Cyclopropylamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 20,1997 to July 25, 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: European Economic Community(EEC):Annex V.,Test B.1, Acute Toxicity(oral)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Cyclopropylamine

EC Number:

212-142-2

EC Name:

Cyclopropylamine

Cas Number:

765-30-0

Molecular formula:

C3H7N

IUPAC Name:

cyclopropanamine

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source of test material：Eastman Chemical Company
- lot number of test material:X25192-033

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test substance,a liquid,was administered as received.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SASCO,Inc.,Stone Ridge(Kingston),NY
- Females (if applicable) nulliparous and non-pregnant: [yes]
- Age at study initiation: 8 weeks for male rats and 8-9 weeks for female rats
- Weight at study initiation: 171-239 grams for male rats and 152-182 grams for female rats
- Housing:
Animals were housed in an American Association for Accreditation of Laboratory Animal Care-accredited vivarium in accordance with the Guide for the Care and Use of Laboratory Animals (National Research Council, 1996). The rats were singly housed in suspended. stainless-steel,wire mesh cages.Cages and racks were washed once a week.Absorbent paper, used to collect excreta, was changed at least three times a week.

- Diet (e.g. ad libitum):
Certified Rodent Diet (PMI#5002, pelleted) was available ad libitum. Feed containers were cleaned weekly and refilled at least once a week. No known contaminants which would interfere with the outcome of this study were present in the feed. Analyses of feed are maintained on file within the testing laboratory.

- Water (e.g. ad libitum):Water was available ad libitum through an automatic watering system. The source of the water was the local public water system. There have been no contaminants dentified in periodic water analyses that would be expected to interfere with the conduct of the study. Semiannual analyses of water are maintained on file within the testing laboratory

- Method of randomisation in assigning animals to test and control groups :
The procedure for including animals inthe study was to randomly select and assign animals from the same shipment to the study. Randomization was done by computer-generated lists. After assignment of animals to the study, the body weights were determined to ensure that variation in individual body weights did not exceed 20% of the mean weight for each sex.

-Acclimation period:
The animals were isolated upon arrival and allowed to acclimate for a period of 5 days. Animals were judged to be healthy prior to testing.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 °C
- Humidity (%): 47-59% reIative humidity
- Photoperiod (hrs dark / hrs light): 12 hours light from. 6 a.m. to 6 p.m.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

A single dose ofthe test substance was administered by gavage to animals that had been fasted overnight.

Doses:

Based on results of a range-finding test, doses of 250, 500, and 1000 mg/kg ofthe test
substance were selected as the dose levels for the oral toxicity study.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days

- Body weight:
Body weights were collected on Days 0 (prior to tremment), 7, and 14.

- Clinical Observations:
Animals were observed three times on the day of dosing (Day 0), and once each day thereafter for the duration of the 15-day observation period. Observations included, but were not limited to, examination of the hair, skin, eyes, mucous membranes, motor activity, feces, urine, respiratory system, circulatory system, autonomic nervous system, central nervous system, and behavior patterns.

- Necropsy
Any animal that died during the study was necropsied on the day of death. All surviving animals were euthanatized and necropsied at the completion ofthe 15-day observation period.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

545 mg/kg bw

Based on:

test mat.

95% CL:

400 - 473

Effect levels 2

Sex:

male

Dose descriptor:

LD100

Effect level:

1 000 mg/kg bw

Effect levels 3

Sex:

male

Dose descriptor:

LD0

Effect level:

250 mg/kg bw

Effect levels 4

Sex:

male

Dose descriptor:

other: LD20

Effect level:

500 mg/kg bw

Effect levels 5

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

616 mg/kg bw

95% CL:

467 - 812

Effect levels 6

Sex:

female

Dose descriptor:

other: LD20

Effect level:

250 mg/kg bw

Effect levels 7

Sex:

female

Dose descriptor:

other: LD60

Effect level:

500 mg/kg bw

Effect levels 8

Sex:

female

Dose descriptor:

other: LD80

Effect level:

1 000 mg/kg bw

Effect levels 9

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

445 mg/kg bw

95% CL:

230 - 864

Mortality:

For male rats, mortality was 0% at the 250 mg/kg dose level, 20% at the 500 mg/kg dose level, and 100% at the 1000 mg/kg dose leveL .For female rats,mortality was 20% at the 250 mg/kg dose level, 60% at the 500 mg/kg dose level, and 80% at the1000 mg/kg dose leveL.

Clinical signs:

other: The major clinical signs of abnormality observed during the 15-day observation period included body weight loss or a reduced body weight gain, slight to moderate weakness, a reduced amount of faces, porphyrin staining of the hair of the face, inguinal hai

Gross pathology:

At necropsy. treatment-related changes seen in rats which died within 48 hours of dosing included blood in the stomach and intestinal tract. edema and red discoloration of the gastric mucosa,blood in the urinary bladder. dark and enlarged spleens,wet facial hair caused by salvia,
and inguinal hair that was either stained by urine or discolored red by urine.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Executive summary:

In an acute oral toxicity study , 3 groups of five male and five female Sprague Dawley Rat were given a single oral dose of Cyclopropylamine at doses of 250, 500,1000 mg/kg bw and observed for 15 days.The test substance, a liquid, was administered as received.

 

Oral LD50 Males =  616 mg/kg bw   (95%C.I.=467-812）

Oral LD50 Females =  445 mg/kg bw (95%C.I.=230-864）

Oral LD50 for the combined sex=545 mg/kg bw (95%C.I.=400-743）

 

Cyclopropylamine is classified as Category 4 based on the LD50 in females accorrding to GHS criteria.