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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March 14, 1985 -April 2, 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report date:
1985

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study is well-documented and performed according to generally accepted scientific standards.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
3,6-dioxaoctamethylenediamine
EC Number:
213-203-6
EC Name:
3,6-dioxaoctamethylenediamine
Cas Number:
929-59-9
Molecular formula:
C6H16N2O2
IUPAC Name:
3,6-dioxaoctamethylenediamine
Test material form:
liquid
Details on test material:
- Physical state: liquid
- Appearance: colourless liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 5601-49-1, J-243

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Stability under test conditions: there was no apparent change in the physical state of the test article during administration

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Labs, Wilmington, Mass.
- Females, nulliparous and non-pregnant: yes, and Males
- Weight at study initiation: 180-360 g after fasting, weight variation not to exceed 20% in or between groups.
- Fasting period before study: 18 h
- Housing: standard steel wire mesh cages, individually or in groups by sex.
- Diet (e.g. ad libitum): ad libitum, Wayne Lab Blox
- Water (e.g. ad libitum): ad libitum, fresh tap water, fir for human consumption, using an automatic watering system supplied by Edstrom Industries, Inc., Waterford, Wisconsin.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C, +/- 3 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12 hr dark/12 hr light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
No Vehicle

MAXIMUM DOSE VOLUME APPLIED: 2500 mg/kg

DOSAGE PREPARATION (if unusual): as received

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on range finding study
Doses:
1000, 3000, 6300, 10000 mg/kg (dose range finding study)
1000, 1600, 2000, and 2500 mg/kg (main study)
No. of animals per sex per dose:
2 males, 2 females (dose range finding study)
5 males, 5 females (main study)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed immediately after dosing, and at 1 and 4 hours after dosing, then once daily for 14 days. Body weight recorded days 7 and 14.
- Necropsy of survivors performed: yes, sacrified by CO2 inhalation
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
according to the method of Litchfield and Wilcoxon

Results and discussion

Preliminary study:
In a dose range finding study, 4 fasted animals, 2 per sex, were dosed with the test substance at 1000, 3000, 6300 and 10000 mg/kg via oral gavage. Signs observed were decreased activity, ptosis, salivation, decreased muscle tone, dyspnea, abnormal gait, abnormal stance, ataxia, discoloration around the mouth and anus and prostration. None of the rats died at 1000 mg/kg. All of the rats died at 3000, 6300, and 10000 mg/kg.
Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 569 mg/kg bw
Based on:
test mat.
95% CL:
ca. 1 243 - ca. 1 980
Sex:
male
Dose descriptor:
LD50
Effect level:
1 960 mg/kg bw
Based on:
test mat.
95% CL:
ca. 1 376 - ca. 2 792
Sex:
female
Dose descriptor:
LD50
Effect level:
1 231 mg/kg bw
Based on:
test mat.
95% CL:
ca. 860 - ca. 1 761
Mortality:
2 of 10 rats died at 1000 mg/kg, 5 of 10 died at 1600 mg/kg, 7 of 10 died at 2000 mg/kg, and 8 of 10 died at 2500 mg/kg.
Clinical signs:
Decreased activity, dyspnea, decreased muscle tone, salivation, ptosis, nasal discharge, chromodacryorrhea, diarrhea, abnormal stance, abnormal gait, lacrimation and prostration.
Gross pathology:
Necropsy of animals dying during study revealed fluid-filled stomachs and intestines, and multiple lesions in stomach. Terminal necropsy of the suriving animals revealed no visible lesions.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based upon the results, the calculated acute oral LD50 value for male and female rats treated with the test substance was determined to be 1569 mg/kg bw, with a 95% CL of 1243-1980 mg/kg. The test substance is therefore considered classified as acute oral toxicant category 4 according to CLP regulation.
Executive summary:

In the dose-range finding study, four fasted animals per dose level, two per sex, were administered the test article at 1000 / 3000 / 6300 and 10000 mg/kg, orally, by gavage.

Signs observed were decreased, activity, ptosis, salivation, decreased muscle tone, dyspnea, abnormal gait, abnormal stance, ataxia, discoloration around mouth and anus and prostration. None of the rats died at 1000 mg/kg. All of the rats died at the 3000 / 6300 and 10000 mg/kg dose levels.

Four groups of ten rats (five males and five females) were fatsed for eighteen hours and administered the test item at a dose levels of 1000 / 1600 / 2000 and 2500 mg/kg by oral gavage. Signs observed included decreased activity, dyspnea, decreased muscle tone, salivation, ptosis, nasal discharge, chromodacryorrhea, diarrhea, abnormal stance, abnormal gait, lacrimation and prostration. Two of ten rats died at 1000 mg/kg, five died at 1600 mg/kg, seven died at 2000 mg/kg and eight died at 2500 mg/kg. Necropsy of the animals dying on study revealed fluid-filled stomachs and intestines with multiple lesions in the stomach. No visible lesions were observed at terminal necropsy.

Based upon the results of the acute oral toxicity study in rats, the calculated acute oral LD50 for male and female rats treated with the test item, was determined to be 1569 mg/kg with 95% confidence limits of 1243 to 1980 mg/kg. The calculated acute oral LD50 in males was determined to be 1960 mg/kg with 95% confidence limits of 1376 to 2792 mg/kg. The calculated acute oral LD50 in females was determined to be 1231 mg/kg with 95% confidence limits of 860 to 1761 mg/kg.