N,N'-bis(3-aminopropyl)piperazine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 1979 - January 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N'-bis(3-aminopropyl)piperazine

EC Number:

230-589-1

EC Name:

N,N'-bis(3-aminopropyl)piperazine

Cas Number:

7209-38-3

Molecular formula:

C10H24N4

IUPAC Name:

3-[4-(3-aminopropyl)piperazin-1-yl]propan-1-amine

Test material form:

liquid

Details on test material:

- name (as stated in the report): N,N'-Bis-aminopropyl-piperazin
- chemical name: 1,4-Bis-(aminopropyl)-piperazin

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Fasting period before study: 15 - 20 hours
- Diet: Herilan MRH-Haltung, Eggersmann KG
- Weight at study initiation: males: 140 - 210 g, females: 160 - 190 g

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

water

Details on oral exposure:

Substance was diluted in water

Doses:

5000 mg/kg bw (50 % dilution); 3160 mg/kg bw (31.6 %); 2150 mg/kg bw (21.5 %); 1470 mg/kg bw (14,7 %); 1000 mg/kg bw (10 %)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

The test compound was administered orally to 5 groups of 10 rats (5 male, 5 female) fasted for 15 - 20 hours prior to dosing. The animals were observed during the day of dosing and daily thereafter for 14 days. Decents during the study were examined for gross lession.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 980 mg/kg bw

95% CL:

>= 1 694 - <= 2 330

Mortality:

1000 mg/kg bw: 0/5 (females) and 0/5 (males)
1470 mg/kg bw: 1/5 (females) and 0/5 (males), The decedent was found within 1 day post-treatment.
2150 mg/kg bw: 4/5 (females) and 2/5 (males), The male decedents were found within 1 day post-treatment. 3 female decedents were found within 1 day post-treatment, the other one on the second day.
3160 mg/kg bw: 5/5 (females) and 5/5 (males), The decedents were found within 1 day post-treatment.
5000 mg/kg bw: 5/5 (females) and 5/5 (males), 2 female decedents were found after the first hour post-treatment. The rest were found within 1 day post-treatment.

Clinical signs:

other: 1000 mg/kg bw: no clinical signs 1470 mg/kg bw: dyspnea, apathy, hunched posture, uncoordinated movements, atony, disrupted nociceptive reflex, coma, spastic gait, strongly yellow urine, shaggy fur, cyanose, bad general condition 2150 mg/kg bw: dyspnea, a

Gross pathology:

dead rats:
heart: acute dilatation, hyperaemia
stomach: diffuse redness of gastric mucosa
intestine: diffuse redness of intestinal mucosa
liver: enlarged liver, confluent clay-coloured lobular pattern

killed rats: no findings

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50: 1980 mg/kg/bw
EU CLP / UN GHS: Acute toxicity category 4: harmful if swallowed

Executive summary:

N,N'-bis-(3 -aminopropyl)piperazine was administered orally to 5 groups of 10 rats (5 male, 5 female). The substance was delivered as formulation in water in 5 different concentrations 50 % (5000 mg/kg bw), 31.6 % (3160 mg/kg bw), 21.5 % (2150 mg/kg bw), 14.7 % (1470 mg/kg bw), 10 % (1000 mg/kg bw). All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 14).

The body weight gain shown by the surviving animals over the study period was considered to be normal.

Macroscopic post mortem examination of the animals found dead during the study revealed abnormalities in the heart (acute dilatation, hyperaemia), stomach (diffuse redness of gastric mucosa), intestine (diffuse redness of intestinal mucosa), liver (enlarged liver, confluent clay-coloured lobular pattern. No abnormalities were revealed in the surviving animals.

The oral LD50 value of N,N'-bis(3 -aminopropyl)piperazine in rats was established to be 1980 mg/kg/bw.

Based on these results:

- according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations, N,N'-bis(3 -aminopropyl)piperazine should be classified as: harmful if swallowed (Category 4) for acute toxicity by the oral route.