Nonamethylenediamine

Endpoint summary

Description of key information

The acute lethal oral dose (LD50) to mice for NMDA was determined to be 500 mg/kg bw. No fatalities occurred at the lower dose of 250 mg/kg.  Inhalation and dermal studies were not conducted due to the corrosive properties of the substance. 
The data justify the classification according to Regulation (EC) No 1272/2008 as Acute Tox. 4 (oral); H302, harmful if swallowed.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

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

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

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:

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

500 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The key acute oral study, conducted in similar to OECD 401, involved gavage administration. 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, and whitish foci were found on the liver of the mice which 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) of the test substance was estimated to be greater than 250 and less than 1000 mg/kg. A LD50 value of 500 mg/kg was taken as effect level based on the observed 50% survival rate at this dose level.

Justification for selection of acute toxicity – oral endpoint
valid study with Klimisch 2 rating. No further studies were carried out due to highly corrosive proerties of the substance.

Justification for classification or non-classification

LD50 (500 mg/kg) for mouse has been accepted in place of rat for the purposes of classification. Reasons for this are:

i) To reduce the numbers of animals used for toxicity testing as the substance is corrosive.

ii) Current acute oral test methods allow the use of the mouse as an alternative rodent species (e.g. OECD Methods 420, 423 and 425).

 

An LD50 of 500 mg/kg bw meets the criteria for classification as Acute Tox. 4 (oral) according to Regulation (EC) No 1272/2008.