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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to
Guideline:
other: Code of Federal Regulations, Title 16, Section 1500.42
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: W. Ostrop/Meerbusch
- Weight at study initiation: mean weight: 2.1 kg
- Housing: one per cage
- Diet (e.g. ad libitum): "muemmel z" (ssniff/Soest)
- Water (e.g. ad libitum): water ad libitum
- Acclimation period: 4-6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 18
- Humidity (%): 40 (relative humidity)
- Photoperiod (hrs dark / hrs light): according to the day light rhythm
Type of coverage:
occlusive
Preparation of test site:
other: shaved intact and damaged skin
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg compound slightly thickened with water
Duration of treatment / exposure:
24 hours
Observation period:
8 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: double layer gauze covered by indifferent impermeable PVC (5x5 cm) foil and elastic bandage (ElastoflexR)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize numerical scores.
Irritation parameter:
erythema score
Remarks:
intact and damaged skin
Basis:
mean
Time point:
24 h
Remarks on result:
other: scoring not possible due to the skin coloring by the substance
Irritation parameter:
erythema score
Remarks:
intact and damaged skin
Basis:
mean
Time point:
48 h
Remarks on result:
other: timepoint not evaluated
Irritation parameter:
erythema score
Remarks:
intact and damaged skin
Basis:
mean
Time point:
72 h
Remarks on result:
other: scoring not possible due to the skin coloring by the substance
Irritation parameter:
erythema score
Remarks:
intact and damaged skin
Basis:
mean
Time point:
other: 8 days
Remarks on result:
other: scoring not possible due to the skin coloring by the substance
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
mean
Time point:
24 h
Score:
2.33
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
mean
Time point:
48 h
Remarks on result:
other: timepoint not evaluated
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
mean
Time point:
72 h
Score:
0.83
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
mean
Time point:
other: 8 days
Score:
0.33
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
edema score
Remarks:
damaged skin
Basis:
mean
Time point:
24 h
Score:
1.83
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
edema score
Remarks:
damaged skin
Basis:
mean
Time point:
48 h
Remarks on result:
other: time point not evaluated
Irritation parameter:
edema score
Remarks:
damaged skin
Basis:
mean
Time point:
72 h
Score:
1.17
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
edema score
Remarks:
damaged skin
Basis:
mean
Time point:
other: 8 days
Score:
0.33
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritant / corrosive response data:
The test article caused edema formation below the threshold of regulatory significance. In two animals, the edema was not fully reversed after 8 days but is expected to have cleared after 14 days. The erythema reactions could not be scored due to coloring effects of the test substance. Erythema was assumed to be equal to edema based on the correlation existing (Marzulli and Maibach, Foi. Cosm. Tox. 13, 355, 1975).

Overview of results:

Animal 1 Animal 2 Animal 3 Animal 4 Animal 5 Animal 6
intact skin
erythema 24 h * * * * * *
72 h * * * * * *
8 days * * * * * *
edema 24 h 3 3 1 2 3 2
72 h 0 1 1 1 1 1
8 days 0 0 0 1 1 0
damaged skin
erythema 24 h * * * * * *
72 h * * * * * *
8 days * * * * * *
edema 24 h 2 2 0 2 3 2
72 h 1 0 0 2 2 2
8 days 1 0 0 0 1 0

* could not be scored due to coloration of the skin from the substance

Interpretation of results:
GHS criteria not met
Conclusions:
The results show that there is no corrosive potential of the substance. However, the substance can not be properly evaluated due to substance residues / coloring. The substance is regarded as slightly irritatin, however below the level of regulatory significance.
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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to
Guideline:
other: Code of Federal Regulations, Title 16, Section 1500.42
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: W. Ostrop, Meerbusch
- Weight at study initiation: mean weight: 2.1 kg
- Housing: one per cage
- Diet (e.g. ad libitum): "muemmel z" (ssniff/Soest)
- Water (e.g. ad libitum): Water ad libitum
- Acclimation period: 4 - 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 18
- Humidity (%): 40 (relaive humidity)
- Photoperiod (hrs dark / hrs light): according to the day light rhythm
Vehicle:
unchanged (no vehicle)
Controls:
other: other untreated eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 µL bulk volume
Duration of treatment / exposure:
One single application. Lids have been gently hold together for 1 sec. The eye was left unwashed.
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
6 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize numerical scores.

TOOL USED TO ASSESS SCORE: Ophtalmoscop; after 8 days with fluorescein and UV-light
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: no effects
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritant / corrosive response data:
All scores at all time points were zero.
Interpretation of results:
GHS criteria not met
Conclusions:
In conclusion, the test substance was investigated for its irritating potential. All scores were noted to be zero at all observation time points and thus, the test substance was concluded to be not irritating.
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

The test substance slightly thickened with water (500 mg) was applied to intact and damaged skin of six New Zealand White rabbits in a skin irritation study comparable to OECD guideline 404 (BASF, 1978). The test substance was applied on a tissue (2.5 x 2.5 cm) held in place by an occlusive dressing for 24 hours. The test rabbits were observed for 8 days. Application caused forming of edema (mean scores (24 and 72 hours) for intact and damaged skin were 1.6 and 1.5, respectively). Determination of erythema was not possible at 24 and 72 hours and at day 8 after treatment, due to substance induced coloration of the skin. Therefore, based on the result of this study, the test substance does not have high potential to cause skin irritation, however a definitive conclusion cannot be drawn.

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 an eye irritation study comparable to guideline 405, 100 µl of the test article was applied unchanged into the conjunctival sac of the right eye of six New Zealand White rabbits (BASF AG, 1978). Eyes were not rinsed. The left eyes remained untreated and served as controls. Animals were observed 24, 48 and 72 hours and 8 days after the treatment and the irritation parameters were scored. The cornea, iris, conjuctivae and chemosis scores were 0 at all time points (24, 48 and 72 hours) for all animals. Therefore, based on the results of this study, the test article was considered to be not irritating to the eye.

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.