4,4'-diamino[1,1'-bianthracene]-9,9',10,10'-tetraone

Endpoint summary

Description of key information

The substance did not cause adverse effects upon a single oral dose of 10000 mg/kg bw  in rats in a study design similar to that of OECD guideline 423 (BASF 1973). It did not cause acute dermal toxicity at the limit dose of 2000 mg/kg bw in a GLP compliant study following OECD guideline 402 (BASF 2012a). 

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Equivalent or similar to the OECD Guideline 401 (TS purity not specified; 7-day observation period; body weights determined only at study start; no GLP)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

7-day observation period; body weights determined only at study start

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Tif. RAI SPF own breeeding rats from Ciba-Geigy Ltd.
- Age at study initiation: 6-7 weeks
- Weight at study initiation: 160-180 g
- Fasting period before study: overnight prior to dosing
- Housing: caged in groups of 5 (segregated in males and females) in Macrolon cages type 3
- Diet (e.g. ad libitum): Rat food, NAFAG, Gossau, SG, rat food; ad libitum
- Water (e.g. ad libitum): drinking water; ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS (the animal room was air conditioned)
- Temperature (°C): 22±1°C
- Humidity (%): approx. 50%

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

2%

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50% (w/v)

DOSAGE PREPARATION (if unusual):
The test substance was weighed into an Erienmeyer flask on a Mettler balance. It was suspended at 50 % with CMC (2%). Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.

Doses:

6000 and 10000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: daily for mortality and clinical signs of toxicity; body weights were not determined
- Necropsy of survivors performed: yes; the animals were killed and autopsied after an observation period.

Statistics:

None conducted

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed up to this dose level

Mortality:

No mortality occurred

Clinical signs:

other: Within 2 hours after treatment the rats of both dosage groups showed dyspnoea, exophthalmus, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. The animals had recovered within 3 to 6 days. They were killed

Gross pathology:

No substance related gross organ changes were seen

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

10 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and OECD guideline compliant study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, 97633 Sulzfeld, Germany

- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: average 202g (females) and 237g (males)
- Fasting period before study: none
- Housing: single
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 30 – 70%
- Air changes (per hr): no data, air-conditioned room used.
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

IN-LIFE DATES: From: 2011-11-01 To: 2011-11-15

- Fur clipping about 24 hours before administration

Type of coverage:

semiocclusive

Vehicle:

olive oil

Details on dermal exposure:

TEST SITE
- Area of exposure: About 40 cm²
- % coverage: 10%
- Type of wrap if used: semi- occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with warm water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied: 5g/kg bw
- Concentration (if solution): 40g/100ml
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 3 g/kg bw

Duration of exposure:

24h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals. Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality

Statistics:

not required

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality occurred.

Mortality:

none

Clinical signs:

other: No systemic clinical signs were observed during clinical examination.

Gross pathology:

No effects

Other findings:

Due to the red discoloration of the application area reading of skin redness could not be determined from study day 1 until study day 3. Thereafter no erythema was noted. No edema was noted during observation period.
Additionally test item residues were noted on study day 6 and persisted in two animals until study day 8.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

The acute oral LD50 in rats of both sexes observed over a period of 7 days is greater than 10'000 mg/kg (BASF 1973). The study was performed prior to the introduction of GLP but is reported in adequate detail for evaluation. The design deviates from the OECD testing guideline in the higher dose and the shorter observation period. Considering that none of the animals showed severe signs of toxicity at 6000 or 10000 mg/kg bw, the shorter duration is an acceptable deviation. The test item was suspended at 50 % with carboxymethyl-cellulose 2 % and administered by oral intubation to each male and females per dose group. Within 2 hours after treatment the rats in both dosage groups showed dyspnoea, exophthalmus, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. The animals had recovered within 3 to 6 days. They were killed and autopsied after an observation period of 7 days, no substance related gross organ changes were seen.

In the acute dermal toxicity study, young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw (as suspension in olive oil Ph.Eur.) to the clipped skin (dorsal and dorsolateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours (BASF 2012a). The study followed GLP and OECD testing guideline 402. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days.

No mortality occurred. No signs of systemic toxicity effects occurred. The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weight of the female animals did not adequately increase during

the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. Red discoloration by the test item of the application area and test item residues were found at the end of the observation period.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for acute oral or dermal toxicity under Directive 67/548/EEC, as amended for the 31st time in Directive2009/2/EG.

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the third time in Directive EC 618/2012.