4-methylmorpholine 4-oxide, monohydrate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From November 17, 1981 through November 21, 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Also abraded skin was exposed. Exposure for 24h. Occlusive dressing used.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-methylmorpholine 4-oxide, monohydrate

EC Number:

231-391-8

EC Name:

4-methylmorpholine 4-oxide, monohydrate

Cas Number:

7529-22-8

Molecular formula:

C5H11NO2

IUPAC Name:

4-methyl-4λ⁵-morpholin-4-one

Specific details on test material used for the study:

- Name of test material (as cited in study report): 4236-43-5, Order #J-86
- Substance type: Yellow liquid
- Physical state: liquid
- Purity: responsibility of the sponsor
- Stability: There was no apparent change in the physical state of the test article during administration
- Other: pH 10.2-10.3

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Perfection Breeders, Inc., Douglasville, Pennsylvania
- Weight at study initiation: 2 - 3 kilograms
- Housing: Separate isolation by the test system; rabbits were housed individually in cages sized in accordance with the "Guide for the Care of Laboratory Animals" of the Institute of Laboratory Resources, National Research Council.
- Diet (e.g. ad libitum): Wayne Rabbit Ration, ad libitum, checked daily and added or replaced as needed. Feeders are designed to reduce soiling, bridging, and scattering
- Water (e.g. ad libitum): Availability - fresh tap water, fit for human consumption, ad libitum, using 16 ounce glass bottles with rubber stopper and stainless steel sipper tube or an automatic watering system supplied by Edstrom Industries Inc., Waterford, Wisconsin.
- Acclimation period: five days

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

Test system

Type of coverage:

occlusive

Preparation of test site:

other: shaved and abraded

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL/site

Duration of treatment / exposure:

24 hours

Observation period:

Animals were observed for signs of erythema and edema and scored according to the Draize scale at 1, 24, 48 and 72 hours after application of the test material.

Number of animals:

Six (three males, three females)

Details on study design:

TEST SITE
- Area of exposure: The test article was administered at two skin sites, one abraded and one intact site.
- Type of wrap if used: Following nthe application of the test material, one-inch square gauze patches were applied to each of the two sites. The trunk of the animal was then wrapped with a rubber dam and an Ace bandage to retard evaporation.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the 24 hour exposure period, the wrappings were removed and the skin wiped to remove any remaining material. Animals were observed for signs of erythema and edema and scored according to the Draize scale at 1, 24, 48 and 72 hour after the application of the test material.

SCORING SYSTEM: Draize evaluation of dermal irritation

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Remarks:

based on 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Only intact skin taken into account

Results 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

based on 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Only intact skin taken into account

Irritant / corrosive response data:

Slight erythema was visible only at one hour after bandage removal in 3 animals. No edema was observed throughout the study.

Other effects:

No effects on body weight.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the observations made in the primary dermal irritation study in rabbits, the test article was not considered to be a dermal irritant. Based on the results of this test and the criteria of the CLP Regulation, the substance should not be classified for skin irritation.

Executive summary:

In a primary dermal irritation study performed equivalent/similar to OECD TG 404, three New Zealand White rabbits/sex were dermally exposed to 0.5 ml/site of 4-methylmorpholine 4-oxide. Test sites were covered with an occlusive dressing for 24 hours. Animals were then observed for 72 hours. Irritation was scored by the method of Draize.

Slight erythema was visible only at one hour after bandage removal in 3 animals. No edema was observed throughout the study.

In this study, the test materials is not a dermal irritant to the skin based on the lack of findings for edema and a transient observation of slight erythema.

Based on the results of this test and the criteria of the CLP Regulation, the substance should not be classified for skin irritation.