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Toxicological information

Acute Toxicity: oral

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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

Constituent 1
Chemical structure
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:
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 showed a moderate effect on ruffled fur (2 hours - day 7) and dyspnea (days 4-6). Slight effects recorded were sedation (2 hours - day 6), ruffled fur (1 hour plus days 7-11), dyspnea (1 hour - day 3 plus day 7 - day 10), exophthalmos (1 hour - day 7), diarrhea (24 hours - day 6) and curved body position (1 hour - day 10).

Animals treated with 1000 mg/kg bw showed a moderate effect on ruffled fur (3 hours - day 6). Slight effects recorded were sedation (2 hours - 5 hours), ruffled fur (1 hour - 2 hours plus days 7 and 8), dyspnea (1 hour - day 6), exophthalmos (1 hour - day 7), diarrhea (24 hours - day 3) and curved body position (1 hour - day 6).

Animals treated with 400 mg/kg bw showed slight effects on dyspnea (1 hour - day 6), exophthalmos (24 hours - day 4), ruffled fur (1 hour - day 8) and curved body position (1 hour - day 6).
Body weight:
Dose sex bw changes bw changes

400 mg/kg bw males: First week: 24% 2nd week: 20%
1000 mg/kg bw males: First week: -19% 2nd week: 40%
2000 mg/kg bw males: First week: -17% 2nd week: 24%
3000 mg/kg bw males: First week: --- 2nd week: ---

400 mg/kg bw females: First week: 11% 2nd week: 14%
1000 mg/kg bw females: First week: -12% 2nd week: 26%
2000 mg/kg bw females: First week: -27% 2nd week: 4%
3000 mg/kg bw females: First week: --- 2nd week: ---

The bw changes in both weeks could not be calculated for both males and females treated with a dose of 3000 mg/kg.

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).