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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 4th 1982 to February 18th 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 402 (Acute Dermal Toxicity)

Deviations:

not specified

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

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:
Colourless liquid

- Analytical purity:
Assumed 100% pure

- Storage condition of test material:
Room temperature, airtight container

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
Dutchland Laboratory Animals, Denver, PA

- Age at study initiation:
Approximately 12 weeks

- Weight at study initiation:
2.6 to 3.5 kg

- Fasting period before study:
- Housing:
Individual in suspended stainless steel caging

- Diet (e.g. ad libitum):
Purina Certified Rabbit Chow (pellets) ad libitum

- Water (e.g. ad libitum):
Automatic watering system ad libitum

- Acclimation period:
30 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C):
Monitored twice daily; maintained range of 65 to 71 degrees Fahrenheit

- Humidity (%):
Monitored once daily; maintained range of 40 to 70% relative humidity

- Photoperiod (hrs dark / hrs light):
12 hours light, 12 hours dark by automatic timer

IN-LIFE DATES: From: Day 1 To: Day 14

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure:
The dorsal surface from the shoulder to the lumber region (approximately 200 square centimeters)

- % coverage:
10%

- Type of wrap if used:
Covered with a gauze patch which was secured with tape. To retard evapouration, to prevent ingestion of the test material, and to keep the substance in contact with the skin, the gauze patches were secured to the trunk of the animals with tape and a plastic sleeve.

REMOVAL OF TEST SUBSTANCE
- Washing (if done):
The plastic sleeve, tape, and gauze patches were removed and the skin was wiped (but not washed) to remove any test material still remaining.

- Time after start of exposure:
After approximtely 24 hours

TEST MATERIAL
- Amount applied (volume or weight with unit):
3.16 g/kg

- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

3160 mg/kg bw

No. of animals per sex per dose:

6 Male and 6 Female rabbits were abraded, 3 Male and 3 Female rabbits skin was left intact (but still exposed to the test material).

Control animals:

no

Details on study design:

- Duration of observation period following administration:
14 days

- Frequency of observations and weighing:
The animals were checked for viability once in the morning (before approximatel 10:30am) and once in the afternoon (after approximately 3:00pm).
The dermal responses were evaluated at approximately 24 hours after dosing (after removing the patched), and on Days 3, 7, 10 and 14 according to the Draize Method of Scoring.
Body weights were recorded the day of dosing and at death should an animal succumb prior to study termination.

- Necropsy of survivors performed:
yes

- Other examinations performed:
Clinical Observations were made for the nature, onset, severity, and duration of toxicological signs at 2 and 24 hours immediately after dosing, nd once a day thereafter for a total of 14 days.

Statistics:

The means and standard deviations of initial body weights are presented below.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 160 mg/kg bw

Mortality:

There was one spontaneous death during the study, Animal No. 349M, on Day 4 post-dosing (test day 5). The cause of death for this animal was not determined.

Clinical signs:

other: Clinical observations included: nasal discharge, respiratory rate increase, ocular discharge, activity decrease, fine tremors, respiratory rate decrease, no stool, emaciation, food consumption decrease, soft stool, labored breathing, urinary staining, ora

Gross pathology:

Necropsy observations included:
skin of dosing site thickened, with red exudate, dark red to black, some with scabbing, surface hard or soft, all animals exept Animal No. 349M which died on Test Day 5.
In addition to the observations noted for the dorsal skin, Animal No. 327M showed ocular discharge, red lungs, and an accessory lobe on the left adrenal; Animal No. 351M showed nasal and ocular discharge, alopecia, a cavernous subcutaneous skin region filled with red fluid, vascularity of the subcutaneous skin, enlarged submaxillary gland with scattered fluid-filled areas, hair ball in stomach, and a general condition of emaciation; Naimal No. 361M showed tan and dark red mottling of the right apical lobe of the lung; Animal No, 363M showed a small gall bladder; Animal No. 367M showed surfaces on the ventral abdomen that were extremely thickened, releaseing fluid on incision, and moderate reddening of the duodenum and descending colon, and hair balls in stomach; Animal No. 328F showed hair matted in stomach, and grey foci on all lobes and surfaces of lungs; Animal No. 334F showed scattered hair balls in the stomach and modorate dark red foci on all lobes and surfaces of the lungs; Animal 350F showed ocular and nasal discharge, red foci and general bright redness of lungs, and a small hair ball in stomach; Animal No. 354F showed scattered lesions on ventral abdomen, and hair ball in stomach; Animal No. 366F showed hair in stomach contents, scattered dark red and grey foci on lungs; Animal No. 368F had moderate to extreme pitting on both kidney surfaces.

Other findings:

Not applicable.

Any other information on results incl. tables

Necropsy observations of Animal 349M:

The dorsal skin of this animal showed moderate to extreme reddened areas, slightly raised and filled with a clear, viscous tan fluid. This animal also showed extreme reddening of colon, rectum, G.I tract, and fecal, urinary staining, nasal discharge.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal toxicity of MRD-82 -10 was evaluated following administration by the dermal route at 3160 mg/kg body weight to 6 male and 6 femal rabbits and was found to be >3160 mg/kg.

Executive summary:

The acute dermal toxicity of MRD-82 -10 was evaluated following administration by the dermal route at 3160 mg/kg body weight to 6 male and 6 femal rabbits. The animals' backs were clipped, the skin was left intact for 6 animals, and each rabbit was fitted with an Elizabethan-type collar during the day prior to administration of the test material.

Immediately prior to dosing, the exposed skin of the remaining six animals was abraded longitudinally every two to three centimeters. The abrasions were deep enough to penetrate the stratum corneum, but not so deep as to disturb the dermis or produce bleeding. The test material was held in place with a gauze patch which was secured with tape. After approximately twenty-four hours of exposure, the gauze patches were removed and the amount of the excess material remaining was noted and gently wiped from the skin. Observations for toxicological signs were made at 2 and 24 hours immediately after dosing, and once each day for a total of 14 days. Dermal responses were evaluated at approximately 24 hours post exposure (after removal of the gauze patches), and on Days 3, 7, 10 and 14 days after test material administration. Body weights were recorded the day of dosing, or at death if an animal died spontaneously. Animals that did not succumb were sacrificed at Day 14.

There was one spontaneous death during the study, Animal No. 349M on Day 4 post-dosing (Test Day 5). The cause of death for this animal was not determined.

Necrosis was observed in all animals from the 24 -hour observation through study termination. Other findings included: atonia, leathery skin, fissurins, desquamation, eschar and exfoliation. There was no lessening of the severity of irritation over time.