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Administrative data

Description of key information

Skin irritation:
In an OECD guideline and GLP compliant primary skin irritation test in rabbits with the test item neither erythema nor edema were

observed at reading times 24, 48 and 72 h in any animal. Therefore, Pigment Yellow 191 can be regarded as not skin irritating.
Eye irritation:
In an OECD guideline and GLP compliant primary eye irritation test in rabbits with the test item only slight ocular reactions were observed for conjunctival redness in 2 animals (mean 0.33 of 24, 48, 72 h readings), which were fully reversible within 48 h. Therefore, Pigment Yellow 191 can be regarded as not eye irritating.
Respiratory tract:
Based on available data the substance is considered likely to behave like an inert dust. Consequently the substance is considered not to exert any local irritative effects. Therefore, it is concluded, that testing is not necessary to reach the scientific conclusion that classification is not warranted.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
well performed GLP and OECD 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)
Version / remarks:
84/449/EEC
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
- Animal specifics: Hoechst AG, conventional breed
- Source: Hoechst AG breeding colony
- Age at study initiation: 3 months to 5 months
- Weight at study initiation: 2.1 kg to 2.3 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls
- Diet (e.g. ad libitum): standard laboratory diet (Altromin 2123) and appr. 15 g hay daily, ad libitum
- Water (e.g. ad libitum): deionized chlorinated water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20° ± 3°C (air-condition)
- Humidity (%): 50 ± 20 %
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: Polyethyleneglycol 400
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.9 mL
- Lot/batch no. (if required): Ch-B 2322 , Riedel de Haen AG
Duration of treatment / exposure:
4 hours
Observation period:
3 days
Number of animals:
3
Details on study design:
TEST SITE
About 24 h before the start of the study the hair in the dorsal region of the body of the animals was removed with an electric clipper over an area of about 25 cm2.
- Area of exposure: approximately 2.5 cm x 2.5 cm
- Type of wrap if used: surgical gauze patch (Beiersdorf AG), fixed to the prepared skin area and covered with a semi-occlusive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): flushed with lukewarm tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM:
as in EU Method B.4, assessed approximately 30 - 60 min, 24, 48, and 72 h after the removal of the patches
Irritation parameter:
erythema score
Basis:
animal: # 76, 77, 78 each
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: initial signs of slight irritation (erythema) were fully reversible within 24 hours
Irritation parameter:
edema score
Basis:
animal: # 76, 77, 78 each
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: reversibility not relevant since no effects occured
Irritant / corrosive response data:
Scores (oedema or erythema) were 0 at 24, 48 and 72 h readings after removal of dressing in all animals.
Other effects:
Yellow staining produced by the yellow colour of the test item was present at all reading time points.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
no effects (erythema and oedema) were observed at 24, 48 and 72 h readings. Therfore, the test item is regarded as not irritating to the skin.
Executive summary:

The primary skin irritation potential of the test item was investigated according to OECD test guideline no. 404. The test item was applied by semi-occlusive application of 0.5 g of the test item mixed with 0.9 mL of Polyethyleneglycol 400 to the intact dorsal region of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 30 - 60 min, 24, 48 and 72 hours after removal of the dressing. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. The application of the test item to the skin resulted in mild, early-onset and transient signs of irritation such as erythema. These effects were reversible and were no longer evident 24 hours after treatment for all animals. Staining of the treated skin was noted in all animals throughout the whole study. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the skin.

Therefore, the test item has not to be classified as irritating to the skin according to Regulation (EC) no 1272/2008.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
erythema score
Basis:
animal: # 76, 77, 78 each
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: initial signs of slight irritation (erythema) were fully reversible within 24 hours
Irritation parameter:
edema score
Basis:
animal: # 76, 77, 78 each
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: reversibility not relevant since no effects occured
Interpretation of results:
not irritating
Conclusions:
no effects (erythema and oedema) were observed at 24, 48 and 72 h readings. Therfore, the test item is regarded as not irritating to the skin.
Executive summary:

The primary skin irritation potential of the test item was investigated according to OECD test guideline no. 404. The test item was applied by semi-occlusive application of 0.5 g of the test item mixed with 0.9 mL of Polyethyleneglycol 400 to the intact dorsal region of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 30 - 60 min, 24, 48 and 72 hours after removal of the dressing. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. The application of the test item to the skin resulted in mild, early-onset and transient signs of irritation such as erythema. These effects were reversible and were no longer evident 24 hours after treatment for all animals. Staining of the treated skin was noted in all animals throughout the whole study. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the skin.

Therefore, the test item has not to be classified as irritating to the skin according to Regulation (EC) no 1272/2008.

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

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
well performed GLP and OECD guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
84/449/EEC
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Animal specifics: Hoechst AG, conventional breed
- Source: Hoechst AG breeding colony
- Age at study initiation: 3 months to 5 months
- Weight at study initiation: 2.3 kg to 2.6 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls
- Diet (e.g. ad libitum): standard laboratory diet (Altromin 2123) and appr. 15 g hay daily, ad libitum
- Water (e.g. ad libitum): deionized chlorinated water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20° ± 3°C (air-condition)
- Humidity (%): 50 ± 20 %
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye of each treated animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
Duration of treatment / exposure:
Single instillation, exposure period: 24 hours (washing 24 h after instillation)
Observation period (in vivo):
3 days
Number of animals or in vitro replicates:
3
Details on study design:
Application of the substance to the conjunctival sac of the left eye of each animal, the right eyes served as control respectively

REMOVAL OF TEST SUBSTANCE
- Washing: Washing with physiological saline at approx. 37 °C 24 h after administration and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein sodium solution (24, 48 and 72 h after administration) took place
The eyes were examined 1, 24, 48 and 72 hours after application of the test item

TOOL USED TO ASSESS SCORE: 0.01 % solution of fluorescein sodium, under UV light (24 and 72 hour readings)
Irritation parameter:
cornea opacity score
Basis:
animal: # 1, 2, 3 each
Time point:
other: mean of 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not relevant since on effects occured
Irritation parameter:
iris score
Basis:
animal: # 1, 2, 3 each
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: 1 hour after application inflammation grade 1 was observed in all animals, which was fully reversible after 24 h.
Irritation parameter:
chemosis score
Basis:
animal: # 1, 2, 3 each
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: 1 hour after application grade 1 and 2 chemosis was observed in all animals, which was fully reversible within 24 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: 1 hour after application grade 2 conjunctival redness was observed in all animals, which was fully reversible for animal #2 within 24 h
Irritation parameter:
conjunctivae score
Basis:
animal: # 1, 3 each
Time point:
other: mean of 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: 1 hour after application grade 2 conjunctival redness was observed in all animals, which was fully reversible for animals #1 and #3 within 48 h
Irritant / corrosive response data:
1 hour after application the treated eyes of all animals exhibited a slight injection of conjunctival blood vessels up to a diffuse, beefy red colour as well as slight swellings. the iris of all animals was reddened. Additionally yellow discharge was noted.
Other effects:
no other effects reported
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
All recorded ocular reactions were fully reversible within 48 h an all mean scores were well below the threshold values for classification. Therefore, the test item has not to be classified as irritation to the eyes according to Regulation (EC) No 1272/2008.
Executive summary:

A study with the test item according to OECD Guideline 405 and EU Method B.5 was performed to investigate the irritation potential to the rabbit eye.

1 hour after application the treated eyes of all animals exhibited a slight injection of conjunctival blood vessels up to a diffuse, beefy red colour as well as slight swellings and the iris of all animals was reddened. Additionally yellow discharge was noted. But mean scores (mean of 24, 48, and 72 h) of all animals were well below the threshold values for classification. 48 hours after treatment all signs of irritation were fully reversible.

Therefore, the test item has not to be classified as irritation to the eyes according to Regulation (EC) No 1272/2008.

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reason / purpose for cross-reference:
read-across source
GLP compliance:
yes
Irritation parameter:
cornea opacity score
Basis:
animal: # 1, 2, 3 each
Time point:
other: mean of 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not relevant since on effects occured
Irritation parameter:
iris score
Basis:
animal: # 1, 2, 3 each
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: 1 hour after application inflammation grade 1 was observed in all animals, which was fully reversible after 24 h.
Irritation parameter:
chemosis score
Basis:
animal: # 1, 2, 3 each
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: 1 hour after application grade 1 and 2 chemosis was observed in all animals, which was fully reversible within 24 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: 1 hour after application grade 2 conjunctival redness was observed in all animals, which was fully reversible for animal #2 within 24 h
Irritation parameter:
conjunctivae score
Basis:
animal: # 1, 3 each
Time point:
other: mean of 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: 1 hour after application grade 2 conjunctival redness was observed in all animals, which was fully reversible for animals #1 and #3 within 48 h
Irritant / corrosive response data:
1 hour after application the treated eyes of all animals exhibited a slight injection of conjunctival blood vessels up to a diffuse, beefy red colour as well as slight swellings. the iris of all animals was reddened. Additionally yellow discharge was noted.
Interpretation of results:
not irritating
Conclusions:
All recorded ocular reactions were fully reversible within 48 h an all mean scores were well below the threshold values for classification. Therefore, the test item has not to be classified as irritation to the eyes according to Regulation (EC) No 1272/2008.
Executive summary:

A study with the test item according to OECD Guideline 405 and EU Method B.5 was performed to investigate the irritation potential to the rabbit eye.

1 hour after application the treated eyes of all animals exhibited a slight injection of conjunctival blood vessels up to a diffuse, beefy red colour as well as slight swellings and the iris of all animals was reddened. Additionally yellow discharge was noted. But mean scores (mean of 24, 48, and 72 h) of all animals were well below the threshold values for classification. 48 hours after treatment all signs of irritation were fully reversible.

Therefore, the test item has not to be classified as irritation to the eyes according to Regulation (EC) No 1272/2008.

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

Additional information

Justification for selection of skin irritation / corrosion endpoint:
only one study available

Justification for selection of eye irritation endpoint:
only one study available

Justification for classification or non-classification

Pigment Yellow 191 has been tested in vivo for skin irritative properties in rabbits. In this OECD guideline and GLP compliant study, the substance did not cause any skin reactions at reading times 24, 48 and 72 h in any animal. Therefore, Pigment Yellow 191 does not have to be classified as skin irritating according to Directive 67/548/EEC and Regulation (EU) No 1272/2008.

 

Pigment Yellow 191 has been tested in vivo for eye irritative properties in rabbits according to OECD guideline and GLP. In this study slight signs of irritation were observed for conjunctival redness in 2 animals. The mean of scores read 1, 2 and 3 days after treatment were well below the classification criteria laid down in the Directive 67/548/EEC and Regulation (EC) No 1272/2008. Therefore, Pigment Yellow 191 does not have to be classified as eye irritating.

 

It can reasonably be deduced that Pigment Yellow 191 does not cause respiratory tract irritation and thus does not have to be classified according to the criteria laid down in Directive 67/548/EEC and in Regulation (EC) No 1272/2008, because Pigment Yellow 191 did cause only very slight, fully reversible irritative effects in the eyes and no skin reactions 1, 2 and 3 days after treatment and does not have to be classified as either skin or eye irritating. Moreover, Pigment Yellow 191, in the unlikely event of being inhaled as a dust, is considered not to cause more severe effects than an inert dust.