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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:
experimental study
Adequacy of study:
key study
Study period:
From 03 SEP 1996 to 10 SEP 1996.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Chemical pharmaceutical factory, Dr. K. Thomae, Biberach
- Weight at study initiation: 2.5-3.2 kg
- Housing: individually
- Diet: ssniff K-H (V2333), ad libitum and hay (approx. 15 g daily)
- Water: ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 50 +/- 20
- Photoperiod (hrs dark / hrs light): 12 h / 12 h
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: polyethylene glycol 400
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g pasted with 0.8 ml polyethylene glycol 400 (Riedel-de Haen)
Duration of treatment / exposure:
4 h
Observation period:
7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5x2.5 cm² cellulose patch of surgical plaster (Beiersdorf)
- Type of wrap: semiocclusive bandage

REMOVAL OF TEST SUBSTANCE
- Washing: with warm tap water
- Time after start of exposure: 4 h

SCORING SYSTEM: according to OECD TG 404
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible
Remarks:
7 days after exposure.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks:
72 h after exposure.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible
Remarks:
7 days after exposure.
Irritant / corrosive response data:
From one hour up to 3 days after removal of the patches the treated skin of the animals showed very slight up to well defined erythema. 7 days after removal of the patches no signs of skin irritation were observed. Very slight edema was noted in 2/3 animals one hour after exposure. No edema were noted at any other time point.
Other effects:
The skin surface of the animals was dry, rough and light yellow discoloured.
Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP regulation
Conclusions:
According to the classification criteria of Regulation (EC) No 1272/2008 the test item is not irritating to skin under these test conditions. The test material contains relevant amounts of the submission substance. Therefore the test results are considered adequate to fulfil the endpoint requirements.
Executive summary:

The test item material was subject to an Acute Dermal Irritation/Corrosion Test in the rabbit according to OECD TG 404. Very slight up to well defined erythema were observed in every animal, fully reversible within seven days. Very slight edema were observed in 2/3 animals only one hour after exposure, fully reversible within one day. Therefore, the test item has not to be classified for skin irritation according to Regulation (EC) No 1272/2008.

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:
1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to
Guideline:
other: 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)
Deviations:
not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
other: English Silver
Details on test animals or tissues and environmental conditions:
TEST ANIMALS:
- Housing: individually
- Diet: NAFAG, Gossau SG, rabbit food, ad libitum
- Water: ad libitum
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 g
Duration of treatment / exposure:
No rinsing of eyes in 3 animals (group 1), rinsing after 30 seconds in other 3 animals (group 2)
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
No rinsing of eyes in 3 animals (group 1), rinsing after 30 seconds in other 3 animals (group 2) with 10 ml lukewarm water

SCORING SYSTEM: basically in accordance with OECD TG 405

TOOL USED TO ASSESS SCORE: slit lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: group 1 + group 2
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: group 1 + group 2
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2 (group 1), #3, #4, #5 (group 2)
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: no differentiation between redness, chemosis, discharge
Irritation parameter:
chemosis score
Basis:
animal: #1, #2 (group 1), #3, #4, #5 (group 2)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: no differentiation between redness, chemosis, discharge
Irritant / corrosive response data:
No eye responses were observed except conjunctivae score 6 (incl. chemosis, discharge) in animal #3 (group 1) 24 h after application, fully reversible by 48 h after application.

         Rabbit #3 (group 1)
 Days after appl.  Cornea  Iris  Conjunctivae
 1  0  0  6
 2  0  0  0
 3  0  0  0
 4  0  0  0
 7  0  0  0

Conjunctivae = [Redness (max. score 3) + Chemosis (max. score 4) + Discharge (max. score 3)] x 2

The conjunctivae score for animal #3 one day after application is put together like (3 + 0 + 0) for redness score 3 or (0 + 3 + 0) for chemosis score 3 in the worst case. Discharge is not relevant for classification according to the criteria of Regulation (EC) No 1272/2008. Therefore, the maximum mean value for either conjunctival redness or chemosis over 24 h, 48 h and 72 h after application is 1, which falls below critical values for classification according to the criteria of Regulation (EC) No 1272/2008.

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP regulation
Conclusions:
According to the classification criteria of Regulation (EC) No 1272/2008 the test material is not irritating to eyes under these test conditions. This conclusion is legitimate as three animals (group 1) were tested basically in accordance with today's standard methods regarding dosing, exposure duration, scoring system, reading time points and the observed eye responses were fully reversible 48 hours after application.
Executive summary:

The test material was tested for eye irritancy according to 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). 0.1 g test substance was applied to the conjunctival sac of one eye each of 6 animals (no washing in 3 animals, group 1, washing after 30 seconds in other 3 animals, group 2) and eye responses were watched for seven days. No eye responses were observed except conjunctival score 6 (incl. redness, chemosis, discharge) in animal #3 (group 1) 24 h after application, fully reversible by 48 h after application. As the mean values of the observed eye responses fall below the critical values for classification according to the criteria of Regulation (EC) No 1272/2008, the test material is not irritating to eyes and has not to be classified for eye irritation.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

Reliable studies (reliability 1 or 2) on skin irritation are available for the Diarylide Yellow Pigments Pigment Yellow 83 and its structural analogues, Pigment 12, Pigment Yellow 13, Pigment Yellow 14, Pigment Yellow 17, Pigment Yellow 55, Pigment Yellow 126, Pigment Yellow 127, Pigment Yellow 174 and Pigment Yellow 176. The Diarylide Yellow Pigments caused no skin effects (mean erythema or edema score = 0) or only slight transient effects (mean scores </= 2, i.e. well below the critical values for classification), which were fully reversible within the observation time, independently whether the exposure duration was 4 or 24 hours. Additional studies which are considered not to be reliable (reliability 3; Pigment Yellow 81 and Pigment Yellow 55) also reported that the tested substances did not cause skin irritation under the test conditions. In summary, it is concluded that Diarylide Yellow Pigments of this category are not irritating to skin and have not to be classified as skin irritants.

Eye irritation

Reliable studies (reliability 1 or 2) on eye irritation are available for the Diarylide Yellow Pigments Pigment Yellow 83 and its strucutral analogues, Pigment Yellow 12, Pigment Yellow 13, Pigment Yellow 14, Pigment Yellow 17, Pigment Yellow 55, Pigment Yellow 126, Pigment Yellow 127, Pigment Yellow 170, Pigment Yellow 174 and Pigment Yellow 176.

Diarylilde Yellow Pigments showed no effects or only some slight effects in the eyes. As the observed eye responses were all below the critical values for classification according to the criteria of Regulation (EC) No 1272/2008, Diarylide Yellow Pigments are considered not to be irritating to eyes and therefore have not to be classified for eye irritation.

Respiratory tract irritation

In three acute inhalation toxicity studies performed with the structural analogues, Pigment Yellow 13 and Pigment Yellow 17 and in two subacute inhalation studies performed with Pigment Yellow 13 no indications for respiratory tract irritation were obtained at gross pathology. No further studies with inhalation exposure are available for Diarylide Yellow Pigments. Based on these data it is concluded that Diarylide Yellow Pigments are not irritating to the respiratory tract and have not to be classified as respiratory tract irritants.

Refer also to Read across justification document, IUCLID Chapter 13.

Justification for classification or non-classification

Studies investigating skin or eye irritation did not reveal any or – if at all – only minimal evidence of irritant potential of Diarylide Yellow Pigments, which were fully reversible. Therefore, Diarylide Yellow

Pigments 83 has not to be classified as skin, eye or respiratory tract irritants according to Regulation (EC) No 1272/2008.