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

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 23 SEP 1970 to 23 Oct 1970

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Basic data given: comparable to guidelines (limitations: e.g. no clinical biochemistry, no detailed clinical observations, no functional observations, only 4-5 days post observation period, no reporting of individual/mean data, especially on food consumption and body weight development)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1971

Report date:

1971

Materials and methods

Principles of method if other than guideline:

subacute toxicity test

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

254-100-6

EC Name:

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

Cas Number:

38720-66-0

Molecular formula:

C20H10Cl2N2O2

IUPAC Name:

1,8-dichloro-5,7,12,14-tetrahydro-5,12-diazapentacene-7,14-dione; 1,9-dichloro-5,7,12,14-tetrahydro-5,12-diazapentacene-7,14-dione; 2,9-dichloro-5,7,12,14-tetrahydro-5,12-diazapentacene-7,14-dione

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: in house breeding; SPF
- Weight at study initiation: males: mean 147 g (122 g - 172 g); females: mean 110 g (90 g - 126 g)
- Fasting period before study: no
- Housing: 5 animals/sex/cage
- Diet: Standard diet Altromin R (Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25
- Humidity (%): 35-60

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): once at the beginning of the study
- Mixing appropriate amounts with standard diet using a "Lödige-Präzisions-Minuten-Mischer Modell M 20 E"
- Preparation of pellets using a "Templewood-Mischfutterpresse"
- Storage temperature of food: no data

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

30 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 0.2, 1.0 and 5% in diet
Basis:
nominal in diet

No. of animals per sex per dose:

10

Control animals:

yes, plain diet

Details on study design:

- Dose selection rationale: LD50 after single oral application > 15000 mg/kg bw; pretest (10 days feeding study) with rats receiving feed with 5%, 1% and 0.2% of the test item

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined: YES
- mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: before the beginning and at the end of the experiment
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: from each animal
- Parameters examined: haemoglobin concentration, erythrocyte count, leucocyte count, differential blood count, appearance of Heinz bodies

CLINICAL CHEMISTRY: No

URINALYSIS: Yes
- Time schedule for collection of urine: before the beginning and at the end of the experiment
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters examined: appearance, colour, protein, glucose, bilirubin, specific weight (urine collected from 5 animals), sediment


NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (heart, lung, liver, spleen, adrenals, kidney)

Other examinations:

- heart, lung, liver, spleen, adrenals, kidney

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

not examined

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
- no effects

BODY WEIGHT AND WEIGHT GAIN
- no differences between treated animals and controls

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
-no effects

HAEMATOLOGY
- no pathological findings

URINALYSIS
- no test item related effects
- at the end of the study male rats excreted protein in the urine which was judged to be normal in adult male rats

ORGAN WEIGHTS
- no effects

GROSS PATHOLOGY
- no effects

HISTOPATHOLOGY: NON-NEOPLASTIC
- no effects

Effect levels

Dose descriptor:

NOAEL

Effect level:

>= 50 000 mg/kg diet

Sex:

male/female

Basis for effect level:

other: no toxic effects observed, 5% in diet correspond to 2000 and 2500 mg/kg bw/day for males and females, respectively, calculated according to ECHA Guidance on information requirements R.8

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Compared to the control group, no alterations in the general behaviour, food uptake and body weight gain of the treated animals were observed. The examination of blood and urine revealed no toxic responses (proteinuria in all males was regarded as typical for male rats).

Organ weights of the animals were within the normal range. Macroscopic and microscopic examination of heart, lung, liver, spleen, adrenals and kidneys revealed no pathological findings.

Applicant's summary and conclusion

Conclusions:

Under the conditions of this study the test item did not produce toxic responses in the treated animals.

Executive summary:

Wistar rats (10 per sex and group) were fed diets with the test item in concentrations of 0, 0.2, 1 and 5% for 30 consecutive days. There were no toxic responses compared to the controls with respect to general behaviour, food uptake, body weight gain. The examination of blood and urine revealed no toxic responses (proteinuria in all males was regarded as typical for male rats). Organ weights of the animals were within the normal range. Macroscopic and microscopic examination of heart, lung, liver, spleen, adrenals and kidneys revealed no pathological findings. The NOAEL was 5% test item in the diet (corresponding to 2000 and 2500 mg/kg bw/day for males and females, respectively).