4-methylmorpholine

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-10-10 - 1990-10-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-methylmorpholine

EC Number:

203-640-0

EC Name:

4-methylmorpholine

Cas Number:

109-02-4

Molecular formula:

C5H11NO

IUPAC Name:

4-methylmorpholine

Test material form:

liquid

Specific details on test material used for the study:

- Name of test material (as cited in study report): 6398-24-20, Project #90-005
- Substance type: clear, colorless liquid
- Physical state: liquid
- Stability under test conditions: There was no apparent change in the physical characteristics of the test article during administration.
- Other: specific gravity: 0.92 g/mL; pH 10.8 (taken from MSDS)

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hare-Marland, Hewitt, New Jersey, USA
- Age at study initiation: young adult animals
- Weight at study initiation: males 2224-2691 g (mean 2430 g); females 2224-2775 g (mean 2380.6 g)
- Housing: Rabbits were housed individually in cages sized in accordance with the "Guide for the care and use of laboratory animals' of the Institute of Laboratory Animal Resources, National Research Council
- Diet (e.g. ad libitum): Purina Rabbit Ration, H.F., ad libitum, checked daily and added or replaced as needed. Feeders are designed to reduce soiling, bridging and scattering
- Water (e.g. ad libitum): fresh tap water, ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C
- Humidity (%): 30 to 70%
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
Approximately 24 hours before testing, fur was clipped from the dorsal area of the trunk of the test animals. The test article was applied directly onto the exposed intact skin of the animals taking care to spread the substance evenly over the entire area. A square gauze patch was placed on the animals to cover the dosed area. A square gauze patch was placed on the animals to cover the dosed area. The animals were wrapped with rubber dam and an elastic bandage to retard evaporation.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test article was held in contact with the skin for twenty-four hours. Following the twenty-four hour period of exposure, the wrappings were removed.

Duration of exposure:

24 hours

Doses:

3000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Observations were recorded daily through day 14. Body weights were recorded at initation and on days 7 and 14 or upon death. All surviving rabbits were sacrificed by a lethal injection of BeuthanasiaR solution on day 14 and a gross necropsy was performed.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 000 mg/kg bw

Based on:

test mat.

Mortality:

Three of ten rabbits died during the study (2 males, 1 female).

Clinical signs:

other: Clinical signs observed during the limit test included decreased activity, decreased muscle tone, abnormal stance, abnormal gait, hind end drop and dyspnea.

Gross pathology:

Necropsy of the animals dying on study included pale and/or mottled liver, pale and/or mottled kidneys, dark red and mottled lungs, oral and/or nasal discharge, and severe irritation of the underlying muscle at the application site.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the observations made in this Acute Exposure Dermal Toxicity Study in rabbits, the estimated dermal LD50 for the substance was determined to be greater than 3000 mg/kg. The substance is considered not classified as acute dermal toxicant according to criteria laid down in the CLP Regulation.