4-ethylmorpholine

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991-10-08 to 1991-11-5

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

Well documented study, GLP compliant, similar to OECD guideline 402. No deviations were recorded.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-ethylmorpholine

EC Number:

202-885-0

EC Name:

4-ethylmorpholine

Cas Number:

100-74-3

Molecular formula:

C6H13NO

IUPAC Name:

4-ethylmorpholine

Test material form:

liquid

Details on test material:

- Alternative names of reference substance: Jeffcat NEM; N-ethylmorpholine; 4-ethylmorpholin; Morpholine, 4-ethyl-
- Molecular formula: C6H13NO
- Molecular weight: 115.17
- SMILES notation: CCN1CCOCC1
- InChl: InChI=1/C6H13NO/c1-2-7-3-5-8-6-4-7/h2-6H2,1H3

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Stability under test conditions: no apparent change in the physical characteristics of the test article during administration

OTHER SPECIFICS:
Name of test material: 6398-36-20

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: 30 animals, from Hazleton reseach Products, denver, Pennsylvania and CAMM Research Lab Animals, Wayne, New Jersey
- Age at study initiation: young adult
- Weight at study initiation: 2180-2488 grams
- Fasting period before study:
- Housing: 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. Waste material was removed twice weekly. Cages and feeders were sanitized every two weeks.
- Diet (e.g. ad libitum): ad libitum, Purina Rabbit Chow
- Water (e.g. ad libitum): ad libitum, fresh tap water
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/-3°C
- Humidity (%): 30-70%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: fur was clipped from the dorsal area of the trunk of the test animals.
- % coverage: a square gauze patch was placed on the animals to cover the dosed area. Animals were wrapped with rubber dam and an elastic bandage to retard evaporation
- Type of wrap if used: Test material was applied directly on intact skin sites

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wrappings were removed and the skin sites were wiped with water and gauze to remove any residual test article.
- Time after start of exposure:24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): no data. test article was dosed as received using specific gravity calculations.

Duration of exposure:

24 hours (single exposure)

Doses:

1000, 2000 and 3000 mg/kg

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- observations: daily through day 14
- body weight: at initiation and on days 7 and 14
- Necropsy of survivors performed: yes. all surviving rabbits were sacrificed by a lethal injection on day 14 and a gross necropsy was performed
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Statistics:

LD50 calculations were performed via Litchfield and Wilcoxon on Pharmaceutical Calculations System, version 4.1.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 980.4 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 570.7 - <= 2 497

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

1 924 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 392.2 - <= 2 659

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

2 031.2 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 458.1 - <= 2 829.5

Mortality:

1000 mg/kg - 0/10
2000 mg/kg - 7/10
3000 mg/kg - 10/10

Clinical signs:

Decreased activity was observed during the study. Necrosis of the skin at the application sites was also observed.

Body weight:

no data

Gross pathology:

Necropsy of the animals dying on study revealed irritation of the underlying muscle at the application site. No visible lesions were observed in any animal at terminal necropsy.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute dermal LD50 in males and females was determined to be 1980.4 mg/kg (males 1924.0 mg/kg, females 2031.2 mg/kg). Therefore the substance is considered classified for acute dermal toxicant categoru 4.