Trisodium bis[4-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]-3-hydroxynaphthalene-1-sulphonato(3-)]chromate(3-)

Endpoint summary

Description of key information

Not skin irritating

Eye Irrit. 2, H319

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 December 13rd to 20th, 2001

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:

1992

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Males

Type of coverage:

semiocclusive

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

Three rabbits

Details on study design:

TEST SITE
- Area of exposure: intact skin.

SCORING SYSTEM
Skin reactions were recorded 1,24,48,72 hours and 7 days after administration. The reactions were assessed according to the Draize J H (1959) "Dermal Toxicity" in Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Assoc. of Food and Drug Officials of the US, Austin, Texas p47.

Primary Irritation Index / Classification
0 Non-iritant
> 0 - 2 Mild initant
> 2 - 5 Moderate initant
5 - 8 Severe initant

Irritation parameter:

erythema score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

< 2.3

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

< 2.3

Reversibility:

fully reversible

Irritant / corrosive response data:

Primary Irritation Index: 2.8
Very slight to well-defined erythema and very slight to slight oedema were noted at all treated skin sites. No other signs of skin irritation were noted. Pink coloured staining was noted at all treated skin sites.

Individual Skin Reactions Following 4-hour Exposure Period

Animal No. Sex	Skin reaction	1 hr	24 hrs	48 hrs	72 hrs	7 days	Mean 24, 48, 2 hrs
124 M	Erythema	1 STA	2 STA	2 STA	1 STA	0	1.7
141 M	Erythema	2 STA	2 STA	2 STA	1 STA	0	1.7
145 M	Erythema	2 STA	2 STA	2 STA	1 STA	0	1.7
Total		(5)	6	(6)	3	0	-
124 M	Oedema	1	2	2	1	0	1.7
141 M	Oedema	2	2	2	1	0	1.7
145 M	Oedema	2	2	1	0	0	1.0
Total		(5)	6	(5)	2	0	-

STA = Pink coloured staining

( ) = Total values not used for calculation of primary irritation index

Sum of 24 and72 How Readings (S): 17

Primary Irritation Index (S/6) and Classification*: 2.8; moderate irritant

Interpretation of results:

other: CLP criteria not met

Conclusions:

Moderate irritant

Executive summary:

The study was performed to assess the irritation of the test material to the skin of the New Zealand White rabbit (SPL Standard Test Method 540.06). The method followed OECD Guidelines for Testing of Chemicals (1992) No. 404 "Acute Dermal Initation/Corrosion" and Method B4 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). A single 4-hour semi-occluded application (0.5 g) of the test material was administered to the intact skin of three rabbits. Skin reactions were recorded 1, 24, 48, 72 hours and 7 days after administration.

Very slight to well-defined erythema and very slight to slight oedema were noted at all treated skin sites. No other signs of skin irritation were noted. Pink coloured staining was noted at all treated skin sites. Primary Irritation Index resulted to be 2.8.

The mean values from gradings at 24, 48 and 72 hours after patch removal were lower than 2.3 in all animals for both erythema/eschar and oedema reactions.

Conclusion

The test material did not meet the criteria for classification as irritant or corrosive according to the CLP Regulations EC 1272/2008. No symbol and risk phrase are required.

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 December 17th, 2001 to January 28th, 2002

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:

1987

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 ml (85 mg) of the test material was administered to the non inigated eye.

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

Three rabbits (1 female and 2 males)

Details on study design:

SCORING SYSTEM
Ocular reactions were recorded 1, 24, 48 and 72 hours, 7, 14 and 21 days after administration.

Irritation parameter:

cornea opacity score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

>= 1 - < 3

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

>= 2

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

>= 2

Reversibility:

fully reversible

Irritant / corrosive response data:

Maximum Group Mean Score: 41.0; at least a moderate irritant (class 5 ona 1- 8 scale).

The test material produced scattered or diffuse to translucent corneal opacity, iridial inflammation and moderate to severe conjunctival irritation. Other ocular effects noted were petechial haemorrhage of the nictitating membrane or haemorrhage of the nictitating and lower conjunctival membranes.

Individual and Mean Scores for Cornear lris and Conjunctivae for EU Labelling Regulations

	33 Female			Mean 24/48/72 hrs	18 Male			Mean 24/48/72 hrs	25 Male			Mean 24/48/72 hrs
Time After Treatment	24 hrs	48 hrs	72 hrs		24 hrs	48 hrs	72 hrs		24 hrs	48 hrs	72 hrs
Degree of Comeal Opacity	2S	2S	1	1.7	1	1	1	1.0	1S	2S	2S	1.7
Iridial Inflammation	1S	1S	1	1.0	1	1	1	1.0	1S	1S	1S	1.0
Conjunctival Redness	2S	2S	2H	2.0	2SPt	2S	2	2.0	3S H*	3S H*	2S H*	2.7
Conjunctival Chemosis	2	2	2	2.0	3	2	1	2.0	3	3	2	2.7

Individual Scores for Ocular Irritation

	33 Female							18 Male						25 Male
Time After Treatment	1hr	24 hrs	48 hrs	72 hrs	7 dy	14 dy	21 dy	1hr	24 hrs	48 hrs	72 hrs	7 dy	14 dy	1hr	24 hrs	48 hrs	72 hrs	7 dy	14 dy	21 dy
Degree of Comeal Opacity (E)	?s	2S	2S	1	0	0	0	?s	1	1	1	0	0	?s	1S	2S	2S	1S	1	0
Area of Corneal Opacity (F)	?s	2	1	1	0	0	0	?s	4	3	2	0	0	?s	4	4	3	2	1	0
Score (ExF)x5	0-80	20	10	5	0	0	0	0-80	20	15	10	0	0	0-80	20	40	30	10	5	0
Iridial Inflammation (D)	?s	1S	1S	1	0	0	0	?s	1	1	1	1	0	?s	1S	1S	1S	1S	1	0
Score (Dx5)	0-10	5	5	5	0	0	0	0-10	5	5	5	5	0	0-10	5	5	5	5	5	0
Conjunctival Redness (A)	?s	2S	2S	2H	1H	1H	0	?s	2SPt	2S	2	1	0	?s	3S H*	3S H*	2S H*	2 H*	1	0
Conjunctival Chemosis (B)	2	2	2	2	0	0	0	2	3	2	1	1	0	2	3	3	2	1	1	0
Conjunctival Discharge (C)	3Sf	3Sf	2Sf	1Sf	0Sf	0Sf	0Sf	3Sf	3Sf	2	1	0Sf	0Sf	3Sf	3Sf	3Sf	2Sf	1Sf	0Sf	0Sf
Score (A+B+C)x2	10-16	14	12	10	2	2	0	10-16	16	12	8	4	0	10-16	18	18	12	8	4	0
Total Score	10-106	39	27	20	2	2	0	10-106	41	32	23	9	0	10-106	43	63	47	23	14	0

IPR = initial pain reaction

?s = purple/pink caloured staining prevented evalualion

S = purple/pink caloured staining

Sf = purple/pink caloured staining of the fur

H* = two areas of haemorrhage, approximately 2 mm x 2 mm in size, on edge of the nictitating membrane and lower conjunctival membrane

Pt = Petechial haemorrhage over the nictitating membrane

Interpretation of results:

other: Eye Irrit. 2 (H319) according to the CLP Regulation (EC 1272/2008)

Conclusions:

Eye irritant

Executive summary:

The study was performed to assess the irritation of the test material to the eye of the New Zealand White rabbits (SPL Standard Test Method 560.07). The method followed OECD Guidelines for Testing of Chemicals (1987) No. 405 "Acute Eye Irritation/Corrosion" and Method B5 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

A single application of 0.1 ml (85 mg) of the test material was administered to the eye of three rabbits. Ocular reactions were recorded 1, 24, 48 and 72 hours, 7, 14 and 2l days after administration.

Maximum Group Mean Score: 41.0; at least a moderate irritant (class 5 ona 1- 8 scale). The test material produced scattered or diffuse to translucent corneal opacity, iridial inflammation and moderate to severe conjunctival irritation. Other ocular effects noted were petechial haemorrhage of the nictitating membrane or haemorrhage of the nictitating and lower conjunctival membranes.

The mean values from gradings at 24, 48 and 72 hours were:

- cornea score was equal/higher than 1 and lower than 3 in all the animals tested;

- iris score was equal to 1 in all rabbits;

- redness and oedema scores were equal/higher than 2 in all rabbits.

All the reactions resulted to be reversible within 21 days.

Conclusion

The test material meets the criteria for classification as eye irritant, category 2 (H319) of the CLP Regulations EC 1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

SKIN IRRITATION/CORROSION

A study was performed to assess the irritation of the Acid Violet 090 (AV090) to the skin of the New Zealand White rabbit. A single 4-hour semi-occluded application (0.5 g) of the test material was administered to the intact skin of three rabbits. Very slight to well-defined erythema and very slight to slight oedema were noted at all treated skin sites. No other signs of skin irritation were noted. Pink coloured staining was noted at all treated skin sites (Clariant SE, 2002).

An available summary reported some toxicological characteristics of AV090 (85 %; remaining composition sodium chloride and sodium sulfate) and included information on irration supports the study outcomes. Unfortunately the original study report is no more available. The information included in the toxicological characteristics sheet indicate the substance as not skin irritating (BASF SE, 1976).

EYE IRRITATION

The eye irritation potential of AV090 has been investigated following the OECD Guidelines 405 testing procedures. The test material produced scattered or diffuse to translucent corneal opacity, iridial inflammation and moderate to severe conjunctival irritation. Other ocular effects noted were petechial haemorrhage of the nictitating membrane or haemorrhage of the nictitating and lower conjunctival membranes. The substance was judged as at least a moderate irritant (class 5 ona 1- 8 scale) (Clariant SE, 2002).

The experiment conclusions agree with the information included into an available summary, which reports some toxicological characteristics of AV090 (85 %; remaining composition sodium chloride and sodium sulfate). Unfortunately the original study report is no more available. The information included in the toxicological characteristics sheet indicate the substance as slightly eye irritating (BASF SE, 1976).

REFERENCE

BASF SE. 1976. Ergrbnis der gewerbetoxikologischen vorprüfung. Testing laboratory: BASF AG. Date: 1976-11-26

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), 3.2 Skin corrosion/irritation section, skin Irritation means the production of reversible damage to the skin following the application of a test substance for up to 4 hours.

The mean values from gradings at 24, 48 and 72 hours after patch removal were lower than 2.3 in all animals for both erythema/eschar and oedema reactions.

According to the Regulation 1272/2008 (CLP) substances that have the potential to induce reversible eye irritation are classified in Category 2 (irritating to eyes) 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 mean values from gradings at 24, 48 and 72 hours were:

- cornea score was equal/higher than 1 and lower than 3 in all the three animals tested;

- iris score was equal to 1 in all three rabbits;

- redness and oedema scores were equal/higher than 2 in all three rabbits.

All the reactions resulted to be reversible within 21 days.

In conclusion, Acid Violet 090 is not classified for the skin irritation. On the contrary, it is classified as Eye. Irrit. 2 (H319), according to the CLP Regulation (EC 1272/2008).