Nonamethylenediamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 Feb. 1996 to 8 Mar. 1996

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:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Nonamethylenediamine

EC Number:

211-470-3

EC Name:

Nonamethylenediamine

Cas Number:

646-24-2

Molecular formula:

C9H22N2

IUPAC Name:

nonane-1,9-diamine

Details on test material:

- Name of test material: Nonane-1,9-diamine
- Physical state: White crystalline solid
- Analytical purity: > 99%
- Lot/batch No.: 960201
Test substance was formulated in distilled water.

Test animals

Species:

mouse

Strain:

other: SPF Crlj:CD1(ICR)

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hino Breeding Center of Charles River Japan, Ltd.
- Age at study initiation: 8 days.
- Weight at study initiation: between 28 and 30g.
- Housing: in polycarbonate solid-floored cages with wood flakes (White Flake TM, Oriental Yeast Co., Ltd., Japan) in the animal room
- Diet (e.g. ad libitum): standard rodent diet (CRF-1 TM, Oriental Yeast Co., Ltd.) and drinking water provided ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26 °C
- Humidity (%): 45-46%
- Air changes (per hr): 15 times
- Photoperiod (hrs dark / hrs light): Artificial lighting of the room was controlled to give a cycle of 12 hours continuous light and 12 hours continuous dark per 24 hours

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0 / 12.5 / 25 / 50 / 100 mg/mL.
- Amount of vehicle (if gavage): 0.1 mL/10 g bw

MAXIMUM DOSE VOLUME APPLIED: 1000 mg/kg bw

Doses:

0 / 125 / 250 / 500 / 1000 mg/kg bw.

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations once in the morning and once in the evening. Weighing on days 0 (prior to dosing), 7 and 14.
- Necropsy of survivors performed: yes, a macroscopic examination, which consisted of opening abdominal and thoracic cavities. The macroscopic appearance of abnormal organs was recorded.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

> 500 < mg/kg bw

Based on:

not specified

Mortality:

Mortality of the mice that received the test substance and their macroscopic findings were summarized in Table 2. Lethal toxicity to the mice was observed at the doses of 500 and 1000 mg/kg in early period (Day 0 – 3) after dosing.

Clinical signs:

other: Hemorrhage in stomach and intestine was observed in the mice that died on Day 0 – 1, and whitish foci were found on the liver of witch mice died on Day 1 – 3. Macroscopic abnormality was not found in all mice that survived at the end of study (Day 14).

Gross pathology:

No abnormalities were found in the mice dosed at 125 or 250 mg/kg throughout the study.

Any other information on results incl. tables

Table 2: Mortality after dosing of nonane-1,9-diamine and macroscopic organ findings in died during the observation period or killed on the study termination

Group [No. of micedosed]	Dose(mg/kg)	Mortality data	Organ findings/No. of mice showed the finding	%Mortality
A      [5]	1000	Two mice died on Day 0(the day of dosing).	Hemorrhage in stomach and intestine 2	100
		Three mice died onDay 1.	Hemorrhage in stomachand in testine 3 Whitish foci on liver 3
		No mouse survived onDay 14.
B      [5]	500	Two mice died on Day1.	Hemorrhage in stomachand intestine 2]Whitish foci on liver[2]	60
		A mouse died on Day 3.	Whitish foci on liver[1]
		Two mice survived onDay 14.	No abnormal finding[2]
C[5]	250	All mice survived onDay 14.	No abnormal finding[5]	0
D [5]	125	All mice survived onDay 14.	No abnormal finding[5]	0
E  [ 5]	0	All mice survived onDay 14.	No abnormal finding[5]	0

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute lethal oral dose (LD50) to mice of the test substance was demonstrated to be greater than 250 and less than 1000 mg/kg in this study. A LD50 value of 500 mg/kg was taken as effect level based on the observed 50% survival rate at this dose level

Executive summary:

This study was performed to evaluate the acute oral toxicity of nonane-1,9-diamine to mice. The male mice received a single oral gavage dose of the test substance at a dose level of 125, 250, 500 or 1000 mg/kg-bodyweight, and were observed for 14 days after dosing. Lethal toxicity was found at the dose levels of 500 and 1000 mg/kg. Hemorrhage in stomach and intestine was observed in the mice that died on Day 0 – 1, caused by the corrosion effects of the substance. Whitish foci were found on the liver of mice that died on Day 1 – 3. No abnormalities were found in the mice dosed at 125 or 250 mg/kg throughout the study. The acute lethal oral dose (LD50) to mice for NMDA was determined to be 500 mg/kg bw.