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

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Dosing initiated: November 5 1985, Study termination (in vivo phase): November 8 1985

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:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

not specified

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-82-178
- Batch No: 3
- Physical state: Amber liquid
- Analytical purity: Assumed to be 100% pure.
- Storage condition of test material: Room temperature under nitrogen.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products, Inc., Denver, PA
- Age at study initiation: Approximately 16 weeks
- Weight at study initiation: Males: 2.54 to 3.29 kg, Females: 2.41 to 3.41 kg
- Housing: Individual suspended stainless steel cagel.
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow HF (pellets), ad libitum
- Water (e.g. ad libitum): Automatic watering system, ad libitum
- Acclimation period: 29 days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Maintained range of 65 to 71 degrees Fahrenheit
- Humidity (%): Maintained range of 40 to 70% relative humidity.
- Photoperiod (hrs dark / hrs light): Approximately 12 hours light and 12 hours dark by automatic timer.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Single 0.5 ml dose of test material.


VEHICLE
Not applicable.

Duration of treatment / exposure:

4 hours.

Observation period:

72 hours.

Number of animals:

6 (3 males, 3 females).

Details on study design:

TEST SITE
- Area of exposure: The day prior to topical administration of the test material, the hair of each rabbit on the dorsal surface from the shoulder region to the lumbar region was closely clipped with an electronic clipper. The skin was left intact. Elizabethan-type collars were placed around the neck of each rabbit at this time to acclimate them to wearing collars.
- Type of wrap if used: The test material was introduced under a gauze patch which was secured with tape. The patch was loosely held in contact with the skin by means of a semi-occlusive dressing for the duration of the exposure period.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): After exposure the dressing and gauze patch were removed. The skin was then washed with distilled water and paper towel to remove any remaining test material.
- Time after start of exposure: 4 hours.


SCORING SYSTEM:
Dermal responses were evaluated approximately 45 minutes, 24, 48 and 72 hours following patch removal. All scoring was made according to the Draize Method of Scoring.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Results 4

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Results 5

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Results 6

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints apart from 45 minutes

Results 7

Irritation parameter:

erythema score

Basis:

mean

Remarks:

: Mean result over all 6 animals

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Results 8

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Results 9

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Results 10

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Results 11

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Results 12

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Results 13

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpointsapart from 45 minutes

Results 14

Irritation parameter:

edema score

Basis:

mean

Remarks:

: Mean result over all 6 animals

Time point:

other: mean of 24, 48 and 72 hours

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Irritant / corrosive response data:

All animals survived to study termination. Two animals were noted with their collars off and one animal was noted with its collar in its mouth at the time off undamming.

Signs of dermal corrosion, necrosis, were observed in 5 animals at the 45 minute observation and in all 6 animals at the remaining intervals.

Erythema was noted in all animals during the study. Five animals were noted with severe erythema at the 45 minute observation, while one animal displayed moderate-to-severe erythema. All animals displayed severe erythema at the 24, 48 and 72 hour observations.

Edema was also noted in all animals during the study. At the 45 minute observations five animals were scored with slight edema and one animal was noted with very slight erythema. From 24 hours through to study termination all animals displayed slight edema.

Other effects:

During the test period, atonia was noted for 4 animals, blanching was noted for 3 animals, and leathery skin was noted for 2 animals. One animal was noted to have an area of eschar measuring approximately 3.0 x 2.0 cm on the upper edge of the dose site at the 48 hour observation.

Applicant's summary and conclusion

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

All animals exhibited necrosis, a sign of dermal corrosion during the test period.

Executive summary:

The dermal corrosivity potential of the test substance was evaluated following its application to the clipped backs of six New Zealand White rabbits. The test material was administered as a single 0.5 ml dose introduced under a gauze patch which was secured with tape. The patch was loosely held in contact with the skin by means of a semi-occlusive dressing. The dressing remained in place for four hours. After exposure was completed, the dressing and gauze were removed and the test site graded for erythema, edma and other signs of dermal irritation at 45 minutes, 24, 48 and 72 hours following patch removal. All dermal scoring was made according to the Draize method of scoring.

All animals survived to study termination.

All animals exhibited necrosis, a sign of dermal corrosion during the test period.

Erythema was noted in all animals during the test period, ranging from moderate-to-severe to severe. Edema was also noted in all animals ranging from very slight to slight.

Supplemental dermal observations noted over the study period included blanching, eschar, atonia and leathery skin.

Based on these findings, the test substance should be considered corrosive to rabbit skin.