2-[(2-methoxy-4-nitrophenyl)azo]-N-(2-methoxyphenyl)-3-oxobutyramide

Endpoint summary

Description of key information

Skin irritation:
Pigment Yellow 74 has been tested in vivo for irritative properties in several skin irritations tests in rabbits (including studies

done according to the OECD test guideline and GLP). The substance caused no or only slight, transient irritation to the skin. The individual and group mean of scores read 1, 2 and 3 days after treatment were well below the classification criteria of the EU dangerous substances directive. Therefore, the test item (Pigment Yellow 74) can be regarded as not skin irritating.
Eye irritation:
Pigment Yellow 74 has been tested in vivo for irritative properties in several eye irritations tests in rabbits (including studies done according to the OECD test guideline and GLP). The substance caused no or only slight, transient irritation to the eye. The individual and group mean of scores read 1, 2 and 3 days after treatment were well below the classification criteria of the EU dangerous substances directive. Therefore, the test item (Pigment Yellow 74) can be regarded as not eye irritating.
Respiratory tract:
Study was waived; substance is not classified for this endpoint. The substance is considered not to exert any special local irritative or systemic adverse effects; the substance is considered likely to behave like an inert dust.
Non-human information: This information is not available.
Human information: No human information is available

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:

7 Feb - 16 Apr 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The test was performed in accordance with OECD and GLP guidelines.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Toxicology Department Rallis Research Centre, Bangalore, India
- Age at study initiation: 4 months
- Weight at study initiation: 2.37-2.68 kg
- Housing: individually in fibreboard cages
- Diet (e.g. ad libitum): Amrut rabbit feed, Nav Maharashta Chakan Oil Mills Ltd, Pune, India, ad libitum
- Water (e.g. ad libitum): purified deep bore well water, ad libitum
- Acclimation period: 7-8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23 °C
- Humidity (%): 30-70 % relative humidity
- Air changes (per hr): adequate fresh air supply
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: paraffin oil

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g, a paste was prepared with paraffin oil
- Treatment: On each animal, one patch with the test substance for every exposure period and one patch with the the vehicle alone were applied.

Duration of treatment / exposure:

3 minutes, 1 and 4 hours

Observation period:

1, 24, 48 and 72 hours after patch removal

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2x3 cm cotton gauze with test substance on it
- Type of wrap if used: Johnson-plast USP adhesive tape and crepe bandage


REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure: 3 minutes, 1 and 4 hours


SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

mean

Remarks:

mean of 3 animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not relevant since no effects occurred

Irritation parameter:

edema score

Basis:

mean

Remarks:

mean of 3 animals

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not relevant since no effects occurred

Irritant / corrosive response data:

No skin reactions were observed. At 1, 24, 48 and 72 hours erythema and edema scores were 0 for all three animals and all treatment periods.

Other effects:

No pre-terminal deaths were observed. Body weights of all the rabbits increased during the observation period.

Interpretation of results:

not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

67/548/EEC: Skin irritation: no classification warranted
1272/2008/EC: Skin irritation: no classification warranted

In a OECD guideline and GLP compliant skin irritation test in rabbits, Hansa Brilliant Yellow 5GX IN (Pigment Yellow 74) did not cause signs of skin irritation.

Reference 2

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

Reference

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:

other: The test was performed in accordance with OECD and GLP guidelines.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Toxicology Department Rallis Research Centre, Bangalore, India
- Age at study initiation: 4 months
- Weight at study initiation: 2.43-2.66 kg
- Housing: individually in fibreboard cages
- Diet (e.g. ad libitum): Amrut rabbit feed, Nav Maharashta Chakan Oil Mills Ltd, Pune, India, ad libitum
- Water (e.g. ad libitum): purified deep bore well water, ad libitum
- Acclimation period: 7-8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23 °C
- Humidity (%): 30-70 % relative humidity
- Air changes (per hr): adequate fresh air supply
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 14 mg, equivalent to 0.1 ml

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

1, 24, 48 and 72 hours after treatment end

Number of animals or in vitro replicates:

3

Details on study design:

SELECTION OF ANIMALS: The eyes of the rabbits were observed one day prior to the test item instillation for signs of eye irritation, ocular defects or pre-existing corneal injury and as the rabbits were free of all these signs, they were selected for the study.

REMOVAL OF TEST SUBSTANCE
- Washing: after 24 hours, the treated eye was irrigated with deionised water to remove residual test item; the control eye was washed similarly.
- Time after start of exposure: 24 hours


SCORING SYSTEM: Draiz scoring system

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: after 24, 48 and 72 hrs

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable since no effect

Remarks on result:

other: including opacity and area

Irritation parameter:

iris score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable since no effect

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hrs

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable since no effect

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0.11

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

One animal showed a grade 1 conjunctival redness at the 24 hour reading. All other readings of conjunctival redness, chemosis, discharge, iris or cornea effects in all three animals at all reading times (1 hour, 24, 48 and 72 hours) were grade 0.

Other effects:

No pre-terminal deaths were observed. Body weights of all the rabbits increased during the observation period. No abnormal necropsy findings were observed.

Interpretation of results:

not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

67/548/EEC: Eye irritation: no classification warranted
1272/2008/EC: Eye irritation: no classification warranted

In an OECD guidline and GLP compliant eye irritation test in rabbits, a Hansa Brilliant Yellow 5GX IN (Pigment Yellow 74) did only cause very mild, transient signs of eye irritation, but has not to be classified as eye irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation was tested in a guideline study according to OECD guideline 404 and GLP in rabbits (Rallis, 2001). 0.5 g test substance were applied semi-occlusively to the shaved skin of rabbits. Patches were removed after 3 minutes, 1 hours or 4 hours. No skin reactions were observed. In another guideline study (Hoechst, 1977), one hour up to three days after treatment, the skin showed very slight to well-defined erythema and at one hour also very slight oedema. Mean scores on days 1, 2 and 3 after application were 0.7, 1.7 and 1.0 for the three animals. Maximum values did not exceed a score of 2. The irritative effects can probably be attributed to the resin component of the test substance and not to Pigment Yellow 74 itself. This was also confirmed in another study (Hoechst, 1975) that was conducted similar to OECD guideline 404 and in which Pigment Yellow 74 did not cause any erythema or oedema at any time point. Two further studies that were considered unreliable also did not find any skin irritation properties of the diluted or water-extracted substance.

Eye irritation was tested in two guideline studies according to OECD guideline 405 and GLP in rabbits. In both studies, the test substance did not influence the cornea or iris. In one study (Rallis, 2001), a grade 1 conjunctival redness was observed in one of three rabbits only at the 24 hour reading. No other effects occurred. The mean score for three animals on day 1, 2 and 3 for redness of the conjunctiva was 0.1. In the second study (Anon., 1992), the mean score for three animals on day 1, 2 and 3 for chemosis and redness of the conjunctiva was 0.1 and 0.7, respectively. The irritative effects was probably caused by the resin component of the test substance and to a far lesser degree by Pigment Yellow 74 itself. This was confirmed in another two studies (Hoechst, 1977; 1975) that were conducted similar to OECD guideline 405 and in which Pigment Yellow 74 caused similar slight transient eye irritation. One further study that was considered unreliable did not find any eye irritation properties of the water-extracted substance.

Justification for classification or non-classification

Pigment Yellow 74 has been tested in vivo for irritative properties in skin irritation tests in rabbits. The substance caused no irritation to the skin. The individual and group mean of scores read 1, 2 and 3 days after treatment were well below the classification criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC). Therefore, Pigment Yellow 74 does not have to be classified as skin irritating.

 

Pigment Yellow 74 has been tested in vivo for irritative properties in four eye irritation tests in rabbits. The substance caused only very slight, transient irritation to the eyes. The individual and group mean of scores read 1, 2 and 3 days after treatment were well below the classification criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC). Therefore, Pigment Yellow 74 does not have to be classified as eye irritating.

 

It can reasonably be deduced that Pigment Yellow 74 does not cause respiratory tract irritation and thus does not have to be classified according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC), because Pigment Yellow 74 did cause no or only slight, fully reversible irritative effects in the eyes and on the skin and does not have to be classified as either skin or eye irritating. Moreover, Pigment Yellow 74, in the unlikely event of being inhaled as a dust, is considered not to cause more severe effects than an inert dust, because its chemical inertness and extremely low solubility in water and n-octanol largely prevent interaction with living cells and tissues.