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

Endpoint summary

Description of key information

Skin irritation:

In an OECD guideline Acute Demal Irritation/Corrosion study in rabbits with Pigment Orange 43 neither erythema nor edema were observed at any reading time in any animal. Therefore, Pigment Orange 43 can be regarded as not skin irritating/corrrosive.

Eye irritation:

In an OECD guideline Acute Eye Irritation/Corrosion study in rabbits with Pigment Orange 43 no relevant ocular reactions were observed at any time in any animal. All signs of irritation were fully reversible within 24 h. Therefore, the test item (Pigment Orange 43) can be regarded as not eye irritating.

Respiratory tract:

Based on available data  the substance is considered likely to behave like an inert dust. Consequently the substance is considered not to exert any local irritative effects. Therefore, it is concluded, that testing is not necessary to reach the scientific conclusion that classification is not warrantable.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

According to OECD 404 and GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

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]

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

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.

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

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.

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.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

According to OECD TG 405 and GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, Stolzenseeweg 32-36, 88353 Kisslegg, Germany (SPF breed)
- Age at study initiation: 11 to 12 weeks (male and females)
- Weight at study initiation (animal#77 male/#78 female/#79 female at the first day of treatment): 2264/2654/2511 g
- Housing: individually in stainless steel cages equipped with feed hoppers and drinking water bowles.
- 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

Vehicle:

unchanged (no vehicle)

Controls:

other: the right eye remained untreated and served as control respectively

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
The pH of a 1 % (w/w) suspension was measured in RCC study No A13195 and was found to be 7.12.

Duration of treatment / exposure:

single instillation (not rinsed after instillation)

Observation period (in vivo):

1, 24, 48, 72 h and 7 d after instillation

Number of animals or in vitro replicates:

3 (1 male, 2 females)

Details on study design:

Application of the substance to the conjunctival sac of the left eye of each animal, the right eye served as control respectively

- Instillation: 100 mg of the undiluted substance

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not rinsed after instillation

SCORING SYSTEM: according to OECD TG 405. Additionally, ocular discharge, reddening of sclerae and staining of conjunctivae, sclerae and cornea by the test item was assessed.

TOOL USED TO ASSESS SCORE: Varta Cliptrix diagnostic -lamp


The eyes are examined and the grade of ocular reaction is recorded at 1, 7, 24, 48, 72 h and 7 d.

The mean scores were calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately.

Irritation parameter:

cornea opacity score

Basis:

animal: # 77, 78, 79 each

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

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

Irritation parameter:

iris score

Basis:

animal: # 77, 78, 79 each

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

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

Irritation parameter:

conjunctivae score

Basis:

animal: # 77

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: initial signs of irritation (conjunctiva) were fully reversible within 24 h

Irritation parameter:

conjunctivae score

Basis:

animal: # 78

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal: # 79

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal: # 77, 78, 79 each

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: initial signs of irritation (chemosis) were fully reversible within 24 h

Irritant / corrosive response data:

No corrosion of the cornea was observed at any of the reading times.

Other effects:

After one hour there were still remnants in the eye or the conjunctival sac in all three animals. Slight discharge was observed in all animals at the 1 h readings. Orange staining was noted 1 h up to 48 h.

Interpretation of results:

GHS criteria not met

Remarks:

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

Conclusions:

All (initial) signs of irritation noted were fully reversible within 72 h. According to the classification criteria of Regulation (EC) No 1272/2008 the test material is not irritating to eyes under these test conditions.

Executive summary:

The test material was subject to a primary eye irritation/corrosion test in 3 New Zealand White rabbits according to OECD 405. No corneal or iridial effects were observed. Conjunctival redness was observed in all animals at one hour after instillation of the test item (scores (redness): 1-1-2) and persisted up to the 48 hour examination in one of these animals. Slight to moderate reddening of the sclerae was present in all animals at the 1 hour reading. Slight ocular discharge was noted at the same time in all animals. As no abnormal findings were observed in the treated eye of any animal 72 hours after treatment or later and the mean values of the observed eye responses fall well below the critical values for classification according to the criteria of Regulation (EC) No 1272/2008, the test material is not irritating to eyes and has not to be classified for eye irritation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin irritation/corrosion:

Mean scores (mean of the 24/48/72 h reading calculated for each animal) for erythema and oedema were below the threshold for classification.

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

Eye irritation/corrosion:

Mean scores (mean of the 24/48/72 h reading calculated for each animal) for conjunctivae, cornea, and iris were below the threshold for classification.

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