2,20-dichloro-13,31-diethyl-4,22-dioxa-13,18,31,36-tetraazanonacyclo[19.15.0.03,19.05,17.06,14.07,12.023,25.024,32.025,30]hexatriaconta-1(36),2,5,7,9,11,14,16,18,20,23,25,27,29,32,34-hexadecaene

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study meets the requirements of OECD Guideline 404 and EU Method B.4 (84/449/EEC)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

84/449/EEC

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,20-dichloro-13,31-diethyl-4,22-dioxa-13,18,31,36-tetraazanonacyclo[19.15.0.0³,¹⁹.0⁵,¹⁷.0⁶,¹⁴.0⁷,¹².0²³,³⁵.0²⁴,³².0²⁵,³⁰]hexatriaconta-1(36),2,5,7(12),8,10,14,16,18,20,23(35),24(32),25,27,29,33-hexadecaene

EC Number:

606-790-9

Cas Number:

215247-95-3

Molecular formula:

C34H22Cl2N4O2

IUPAC Name:

2,20-dichloro-13,31-diethyl-4,22-dioxa-13,18,31,36-tetraazanonacyclo[19.15.0.0³,¹⁹.0⁵,¹⁷.0⁶,¹⁴.0⁷,¹².0²³,³⁵.0²⁴,³².0²⁵,³⁰]hexatriaconta-1(36),2,5,7(12),8,10,14,16,18,20,23(35),24(32),25,27,29,33-hexadecaene

Test material form:

solid: nanoform

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Animal specifics: Hoechst AG, conventional breed
- Source: Hoechst AG, Kastengrund
- Age at study initiation: 2 months to 5 months
- Weight at study initiation: 2,2 kg to 4,1 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls
- Diet (e.g. ad libitum): standard laboratory diet (Albtromin 2123) ad libitum, appr. 15 g hay daily
- Water (e.g. ad libitum): deionized chlorinated water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20° ± 3°C (air-condition)
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: Polyethyleneglycol 400

Controls:

not required

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):1.0 ml to moisten the test item
- Lot/batch no. (if required): Ch-B 2322 , Riedel de Haen AG

Duration of treatment / exposure:

4 hours

Observation period:

3 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: approximately 2.5 cm x 2.5 cm
- Type of wrap if used: surgical gauze patch (Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): flushed with lukewarm tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM:
as in EU Method B.4, assessed approximately 30 - 60 min, 24, 48, and 72 h after the romoval of the test item

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: erythema grade 0, 1 and 2 observed in the three animals at 30-60 min reading were fully reversible within 24 hours

Results 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effects occured

Irritant / corrosive response data:

Scores (oedema or erythema) were 0 at 24, 48 and 72 h after removal of dressing in all animals (see table below for individual data).

Other effects:

Staining produced by the test item was present at all reading time points.

Any other information on results incl. tables

Animal number	Evaluation interval (after removal of dressing)	Erythema score	Oedema score	Violet staining
#1	30 - 60 min	2	0	x
#2		1	0	x
#3		0	0	x
#1	24 hours	0	0	x
#2		0	0	x
#3		0	0	x
#1	48 hours	0	0	x
#2		0	0	x
#3		0	0	x
#1	72 hours	0	0	x
#2		0	0	x
#3		0	0	x

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

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

In a OECD guideline and GLP compliant primary skin irritation test in rabbits, Hostaperm-Violett RL spez. (Pigment Violet 23) caused grade 0-2 erythema after 30-60 minutes, while neither erythema nor edema were observed 24, 48 and 72 hours after application of the test substance. Therefore, Hostaperm-Violett RL spez. (Pigment Violet 23) can be regarded as not skin irritating.

Executive summary:

The primary skin irritation potential of the test item was investigated according to OECD test guideline no. 404. The test item was applied by topical semi-occlusive application of 0.5 g to the intact flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 30 - 60 min, 24, 48 and 72 hours after removal of the dressing. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. The application of the test item to the skin resulted in mild, early-onset and transient signs of irritation such as erythema. These effects were reversible and were no longer evident 24 hours after treatment for all animals. Staining of the treated skin was noted in all animals throughout the whole study. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the skin. Based upon the referred classification criteria (Commission Directive 84/449/EC of April 1984), the test item is considered to be "not irritating" to rabbit skin.