N,N-dimethyl-N'-(2,2,6,6-tetramethylpiperidin-4-yl)propane-1,3-diamine

Endpoint summary

Description of key information

oral: LD50 is approx. 500 mg/kg bw
dermal/inhalation: the study does not need to be conducted since the substance is classified as corrosive to the skin

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8-12 weeks (at study initiation)
- Weight at study initiation: 145-160 g
- Fasting period before study: overnight and approximately 3-4 hours after dosing
- Housing: 3 animals/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

For the purpose of the study the test item was freshly prepared, as required, as a solution at the appropriate concentration in distilled water.

Doses:

2000 and 300 mg/kg b.w.

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: at 0.5, 1, 2 and 4 h after dosing and once daily thereafter
- Frequency of weighing: day 0 (prior to dosing), day 7 and day 14
- Necropsy of survivors performed: yes
- Other examinations performed: gross examination of organs at necropsy

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 500 mg/kg bw

Based on:

test mat.

Mortality:

Animals treated at a dose level of 2000 mg/kg bw were found dead six hours or one day after dosing. There were no deaths at a dose level of 300 mg/kg bw.

Clinical signs:

other: Signs of systemic toxicity noted at both dose levels were hunched posture, ataxia and ptosis. Noisy respiration and/or lethargy were also noted in animals treated at a dose level of 2000 mg/kg. Surviving animals appeared normal one hour to one day after d

Gross pathology:

Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver, gaseous stomach, haemorrhage,
epithelial sloughing and raised limiting ridge of the gastric mucosa, epithelial sloughing and reddened non-glandular region of the stomach,
gaseous small intestine, solid food matter and/or green, clear red or reddish/brown coloured liquid present in the stomach and dark green
substance present in the large intestine. No abnormalities were noted at necropsy of animals treated at a dose level of 300 mg/kg.

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The LD50 of the test item in the female Wistar strain rat was approximately 500 mg/kg bw.

Executive summary:

A group of three fasted female Wistar rats was treated with the test item at a dose level of 2000 mg/kg bw. Based on the results from this dose level further groups of fasted females were treated at a dose level of 300 mg/kg bw.

Animals treated at a dose level of 2000 mg/kg bw were found dead six hours or one day after dosing. There were no deaths at a dose level of 300 mg/kg bw.

Signs of systemic toxicity noted were hunched posture, ataxia and ptosis. Noisy respiration and/or lethargy were also noted in animals treated at a dose level of 2000 mg/kg bw. Surviving animals appeared normal one hour to one day after dosing. The surviving animals showed expected gains in bodyweight over the study period.

Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver, gaseous stomach, haemorrhage, epithelial sloughing and reddened non-glandular region of the stomach, gaseous small intestine, solid food matter and/or liquid present in the stomach and dark green substance present in the large intestine. No abnormalities were noted at necropsy of animals treated at a dose level of 300 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

500 mg/kg bw

Quality of whole database:

reliable without restriction

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 acute oral toxicity of the substance was tested in the rat according to the acute toxic class method (OECD 423). A group of three fasted females was treated with the test item solved in distilled water at a dose level of 2000 mg/kg bw. Animals treated at a dose level of 2000 mg/kg were found dead six hours or one day after dosing. Based on the results from this dose level further groups of fasted females were treated at a dose level of 300 mg/kg bw. No deaths occurred at a dose level of 300 mg/kg bw. Signs of systemic toxicity noted were hunched posture, ataxia and ptosis. Noisy respiration and/or lethargy were also noted in animals treated at a dose level of 2000 mg/kg bw. Surviving animals appeared normal one hour to one day after dosing. Abnormalities noted at necropsy of animals dosed with 2000 mg/kg bw were haemorrhagic lungs, dark liver, gaseous stomach, haemorrhage, epithelial sloughing and raised limiting ridge of the gastric mucosa, epithelial sloughing and reddened non-glandular region of the stomach, gaseous small intestine, solid food matter and/or liquid present in the stomach and dark green substance present in the large intestine. No abnormalities were noted at necropsy of animals treated at a dose level of 300 mg/kg bw. The acute oral median lethal dose (LD50) of the test item in the female

Wistar strain rat was approx. 500 mg/kg bw.

Due to the corrosive properties of the substance no acute dermal or inhalation toxicity studies were performed.

Justification for selection of acute toxicity – oral endpoint
One valid GLP compliant acute oral toxicity study is available.

Justification for classification or non-classification

The acute oral toxicity of the substance was tested in the female Wistar rat according to the acute toxic class method (OECD 423). The LD50 cut-off according to OECD TG 423 was 500 mg/kg bw. Thus, the substance is classified in Category 4 according to Regulation (EC) No 1272/2008 (CLP).