Cyclopropylamine

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 30,1984 toJuly 31,1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: EC Directive 83/467/EEC of 29 July 1983

GLP compliance:

not specified

Test type:

traditional 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
-Date of manufacture, filling:August 1983

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Stability: At least 2 years when light and air are excluded.

Test animals

Species:

rat

Strain:

Wistar

Remarks:

SPF

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-Male and female Wistar rates (strain: SPF-Wistar/Chbb:THOM; Breeder: Dr. K. Thomae GmbH, 7950 Biberach)
-Mean baseline body weight: male animals 248 (215-285) g, female animals 182 (156-207) g.
-Age at the start of testing: 8 weeks.
-The feed used for the animals was the KLIBA Laboratory Diet Rat/Mouse A 343 10 mm pellets from Klingentalmühle AG, CH-4303 Kaiseraugst together with drinking water ad libitum during the observation period.The feed used during the test was checked for impurities. Impurities of the type found in commercial animal feed should not affect the outcome of the test, given the objective and duration of the test.
-The drinking water is regularly checked for impurities by the town of Frankenthal and by the Water Chemistry and Technical Services Department of BASF Aktiengesellschaft. Based on the results, the suitability of the drinking water used could be certified. The Drinking Water Ordinance of 31.01.75 served as a guideline.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24℃
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 hours

Administration / exposure

Route of administration:

inhalation: mixture of gas and vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

-Exposure system
Whole-body inhalation system, wire cages, each with 5 animals, inside a glass-steel inhalation chamber, V = approximately 200 L.
-Generator system
A vapour-air mixture was generated using an INFU 362 continuous infusion pump (INDIGEL/ Switzerland) and a glass evaporator with thermostat (BASF) and downstream cooler.
-Test set-up
The substance to be tested was fed at a constant rate by means of a metering pump to an evaporator heated to 40°C. The resulting vapour was passed through a cooler set to 30°C, mixed with a stream of fresh air and fed to the inhalation system.
The nominal concentration was determined from the consumption of the substance and the air flow.
The air supply was conditioned by the central air conditioning system, so that the temperature in the exposure apparatus was 19-25°C. There were no deviations from this requirement that could have affected the test results.
The inhalation mixture was supplied to the animals for inhalation over a period of 4 hours.
The air extraction system was set to be 100 L/hour higher than the air supply system (negative pressure mode). This ensured that no contamination of the laboratory could occur as a result of potential leaks in the inhalation chambers.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

13.1 mg/L,10.5 mg/,9.9 mg/L, 8.0 mg/L,3.5 mg/L

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Clinical:
The body weights of the animals were determined at baseline, after 7 and 8 days and at the end of the observation period and were presented graphically. Clinical assessments were performed each working day and lethality was monitored daily.
- Dissection
After the observation period, surviving animals were sacrificed using CO2 and, like all animals that had died previously, were subjected to a pathological-anatomical assessment.

Statistics:

The statistical evaluation of the concentration-effect relationship was based on a probit analysis according to D.J. Finney (Finney, D.J: Probit analysis 1971, pages 1 - 150. Published by the Syndics of the Cambridge University Press, Bentley House, 200 Euston Road, London N.W. 1).

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LC50

Effect level:

ca. 10.5 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 9.9 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

10.5 - 13.1 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

refer to "Any other information on results incl. tables"

Clinical signs:

bodyweight loss

Body weight:

- lower than 10% body weight loss

Gross pathology:

Animals that had died (male and female):
General congestive hyperaemia
Lungs: mild to moderate emphysema in one male animal, patchy perfusion patten with mild oedema.
Liver: isolated anaemic pressure patterns with mild steatosis or enlarged lobular peripheral regions .
Sacrificed (male and female) animals:
Organs unremarkable.

Any other information on results incl. tables

Time to lethality	Test group (concentration)      1 (13.1 mg/L)       2 (10.5 mg/L)         3 (9.9 mg/L)           4 (8.0 mg/L)            5 (3.5 mg/L)
	Number of dead animals/Number of exposed animals
	m	f	m	f	m	f	m	f	m	f
4 hours	3/10	8/10	1/10	1/10	1/10	0/10	0/10	0/10	0/10	0/10
1 day	10/10	10/10	2/10	4/10	4/10	1/10	-	-	-	-
2 days	-	-	-	-	-	-	-	-	-	-
7 days	-	-	-	-	5/10	-	-	-	-	-
14 days	-	-	-	-	-	-	-	-	-	-
Total at the end of the test	20/20		6/20		6/20		0/20		0/20

 

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Executive summary:

In an acute inhalation toxicity study , groups of young adult SPF-Wistar rats (10 animals in each Male and Female group) were exposed by inhalation route to Cyclopropanamine in a vapour-air mixture for 4 hours to whole body at concentrations of  3.5, 8.0 ,9.9,10.5 and 13.1 mg/L.  Animals then were observed for 14 days.

 

LC₅₀ Males =  approximately 9.9  mg/L 

      Females =  approximately 10.5mg/L 

      Combined = 10.5 mg/L < LC₅₀ < 13.1 mg/L 

  

Cyclopropanamine is classified as Category 4 accroding to GHS criterion based on males.