Registration Dossier

Administrative data

Description of key information

The test substance is considered as not irritating to the skin and eyes of rabbits.

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:
July 5th, 1983 - July 8th, 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Remarks:
but QAU statement included
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HOECHST AG, Kastengrund
- Weight at study initiation: 2.7 - 3.2 kg
- Housing: individually
- Diet (e.g. ad libitum): Altromin 2013 breeding diet - rabbit (Altromin GmbH, Lage/Lippe), ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): fully conditioned room
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: polyethylenglycol 400
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg in 0.3 mL polyethylenglycol 400
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: cellulose gauze held in place with an adhesive plaster (Fa. Baiersdorf AG, Hamburg)

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

SCORING SYSTEM: According to OECD guidelines
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.2
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
0.5 - 1 hour after treatment, erythema score 1 was observed in 1/3 animals and edema score 1 was observed in 3/3 animals.
The treated skin was red colored from the test substance.
At 72 hours after treatment two animals showed a dry and rough skin.
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was investigated for its potential to irritate the skin. Under the conditions chosen, the test substance was concluded to be not irritating.
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:
July 5th, 1983 - July 8th, 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Remarks:
but QAU statement included
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: HOECHST AG breed
- Weight at study initiation: 3.5 - 3.9 kg
- Housing: individually
- Diet (e.g. ad libitum): Altromin 2013 breedingdiat - rabbit (Altromin GmbH, Lage/Lippe), ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): fully conditioned room
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
other: polyethylenglycol 400
Controls:
other: untreated eye of the same animal
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg in 0.01 mL polyethylenglycol 400
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with physiological NaCl solution of 37 °C (0.01%)
- Time after start of exposure: 24 hours

SCORING SYSTEM: According to OECD test guideline

TOOL USED TO ASSESS SCORE: magnifier, fluorescein solution (0.01%) and UV light
Irritation parameter:
other: fluorescent test
Basis:
mean
Time point:
other: 24 h - 72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
0
Max. score:
2
Remarks on result:
other: after 1 h of exposure the iris was brownish colored in two of the animals
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 h - 48 h - 72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
No signs of irritation were observed for the iris and the cornea. After 1 h of exposure the iris was brownish colored in two of the animals. A moderate (grade 1) redness and swelling of the conjunctival sac was observed after 1 h of exposure which both decreased gradually. No swelling was observed from 24 hours onwards and no redness was observed at 72 hours.
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was investigated for its potential to be irritant to eyes. All effects observed were fully reversible within 72 h and thus, it was concluded that the test substance is not irritating to eyes.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Reliable data from several studies on irritation are available for the test article and for other members of the "perylene based pigments" category (see attached category justification). All of these data are taken into account for the evaluation and assessment of the irritation potential of the test article.

Skin irritation

In the key study (Hoechst, 1983) 0.5 g of the test substance in 0.3 ml PEG 400 was applied to the skin of three New Zealand White rabbits in a study according to OECD guideline 404. The animals were observed for 72 hours (Hoechst AG, 1983). 0.5 - 1 hour after treatment, erythema score 1 was observed in 1/3 animals and edema score 1 was observed in 3/3 animals. The mean scores (24, 48 and 72 hours) for erythema and edema were 0.2 and 0, respectively. The treated skin was red coloured from the test substance. At 72 hours after treatment two animals showed a dry and rough skin. Based on the results of this study, the test article was considered to be not irritating to the skin.

In another study performed according to the Code of Federal Regulations Title 16, the test substance (0.5 g) was applied to the skin of six New Zealand White rabbits (Hazleton Laboratories Europe Ltd., 1978). The treatment duration was 24 hours (under occlusive conditions) and the animals were observed for 7 days thereafter. The mean (24 and 72 hours) scores for erythema and edema were 0. Based on the results of this study, the test article was considered to be not irritating to the skin.

In a supporting non-GLP study according to a method comparable to OECD guideline 404, the test substance was applied as moistened powder (50% in water) for 20 hours to the back of two rabbits (BASF, XXIV/269, 1976). Remaining colored test substance was observed at 24 hours and erythema could not be scored. No erythema was reported 8 days after treatment. No edema was reported at 24 hours and 8 days.

In a second supporting non-GLP study according to a method comparable to OECD guideline 404, a mixture containing 18.5% of the test substance was applied for 20 hours to the back of two rabbits (BASF, XXIV/334, 1976). Remaining colored test substance was observed at both observation time points (24 hours and 8 days) and therefore erythema could not be scored. No edema was reported at the 24 hours and 8 days observation time points.

In several studies performed with other category members the potential to cause skin irritation was found to be very low. None of these studies raised any concerns regarding irritation and therefore none of the substances require classification. All compounds were considered to be not irritating to skin.

Conclusion: Based on the available data for the test substance and taking the data of category members into account, no classification for skin irritation is warranted. The test substance is considered to be not irritating.

Eye irritation

In the key study according to OECD guideline 405, the test article (0.1 g in 0.01 ml polyethylenglycol 400) was applied into the left conjunctival sac of three New Zealand White rabbits (Hoechst AG, 1983). The untreated right eyes served as controls. The treated eyes were washed with physiological NaCl solution 24 hours after instillation. Animals were observed 1, 24, 48 and 72 hours after test item instillation. After 1 h of exposure the iris was brownish colored in two of the animals. A moderate (grade 1) redness and swelling of the conjunctival sac was observed after 1 h of exposure which both decreased gradually. No swelling was observed from 24 hours onwards and no redness was observed at 72 hours. The mean (24, 48, 72 hours) cornea, iris and chemosis scores were 0. The mean (24, 48, 72 hours) conjunctivae score was 0.3 (fully reversible within 72 hours). Based on the result of this study, the test article was considered to be not irritating to the eye.

In another study performed according to the Code of Federal Regulations Title 16, the test substance (0.1 g) was instilled into the eyes of six New Zealand White rabbits (Hazleton Laboratories Europe Ltd., 1978). The treated eyes were not washed. The mean (24, 48, 72 hours) cornea, iris and chemosis scores were 0. The mean (24, 48, 72 hours) conjunctivae score was 0.056 (fully reversible within 48 hours). Therefore, the test article was considered to be not irritating.

In a supporting study performed with two rabbits, 50 µl of the test article was applied into the conjunctival sac of the right eyes (BASF, XXIV/269, 1976). The left eyes was treated with talcum powder and served as controls. The eyes were not rinsed. Animals were observed after 1 and 24 hours and after 8 days after the treatment. After 1 hour, remaining substance was observed. The application caused slight redness of the conjunctivae at 1 and 24 hours. Redness was fully reversible within 8 days. One animal displayed a minimal corneal reaction at the end of the observation perio. The irritation observed caused by the test article was not clearly different from the control substance talcum powder. The test article was therefore judged to be not irritating to the eyes.

In a second supporting study (BASF, XXIV/334, 1976), 50 µl of a mixture containing 18.5% of the test article was instilled into conjunctival sac of the right eyes of two rabbits. Physiological sodium chloride solution (50 µl) was instilled into the left eyes and served as controls. The eyes were not rinsed. Animals were observed after 1 and 24 hours and after 8 days after the treatment. After 1 hour, remaining substance was observed. The application did not cause any irritating effects. One animal displayed a minimal corneal reaction at the end of the observation period. This reaction was however also observed with the control substance, therefore the test article was considered to be not irritating.

In several studies performed with other category members the potential to cause eye irritation was found to be very low. None of these studies raised any concerns regarding irritation and therefore none of the substances require classification. All compounds were considered to be not irritating to the eye.

Conclusion: Based on the available data for the test substance and taking the data of category members into account, no classification for eye irritation is warranted. The test substance is considered to be not irritating.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, classification for irritation is not warranted under Regulation (EC) No.1272/2008.