7,7-dimethyl-3-oxa-6-azaoctan-1-ol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Dosing initiated February 3 1982, Study termination 17 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

7,7-dimethyl-3-oxa-6-azaoctan-1-ol

EC Number:

400-390-6

EC Name:

7,7-dimethyl-3-oxa-6-azaoctan-1-ol

Cas Number:

87787-67-5

Molecular formula:

Hill formula: C8 H19 N O2 CAS formula: C8 H19 N O2

IUPAC Name:

2-[2-(tert-butylamino)ethoxy]ethan-1-ol

Details on test material:

- Name of test material (as cited in study report): MRD-82-10
- Physical state: Colorless liquid
- Analytical purity: Assumed to be 100% pure for purposes of dosing
- Storage condition of test material: Room temperature in airtight container.

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, Kingston, NY
- Age at study initiation: Approx. 12 weeks
- Weight at study initiation: Males: 302-380 g, Females: 205-265 g.
- Fasting period before study: All food was removed at approximately 4.00pm during the evening immediately prior to the day of administration of the test material. Food was withheld until completion of dosing the following morning.
- Housing: 5 animals per cage per sex. Suspended stainless steel.
- Diet (e.g. ad libitum): Purina Certified Rat Chow (ad libitum)
- Water (e.g. ad libitum): Automatic watering system (ad libitum)
- Acclimation period: 29 days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Maintained range of 68 to 76 degrees Fahrenheit during study.
- Humidity (%): Maintained range of 40 to 70% RH during study.
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark by automatic timer.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE:
Not applicable.

DOSAGE PREPARATION (if unusual): The undiluted test material was administered by a single oral intubation via syringe and a No. 13 stainless steal, straight ball-tipped feeding needle.

Doses:

Seven dose levels: 1000 mg/kg, 1470 mg/kg, 2150 mg/kg, 3160 mg/kg, 4640 mg/kg, 6810 mg/kg, 10000 mg/kg

No. of animals per sex per dose:

5 per sex per dose.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made as to the nature onset, severity, and duration of toxicological signs at 1, 2, 4 and 6 hours immediately after dosing and once a day thereafter for a total of 14 days.
Bodyweights were recorded immediately before dosing and at Day 7, 14 and at death if before day 14.
- Necropsy of survivors performed: yes

Statistics:

The means and standard deviations of the body weights were calculated.

The estimated LD50 was calculated (using probit and low-dose values) using maximum likelihood estimates or the Litchfield-Wilcoxon Method. The dose-response curve slope, intercept and 95% confidence interval for the LD50 were calculated.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

1 713.01 mg/kg bw

95% CL:

1 209.7 - 2 425.74

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

1 395.61 mg/kg bw

95% CL:

905.98 - 2 149.87

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 467.12 mg/kg bw

95% CL:

1 150.28 - 1 871.24

Mortality:

A total of 53 out of 70 animals succumbed during the study.
Animals died in every dose group.
Group 1 (1000 mg/kg): 3 animals died.
Group 2 (1470 mg/kg): 1 animal died.
Group 3 (2150 mg/kg): 9 animals died.
Group 4 (3160 mg/kg): 10 animals died.
Group 5 (1640 mg/kg): 10 animals died.
Group 6 (6810 mg/kg): 10 animals died.
Group 7 (10000 mg/kg): 10 animals died.

Clinical signs:

other: The most frequently observed toxicological signs were: dry rales, hypoactivity, oral discharge, and in Group 7, ataxia. Less frequent observations included nasal discharge, hypopnea, dyspnea, wet rales, ocular discharge, A/G staining, unthrifty coat, alo

Gross pathology:

There was a high incidence of internal abnormalities noted during necropsy, especially in the higher dose groups. The most frequent observation was reddening and/or distension of the gastro-intestinal tract, appearing in forty-one out of seventy animals. Twenty-one animals had distended stomachs containing either gas or fluid, and in sixteen animals the stomach was reddened. In seventeen animals the stomach fundus was dark red to black in colour, and in foureen animals it was thickened and reddened. The cecum appeared distended in six animals.

The brain was vascularized in twenty animals, the liver contained an accentuated lobular pattern in nine animals, four animlas had red fluid in the urinary bladder, and the thymus of seven animals contained foci. There was scattered foci and/or redness in the lungs of twenty-nine animals, however this observation could be a result of euthanizing with CO2.

Observations of less frequency included reddened megenteric lymph nodes in two animals, enlarged lymph nodes in one. Three animals had vascularized cecums.

There were two observations each of the following: thickened and congested liver, dilated renal pelvis of the kidneys, undescended testes, red material in the stomach, reddended acities of the abdominal cavity and dark red liver and kidneys, and reddened cervical lymph nodes.

There was one observation each of the following: enlarged testes, reddened mucosa in the jejunum, uterus diminished in size, yellow material in the stomach, reddened stomach mucosa, brown material in the cecum, red striations of the kidney cortex, vascularized testes, red fluid in the scrotal sac, reddened duodenum, and reddended abdominal muscles. It cannot be conclusively determined which of these observations were a result of treatment with the test substance or were part of the post-mortem antolysis observed in seventeen animals.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance is harmful based upon the LD50 results according the EU classification guidelines.

Executive summary:

The acute toxicity of the test substance was evaluated when administered by the oral route at seven different dose levels: 1000 mg/kg, 1470 mg/kg, 2150 mg/kg, 3160 mg/kg, 4640 mg/kg, 6810 mg/kg and 10000 mg/kg. The animals were fasted during the evening prior to administration of the test material. Observations for toxicological signs were made at 1, 2, 4, and 6 hours immediately after dosing and once each day for a total of 14 days. Body weights were recorded the day prior to dosing (pre-dose), on the day of dosing (fasted bodyweights), at Day 7, at Day 14, or whenever animals succumbed. Animals that did not succumb were sacrificed on Day 14.

The LD50 for males was calculated to be 1713.01 mg/kg with 95% confidence interval of 2425.74 - 1209.70 mg/kg; female LD50 was calculated to be 1395.61 with a 95% confidence interval of 2149.87 - 905.98; the combined (male and female) LD50 was calculated to be 1467.12 mg/kg with a 95% confidence interval of 1871.24 - 1150.28 mg/kg.

A total of fifty-three animals out of seventy succumbed during the course of the study. Animals died in every dose group. Group 4 (3160 mg/kg), Group 5 (1640 mg/kg), Group 6 (6810 mg/kg) and Group 7 (10000 mg/kg) each lost ten animals.

The most frequently observed toxicological signs were dry rales, hypoactivity, oral discharge, and in Group 7 ataxia. Also observed were: wet rales, dyspnea, hypopnea and nasal discharge.

Mean body weights at the end of the study showed an increase over the pre-dose mean weights for the animals that survived, those that succumbed had a loss in weight from the pre-dose mean.

The most frequently observed internal abnormalities at necropsy were reddening and/or distension of the gastro-intestinal tract (forty-one animals), distended stomachs containing either gas or fluid (twenty-one animals), reddened stomachs (sixteen animals), dark red to black stomach fundus (seventeen animals), and thickened and reddened stomach fundus (fourteen animals).