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

Endpoint summary

Description of key information

Acute oral toxicity:

The test item (Pigment Orange 43) did not cause any mortality or clinical signs after single oral gavage administration to female rats at 2000 mg/kg bw in a valid guideline study. The relevance and the reason for the congestion in the lungs in three of six animals at necropsy was unclear beacause

• no impairment of breathing was observed
• no signs of toxicity were observed in another acute oral toxicity study in mice (max. dose 10000 mg/kg) and
• no congestion in the lungs or impairment of breathing were observed in a Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test in rats (max. dose: 1000 mg/kg bw/d).

Acute dermal toxicity:

Study was waived and classification for this endpoint is considered unwarranted, beacause the substance is not likely to become systemically available after dermal exposure and there was no evidence of toxicity observed in any of the endpoints tested.

Acute inhalation toxicity:

Study was waived and classification for this endpoint is considered unwarranted. When aerosolized in respirable form, the substance is considered likely to behave like an inert dust.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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 or exceeds requirements of OECD Guideline 423 and Directive 2004/73/EEC B.1 tris

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

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 type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain specifics: HanRcc:WIST (SPF)
- Source: RCC Ltd, Laboratory Animal services, 4414 Füllinsdorf, Switzerland
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 180.2-197.8 g (mean 189.4) on day 1 (treatment)
- Fasting period before study: approximately 18 hours before treatment, access to water permitted)
- Housing: in groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): Provimi Kliba 3433 standard rat/mouse maintenance diet, ad libitum
- Water (e.g. ad libitum): community tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: polyethylene glycol 300

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: solubility trial before the study initiation date (excluded from GLP statement of compliance)
- Vehicle Lot/batch no. (if required): 1107712 24104041 (Fluka Chemie GmbH)

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days starting with treatment day 1
- Frequency of observations and weighing:
mortality/viability: during the first 30 minutes and approximately 1, 2, 3 and 5 h after administration on day 1 and twice daily on days 2-15
clinical signs: during the first 30 minutes and approximately 1, 2, 3 and 5 h after administration on day 1 and daily on days 2-15
body weights: on days 1 (prior to administration), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination

Statistics:

None

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths

Clinical signs:

other: Orange discoloration of the feces was noted for all animals at the examinations performed on test day 2 and persisted up to test day 3 in three of the animals.

Gross pathology:

Congestion in the lungs was noted for three animals upon scheduled necropsy. No macroscopic findings were recorded for the remaining animals.

Other findings:

none

Interpretation of results:

other: not classified according to EU CLP

Remarks:

The test item has not to be classified as acutely toxic by the oral route according to Regulation (EC) No 1272/2008.

Conclusions:

The LD50 of the test item after a single oral administration to female rats, observed over a period of 14 days, was greater than 2000 mg/kg body weight. Therefore, the test item has not to be classified as acutely toxic by the oral route according to Regulation (EC) No 1272/2008.

Executive summary:

Two groups, each of three female HanRcc:WIST (SPF) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (PEG 300) at a concentration of 0.2 g/mL and administered at a volume dosage of 10 mL/kg bw.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study period.

Orange feces were observed in all animals from day 2 and persisted in 3 animals until day 3.

The body weight of the animals was within the range commonly recorded for this strain and age.

Congestion in the lungs was noted in 3 animals whereas no macroscopic findings were recorded in the remaining animals at scheduled necropsy.

The median lethal dose of the test item after single oral administration to female rats, observed over a period of 14 days is:

LD50 (female rat) > 2000 mg/kg bw

Therefore, the test item has not to be classified as acutely toxic by the oral route according to Regulation (EC) No 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

reliable

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The LD50 of the test item after a single oral administration to female rats, observed over a period of 14 days, was greater than 2000 mg/kg body weight. In this study no target organ effects were observed that could be clearly attributed to treatment or that could be clearly presumed to be harmful to human health.

Therefore, the test item has not to be classified as acutely toxic by the oral route (including STOT SE) according to Regulation (EC) No 1272/2008.