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EC number: 204-817-5 | CAS number: 126-98-7
- 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:
- no data
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 001
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- no
Test material
- Reference substance name:
- Methacrylonitrile
- EC Number:
- 204-817-5
- EC Name:
- Methacrylonitrile
- Cas Number:
- 126-98-7
- Molecular formula:
- C4H5N
- IUPAC Name:
- 2-methylprop-2-enenitrile
- Details on test material:
- - Name of test material (as cited in study report): 2-methyl-2-propenenitrile (MAN)
- Substance type: Colourless liquid at room temperature
- Physical state: Liquid
- Analytical purity: 99%.
- Stability under test conditions: Tested by the provider of the test material
- Storage condition of test material: In a hermetic container, shield from the light at 4 - 10 degrees Centigrade
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River (Japan) Ltd, Atsugi, Japan
- Age at study initiation: 5 weeks old
- Weight at study initiation: Mean of 146.4 g (140 to 153 g) for males, mean of 117.5 g (110 to 125 g) for females
- Housing: The animals were housed individually in metal wire netting cages
- Diet (e.g. ad libitum): CRF-1 (Lot No. of 980904, 981209, Oriental Yeast Co., Ltd.), ad libitum. The diet was analysed and were considered not to contain any contaminants that would exceed the standard levels of contaminants
- Water (e.g. ad libitum): Mains water (Sapporo-shi, Hokkaido, Japan), ad libitum. The mains water was analysed and were considered not to contain any contaminants that would exceed the standard levels of contaminants
- Acclimation period: 7 days.
ENVIRONMENTAL CONDITIONS
- Temperature: 21 to 23 degrees Centigrade
- Humidity: 52 to 59 %.
- Air changes (per hr): 10 to 15 changes per hour.
- Photoperiod (hrs dark / hrs light): Twelve hours continuous light (08:00 to 20:00) and 12 hours darkness.
IN-LIFE DATES: From: Day 0 Up To: Day 14
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Details on oral exposure:
- VEHICLE
- Amount of vehicle (if gavage): 5 mL/kg
- Lot/batch no. (if required): 807089 (Yakuhan Pharmaceutical Co., Ltd., Japan)
MAXIMUM DOSE VOLUME APPLIED:
100 mg/kg for males, 120 mg/kg for females
- Doses:
- Zero, 50, 60, 70, 85 and 100 mg/kg bw for males
Zero, 60, 70, 85, 100 and 120 mg/kg bw for females - No. of animals per sex per dose:
- 5 males and 5 females per dose level
- Control animals:
- yes
- Details on study design:
- - Duration of observation period following administration: Day zero (the day of dosing) up to Day 14
- Frequency of observations and weighing: Deaths, cage side observation and behaviour were recorded continuously on Day 0 to 1 hour after dosing, then 2, 3, 4, 5 and 6 hours and then daily for 14 days
- Necropsy: Dead animals during the study period and surviving animals. macroscopic observation of the organs (brain, liver, kidneys, spleen, heart, lung, stomach, duodenum, celenteron, ileum, cecum, colon, intestinum, testes, epididymides and ovaries)
- Other examinations performed: body weight,histopathology - Statistics:
- Mortality data was used for the estimation of LD50 and 95 % CI by the probit method
Results and discussion
- Preliminary study:
- Mortality 1/3 males at 60 mg/kg, 2/3 males at 70 mg/kg, and 3/3 at and above 85 mg/kg; 2/3 females at 70, 85 and 100 mg/kg, 3/3 at and above 150 mg/kg
Effect levelsopen allclose all
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 64 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- >= 49 - <= 76
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 73 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- >= 49 - <= 87
- Mortality:
- See Table 2 (below) for the mortality and LD50
- Clinical signs:
- other: Treatment-related effects such as decrease in locomotor activity, prone/side position, hyperpnea, clonic convulsion, salivation, diarrhaea and soiling of perigenital, perianal, and perioral fur were observed in both sexes (see Table 3, below)
- Gross pathology:
- Postmortem findings included a dark red patch in the mucosa of the glandular stomach, pale red discoloration in small intestine, bright orange discoloration and dilation in right atrium were observed in both sexes (see Table 6, below).
Dark red patch in mucosa in glandular stomach, pale red discoloration in small intestine were considered to be caused by the corrosive nature of the test substance. Bright orange discoloration and hyperpnea (as clinical sign of dilation in right atrium) were attributed to effects of the test substance to the lungs and breathing, as most of the test substance would be excreted to the air in other available oral gavage studies in rats. Bright orange discoloration might have been related to the effects in haematological parameters such as decreases in red blood cells and haemoglobin (haemolytic changes) in the past studies. No mode of action could have been identified between dilation in right atrium and effects in the lungs. - Other findings:
- No data
Any other information on results incl. tables
Table 2: Mortality
Males |
||||||
Dose (mg/kg) |
0 |
50 |
60 |
70 |
85 |
100 |
Number of animals |
5 |
5 |
5 |
5 |
5 |
5 |
Number of deaths |
0 |
1 |
2 |
3 |
4 |
5 |
Females |
||||||
Dose (mg/kg) |
0 |
60 |
70 |
85 |
100 |
120 |
Number of animals |
5 |
5 |
5 |
5 |
5 |
5 |
Number of deaths |
0 |
2 |
1 |
4 |
4 |
5 |
Table 3: General appearance of rats in acute oral toxicity test of 2-methyl-2-propenenitrile (MAN)
Item |
Male |
Female |
||||||||||
MAN (mg/kg) |
MAN (mg/kg) |
|||||||||||
Control |
50 |
60 |
70 |
85 |
100 |
Control |
60 |
70 |
85 |
100 |
120 |
|
Administration day No. of animals examined |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
No abnormal findings |
5a |
0 |
0 |
0 |
0 |
0 |
5 |
2 |
0 |
0 |
0 |
0 |
Decrease in locomotor activity |
0 |
4 |
3 |
4 |
2 |
2 |
0 |
2 |
5 |
5 |
3 |
5 |
Prone/side position |
0 |
5 |
4 |
3 |
5 |
5 |
0 |
1 |
1 |
4 |
3 |
4 |
Hyperpnoea |
0 |
5 |
5 |
5 |
5 |
5 |
0 |
3 |
5 |
5 |
4 |
5 |
Colonic convulsion |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
1 |
0 |
0 |
0 |
0 |
Salivation |
0 |
0 |
1 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
2 |
0 |
Diarrhoea |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
Soiled perioral fur |
0 |
0 |
0 |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
Soiled perigenital fur |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
1 |
3 |
0 |
2 |
Soiled perianal fur |
0 |
1 |
0 |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Dead |
0 |
1 |
2 |
2 |
4 |
5 |
0 |
1 |
1 |
4 |
3 |
2 |
|
||||||||||||
1-14 days after administration No. of animals examined |
5 |
4 |
3 |
3 |
1 |
0 |
5 |
4 |
4 |
1 |
2 |
3 |
No abnormal findings |
5 |
4 |
3 |
2 |
1 |
-b |
5 |
3 |
3 |
1 |
1 |
0 |
Soiled perigenital fur |
0 |
0 |
0 |
0 |
0 |
- |
0 |
0 |
1 |
0 |
0 |
2 |
Dead |
0 |
0 |
0 |
1 |
0 |
- |
0 |
1 |
0 |
0 |
1 |
3 |
a: Values are no. of animals with findings
b: - = blank value
Table 4: Bodyweight changes of male rats in acute toxicity test of 2-methyl-2-propenenitrile (MAN)
Group |
No. of animals |
Day after administration |
Bodyweight gain |
|||||||
0 |
1 |
3 |
5 |
7 |
10 |
14 |
Day 0-14 |
%a |
||
|
||||||||||
Control |
5
|
124.6b 3.4 |
146.8 3.3 |
171.8 5.8 |
191.0 5.3 |
209.2 5.5 |
237.4 7.8 |
273.4 11.0 |
148.8 10.9 |
119.516 9.688 |
MAN 50 mg/kg |
5 |
123.6 1.5 |
(4)c 141.3 4.7 |
(4) 166.0 3.5 |
(4) 188.3 5.1 |
(4) 207.8 7.3 |
(4) 237.5 7.6 |
(4) 276.3 11.2 |
(4) 153.0 10.2 |
(4) 124.108 7.487 |
MAN 60 mg/kg |
5 |
124.0 3.8 |
(3) 141.7 4.9 |
(3) 171.0 2.6 |
(3) 193.7 2.5 |
(3) 214.0 2.6 |
(3) 244.7 3.1 |
(3) 285.7 8.6 |
(3) 159.7 7.8 |
(3) 126.790 7.135 |
MAN 70 mg/kg |
5 |
122.2 3.0 |
(2) 136.5 9.2 |
(2) 168.0 5.7 |
(2) 190.0 8.5 |
(2) 212.0 4.2 |
(2) 244.0 7.1 |
(2) 287.5 7.8 |
(2) 167.5 7.8 |
(2) 139.585 6.484 |
MAN 85 mg/kg |
5 |
124.0 5.2 |
(1) 138.0 |
(1) 173.0 |
(1) 193.0 |
(1) 213.0 |
(1) 241.0 |
(1) 273.0 |
(1) 146.0 |
(1) 114.960 |
MAN 100 mg/kg |
5 |
124.6 3.4 |
-d |
- |
- |
- |
- |
- |
- |
- |
a: (Bodyweight gain / bodyweight on day 0) x 100
b: Values are means and S.D. there under, expressed in grams
c: Values in parentheses are no. of animals examined
d: - = blank value
Table 5: Bodyweight changes of female rats in acute toxicity test of 2-methyl-2-propenenitrile (MAN)
Group |
No. of animals |
Day after administration |
Bodyweight gain |
|||||||
0 |
1 |
3 |
5 |
7 |
10 |
14 |
Day 0-14 |
%a |
||
|
||||||||||
Control |
5
|
98.8b 4.0 |
117.6 4.6 |
134.8 6.4 |
144.8 5.3 |
155.0 5.4 |
165.6 9.2 |
180.2 8.8 |
81.4 7.8 |
82.486 8.184 |
MAN 60 mg/kg |
5 |
100.0 3.9 |
(3)c 111.3 5.5 |
(3) 136.0 2.0 |
(3) 149.0 5.6 |
(3) 161.3 4.5 |
(3) 172.0 5.6 |
(3) 184.0 6.6 |
(3) 84.7 4.5 |
(3) 85.197 2.830 |
MAN 70 mg/kg |
5 |
98.2 4.8 |
(4) 100.8* 7.9 |
(4) 130.8 11.4 |
(4) 144.8 9.0 |
(4) 158.0 12.6 |
(4) 171.0 13.3 |
(4) 184.5 13.1 |
(4) 86.3 9.9 |
(4) 87.828 9.821 |
MAN 85 mg/kg |
5 |
98.6 2.7 |
(1) 89.0
|
(1) 124.0 |
(1) 143.0 |
(1) 146.0 |
(1) 157.0 |
(1) 171.0 |
(1) 72.0 |
(1) 72.730 |
MAN 100 mg/kg |
5 |
98.4 3.8 |
(1) 112.0 |
(1) 137.0 |
(1) 148.0 |
(1) 163.0 |
(1) 168.0 |
(1) 197.0 |
(1) 94.0 |
(1) 91.260 |
MAN 120 mg/kg |
5 |
98.8 4.1 |
-d |
- |
- |
- |
- |
- |
- |
- |
a: (Bodyweight gain / bodyweight on day 0) x 100
b: Values are means and S.D. there under, expressed in grams
c: Values in parentheses are no. of animals examined
d: - = blank value
*: Differs from control, p≤0.05
Table 6: Gross findings of rats in acute oral toxicity test of 2-methyl-2-propenenitrile (MAN)
Item |
Male |
Female |
||||||||||
MAN (mg/kg) |
MAN (mg/kg) |
|||||||||||
Control |
50 |
60 |
70 |
85 |
100 |
Control |
60 |
70 |
85 |
100 |
120 |
|
Total no. of animals examined |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Findings of dead animals No. of animals examined |
0 |
1 |
2 |
3 |
4 |
5 |
0 |
2 |
1 |
4 |
4 |
5 |
Organ: Findings |
||||||||||||
Lung: Bright orange discolouration |
-a |
1b |
2 |
3 |
2 |
4 |
- |
1 |
1 |
3 |
3 |
2 |
Glandular stomach: Dark red patch, mucosa |
- |
0 |
2 |
3 |
2 |
1 |
- |
0 |
1 |
3 |
3 |
5 |
Small intestine: Pale red discolouration |
- |
1 |
0 |
0 |
1 |
3 |
- |
0 |
1 |
0 |
1 |
1 |
Heart: Dilation, right atrium |
- |
1 |
2 |
3 |
4 |
3 |
- |
2 |
1 |
3 |
4 |
4 |
Findings of surviving animals No. of animals examined |
5 |
4 |
3 |
2 |
1 |
0 |
5 |
3 |
4 |
1 |
1 |
0 |
Abnormal findings |
0 |
0 |
0 |
0 |
0 |
- |
0 |
0 |
0 |
0 |
0 |
- |
a: - = blank value
b: Values are no. of animals with findings
Applicant's summary and conclusion
- Conclusions:
- As a result of the acute oral study in rats, decrease in locomotor activity, prone/side position, hyperpnea and deaths were observed. The acute oral lethal dose (LD50) of the test material in the rat was 64 mg/kg bodyweight (95%CI 49 - 76) in males and 73 mg/kg bodyweight (95%CI 49 - 87) in females under the test condition.
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