4-ethylmorpholine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Justification for type of information:

acute toxicity study performed according to OECD guideline 401, considered reliable in OECD SIDS document, compliant to GLP.

Data source

Reference

Reference Type:

publication

Title:

Acute oral toxicity

Author:

Japanese government

Year:

2005

Bibliographic source:

OECD SIDS Initial Assessment Report for SIAM21 and OECD Agreed Conclusions

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

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:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 2901P0 (obtained from Nippon Nyukazai Co., Ltd. (Tokyo, Japan))
- Expiration date of the lot/batch: no data
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: stable for 8 days as diluted solution in refrigerator
- Stability under test conditions: stable for 8 days as diluted solution in refrigerator

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Crj:CD(SD)IGS rats bought from Charles River Japan, Inc.
- Age at study initiation: 4 week old
- Weight at study initiation: no data
- Fasting period before study:no data
- Housing:no data
- Diet (e.g. ad libitum):no data
- Water (e.g. ad libitum):no data
- Acclimation period: for 8 days before use

ENVIRONMENTAL CONDITIONS
- Temperature (°C):no data
- Humidity (%):no data
- Air changes (per hr):no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

water for injection

Details on oral exposure:

VEHICLE
- no data

MAXIMUM DOSE VOLUME APPLIED:no data

DOSAGE PREPARATION (if unusual): On the previous day of the administration, the test solution was prepared and diluted to dosing concentrations by injection solvent. They were kept in a refrigerator. The diluted solution was also confirmed to be stable for 8 days

CLASS METHOD (if applicable)
no data

Doses:

500, 1000, 1500, 2000 mg/kg bw

No. of animals per sex per dose:

40 animals in total
5 males and 5 females per group

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Mean body weights and their standard deviations were calculated for every group

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

> 1 500 - < 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Males: mortality occurred at 1500 mg/kg bw and higher from 1 hour after treatment until day 2 of the observation period. The LD50 for NEM was estimated to be between 1500 and 2000 mg/kg bw.
- 500 mg/kg bw : 0/5
- 1000 mg/kg bw : 0/5
- 1500 mg/kg bw : 1/5
- 2000 mg/kg bw : 3/5
Females: mortality occurred at 1000 and 2000 mg/kg bw from 1 to 3 hours after treatment. The LD50 for NEM was estimated to be approx. 2000 mg/kg bw.
- 500 mg/kg bw : 0/5
- 1000 mg/kg bw : 1/5
- 1500 mg/kg bw : 0/5
- 2000 mg/kg bw : 2/5

Clinical signs:

Most males and females given 1000 mg/kg b.w. and higher showed tonic and/or clonic convulsions just after administration and then showed decrease in locomotor activity. These clinical signs disappeared by day 2 of observation, except for decrease of amount of stool at 1500 or 2000 mg/kg b.w. No abnormal signs were observed after day 3.

Body weight:

Body weight gain of both sexes was suppressed at 1500 mg/kg b.w. and higher until the day 4 of observation.

Gross pathology:

Dead animal: edema and red areas in the glandular stomach were found
survival animals: no abnormalities were found in the surviving animals

Other findings:

no data

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 values for NEM are considered to be between 1500 and 2000 mg/kg bw for males and approx 2000 mg/kg bw for females. Therefore the test substance NEM is considered to be classified as category 4 according to CLP classification.