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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:
From 10 to 31 July 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study run to a reliable method but not GLP and no guideline followed.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Five dose levels were selected in which 5 groups of 5 males and 5 females mice were dosed once. An additional group of 5 male and 5 female mice was dosed with vehicle only. The mice were observed in the morning and afternoon for 14 days following administration of the test substance. At death, or at the end of the observation period and at termination, each animal was subjected to a gross post mortem examination.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Limited
- Weight at study initiation: The mean body weight on being dosed was 22 g (range 20-22 g) in the dose ranging study for males and 21 g (range 19-22 g) in the dose ranging study for females. The mean body weight in the main study was 22 g (range 18-24 g) for males and 18.5 g (range 16-21 g) for females.
- Fasting period before study: The animals were deprived of food for a 4 h period prior to dosing.
- Housing: They were housed individually in polypropylene cages with stainless steel grid tops and sterilised wood shavings.
- Diet (e.g. ad libitum): The animals were fed on BP Nutrition expanded Mouse Maintenance Diet No. 1.
- Water (e.g. ad libitum): Water was available ad libitum throughout the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C (extremes of 19°C-25°C)
- Humidity (%): 57% (extremes of 52%-74%)

IN-LIFE DATES: From 10 to 31 July 1980

No additional data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5% low viscosity CMC
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 20 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg

No additional data
Doses:
Dose ranging study:
300, 700, 1500, 5000 and 15000 mg wet test substance/kg
247, 577, 1236, 4120 and 12360 mg dry test substance/kg

Main study:
1200, 2040, 3468, 5895.6 and 10022.5 mg wet test substance/kg
956, 1626, 2764, 4699 and 7988 mg dry test substance/kg
No. of animals per sex per dose:
Dose ranging study: one male and one female
Main study: 5 males and 5 females
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The mice were observed on the morning and afternoon for 14 days following administration of the test substance.
- Necropsy of survivors performed: yes, At death, or at the end of the observation period and sacrifice, each animal was subjected to a gross post mortem examination.
- Other examinations performed: clinical signs, gross pathology
Statistics:
The LD50 was calculated using a method based on the following:
Finney (1971) "Probit Analysis", Cambridge University Press.

Results and discussion

Preliminary study:
In the dose ranging study in pairs of mice, mortality was 0/2, 0/2, 1/2, 1/2 and 1/2 in the dose group 247, 577, 1236, 4120 and 12360 mg dry test substance/day dose groups, respectively.
Clinical signs included piloerection, hypokinesia and ataxia, lasting for up to 3 days after dosing.
Post mortem observations included white fluid in stomach and upper gastro-intestinal tract with kidneys pale and mottled.
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 670 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 440 - <= 1 890
Remarks on result:
other: Based on dry test substance
Sex:
female
Dose descriptor:
LD50
Effect level:
3 240 mg/kg bw
Based on:
test mat.
95% CL:
>= 2 920 - <= 3 570
Remarks on result:
other: Based on dry test substance
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 300 mg/kg bw
Based on:
test mat.
95% CL:
>= 2 110 - <= 2 500
Remarks on result:
other: Based on dry test substance
Mortality:
In the main study, mortality was 0/10, 4/10, 5/10, 10/10 and 10/10 in the 956, 1626, 2764, 4699 and 7988 mg dry test substance/kg dose groups, respectively.
Clinical signs:
Clinical signs included piloerection, soiled coat, hyperkinesia, hypokinesia, ataxia, sedation, eyes half shut and penis protruded. In one animal the penis was very swollen and stained with blood with a constant stream of urine.
Body weight:
No information provided
Gross pathology:
Post mortem observations included stomach and gastro-intestinal tract filled with white fluid, gut contents fluid, blood filled gut, stomach wall white, penis extended and dark red and lungs red.
Other findings:
No information provided

Any other information on results incl. tables

There were no deaths or clinical signs recorded in the control group.

No abnormalities were detected at post mortem observations in the control group.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The Oral Median Lethal Doses (LD50s) of dry test substance were calculated to be 1960 mg/kg for male, 3240 mg/kg for female and 2300 mg/kg for male and female B6C3F1 mice.