Disodium 4,4'-bis(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-ylazo)-1,1'-biphenyl-2,6'-disulphonate

Endpoint summary

Description of key information

Skin Irritation/Corrosion

Non irritant

Eye Irritation/Corrosion

Non irritant

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 April 23 to October 23, 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Abbaye de Bellefontaine (49122 Bêgrolles en Mauges, France)
- Age at study initiation:
- Weight at study initiation: mean weight of 3 kg
- Housing: the rabbits were individually housed in polystyrene cages 0.35 x 0.55 x 0.32 M. Each cage was equipped with a food container and a water bottle.
- Diet (e.g. ad libitum): animals fed ad libitum with a certified pelleted Rabbit diet Ref. 112C (U.A.R., villemoisson sur Orge, France)
- Water: free access to tap water filtered with Millipore filters in water bottles. Routine bacteriological and chemical analysis of water were made, in order to detect major contaminants, by the Laboratoire Municipal, 76000 Rouen, France.
- Acclimation period: for at least seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 50 ± 20 %
- Photoperiod (hrs dark / hrs light): the light/dark cycle was 12 hours per day

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes

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): 0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

3 days

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 6 cm 2
- Type of wrap if used: hydrophilic gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test sample removed by swabbing with a gauze saturated with distilled water.

OBSERVATION TIME POINTS
(indicate if minutes, hours or days)
at 24, 48 and 72 hours

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Reversibility:

other: no clinical signs

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Reversibility:

other: no clinical signs

Irritant / corrosive response data:

As the test sample stained the treated flank, it was impossible to detect slight erythema, but it was considered possible to evaluate well-defined
to severe erythema, had it been present.

Interpretation of results:

other: not classified under Regulation 1272/2008

Conclusions:

Non irritant

Executive summary:

Method

The study was conducted in six New-Zeland white rabbits, according to the recommendations of the OECD Guideline 404.

Results

One hour after the application of the test sample, the staining of the skin of four animals (01, 03, 05, 06) presented observation of slight erythema. However, well-defined erythema, if present, would have been visible. On Day 2, the staining persisted in two animals (03, 06). On Day 3, no erythema and oedema was observed in any animal. The mean erythema score was 0, and the mean oedema score was 0.

Conclusion

Non irritant

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:

From April 23 to October 25, 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1981

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Abbaye de Bellefontaine (49122 Bégrolles en Mauges, France)
- Weight at study initiation: mean weight of 2.5 kg
- Housing: the rabbits were individually housed in polystyrene cages 0.35 x 0.55 x 0.32 m. Each cage was equipped with a food container and a water bottle.
- Diet: animals were fed ad libitum with a certified pelleted Rabbit diet Ref. 112C (U.A.R., Villemoisson sur Orge, France) during the study.
- Water: free access to tap water filtered with Millipore filters in water bottles. Routine bacteriological and chemical analysis of water were made, in order to detect major contaminants, by the Laboratoire Municipal, 76000 Rouen, France.
- Acclimation period: at least seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 50 ± 20 %
- Air changes: the incoming non-recycled air was filtered by an absolute filter
- Photoperiod (hrs dark / hrs light): the light/dark cycle was 12 hours per day.

Vehicle:

not specified

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

Thirty seconds

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: both eyes of three animals (n° 01, 02, 03) were rinsed with 10 ml of sterile salinc solution.

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal: 01, 02, 03

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Reversibility:

other: no clinical signs

Irritation parameter:

iris score

Basis:

animal: 01, 02, 03

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Reversibility:

other: no clinical signs

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: 01

Time point:

24/48/72 h

Score:

ca. 1.66

Max. score:

2

Reversibility:

fully reversible within: 4 days

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: 02, 03

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

2

Reversibility:

fully reversible within: 3 days

Irritation parameter:

chemosis score

Basis:

animal: 01

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

2

Reversibility:

fully reversible within: 3 days

Irritation parameter:

chemosis score

Basis:

animal: 02

Time point:

24/48/72 h

Score:

ca. 0.33

Max. score:

1

Reversibility:

fully reversible within: 2 days

Irritation parameter:

chemosis score

Basis:

animal: 03

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Reversibility:

other: no clinical signs

Irritant / corrosive response data:

One hour after application, conjunctival reactions were observed in all animals. From D6, no ocular reactions were observed in animals no 01, 02, 03, 04, 05. For animal 06, a slight chemosis persisted until D14, and an opacity persisted from D2 to D21.

Interpretation of results:

other: not classified under Regulation 1272/2008

Conclusions:

Non irritant

Executive summary:

Method

The test sample was applied into the conjunctival sac of six New-Zealand rabbits. The eyes of the first three animals were rinsed thirty seconds after application. The study was conducted according to the recommendations of the OECD Guideline 405.

Results

One hour after application, a slight conjunctival reactions were observed in all animals. On Day 5, they had disappeared in five animals. A slight chemosis persisted until Day 14 in animal 06. On Day 2, a diffuse area of opacity, greater than half the corneal surface, was observed in one animal (n° 06). The reaction regressed but persisted until Day 21.

No effect on the iris and cornea of the rinsed animals was observed.

Conclusion

Non irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation/Corrosion

The study was conducted in six New-Zealand white rabbits, according to the recommendations of the OECD Guideline 404.

One hour after the application of the test sample, the staining of the skin of four animals (01, 03, 05, 06) presented observation of slight erythema. However, well-defined erythema, if present, would have been visible. On Day 2, the staining persisted in two animals (03, 06). On Day 3, no erythema and oedema was observed in any animal. The mean erythema score was 0, and the mean oedema score was 0.

Eye Irritation/Corrosion

The test sample was applied into the conjunctival sac of six New-Zealand rabbits. The eyes of the first three animals were rinsed thirty seconds after application. The study was conducted according to the recommendations of the OECD Guideline 405.

One hour after application, slight conjunctival reactions were observed in all animals. On Day 5, they had disappeared in five animals. A slight chemosis persisted until Day 14 in animal 06. On Day 2, a diffuse area of opacity, greater than half the corneal surface, was observed in one animal (n. 06). The reaction regressed but persisted until Day 21.

No effect on the iris and cornea of the rinsed animals was observed.

Justification for classification or non-classification

SKIN IRRITATION/CORROSION

To classify a substance as irritant, the major criterion is that at least 2 of 3 tested animals have a mean score of ≥ 2,3 - ≤ 4,0.

Category 2:

- 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

- 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

- 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.

The substance is not classified a skin irritant because in the performed tests it doesn't meet the classification criteria of the CLP regulation n. 1272/2008.

EYE IRRITATION

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.

Irritating to eyes (Category 2)

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 doesn't meet the classification criteria of the CLP regulation n. 1272/2008.