4-methylmorpholine 4-oxide, monohydrate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From November 17, 1981 through November 24, 1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

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 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

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 under test conditions: There was no apparent change in physiological state of the test article during administration

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Perfection Breeders, Inc., Douglassville, Pennsylvania
- Weight at study initiation: males 2.021-2.096 kg; females 2.103-2.124 kg
- Housing: Separate isolation by 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 boiling, 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): 20-21°C
- Humidity (%): 51-58%
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the contralateral eye remained untreated and served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

Single exposure

Observation period (in vivo):

The eyes were examined at 1, 24, 48 and 72 hours and 7 days after treatment.

Number of animals or in vitro replicates:

six animals

Details on study design:

SCORING SYSTEM: An animal exhibited a positive reaction when the test substance produced one or more of the following signs: ulceration of the cornea (other than a fine stippling), opacity of the cornea (other than a slight dulling of the normal luster), inflammation of the iris (other than a slight deepening of the rugae or a light hyperemia of the circumcorneal blood vessels), and obvious swelling in the conjunctivae (excluding the cornea and iris) with partial eversion of the eyelids and a diffuse crimson color with individual vessels not easily discernible.

Grading: according to the method of Draize

Classification of the test substance:
Non-irritant: 0 or 1 rabbit with positive scores
Indeterminate: 2 or 3 rabbtis with positive scores
Irritant: 4 to 6 rabbits with positive scores

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

based on 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

based on 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

based on 6 animals

Time point:

24/48/72 h

Score:

0.44

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

based on 6 animals

Time point:

24/48/72 h

Score:

0.22

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 5

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

mean

Remarks:

based on 6 animals

Time point:

other: 24, 48, 72 hours

Score:

0.22

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

Five rabbits exhibited a positive response at the one hour observation period. Two rabbits exhibited a positive response at the 24 hour reading. One positive response was observed at the 48 hour reading. No positive responses were observed at 72 hour or on day 7. Eight positive responses were recorded during the course of 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 Acute Eye Irritation Test in Rabbits, the substance was determined to be a mild eye irritant. Based on the CLP classification criteria, the substance does not need to be classified for eye irritation.

Executive summary:

In a primary eye irritation study performed equivalent/similar to OECD TG 405, 0.1 ml of 4-methylmorpholine 4-oxide was instilled into the conjunctival sac of six New Zealand White rabbits. Animals were then examined at 1, 24, 48 and 72 hours and 7 days after treatment. Irritation was scored by the method of Draize.

The mean cornea opacity and iris score from the 24, 48 and 72 hours time-points were 0, based on six animals. The mean conjunctivae score for redness was 0.44 and for discharge was 0.22. The mean chemosis score was 0.22. All effects were fully reversible, as there were no positive responses observed after 72 hours or on day 7.

In this study, the test material is not an eye irritant. Based on the CLP classification criteria, the substance does not need to be classified for eye irritation.