1,3-Isobenzofurandione, hexahydro-, reaction products with epichlorohydrin

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 7, 1979 to October 4, 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well-documented pre-guideline study without GLP, testing protocol similar to OECD 401

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

pre-guideline and pre-GLP study

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Test material form:

liquid

Details on test material:

Batch: 502834

Test animals

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Healthy random bred rats of 7-8 weeks age were raised on the premises and kept at room temperature of 22 +/- 2 deg. C, at relatie humidity of 55 +/- 10% and on a 10 hour light cylce day. They received ad libitum rat food (supplier: NAFAG, Gossau, Switzerland) and water. They were adapted to the laboratory for a minimum of 4 days before treatment. During treatment and observation period the animals were housed in groups of 5 animals in Macrolon cages type 3. Animals were individually marked with picric acid.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw.

Doses:

600, 1000, 2000 and 5000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Details on study design:

- Prior to dosing the animals were fasted overnight.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations: 1 / hour for the first 5 hours, thereafter at least 1 / day. Body weight determination 1 / week
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

LD50 including 95% confidence intervals were calculated by the logit model

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 026 mg/kg bw

Based on:

test mat.

95% CL:

> 1 508 - < 3 096

Mortality:

Males: 5000 mg/kg 1 ( 3 hours), 3 ( 5 hours), 1 ( 24 hours) : 5/5
Males: 2000 mg/kg 1 ( 24 hours) : 1/5
Males: 1000 mg/kg : 0/5
Males: 600 mg/kg : 0/5
Females: 5000 mg/kg 3 ( 3 hours), 2 ( 5 hours) : 5/5
Females: 2000 mg/kg 2 ( 24 hours), 1 ( day 2) : 3/5
Females: 1000 mg/kg 1 ( 24 hours), 1 (day 6) : 1/5
Females: 600 mg/kg : 0/5

Clinical signs:

other: Animals treated with 5000 mg/kg bw showed severe sedation, a moderate effect on ruffled fur and cynosis and slight effects as dyspnoea, exophthalmos, convulsion and curved body position on the day of treatment. Animals treated with 2000 mg/kg bw showed a

Gross pathology:

no findings observed in the dead and killed animals

Applicant's summary and conclusion

Interpretation of results:

relatively harmless

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute toxicity is similar for males and females. The LD50 is 2026 (1508-3096) mg/kg bw.

Executive summary:

The acute toxicity has been investiagated in a pre-guideline and pre-GLP study performed and recorded similarly to the later standards. The doses selected were 5000 -2000 -1000 and 600 mg/kg bw. Each 5 male and 5 female animals were treated by gavage application with the test substance suspended in PEG 400. Mortality was 100% at the top dose in females and 80% in the top dose in males.Mortality at the lower dose was 20% in males and 60% in females. Mortality was 0% in males and 20% in females at 1000 mg/kg bw. The low dose was without mortality in males and females. At all doses there were the usual clinical symptoms in animals of both sexes. Mortality occurred within 4 days after treatment. The LD50 calculated is 2026 mg/kg bw (95% confidence limits are 1508 -3096 mg/kg).