2-(3-hydroxypropyl)-6-[(3-hydroxypropyl)amino]-1H-benz[de]isoquinoline-1,3(2H)-dione

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from secondary source

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

1,3-dioxo-1H-benz(de)isoquinoline-2(3H) butyric acid, pharmacologically acceptable salts thereof and compositions containing the same for treatment of diabetes mellitus complications

Author:

Efimov , et al.

Year:

1986

Bibliographic source:

United States Patent Document. #4598081

Reference 2

Reference Type:

other: Authoritative database

Title:

RTECS Number: CF6559500

Author:

RTECS database

Year:

2017

Bibliographic source:

RTECS (Registry of Toxic Effects of Chemical Substances); CCECAU Criticial Reviews in Environmental Control. (Chemical Rubber Company, Cleveland, OH) V.1- 1970- Volume(issue)/page/year: 7,91,1977

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: refer below

Principles of method if other than guideline:

The acute toxicity study was conducted to evaluate the toxic effects of administration of 1,3-dioxo-1H-benz(de)isoquinoline-2(3H) butyric acid (Isodibut) (CAS No. 88909-96-0) in rat by the oral route.

GLP compliance:

not specified

Test type:

other: No data available

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

Cas Number:

88909-96-0

Molecular formula:

C16H13NO4

Details on test material:

- Name of test material: Isodibut (1,3-dioxo-1H-benz(de)isoquinoline-2(3H) butyric acid)
- Molecular formula: C16H13NO4
- Molecular weight: 283.282 g/mol
- Smiles notation: C1(N(C(c2c3c(cccc13)ccc2)=O)CCCC(=O)O)=O
- InChl: 1S/C16H13NO4/c18-13(19)8-3-9-17-15(20)11-6-1-4-10-5-2-7-12(14(10)11)16(17)21/h1-2,4-7H,3,8-9H2,(H,18,19)
- Substance type: Organic

Specific details on test material used for the study:

- Name of test material: Isodibut (1,3-dioxo-1H-benz(de)isoquinoline-2(3H) butyric acid)
- Molecular formula: C16H13NO4
- Molecular weight: 283.282 g/mol
- Smiles notation: C1(N(C(c2c3c(cccc13)ccc2)=O)CCCC(=O)O)=O
- InChl: 1S/C16H13NO4/c18-13(19)8-3-9-17-15(20)11-6-1-4-10-5-2-7-12(14(10)11)16(17)21/h1-2,4-7H,3,8-9H2,(H,18,19)
- Substance type: Organic

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data available
- Females (if applicable) nulliparous and non-pregnant: No data available
- Age at study initiation: Mature animals were used for the experiment.
- Weight at study initiation: 180 to 220 g
- Fasting period before study: No data available
- Housing: No data available
- Diet (e.g. ad libitum): No data available
- Water (e.g. ad libitum): No data available
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%): No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available

IN-LIFE DATES: From: To: No data available

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

VEHICLE
- Concentration in vehicle: No data available
- Amount of vehicle (if gavage): No data available
- Justification for choice of vehicle: No data available
- Lot/batch no. (if required): No data available
- Purity: No data available

MAXIMUM DOSE VOLUME APPLIED: No data available

DOSAGE PREPARATION (if unusual): No data available

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: No data available

Doses:

3000 mg/kg bw
3500 mg/kg bw
4000 mg/kg bw
4500 mg/kg bw
5000 mg/kg bw
5500 mg/kg bw
6000 mg/kg bw

No. of animals per sex per dose:

A total of 36 rats were used in the experiment.
3000 mg/kg bw : 5 animals
3500 mg/kg bw : 5 animals
4000 mg/kg bw : 4 animals
4500 mg/kg bw : 5 animals
5000 mg/kg bw : 7 animals
5500 mg/kg bw : 5 animals
6000 mg/kg bw : 5 animals

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 5 days
- Frequency of observations and weighing: No data available
- Necropsy of survivors performed: No data available
- Other examinations performed: clinical signs, mortality.

Statistics:

LD50 determined by the Lichfield and Wilcoxon method, or the Van der Waerden method was used as an index of high toxicity.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 000 mg/kg bw

Based on:

test mat.

95% CL:

3 030 - 5 280

Mortality:

Only a few animals showed a short-time initial excitation. 6-8 hours later the animals laid down on the side, their condition became comatose, followed by death. That is the animals died slowly, as a rule, during the first 24-26 hours.
3000 mg/kg bw : 0/5
3500 mg/kg bw : 2/5
4000 mg/kg bw : 1/4
4500 mg/kg bw : 3/5
5000 mg/kg bw : 4/7
5500 mg/kg bw : 4/5
6000 mg/kg bw : 5/5

Clinical signs:

other: The symptoms of the acute lethal poisoning by 1,3-dioxo-1H-benz(de)isoquinoline-2(3H) butyric acid (Isodibut) was characterized by flaccidity, hypodynamia, and lower respiration rhythm.

Gross pathology:

No data available

Other findings:

No data available

Applicant's summary and conclusion

Interpretation of results:

other: not classified based on CLP criteria

Conclusions:

The acute oral median lethal dose (LD50) of 1,3-dioxo-1H-benz(de)isoquinoline-2(3H) butyric acid (Isodibut) (CAS No. 88909-96-0) in rat was observed to be 4000 (3030 to 5280) mg/kg b.wt.

Executive summary:

The toxicity of 1,3-dioxo-1H-benz(de)isoquinoline-2(3H) butyric acid (Isodibut) (CAS No. 88909-96-0) was examined by way of experiment performed on rats. Mature animals both male and female, weighting 180 to 220 g (rats) were used for said experiment. 1,3-dioxo-1H-benz(de)isoquinoline-2(3H) butyric acid (Isodibut) was administered perorally. The drug was introduced in the form of a starch suspension through a gastric tube. A total of 36 rats were used in the experiment. Rats were given dosages of 3000 mg/kg bw to 6000 mg/kg bw. The animals were kept under observation for 5 days. The symptoms of the acute lethal poisoning by 1,3-dioxo-1H-benz(de)isoquinoline-2(3H) butyric acid (Isodibut) was characterized by flaccidity, hypodynamia, and lower respiration rhythm. Only a few animals showed a short-time initial excitation. 6-8 hours later the animals laid down on the side, their condition became comatose, followed by death. That is the animals died slowly, as a rule, during the first 24-26 hours. Doses of up to 3000 mg/kg bw caused no deaths but 2 animals died at 3500 mg/kg bw, 1 animal died at 4000 mg/kg bw, 3 animals died at 4500 mg/kg bw, 4 animals died at 5000 mg/kg bw, 4 animals died at 5500 mg/kg bw and 5 animals died at 6000 mg/kg bw. Thus, the acute oral median lethal dose (LD50) of 1,3-dioxo-1H-benz(de)isoquinoline-2(3H) butyric acid (Isodibut) (CAS No. 88909-96-0) in rat was observed to be 4000 (3030 to 5280) mg/kg b.wt. Therefore, according to CLP criteria for acute toxicity rating for the chemicals, it infers that 1,3-dioxo-1H-benz(de)isoquinoline-2(3H) butyric acid (Isodibut) (CAS No. 88909-96-0) does not exhibit acute toxicity via the oral route.