabbits.

 

The overall results were further supported by the ocular irritation study for test chemical. About 50mm3 (mg) of the test chemical was instilled into the conjunctival sac of eye of 2 (male, female rabbits). Talcum (amorphous) was instilled into the other eye. The treatment and control eye were observed and scored for effects 1,24 hours till 8 days after instillation. Red substance residues were observed in the treated eyes and the residues of the talcum were observed in the control eyes. Signs of irritation were observed in the treated eyes at 1,24 hours till 8days. Hence, the test chemical can be considered to be irritating to eyes.

Thus based on the available data for the target as well as supporting studies, it can be concluded that test chemical is able to cause severe eye irritation and considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2”.

 

Justification for classification or non-classification

The skin and eye irritation potential of test chemical were observed in various studies. The results obtained from these studies indicates that the chemical is unlikely to cause skin irritation but can cause severe eye damage. Hence the test chemical can be classified under the category “Not Classified” for skin and “Category 2” for eye as per CLP.