3-morpholinopropylamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992-07-13 to 1992-07-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-morpholinopropylamine

EC Number:

204-590-2

EC Name:

3-morpholinopropylamine

Cas Number:

123-00-2

Molecular formula:

C7H16N2O

IUPAC Name:

3-morpholin-4-ylpropan-1-amine

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: no data
- Expiration date of the lot/batch: The identity, purity, strength and stability of the test article were the responsibility of the Sponsor.


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: no data, there was no apparent change in the physical state of the test article during storage or administration.
- Solubility and stability of the test substance in the solvent/vehicle: no data


OTHER SPECIFICS:
Specific gravity: 0.9888 gm/mL

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles Riv:er Laboratories, Inc., Wilmington, Massachusetts
- Age at study initiation: 6-10 weeks
- Fasting : yes
- Weight at study initiation: 180-294 grams (dose-range finding test); definitive test: 168-247 grams
- Fasting period before study: no data, however animals were fasted
- Housing: Rats were housed individually in stainless steel " wire mesh 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): Harlan Teklad Lab Blox@, ad libitum, checked daily and added or replaced as needed.
- Water (e.g. ad libitum): Water was monitored for contaminants at periodic intervals according to Standard Operating Procedure PH-018.
- Acclimation period: Minimum of five (5) days

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

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test article was dosed as received using specific gravity calculations.

Doses:

dose-range finding study: 500, 2500 and 5000 mg/kg
definitive study: 800, 1250 and 2000 mg/kg

No. of animals per sex per dose:

Dose-range finding study: 1
Definitive study: 5

Control animals:

no

Details on study design:

Dose-range finding study:
The rats were observed at approximately 1, 4, 24, 48 and 72 hours after dosing for pharmacological and toxicological effects.

Definitive study:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Pharmacological and toxicological effects - at approximately 1, 4 and 24 hours after dosing and once daily through Day 14
Viability - daily
Body weights - at study initiation, Days 7 and 14 or when found dead
- Necropsy of survivors performed: yes
All surviving rats were sacrificed by CO2 inhalation and a gross necropsy was performed at termination of the study

Statistics:

By the method of Litchfield and Wilcoxon via Innovative Programming Associates, LABCAT Module Version 4.22.

Results and discussion

Preliminary study:

Signs observed included decreased activity, abnormal gait, abnormal stance, dyspnea and prostration. None of the animals died at the 500 mg/kg dose level. Two of two animals died both at the 2500 and 5000 mg/kg dose levels.

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 790.9 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

2 888.2 mg/kg bw

Based on:

test mat.

Mortality:

In the main study one of ten animals died at the 800 mg/kg dose level.
None of the animals died at the 1250 mg/kg dose level and seven of ten animals died at 2000 mg/kg.

Clinical signs:

In the main study the effects observed included decreased activity, abnormal gait, abnormal stance, salivation, red urine, dyspnea, poor grooming and decreased muscle tone.

Body weight:

With the exception of a slight decrease in body weight of one male in the 2000 mg/kg dose level, there was an apparent increase in body weight of all surviving animals.

Gross pathology:

Necropsy of the animals dying on study revealed fluid-filled and/or distended stomachs and intestines.
No visible lesions were observed in any animal at terminal necropsy.

Any other information on results incl. tables

The data generated for the acute LD50 in females did not lend itself to the statistical method employed.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on the results from the Acute Exposure Oral Toxicity in rats, the, definitive acute oral LD 50 for males and combined sexes for the test item was determined to be 2888.2 mg/kg and 1790.9 mg/kg. Based on the LD50 for combined sexes and the criteria of the CLP Regulation, the test item is classified for acute oral toxicity category 4.