2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[N-(4-chloro-2,5-dimethoxyphenyl)-3-oxobutyramide]

Endpoint summary

Description of key information

PY 83 was non irritant in rabbit skin and eyes in vivo.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

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

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

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 or test system 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.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

See justification doocument in Chapter 13

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Interpretation of results:

GHS criteria not met

Reference 3

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

other:

Reference 4

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

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

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.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

See Read across justification document in chapter 13

Reason / purpose for cross-reference:

read-across source

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

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

See Read across justification document in chapter 13

Reason / purpose for cross-reference:

read-across source

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

Reference 4

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Reference 5

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Studies investigating skin or eye irritation did not reveal any evidence of irritant potential of Pigment Yellow 83. Therefore, Pigment Yellow 83 is not

classified as skin, eye or respiratory tract irritant according to Regulation (EC) No 1272/2008.