p-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 9 - April 30, 1980

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:

1980

Report date:

1980

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

Reference substance name:

p-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline

EC Number:

225-716-2

EC Name:

p-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl)aniline

Cas Number:

5026-74-4

Molecular formula:

C15H19NO4

IUPAC Name:

4-[(oxiran-2-yl)methoxy]-N,N-bis[(oxiran-2-yl)methyl]aniline

Test material form:

liquid: viscous

Details on test material:

- Substance type: organic
- Physical state: liquid
- Storage condition of test material: In refrigerator (2-8°C) in the dark

Test animals

Species:

rat

Strain:

other: T1f: 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

Remarks:

PEG 400, Fluka AG, Art. 81170

Details on oral exposure:

Animals fasted overnight were treated by single oral intubation.

Doses:

400 - 1000 - 2000 - 3000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- 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:

ca. 1 037 mg/kg bw

Based on:

test mat.

95% CL:

> 668 - < 1 403

Mortality:

Males: 3000 mg/kg 2 (3 hours), 1 (5 hours), 2 (24 hours) : 5/5
Males: 2000 mg/kg 1 (24 hours), 1 (day 2), 1 (day 4), 1 (day 6) : 4/5
Males: 1000 mg/kg 2 (24 hours): 2/5
Males: 400 mg/kg : 0/5

Females: 3000 mg/kg 1 (2 hours), 3 (5 hours), 1 ( 24 hours) : 5/5
Females: 2000 mg/kg 1 (24 hours), 1 (day 3), 1 (day 4), 1 (day 6) : 4/5
Females: 1000 mg/kg 3 (24 hours), 1 (day 6) : 4/5
Females: 400 mg/kg : 0/5

Clinical signs:

other: Animals treated with 3000 mg/kg bw showed a moderate effect on ruffled fur for the first 5days and slight effects as sedation, dyspnea, exophthalmos, diarrhea and curved body position (all on on the first 5 hours). Animals treated with 2000 mg/kg bw show

Applicant's summary and conclusion

Interpretation of results:

sligthly toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute toxicity is similar for males and females. The LD50 is 1037 (668-1403) 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 3000 -2000 -1000 and 400 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 both sexes. Mortality at the lower dose was 80% in both sexes, 40% in males and 80% in females at 1000 mg/kg bw. The low dose was without mortality in both sexes. At all doses there were the usual clinical symptoms in animals of both sexes. Mortality occurred within 6 days after treatment. The LD50 calculated is 1037 mg/kg bw (95% confidence limits are 668 -1403 mg/kg).