1,3-Cyclohexanedimethanamine

Acute Toxicity: oral

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-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

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

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

1,3-Cyclohexanedimethanamine

EC Number:

219-941-5

EC Name:

1,3-Cyclohexanedimethanamine

Cas Number:

2579-20-6

Molecular formula:

C8H18N2

IUPAC Name:

1,3-Cyclohexanedimethanamine

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 or test system 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 levels

Effect levels 1

Sex:

female

Dose descriptor:

LD100

Effect level:

2 000 mg/kg bw

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - ca. 2 000 mg/kg bw

Effect levels 3

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:

other: 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 th

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.