N-hydroxyphthalimide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from peer- reviewed journal

Data source

Reference

Reference Type:

publication

Title:

Acute Toxicity of IV-(2,3-Epoxy-propyl)-Phthalimide

Author:

Elliott J. Greene, Marvin A. Friedman, Michael A. Gallo. Kent R. Stevens

Year:

1979

Bibliographic source:

TOXICOLOGY AND APPLIED PHARMACOLOGY 51, 197-199 (1979)

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Acute oral toxicity study of 2-[(trichloromethyl)sulfanyl]-1H-isoindole-1,3(2H)-dione in rats

GLP compliance:

not specified

Test type:

other: No data

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-[(trichloromethyl)sulfanyl]-1H-isoindole-1,3(2H)-dione

Cas Number:

133-07-3

Molecular formula:

C9H4Cl3NO2S

IUPAC Name:

2-[(trichloromethyl)sulfanyl]-1H-isoindole-1,3(2H)-dione

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report): 2-[(trichloromethyl)sulfanyl]-1H-isoindole-1,3(2H)-dione
- Molecular formula : C9H4Cl3NO2S
- Molecular weight : 296.5606 g/mole
- Substance type: Organic
- Physical State: Solid

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2-[(trichloromethyl)sulfanyl]-1H-isoindole-1,3(2H)-dione
- Molecular formula (if other than submission substance): C9H4Cl3NO2S
- Molecular weight (if other than submission substance): 296.5606 g/mole
- Substance type: Organic

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Weight at study initiation: 180 and 250 g

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

1 %

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 1000, 3000, 3500, 4000, 8000 and 1200 mg/kg
- Amount of vehicle (if gavage):
- Justification for choice of vehicle: 1% carboxymethyl cellulose

DOSAGE PREPARATION (if unusual): Dose was administered as a 25 % (w/v) water suspension with 1% carboxymethyl cellulose as a stabilizer.

Doses:

1000, 3000, 3500, 4000, 8000 and 12000 mg/kg

No. of animals per sex per dose:

Total : 50
1000 mg/kg: 5 male, 5 female
3000 mg/kg: 5 male, 5 female
3500 mg/kg: 5 male, 5 female
4000 mg/kg: 5 male, 5 female
8000 mg/kg: 5 male, 5 female
1200 mg/kg : 5 male, 5 female

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily
- Necropsy of survivors performed: no
- Other examinations performed: Mortality, Clinical sign and gross pathology were examined.

Statistics:

The acute oral LD50 was calculated according to Knudsen and Curtis (1947).

Results and discussion

Preliminary study:

No data available

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

47 000 mg/kg bw

Based on:

test mat.

95% CL:

3 500 - 5 900

Remarks on result:

other: 50 % mortality observed

Mortality:

When treated with 4000, 8000 and 12000 mg/kg, all animals died on day 0 and Day 1, except one animal at 4000 mg/kg which died on Day 3.

Clinical signs:

other: Salivation, decreased activity, bloody nasal discharge, and ataxia at 3000 and 3500 mg/kg and, in addition, decreased respiration, in coordination, and gasping at 4000, 8000 and 12000 mg/kg With the exception of salivation and incoordination which disa

Gross pathology:

In lungs, liver and gastrointestinal tract toxicity were observed
At all doses, the lungs were dark and mottled and the gastrointestinal tract was vascularized.
The liver was pale or pale and mottled at 3500 and 3000 mg/kg, respectively, and dark or dark and mottled at 4000, 8000 and 12000 mg/kg.

Other findings:

No data available

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was considered to be 4700 mg/kg bw when Sprague-Dawley male rats were treated with 2-[(trichloromethyl)sulfanyl]-1H-isoindole-1,3(2H)-dione orally by gavage.

Executive summary:

In a acute oral toxicity studySprague-Dawley male rats were treated with 2-[(trichloromethyl)sulfanyl]-1H-isoindole-1,3(2H)-dione in the concentration of 1000, 3000, 3500, 4000, 8000 and 12000 mg/kg orally by gavage and observed for 14 days. At 4000, 8000 and 12000 mg/kg, All animals died on day 0 and Day 1, except one animal at 4000 mg/kg which died on Day 3. Salivation, decreased activity, bloody nasal discharge, and ataxia at 3000 and 3500 mg/kg and, in addition, decreased respiration, in coordination, and gasping at 4000, 8000 and 12000 mg/kg With the exception of salivation and incoordination which disappeared within 24 hr, these signs persisted for several days. In addition, In lungs, liver and gastrointestinal tract toxicity was observed at all doses, the lungs were dark and mottled and the gastrointestinal tract was vascularized.

 The liver was pale or pale and mottled at 3500 and 3000 mg/kg, respectively, and dark or dark and mottled at 4000, 8000 and 12000 mg/kg. Therefore,LD50 was considered to be4700mg/kg bw whenSprague-Dawley male rats were treated with 2-[(trichloromethyl)sulfanyl]-1H-isoindole-1,3(2H)-dione orally by gavage.