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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:
not specified
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: 59 NohSan No. 4200
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Remarks:
SPF rats
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation: 7 weeks old
- Weight at study initiation: 189 to 211 g in males and 132 to 154 g in females
- Fasting period before study: overnight prior to administration. Animals were fed once again 2 hours after administration.
- Housing: The animals were housed in groups of 2 to 3 in stainless steel wire mash cages
- Diet: A pellet diet ad libitum
- Water: Tap water ad libitum
- Acclimation period: Approximately 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 3
- Humidity (%): 50 ± 20
- Air changes: 11 to 13 minutes per hour
- Photoperiod (hrs dark / hrs light): 12 /12

IN-LIFE DATES: From: To: Start: 6 Oct., 1995; End: 23 May 1996

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Remarks:
0.5%
Details on oral exposure:
PRELIMINARY TOXICITY STUDY
In a preliminary acute oral toxicity study, three groups were used. Each consisted of three male and three female 7 week old CD(SD) rats. These groups had the test article administered at dose levels of 800, 2000 and 5000 mg/kg bw. 1 animal of each sex in the 2000 mg/kg bw group and 2 animals of each sex in the 5000 mg/kg bw group died. Consequently 5 dose levels, 900, 1500, 2300, 3800 and 6000 mg/kg bw were selected for both sexes in the main study.

VEHICLE:
- Amount of vehicle (if gavage): 20 mL/ kg bw

MAXIMUM DOSE VOLUME APPLIED: 6000 mg/kg bw
Doses:
900, 1500, 2300, 3800 and 6000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
yes
Remarks:
vehicle (0.5% methylcellulose solution)
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were examined frequently for the first six hours after dosing and twice daily in the morning and afternoon thereafter for 14 days for mortality and clinical abnormalities during the study. Body weights were recorded immediately prior to administration and the dose volume for each animal was calculated based on the weights. Body weights were also recorded on days 1, 2, 3, 7, 10 and 14 after administration at a set time.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, macroscopic examinations
Statistics:
The oral LD50 and the 95% confidence limits were calculated using the Probit method from the cumulative mortality rate 14 days after administration. For body weights, group mean values with standard deviation were calculated.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 563 mg/kg bw
Based on:
test mat.
95% CL:
> 1 086 - < 2 174
Mortality:
3 animals of each sex treated at a dose level of 1500 mg/kg bw were found dead 2 to 6 hours after dosing. The same results was also seen at 2300 mg/kg bw. At the test doses of 3800 and 6000 mg/kg bw all test animals in the groups were killed after dosing.
Clinical signs:
Decrease in spontaneous movement, tonic convulsions and ptosis were observed, beginning from 1 hour after dosing in each sex in the 1500 mg/kg bw and above groups. The surviving animals returned to normal on the day following dosing.
Body weight:
The body weight of the animals was within the range commonly recorded for this age and strain.
Gross pathology:
There were no macroscopic abnormalities observed.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 values were 1563 mg/kg bw (95% CI 1086 – 2174 mg/kg bw) in both sexes and 1563 mg/kg bw (95% CI 1267 – 1905 mg/kg bw) in both sexes combined.
Executive summary:

In an acute oral toxicity study, 6 groups of 7 week old Crj:CD (SD) strain rats (each group consisting of 5 animals of each sex), were given a single oral dose of the test substance (98.60%.) in methylcelluloseat doses of 900, 1500, 2300, 3800 or 6000 mg/kg bw and observed for 14 days. A control group consisting of 5 male and 5 female rats were treated with 0.5% methylcellulose solution alone and were also observed. The animals were examined frequently for the first six hours after dosing and twice daily in the morning and afternoon thereafter for 14 days for mortality and clinical abnormalities during the study. Body weights were recorded throughout the study. In the males and females in each group, ptosis was observed beginning from one hour after dosing. In each sex in the 1500mg/kg bw and above groups, decrease in spontaneous movement and tonic convulsion were also observed. Initial deaths were seen at the 1500 mg/kg bw group with 3 animals of each sex, this was also seen with 4 animals of each sex in the 2300 mg/kg bw group and all animals in the 3800 and 6000 mg/kg bw group. The oral LD50 for males and for females is 1563 mg/kg bw (95% CI 1086 – 2174 mg/kg bw). The combined (males and females) oral LD50 1563 mg/kg bw (95% CI 1267 – 1905 mg/kg).