Sodium bis[2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]chromate(1-)

Endpoint summary

Description of key information

Non irritant to intact rabbit skin.

Non irritant to rabbit eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

From November 18 to November 25,1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The complete read across justification is detailed in section 13. Source study has reliability 2.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG 4414 Fuellinsdorf / Switzerland
- Age at study initiation: ca. 14 weeks
- Weight at study initiation: 2.3 - 3.0 kg
- Housing: animals were caged individually in stainless steel cages with automatic drinking water supply and cleaning system
- Diet: pelleted standard kliba 23/341/1, rabbit maintenance diet defined for acceptable contaminant level, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 55 ± 10 %
- Photoperiod: 12 hours cycle dark/light

Type of coverage:

occlusive

Preparation of test site:

clipped

Remarks:

ca 10 × 10 cm

Vehicle:

other: PEG 400 + physiological saline solution (70:30)

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 1 g of a 50 % diluition of test material in polyethylene glycol (PEG400) + saline (70:30) was applied under a patch of surgical gauze ca. 3 × 3 cm.

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, 72 hours after treatment.

Number of animals:

3 rabbits (1 male and 2 females)

Details on study design:

TEST SITE
- Clipped area: 10 x 10 cm
- Type of wrap if used: surgical gauze 3 cm x 3 cm. When the patch was in place it was covered with impermeable material and fastened to the body with adhesive tape

SCORING SYSTEM: Draize J.H 1959
Erythema and eschar formation
0 no erythema
1 very slight erythema (barely perceptible)
2 well defined erythema
3 moderate to severe erythema
4 severe erythema (beet redness) to slight eschar formation (injuries in depth)

Edema formation
0 no edema
1 very slight edema (barely perceptible)
2 slight edema (edges of area well defined by definite raising)
3 moderate edema (raised approximately 1 mm)
4 severe edema (raised more than 1 mm and extending beyond area of exposure)

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: no skin reaction observed

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: no skin reaction observed

Test substance showed no irritation, when applied to intact rabbit skin. No destruction or irreversible alterations of the treated skin were observed.

In the area of application a marked to slight orange discolouration of the skin was observed in all rabbits within 1 to 72 hours after removal of the bandage.

No acute toxicological signs were observed in the animals durin g the test period.

All rabbits were killed at the end of the observation period. Due to the results obtained, no macroscopical organ examination was indicated.

Interpretation of results:

other: Not classified according to the CLP Regulation (EC n. 1272/2008)

Conclusions:

Under the conditions of the experiment the test material was found to cause no irritation when applied to intact rabbit skin.

Executive summary:

Method

The substance was tested for skin irritation according to the OECD guideline 404. The dorsal area of 3 rabbits was clipped and test substance was applied under occlusive patch for 4 hours. Reactions were scored 1 hour, 24, 48 and 72 hours after removal according to the Draize score.

Results

Under test conditions, the substance was found to cause no irritation when applied to intact rabbit skin. In the area of application a marked to slight orange discoloration of the skin was observed in all rabbits within 1 to 72 hours after removal of the bandage. No corrosion effect had occurred on the skin.

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:

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

Adequacy of study:

key study

Study period:

From November 18 to 25, 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The complete read across justification is detailed in section 13. Source study has reliability 2.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1981

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG 4414 Fuellinsdorf / Switzerland
- Age at study initiation: ca. 14 weeks
- Weight at study initiation: 2.3 - 3.0 kg
- Housing: animals were caged individually in stainless steel cages with automatic drinking water supply and cleaning system
- Diet: pelleted standard Kliba 23/341/1, rabbit maintenance diet defined for acceptaeble contaminant level, ad libitum
- Water: tap water, ad libitum.
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 55 ± 10 %
- Photoperiod: 12 hours cycle dark/light

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 g to the left eye of each animal

Duration of treatment / exposure:

single application into conjunctival sac

Observation period (in vivo):

1, 24, 48, 72 hours after treatment.

Number of animals or in vitro replicates:

3 rabbits (1 male and 2 females)

Details on study design:

SCORING SYSTEM: Draize J.H. 1959
Cornea opacity and degree of density (most dense area scored)
0 no opacity
1 scattered or diffuse area, details of iris clearly visible
2 easily discernible translucent areas, details of iris slightly obscured
3 opalescent areas, no details of iris visible, siz eof pupils barely discernible
4 opaque, iris invisible

Iris
0 normal
1 folds above normal, congestion, swelling, circumcornea injection (nay or all of these or combination of any thereof) iris still reacting to light (sluggish reaction is positive)
2 no reaction to light, hemorrage, gross destruction (any or all of these)

Conjunctivae redness (refers to palpebral and bulbar conjunctiva excluding cornea and iris)
0 vessels normal
1 vessels definitely injected above normal
2 more diffuse, deeper crimson red, individual vessels not easily discernible
3 diffuse beefy red

Conjuctivae chemosis
0 no swelling
1 any swelling above normal (includes nictitating membrane)
2 obvious swelling with partial eversion of lids
3 swelling with lids about half closed
4 swelling with lids about half to completely closed

Irritation parameter:

cornea opacity score

Basis:

animal: all

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: no eye reaction observed

Remarks on result:

other: not rinsed

Irritation parameter:

iris score

Basis:

animal: all

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

2

Reversibility:

other: no eye reaction observed

Remarks on result:

other: not rinsed

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: all

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

3

Reversibility:

other: no eye reaction observed

Remarks on result:

other: not rinsed

Irritation parameter:

chemosis score

Basis:

animal: all

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: no eye reaction observed

Remarks on result:

other: not rinsed

Other effects:

No discoloration of the cornea and conjunctivae was observed in the rabbits during the entire test period, which could be related to compound effects.
No acute toxicological signs were observed in the rabbits during the test period.

Upon sacrifice, no macroscopical organ examination was indicated, due to the results obtained.

Interpretation of results:

other: Not classified according to the CLP Regulation (EC n. 1272/2008)

Conclusions:

Under test conditions, test substance was found to cause no irritation when applied to the rabbit eye mucosa.

Executive summary:

Method

The substance was evaluated for eye irritation/corrosion according to the OECD guideline 405. Test substance was applied to the left eye of each animal and the eye was not rinsed. The right eye served as control.Reactions were scored 1 hour, 24, 48 and 72 hours after application.

Results

Under test conditions, the substance was found to cause no irritation when applied to the rabbit eye mucosa. No discoloration of the cornea and conjunctiva which could be related to compound effect was observed. No corrosion effect was observed at each of the measuring intervals.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No information is available on the substance itself, i.e. Solvent Orange 062 acid. However, a study on a read across substance, i.e. Solvent Orange 062 sodium salt containing some amounts of its acid form, was available and used for the assessment. A detailed description of the read across process was attached in section 13.

Skin irritation

The substance was tested for skin irritation according to OECD guideline 404. Under test conditions, no signs of skin irritation were noted. In the area of application a marked to slight orange discolouration of the skin was observed in all rabbits within 1 to 72 hours after removal the bandage. No acute toxicological signs were seen in animals during the test period.

Eye irritation

The substance was tested for eye irritation/corrosion according to OECD guideline 405. During the test, the eye was not rinsed, however, no signs of irritation were noted. No discolouration of the cornea and conjunctivae, related to compound effects, was observed. No acute toxicological signs were seen in animals during the test period.

Justification for classification or non-classification

Skin Irritation

According to the CLP Regulation (EC 1272/2008), skin corrosion means the production of irreversible damage to the skin, and skin irritation means the production of reversible damage to the skin following the application of a test substance for up to 4 hours.

A substance has to be classified as category 1 (corrosive) if it produces destruction of skin tissue, namely, visible necrosis through the epidermis and into the dermis, in at least 1 tested animal after exposure up to a 4 hour duration.

 

A substance has to be classified as category 2 (irritant) if shows:

(1) mean value of ≥ 2,3 - ≤ 4,0 for erythema/ eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions; or

(2) inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or

(3) in some cases where there is pronounced variability of response among animals, with very definite positive effects related to chemical exposure in a single animal but less than the criteria above.

 

Under the test condition, no signs of irritation were observed, thus no classification applied. Based on the read across approach, Solvent Orange 062 was considered as non irritant to skin.

 

Eye Irritation

According to the CLP Regulation (EC 1272/2008), serious eye damage means the production of tissue damage in the eye, or serious physical decay of vision, following application of a test substance to the anterior surface of the eye, which is not fully reversible within 21 days of application .

Eye irritation means the production of changes in the eye following the application of test substance to the anterior surface of the eye, which are fully reversible within 21 days of application.

 

A substance has to be classified as category 1 (Irreversible effects on the eye), If, when applied to the eye of an animal, a substance produces:

— at least in one animal effects on the cornea, iris or conjunctiva that are not expected to reverse or have not fully reversed within an observation period of normally 21 days; and/ or

— at least in 2 of 3 tested animals, a positive response of:

— corneal opacity ≥ 3 and/or

— iritis > 1,5 calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material.

 

A substance has to be classified as category 2 (irritating to eye) if, when applied to the eye of an animal, a substance produces:

at least in 2 of 3 tested animals, a positive response of:

-          corneal opacity ≥ 1 and/or

-          iritis ≥ 1, and/or

-          conjunctival redness ≥ 2 and/or

-          conjunctival oedema (chemosis) ≥ 2

calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days.

The substance did not show any effect on eye, thus no classification applied. Based on a read across approach, Solvent Orange 062 was considered as non irritant to eye.