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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:
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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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:
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 slight to moderate effect on ruffled fur (1 hour - day 6) and slight effects on dyspnoea (1 hour - day 6), sedation (3 hours - 5 hours), exophthalmos (1 hour - day 5) and curved body position (1 hour - day 4).
Animals treated with 1000 mg/kg bw showed a slight to moderate effect on ruffled fur (1 hour - day 6) and slight effects on dyspnoea (1 hour - day 6), sedation (5 hours), exophthalmos (1 hour - day 5) and curved body position (1 hour - day 4).

Animals treated with 600 mg/kg bw showed slight effects on dyspnoea (1 hour - day 7), exophthalmos (1 hour - day 6), ruffeld fur (1 hour - day 7) and curved body position (1 hour - day 4).
Body weight:
Dose sex bw changes bw changes

600 mg/kg bw males: First week: 30% 2nd week: 16%
1000 mg/kg bw males: First week: 28% 2nd week: 14%
2000 mg/kg bw males: First week: 24% 2nd week: 20%
5000 mg/kg bw males: First week: --- 2nd week: ---

600 mg/kg bw females: First week: 14% 2nd week: 10%
1000 mg/kg bw females: First week: 12% 2nd week: -1%
2000 mg/kg bw females: First week: 17% 2nd week: 9%
5000 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 5000 mg/kg
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).