5,12-dihydroquino[2,3-b]acridine-7,14-dione

Endpoint summary

Description of key information

Oral:

LD50 (Pigment Violet 19, nano form) >10000 mg/kg

 

Inhalation:

LC0 (structural analogue Pigment Red 122, nano form) 3.055 mg/L (highest technicallly achivable concentration)

LC50 (Pigment Violet 19, not specified form) > 3.1 mg/L

 

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

Study period:

From 5 APR 1979 to 19 APR 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given: comparable to guidelines

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

: no individual data included in report

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: in-house breeding (Hoe WISKf (SPF71))
- Weight at study initiation: 160 to 176 g
- Fasting period before study: 16 hours
- Housing: in plastic cages in groups
- Diet: Altromin 1324 (Altromin GmbH, Lage/lippe, Germany), ad libitum
- Water: tap water, ad libitum

Route of administration:

oral: gavage

Vehicle:

other: starch mucilage (2%)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 12.5% suspension in 2% starch mucilage

Doses:

10000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Sex:

female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Remarks on result:

other: no animals died within the 14 days observation period

Mortality:

- no deaths occured

Clinical signs:

other: - dye was excreted in the faeces - no other clinical signs observed

Gross pathology:

- in the animals sacrificed at the end of the observation period no macroscopically visible changes were found

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP Regulation

Conclusions:

Single application of the limit dose of 10000 mg test item per kg bw did not cause lethality in female rats during the 14 days observation period, resulting in a LD50 > 10000 mg/kg bw.

Executive summary:

Female Wistar rats were subjected to test acute oral toxicity. The test item was administered at the limit dose of 10000 mg/kg bw to ten rats. During the 14 days observation period no animals died and there were no changes found in necropsy, thus leading to a median lethal dose (LD50) > 10000 mg/kg bw.

Therefore, the test item has not to be classified for acute oral toxicity 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

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 23 SEP 1982 to 27 OCT 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (MMAD not calculated, no necropsy performed, no observation on the weekends, individual raw data not included in report, only 6 males/group)

Principles of method if other than guideline:

- acute inhalation toxicity (4 h exposure)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Crl:CD

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7 to 8 weeks
- Weight at study initiation: 226 to 250 g
- Housing: stainless steel wire mesh cages (8" x 8" x 14") in pairs
- Diet: Purina certified chow #5002; ad libitum
- Water: ad libitum

Route of administration:

inhalation: dust

Type of inhalation exposure:

head only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- System of generating particulates: Dust atmosphere of the test item was generated with a vertical two-stage glass generator consisting of a dust reservoir and a cyclone elutriator. An electric steel motor and steel rod with plastic paddles agitated dust in the generator. Air introduced at the reservoir carried dust particles upward to the elutriator. Additional houseline air carried airborne dust into the chamber.

TEST ATMOSPHERE
- Brief description of analytical method used: Samples from chamber were analyzed at 30-minute intervals. Calibrated volumes of test atmosphere were passed through preweighed glass fiber filters (Gelman Type AE, 25 mm) and atmospheric concentrations determined from filter weight gain. Airborne particle size measurements were obtained using Sierra 8-stage cascade impactor.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
at concentration of 3.1 mg/L: 21 % have an aerodynamic diameter < 13 µm
at concentration of 2.6 mg/L: not determined
at concentration of 2.4 mg/L: not determined
at concentration of 1.6 mg/L: 17 % have an aerodynamic diameter < 13 µm
at concentration of 1.5 mg/L: 12 % have an aerodynamic diameter < 13 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not calculated

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric measurement

Duration of exposure:

4 h

Concentrations:

1.5, 1.6, 2.4, 2.6, 3.1 mg/L

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily (already one week before treatment, but the weekends excepted)
- Necropsy of survivors performed: no

Sex:

male

Dose descriptor:

LC50

Effect level:

> 3.1 mg/L air (analytical)

Remarks on result:

other: no animals died within the 14 day observation period; exposure concentration of 3.1 mg/L corresponds to about 0.65 mg/L respirable dust (21% of dust particles had an aerodynamic diameter < 13 µm)

Mortality:

- no deaths occurred

Clinical signs:

other: - after exposure all animals had red stained fur

Body weight:

- immediately after exposure mild but transient weight loss but resumed a normal weight gain rate two days later

Gross pathology:

- not performed

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP Regulation

Conclusions:

In an acute inhalation toxicity test male rats were exposed to dust concentrations up to 3.1 mg/L test item for 4 hours. Under the conditions tested no animal died during a 14 day observation period, resulting in a LC50 value of > 3.1 mg/L (corresponding to 0.651 mg/L respirable test item).

Executive summary:

Acute inhalation toxicity of the test item has been investigated in male rats. They were exposed to 3.1 mg test substance per litre for 4 h. The test atmosphere contained only about 21% particles with an aerodynamic diameter (corresponding to 0.651 mg test item of respirable size). All animals survived the 14 day observation period, resulting in a LC50 value of > 3.1 mg/L (corresponding to 0.651 mg/L respirable test item) for the inhalation of dust.

Classification for acute inhalation toxicity is not necessary according to Regulation (EC) No 1272/2008.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Please refer to attached read across justification document (Chapter 13).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to attached read across document (Chapter 13).

3. ANALOGUE APPROACH JUSTIFICATION
Please refer to attached read across justification document (Chapter 13).

4. DATA MATRIX
Please refer to attached read across justification document (Chapter 13).

Reason / purpose for cross-reference:

read-across source

Duration of exposure:

4 h

Sex:

male

Dose descriptor:

LC50

Effect level:

> 3.1 mg/L air (analytical)

Remarks on result:

other: no animals died within the 14 day observation period; exposure concentration of 3.1 mg/L corresponds to about 0.65 mg/L respirable dust (21% of dust particles had an aerodynamic diameter < 13 µm)

Mortality:

- no deaths occurred

Clinical signs:

other: - after exposure all animals had red stained fur

Body weight:

- immediately after exposure mild but transient weight loss but resumed a normal weight gain rate two days later

Gross pathology:

- not performed

Interpretation of results:

GHS criteria not met

Remarks:

CLP Regulation

Conclusions:

The toxicity profile of Pigment Violet 19 is assessed based on analogue approaches:
In an acute inhalation toxicity test male rats were exposed to dust concentrations up to 3.1 mg/L test item for 4 hours. Under the conditions tested no animal died during a 14 day observation period, resulting in a LC50 value of > 3.1 mg/L (corresponding to 0.651 mg/L respirable test item).

Executive summary:

Acute inhalation toxicity of the test item has been investigated in male rats. They were exposed to 3.1 mg test substance per litre for 4 h. The test atmosphere contained only about 21% particles with an aerodynamic diameter (corresponding to 0.651 mg test item of respirable size). All animals survived the 14 day observation period, resulting in a LC50 value of > 3.1 mg/L (corresponding to 0.651 mg/L respirable test item) for the inhalation of dust.

Classification for acute inhalation toxicity is not necessary according to Regulation (EC) No 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 3.1 mg/L air

Quality of whole database:

reliable

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

no classification

Neither in studies witn oral nor inhaltion nor dermal exposure any adverse effects were observed at / above limit doses.