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EC number: 219-102-3 | CAS number: 2359-15-1
- 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
Acute Toxicity: oral
Administrative data
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1990-08-17 to 1990-09-20
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 990
- Report date:
- 1990
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 (Acute Toxicity (Oral))
- Version / remarks:
- 1984-09-19
- GLP compliance:
- yes
- Test type:
- standard acute method
Test material
- Reference substance name:
- N,N'-methylenebis[methacrylamide]
- EC Number:
- 219-102-3
- EC Name:
- N,N'-methylenebis[methacrylamide]
- Cas Number:
- 2359-15-1
- Molecular formula:
- C9H14N2O2
- IUPAC Name:
- N,N'-methylenebis(2-methylacrylamide)
- Test material form:
- solid: particulate/powder
- Details on test material:
- - Designation: N,N’-Methylene-bis-methacrylamide
- Chemical name: 2-Propenamide, N,N’-methylene-bis (2-methyl)
- Characteristics: white powder
- Storage conditions: at room temperature in the dark
Constituent 1
- Specific details on test material used for the study:
- The test item was prepared at various (w/v) concentrations in 1 % w/v aqueous methylcellulose and administered at a volume of 10.0 mL/kg bodyweight.
The test substance was prepared on the day of dosing.
The absorption of the test substance was not determined.
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Remarks:
- CD rats (Sprague-Dawley origin Crl. CD (SD) BR VAF plus)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River U.K. Limited, Margate, Kent, England.
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 119-149 g prior to dosing (Day 1)
- Fasting period: access to food was prevented overnight prior to and approximately 4 hours after dosing.
- Housing: The rats were allocated without conscious bias to cages within the treatment groups. They were housed in groups of up to five rats of the same sex in metal cages with wire mesh floors.
- Diet: standard laboratory rodent diet (Biosure LAD 1) ad libitum. The batch of diet used for the study was analysed for certain chemical and microbiological contaminants.
- Water (e.g. ad libitum): domestic quality potable water ad libitum. Results of routine chemical examination of drinking water at source (Grafham Final Water - Huntingdon North supply zone) as conducted by the Anglian Water Services Ltd., are made available to Huntingdon Research Centre.
- Acclimation period: minimum 8 days prior to the start of the study
ENVIRONMENTAL CONDITIONS
- Temperature (°C): mean daily minimum and maximum temperatures of the animal room were 21°C and 24°C, respectively
- Humidity (%): mean daily relative humidity value was 59 %
- Air changes (per hr): rate of air exchange was maintained at approximately 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial light in each 24-hour period.
- Identification: Each animal was identified by cage number and ear punching. Each cage was identified by a coloured label displaying the dose level, study schedule number, animal mark and the initials of the Study Director and Home Office Licensee.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- methylcellulose
- Details on oral exposure:
- VEHICLE
1 % (w/v) aqueous methylcellulose
- Concentration in vehicle: 20, 32, 40 and 50 % (w/v)
- Amount of vehicle: 10.0 mL/kg bodyweight
MAXIMUM DOSE VOLUME APPLIED: 5.0 g/kg bodyweight - Doses:
- 2.0, 3.2, 4.0, 5.0 g/kg bw
- No. of animals per sex per dose:
- Please see table 1 in section "any other details on materials and methods incl. tables"
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Bodyweight was determined on day 1, 8 and 15 or at death.
Observations: animals surviving treatment were observed once in the morning and again at the end of the experimental day. This latter observation was at approximately 16.30 hours on week days or 11.30 hours on public holidays, including Saturdays and Sundays. Clinical signs were recorded at each observation.
- Necropsy of survivors performed: yes
- Examinations performed: clinical signs, body weight, macroscopic examination - Statistics:
- Probit analysis, Chi-Square test
Results and discussion
- Preliminary study:
- Initially, a group of five male and five female rats were treated at 5.0 g/kg bodyweight. Further groups of five male and/or five females were then dosed, to obtain a dose response curve and permit estimation of a median lethal dose.
Effect levelsopen allclose all
- Key result
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 2 500 mg/kg bw
- Based on:
- act. ingr.
- 95% CL:
- >= 2 000 - <= 3 300
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 4 300 mg/kg bw
- Based on:
- act. ingr.
- 95% CL:
- >= 3 700 - <= 5 100
- Mortality:
- Deaths following a single oral dose of the test item occurred among male rats dosed at 3.2 g/kg bodyweight and above and among female rats dosed at 4.0 g/kg bodyweight and above. Deaths occurred on Days 2 and 3.
- Clinical signs:
- - abnormal body carriage (hunched posture)
- abnormal gait (waddling)
- lethargy
- decreased respiratory rate
- pallor of the extremities in all rats
- ptosis in a majority of rats
- increased sensitivity to disturbance in two females dosed at 5.0 g/kg. - Body weight:
- Slightly lower bodyweight gains were recorded for a majority of rats on Day 8; remaining rats achieved anticipated gains during this period. All rats achieved anticipated bodyweight gains during the second week of the study.
- Gross pathology:
- Terminal autopsy revealed no macroscopic abnormalities.
Any other information on results incl. tables
DETAILS ON RESULTS
1. Groups of five male and/or five female rats were dosed at 2.0, 3.2, 4.0 and 5.0 g/kg bodyweight to determine the acute toxicity of the test substance.
2. Mortality (Table 2)
There were deaths following a single oral dose of the test item among male rats dosed at 3.2 g/kg bodyweight and above and among female rats dosed at 4.0 g/kg bodyweight and above. Deaths occurred on Days 2 and 3. Bodyweight losses were recorded for all decedents. Post mortem examination of rats that died during the study revealed no macroscopic abnormalities.
3. Clinical signs (Table 3)
Pilo-erection was observed in all rats within five minutes of dosing and throughout the remainder of Day 1. This sign was accompanied on Day 1and/or at later intervals by abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, decreased respiratory rate and pallor of the extremities in all rats; ptosis in a majority of rats; increased sensitivity to disturbance in two females dosed at 5.0 g/kg.
Recovery of surviving rats, as judged by external appearance and behaviour, was complete by Day 3 (2.0, 4.0 and females at 3.2 g/kg) or Day 7 (females at 5.0 g/kg).
4. Bodyweight (Table 4)
Slightly low bodyweight gains were recorded for a majority of rats on Day 8; remaining rats achieved anticipated gains during this period. All rats achieved anticipated bodyweight gains during the second week of the study.
5. Post mortem examination: Terminal autopsy revealed no macroscopic abnormalities.
6. Estimation of LD50 values
When probit analysis was carried out by fitting two parallel lines the values were:
Males: 2.5 (2.0 to 3.3) g/kg bodyweight
Females: 4.3 (3.7 to 5.1) g/kg bodyweight
The slope of the parallel probit lines was 14.3 with a standard error of 4.4 using log Transformation of dose. The heterogeneity factor was not significant.
In the mortality response curves, the difference between the lines for male and female rats was statistically significant (P <0.001). Hence, there is a difference in the susceptibility of each sex to the test compound. A combined LD50 value was not therefore given since, as this is the mean value of the male and female LD50 estimations, 50 % mortality would be expected, but would not actually occur, at this dose level. The chi-square test for parallelism gave no evidence of non-parallelism.
Table 2: time and number of deaths of rats dosed orally. The hour/day indicated is the time that the animal was observed to die or found dead. a = First observation; b = Second observation.
Sex |
Dose (g/kg) |
Number of deaths in a group of 5 |
Day |
||||||||||||
|
|
|
1 |
2 |
3 |
4 to 15 |
|||||||||
|
|
|
Hours after dosing |
|
|
|
|
|
|
||||||
|
|
|
0.5 |
1 |
2 |
3 |
4 |
5 |
6 |
a |
b |
a |
b |
a |
b |
males |
2.0 |
0 |
|
|
|
|
|
|
|
|
|
|
|
|
|
3.2 |
5 |
|
|
|
|
|
|
|
4 |
|
1 |
|
|
|
|
5.0 |
5 |
|
|
|
|
|
|
|
4 |
|
1 |
|
|
|
|
females |
3.2 |
0 |
|
|
|
|
|
|
|
|
|
|
|
|
|
4.0 |
3 |
|
|
|
|
|
|
|
3 |
|
|
|
|
|
|
5.0 |
3 |
|
|
|
|
|
|
|
2 |
|
1 |
|
|
|
Table 3: signs of reaction to treatment observed in rats dosed orally.
Signs |
No. of rats in a group of five showing signs |
|||||
|
Dose (g/kg) |
|||||
|
2.0 |
3.2 |
4.0 |
5.0 |
||
|
male |
male |
female |
female |
male |
female |
Pilo-erection |
5 |
5 |
5 |
5 |
5 |
5 |
Abnormal body carriage (hunched posture) |
5 |
5 |
5 |
5 |
5 |
5 |
Abnormal gait (waddling) |
5 |
5 |
5 |
5 |
5 |
5 |
Lethargy |
5 |
5 |
5 |
5 |
5 |
5 |
Decreased respiratory rate |
5 |
5 |
5 |
5 |
5 |
5 |
Ptosis |
0 |
5 |
5 |
1 |
5 |
5 |
Pallor of the extremities |
5 |
5 |
5 |
5 |
5 |
5 |
Increased sensitivity to disturbance |
0 |
0 |
0 |
0 |
0 |
2 |
Table 4: Individual and group mean bodyweights (g) of male rats dosed orally.
Sex |
Dose (g/kg) |
Animal number & ear mark |
Bodyweight (g) at: |
|||
Day 1 |
Day 8 |
Day 15 |
Death |
|||
male |
2.0 |
21 RP |
119 |
183 |
240 |
- |
22 LP |
125 |
190 |
246 |
- |
||
23 RPLP |
127 |
211 |
278 |
- |
||
24 RIRO |
130 |
192 |
242 |
- |
||
25 LILO |
126 |
207 |
267 |
- |
||
mean |
|
125 |
197 |
255 |
- |
|
3.2 |
11 RP |
122 |
- |
- |
116 |
|
12 LP |
130 |
- |
- |
117 |
||
13 RPLP |
128 |
- |
- |
117 |
||
14 RIRO |
132 |
- |
- |
125 |
||
15 LILO |
131 |
- |
- |
122 |
||
mean |
|
129 |
- |
- |
|
|
5.0 |
1 RP |
136 |
- |
- |
118 |
|
2 LP |
131 |
- |
- |
113 |
||
3 RPLP |
149 |
- |
- |
134 |
||
4 RIRO |
149 |
- |
- |
131 |
||
5 LILO |
140 |
- |
- |
113 |
||
mean |
|
141 |
- |
- |
|
Table 5: Individual and group mean bodyweights (g) of female rats dosed orally.
Sex |
Dose (g/kg) |
Animal number & ear mark |
Bodyweight (g) at: |
|||
Day 1 |
Day 8 |
Day 15 |
Death |
|||
female |
2.0 |
16 RP |
133 |
172 |
204 |
- |
17 LP |
132 |
174 |
207 |
- |
||
18 RPLP |
145 |
201 |
233 |
- |
||
19 RIRO |
128 |
167 |
207 |
- |
||
20 LILO |
129 |
172 |
212 |
- |
||
mean |
|
133 |
177 |
213 |
|
|
3.2 |
26 RP |
127 |
169 |
195 |
- |
|
27 LP |
124 |
- |
- |
109 |
||
28 RPLP |
130 |
183 |
216 |
- |
||
29 RIRO |
122 |
- |
- |
109 |
||
30 LILO |
121 |
- |
- |
112 |
||
mean |
|
125 |
176 |
206 |
|
|
5.0 |
6 RP |
120 |
154 |
186 |
- |
|
7 LP |
131 |
- |
- |
109 |
||
8 RPLP |
121 |
- |
- |
118 |
||
9 RIRO |
131 |
- |
- |
117 |
||
10 LILO |
134 |
163 |
213 |
- |
||
mean |
|
127 |
159 |
200 |
|
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The acute median lethal oral doses (LD50) and their 95 % confidence limits to rats of the test item were estimated to be:
Males only: 2.5 (2.0 to 3.3) g/kg bodyweight
Females only: 4.3 (3.7 to 5.1) g/kg bodyweight - Executive summary:
In an acute oral toxicity study according to EU method B.1, version 1984-09-19, groups of five male and/or five female fasted rats were dosed with N,N’-methylenebis[methacrylamide] at 2.0, 3.2, 4.0 and 5.0 g/kg bodyweight. The rats were in the weight range of 119 to 149 g prior to dosing and approximately four to six weeks of age. The test item was dissolved in 1 % w/v aqueous methylcellulose and administered via gavage. The rats were observed for 14 days.
Deaths occurred following a single oral dose of N,N’-methylenebis[methacrylamide] among male rats dosed at 3.2 g/kg bodyweight and above and among female rats dosed at 4.0 g/kg bodyweight and above. Deaths occurred on Days 2 and 3.
Pilo-erection was observed in all rats within five minutes of dosing and throughout the remainder of Day 1. This sign was accompanied on Day 1 and/or at later intervals by abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, decreased respiratory rate and pallor of the extremities in all rats; ptosis in a majority of rats and increased sensitivity to disturbance in two females dosed at 5.0 g/kg.
Recovery of surviving rats, as judged by external appearance and behaviour, was complete by Day 3.
Slightly lower bodyweight gains were recorded for a majority of rats on Day 8; the remaining rats achieved anticipated gains during this period. All rats achieved anticipated bodyweight gains during the second week of the study.
Terminal autopsy revealed no macroscopic abnormalities.
The acute median lethal oral doses (LD50) and their 95 % confidence limits to rats of N,N’-methylenebis[methacrylamide] were estimated to be:
Oral LD50 (rat, males): 2.5 (2.0 to 3.3) g/kg bodyweight
Oral LD50 (rat, females): 4.3 (3.7 to 5.1) g/kg bodyweight
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