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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:
30 May 2005-23 January 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to international guidelines and GLP standards.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1,3-Bis(aminomethyl)cyclohexane
- Physical state: liquid
- Stability under test conditions: confirmed stable (IR spectrophotometry)
- Storage condition of test material: Refrigeration (actual temperature: 2.8°C to 8.4°C, permissible range: 1°C to 10°C), shielded from light, nitrogen-sealed

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 to 9 weeks
- Weight at study initiation: 179-199g
- Fasting period before study: 17 hours before to 3 hours after administration
- Housing:Autoclave-sterilized polycarbonate cages (265W×426D×200H mm, Tokiwa Kagaku Kikai Co., Ltd.) were used and replaced on the day of grouping and Day 8. The cages for the animals in the second administration group were also replaced on the day before the administration. Animals were housed 4 animals per cage before grouping, and 3 animals per cage thereafter.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0-22.6
- Humidity (%): 51.5-66.5
- Air changes (per hr): 6 to 20 times per hour
- Photoperiod (hrs dark / hrs light): 12 hours/day


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:Three females were subjected to each dosing. According to information obtained from the test substance supplier (manufacturer), the approximate lethal dose 50% (LD50) for male rats is 700 mg/kg. Accordingly, the dose level for the first administration was set at 300 mg/kg, and this study was conducted in accordance with the GHS flow chart.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
3 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:before dosing, and post dosing: 10 min, 30 min, 1 hour, 3 hours, 6 hours. Body weights recorded prior to dosing,and on days 4, 8, and 15.
- Necropsy of survivors performed: no survivors
- Other examinations performed: clinical signs, body weight, pathological examination/necropsy
Statistics:
Not Applicable

Results and discussion

Preliminary study:
Not Applicable
Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD100
Effect level:
2 000 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - ca. 2 000 mg/kg bw
Sex:
female
Dose descriptor:
LD0
Effect level:
> 300 mg/kg bw
Mortality:
In the first and second administration at 300 mg/kg, no deaths or abnormalities in clinical signs were observed.
At the third administration at 2000 mg/kg, one animal died on Day 1 (day of administration), and two animals died on Day 2.
Clinical signs:
In the first and second administration at 300 mg/kg, no abnormalities in clinical signs were observed. At the third administration at 2000 mg/kg, decreases in locomotor activity and irregular respiration were noted in all animals from 10 minutes after the administration. In addition, ptosis and prone or supine position were noted in all animals 30 minutes after the administration. Moderate decreases in locomotor activity, ptosis, bradypnea, or crouching position were noted in all animals 1 and 3 hours after administration. One animal (No. 70102) was found dead 6 hours after the administration, and two animals showed hypothermia and died the next day.
Body weight:
No abnormalities were noted in body weight gain in the first or second administration at 300 mg/kg.
Gross pathology:
No abnormalities were noted in the first or second administration at 300 mg/kg.
In all dead animals, reddish change and edema were noted in the forestomach and glandular stomach, and abnormal contents were observed in the stomach and intestine. Moreover, reddish ascites was noted in the abdominal cavity in the animal found dead on the day of administration.
Other findings:
Not applicable

Any other information on results incl. tables

Not applicable

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
1,3-BAC was classified into Category 4 (>300-2000 mg/kg b.w.) in accordance with the Globally Harmonized Classification System (GHS), under the conditions of this study.
Executive summary:

This study was conducted to assess the acute toxicity of 1,3-BAC in female rats administered by oral gavage at the single doses of 300 mg/kg (first and second administration) and 2000 mg/kg (third administration).

At the third administration at 2000 mg/kg, decreases in locomotor activity, ptosis, hypothermia, and abnormalities in respiration and posture were observed, and all animals died by Day 2. In necropsy, abnormalities in the stomach and intestine were observed. The changes in the stomach and intestine were considered to be attributed to irritation caused by the test substance. In the first and second administration at 300 mg/kg, no deaths or abnormalities attributed to the test substance were observed in the clinical signs, body weight, or necropsy findings.

Therefore, 1,3-BAC was classified into Category 4 (>300-2000 mg/kg b.w.) in accordance with the Globally Harmonized Classification System (GHS), under the conditions of this study.