5,12-dihydro-2,9-dimethylquino[2,3-b]acridine-7,14-dione

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 June 2005 to 10 August 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study meets or exceeds the requirements of OECD Guideline 404 and EU Method B.4

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

A gauze patch of approximately 4 cm x 4 cm (instead of 6 cm2) was used to guarantee good contact and uniform distribution of the test substance on the skin

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

as above

GLP compliance:

yes (incl. QA statement)

Remarks:

Study in compliance with Swiss Ordinance relating to GLP, which is based on OECD Principles of GLP

Test material

Test material information

Constituent 1

Reference substance name:

5,12-dihydro-2,9-dimethylquino[2,3-b]acridine-7,14-dione

EC Number:

213-561-3

EC Name:

5,12-dihydro-2,9-dimethylquino[2,3-b]acridine-7,14-dione

Cas Number:

980-26-7

Molecular formula:

C22H16N2O2

IUPAC Name:

2,9-dimethyl-5,7,12,14-tetrahydro-5,12-diazapentacene-7,14-dione

Test material form:

solid: nanoform

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Animal specifics: SPF
- Source: Charles River Laboratories, L'Arbresle, France
- Age at study initiation: 12 weeks (male), 12-13 weeks (females)
- Weight at study initiation: 2741 g for the male, 2873 g and 2674 g for the two females, all within the normal range of variability
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls
- Diet (e.g. ad libitum): standard laboratory diet ad libitum
- Water (e.g. ad libitum): community tap water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C (air-condition)
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

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): 0.5 ml of purified water were used to moisten the test item

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: approximately 4 cm x 4 cm
- Type of wrap if used: surgical gauze patch

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 1, 24, 48, and 72 h after the romoval of the test item as well as after 7, 10 and 14 d

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not relevant since no effects

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h after treatment

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not relevant since no effects

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not relevant since no effects

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not relevant since no effects

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not relevant since no effects

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Apart from animal #2 at 24 h, all other scores (oedema or erythema) were 0 at all time points in all animals (see below for individual data).

Other effects:

No clinical signs or effects on body weight were observed. Erythema scores could not be assessed in all animals at 1 h due to marked staining produced by the test item

Any other information on results incl. tables

Animal number	Sex	Evaluation interval (after removal of dressing )	Erythema score	Oedema score
#1	M	1 hour	not assessible due to staining	0
#2	F			0
#3	F			0
#1	M	24 hours	0	0
#2	F		1	0
#3	F		0	0
#1	M	48 hours	0	0
#2	F		0	0
#3	F		0	0
#1	M	72 hours	0	0
#2	F		0	0
#3	F		0	0
#1	M	7 days	0	0
#2	F		0	0
#3	F		0	0
#1	M	10 days	0	0
#2	F		0	0
#3	F		0	0
#1	M	14 days	0	0
#2	F		0	0
#3	F		0	0

Applicant's summary and conclusion

Interpretation of results:

not irritating

Conclusions:

According to the classification criteria of Regulation (EC) No 1272/2008 the test item is not irritating to skin under these test conditions.

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 left 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 1, 24, 48 and 72 hours, as well as 7, 10 and 14 days 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 mean erythema/eschar score of the three animals was 0.00, 0.33 and 0.00, respectively and the mean oedema score was 0.00 for all three animals.

The application of the test item to the skin resulted in mild, early-onset and transient signs of irritation such as redness. These effects were reversible and were no longer evident 48 hours after treatment for all animals. However, staining by the red test item prevented the assessment of a possible erythema in all animals one hour after treatment. The slight to marked staining of the treated skin was noted in all animals throughout the whole study, effectively. 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.

Therefore, the test item has not to be classified for skin irritation according to Regulation (EC) No 1272/2008.