Bisbenzimidazo[2,1-b:2',1'-i]benzo[lmn][3,8]phenanthroline-8,17-dione

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:

According to OECD 404 and GLP

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:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

according to the Swiss Ordinance relating to GLP [RS 813.016.5]

Test material

Test material information

Constituent 1

Reference substance name:

Bisbenzimidazo[2,1-b:2',1'-i]benzo[lmn][3,8]phenanthroline-8,17-dione

EC Number:

224-597-4

EC Name:

Bisbenzimidazo[2,1-b:2',1'-i]benzo[lmn][3,8]phenanthroline-8,17-dione

Cas Number:

4424-06-0

Molecular formula:

C26H12N4O2

IUPAC Name:

bisbenzimidazo[2,1-b:2',1'-i]benzo[lmn][3,8]phenanthroline-8,17-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
- Source: Charles River Laboratories France, 69592 L'Arbresle, France (SPF breed)
- Age at study initiation: 14 to 15 weeks (male); 12 -14 weeks (females)
- Weight at study initiation (animal#73 male/#74 female/#75 female at the first day of treatment): 2747/2856/2839 g
- Housing: individually in stainless steel cages equipped with feed hoppers and drinking water bowls
- Diet: pelleted standard Provimi Kliba 3418 rabbit maintenance diet; ad libitum
- Water: community tap water; ad libitum
- Acclimation period: 6 days

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

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g test item/per animal was moistened with approximately 0.5 mL of purified water
The pH of the test item was measured before study initiation date. A formulation of a 1 % (w/w) suspension was prepared. The pH value was found to be 7.12.

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3 (1 male, 2 females)

Details on study design:

TEST SITE
- Area of exposure: 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: according to OECD 404 appr. 1, 24, 48 and 72 hours as well as 7, 10 and 14 days after removal of the test item.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

mean

Remarks:

of animals #73, 74, 75 each

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Reversibility inapplicable since no signs of irritation (edema) at any time

Results 2

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of animals #73, 74, 75 each

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Reversibility inapplicable since no signs of irritation (erythema) at any time

Remarks on result:

other: not assessable after 1 h due to staining produced by the test item

Irritant / corrosive response data:

Overall the observations continued for 14 days due to staining present on the skin, not because of positive dermal reactions.

Other effects:

Signs such as erythema could not be evaluated in all animals 1 hour after treatment due to presence of staining produced ba the test item at the application site. Where evaluation was possible, the test item did not cause any skin reactions at the application site of any animal at any of the observation times.
The test item caused a marked orange staing at the test site of all animals 1 hour after treatment and slight orange staining persisted throughout the whole study.
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

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

Conclusions:

Test material is not irritating to skin under these test conditions. Therefore, the test item has not to be classified for skin irritation according to Regulation (EC) No 1272/2008.

Executive summary:

Test material was subject to an acute dermal irritation/corrosion test in 3 New Zealand White rabbits (one male, two females) according to OECD TG 404. No skin reactions occurred during the 4 h exposure to 500 mg of test item (moistened with 0.5 mL purified water) as well as during the following 14 days observation period.

The mean score for oedema and erythema grades was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal separately. The mean score for oedema and erythema was 0 for all three animals. The application of the test item to the skin resulted in slight to marked orange staining produced by the test item of the treated skin in all animals at the 1- hour reading and persisted in all animals up to test day 14, the end of the observation period. Marked orange staining produced by the test item prevented the observation of any possible erythema in all animals at the 1-hour reading. From the 24 -hour reading the assessment of erythema was possible in all animals and no erythema was observed at any time. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed.

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