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EC number: 231-034-6 | CAS number: 7417-99-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
![](https://echa.europa.eu./o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Acute Toxicity: oral
Administrative data
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 01 December 2017 - 25 December 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- acute toxic class method
- Limit test:
- no
Test material
- Reference substance name:
- N,N'-(methylenedi-p-phenylene)bis(aziridine-1-carboxamide)
- EC Number:
- 231-034-6
- EC Name:
- N,N'-(methylenedi-p-phenylene)bis(aziridine-1-carboxamide)
- Cas Number:
- 7417-99-4
- Molecular formula:
- C19H20N4O2
- IUPAC Name:
- N-[4-({4-[(aziridine-1-carbonyl)amino]phenyl}methyl)phenyl]aziridine-1-carboxamide
- Test material form:
- solid
1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Remarks:
- RccHan: WIST
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation, India
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9 to 11 weeks
- Weight at study initiation: 166.9 to 188.5 g
- Fasting period before study: overnight prior to dosing until three hours post-dosing
- Housing: 3 females in polypropylene rat cages covered with stainless steel grid top. Autoclaved clean rice husk was used as the bedding material. Wooden blocks were provided as enrichment material.
- Diet (e.g. ad libitum): Ad libitum. Teklad Certified Global High Fiber Rat/Mice Feed manufactured by Envigo, USA. The quality of feed is regularly monitored at Jai Research Foundation.
- Water (e.g. ad libitum): Ad libitum. UV sterilized water filtered through Reverse Osmosis water filtration system. The quality of water is regularly monitored at Jai Research Foundation.
- Acclimation period: 6 to 12 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23°C
- Humidity (%): 49 to 66%
- Air changes (per hr): At least 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light (06.00 to 18.00 h) and 12 hours darkness.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: 30 mg/mL and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL
- Justification for choice of vehicle: recommended by OECD 423 guideline
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: without preliminary information, the selected starting dose is 300 mg/kg body weight. - Doses:
- 300 and 2000 mg/kg bw
- No. of animals per sex per dose:
- Set I (300 mg/kg bw): 3 animals; Set II (300 mg/kg bw): 3 animals; Set III (2000 mg/kg bw): 3 animals
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: toxicity and mortality at 30 min, 1h, 2 h, 3h, 4h, 6 h after adminitration. Morbidity and mortality twice a day and clinical sings daily during 14 days. Weighing= D0 (prior to dosing) then on D7, and D14.
- Necropsy of survivors performed: yes. At termination, macroscopic observation was observed.
- Other examinations performed:
Clinical observations: evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic effects and central nervous system effects, behavioural pattern, somatomotor activity and observation of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Results and discussion
Effect levelsopen allclose all
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 300 - <= 2 000 mg/kg bw
- Based on:
- test mat.
- Key result
- Sex:
- female
- Dose descriptor:
- LD50 cut-off
- Effect level:
- ca. 500 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No mortality was observed in set I and set II treated at the dose level of 300 mg/kg bw.
All the rats were found dead in set III treated at the dose level of 2000 mg/kg bw. - Clinical signs:
- other: No clinical sign was observed in rats treated with 300 mg/kg bw. Clinical sign like lethargy was observed in all the rats treated with 2000 mg/kg bw.
- Gross pathology:
- External examination of found dead and terminally sacrificed rats did not reveal any abnormality.
Visceral examination of found dead rats revealed pale liver (rats treated with 2000 mg/kg bw) whereas terminally sacrificed rats did not reveal any lesion.
Lesion observed in the found dead rats could be correlated with the test item used in the present study.
Any other information on results incl. tables
Table 1: Mortality
Dose (mg/kg body weight) |
Set N° |
Number of Rats Used |
Mortality after Dosing |
||||||
At Hour |
On Day |
||||||||
0.5 – 4 |
6 |
1 |
2 |
3 |
4 - 7 |
8 - 14 |
|||
300 |
I |
3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
II |
3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
2000 |
III |
3 |
0 |
0 |
0 |
0 |
0 |
0 |
3 |
Table 2: Individual and Mean Body Weight (g) and Body Weight Change (%)
Dose (mg/kg body weight) |
Rat N° |
Date and Time of Dosing |
Volume of Test Item Administered (mL) |
Body Weight (g) on Day |
Percent Body Weight Change on Day |
||||
0 |
7 |
14 |
At Death |
7 |
14 |
||||
300 |
1 |
December 07, 2017 and 10:00 am |
1.67 |
166.9 |
170.4 |
207.1 |
- |
2.1 |
24.1 |
2 |
1.71 |
170.8 |
181.3 |
193.2 |
- |
6.1 |
13.1 |
||
3 |
1.73 |
173.3 |
185.6 |
200.5 |
- |
7.1 |
15.7 |
||
Mean |
170.3 |
179.1 |
200.3 |
- |
5.1 |
17.6 |
|||
Standard Deviation (±) |
3.2 |
7.8 |
7.0 |
- |
2.6 |
5.7 |
|||
4 |
December 11, 2017 and 10:30 am |
1.88 |
187.7 |
199.3 |
209.4 |
- |
6.2 |
11.6 |
|
5 |
1.89 |
188.5 |
191.9 |
196.3 |
- |
1.8 |
4.1 |
||
6 |
1.86 |
186.4 |
195.9 |
204.5 |
- |
5.1 |
9.7 |
||
Mean |
187.5 |
195.7 |
203.4 |
- |
4.4 |
8.5 |
|||
Standard Deviation (±) |
1.1 |
3.7 |
6.6 |
- |
2.3 |
3.9 |
|||
2000 |
7 |
December 13, 2017 and 10:30 am |
1.82 |
181.7 |
154.9 |
- |
134.1 |
-14.7 |
- |
8 |
1.85 |
185.1 |
155.7 |
- |
132.3 |
-15.9 |
- |
||
9 |
1.80 |
180.2 |
151.5 |
- |
130.6 |
-15.9 |
- |
||
Mean |
182.3 |
154.0 |
- |
- |
-15.5 |
- |
|||
Standard Deviation (±) |
2.5 |
2.2 |
- |
- |
0.7 |
- |
Key: Day 0 = Before dosing , - = Not applicable
Table 3: Individual clinical observations
Set I
Dose (mg/kg body weight) |
Rat N° |
Clinical Signs Observed Post-dosing |
|||||
At Hour (Day 0) |
|||||||
0.5 |
1 |
2 |
3 |
4 |
6 |
||
300 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
2 |
1 |
1 |
1 |
1 |
1 |
1 |
|
3 |
1 |
1 |
1 |
1 |
1 |
1 |
Dose (mg/kg body weight) |
Rat N° |
Clinical Signs Observed Post-dosing |
|||||||||||||
On Days |
|||||||||||||||
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
||
300 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
2 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
|
3 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
Set II
Dose (mg/kg body weight) |
Rat N° |
Clinical Signs Observed Post-dosing |
|||||
At Hour (Day 0) |
|||||||
0.5 |
1 |
2 |
3 |
4 |
6 |
||
300 |
4 |
1 |
1 |
1 |
1 |
1 |
1 |
5 |
1 |
1 |
1 |
1 |
1 |
1 |
|
6 |
1 |
1 |
1 |
1 |
1 |
1 |
Dose (mg/kg body weight) |
Rat N° |
Clinical Signs Observed Post-dosing |
|||||||||||||
On Days |
|||||||||||||||
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
||
300 |
4 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
5 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
|
6 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
Set III
Dose (mg/kg body weight) |
Rat N° |
Clinical Signs Observed Post-dosing |
|||||
At Hour (Day 0) |
|||||||
0.5 |
1 |
2 |
3 |
4 |
6 |
||
2000 |
7 |
1 |
1 |
1 |
1 |
1 |
1 |
8 |
1 |
1 |
1 |
1 |
1 |
1 |
|
9 |
1 |
1 |
1 |
1 |
1 |
1 |
Dose (mg/kg body weight) |
Rat N° |
Clinical Signs Observed Post-dosing |
|||||||||||||
On Days |
|||||||||||||||
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
||
2000 |
7 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
11 |
11 |
11, 2 |
- |
- |
- |
- |
8 |
1 |
1 |
1 |
1 |
1 |
11 |
11 |
11 |
11 |
2 |
- |
- |
- |
- |
|
9 |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
11 |
11 |
11, 2 |
- |
- |
- |
- |
Clinical Signs: 1 = Normal, 2 = Dead, 11 = Lethargy
Note: Day 0 = Day of dosing, - = Not Applicable
Table 4: Individual necropsy findings
Dose (mg/kg body weight) |
Set N° |
Rat N° |
Mode of Death |
External |
Internal |
300 |
I |
1 |
Terminal sacrifice |
No abnormality detected |
No abnormality detected |
2 |
Terminal sacrifice |
No abnormality detected |
No abnormality detected |
||
3 |
Terminal sacrifice |
No abnormality detected |
No abnormality detected |
||
II |
4 |
Terminal sacrifice |
No abnormality detected |
No abnormality detected |
|
5 |
Terminal sacrifice |
No abnormality detected |
No abnormality detected |
||
6 |
Terminal sacrifice |
No abnormality detected |
No abnormality detected |
||
2000 |
III |
7 |
Found dead |
No abnormality detected |
Liver:Pale (1+) |
8 |
Found dead |
No abnormality detected |
Liver:Pale (2+) |
||
9 |
Found dead |
No abnormality detected |
Liver:Pale (+) |
Key: + = Minimal, 1+ = Mild, 2+ = Moderate
Applicant's summary and conclusion
- Interpretation of results:
- other: Category 4 (CLP Regulation EC no. 1272/2008)
- Conclusions:
- The LD50 of the test item is lower than 2000 mg/kg body weight by oral route in the rat. The LD50 cut-off may be considered to be 500 mg/kg body weight by oral route in the rat.
- Executive summary:
The acute oral toxicity of the test item has been tested in accordance with OECD Test Guideline 423, following GLP. 9 female Wistar rats divided in 3 groups were administered sequentially with test item by oral gavage. The first set of 3 female rats was given a single dose of 300 mg/kg body weight. No mortality was observed at this dose level, so the second set of 3 female rats was treated at the same dose level. No mortality was observed at this dose level, so the third set of 3 female rats was treated at the higher dose level of 2000 mg/kg bw. All the rats were found dead at this dose level. Clinical sign like lethargy was observed from day 6 until day of death and also decrease in body weight was observed on day 7 in rats treated at this high dose. External examination of found dead and terminally sacrificed rats did not reveal any abnormality. Visceral examination of found dead rats revealed pale liver whereas terminally sacrificed rats did not reveal any lesion. Based on these results, the LD50 of the test item is lower than 2000 mg/kg body weight by oral route in the rat. The LD50 cut-off of the test item may be considered to be 500 mg/kg body weight by oral route in the rat.
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