Chromate(1-), bis[4-[[4-(ethylsulfonyl)-2-hydroxyphenyl]azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, compd. with 1,6-hexanediamine (2:1)

Endpoint summary

Description of key information

The test article was not irritating to the rabbit skin and to the 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:

experimental study

Adequacy of study:

key study

Study period:

March 10, 2015 - March 31, 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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: Harlan Laboratories, Netherlands
- Age at study initiation: Approx. 6 - 8 months
- Weight at study initiation: 3.50 kg – 4.34 kg
- Housing: Single housing in stainless steel wire mesh cages with grating with shallow cage body; floor area: 4225 cm2
- Diet: STANRAB (P) SQC; SDS Special Diets Services, 67122 Altrip, Germany
- Water: tap water ad libitum
- Acclimation period: at least 5 days before application

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): Approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: March 16, 2015 To: March 30, 2015

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: Minimally moistened with highly deionized water

Controls:

other: Untreated skin sites of the same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g

Duration of treatment / exposure:

4 h

Observation period:

7 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Flank
- Type of wrap if used: The test item was covered with a test patch (Idealbinde, Pfälzische Verbandstoff-Fabrik, Kaiserslautern) and Fixomull® stretch (adhesive fleece), Beiersdorf AG

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test item was removed at the end of the exposure period with Lutrol® and Lutrol® / water (1 : 1).

SCORING SYSTEM: according to OECD guideline 404:

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 eschar formation preventing grading of erythema

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 approx. 1 mm)
4: Severe edema (raised more than 1 mm and extending beyond area of exposure)

Irritation parameter:

erythema score

Basis:

mean

Remarks:

all three animals

Time point:

24/48/72 h

Score:

0.8

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

mean

Remarks:

all three animals

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

In two animals very slight erythema (grade 1) was noted immediately after removal of the patch and persisted in one of these animals up to hour 24. In the other animal well-defined erythema (grade 2) was observed from hour 1 until hour 24 after removal of the patch. Thereafter, erythema decreased to very slight erythema (grade 1) from hour 48 until hour 72. Due to the red discoloration of the application area, erythema was not assessable immediately and one hour after removal of the patch in the third animal. Thereafter, erythema could be determined and very slight erythema (grade 1) was observed from hour 24 until hour 48. The cutaneous reactions were reversible in two animals within 72 hours and in one animal within 7 days after removal of the patch.

Interpretation of results:

GHS criteria not met

Conclusions:

Considering the described cutaneous reactions as well as the average score for irritation, the test article does not show a skin irritating potential under the test conditions chosen.

Executive summary:

The potential of the test article to cause acute dermal irritation or corrosivity was assessed by a single topical application of an amount of 0.5 g of the test item for 4 hours to the intact skin of three New Zealand White rabbits (stepwise procedure starting with one animal and supplementing two additional animals), using a patch of 2.5 cm x 2.5 cm, covered with semi-occlusive dressing. After removal of the patch the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch and on study day 7. Very slight to well-defined erythema (grade 1 to 2) were recorded during the course of the study. Due to the red discoloration of the application area, erythema was not assessable in one animal immediately and one hour after removal of the patch. The cutaneous reactions were reversible in two animals within 72 hours and in one animal within 7 days after removal of the patch. Mean scores over 24, 48 and 72 hours for each animal were 0.7, 1.3 and 0.3 for erythema and 0.0, 0.0 and 0.0 for edema. Considering the described cutaneous reactions as well as the average score for irritation, the test article does not show a skin irritating potential under the test conditions chosen.

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:

1980-01-07 to 1980-01-21

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: Guidelines of the United States Environmental Protection Agency (EPA) § 163.81-4 "Primary eye irritation study". Federal Register, Vol. 43, No. 163, August 22, 1978

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: in house breed
- Weight at study initiation: 2 - 3 kg
- Housing: individually in metal cages
- Diet: ad libitum, standard diet (NAFAG, No. 814, Gossau SG)
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 55±10
- Photoperiod (hrs dark / hrs light): 14/10

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 g

Duration of treatment / exposure:

single instillation, washing out was conducted for 3/6 animals after 30 sec.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: 10 mL physiological saline
- Time after start of exposure: 30 sec

SCORING SYSTEM: According to Draize et al. (1959)

TOOL USED TO ASSESS SCORE: hand-slit lamp

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: unrinsed

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: unrinsed

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

other: unrinsed

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: unrinsed

Irritant / corrosive response data:

No irritations were seen in any of the tested animals.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this experiment the test material was found to cause no irritation when applied to the rabbit eye mucosa.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation

The potential of the test article to cause acute dermal irritation or corrosivity was assessed by a single topical application of an amount of 0.5 g of the test item for 4 hours to the intact skin of three New Zealand White rabbits (stepwise procedure starting with one animal and supplementing two additional animals), using a patch of 2.5 cm x 2.5 cm, covered with semi-occlusive dressing. After removal of the patch the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch and on study day 7. In two animals very slight erythema (grade 1) was noted immediately after removal of the patch and persisted in one of these animals up to hour 24. In the other animal well-defined erythema (grade 2) was observed from hour 1 until hour 24 after removal of the patch. Thereafter, erythema decreased to very slight erythema (grade 1) from hour 48 until hour 72. Due to the red discoloration of the application area, erythema was not assessable immediately and one hour after removal of the patch in the third animal. Thereafter, erythema could be determined and very slight erythema (grade 1) was observed from hour 24 until hour 48. The cutaneous reactions were reversible in two animals within 72 hours and in one animal within 7 days after removal of the patch. Mean scores over 24, 48 and 72 hours for each animal were 0.7, 1.3 and 0.3 for erythema and 0.0, 0.0 and 0.0 for edema. Considering the described cutaneous reactions as well as the average score for irritation, the test article does not show a skin irritating potential under the test conditions chosen.

Two older supporting studies with more stringent procedures (24 h exposure) yielded similar non-irritating results.

Eye irritation

Following the experimental design according to Federal Register, Vol. 43, No. 163, § 163.81-4, 22. Aug. 1978 (EPA), 0.1 g of the test substance was instilled into the conjunctival sac of 6 New Zealand White rabbits (3/sex). In three out of 6 animals the treated eye was washed with 10 mL of physiological saline after 30 sec of treatment. Animals were then observed for 7 days. Irritation was scored by the method of Draize. No irritations were seen in any of the tested animals either with washed or unwashed eyes. The substance is not regarded as eye irritating under the above test conditions (Ciba-Geigy, 1980).

In a supporting study performed by a similar method, no irritations were seen in any of the tested animals either with washed or unwashed eyes. The substance is not regarded as eye irritating under the above test conditions.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance does not need to be classified and labelled for eye and skin irritation under Regulation (EC) No 1272/2008.